FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mumm, S Zhang, X Nesbit, MA Mazzarella, R Schlessinger, D Thakker, RV Chen, E Parvari, R Whyte, MP AF Mumm, S Zhang, X Nesbit, MA Mazzarella, R Schlessinger, D Thakker, RV Chen, E Parvari, R Whyte, MP TI New candidate genes for X-linked recessive hypoparathyroidism. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO USA. Hammersmith Hosp, MRC, London, England. NIA, NIH, Baltimore, MD 21224 USA. ABD, Foster City, CA USA. Soroka Med Ctr, IL-84101 Beer Sheva, Israel. Shriners Hosp Children, MRU, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU058 BP S446 EP S446 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101248 ER PT J AU Nagata, M Shum, L Takahashi, K Cho, A Kulkarni, AB Slavkin, HC Nuckolls, GH AF Nagata, M Shum, L Takahashi, K Cho, A Kulkarni, AB Slavkin, HC Nuckolls, GH TI Transgenic mice expressing the P253R mutation of FGFR2 in chondrocytes exhibit craniofacial dysmorphology similar to Apert syndrome. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIAMS, Craniofacial Dev Sect, NIH, Bethesda, MD USA. NIDCR, Funct Gen Unit & Gene Targeting Facil, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1183 BP S178 EP S178 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100185 ER PT J AU Nilsson, O Abad, V Savendahl, LSG Baron, J AF Nilsson, O Abad, V Savendahl, LSG Baron, J TI Expression of estrogen receptor-beta in rabbit growth plate cartilage. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Karolinska Inst, Inst Women & Child Hlth, Pediat Endocrinol Unit, Stockholm, Sweden. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU084 BP S452 EP S452 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101274 ER PT J AU Prufer, K Barsony, J AF Prufer, K Barsony, J TI Vitamin D and retinoid x receptor expressions are selectively downregulated in rat osteosarcoma cells through distinct posttranslational mechanisms. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F465 BP S303 EP S303 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100679 ER PT J AU Riminucci, M Satomura, K Kuznetsov, SA Bianco, P Robev, PG AF Riminucci, M Satomura, K Kuznetsov, SA Bianco, P Robev, PG TI Defective TGF-beta/BMP signalling systems in GNAS-1 mutated stromal cells from fibrous dysplasia of bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Univ Tokushima, Sch Dent, Tokushima 770, Japan. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA T061 BP S190 EP S190 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100232 ER PT J AU Riminucci, M Fisher, LW Majolagbe, A Lala, R Robey, PG Bianco, P AF Riminucci, M Fisher, LW Majolagbe, A Lala, R Robey, PG Bianco, P TI A novel GNAS1 mutation, R201G, in McCune-Albright syndrome (MAS). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. NIDCR, NIH, Bethesda, MD USA. Osped Regina Margherita, Turin, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F056 BP S224 EP S224 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100367 ER PT J AU Sekiya, I Tsuji, K Koopman, P Ito, Y Yamada, Y Shinomiya, K Nifuji, A Noda, M AF Sekiya, I Tsuji, K Koopman, P Ito, Y Yamada, Y Shinomiya, K Nifuji, A Noda, M TI Dexamethasone promotes chondrocyte differentiation through enhancement of Sox9 expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Tokyo Med & Dent Univ, Tokyo, Japan. Univ Queensland, St Lucia, Qld 4067, Australia. Kyoto Univ, Kyoto, Japan. NIDR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA Su022 BP S437 EP S437 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101212 ER PT J AU Sjogren, K Liu, JL Blad, K Skrtic, S Vidal, O Wallenius, V LeRoith, D Tornell, J Isaksson, OG Jansson, JO AF Sjogren, K Liu, JL Blad, K Skrtic, S Vidal, O Wallenius, V LeRoith, D Tornell, J Isaksson, OG Jansson, JO TI Liver-derived IGF-I regulates GH-secretion but is not required for postnatal body growth. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Res Ctr Endocrinol & Metab, Dept Internal Med, Gothenburg, Sweden. Gothenburg Univ, Dept Physiol, Div Endocrinol, Gothenburg, Sweden. NIH, Sect Cellular & Mol Physiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA T101 BP S192 EP S192 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100241 ER PT J AU Taaffe, DR Harris, T Cauley, J Danielson, M Nevitt, M Lang, T Bauer, DC AF Taaffe, DR Harris, T Cauley, J Danielson, M Nevitt, M Lang, T Bauer, DC TI Effects of gender and race on the relationships between muscle strength and soft-tissue with bone mineral density in healthy elders: the Health ABC study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA, EDB Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA316 BP S387 EP S387 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101017 ER PT J AU Tylavsky, FA Fuerst, T Dockrell, M Wan, JY Cauley, JA Nevitt, M Harris, T AF Tylavsky, FA Fuerst, T Dockrell, M Wan, JY Cauley, JA Nevitt, M Harris, T TI The relationship between change in bone mass with weight changes: Pencil versus fan beam DXA. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU237 BP S491 EP S491 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101427 ER PT J AU Miki, K AF Miki, K TI Volume of liquid below the epithelium of an F9 cell as a signal for differentiation into visceral endoderm SO JOURNAL OF CELL SCIENCE LA English DT Article DE egg cylinder; embryoid body; epithelium; cell aggregate; differentiation ID EMBRYONIC STEM-CELLS; RECONSTITUTED BASEMENT-MEMBRANE; GENE-EXPRESSION; RETINOIC ACID; IN-VITRO; TERATOCARCINOMA CELLS; PARIETAL ENDODERM; CARCINOMA-CELLS; INDUCTION; MATRIX AB When retinoic acid-primed F9 cells are allowed to aggregate, they form embryoid bodies with an outer layer of alpha-fetoprotein-producing visceral endoderm cells and an internal cavity. I show that maturation of the visceral endoderm is dependent on the size of F9 aggregates. Size fractionation of aggregates of retinoic acid-primed F9 cells on Percoll density gradients revealed that only aggregates with diameters larger than 180 mu m developed into embryoid bodies with an endoderm layer secreting alpha-fetoprotein. Size dependent alpha-fetoprotein-secretion was also observed when retinoic acid-primed F9 cells were cultured on porous microcarrier beads larger than 185 mu m. Retinoic acid-primed F9 cells on flat microporous membranes did not differentiate and secrete alpha-fetoprotein unless exposed to a limited volume of medium at their basolateral surface. This suggested that maturation of the visceral endoderm is signaled by the volume of liquid phase below the epithelium. I postulate that the epithelial layer of an F9 aggregate encloses liquid and forms a barrier to diffusion of some critical factor(s). The concentration of such a factor may reach a threshold due to enlargement of the liquid phase during growth of the F9 aggregate and thereby signal maturation of the outer layer of cells into visceral endoderm. C1 Nagoya Univ, Biosci Ctr, Chikusa Ku, Nagoya, Aichi 4648601, Japan. RP Miki, K (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1999 VL 112 IS 18 BP 3071 EP 3080 PG 10 WC Cell Biology SC Cell Biology GA 243VT UT WOS:000083018700009 PM 10462523 ER PT J AU Weinberg, NZ Glantz, MD AF Weinberg, NZ Glantz, MD TI Child psychopathology risk factors for drug abuse: Overview SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID SUBSTANCE USE DISORDERS; PAST 10 YEARS; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; ADDICTIVE PERSONALITY; HYPERACTIVE BOYS; ALCOHOL-USE; COMORBIDITY; ADOLESCENTS; BEHAVIOR AB Introduces the special section on Child Psychopathology Risk Factors for Substance Use Disorders. This article summarizes important principles, the current literature, contributions to this section, and issues for future research. Psychopathological conditions are strongly associated with substance use disorders, and some childhood psychogathological conditions may constitute precursors to this comorbidity. Conduct disorder constitutes a strong risk factor for substance use disorders, and bipolar disorder, although more rare, may also constitute a significant risk. Data for other child psychiatric conditions are mixed or lacking; however, important subgroups may be at risk and merit further attention. Underlying characteristics, such as temperament and self-regulation, merit further study as possible explanatory variables. Such studies hold the key for targeting and improving preventive and therapeutic interventions. C1 NIDA, Bethesda, MD 20892 USA. RP Weinberg, NZ (reprint author), NIDA, 6001 Execut Blvd,Room 5153,MSC 9589, Bethesda, MD 20892 USA. RI Hizukuri, Tatiana/H-6593-2016 NR 50 TC 47 Z9 48 U1 2 U2 7 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD SEP PY 1999 VL 28 IS 3 BP 290 EP 297 DI 10.1207/S15374424jccp280301 PG 8 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 223KQ UT WOS:000081840600001 PM 10446678 ER PT J AU Marx, SJ AF Marx, SJ TI Contrasting paradigms for hereditary hyperfunction of endocrine cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEOPLASIA TYPE-I; NEONATAL SEVERE HYPERPARATHYROIDISM; COMPARATIVE GENOMIC HYBRIDIZATION; FOCAL ADENOMATOUS HYPERPLASIA; PARATHYROID-HORMONE RELEASE; CALCIUM-SENSING RECEPTOR; PANCREATIC BETA-CELL; JAW TUMOR SYNDROME C1 NIDDKD, Genet & Endocrinol Sect, NIH, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDKD, Genet & Endocrinol Sect, NIH, Bld 10,Room 9C-101, Bethesda, MD 20892 USA. EM StephenM@INTRA.NIDDK.NIH.GOV NR 102 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3001 EP 3009 DI 10.1210/jc.84.9.3001 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600001 PM 10487655 ER PT J AU Koch, CA Tsigos, C Patronas, NJ Papanicolaou, DA AF Koch, CA Tsigos, C Patronas, NJ Papanicolaou, DA TI Cushing's disease presenting with avascular necrosis of the hip: An orthopedic emergency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FEMORAL-HEAD; BONE; MANIFESTATION; THERAPY; FEMUR AB Nontraumatic avascular necrosis (AVN) of the hip is commonly caused by exogenous glucocorticoid administration, whereas it has rarely been associated with endogenous hypercortisolism. We report a 30-yr-old woman with Cushing's disease whose presenting manifestation was early AVN of the hip. Although plain x-ray was negative, magnetic resonance imaging (MRI) of the hip showed stage 2 AVN. Her orthopedic disease was considered an emergency, and thus, it was treated with core decompression before the diagnosis of Cushing's syndrome (CS) was pursued further. The femur recovered fully, as demonstrated by her improved clinical picture and a subsequent MRI. AVN carries a poor prognosis, if not treated early. The diagnostic procedure of choice is MRI, because plain radiographs are falsely negative in early stages. This case illustrates that AVN can be the presenting manifestation of CS; to prevent irreversible effects on the femoral head, core decompression should not be delayed for the purpose of evaluation and treatment of CS. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Natl Diabet Ctr, Athens, Greece. RP Papanicolaou, DA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM papanicd@mail.nih.gov RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 18 TC 13 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3010 EP 3012 DI 10.1210/jc.84.9.3010 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600002 PM 10487656 ER PT J AU Stock, JL Brown, RS Baron, J Coderre, JA Mancilla, E De Luca, F Ray, K Mericq, MV AF Stock, JL Brown, RS Baron, J Coderre, JA Mancilla, E De Luca, F Ray, K Mericq, MV TI Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAMILIAL ISOLATED HYPOPARATHYROIDISM; CALCIUM-SENSING RECEPTOR; CA2+-SENSING RECEPTOR; SPORADIC HYPOPARATHYROIDISM; HORMONE GENE; MUTATIONS; HYPOCALCEMIA AB Familial hypoparathyroidism is an unusual and genetically heterogeneous group of disorders that may be isolated or may be associated with congenital or acquired abnormalities in other organs or glands. We have evaluated a family with a novel syndrome of autosomal dominant hypoparathyroidism, short stature, and premature osteoarthritis. A 74-yr-old female (generation I) presented with hypoparathyroidism, a movement disorder secondary to ectopic calcification of the cerebellum and basal ganglia, and a history of knee and hip replacements for osteoarthritis. Two members of generation II and one member of generation III were also documented with hypoparathyroidism, short stature, and premature osteoarthritis evident as early as 11 yr. Because of the known association between autosomal dominant hypoparathyroidism and activating mutations of the calcium-sensing receptor (CaR) gene, further studies were performed. Sequencing of PCR-amplified genomic DNA revealed a leucine to valine substitution at position 616 in the first transmembrane domain of the CaR, which cosegregated with the disorder. However, this amino acid sequence change did not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected HEK-293 cells. In conclusion, a sequence alteration in the coding region of the CaR gene was identified, but is not conclusively involved in the etiology of this novel syndrome. The cosegregation of hypoparathyroidism, short stature, and osteoarthritis in this kindred does suggest a genetic abnormality involving a common molecular mechanism in parathyroid, bone, and cartilage. C1 Univ Massachusetts, Div Endocrinol, Worcester, MA 01605 USA. Univ Massachusetts, Div Pediat Endocrinol Diabet, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Stock, JL (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 4121, Indianapolis, IN 46285 USA. EM jlstock@lilly.com NR 20 TC 14 Z9 16 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3036 EP 3040 DI 10.1210/jc.84.9.3036 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600007 PM 10487661 ER PT J AU Yu, DW Yu, SH Schuster, V Kruse, K Clericuzio, CL Weinstein, LS AF Yu, DW Yu, SH Schuster, V Kruse, K Clericuzio, CL Weinstein, LS TI Identification of two novel deletion mutations within the G(s)alpha gene (GNAS1) in albright hereditary osteodystrophy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PSEUDOHYPOPARATHYROIDISM TYPE-IA; GRADIENT GEL-ELECTROPHORESIS; STIMULATORY G-PROTEIN; ALPHA-SUBUNIT GENE; PARATHYROID-HORMONE; BINDING PROTEIN; RECEPTOR; GS; FAMILY; HYPOPARATHYROIDISM AB Albright hereditary osteodystrophy (AHO) is a genetic disorder characterized by short stature, skeletal defects, and obesity. Within AHO kindreds, some affected family members have only the somatic features of AHO [pseudopseudohypoparathyroidism (PPHP)I, whereas others have these features in association with resistance to multiple hormones that stimulate adenylyl cyclase within their target tissues [pseudohypoparathyroidism type Ia (PHP Ia)]. Affected members of most AHO kindreds (both those with PPHP and those with PHP Ia) have a partial deficiency of G(s)alpha, the alpha-subunit of the G protein that couples receptors to adenylyl cyclase stimulation, and in a number of cases heterozygous loss of function mutations within the G(s)alpha gene (GNAS1) have been identified. Using PCR with the attachment of a high melting domain (GC-clamp) and temperature gradient gel. electrophoresis, two novel heterozygous frameshift mutations within GNAS1 were found in two AHO kindreds. In one kindred all affected members (both PHP Ia and PPHP) had a heterozygous 2-bp deletion in exon 8, whereas in the second kindred a heterozygous 2-bp deletion in exon 4 was identified in all affected members examined. In both cases the frameshift encoded a premature termination codon several codons downstream of the deletion. In the latter kindred affected members were previously shown to have decreased levels of GNAS1 messenger ribonucleic acid expression. These results further underscore the genetic heterogeneity of AHO and provides further evidence that PHP Ia and PPHP are two clinical presentations of a common genetic defect. Serial measurements of thyroid function in members of kindred 1 indicate that TSH resistance progresses with age and becomes more evident after the first year of life. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Childrens Hosp, D-97080 Wurzburg, Germany. Univ Lubeck, Childrens Hosp, D-23538 Lubeck, Germany. Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov NR 34 TC 38 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3254 EP 3259 DI 10.1210/jc.84.9.3254 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600042 PM 10487696 ER PT J AU Di Cerbo, A Di Paola, R Menzaghi, C De Filippis, V Tahara, K Corda, D Kohn, LD AF Di Cerbo, A Di Paola, R Menzaghi, C De Filippis, V Tahara, K Corda, D Kohn, LD TI Graves' immunoglobulins activate phospholipase A(2) by recognizing specific epitopes on thyrotropin receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the Endocrine-Society CY JUN 10-14, 1997 CL MINNEAPOLIS, MN SP Endocrine Soc ID THYROID-STIMULATING ANTIBODIES; IDIOPATHIC MYXEDEMA PATIENTS; HUMAN TSH RECEPTOR; GONADOTROPIN RECEPTORS; BLOCKING ANTIBODIES; DISEASE PATIENTS; DIFFERENT SITES; BINDING; SERA; IDENTIFICATION AB Thyroid-stimulating IgG from Graves' patients bind to the TSH receptor and activate both adenylyl cyclase (AC) and phospholipase A(2)(PLA(2)) in FRTL5 thyroid cells. Both activities have been associated with increased thyroid cell growth and function; evidence exists that subpopulations of Graves' IgG can stimulate either AC or PLA(2) cascades and that the activation of both is associated with the largest goiters in patients. Studies using chimeras of the human TSHR receptor (hTSHR) and the LH-CG receptor show that most patients with Graves' disease have cAMP-stimulating IgG that require epitopes on the N-terminal portion of the TSHR extracellular domain; epitopes associated with PLA(2) activation are not clear. To address this question we used stably transfected Chinese hamster ovary (CHO) cells containing the wild-type hTSHR and the hTSHR chimera with residues 8-165 (Mc1+2) substituted by equivalent residues of the LH-CG receptor. PLA, activity, measured as arachidonic acid (AA) release, was determined in 32 patients with Graves' disease. We show that 72% of Graves' patients have IgG able to stimulate PLA, in CHO cells transfected with the TSHR and that AA release induced by Graves' IgG was significantly reduced (P = 0.022) in the CHO-Mc1+2- transfected cells (193 +/- 88% vs. 131 +/- 67%, respectively). Unlike IgG, the effect of TSH was not modified in the CHO-Mc1+2-transfected cells. When we compared the AC- and PLA,-stimulating activities of these 32 IgG in wild-type TSHR transfectants, we found that 63% of Graves' patients have antibodies able to stimulate both PLA, and AC, whereas some patients' IgG were active only in AC or PLA, assays. Of the patients with IgG having activity in both assays in wild-type TSHR transfectants, 50% of the IgG lost their stimulatory activities in both AA release and cAMP assays in Mc1+2 cells. Of the remainder, some IgG maintained their activity in one (AA release) or the other (cAMP) assay when measured in Mc1+2 chimeras. Thus, our data show that the N-terminal portion of extracellular domain of the TSHR is required for PLA, as well as AC activation by IgG from patients with Graves' disease. These data also demonstrate that patients with Graves' disease have heterogeneous autoantibodies that selectively activate AC and PLA, pathways and suggest that patients with autoantibodies active in both assays have more severe disease, with higher thyroid hormone levels and larger goiters. C1 IRCCS, Div & Res Unit Endocrinol, Casa Sollievo Sofferenza, Ist Ricovero & Cura Carattere Sci,Gen Hosp, I-71013 San Giovanni Rotondo, Foggia, Italy. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Chieti, Italy. RP Di Cerbo, A (reprint author), IRCCS, Div & Res Unit Endocrinol, Casa Sollievo Sofferenza, Ist Ricovero & Cura Carattere Sci,Gen Hosp, I-71013 San Giovanni Rotondo, Foggia, Italy. EM adicerb@tin.it RI Di Paola, Rosa/G-7813-2011; Corda, Daniela/K-6385-2016; OI Di Paola, Rosa/0000-0001-5837-9111; Corda, Daniela/0000-0002-3614-751X; Menzaghi, Claudia/0000-0002-7438-8955 NR 34 TC 12 Z9 12 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3283 EP 3292 DI 10.1210/jc.84.9.3283 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600046 PM 10487700 ER PT J AU Garg, A Wilson, R Barnes, R Arioglu, E Zaidi, Z Gurakan, F Kocak, N O'Rahilly, S Taylor, SI Patel, SB Bowcock, AM AF Garg, A Wilson, R Barnes, R Arioglu, E Zaidi, Z Gurakan, F Kocak, N O'Rahilly, S Taylor, SI Patel, SB Bowcock, AM TI A gene for congenital generalized lipodystrophy maps to human chromosome 9q34 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LINKAGE ANALYSIS; INSULIN-RESISTANCE; DIABETES-MELLITUS; ADIPOSE-TISSUE; RECEPTOR GENE; EXCLUSION; MUTATIONS; SIBLINGS; FAMILIES AB Congenital generalized lipodystrophy (CGL, Berardinelli-Seip Syndrome, OMIM # 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (theta(max) = 0.05). There was evidence for genetic heterogeneity (alpha = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL1 critical region harbors a plausible candidate gene encoding the retinoid X receptor alpha (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. Zinnah Postgrad Med Ctr, Dept Dermatol, Karachi, Pakistan. Hacettepe Univ, Fac Med, Dept Pediat, Gastroenterol Unit, TR-06100 Ankara, Turkey. Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. Univ Cambridge, Dept Clin Biochem, Cambridge CB2 2QQ, England. RP Garg, A (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM agarg@mednet.swmed.edu; bowcock@genetics.wustl.edu OI Oral, Elif/0000-0002-9171-1144; Patel, Shailendra/0000-0003-0046-5513 FU NCRR NIH HHS [M01-RR00633]; NIDDK NIH HHS [R01-DK54387] NR 28 TC 109 Z9 112 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3390 EP 3394 DI 10.1210/jc.84.9.3390 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600062 PM 10487716 ER PT J AU Torpy, DJ Chen, CC Mullen, N Doppman, JL Carrasquillo, JA Chrousos, GP Nieman, LK AF Torpy, DJ Chen, CC Mullen, N Doppman, JL Carrasquillo, JA Chrousos, GP Nieman, LK TI Primary localization of an ectopic ACTH-producing bronchial carcinoid tumor by indium (111)Pentetreotide scintigraphy - Authors' response SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Torpy, DJ (reprint author), NICH, HD, Dev Endocrinol Branch, Bldg 10,Room 10N262,10 Ctr Dr, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1999 VL 84 IS 9 BP 3402 EP 3403 DI 10.1210/jc.84.9.3402 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600068 ER PT J AU Howard, OMZ Oppenheim, JJ Wang, JM AF Howard, OMZ Oppenheim, JJ Wang, JM TI Chemokines as molecular targets for therapeutic intervention SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE chemokines; chemokine receptors; antagonists ID CHEMOATTRACTANT PROTEIN-1 MCP-1; MONOCYTE CHEMOTACTIC PROTEIN-1; TROPIC HIV-1 INFECTION; EPITHELIAL-CELLS; HUMAN NEUTROPHILS; AUTOIMMUNE ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; INTERLEUKIN-8 IL-8; PEPTIDE INHIBITOR; LIPOSOMAL HAMYCIN AB Despite the youth of the chemokine field, many antagonists of chemokine function have already been identified and tested at the preclinical level. These include neutralizing antibodies, peptidyl and non-peptidyl antagonists and non-specific immunosuppressive agents. These early studies suggest that chemokine agonists have the potential to regulate many diseases, ranging from HIV-1 infection and tumor growth to acute and chronic inflammation. Clinical application will depend on pharmaceutical development. Great strides have been made in defining structural domains of the chemokines involved in receptor binding and activation. The identification of receptors is rapidly progressing, but with 50 potential ligands and 15 characterized receptors, it is obvious that additional molecular studies are needed. The intriguing observation that several pathogens either use chemokine receptors as entry portals or produce chemokine decoys to subvert the immune system suggests that there is much to be learned about the immune system from studies of "virokines." Future studies should lead to the discovery and design of more effective inhibitors and antagonists with therapeutic benefit. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21701 USA. SAIC Frederick, IRSP, Frederick, MD USA. RP Howard, OMZ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21701 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000] NR 98 TC 40 Z9 40 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 1999 VL 19 IS 5 BP 280 EP 292 DI 10.1023/A:1020587407535 PG 13 WC Immunology SC Immunology GA 247FU UT WOS:000083211100005 PM 10535604 ER PT J AU Gavett, SH Madison, SL Chulada, PC Scarborough, PE Qu, W Boyle, JE Tiano, HF Lee, CA Langenbach, R Roggli, VL Zeldin, DC AF Gavett, SH Madison, SL Chulada, PC Scarborough, PE Qu, W Boyle, JE Tiano, HF Lee, CA Langenbach, R Roggli, VL Zeldin, DC TI Allergic lung responses are increased in prostaglandin H synthase-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ARACHIDONIC-ACID; INDUCED BRONCHOCONSTRICTION; AIRWAY RESPONSIVENESS; SELECTIVE-INHIBITION; RESPIRATORY SYSTEM; GENE DISRUPTION; IGE PRODUCTION; ASTHMA; INFLAMMATION; CYCLOOXYGENASE-2 AB To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1(-/-) and PGHS-2(-/-) mice. Among non-immunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE(2) was dramatically reduced in bronchoalveolar lava,ae (BAL) fluid from PGHS-1(-/-) mice, relative to wild-type or PGHS-2(-/-) mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1(-/-) mice compared with PGHS-2(-/-) mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1(-/-) and PGHS-2(-/-) mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1(-/-) mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE(2) in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE(2) in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2(-/-) mice. C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Expt Toxicol Div, Res Triangle Pk, NC 27711 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Zeldin, DC (reprint author), NIEHS, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 148 Z9 150 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1999 VL 104 IS 6 BP 721 EP 732 DI 10.1172/JCI6890 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WG UT WOS:000083468900009 PM 10491407 ER PT J AU Chiaramonte, MG Donaldson, DD Cheever, AW Wynn, TA AF Chiaramonte, MG Donaldson, DD Cheever, AW Wynn, TA TI An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MURINE SCHISTOSOMIASIS-MANSONI; GRANULOMA-FORMATION; MESSENGER-RNA; IFN-GAMMA; TH2 CELLS; INTERLEUKIN-13 RECEPTOR; IL-4-DEFICIENT MICE; INFECTED MICE; CYTOKINE; CLONING AB In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to tissue destruction and fibrosis, which causes much of the morbidity and mortality associated with this disease. Here we show the importance of IL-13 in the pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the therapeutic efficacy of an IL-13 inhibitor, sIL-13R alpha 2-Fc, in the control of hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in mice infected with Schistosoma mansoni, yet the specific contributions of IL-13 and IL-4 to the development of fibrosis were not previously investigated. Our studies demonstrate that both cytokines play redundant roles in granuloma formation, which explains the ability of IL-4-deficient mice to form granulomas around eggs. More importantly, however, these studies demonstrate that IL-13 is the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen production in fibroblasts, and procollagen I and procollagen III mRNA expression was decreased in sIL-13R alpha 2-Fc-treated mice. Moreover, the reduction in fibrosis observed in IL-4-deficient mice was much less pronounced than that in sIL-13R alpha 2-Fc-treated animals. Fibrosis is a major pathological manifestation of a number of allergic, autoimmune, and infectious diseases. Thus, our findings provide evidence that IL-13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory responses. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, Schistosomiasis Immunol & Pathol Unit,NIH, Bethesda, MD 20892 USA. Genet Inst, Cambridge, MA 01810 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, Schistosomiasis Immunol & Pathol Unit,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 44 TC 362 Z9 384 U1 2 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1999 VL 104 IS 6 BP 777 EP 785 DI 10.1172/JCI7325 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WG UT WOS:000083468900015 PM 10491413 ER PT J AU Weyer, C Bogardus, C Mott, DM Pratley, RE AF Weyer, C Bogardus, C Mott, DM Pratley, RE TI The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL DYSFUNCTION; BODY-FAT DISTRIBUTION; PIMA-INDIANS; FOLLOW-UP; RISK-FACTORS; INTRAVENOUS GLUCOSE; METABOLIC DEFECTS; NIDDM PARENTS; EARLY-PHASE AB The pathogenesis of type 2 diabetes involves abnormalities in insulin action, insulin secretion, and endogenous glucose output (EGO). However, the sequence with which these abnormalities develop and their relative contributions to the deterioration in glucose tolerance remain unclear in the absence of a detailed longitudinal study. We measured insulin action, insulin secretion, and EGO longitudinally in 17 Pima Indians, in whom glucose tolerance deteriorated from normal (NGT) to impaired (IGT) to diabetic over 5.1 +/- 1.4 years. Transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response (AIR) to intravenous glucose, but no change in EGO. Progression from IGT to diabetes was accompanied by a further increase in bodyweight, further decreases in insulin-stimulated glucose disposal and AIR, and an increase in basal EGO. Thirty-one subjects who retained NGT over a similar period also gained weight, but their AIR increased with decreasing insulin-stimulated glucose disposal. Thus, defects in insulin secretion and insulin action occur early in the pathogenesis of diabetes. Intervention to prevent diabetes should target both abnormalities. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. NR 65 TC 982 Z9 1036 U1 5 U2 57 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1999 VL 104 IS 6 BP 787 EP 794 DI 10.1172/JCI7231 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WG UT WOS:000083468900016 PM 10491414 ER PT J AU Glushakova, S Yi, YJ Grivel, JC Singh, A Schols, D De Clercq, E Collman, RG Margolis, L AF Glushakova, S Yi, YJ Grivel, JC Singh, A Schols, D De Clercq, E Collman, RG Margolis, L TI Preferential coreceptor utilization and cytopathicity by dual-tropic HIV-1 in human lymphoid tissue ex vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISEASE PROGRESSION; CC-CHEMOKINES; T-CELLS; INFECTION; AIDS; PHENOTYPE; STRAINS; CXCR4; ENTRY AB Many HIV-1 isolates at the late stage of disease are capable of using both CXCR4 and CCR5 in transfected cell lines, and are thus termed dual-tropic. Here we asked whether these dual-tropic variants also use both coreceptors for productive infection in a natural human lymphoid tissue microenvironment, and whether use of a particular coreceptor is associated with viral cytopathicity. We used 3 cloned dual-tropic HIV-1 variants, 89.6 and its chimeras 89-v345.SF and 89-v345.FL, which use both CCR5 and CXCR4 in transfected cell lines. In human lymphoid tissue ex vivo, one variant preferentially used CCR5, another preferentially used CXCR4, and a third appeared to be a true dual-tropic variant. The 2 latter variants severely depleted CD4(+)T cells, whereas cytopathicity of the virus that used CCR5 only in lymphoid tissue was mild and confined to CCR5(+)/CD4(+) T cells. Thus, (a) HIV-1 coreceptor usage in vitro cannot be unconditionally extrapolated to natural microenvironment of human lymphoid tissue; (b) dual-tropic viruses are not homogeneous in their coreceptor usage in lymphoid tissue, but probably comprise a continuum between the 2 polar variants that use CXCR4 or CCR5 exclusively; and (c) cytopathicity toward the general CD4(+) T cell population in lymphoid tissue is associated with the use of CXCR4. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NICHHD, Lab Mol & Cellular Biophys, NIH, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RP Collman, RG (reprint author), Univ Penn, Sch Med, 522 Johnson Pavil, Philadelphia, PA 19104 USA. EM collmanr@mail.med.upenn.edu; margolis@helix.nih.gov FU NHLBI NIH HHS [HL-58004]; NIAID NIH HHS [R01 AI035502, AI-35502] NR 30 TC 83 Z9 84 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1999 VL 104 IS 5 BP R7 EP R11 DI 10.1172/JCI7403 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WF UT WOS:000083468800017 PM 10487781 ER PT J AU Peruski, LF Kay, BA Abu El-Yazeed, R El-Etr, SH Cravioto, A Wierzba, TF Rao, M El-Ghorab, N Shaheen, H Khalil, SB Kamal, K Wasfy, MO Svennerholm, AM Clemens, JD Savarino, SJ AF Peruski, LF Kay, BA Abu El-Yazeed, R El-Etr, SH Cravioto, A Wierzba, TF Rao, M El-Ghorab, N Shaheen, H Khalil, SB Kamal, K Wasfy, MO Svennerholm, AM Clemens, JD Savarino, SJ TI Phenotypic diversity of enterotoxigenic Escherichia coli strains from a community-based study of pediatric diarrhea in Periurban Egypt SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COLONIZATION FACTOR ANTIGENS; MONOCLONAL-ANTIBODIES; B-SUBUNIT; CHILDREN; VACCINE; DISEASE; SEROTYPES; COUNTRIES; COHORT; HUMANS AB No past studies of diarrhea in children of the Middle East have examined in detail the phenotypes of enterotoxigenic Escherichia coli (ETEC) strains, which are important pathogens in this setting During a prospective study conducted from November 1993 to September 1995 with 242 children under 3 years of age with diarrhea living near Alexandria, Egypt, 125 episodes of diarrhea were positive for ETEC;ETEC strains were available for 98 of these episodes, from which 100 ETEC strains were selected and characterized on the basis of enterotoxins, colonization factors (CFs), and O:H serotypes. Of these representative isolates, 57 produced heat-stable toxin (ST) only, 34 produced heat-labile toxin (LT) only, and 9 produced both LT and ST. Twenty-three ETEC strains expressed a CF, with the specific factors being CF antigen TV (CFA/IV; 10 of 23; 43%), CFA/II (5 of 23; 22%), CFA/I (3 of 23; 13%), PCFO166 (3 of 23; 13%), and CS7(2 of 23; 9%). No ETEC strains appeared to express CFA/III, CS17, or PCFO159. Among the 100 ETEC strains, 47 O groups and 20 H groups were represented, with 59 O:H serotypes. The most common O serogroups were O159 (13 strains) and O43 (10 strains). O148 and O21 were each detected in five individual strains, O7 and O56 were each detected in four individual strains, O73, O20, O86, and O114 were each detected in three individual strains, and O23, O78, O91, O103, O128, and O132 were each detected in two individual strains. The most common H serogroups were H4 (16 strains), 12 of which were of serogroup O159; H2 (9 strains), all of which were O43; H18 (6 strains); H30 (6 strains); and H28 (5 strains); strains of the last three H serogroups were all O148. Cumulatively, our results suggest a high degree of clonal diversity of disease-associated ETEC strains in this region. As a low percentage of these strains expressed a CF,it-remains possible that other adhesins for which we either did not assay or that are as yet undiscovered are prevalent in this region. Our findings point out some potential barriers to effective immunization against ETEC diarrhea in this population and emphasize the need to identify additional protective antigens commonly expressed by ETEC for inclusion in future vaccine candidates. C1 USN, Med Res Unit 3, Cairo, Egypt. Univ Nacl Autonoma Mexico, Fac Med, Mexico City 04510, DF, Mexico. NICHHD, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Med Microbiol & Immunol, Gothenburg, Sweden. RP Peruski, LF (reprint author), USN, Med Res Unit 3, PSC 452,Box 5000, FPO, AE 09835 USA. FU NICHD NIH HHS [Y1-HD-0026-01] NR 44 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1999 VL 37 IS 9 BP 2974 EP 2978 PG 5 WC Microbiology SC Microbiology GA 226TV UT WOS:000082038900040 PM 10449484 ER PT J AU Fedorko, DP Engler, HD O'Shaughnessy, EM Williams, EC Reichelderfer, CJ Smith, WI AF Fedorko, DP Engler, HD O'Shaughnessy, EM Williams, EC Reichelderfer, CJ Smith, WI TI Evaluation of two rapid assays for detection of Clostridium difficile toxin A in steal specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MULTICENTER EVALUATION; DIARRHEA; DIAGNOSIS; CULTURE; STRAIN AB Rapid laboratory diagnosis of Clostridium difficile-associated diarrhea (CDAD) is highly desirable in the setting of hospital cost containment. We tested 654 stool specimens to compare the performance of two assays for rapid detection of toxin A, the Immunocard Toxin A test (Meridian Diagnostics, Inc.) and the Culturette Brand Toxin CD enzyme immunoassay (EIA) (Becton Dickinson Microbiology Systems), with a cytotoxin assay (Cytotoxi Test; Advanced Clinical Diagnostics) and culture on cycloserine-cefoxitin-fructose agar followed by determination of the production of toxins A and B. A chart review was performed for patients whose stool specimens provided positive results on one to three of the assays. With the "gold standard" of all four assays positive or chart review evidence of CDAD, 97 (14.8%) stool specimens were positive by one or more assays and 557 (85.2%) were negative by all methods. Total agreement for all assays was 90.5% (592 of 654). The sensitivity, specificity, positive predictive value, and negative predictive value for toxigenic culture were 94.7, 98.6, 87.1, and 99.5%, respectively, for toxigenic culture; 87.7, 98.6, 86.2, and 98.8%, respectively, for the cytotoxin assay; 71.9, 99.3, 91.1, and 97.3%, respectively, for the Immunocard; and 68.4, 99.1, 88.6, and 96.9%, respectively, for the Culturette EIA. While easy to perform and highly specific, these rapid assays do not appear to be sufficient for accurate diagnosis of CDAD. C1 NIH, Microbiol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Suburban Hosp, Dept Clin Pathol, Bethesda, MD 20814 USA. RP Fedorko, DP (reprint author), NIH, Microbiol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 2C385,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 23 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1999 VL 37 IS 9 BP 3044 EP 3047 PG 4 WC Microbiology SC Microbiology GA 226TV UT WOS:000082038900059 PM 10449503 ER PT J AU Wandinger, KP Trillenberg, P Kluter, H Wessel, K Kirchner, H AF Wandinger, KP Trillenberg, P Kluter, H Wessel, K Kirchner, H TI Clinical and molecular findings in multiple sclerosis patients with type 1 diabetes mellitus SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE multiple sclerosis; diabetes mellitus; genetic susceptibility; HLA-DR; HLA-DQ ID ASSOCIATION; DISEASES AB The clinical and molecular findings in three patients with multiple sclerosis (MS) and additional type 1 diabetes mellitus are described. These patients all presented with a severe and progressive disease course of MS. Molecular testing for HLA class II genes demonstrated the presence of the haplotype DRB1*0401, DQB1*0302 in all patients. This haplotype is closely linked to type 1 diabetes mellitus and is increased among patients with the primary progressive subtype of MS. We conclude that the immunogenetic background in patients with diabetes mellitus may determine the severity and clinical course of MS in these individuals. (C) 1999 Harcourt Publishers Ltd. C1 Univ Lubeck, Sch Med, Inst Immunol & Transfus Med, D-23538 Lubeck, Germany. Univ Lubeck, Sch Med, Dept Neurol, D-23538 Lubeck, Germany. RP Wandinger, KP (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. NR 10 TC 5 Z9 5 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 1999 VL 6 IS 5 BP 373 EP 374 DI 10.1016/S0967-5868(99)90027-9 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 247VB UT WOS:000083240600002 ER PT J AU Day, R Ganz, PA Costantino, JP Cronin, WM Wickerham, DL Fisher, B AF Day, R Ganz, PA Costantino, JP Cronin, WM Wickerham, DL Fisher, B TI Health-related quality of life and tamoxifen in breast cancer prevention: A report from the National Surgical Adjuvant Breast and Bowel Project P-1 study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECEPTOR-POSITIVE TUMORS; POSTMENOPAUSAL WOMEN; ENDOMETRIAL CANCER; TRIAL; DEPRESSION; SYMPTOMS AB Purpose: This is the initial report from the health-related quality of life (HRQL) component of the National Surgical Adjuvant Breast and Bowel project Breast Cancer Prevention Trial. This report provides an overview of HRQL findings, comparing tamoxifen and placebo groups, and advice to clinicians counseling women about the use of tamoxifen in a prevention setting. Patients and Methods: This report covers the baseline and the first 36 months of follow-up data on 11,064 women recruited over the first 24 months of the study Findings are presented from the Center for Epidemiological Studies-Depression Scale (CES-D), the Medical Outcomes Study 36-item Short Form Health Status Survey (MOS SF-36) and sexual functioning scale, and a symptom checklist. Results: No differences were found between placebo and tamoxifen groups for the proportion of participants scoring above a clinically significant level on the CES-D, No differences were found between groups for the MOS SF-36 summary physical and mental scores. The mean number of symptoms reported was consistently higher in the tamoxifen group and was associated with vasomotor and gynecologic symptoms. Significant increases were found in the proportion of women on tamoxifen reporting problems of sexual functioning at a definite or serious level, although overall rates of sexual activity remained similar. Conclusion: Women need to be informed of the increased frequency of vasomotor and gynecologic symptoms and problems of sexual functioning associated with tamoxifen use. Weight gain and depression, two clinical problems anecdotally associated with tamoxifen treatment, were not increased in frequency in this trial in healthy women, which is good news that also needs to be communicated. (C) 1999 by Americcn Society of Clinical Oncology. C1 Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Day, R (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, 130 DeSoto St, Pittsburgh, PA 15261 USA. FU NCI NIH HHS [NCI-U10-CA-69974, NCI-U10-CA-37377] NR 25 TC 283 Z9 287 U1 1 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1999 VL 17 IS 9 BP 2659 EP 2669 PG 11 WC Oncology SC Oncology GA 232QG UT WOS:000082381000006 PM 10561339 ER PT J AU Peters, AA Oger, JJF Coulthart, MB Waters, DJ Cummings, HJ Dekaban, GA AF Peters, AA Oger, JJF Coulthart, MB Waters, DJ Cummings, HJ Dekaban, GA TI An apparent case of human T-cell lymphotropic virus type II (HTLV-II)-associated neurological disease: a clinical, molecular, and phylogenetic characterisation SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HTLV-II; phylogenetic tree; neurological disease; ataxia; myelopathy ID TROPICAL SPASTIC PARAPARESIS; INTRAVENOUS-DRUG-USERS; HTLV-II; NUCLEOTIDE-SEQUENCE; SEXUAL TRANSMISSION; SUBTYPE-B; INFECTION; LEUKEMIA; PATIENT; MYELOPATHY AB Several studies have reported an association between HTLV-II and a neurological condition which has come to be called HTLV-II-associated myelopathy and is similar, in some cases, to HTLV-I-associated myelopathy. To further explore the establishment of an etiological link between this virus and neurological disease, we determined the HTLV status of three individuals, one of which presented with symptoms of progressive ataxia. Since the patient with neurological disease and her husband were HTLV-II positive, we had the potential to study one of few cases of an HTLV-II-associated neurological disorder, and the first case in Canada. However, although the individual with the neurological disease was HTLV-II positive, we discovered that her brother, who displays the same clinical symptoms, was not positive for either HTLV-II or HTLV-I. Thus, disease association with HTLV-II became unsupportable. We present here, nevertheless, the first sequence and phylogenetic analysis of an HTLV-II isolate in Canada. This study suggests that cases of HTLV-II and neurological disease must be carefully investigated before any etiological conclusions can be made. (C) 1999 Elsevier Science B.V. All rights reserved. C1 John P Robarts Res Inst, Gene Therapy & Mol Virol Grp, London, ON N6A 5K8, Canada. Univ Western Ontario, Dept Microbiol & Immunol, London, ON, Canada. Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC, Canada. Hlth Canada, Fed Labs, Bur Microbiol, Winnipeg, MB, Canada. NCI, NIH, Frederick, MD 21701 USA. RP Dekaban, GA (reprint author), John P Robarts Res Inst, Gene Therapy & Mol Virol Grp, Rm 2-12,100 Perth Dr, London, ON N6A 5K8, Canada. RI Dekaban, Gregory/L-1987-2013 OI Dekaban, Gregory/0000-0002-3087-4660 NR 54 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD SEP PY 1999 VL 14 IS 1 BP 37 EP 50 DI 10.1016/S1386-6532(99)00041-4 PG 14 WC Virology SC Virology GA 247YP UT WOS:000083248800006 PM 10548129 ER PT J AU Zeh, H Choyke, PL Alexander, HR Bartlett, DL Libutti, SK Chang, R Summers, RM AF Zeh, H Choyke, PL Alexander, HR Bartlett, DL Libutti, SK Chang, R Summers, RM TI Gadolinium-enhanced 3D MRA prior to isolated hepatic perfusion for metastases SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE magnetic resonance angiography; liver, blood supply; liver, anatomy; liver ID MAGNETIC-RESONANCE ANGIOGRAPHY; COLORECTAL LIVER METASTASES; MANAGEMENT STRATEGIES; AORTA; TRANSPLANTATION; ACQUISITION; MELPHALAN; ARRIVAL; CANCER; ORDER AB Purpose: Isolated hepatic perfusion (IHP) is a new treatment for patients with isolated unresectable liver metastases, which can result in a partial or complete response in similar to 75% of patients. Preoperative knowledge of hepatic arterial anatomy is important to adequately perfuse the liver. Digital subtraction angiography (DSA) is currently used to identify the hepatic arterial anatomy. The purpose of this study was to determine if MR angiography (MRA) could replace DSA prior to IHP. Method: Twenty-seven patients scheduled to undergo MP underwent MRA with a contrast-enhanced 3D time-of-flight gradient echo sequence. Both maximal intensity projections (MIPs) and source coronal images were used to evaluate thr images. The results of the MRA were interpreted by two readers who were blinded to the surgical results. The first 17 patients also underwent DSA, and a separate comparison was made with those results. Anatomy was characterized as either normal hepatic arteries (NHAs), normal vasculature with an accessory left hepatic artery (aLHA), or a replaced right hepatic artery (rRHA). Results: MRA correctly detected all 22 patients with NHAs but also identified aLHAs, of which only 2 were confirmed surgically. MRA correctly detected all five rRHAs. MIP images alone accurately depicted the hepatic arterial anatomy in only 9 of 27 (33%), usually because significant vessels were not visualized or their origin could not be determined. Source coronal images were required to accurately determine the anatomy in all patients. Among the 17 patients who underwent DSA, MRA detected 14 of 14 with NHA and 3 of 3 with rRHA. Six aLHAs were identified by MRA and five were confirmed by DSA. Conclusion: Enhanced 3D MRA is an accurate method of depicting the hepatic arterial supply. In comparison to surgery, MRA overestimates thr number of aLHAs, but this may be because these small vessels are not detected at surgery. Based on the results of this study, DSA has been replaced by MRA in the planning of IHP at our institution. A better display of MRA images is needed as MIP images were usually insensitive for the small caliber arteries supplying the liver. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NIH, Dept Radiol, Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. NR 22 TC 13 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1999 VL 23 IS 5 BP 664 EP 669 DI 10.1097/00004728-199909000-00003 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 241LR UT WOS:000082885200003 PM 10524842 ER PT J AU Marrogi, AJ Khan, MA Vonderheid, EC Wood, GS McBurney, E AF Marrogi, AJ Khan, MA Vonderheid, EC Wood, GS McBurney, E TI p53 tumor suppressor gene mutations in transformed cutaneous T-cell lymphoma: A study of 12 cases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; BREAST-CANCER; PROTEIN EXPRESSION; LUNG-CANCER; PROGNOSIS; C-ERBB-2; ADENOCARCINOMA; OVEREXPRESSION AB The transformation of cutaneous T-cell lymphoma (t-CTCL) is an uncommon phenomenon that is associated with histopathologic changes and follows an aggressive course. The factors contributing to this transformation are poorly understood. The aim of this study was to analyze the p53 status in t-CTCL and to correlate it with disease outcome. The p53 status was investigated by immunohistochemistry, single-strand conformation polymorphism (SSCP) and DNA sequencing in 12 patients with t-CTCL. Eight mutations were detected; including four in exon 5, one in exon 6 and three in exon 7. Five were point mutations and three were deletions. Paired samples from nontransformed patch and plaque lesions showed no p53 over-expression. Eight disease-related deaths were reported, six to 23 months after transformation, all of which had p53 mutations. Three other patients with wild phenotype (WT-p53) were last reported alive with the disease 19-33 months after transformation (p<0.0002). One other case had a p53 mutation but a short period of follow-up. Our results suggest that phenotypic changes of t-CTCL are frequently associated with genotype alterations in the p53 gene. Because 70% of the mutations detected were either G to C transversions or deletions, nucleotide-pairing mismatch and not DNA damage by UVB represents a likely mechanism for mutagenesis. Furthermore, the data may help in the design of gene transfer therapies that target the p53 molecule. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Sch Med, Dept Surg, New Orleans, LA 70112 USA. Louisiana State Univ, Sch Med, Dept Dermatol, New Orleans, LA 70112 USA. Allegheny Sch Med, Dept Dermatol, Pittsburgh, PA USA. VA Med Ctr, Dept Dermatol, Cleveland, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Marrogi, AJ (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Rm 2D 14, Bethesda, MD 20892 USA. FU NCI NIH HHS [R21-CA75201]; PHS HHS [P30-39750] NR 68 TC 25 Z9 25 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD SEP PY 1999 VL 26 IS 8 BP 369 EP 378 DI 10.1111/j.1600-0560.1999.tb01860.x PG 10 WC Dermatology; Pathology SC Dermatology; Pathology GA 247JD UT WOS:000083216900001 PM 10551408 ER PT J AU Hayman, JR Nash, TE AF Hayman, JR Nash, TE TI Isolating expressed microsporidial genes using a cDNA subtractive hybridization approach SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 5th International Workshop on Opportunistic Protists CY 1997 CL LILLE, FRANCE C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hayman, JR (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1999 VL 46 IS 5 BP 21S EP 24S PG 4 WC Microbiology SC Microbiology GA 242TZ UT WOS:000082958900024 PM 10519231 ER PT J AU Lasbury, ME Angus, CW Klivington, D Durant, PJ Bartlett, MS Smith, JW Lee, CH AF Lasbury, ME Angus, CW Klivington, D Durant, PJ Bartlett, MS Smith, JW Lee, CH TI Recombinant major surface glycoprotein of Pneumocystis carinii elicits a specific immune response but is not protective in immunosuppressed rats. SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 5th International Workshop on Opportunistic Protists CY 1997 CL LILLE, FRANCE ID IMMUNIZATION; EXPRESSION; MICE C1 Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Lasbury, ME (reprint author), Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1999 VL 46 IS 5 BP 136S EP 137S PG 2 WC Microbiology SC Microbiology GA 242TZ UT WOS:000082958900082 PM 10519289 ER PT J AU Jimenez, N Calvo, A Martinez, A Rosell, D Cuttitta, F Montuenga, LM AF Jimenez, N Calvo, A Martinez, A Rosell, D Cuttitta, F Montuenga, LM TI Expression of adrenomedullin and proadrenomedullin N-terminal 20 peptide in human and rat prostate SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE adrenomedullin; proadrenomedullin N-terminal 20 peptide; adrenomedullin receptor; prostate; immunocytochemistry; in situ hybridization; RT-PCR; Western blot ID GENE-RELATED PEPTIDE; HYPOTENSIVE PEPTIDE; REGIONAL VARIATION; PULMONARY TUMORS; DUCTAL SYSTEM; HUMAN LUNG; CELLS; RECEPTOR; CLONING; PHEOCHROMOCYTOMA AB Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two recently discovered hypotensive peptides translated from the same message transcript (preproAM mRNA). In this article we report the presence of AM, PAMP, and their mRNA in human and rat prostate and of AM receptor mRNA in rat prostate. PreproAM mRNA was found in the epithelium of normal human and rat prostate glands by in situ hybridization. In humans, it was mainly expressed in the basal cells. In rat, its expression was higher in the ducts than in the acini of all the prostate lobes. Immunocytochemistry identified a similar distribution pattern for AM compared with its mRNA but showed different locations for AM and PAMP immunoreactivity. The former was widespread in the epithelial whereas the latter was almost exclusively found in neuroendocrine cells. In rat, Western blot analysis confirmed the presence of high levels of AM peptide in the ventral robe and of its precursor in the ventral and dorsolateral robes. Immunoreactivity for serotonin, chromogranin A, PAMP, and AM defined four subpopulations of prostate neuroendocrine-like cells in rat, a cell type that has not been previously described. C1 Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. Univ Navarra, Dept Urol, E-31080 Pamplona, Spain. RP Calvo, A (reprint author), Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. RI Martinez, Alfredo/A-3077-2013; Jimenez, Nuria/C-6374-2012 OI Martinez, Alfredo/0000-0003-4882-4044; NR 40 TC 38 Z9 38 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1999 VL 47 IS 9 BP 1167 EP 1177 PG 11 WC Cell Biology SC Cell Biology GA 230EP UT WOS:000082239100009 PM 10449538 ER PT J AU Owais, M Arya, SK AF Owais, M Arya, SK TI Antiviral chemokines: Intracellular life of recombinant C-C chemokine RANTES SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE chemokines; HIV; mutational analysis; lentiviral vector ID SMALL-MOLECULE INHIBITOR; LONG TERMINAL REPEAT; HIV-1 ENTRY; RECEPTOR CXCR4; ENDOPLASMIC-RETICULUM; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; T-CELLS; CCR5; CORECEPTOR AB Objective: Select C-C and C-X-C chemokines can suppress HN infection. This is because their receptors are the gateways for HIV-1 entry, determinants of viral tropism and sensitivity. C-C chemokines are most effective against macrophage-tropic viruses, and C-X-C chemokines are most effective against T-tropic viruses. The epitopes on the chemokine molecule responsible for virus inhibition and for chemokines' specificities are not known. The objective of this study was to map the functional domains of prototypic antiviral chemokine, namely, RANTES (regulated-on-activation normal T-expressed and secreted). Study Design: Optimal folding of the chemokine molecule is thought to be important for its biologic activity. Anticipating that it will provide a native milieu for folding, we expressed recombinant RANTES molecules in an HIV-2-derived lentivirus mammalian expression system. We focused on the structural landmarks of RANTES to determine their role in its life and function. Results: We found that the flexible amino-terminal region of RANTES was not important for its structural integrity or antiviral activity, either positively or negatively. It was also not important for binding to the CCR5 receptor. Modification of all other domains was detrimental, implying a functional role. However, a more careful analysis revealed that these domains were crucial for controlling stability, transport, and secretion of the molecule. Although all recombinant clones contained signal sequence and were transcriptionally active, they presented three different phenotypes: normal synthesis and secretion, normal synthesis but blocked secretion, and presumed normal synthesis but rapid degradation. Structural considerations and preliminary experiments showing a lack of effect of proteasome inhibitors suggested that the signal recognition particle pathway of translocation and proteasomal pathway of destruction may not be the major determinant of the life of the chemokine. Conclusions: The amino-terminal domain of RANTES was not essential for its antiviral activity of for its binding to the CCR5 receptor. Although the I-domain of the core and carboxyterminal domain may contribute to the antiviral activity of RANTES, they were more important for its intracellular life. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Arya, SK (reprint author), NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NR 56 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD SEP-OCT PY 1999 VL 2 IS 5 BP 270 EP 282 PG 13 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 246ND UT WOS:000083169100002 PM 10551733 ER PT J AU Zhang, J Siraganian, RP AF Zhang, J Siraganian, RP TI CD45 is essential for Fc epsilon RI signaling by ZAP70, but not Syk, in Syk-negative mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; AFFINITY IGE RECEPTOR; LEUKOCYTE-COMMON ANTIGEN; SRC FAMILY KINASES; MONOCLONAL-ANTIBODIES; MEDIATED DEGRANULATION; HISTAMINE-RELEASE; GENETIC-EVIDENCE; RBL-2H3 CELLS; SH2 DOMAINS AB The ZAP70/Syk family of protein tyrosine kinases plays an important role in Ag receptor signaling. Structural similarity of Syk and ZAP70 suggests their functional overlap. Previously, it was observed that expression of either ZAP70 or Syk reconstitutes Ag receptor signaling in Syk-negative B cells. However, in CD45-deficient T cells, Syk, but not ZAP70, restores cell receptor-signaling pathway. To study the function of Syk, ZAP70, and CD45 in mast cells, a Syk/CD45 double-deficient variant of RBL-2H3 cells was characterized. After transfection, stable cell lines were isolated that expressed ZAP70, Syk, CD45, ZAP70 plus CD45, and Syk plus CD45. IgE stimulation did not induce degranulation in parental double-deficient cells, nor in the cells expressing only CD45, ZAP70 expression did not restore Fc epsilon RI signaling unless CD45 was coexpressed in the cells. However, Syk alone restored the IgE signal transduction pathway. The coexpression of CD45 with Syk had no significant effects on the responses to Fc epsilon RI-aggregation. There was much better binding of Syk than ZAP70 to the phosphorylated Fc epsilon RI gamma-ITAM. Furthermore, unlike Syk, ZAP70 required CD45 to display receptor-induced increase in kinase activity. Therefore, in mast cells, ZAP70, but not Syk, requires CD45 for Ag receptor-induced signaling. C1 NIDCR, RAST Sect, OIIB, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NIDCR, RAST Sect, OIIB, NIH, Bldg 10,Room 1N106, Bethesda, MD 20892 USA. NR 58 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2508 EP 2516 PG 9 WC Immunology SC Immunology GA 228FA UT WOS:000082125400023 PM 10452987 ER PT J AU Simonsen, A Pedersen, KW Nordeng, TW von der Lippe, A Stang, E Long, EO Bakke, O AF Simonsen, A Pedersen, KW Nordeng, TW von der Lippe, A Stang, E Long, EO Bakke, O TI Polarized transport of MHC class II molecules in Madin-Darby canine kidney cells is directed by a leucine-based signal in the cytoplasmic tail of the beta-chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-LYMPHOBLASTOID-CELLS; HLA-DR MOLECULES; INVARIANT CHAIN; ANTIGEN PRESENTATION; EPITHELIAL-CELLS; MDCK CELLS; INTRACELLULAR-TRANSPORT; SUBCELLULAR-LOCALIZATION; ENDOCYTIC COMPARTMENTS; RAPID INTERNALIZATION AB MBC class II molecules are found on the basolateral plasma membrane domain of polarized epithelial cells, where they can present Ag to intraepithelial lymphocytes in the vascular space. We have analyzed the sorting information required for efficient intracellular localization and polarized distribution of MHC class II molecules in stably transfected Madin-Darby canine kidney cells. These cells were able to present influenza virus particles to HLA-DR1-restricted T cell clones, Wild-type MHC class II molecules were located on the basolateral plasma membrane domain, in basolateral early endosomes, and in late multivesicular endosomes, the latter also containing the MHC class II-associated invariant chain and an HLA-DM fusion protein, A phenylalanine-leucine residue within the cytoplasmic tail of the P-chain was required for basolateral distribution, efficient internalization, and localization of the MHC class LI molecules to basolateral early endosomes, However, distribution to apically located, late multivesicular endosomes did not depend on signals in the class Il cytoplasmic tails as both wild-type class II molecules and mutant molecules lacking the phenylalanine-leucine moth were found in these compartments, Our results demonstrate that sorting information in the tails of class II diners is an absolute requirement for their basolateral surface distribution and intracellular localization. C1 Univ Oslo, Dept Biol, Oslo, Norway. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bakke, O (reprint author), POB 1050, N-0316 Oslo, Norway. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 66 TC 15 Z9 16 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2540 EP 2548 PG 9 WC Immunology SC Immunology GA 228FA UT WOS:000082125400027 PM 10452991 ER PT J AU Ito, D Back, TC Shakhov, AN Wiltrout, RH Nedospasov, SA AF Ito, D Back, TC Shakhov, AN Wiltrout, RH Nedospasov, SA TI Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: Impaired NK cell development and recruitment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; NECROSIS-FACTOR-ALPHA; BETA-DEFICIENT MICE; T-CELL; MEDIATED CYTOTOXICITY; ABNORMAL-DEVELOPMENT; SURFACE LYMPHOTOXIN; LYMPHOID-TISSUES; INTERFERON-GAMMA; B-LYMPHOCYTES AB Mice deficient in lymphotoxin (LT)-alpha lack peripheral lymph nodes and Peyer's patches and have profound defects in development of follicular dendritic cell networks, germinal center formation, and T/B cell segregation in the spleen. Although LT alpha is known to be expressed by NK cells as well as T and B lymphocytes, the requirement of LT alpha for NK cell functions is largely unknown. To address this issue, we have assessed NK cell functions in LT alpha-deficient mice by evaluating tumor models with known requirements for NK cells to control their growth and metastasis, Syngeneic B16F10 melanoma cells inoculated s.c. grew more rapidly in LT alpha(-/-) mice than in the wild-type littermates, and the formation of experimental pulmonary metastases was significantly enhanced in LT alpha(-/-) mice. Although LT alpha(-/-) mice exhibited almost a normal total number of NK cells in spleen, they showed an impaired recruitment of NK cells to lung and liver. Additionally, lytic NK cells were not efficiently produced from LT alpha(-/-) bone marrow cells in vitro in the presence of IL-2 and IL-15, These data suggest that LT alpha signaling may be involved in the maturation and recruitment of NK cells and may play an important role in antitumor surveillance. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 117984, Russia. Belozersky Inst Physicochem Biol, Moscow, Russia. RP Nedospasov, SA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 31-33, Frederick, MD 21702 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU NCI NIH HHS [N01-CO-56000] NR 54 TC 48 Z9 48 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2809 EP 2815 PG 7 WC Immunology SC Immunology GA 228FA UT WOS:000082125400061 PM 10453025 ER PT J AU Devouassoux, G Metcalfe, DD Prussin, C AF Devouassoux, G Metcalfe, DD Prussin, C TI Eotaxin potentiates antigen-dependent basophil IL-4 production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CCR3; HUMAN BLOOD BASOPHILS; C-C CHEMOKINES; EOSINOPHIL RECRUITMENT; EXPRESSION; CELLS; INFLAMMATION; RELEASE; IDENTIFICATION; HISTAMINE AB Basophils are a major source of IL-4, which is a critical factor in the generation of allergic inflammation. Eotaxin induces chemotaxis mediated through the CC chemokine receptor 3 (CCR3) present on basophils as well as eosinophils and Th2 cells, thereby promoting cell recruitment, To determine whether eotaxin has other proinflammatory activity, we examined the effect of eotaxin on basophil IL-4 expression by flow cytometry, Eotaxin alone had no effect on basophil IL-4 production, but further increased allergen-stimulated IL-4 expression, Eotaxin also enhanced IL-4 release from purified basophils 2- to 4-fold, as determined by ELISA (p < 0.01), Addition of eotaxin to cultures resulted ina 40-fold left shift in the dose response to Ag. This effect was obtained with physiologic concentrations of eotaxin (10 ng/ml), was abrogated by an Ab to the CCR3 receptor, and was noted with other chemokine ligands of CCR3. Additionally, eotaxin augmented IL-3 priming of basophil IL-4 production in a synergistic manner (p < 0.01), In contrast, no priming was observed with either IL-5 or GM-CSF. These results establish a novel function for eotaxin and other chemokine ligands of CCR3: the potentiation of Ag-mediated IL-4 production in basophils, and suggest a potential nonchemotactic role for CC chemokines in the pathogenesis and amplification of inflammation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. OI Prussin, Calman/0000-0002-3917-3326 FU NIAID NIH HHS [ZO1-AI-00709-05 LAD] NR 31 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2877 EP 2882 PG 6 WC Immunology SC Immunology GA 228FA UT WOS:000082125400070 PM 10453034 ER PT J AU Weiss, JM Nath, A Major, EO Berman, JW AF Weiss, JM Nath, A Major, EO Berman, JW TI HIV-1 Tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood-brain barrier and up-regulates CCR5 expression on human monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HUMAN ENDOTHELIAL-CELLS; NF-KAPPA-B; CYTOKINE EXPRESSION; AIDS DEMENTIA; T-CELLS; ASTROCYTES; PROTEIN; INDUCTION; INFECTION AB AIDS dementia is characterized by neuronal loss in association with synaptic damage. A central predictor for clinical onset of these symptoms is the infiltration of monocytes and macrophages into CNS parenchyma, Chronic HIV-1 infection of monocytes also allows these cells to serve as reservoirs for persistent viral infection. Using a coculture of endothelial cells and astrocytes that models several aspects of the human blood-brain barrier, we examined the mechanism whereby the HIV-derived factor Tat may facilitate monocyte transmigration. We demonstrate that treatment of cocultures on the astrocyte side with HIV-1 Tat induced significant monocyte chemoattractant protein (MCP)-1 protein. Astrocytes, but not endothelial cells, were the source of this MCP-1 expression. Supernatants from Tat-treated cocultures induced significant monocyte transmigration, which was detected by 2.5 h after the addition of PBMC, Pretreatment of the supernatants from Tat-stimulated cocultures with an Ab to MCP-1 completely blocked monocyte transmigration. Flow cytometric analysis of Tat-stimulated PBMC demonstrated that Tat upregulated expression of the chemokine receptor, CCR5, on monocytes in a time-dependent manner. Taken together, our data indicate that HIV-1 Tat may facilitate the recruitment of monocytes into the CNS by inducing MCP-1 expression in astrocytes. These recruited monocytes may contribute to the pathogenesis of HIV-l-associated AIDS encephalitis and dementia. C1 Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Immunol Microbiol, Bronx, NY 10461 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. Univ Kentucky, Dept Microbiol, Lexington, KY 40536 USA. Univ Kentucky, Dept Immunol, Lexington, KY 40536 USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Berman, JW (reprint author), Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. FU NCI NIH HHS [5T32-CA09173]; NIMH NIH HHS [MH52974]; PHS HHS [NIH 11920] NR 46 TC 190 Z9 199 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2953 EP 2959 PG 7 WC Immunology SC Immunology GA 228FA UT WOS:000082125400080 PM 10453044 ER PT J AU Fritz, RS Hayden, FG Calfee, DP Cass, LMR Peng, AW Alvord, WG Strober, W Straus, SE AF Fritz, RS Hayden, FG Calfee, DP Cass, LMR Peng, AW Alvord, WG Strober, W Straus, SE TI Nasal cytokine and chemokine responses in experimental influenza A virus infection: Results of a placebo-controlled trial of intravenous zanamivir treatment SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 24-28, 1998 CL SAN DIEGO, CALIFORNIA ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; CHEMOTACTIC CYTOKINES; EPITHELIAL-CELLS; HOST-DEFENSE; MICE; EXPRESSION; MONOCYTE; MIP-1-ALPHA; RECRUITMENT; EFFICACY AB The local immune response to influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers experimentally infected with influenza A/Texas136/91 (H1N1), The study was Dart of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 2 x /day for 5 days), a highly selective inhibitor of influenza A and B virus neuraminidases, on the clinical symptoms of influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-alpha, interferon-gamma, IL-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 alpha and -1 beta increased in response to influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of influenza. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Sci Applicat Int Corp, Data Management Serv, Frederick, MD USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. GlaxoWellcome, Greenford, Middx, England. GlaxoWellcome, Res Triangle Pk, NC USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [CO-56000] NR 27 TC 127 Z9 135 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 586 EP 593 DI 10.1086/314938 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300003 PM 10438343 ER PT J AU LeBlanc, RA Pesnicak, L Godleski, M Straus, SE AF LeBlanc, RA Pesnicak, L Godleski, M Straus, SE TI The comparative effects of famciclovir and valacyclovir on herpes simplex virus type 1 infection, latency, and reactivation in mice SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CELL-MEDIATED-IMMUNITY; GENITAL HERPES; PHARMACOKINETIC PROPERTIES; ANTIVIRAL ACTIVITY; VALACICLOVIR; NEURONS; MODEL; PENCICLOVIR; NUMBER; PATHOGENESIS AB Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, famciclovir and valacyclovir, were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1), Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same. Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences. C1 NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), 10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. NR 29 TC 27 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 594 EP 599 DI 10.1086/314962 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300004 PM 10438344 ER PT J AU Lockett, SF Alonso, A Wyld, R Martin, MP Robertson, JR Gore, SM Leen, CLS Brettle, RP Yirrell, DL Carrington, M Brown, AJL AF Lockett, SF Alonso, A Wyld, R Martin, MP Robertson, JR Gore, SM Leen, CLS Brettle, RP Yirrell, DL Carrington, M Brown, AJL TI Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS ID HIV-1 INFECTION; DISEASE PROGRESSION; GENETIC RESTRICTION; DELETION ALLELE; RISK FACTOR; CCR5; TYPE-1; AIDS; INDIVIDUALS; CCR5-DELTA-32 AB To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped, A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P = .02, relative risk = 1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P <.02), At CCR-5, no difference in the frequency of Delta 32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs, Combining the analysis of the Delta 32 and 64I mutations in index partners suggested an additive effect on transmission (P =.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta 32 at CCR-5 has no detectable effect. C1 Univ Edinburgh, Inst Cell Anim & Populat Biol, Ctr HIV Res, Edinburgh EH9 3JN, Midlothian, Scotland. Univ Edinburgh, Muirhouse Med Grp, Edinburgh Drug Addict Study, Edinburgh EH9 3JN, Midlothian, Scotland. Univ Edinburgh, Dept Gen Practice, Edinburgh EH9 3JN, Midlothian, Scotland. City Hosp Edinburgh, Reg Infect Dis Unit, Edinburgh EH10 5SB, Midlothian, Scotland. Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Brown, AJL (reprint author), Univ Edinburgh, Inst Cell Anim & Populat Biol, Ctr HIV Res, Waddington Bldg,W Mains Rd, Edinburgh EH9 3JN, Midlothian, Scotland. RI Leigh Brown, Andrew/F-3802-2010 FU NCI NIH HHS [CO-56000] NR 39 TC 14 Z9 15 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 614 EP 620 DI 10.1086/314918 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300007 PM 10438347 ER PT J AU Sei, S Sandelli, SL Theofan, G Ratto-Kim, S Kumagai, M Loomis-Price, LD Cox, JH Jarosinski, P Walsek, CM Brouwers, P Venzon, DJ Xu, J Pizzo, PA Moss, RB Robb, ML Wood, LV AF Sei, S Sandelli, SL Theofan, G Ratto-Kim, S Kumagai, M Loomis-Price, LD Cox, JH Jarosinski, P Walsek, CM Brouwers, P Venzon, DJ Xu, J Pizzo, PA Moss, RB Robb, ML Wood, LV TI Preliminary evaluation of human immunodeficiency virus type 1 (HIV-1) immunogen in children with HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Pediatric AIDS CY MAR, 1997 CL THAILAND ID PNEUMOCYSTIS-CARINII PNEUMONIA; DELAYED-TYPE HYPERSENSITIVITY; POLYMERASE CHAIN-REACTION; ENVELOPE SUBUNIT VACCINE; VIRAL LOAD; ANTIRETROVIRAL THERAPY; RECOMBINANT GP160; CUBIC MILLIMETER; IN-VITRO; NONCYTOLYTIC MECHANISMS AB The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1-infected children with disease stage N1,2 or A1,2, Multiple inoculations of 2.5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log(10) HIV-1 RNA at month is, 3.07 vs. 4.01 copies/mL in 10 U [n = 4] vs. 2.5 U [n = 3], respectively; P =.034). Levels of regulated-on-activation, normal T cell-expressed and -secreted chemokine produced from HIV-1 immunogen-stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen-specific antibody responses (P <.02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P<.01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection. C1 NCI, HIV Clin Interface Lab, SAIC Frederick, FCRDC,NIH, Frederick, MD 21702 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. Henry M Jackson Fdn, HIV Lab, Rockville, MD USA. Walter Reed Army Inst Res, Dept Retrovirol, Rockville, MD USA. Immune Response Corp, Carlsbad, CA USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. RP Sei, S (reprint author), NCI, HIV Clin Interface Lab, SAIC Frederick, FCRDC,NIH, Bldg 322,Rm 27B, Frederick, MD 21702 USA. RI Venzon, David/B-3078-2008 NR 75 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 626 EP 640 DI 10.1086/314944 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300009 PM 10438349 ER PT J AU Sterling, TR Lyles, CM Vlahov, D Astemborski, J Margolick, JB Quinn, TC AF Sterling, TR Lyles, CM Vlahov, D Astemborski, J Margolick, JB Quinn, TC TI Sex differences in longitudinal human immunodeficiency virus type 1 RNA levels among seroconverters SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND ID INTRAVENOUS-DRUG-USERS; PLASMA VIRAL LOAD; HIV-1 INFECTION; IMMUNE-RESPONSE; NATURAL-HISTORY; SERUM LEVELS; AIDS; PROGRESSION; RECOMMENDATIONS; LYMPHOCYTES AB Cross-sectional studies have demonstrated lower plasma human immunodeficiency virus type 1 (HIV-1) RNA virus levels (VLs) in women than in men, but it is unknown whether this sex difference is present at the lime of seroconversion and throughout the course of infection. A nested case-control study was performed among HIV-1 seroconverters within a cohort of injection drug users. Plasma VL was determined longitudinally among both rapid progressors to AIDS (24 patients) and nonprogressors (47 controls). The initial median VL among female patients (n = 10) was 14,918 copies/mL, compared with 148,354 copies/mL among male patients (n = 14; P =.001); median plasma VL also tended to be lower among female (n = 10) than among male controls (n = 37; 11,917 vs. 61,311 copies/mL; P = .08), VL increased more rapidly over time in women than in men and subsequently converged in patients and controls, respectively. Understanding the mechanisms responsible for the sex difference in VL may provide insight into HIV-1 pathogenesis. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. RP Sterling, TR (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 1830 E Monument St,Room 444, Baltimore, MD 21287 USA. FU NIDA NIH HHS [DA-05830, DA-04334, DA-08009] NR 37 TC 104 Z9 107 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 666 EP 672 DI 10.1086/314967 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300013 PM 10438353 ER PT J AU Soldan, SS Graf, MD Waziri, A Flerlage, AN Robinson, SM Kawanishi, T Leist, TP Lehky, TJ Levin, MC Jacobson, S AF Soldan, SS Graf, MD Waziri, A Flerlage, AN Robinson, SM Kawanishi, T Leist, TP Lehky, TJ Levin, MC Jacobson, S TI HTLV-I/II seroindeterminate Western blot reactivity in a cohort of patients with neurological disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th International Conference on Human Retrovirology, HTLV, and Related Viruses CY APR 05-09, 1999 CL KAGOSHIMA, JAPAN ID VIRUS TYPE-I; CYTOTOXIC LYMPHOCYTES-T; SPASTIC PARAPARESIS; PLASMODIUM-FALCIPARUM; CEREBROSPINAL-FLUID; CROSS-REACTIVITY; CELL LEUKEMIA; TRANSFUSION; ANTIBODIES; MYELOPATHY AB The human T-cell lymphotropic virus type I(HTLV-I) is associated with a chronic, progressive neurological disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis, Screening for HTLV-I involves the detection of virus-specific serum antibodies by EIA and confirmation by Western blot. HTLV-I/II seroindeterminate Western blot patterns have been described worldwide. However, the significance of this blot pattern is unclear. We identified 8 patients with neurological disease and an HTLV-I/II seroindeterminate Western blot pattern, none of whom demonstrated increased spontaneous proliferation and HTLVI-specific cytotoxic T lymphocyte activity. However, HTLV-I tax sequence was amplified from the peripheral blood lymphocytes of 4 of them. These data suggest that patients with chronic progressive neurological disease and HTLV-I/II Western blot seroindeterminate reactivity may harbor either defective HTLV-I, novel retrovirus with partial homology to HTLV-I, or HTLVI in low copy number. C1 NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. George Washington Univ, Dept Genet, Inst Biomed Sci, Washington, DC USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. NR 31 TC 11 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 685 EP 694 DI 10.1086/314923 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300015 PM 10438355 ER PT J AU Maloney, EM Armien, B Gracia, F Castillo, L Kruger, H Levin, A Levine, PH Kaplan, JE Blattner, WA Giusti, RM AF Maloney, EM Armien, B Gracia, F Castillo, L Kruger, H Levin, A Levine, PH Kaplan, JE Blattner, WA Giusti, RM TI Risk factors for human T cell lymphotropic virus type II infection among the Guaymi Indians of Panama SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th International Conference on Human Retrovirology, HTLV CY JUN 09-13, 1997 CL RIO JANEIRO, BRAZIL ID HTLV-II; SEXUAL TRANSMISSION; DRUG-USERS AB To examine risk factors for human T cell lymphotropic virus type II (HTLV-II) infection, a case-control study was conducted among the Guaymi Indians of Panama. In females, HTLV-II seropositivity was associated with early sexual intercourse (less than or equal to 13 vs. >15 years; odds ratio [OR], 2.50; 95% confidence interval [CI], 1.11-6.14) and number of lifetime sex partners. One partner increased risk of seropositivity by 30% (OR, 1.30; CI, 1.05-1.64), and risk increased with number of partners. Similar risk was associated with number of long-term sexual relationships. Among males, intercourse with prostitutes was associated with HTLV-II seropositivity (OR, 1.68; CI, 1.04-2.72). These data support a role for sexual transmission in HTLV-II infection. Association of seropositivity with primary residence in a traditional village (OR, 3.75; CI, 1.02-15.38) and lack of formal education (0 vs. >6 years [OR, 3.89; CI, 1.67-9.82]) observed in males may reflect differences in sexual practices associated with acculturation. C1 NCI, Viral Epidemiol Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Conmemorativo Gorgas, HTLV Project, Panama City, Panama. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Maloney, EM (reprint author), NCI, Viral Epidemiol Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Eexcut Plaza N,Room 434,6130 Execut Blvd,MSC 7399, Bethesda, MD 20892 USA. FU NCI NIH HHS [CP-33005] NR 8 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 876 EP 879 DI 10.1086/314916 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300044 PM 10438384 ER PT J AU Kadidal, VV Mayo, DJ Horne, MK AF Kadidal, VV Mayo, DJ Horne, MK TI Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE heparin; thrombocytopenia ID DIAGNOSIS; PATIENT AB Three cases of heparin-induced thrombocytopenia (HIT) are reported that were provoked by daily heparin flushes of central venous access devices. Each case had confounding features that delayed recognition of the problem. A review of the literature revealed only 29 previously reported cases of HIT secondary to heparin flushes. However, the true incidence of this problem is unknown. A high index of suspicion and confirmatory laboratory tests are necessary to make the diagnosis. C1 NIH, Hematol Serv, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 46 Z9 47 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD SEP PY 1999 VL 246 IS 3 BP 325 EP 329 DI 10.1046/j.1365-2796.1999.00527.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 239RQ UT WOS:000082783800012 PM 10476001 ER PT J AU Malinda, KM Sidhu, GS Mani, H Banaudha, K Maheshwari, RK Goldstein, AL Kleinman, HK AF Malinda, KM Sidhu, GS Mani, H Banaudha, K Maheshwari, RK Goldstein, AL Kleinman, HK TI Thymosin beta 4 accelerates wound healing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiogenesis; migrations; reepithelialization; thymic peptides ID DEOXYNUCLEOTIDYL TRANSFERASE-ACTIVITY; DIFFERENTIAL EXPRESSION; ANGIOGENIC ACTIVITY; GROWTH-FACTOR; LIVING CELLS; ACTIN; BETA(4); GENE; LYMPHOCYTES; MIGRATION AB Angiogenesis is an essential. step in the repair process that occurs after injury. In this study, we investigated whether the angiogenic thymic peptide thymosin beta 4 (T beta 4) enhanced wound healing in a rat full thickness wound model. Addition of T beta 4 topically or intraperitoneally increased reepithelialization by 42% over saline controls at 4 d and by as much as 61% at 7 d post-wounding. Treated wounds also contracted at least 11% more than controls by day 7. Increased collagen deposition and angiogenesis were observed in the treated wounds. We also found that T beta 4 stimulated keratinocyte migration in the Boyden chamber assay. After 4-5 h, migration was stimulated 2-3-fold over migration with medium alone when as little as 10 pg of T beta 4 was added to the assay. These results suggest that T beta 4 is a potent wound healing factor with multiple activities that may be useful in the clinic. C1 Natl Inst Dent & Craniofacial Res, Dev Biol Lab, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. USUHS, Ctr Combat Casualty & Life Sustainment Res, Dept Pathol, Bethesda, MD USA. George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC USA. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, Dev Biol Lab, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 407,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. NR 30 TC 198 Z9 209 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 BP 364 EP 368 DI 10.1046/j.1523-1747.1999.00708.x PG 5 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000012 PM 10469335 ER PT J AU Vogel, JC AF Vogel, JC TI Transduction of human keratinocytes with a lentiviral vector SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 085 BP 445 EP 445 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000110 ER PT J AU Homey, B Morales, J Wiesenborn, A Assmann, T Vicari, AP Hudak, S Hedrick, J Orozco, R Copeland, NG Jenkins, NA Ruzicka, T Lehmann, P McEvoy, LM Zlotnik, A AF Homey, B Morales, J Wiesenborn, A Assmann, T Vicari, AP Hudak, S Hedrick, J Orozco, R Copeland, NG Jenkins, NA Ruzicka, T Lehmann, P McEvoy, LM Zlotnik, A TI CTACK. A skin-specific chemokine that preferentially attracts skin-homing T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunobiol, Palo Alto, CA 94304 USA. Univ Dusseldorf, Dept Dermatol, D-4000 Dusseldorf, Germany. Schering Plough, Lab Immunol Res, Dardilly, France. Schering Plough Res Inst, Human Genome Res, Kenilworth, NJ USA. Inst Nacl Nutr, Mexico City, DF, Mexico. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 093 BP 446 EP 446 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000117 ER PT J AU Zillikens, D Leverkus, M Lazarova, Z Schmidt, E Brocker, EB Yancey, KB AF Zillikens, D Leverkus, M Lazarova, Z Schmidt, E Brocker, EB Yancey, KB TI Anti-epiligrin (Laminin 5) cicatricial pemphigoid (AECP): An underdiagnosed entity within the group of scarring autoimmune bullous diseases SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Wurzburg, Dept Dermatol, D-8700 Wurzburg, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 104 BP 448 EP 448 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000131 ER PT J AU Jakob, T Vassel, R Udey, MC Scharton-Kersten, T Alving, CR Glenn, GM AF Jakob, T Vassel, R Udey, MC Scharton-Kersten, T Alving, CR Glenn, GM TI Activation of Langerhans cells following transcutaneous immunization SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Tech Univ Munich, Dept Dermatol, D-8000 Munich, Germany. NCI, Dermatol Branch, Bethesda, MD USA. Iomai Corp, Walter Reed Army Inst Res, Washington, DC USA. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 260 BP 474 EP 474 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000285 ER PT J AU von Stebut, E Udey, M AF von Stebut, E Udey, M TI Interactions of murine dendritic cells with Leishmania major SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 270 BP 475 EP 475 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000293 ER PT J AU Nielsen, MB Marincola, FM AF Nielsen, MB Marincola, FM TI Molecular basis for the implementation of antigen-specific anti-melanoma vaccines SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 030 BP 516 EP 516 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000492 ER PT J AU Hearing, VJ AF Hearing, VJ TI Biochemical control of melanogenesis and melanosomal organization SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 47th Montagna Annual Symposium on the Biology of Skin CY AUG 19-23, 1998 CL SNOWMASS, COLORADO SP Orentrich Fdn, Natl Psoriasis Fdn DE melanin; melanoma; photoabsorption; pigmentation ID ULTRAVIOLET-IRRADIATION; MELANIN; COLOR; GENES; SKIN; PIGMENTATION; PATHWAYS; GENETICS; PHEOMELANOGENESIS; DIFFERENTIATION AB Current knowledge on the regulation of mammalian pigmentation at the genetic and biochemical level, and constituents that participate in melanosomal organization, is summarized. Approximately 25% of the more than 80 genes known to regulate pigmentation in mammals have been cloned and characterized to date. Almost half of those encode proteins that localize, either specifically or nonspecifically, to melanosomes; mutations in those genes generally lead to phenotypic changes in pigmentation as well as in other pleiotropic changes. The expression and function of these proteins not only affects phenotypic appearance, but also the properties of melanins, especially their photoprotective characteristics. Because many of those melanosomal proteins also serve as melanoma-specific targets, regulation of their expression has dramatic implications for immune targeting of malignant melanoma. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. NR 52 TC 133 Z9 144 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 1999 VL 4 IS 1 BP 24 EP 28 DI 10.1038/sj.jidsp.5640176 PG 5 WC Dermatology SC Dermatology GA 267GA UT WOS:000084348400006 PM 10537003 ER PT J AU Suzuki, I Im, SB Tada, A Scott, C Akcali, C Davis, MB Barsh, G Hearing, V Abdel-Malek, Z AF Suzuki, I Im, SB Tada, A Scott, C Akcali, C Davis, MB Barsh, G Hearing, V Abdel-Malek, Z TI Participation of the melanocortin-1 receptor in the UV control of pigmentation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 47th Montagna Annual Symposium on the Biology of Skin CY AUG 19-23, 1998 CL SNOWMASS, COLORADO SP Orentrich Fdn, Natl Psoriasis Fdn DE melanocortin-1 receptor (MC1R); alpha-melanocyte stimulating hormone (alpha-MSH); adrenocorticotropic hormone (ACTH); melanocytes; ultraviolet radiation (UVR); eumelanin; MC1R variants ID MELANOCYTE-STIMULATING-HORMONE; PROOPIOMELANOCORTIN-DERIVED PEPTIDES; CULTURED HUMAN MELANOCYTES; AGOUTI-SIGNALING PROTEIN; PROGRAMMED CELL-DEATH; HUMAN KERATINOCYTES; MOLECULAR-CLONING; ULTRAVIOLET-B; MSH-RECEPTOR; HUMAN EPIDERMIS AB The cloning of the melanocortin-1 receptor (MC1R) gene from human melanocytes and the demonstration that these cells respond to the melanocortins alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) with increased proliferation and melanogenesis have renewed the interest in investigation the physiological role of these hormones in regulating human pigmentation. alpha-Melanocyte stimulating hormone and ACTH are both synthesized in the human epidermis, and their synthesis is upregulated by exposure to ultraviolet radiation (UVR). Activation of the MC1R by ligand binding results in stimulation of cAMP formation, which is a principal mechanism for inducing melanogenesis. The increase in cAMP is required for the pigmentary response of human melanocytes to UVR, and for allowing them to overcome the UVR-induced G1. arrest. Treatment of human melanocytes with alpha-MSH increases eumelanin synthesis, an effect that is expected to enhance photoprotection of the skin. Population studies have revealed more than 20 allelic variants of the MC1R gene. Some of these variants are overexpressed in individuals with skin type I or II, red hair, and poor tanning ability, Future studies will aim at further exploration of the role of these variants in MC1R function, and in determining constitutive human pigmentation, the response to sun exposure, and possibly the susceptibility to skin cancer. C1 Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH 45267 USA. POLA Labs, Yokohama, Kanagawa, Japan. Ajou Univ, Dept Dermatol, Suwon 441749, South Korea. Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Genet, Stanford, CA 94305 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Abdel-Malek, Z (reprint author), Univ Cincinnati, Coll Med, Dept Dermatol, POB 670592, Cincinnati, OH 45267 USA. FU NIEHS NIH HHS [R01 ES 06882, R01 ES 09110] NR 94 TC 26 Z9 27 U1 2 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 1999 VL 4 IS 1 BP 29 EP 34 DI 10.1038/sj.jidsp.5640177 PG 6 WC Dermatology SC Dermatology GA 267GA UT WOS:000084348400007 PM 10537004 ER PT J AU Funasaka, Y Sato, H Chakraborty, AK Ohashi, A Chrousos, GP Ichihashi, M AF Funasaka, Y Sato, H Chakraborty, AK Ohashi, A Chrousos, GP Ichihashi, M TI Expression of proopiomelanocortin, corticotropin-releasing hormone (CRH), and CRH receptor in melanoma cells, nevus cells, and normal human melanocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd Annual Meeting of the Dematology Forum for Basic Research and Treatment CY AUG 01, 1998 CL SAPPORO, JAPAN DE immunohistochemistry; PT-PCR ID FACTOR (CRF)-LIKE IMMUNOREACTIVITY; CUTANEOUS MALIGNANT-MELANOMA; STIMULATING-HORMONE; ULTRAVIOLET-B; C-KIT; MURINE MELANOMA; HUMAN SKIN; ALPHA; GENE; RAT AB Proopiomelanocortin (POMC) is a 31 kDa prohormone that is processed to various bioactive peptides, including adrenocorticotropin (ACTH), melanotropins (alpha, beta, gamma-MSH), lipotropins, and endorphins, POMC is expressed not only in the pituitary gland but also in a variety of nonpituitary organs and tumors, including melanomas. We previously showed that normal human melanocytes produce and secrete alpha-MSH and ACTH, and furthermore, that advanced melanoma cells generally produce higher amounts of POMC peptides that correlate with tumor progression. To elucidate the mechanism of this upregulation, the expression of genes encoding corticotropin-releasing hormone (CRH) and its receptor, CRH-R, as well as POMC and the MSH receptor (MC1-R), was evaluated by reverse transcriptase-polymerase chain reaction using cultured human melanoma cells, nevus cells, and normal melanocytes, Our results show that all melanocytic cells express CRH, CRH-R, POMC, and MC1-R, with highest intensities in melanoma cells. Furthermore, immunohistochemistry shows that CRH as well as POMC is strongly expressed in advanced melanomas, such as vertically growing lesions of acral lentiginous, nodular and metastatic melanomas, in contrast to negative expression in nevus cells. These results indicate that tumor progression accentuates CRH, CRH-R, and POMC expression by melanoma cells. C1 Kobe Univ, Sch Med, Dept Dermatol, Chuo Ku, Kobe, Hyogo 6500017, Japan. Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Funasaka, Y (reprint author), Kobe Univ, Sch Med, Dept Dermatol, Chuo Ku, 5-1 Kusunoki Cho 7-Chome, Kobe, Hyogo 6500017, Japan. NR 48 TC 37 Z9 39 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 1999 VL 4 IS 2 BP 105 EP 109 DI 10.1038/sj.jidsp.5640192 PG 5 WC Dermatology SC Dermatology GA 267GB UT WOS:000084348500003 PM 10536983 ER PT J AU Ortaldo, JR Mason, AT Winkler-Pickett, R Raziuddin, A Murphy, WJ Mason, LH AF Ortaldo, JR Mason, AT Winkler-Pickett, R Raziuddin, A Murphy, WJ Mason, LH TI Ly-49 receptor expression and functional analysis in multiple mouse strains SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE flow cytometry analysis; natural killer; Ly-49; tyrosine phosphorylation ID NATURAL-KILLER-CELLS; BONE-MARROW ALLOGRAFTS; NK CELLS; TYROSINE PHOSPHORYLATION; ACTIVATING RECEPTORS; MULTIGENE FAMILY; T-CELLS; REJECTION; MICE; SPECIFICITY AB We present data on the strain distribution and functional characteristics of the Ly-49 receptors A, C/I, D, and G2 on DX5(+) natural killer (NK) cells. We have examined tyrosine phosphorylation of the Ly-49 molecules, regulation of NIC cytotoxic functions, and in vivo marrow rejection capability. The Row cytometry results demonstrate a diverse and complex pattern of expression of the Ly-49 receptors in the 11 strains examined. The vast majority of NK cells express Ly-49s, although some NK1.1(+) CD3(+) cells also express these receptors, The results of our functional analysis indicate that H-2D(d) was able to inhibit the function of Ly-49G2(+) NIC cells, not only in B6 mice, but also by NK cells derived from several haplotypes, The examination of Ly-49 receptor tyrosine phosphorylation, which is a biochemical measure of inhibitory function, was consistently observed in the 11 mouse strains examined. In contrast, analysis of Ly-49D function suggests its expression appears to be more restricted and that H-2D(d) is an activating ligand for this receptor, In addition, the in vivo examination of both inhibitory (Ly-49G2) and activating (Ly-49D) receptors demonstrated regulatory roles of these class I binding receptors in marrow transplantation. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. RP Ortaldo, JR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Bldg 560,Rm 31-93, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 31 TC 47 Z9 47 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1999 VL 66 IS 3 BP 512 EP 520 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 236JH UT WOS:000082596100020 PM 10496323 ER PT J AU Boedeker, JC Doolittle, M Santamarina-Fojo, S White, AL AF Boedeker, JC Doolittle, M Santamarina-Fojo, S White, AL TI Role of N-linked carbohydrate processing and calnexin in human hepatic lipase secretion SO JOURNAL OF LIPID RESEARCH LA English DT Article DE chaperone; endoplasmic reticulum; ER glucosidase; Lec23 cells; Lec1 cells ID LIPOPROTEIN-LIPASE; TRIGLYCERIDE LIPASE; ENDOPLASMIC-RETICULUM; DENSITY-LIPOPROTEIN; POSTHEPARIN PLASMA; CATALYTIC ACTIVITY; HDL CHOLESTEROL; BINDING-PROTEIN; RAT HEPATOCYTES; CDNA SEQUENCE AB The addition and endoplasmic reticulum (ER) glucosidase processing of N-linked glycans is essential for the secretion of rat hepatic lipase (HL), Human HL is distinct from rat HL by the presence of four as opposed to two N-linked carbohydrate side chains. We examined the role of N-linked glycosylation and calnexin interaction in human HL secretion from Chinese hamster ovary (CHO) cells stably expressing a human HL cDNA, Steady-state and pulse-chase labeling experiments established that human HL was synthesized as an ER-associated precursor containing high mannose N-linked glycans, Secreted HL had a molecular mass of similar to 65 kDa and contained mature N-linked sugars, Inhibition of N-linked glycosylation with tunicamycin (TM) prevented secretion of HL enzyme activity and protein mass. in contrast, incubation of cells with the ER glucosidase inhibitor, castanospermine (CST), decreased human HL protein secretion by 60%, but allowed 40% of fully active HL to be secreted, HL protein mass and enzyme activity were also recovered from the media of a CHO-derivative cell line genetically deficient in ER glucosidase I activity (Lec23) that was transiently transfected with a human HL cDNA, Co-immunoprecipitation experiments demonstrated that newly synthesized human HL bound to the lectin-like ER chaperone, calnexin, and that this interaction was inhibited by TM and CST. These results suggest that under normal conditions calnexin may increase the efficiency of HL expert from the ER. Whereas a significant proportion of human HL can attain activity and become secreted in the absence of glucose trimming and calnexin association, these interrelated processes are nevertheless essential for the expression of full HL activity. C1 Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP White, AL (reprint author), Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. FU NCRR NIH HHS [MO-IRR00663]; NHLBI NIH HHS [HL28481] NR 45 TC 11 Z9 11 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 1999 VL 40 IS 9 BP 1627 EP 1635 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233MF UT WOS:000082430100008 PM 10484609 ER PT J AU Aletras, AH Balaban, RS Wen, H AF Aletras, AH Balaban, RS Wen, H TI High-resolution strain analysis of the human heart with fast-DENSE SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE cardiac; function; DENSE; STEAM; tagging; phase contrast; stimulated echoes; fast-DENSE; heart; PC; stimulated echo ID PHASE-CONTRAST; MOTION; MRI; TRACKING; DEFORMATION; WALL AB Single breath-hold displacement data from the human heart were acquired with fast-DENSE (fast displacement encoding with stimulated echoes) during systolic contraction at 2.5 x 2.5 mm in-plane resolution. Encoding strengths of 0.86-1.60 mm/pi were utilized in order to extend the dynamic range of the phase measurements and minimize effects of physiologic and instrument noise. The noise level in strain measurements for both contraction and dilation corresponded to a strain value of 2.8%. In the human heart, strain analysis has sufficient resolution to reveal transmural variation across the left ventricular wall. Data processing required minimal user intervention and provided a rapid quantitative feedback. The intrinsic temporal integration of fast-DENSE achieves high accuracy at the expense of temporal resolution. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010; OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997; Aletras, Anthony/0000-0002-3786-3817 NR 24 TC 81 Z9 81 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 1999 VL 140 IS 1 BP 41 EP 57 DI 10.1006/jmre.1999.1821 PG 17 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 238GZ UT WOS:000082703700005 PM 10479548 ER PT J AU Slavotinek, A Shaffer, LG Shapira, SK AF Slavotinek, A Shaffer, LG Shapira, SK TI Monosomy 1p36 SO JOURNAL OF MEDICAL GENETICS LA English DT Review DE monosomy 1p36; contiguous gene deletion syndrome ID N-MYC AMPLIFICATION; RECIPROCAL TRANSLOCATION; PARTIAL DUPLICATION; TERMINAL DELETION; CHROMOSOME 1P; DISTAL 1P; NEUROBLASTOMA; PATIENT; REGION; CONFIRMATION AB We have reviewed published reports on patients with segmental aneusomy for chromosome 1p36 to help geneticists and other health professionals in the recognition of this emerging chromosomal syndrome. Terminal deletions of the short arm of chromosome 1 are associated with hypotonia and developmental delay (usually severe), growth abnormalities (growth retardation, microcephaly, obesity), and craniofacial dysmorphism with a large anterior fontanelle, prominent forehead, deep set eyes, flat nasal bridge and midface hypoplasia, ear asymmetry, a pointed chin, and orofacial clefting. Minor cardiac malformations, cardiomyopathy, seizures, and ventricular dilatation are the more common additional findings. Sensorineural hearing loss and variable ophthalmological anomalies have also been frequently observed. Although the deletions can be detected by high resolution cytogenetic studies, confirmation by fluorescence in situ hybridisation is required in most cases. The majority of deletions are maternally derived. Molecular characterisation of 1p36 deletions has been undertaken in several cases, and it is likely that this condition is a contiguous gene deletion syndrome. C1 Univ Manchester, St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Univ Manchester, St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Slavotinek, A (reprint author), Natl Human Genome Res Inst, NIH, Bldg 49,Room 4B75,49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA. NR 50 TC 109 Z9 111 U1 0 U2 6 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 1999 VL 36 IS 9 BP 657 EP 663 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 238FE UT WOS:000082699600001 PM 10507720 ER PT J AU Strickler, HD Viscidi, R Escoffery, C Rattray, C Kotloff, KL Goldberg, J Manns, A Rabkin, C Daniel, R Hanchard, B Brown, C Hutchinson, M Zanizer, D Palefsky, J Burk, RD Cranston, B Clayman, B Shah, KV AF Strickler, HD Viscidi, R Escoffery, C Rattray, C Kotloff, KL Goldberg, J Manns, A Rabkin, C Daniel, R Hanchard, B Brown, C Hutchinson, M Zanizer, D Palefsky, J Burk, RD Cranston, B Clayman, B Shah, KV TI Adeno-associated virus and development of cervical neoplasia SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE adeno-associated virus; AAV; cervical cancer; CIN; human papillomavirus; HPV ID HUMAN PAPILLOMAVIRUS TYPE-16; ADENOASSOCIATED VIRUS; HERPES-SIMPLEX; BOVINE PAPILLOMAVIRUS; DNA; ANTIBODIES; PARVOVIRUS; PREVALENCE; CANCER; CELLS AB Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells. (C) 1999 Wiley-Liss, Inc. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ W Indies, Kingston 7, Jamaica. Univ Maryland, Baltimore, MD 21201 USA. Women & Infants Hosp, Providence, RI USA. Cytyc Corp, Marlborough, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Strickler, HD (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, 1300 Morris Pk Ave,Belfer Bldg,Rm 1308-B, Bronx, NY 10461 USA. RI kotloff, karen/E-7768-2012 OI kotloff, karen/0000-0003-1808-6431 NR 23 TC 24 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 1999 VL 59 IS 1 BP 60 EP 65 DI 10.1002/(SICI)1096-9071(199909)59:1<60::AID-JMV10>3.0.CO;2-8 PG 6 WC Virology SC Virology GA 221QW UT WOS:000081738600010 PM 10440809 ER PT J AU Tremper, KE Gershfeld, NL AF Tremper, KE Gershfeld, NL TI Temperature dependence of membrane lipid composition in early blastula embryos of Lytechinus pictus: Selective sorting of phospholipids into nascent plasma membranes SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article ID AIR-WATER-INTERFACE; SURFACE BILAYERS; STATE AB Lytechinus pictus eggs were fertilized and incubated at 10, 16, and 23 degrees C until the early blastula stage of embryonic development. The phospholipid composition of the embryos and control unfertilized eggs remain identical and unchanged as incubating temperatures are varied; thus, neither incubating temperature, fertilization nor membrane assembly affect their total phospholipid composition. This result agrees with metabolic studies by others, using only a single incubation temperature, and indicates that embryonic development to the early blastula stage occurs with little, if any, de novo phospholipid biosynthesis. However, as in all poikilotherms, the phospholipid composition of the nascent plasma membranes varies with the incubation temperature. Thus, until the blastula stage of embryonic development, the lipids of these newly formed plasma membranes are derived from lipid pools within the embryo whose phospholipid composition is static. The variation of plasma membrane composition is primarily reflected in an increase in the phosphatidylethanolamine (PE): phosphatidylcholine (PC) ratio as incubating temperatures decrease; this is achieved by an exchange of PE for PC. Several mechanisms are considered for the specificity of the selective sorting and assembly of these phospholipids into the nascent plasma membranes. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gershfeld, NL (reprint author), NIAMSD, Phys Biol Lab, NIH, Bldg 6,Room 139, Bethesda, MD 20892 USA. NR 28 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP 1 PY 1999 VL 171 IS 1 BP 47 EP 53 DI 10.1007/s002329900557 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 233PD UT WOS:000082434500004 PM 10485993 ER PT J AU Wang, RF AF Wang, RF TI Human tumor antigens: implications for cancer vaccine development SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE melanoma; T cell recognition; major histocompatibility complex immunotherapy; epitopes ID CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA ANTIGEN; TYROSINASE-RELATED PROTEIN-2; BETA-CATENIN GENE; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; DIFFERENTIATION ANTIGEN; HLA-A2 MELANOMAS; BREAST-CANCER; REJECTION ANTIGEN AB The adoptive transfer of tumor-infiltrating lymphocytes along with interleukin 2 into autologous patients resulted in the objective regression of tumor in about 30% of patients with melanoma, indicating that these T cells play a role in tumor rejection. To understand the molecular basis of the T cell-cancer cell interaction we and others started to search for tumor antigens expressed on cancer cells recognized by T cells. This led to the identification of several major histocompatibility complex (MHC) class I restricted tumor antigens. These tumor antigens have been classified into several categories: tissue-specific differentiation antigens, tumor-specific shared antigens, and tumor-specific unique antigens. Because CD4(+) T cells play a central role in orchestrating the host immune response against cancer, infectious diseases, and autoimmune diseases, a novel genetic approach has recently been developed to identify these MHC class II restricted tumor antigens. The identification of both MHC class I and II restricted tumor antigens provides new opportunities for the development of therapeutic strategies against cancer. This review summarizes the current status of tumor antigens and their potential applications to cancer treatment. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Wang, RF (reprint author), NCI, NIH, Bldg 10-2B42, Bethesda, MD 20892 USA. NR 170 TC 45 Z9 45 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 1999 VL 77 IS 9 BP 640 EP 655 DI 10.1007/s001099900042 PG 16 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 247DV UT WOS:000083206100002 PM 10569202 ER PT J AU Jones, TH Flournoy, RC Torres, JA Snelling, RR Spande, TF Garraffo, HM AF Jones, TH Flournoy, RC Torres, JA Snelling, RR Spande, TF Garraffo, HM TI 3-Methyl-4-phenylpyrrole from the Ants Anochetus kempfi and Anochetus mayri SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB The cephalic extracts of the ant Anochetus kempfi were found to contain 2,5-dimethyl-3-isoamylpyrazine (1) and 3-methyl-4-phenylpyrrole (2). The structures of these compounds were established from their spectral data and by comparison with synthetic samples. This is the first report of a phenylpyrrole found in an insect and only the third report of a pyrrole from ants. C1 Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. CUTB, Dept Biol, Bayamon, PR 00959 USA. Los Angeles Cty Museum Nat Hist, Los Angeles, CA 90007 USA. US Forest Serv, IITF, Rio Piedras, PR 00928 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jones, TH (reprint author), Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 1999 VL 62 IS 9 BP 1343 EP 1345 DI 10.1021/np990245t PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 241YE UT WOS:000082910800035 PM 10514333 ER PT J AU Rubio, ME Wenthold, RJ AF Rubio, ME Wenthold, RJ TI Calnexin and the immunoglobulin binding protein (BiP) coimmunoprecipitate with AMPA receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glutamate receptor; immunocytochemistry; endoplasmic reticulum; molecular chaperone ID SMOOTH ENDOPLASMIC-RETICULUM; DELTA-GLUTAMATE RECEPTORS; CELL-SURFACE EXPRESSION; RAT-BRAIN; ACETYLCHOLINE-RECEPTOR; HIPPOCAMPAL-NEURONS; POSTSYNAPTIC DENSITY; SECRETORY PATHWAY; PURKINJE NEURONS; QUALITY-CONTROL AB To identify proteins that interact with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, we carried out coimmunoprecipitation analyses on detergent-solubilized rat forebrain membranes. Membranes were solubilized with Triton X-100, and immunoprecipitation was done using subunit-specific antibodies to G1uR1, GluR2/3, and GluR4 attached to protein A-agarose. Proteins bound to the antibodies were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining and western blotting. With solubilization in low ionic strength buffer, several coimmunoprecipitating proteins, with M-r = 17,000-100,000, were identified in silver-stained gels. Western blots were then probed with antibodies to a series of candidate proteins that were chosen based on the molecular masses of the copurifying proteins. Two of these were identified as the molecular chaperones calnexin (90 kDa) and the immunoglobulin binding protein (BiP; 78 kDa). Immunoprecipitation with antibodies to calnexin and BiP demonstrated that glycosylated AMPA receptor subunits were associated. The relationship between AMPA receptors and calnexin and BiP was further studied with immunocytochemistry of the hippocampus. Both calnexin and BiP labeling was present not only in the cell body but also in dendrites of hippocampal pyramidal neurons, where double-label immunofluorescence also showed the presence of AMPA receptor subunits. C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Rubio, ME (reprint author), NIDCD, Neurochem Lab, NIH, Bldg 36,Rm 5D08,36 Convent Dr, Bethesda, MD 20892 USA. NR 52 TC 36 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1999 VL 73 IS 3 BP 942 EP 948 DI 10.1046/j.1471-4159.1999.0730942.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 226TD UT WOS:000082037000006 PM 10461883 ER PT J AU Gray, AM Rawls, SM Shippenberg, TS McGinty, JF AF Gray, AM Rawls, SM Shippenberg, TS McGinty, JF TI The kappa-opioid agonist, U-69593, decreases acute amphetamine-evoked behaviors and calcium-dependent dialysate levels of dopamine and glutamate in the ventral striatum SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE microdialysis; glutamate; dopamine; ventral striatum; opioid receptors; kappa-opioid receptors ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; RECEPTOR AGONIST; TEGMENTAL AREA; IN-VIVO; LOCOMOTOR-ACTIVITY; PLACE PREFERENCE; DORSAL CAUDATE; NMDA RECEPTORS AB The effects of a kappa-opioid receptor agonist on acute amphetamine-induced behavioral activation and dialysate levels of dopamine and glutamate in the ventral striatum were investigated. Amphetamine (2.5 mg/kg i.p.) evoked a substantial increase in rearing, sniffing, and hole-poking behavior as well as dopamine and glutamate levels in the ventral striatum of awake rats. U-69593 (0.32 mg/kg s.c.) significantly decreased the amphetamine-evoked increase in behavior and dopamine and glutamate levels in the ventral striatum. Reverse dialysis of the selective kappa-opioid receptor antagonist, nor-binaltorphimine, into the ventral striatum antagonized the effects of U-69593 on amphetamine-induced behavior and dopamine and glutamate levels. Reverse dialysis of low calcium (0.1 mM) into the ventral striatum decreased basal dopamine, but not glutamate, dialysate levels by 91% 45 min after initiation of perfusion. Strikingly, 0.1 mM calcium perfusion significantly reduced the 2.5 mg/kg amphetamine-evoked increase in dopamine and glutamate levels in the ventral striatum, distinguishing a calcium-dependent and a calcium-independent component of release. U-69593 did not alter the calcium-independent component of amphetamine-evoked dopamine and glutamate levels. These data are consistent with the view that a transsynaptic mechanism augments the increase in dopamine and glutamate levels in the ventral striatum evoked by a moderately high dose of amphetamine and that stimulation of kappa-opioid receptors suppresses the calcium-dependent component of amphetamine's effects. C1 E Carolina Univ, Sch Med, Dept Anat & Cell Biol, Greenville, NC 27858 USA. NIDA, Integrat Neurosci Unit, Brain Imaging Sect, NIH, Baltimore, MD USA. RP McGinty, JF (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, POB 250677,Suite 607,167 Ashley Ave, Charleston, SC 29425 USA. FU NIDA NIH HHS [DA03982, DA09256] NR 52 TC 83 Z9 84 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1999 VL 73 IS 3 BP 1066 EP 1074 DI 10.1046/j.1471-4159.1999.0731066.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 226TD UT WOS:000082037000019 PM 10461896 ER PT J AU Sihver, T Fasth, KJ Horti, AG Koren, AO Bergstrom, M Lu, L Hagberg, G Lundqvist, H Dannals, RF London, ED Nordberg, A Langstrom, B AF Sihver, T Fasth, KJ Horti, AG Koren, AO Bergstrom, M Lu, L Hagberg, G Lundqvist, H Dannals, RF London, ED Nordberg, A Langstrom, B TI Synthesis and characterization of binding of 5-[Br-76]bromo-3-[[2(S)-azetidinyl]methoxy]pyridine, a novel nicotinic acetylcholine receptor ligand, in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 5-[Br-76]bromo-3-[[2(S)-azetidinyl]methoxy]pyridine; nicotinic receptor binding; in vitro studies; in vivo studies; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; CHOLINERGIC RECEPTORS; H-3 CYTISINE; RADIOIODINATED ANALOG; MONKEY BRAIN; PET; LOCALIZATION; EPIBATIDINE; AFFINITY AB 5-[Br-76]Bromo-3-[[2(S)-azetidinyl]methoxy]-pyridine ([Br-76]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [Br-76]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/mu mol. The binding properties of [Br-76]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [Br-76]BAP binding was obtained after 60 min. The dissociation half-life of [Br-76]BAP was 51 +/- 6 min in cortical membranes and 56 +/- 3 min in thalamic membranes. Saturation experiments with [Br-76]BAP revealed one population of binding sites with dissociation constant (K-D) values of 36 +/- 9 and 30 +/- 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (B-max) values were 90 +/- 17 and 207 +/- 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were <1, suggesting the presence of a lower-affinity binding site. In vitro autoradiography studies showed that binding of [Br-76]BAP was high in the thalamus and presubiculum, moderate in the cortex and striatum, and low in the cerebellum and hippocampus. A similar pattern of [Br-76]BAP accumulation was observed by ex vivo autoradiography. In vivo, binding of [Br-76]BAP in whole rat brain was blocked by preinjection of (S)(-)-nicotine (0.3 mg/kg) by 27, 52, 68, and 91% at survival times of 10, 25, 40, 120, and 300 min, respectively. In a preliminary PET study in rhesus monkeys, the highest [76Br]BAP uptake was found in the thalamus, and radioactivity was displaceable by similar to 60% with cytisine and by 50% with (S)(-)-nicotine. The data of this study indicate that [Br-76]BAP is a promising radioligand for the characterization of nicotinic acetylcholine receptors in vivo. C1 Univ Uppsala, PET Ctr Uppsala, S-75185 Uppsala, Sweden. Univ Uppsala, Dept Med Pharmacol, S-75185 Uppsala, Sweden. Univ Uppsala, Dept Oncol Radiol & Clin Immunol, Div Biomed Radiat Sci, S-75185 Uppsala, Sweden. Huddinge Hosp, Karolinska Inst, Dept Clin Neurosci & Family Med, Div Mol Neuropharmacol, S-14186 Huddinge, Sweden. NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD USA. RP Langstrom, B (reprint author), Univ Uppsala, PET Ctr Uppsala, S-75185 Uppsala, Sweden. RI Hagberg, Gisela/A-2134-2010 OI Hagberg, Gisela/0000-0003-2176-7086 NR 45 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1999 VL 73 IS 3 BP 1264 EP 1272 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 226TD UT WOS:000082037000043 ER PT J AU Gobbini, MI Smith, ME Richert, ND Frank, JA McFarland, HF AF Gobbini, MI Smith, ME Richert, ND Frank, JA McFarland, HF TI Effect of open label pulse cyclophosphamide therapy on MRI measures of disease activity in five patients with refractory relapsing-remitting multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; cyclophosphamide; magnetic resonance; white matter lesion load; gadolinium ID DOSE INTRAVENOUS CYCLOPHOSPHAMIDE; SYSTEMIC LUPUS-ERYTHEMATOSUS; BLOOD-BRAIN-BARRIER; IMMUNOSUPPRESSION AB Objective. To evaluate the response to cyclophosphamide (CTX) of five patients who failed an average three treatments with multiple other therapeutic agents, using serial monthly MRI measures. Methods. Five patients with relapsing-remitting multiple sclerosis (MS) and documented MRT disease activity were started on monthly pulse intravenous CTX at a dose of I g/m(2). CTX was administered without an induction phase according to the protocol similar to the treatment of lupus nephritis. The five patients were followed with monthly MRI and clinical evaluation for a mean of 28 months. Results. All the patients showed a rapid reduction in the contrast-enhancing lesion frequency and in three patients there was a decrease in the T2, lesion load within the first 5 months after starting CTX treatment. The administration of CTX during overnight hospitalization was safe and well tolerated. Conclusions. These findings suggest that aggressive immunosuppressive therapy may be useful in some rapidly deteriorating refractory patients and further controlled study should be considered in order to full evaluate this type of treatment as a potential therapy in MS. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol REs, Off Director, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr MSC-1400, Bethesda, MD 20892 USA. NR 36 TC 49 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP 1 PY 1999 VL 99 IS 1 BP 142 EP 149 DI 10.1016/S0165-5728(99)00039-9 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 233UM UT WOS:000082445700017 PM 10496187 ER PT J AU Mienville, JM Maric, I Maric, D Clay, JR AF Mienville, JM Maric, I Maric, D Clay, JR TI Loss of I-A expression and increased excitability in postnatal rat Cajal-Retzius cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LAYER-I; POTASSIUM CURRENT; SPINAL NEURONS; NEOCORTEX; HIPPOCAMPAL; PROTEINS; BRAIN; GABA AB Although an important secretory function of Cajal-Retzius (CR) cells has been discovered recently, the precise electrical status of these cells among other layer I neurons in particular and in cortical function in general is still unclear. In this paper, early postnatal CR cells from rat neocortex were found to express an inactivating K current whose molecular substrate is likely to be the Kv1.4 channel. Both electrophysiological and immunocytochemical experiments revealed that expression of this A-type current is down-regulated in vivo and virtually disappears by the end of the second postnatal week. At this time, CR cells have become capable of evoked repetitive firing, and their action potentials are larger and faster, yet these electrical properties still appear incompatible with a role in cortical network function, as inferred from comparisons with other cortical neurons. Also at this time, a large proportion of CR cells display spontaneous spiking activity, which suggests the possibility of additional roles for these cells. We conclude that the loss of A channels along with an increase in Na channel density shape the changes in excitability of postnatal CR cells, in terms of both the patterns of evoked firing and the emergence of spontaneous spiking. C1 Univ Illinois, Inst Psychiat, Dept Psychiat, Chicago, IL 60612 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Mienville, JM (reprint author), Univ Illinois, Inst Psychiat, Dept Psychiat, M-C 912,1601 W Taylor St, Chicago, IL 60612 USA. NR 37 TC 18 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1999 VL 82 IS 3 BP 1303 EP 1310 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 239AL UT WOS:000082746600020 PM 10482749 ER PT J AU Wenner, P O'Donovan, MJ AF Wenner, P O'Donovan, MJ TI Identification of an interneuronal population that mediates recurrent inhibition of motoneurons in the developing chick spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spinal interneuron; Renshaw cell; spontaneous activity; imaging; synaptic specificity; spinal cord; chick embryo ID RENSHAW CELLS; MOTOR-NEURONS; LUMBOSACRAL MOTONEURONS; SYNAPTIC DRIVE; EMBRYO; SPECIFICATION; EXPRESSION; PATTERN; CONNECTIVITY; ORGANIZATION AB Studies on the development of synaptic specificity, embryonic activity, and neuronal specification in the spinal cord have all been limited by the absence of a functionally identified interneuron class (defined by its unique set of connections). Here, we identify an interneuron population in the embryonic chick spinal cord that appears to be the avian equivalent of the mammalian Renshaw cell (R-interneurons). These cells receive monosynaptic nicotinic, cholinergic input from motoneuron recurrent collaterals. They make predominately GABAergic connections back onto motoneurons and to other R-interneurons but project rarely to other spinal interneurons. The similarity between the connections of the developing R-interneuron, shortly after circuit formation, and the mature mammalian Renshaw cell raises the possibility that R-interneuronal connections are formed precisely from the onset. Using a newly developed optical approach, we identified the location of R-interneurons in a column, dorsomedial to the motor nucleus. Functional characterization of the R-interneuron population provides the basis for analyses that have so far only been possible for motoneurons. C1 NINDS, Sect Dev Neurobiol, Lab Neural Control, NIH, Bethesda, MD 20892 USA. RP Wenner, P (reprint author), NINDS, Sect Dev Neurobiol, Lab Neural Control, NIH, 49 Convent Dr,Bldg 49,Room 3A50, Bethesda, MD 20892 USA. RI o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Wenner, Peter/0000-0002-7072-2194 NR 42 TC 40 Z9 40 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 1999 VL 19 IS 17 BP 7557 EP 7567 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 233TL UT WOS:000082442600035 PM 10460262 ER PT J AU Oldfield, EH Lonser, RR Heiss, JD AF Oldfield, EH Lonser, RR Heiss, JD TI Intratumoral ethanol injection - Response SO JOURNAL OF NEUROSURGERY LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 1999 VL 91 IS 3 BP 522 EP 523 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 232WN UT WOS:000082393100033 ER PT J AU Panza, JA Dilsizian, V Curiel, RV Unger, EF Laurienzo, JM Kitsiou, AN AF Panza, JA Dilsizian, V Curiel, RV Unger, EF Laurienzo, JM Kitsiou, AN TI Myocardial blood flow at rest and contractile reserve in patients with chronic coronary artery disease and left ventricular dysfunction SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE LV dysfunction; CAD; inotropic stimulation ID DOBUTAMINE STRESS ECHOCARDIOGRAPHY; EMISSION COMPUTED-TOMOGRAPHY; HIBERNATING MYOCARDIUM; INOTROPIC STIMULATION; ISCHEMIC DYSFUNCTION; VIABLE MYOCARDIUM; HEART-DISEASE; REVASCULARIZATION; REINJECTION; PREDICTION AB Background. The mechanisms that determine chronic left ventricular dysfunction in coronary artery disease (in particular, critical reductions in coronary artery blood flow leading to hibernating myocardium) may affect the ability of the myocardium to respond to inotropic stimulation with dobutamine, This study was designed to investigate the relationship between resting myocardial blood flow and contractile reserve in patients with coronary artery disease and chronic left ventricular dysfunction. Methods and Results. Twenty-three patients (21 men and 2 women; age 61 +/- 9 years) underwent transesophageal echocardiography during infusion of dobutamine (2.5 mu g/kg to 40 mu g/kg per minute) and positron emission tomography (PET) with O-15-water (9 patients) or N-13-ammonia (14 patients). Systolic wall thickening at each dose of dobutamine and resting myocardial blood flow were quantitatively analyzed in 8 anatomically matched regions at mid-ventricular level. Myocardial regions with preserved contraction had higher blood flow compared with regions with basal dyssynergy (0.99 +/- 0.3 vs 0.65 +/- 0.3 mL/min/gm; P < .0001). Among myocardial regions with preserved resting contraction, no relation was observed between blood flow and the response to dobutamine (r = 0.06). In contrast, among myocardial regions with diminished resting contraction, a significant correlation was observed between resting blood flow and contractile reserve (r = 0.53; P < .0001). The maximum increase in percent systolic wall thickening with dobutamine was 32.8% +/- 14% in regions with normal blood flow 21.5% +/- 17% in regions with mildly to moderately reduced blood flow, and 10.7% +/- 10% in regions with severely reduced blood flow (P < .0001). Conclusions. These findings emphasize the importance of resting myocardial blood flow for the preservation of contractile reserve in patients with coronary artery disease and left ventricular dysfunction. Because a positive inotropic response to dobutamine is more likely to occur in dyssynergic regions with preserved rather than reduced myocardial blood flow, regional perfusion may determine in which circumstances dobutamine echocardiography contributes to the assessment of myocardial viability. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 35 TC 12 Z9 16 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 1999 VL 6 IS 5 BP 487 EP 494 DI 10.1016/S1071-3581(99)90020-X PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 253HN UT WOS:000083551100003 PM 10548143 ER PT J AU Fleg, JL Schulman, SP AF Fleg, JL Schulman, SP TI Nuclear cardiology approaches to defining normal and abnormal cardiovascular aging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review ID SILENT-MYOCARDIAL-ISCHEMIA; CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR VOLUME; AGE-ASSOCIATED CHANGES; ALL-CAUSE MORTALITY; HEALTHY-MEN; PHYSICAL-ACTIVITY; DYNAMIC EXERCISE; OLDER MEN; PERFORMANCE C1 NIA, Cardiovasc Sci Lab, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA. RP Fleg, JL (reprint author), Gerontol Res Ctr, Human Cardiovasc Studies Unit, Lab Cardiovasc Sci, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 1999 VL 6 IS 5 BP 522 EP 530 DI 10.1016/S1071-3581(99)90025-9 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 253HN UT WOS:000083551100008 PM 10548148 ER PT J AU Aloj, L Jagoda, E Lang, LX Caraco, C Neumann, RD Sung, C Eckelman, WC AF Aloj, L Jagoda, E Lang, LX Caraco, C Neumann, RD Sung, C Eckelman, WC TI Targeting of transferrin receptors in nude mice bearing A431 and LS174T xenografts with [F-18]holo-transferrin: Permeability and receptor dependence SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE transferrin; F-18; neoplasms; pharmacokinetics; liver ID MONOCLONAL-ANTIBODY UPTAKE; SOLID TUMORS; LIVER-CELLS; PET; BINDING; ESTABLISHMENT; TOMOGRAPHY; FRAGMENTS; BENZOATE; KINETICS AB The goal of this study was to investigate whether F-18-labeled transferrin (Tf), which has a molecular weight (M-r) of similar to 79,000, binds to Tf receptor sites in tumors in a specific manner within the time frame commensurate with the half-life of F-18 (109.7 min). We have previously shown that [F-18]holo-Tf ([F-18]TI) maintains all properties of native Tf in vitro and that it can specifically target liver Tf receptor sites in vivo. Methods: The distribution of [F-18]Tf, using [F-18]albumin (Alb) or [C-14]Alb as a control, was studied over a 6-h period in nude mice bearing LS174T and A431 xenografts of a high- and low-permeability tumor, respectively. Results: Measurements of Tf receptor concentration in the tumor extracts suggest similar binding capacities. In vivo, liver uptake values were higher for [F-18]Tf than for both [F-18]Alb and [C-14]Alb throughout the study, indicating specific binding. In contrast, tumor Tf uptake values remained below those of the Alb tracers, and tumor-to-brood ratios of [F-18]Tf in each xenograft increased in parallel with those of the Alb tracers. The permeabilities of [C-14]Alb and [F-18]Tf in LS174T were calculated to be 1.29 +/- 0.49 and 1.03 +/- 0.38 mu L/min/g (mean +/- SD), respectively, whereas the permeabilities of the two tracers in A431 were 0.79 +/- 0.24 and 0.44 +/- 0.04 mu L/min/g. Pharmacokinetic modeling of the data using these permeabilities and the high plasma and extracellular concentrations of endogenous Tf showed that the observed uptake values in the two xenografts are consistent with a non-receptor-mediated distribution. In the liver, the absence of permeability barriers yields specific [F-18]Tf binding to receptors compared with the [C-14]Alb control, within 5 min after injection. Conclusion: Receptor-mediated accumulation of [F-18]Tf in tumor xenografts is impaired by rate-determining permeability and competition from endogenous Tf and is not achieved in a time frame of 6 h. C1 NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, Off Res Serv, Bethesda, MD 20892 USA. RP Aloj, L (reprint author), Univ Naples Federico II, Dipartimento Sci Biomorfol & Funz, Consiglio Nazl Ric, Ctr Studio Med Nucl, Via S Pansini 5, I-80131 Naples, Italy. NR 35 TC 10 Z9 11 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1999 VL 40 IS 9 BP 1547 EP 1555 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234ZU UT WOS:000082514900025 PM 10492378 ER PT J AU Panyutin, IG Sedelnikova, OA Neumann, RD AF Panyutin, IG Sedelnikova, OA Neumann, RD TI Problems associated with oligonucleotide radiotherapy - Reply SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES C1 NIH, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1999 VL 40 IS 9 BP 1582 EP 1582 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234ZU UT WOS:000082514900030 ER PT J AU Troen, G Eskild, W Fromm, SH De Luca, LM Ong, DE Wardlaw, SA Reppe, S Blomhoff, R AF Troen, G Eskild, W Fromm, SH De Luca, LM Ong, DE Wardlaw, SA Reppe, S Blomhoff, R TI Vitamin A-sensitive tissues in transgenic mice expressing high levels of human cellular retinol-binding protein type I are not altered phenotypically SO JOURNAL OF NUTRITION LA English DT Article DE vitamin A; cellular retinol-binding protein I; transgenic mice ID RAT TESTIS; KERATIN EXPRESSION; ACID SYNTHESIS; SERTOLI CELLS; ESTER STORAGE; BIOSYNTHESIS; EPITHELIUM; METABOLISM; SUBSTRATE; LIVER AB The suggested function of cellular retinol-binding protein type I [CRBP(I)I is to carry retinol to esterifying or oxidizing enzymes. The retinyl esters are used in storage or transport, whereas oxidized forms such as all-trans or 9-cis retinoic acid are metabolites used in the mechanism of action of vitamin A. Thus, high expression of human CRBP(I) [hCRBP(I)] in transgenic mice might be expected to increase the production of retinoic acid in tissues, thereby inducing a phenotype resembling vitamin A toxicity. Alternatively, a vitamin A-deficient phenotype could also be envisioned as a result of an increased accumulation of vitamin A in storage cells induced by a high hCRBP(I) level. Signs of vitamin A toxicity or deficiency were therefore examined in tissues from transgenic mice with ectopic expression of hCRBP(I). Testis and intestine, the tissues with the highest expression of the transgene, showed normal gross morphology.: Similarly, no abnormalities were observed in other tissues known to be sensitive to vitamin A status such as cornea and retina, and the epithelia in the cervix, trachea and-skin. Furthermore, hematologic variables known to be influenced by vitamin A status such as the hemoglobin concentration, hematocrits and the number of red blood cells were within normal ranges in the transgenic mice. In conclusion, these transgenic mice have normal function of vitamin A despite high expression of hCRBP(I) in several tissues. C1 Univ Oslo, Inst Nutr Res, Oslo, Norway. Univ Oslo, Inst Med Biochem, Oslo, Norway. Univ Oslo, Mol Embryol Lab, Oslo, Norway. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. RP Blomhoff, R (reprint author), Univ Oslo, Inst Nutr Res, Oslo, Norway. NR 44 TC 4 Z9 4 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 1999 VL 129 IS 9 BP 1621 EP 1627 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 230KZ UT WOS:000082251500001 PM 10460195 ER PT J AU Evans, R Gergen, PJ Mitchell, H Kattan, M Kercsmar, C Crain, E Anderson, J Eggleston, P Malveaux, FJ Wedner, HJ AF Evans, R Gergen, PJ Mitchell, H Kattan, M Kercsmar, C Crain, E Anderson, J Eggleston, P Malveaux, FJ Wedner, HJ TI A randomized clinical trial to reduce asthma morbidity among inner-city children: Results of the National Cooperative Inner-City Asthma Study SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 19-26, 1997 CL SAN FRANCISCO, CA SP Amer Acad Allergy Asthma & Immunol ID PATIENT EDUCATION; SELF-MANAGEMENT; HEALTH; MORTALITY; POVERTY; PROGRAM; CARE AB Objective: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma. Study design: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk. profile assessed at baseline. Results: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days far the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P = .004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with. children in the intervention group (14.8%), a decrease of 4.19% (CI, -8.75 to 0.36, P = .071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor Conclusions: We demonstrated that an individually tailored, multifaceted intervention carried out. by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city. C1 Childrens Mem Hosp, Chicago, IL 60614 USA. NIAID, NIH, Bethesda, MD 20892 USA. Rho Inc, Chapel Hill, NC USA. Mt Sinai Sch Med, New York, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Howard Univ, Coll Med, Washington, DC USA. Washington Univ, Sch Med, St Louis, MO USA. RP Evans, R (reprint author), Childrens Mem Hosp, Box 60,2300 Childrens Plaza, Chicago, IL 60614 USA. FU PHS HHS [A1-30752, A1-30756, UO1 A1-30751] NR 28 TC 203 Z9 207 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1999 VL 135 IS 3 BP 332 EP 338 DI 10.1016/S0022-3476(99)70130-7 PG 7 WC Pediatrics SC Pediatrics GA 237NM UT WOS:000082662800016 PM 10484799 ER PT J AU Laskin, BL Choyke, P Keenan, GF Miller, FW Rider, LG AF Laskin, BL Choyke, P Keenan, GF Miller, FW Rider, LG TI Novel gastrointestinal tract manifestations in juvenile dermatomyositis SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYMYOSITIS; ESOPHAGEAL; ABNORMALITIES; DISEASE AB We report a case of juvenile dermatomyositis in which a dilated atonic esophagus was associated with delayed gastric emptying and intestinal mucosal thickening, resulting in a radiographic "stacked coin" appearance. These findings, which can also occur in infectious, neoplastic, or other immune-mediated diseases, broaden the spectrum of gastrointestinal tract manifestations in juvenile dermatomyositis. Physicians should be alert fbr these treatable manifestations in children with myositis who present with unexplained gastrointestinal symptoms, which are reversible with immunosuppressive therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bldg 29B,Room 2G11,HMF 561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 16 TC 9 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1999 VL 135 IS 3 BP 371 EP 374 DI 10.1016/S0022-3476(99)70137-X PG 4 WC Pediatrics SC Pediatrics GA 237NM UT WOS:000082662800023 PM 10484806 ER PT J AU Li, P Tabibi, SE Yalkowsky, SH AF Li, P Tabibi, SE Yalkowsky, SH TI Solubilization of flavopiridol by pH control combined with cosolvents, surfactants, or complexants SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID CYCLODEXTRINS AB This study investigates the roles of both ionized and unionized species of flavopiridol in solubilization by complexation, micellization, and cosolvency. Control of pH was used in combination with surfactants (polysorbate 20 and polysorbate 80), cosolvents (ethanol and propylene glycol), as well as uncharged and anionic complexing agents [hydroxypropyl beta-cyclodextrin (HP beta CD) and sulfobutyl ether beta-cyclodextrin (SBE beta CD)] to solubilize flavopiridol. These combined techniques increase not only the solubility of the un-ionized flavopiridol but also the solubility of the ionized drug. This study confirms that previously developed equations effectively characterize the roles of pH, pK(a), and either complexation constant, micelle partition coefficient, or cosolvent solubilizing power in determining drug total aqueous solubility. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NCI, Pharmaceut Res Branch, NIH, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. FU NCI NIH HHS [N01-CM-27757] NR 9 TC 36 Z9 39 U1 2 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD SEP PY 1999 VL 88 IS 9 BP 945 EP 947 DI 10.1021/js990097r PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 233BU UT WOS:000082406300015 PM 10479359 ER PT J AU Blanchet, PJ Konitsiotis, S Whittemore, ER Zhou, ZL Woodward, RM Chase, TN AF Blanchet, PJ Konitsiotis, S Whittemore, ER Zhou, ZL Woodward, RM Chase, TN TI Differing effects of N-methl-D-aspartate receptor subtype selective antagonists on dyskinesias in levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HETEROMERIC NMDA RECEPTORS; MOTOR RESPONSE ALTERATIONS; PARKINSONS-DISEASE; L-DOPA; GLUTAMATE ANTAGONIST; SUBUNIT COMPOSITION; NR2B SUBUNIT; IN-VITRO; RAT; BLOCKADE AB The antiparkinsonian and antidyskinetic profile of two N-methyl-D-aspartate (NMDA) receptor antagonists, a competitive antagonist, (R)-4-oxo-5-phosphononorvaline (M DL 100,453), and a novel noncompetitive allosteric site antagonist, 4-hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzl)piperidine (Co 101244/PD 174494), was assessed in six levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine-lesioned parkinsonian monkeys. The effects on motor function of these two drugs, alone and in combination with levodopa, were then correlated with NMDA subtype selectivity and apparent affinity for four diheteromeric NMDA receptor subunit combinations expressed in Xenopus oocytes. MDL 100,453 (300 mg/kg s.c.) by itself increased global motor activity (p = .0005 versus vehicle) and administered 15 min after a low dose of levodopa/benserazide s.c., MDL 100,453 (50, 300 mg/kg s.c.) showed dose-dependent potentiation of antiparkinsonian responses and also produced dyskinesias. Following injection of a fully effective dose of levodopa, MDL 100,453 (300 mg/kg s.c.) also produced a 25% increase in mean dyskinesia score (p =.04). In contrast, Co 101244 did not change motor activity by itself and only showed a tendency to potentiate the antiparkinsonian response when given in combination with a low dose of levodopa, which did not attain statistical significance. However, with a high dose of levodopa, Co 101244 (0.1, 1 mg/kg s.c.) displayed antidyskinetic effects (67 and 71% reduction, respectively) while sparing levodopa motor benefit. In vitro, MDL 100,453 was an NMDA glutamate-site antagonist with similar to 5- to 10-fold selectivity for the NR1A/NR2A subtype combination (K-b = 0.6 mu M) versus NR1A in combination with 2B, 2C, or 2D. In contrast, the allosteric site antagonist Co 101244 showed similar to 10,000-fold selectivity for the NR1A/NR2B (IC50 = 0.026 mu M) versus the other three subunit combinations tested. Taken together, the data suggest that the NR2 subunit selectivity profile of NMDA receptor antagonists can play an important role in predicting behavioral outcome and offer more evidence that NR2B-selective NMDA receptor antagonists may be useful agents in the treatment of Parkinson's disease. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Blanchet, PJ (reprint author), Ctr Hosp Univ Montreal, Hop St Luc, Neurosci Res Unit, Res Ctr, 1058 Rue St Denis,Rm 401, Montreal, PQ H2X 3J4, Canada. NR 35 TC 136 Z9 137 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1999 VL 290 IS 3 BP 1034 EP 1040 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228GM UT WOS:000082128800014 PM 10454475 ER PT J AU Gasior, M Ungard, JT Witkin, JM AF Gasior, M Ungard, JT Witkin, JM TI Preclinical evaluation of newly approved and potential antiepileptic drugs against cocaine-induced seizures SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 1999 Experimental Biology Meeting CY APR 17-21, 1999 CL WASHINGTON, D.C. ID GABA(A) RECEPTOR; PHARMACOLOGICAL MECHANISMS; INDUCED CONVULSIONS; BETA-SUBUNIT; ACID; ANTICONVULSANT; GLUTAMATE; EPILEPSY; DOPAMINE; RELEASE AB Seizures and status epilepticus are among the neurological complications of cocaine overdose in humans. The aim of the present study was to evaluate the protective effectiveness and therapeutic index (separation between anticonvulsive and side effect profiles) of 14 newly approved and potential antiepileptic drugs using a murine model of acute cocaine toxicity and the inverted-screen test for behavioral side effect testing. Cocaine (75 mg/kg l.p.) produces clonic seizures (similar to 90% of mice), and conventional antiepileptic drugs have been reported to be either ineffective or only effective at doses producing significant sedative/ataxic effects. Clobazam, flunarizine, lamotrigine, topiramate, and zonisamide were ineffective against seizures up to doses producing significant motor impairment. In contrast, felbamate, gabapentin, loreclezole, losigamone, progabide, remacemide, stiripentol, tiagabine, and vigabatrin produced dose-dependent protection against cocaine-induced convulsions with varied separations between their anticonvulsant and side effect profiles: the protective index values (toxic TD60/danticonvulsive ED50) ranged from 1.26 (felbamate) to 7.67 (loreclezole), and gabapentin had the highest (protective index >152). Thus, several drugs were identified with greater protective efficacy and reduced motor impairment compared with classic antiepileptic drugs. Based on the proposed mechanism of action of these new anticonvulsants, it is noteworthy that 1) drugs that enhance gamma-aminobulyric acid-mediated neuronal inhibition in a manner distinct from barbiturates and benzodiazepines offer the best protective/behavioral side effect profiles, and 2) functional antagonists of Na+ and Ca2+ channels are generally ineffective. Overall, this study provides the first description of the effectiveness of new antiepileptic drugs against experimentally induced cocaine seizures and points to several drugs that deserve clinical scrutiny for this indication. C1 NIDA, Addict Res Ctr, Drug Dev Grp, Behav Neurosci Branch,Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Gasior, M (reprint author), NIDA, Addict Res Ctr, Drug Dev Grp, Behav Neurosci Branch,Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 73 Z9 74 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1999 VL 290 IS 3 BP 1148 EP 1156 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228GM UT WOS:000082128800028 PM 10454489 ER PT J AU Brandt, MR Negus, SS Mello, NK Furness, MS Zhang, XY Rice, KC AF Brandt, MR Negus, SS Mello, NK Furness, MS Zhang, XY Rice, KC TI Discriminative stimulus effects of the nonpeptidic delta-opioid agonist SNC80 in rhesus monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RECEPTOR-MEDIATED PHENOMENA; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE.; DRUG DISCRIMINATION; OPIATE RECEPTORS; SQUIRREL-MONKEYS; BW373U86; MORPHINE; COCAINE; PIGEONS; STEREOTYPIES AB Five rhesus monkeys were trained to discriminate the nonpeptidic, delta-opioid agonist SNC80 (0.32 mg/kg i.m.) from saline by using a food-reinforced drug-discrimination procedure. Cumulative doses of SNC80 produced a dose-dependent increase in SNC80-appropriate responding and a dose-dependent decrease in response rate. In time-course studies, peak effects of the training dose of SNC80 were observed after 15 min, and these effects diminished over 240 min. In substitution studies, other piperazinyl benzamide delta agonists (SNC86, SNC162, and SNC243A) substituted for SNC80 with relative potencies similar those of SNC80. However, SNC67, the (-)-enantiomer of SNC80, did not occasion SNC80-appropriate responding up to a dose (32.0 mg/kg) that produced convulsions in one monkey. The mu agonists morphine and fentanyl and the kappa agonists U-50,488 and enadoline failed to substitute for SNC80 up to doses that eliminated responding. Two nonopioids (the N-methyl-D-aspartate antagonist ketamine and the monoamine reuptake inhibitor cocaine) also produced primarily saline-appropriate responding. Both the discriminative stimulus and rate-decreasing effects of SNC80 were antagonized by the delta-selective antagonist naltrindole (0.01-1.0 mg/kg) but not by doses of the opioid antagonist quadazocine (0.1-1.0 mg/kg) that block the effects of mu and kappa agonists. These data suggest that the discriminative stimulus effects of SNC80 are mediated by delta-opioid receptors and that the discriminative stimulus effects of delta opioids in primates can be differentiated from the effects of other opioid and nonopioid compounds. C1 Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Brandt, MR (reprint author), Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02178 USA. EM mbrandt@hms.harvard.edu FU NIDA NIH HHS [R01-DA02519, P50-DA04059, T32-DA0752] NR 39 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1999 VL 290 IS 3 BP 1157 EP 1164 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228GM UT WOS:000082128800029 PM 10454490 ER PT J AU Ryan, FR Katsuno, T Mantey, SA Pradhan, TK Weber, HC Coy, DH Battey, JF Jensen, RT AF Ryan, FR Katsuno, T Mantey, SA Pradhan, TK Weber, HC Coy, DH Battey, JF Jensen, RT TI Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HUMAN ORPHAN RECEPTOR; GASTRIN-RELEASING PEPTIDE; BOMBESIN RECEPTOR; HIGH-AFFINITY; GUINEA-PIG; CELL-LINES; RAT-BRAIN; SUBTYPES; EXPRESSION; DISCOVERY AB The mammalian peptide neuromedin B (NMB) and its receptor are expressed in a variety of tissues; however, little is definitively established about its physiological actions because of the lack of potent, specific antagonists. Recently, the peptoid PD 168368 was found to be a potent human NMB receptor antagonist. Because it had been shown previously that either synthetic analogs of bombesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor subtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor subtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor subtype 3, and Bn receptor subtype 4) from human, mouse, rat, and frog. In binding studies, PD 168368 had similar high affinities (K-i = 15-45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor subtype 3 or 4. It inhibited NMB binding in a competitive manner. PD 168368 alone did not stimulate increases in either intracellular calcium concentration or [H-3]inositol phosphates in any of the cells studied but inhibited NMB-Induced responses with equivalent potencies in cells containing NMB receptors. PD 168368 was only minimally soluble in water. When hydroxypropyl-P-cyclodextrin rather than dimethyl sulfoxide was used as the vehicle, both the affinity and the antagonist potency of PD 168368 were significantly greater. The results demonstrate that PD 168368 is a potent, competitive, and selective antagonist at NMB receptors, with a similar pharmacology across animal species. PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIDOCD, Mol Biol Lab, NIH, Bethesda, MD USA. Tulane Univ, Peptide Res Labs, New Orleans, LA 70118 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 40 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1999 VL 290 IS 3 BP 1202 EP 1211 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228GM UT WOS:000082128800035 ER PT J AU Barclay, TB Peters, JM Sewer, MB Ferrari, L Gonzalez, FJ Morgan, ET AF Barclay, TB Peters, JM Sewer, MB Ferrari, L Gonzalez, FJ Morgan, ET TI Modulation of cytochrome P-450 gene expression in endotoxemic mice is tissue specific and peroxisome proliferator-activated receptor-alpha dependent SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 10th International Conference on Cytochrome P450 CY AUG 21-26, 1997 CL SAN FRANCISCO, CALIFORNIA ID ACUTE-PHASE RESPONSE; PPAR-ALPHA; DEFICIENT MICE; RAT-LIVER; INDUCTION; MOUSE; ACID; SUPPRESSION; INFLAMMATION; METABOLISM AB Administration of the bacterial endotoxin lipopolysaccharide (LPS) causes induction of cytochrome P-450 (CYP) 4A mRNAs in rat liver and kidney. Because induction of the CYP4A sub-family by chemicals requires peroxisome proliferator-activated receptor-alpha (PPAR alpha), we determined whether CYP4A induction by LPS also requires PPAR alpha by comparing the responses of PPAR alpha-null (-/-) and wild-type (+/+) mice. Renal expression of CYP4A10, CYP4A14, and acyl-CoA oxidase was induced by LPS treatment in(+/+) mice, and these effects were absent in the (-/-) mice. In contrast, hepatic expression of CYP4A10 was down-regulated in the (+/+) animals, and no significant induction of acyl-CoA oxidase or CYP4A14 was detected in liver. Expression of the peroxisomal bifunctional enzyme was not significantly affected by LPS treatment. These results indicate that PPAR alpha is activated in mouse kidney after LPS treatment and that this leads to modulation of some PPAR alpha-regulated genes. However, the species and tissue specificity of these effects suggest that inflammatory pathways may modulate the induction via PPARa. Mice pair fed with LPS-treated mice showed no induction of renal CYP4A10 or CYP4A14, indicating that renal CYP4A induction during endotoxemia is not due to hypophagia. Down-regulation of CYP2A5, CYP2C29, and CYP3A11 by LPS was attenuated or blocked in the (-/-) mice, suggesting a role for PPAR alpha in CYP downregulation as well. Finally, we found that clofibrate caused an acute induction of two hepatic acute-phase mRNAs that was only partially dependent on PPAR alpha. C1 Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. NCI, Met Lab, NIH, Bethesda, MD 20892 USA. Univ Nancy 1, Ctr Medicament, Nancy, France. RP Morgan, ET (reprint author), Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. RI Peters, Jeffrey/D-8847-2011; OI Ferrari, Luc/0000-0002-3159-6826 FU NIGMS NIH HHS [GM-46897] NR 35 TC 78 Z9 79 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1999 VL 290 IS 3 BP 1250 EP 1257 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228GM UT WOS:000082128800040 PM 10454501 ER PT J AU Ruskin, DN Bergstrom, DA Walters, JR AF Ruskin, DN Bergstrom, DA Walters, JR TI Multisecond oscillations in firing rate in the globus pallidus: Synergistic modulation by D1 and D2 dopamine receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GENE-EXPRESSION; TIME-SERIES; IN-VIVO; NEURONS; D-1; AGONISTS; STIMULATION; INVOLVEMENT; APOMORPHINE; BEHAVIOR AB The firing rates of many basal ganglia neurons recorded in awake rats oscillate at seconds-to-minutes time scales, and the D1/D2 agonist apomorphine has been shown to robustly modulate these oscillations. The use of selective D1 and D2 antagonists suggested that both these receptor subfamilies are involved in apomorphine's effects. In the present study, spectral analysis revealed that baseline multisecond oscillations were significantly periodic in 71% of globus pallidus neurons. Baseline oscillations had a wide range of periods within the analyzed range, with a population mean of 32 +/- 2 a. Administration of the D1 agonist SKF 81297 (6-chloroPB) at 1.0 or 5.0 mg/kg significantly changed these oscillations, reducing means of spectral peak periods to 14 to 16 s (i.e., increasing oscillatory frequency). This effect was attenuated by D2 antagonist pretreatment. The D2 agonist quinpirole did not cause a significant population change in multisecond periodicities. The strongest effects on multisecond periodicities occurred after combined treatment with SKF 81297 and quinpirole. Low, ineffective doses of SKF 81297 and quinpirole, when combined, produced a significant increase in oscillatory frequency. Also, when quinpirole was administered after an already effective dose of SKF 81297, quinpirole shifted oscillations to an even faster range (typically to periods of <10 s). The dopaminergic control of multisecond periodicities in globus pallidus firing rate demonstrates D1/D2 receptor synergism, in that the effects of D1 agonists are potentiated by and partially dependent on D2 receptor activity. Modulation of multisecond oscillations in firing rate represents a novel means by which dopamine can influence globus pallidus physiology. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ruskin, DN (reprint author), Bldg 10,Room 5C-103,10 Ctr Dr, Bethesda, MD 20892 USA. EM dnruskin@helix.nih.gov NR 54 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1999 VL 290 IS 3 BP 1493 EP 1501 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228GM UT WOS:000082128800068 PM 10454529 ER PT J AU Horowitz, AM AF Horowitz, AM TI Challenges of and strategies for changing prescribing practices of health care providers SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE dietary fluoride supplements; providers; changing prescribing practices; educational interventions; policy; guidelines; regulations ID CONTINUING MEDICAL-EDUCATION; DIETARY FLUORIDE SUPPLEMENTS; PHYSICIAN PERFORMANCE; CARIES PREVENTION; APPROPRIATE USE; ATTITUDES; KNOWLEDGE; OUTREACH; DENTISTS; PATTERNS AB Problems related to inappropriate prescribing practices of physicians in general are well recognized. Dietary fluoride supplements have been implicated as one of the contributing factors in an increase in dental fluorosis. Inappropriate prescribing practices of providers have been cited as a major factor in this implication. Numerous studies of physicians and dentists have documented a lack of knowledge and inappropriate prescribing practices regarding fluoride supplements. The purpose of this paper is to identify barriers to changing fluoride-prescribing practices of health care providers and to suggest strategies for implementing change. To increase optimal and appropriate use of fluoride supplements, educational interventions are necessary for all user groups-detail men and women, physicians, dentists, pharmacists, nurse practitioners, dental hygienists, and the public. In addition, environmental supports for the educational activities in the form of policy, regulation, standards of care, and guidelines are recommended for consideration. C1 Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, NIH, Bethesda, MD 20892 USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, NIH, 45 Ctr Dr,MSC 6501,45-3AN-44B, Bethesda, MD 20892 USA. NR 60 TC 3 Z9 4 U1 1 U2 1 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1999 VL 59 IS 4 BP 275 EP 281 DI 10.1111/j.1752-7325.1999.tb03282.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 280XW UT WOS:000085129900013 PM 10682336 ER PT J AU Cheng, N Conway, JF Watts, NR Hainfeld, JF Joshi, V Powell, RD Stahl, SJ Wingfield, PE Steven, AC AF Cheng, N Conway, JF Watts, NR Hainfeld, JF Joshi, V Powell, RD Stahl, SJ Wingfield, PE Steven, AC TI Tetrairidium, a four-atom cluster, is readily visible as a density label in three-dimensional cryo-EM maps of proteins at 10-25 angstrom resolution SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE metal cluster; cryo-electron microscopy; molecular marker; three-dimensional image reconstruction; hepatitis B virus ID VIRUS CAPSID PROTEIN; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL RECONSTRUCTION; ELECTRON-MICROSCOPY; C-TERMINUS; F-ACTIN; HEPATITIS; LOCALIZATION; PROTEASOME; BINDING AB Heavy metal clusters derivatized to bind to designated chemical groups on proteins have great potential as density labels for cryo-electron microscopy. Smaller clusters offer higher resolution and penetrate more easily into sterically restricted sites, but are more difficult to detect. In this context, we have explored the potential of tetrairidium (Ir-4) as a density label by attaching it via maleimide linkage to the C-terminus of the hepatitis B virus (HBV) capsid protein. Although the clusters are not visible in unprocessed cryo-electron micrographs, they are distinctly visible in three-dimensional density maps calculated from them, even at only partial occupancy. The Ir-4 label was clearly visualized in our maps at 11-14 Angstrom resolution of both size variants of the HBV capsid, thus confirming our previous localization of this site with undecagold (Zlotnick, A., Cheng, N., Stahl, S. J., Conway, J. F., Steven, A. C.) and Wingfield, P. T, Proc. Natl. Acad. Sci. USA 94, 9556-9561, 1997). Ir-4 penetrated to the interior of intact capsids to label this site on their inner surface, unlike undecagold for which labelling was achieved only with dissociated dimers that were then reassembled into capsids. The Ir-4 cluster remained visible as the resolution of the maps was lowered progressively to similar to 25 Angstrom. (C) 1999 Academic Press. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Nanoprobes Inc, Stony Brook, NY 11790 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 6,Room B2-34,MSC 2717, Bethesda, MD 20892 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 31 TC 33 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 1999 VL 127 IS 2 BP 169 EP 176 DI 10.1006/jsbi.1999.4120 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 255PJ UT WOS:000083678100011 PM 10527906 ER PT J AU Fitch, WT Giedd, J AF Fitch, WT Giedd, J TI Morphology and development of the human vocal tract: A study using magnetic resonance imaging SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BODY-SIZE; SEX; DIMENSIONS; POSITION; CHILDREN; VOWELS; VOICE; AGES; FOOD AB Magnetic resonance imaging was used to quantify the vocal tract morphology of 129 normal humans, aged 2-25 years. Morphometric data, including midsagittal vocal tract length, shape, and proportions, were collected using computer graphic techniques. There was a significant positive correlation between vocal tract length and body size (either height or weight). The data also reveal clear differences in male and female vocal tract morphology, including changes in overall vocal tract length and the relative proportions of the oral and pharyngeal cavity. These sex differences are not evident in children, but arise at puberty, suggesting that they are part Of the vocal remodeling process that occurs during puberty in males. These findings have implications for speech recognition, speech forensics, and the evolution of the human speech production system, and. provide a nonnative standard for future studies of human vocal tract morphology and development. (C) 1999 Acoustical Society of America. [S0001-4966(99)02008-1]. C1 Harvard Univ, MIT, Speech & Hearing Sci Program, Cambridge, MA 02138 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Fitch, WT (reprint author), Harvard Univ, MIT, Speech & Hearing Sci Program, 33 Kirkland St,Room 982, Cambridge, MA 02138 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU NIDCD NIH HHS [T32 DC00038] NR 76 TC 322 Z9 330 U1 1 U2 43 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 1999 VL 106 IS 3 BP 1511 EP 1522 DI 10.1121/1.427148 PN 1 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 238EW UT WOS:000082698800032 PM 10489707 ER PT J AU Bergasa, NV Alling, DW Talbot, TL Wells, MC Jones, EA AF Bergasa, NV Alling, DW Talbot, TL Wells, MC Jones, EA TI Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: A controlled study SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID NALOXONE INFUSIONS; CONTROLLED TRIAL; DOUBLE-BLIND; ANTAGONIST; OPIOIDS; RAT AB Background: Intravenous naloxone frequently ameliorates the pruritus of cholestasis, but its low oral bioavailability precludes its use as a long-term therapy. Nalmefene is an orally bioavailable opiate antagonist. Objective: We assessed the efficacy of oral nalmefene in ameliorating the pruritus of cholestasis. Methods: In a prospective controlled study conducted in a tertiary referral hospital, 11 patients with generalized pruritus complicating chronic liver disease were randomized to receive either nalmefene or placebo in a double-blinded fashion for 2-month periods. Scratching activity was measured continuously fur 24-hour periods at baseline and at the: end of each treatment period. Results: Data on 8 patients who received at least 1 course of nalmefene were available for comparison with corresponding control data, which consisted of observations obtained during a course of placebo and/or at baseline. Nalmefene therapy was associated with a 75% reduction in the geometric mean hourly scratching activity (P < .01) and a decrease in the mean of a visual analogue score of the perception of pruritus in all 8 patients (mean decrease 77%, P < .01). Conclusion: Oral administration of nalmefene can ameliorate pruritus complicating chronic liver disease. C1 NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, Appl Clin Engn Sect, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Dept Gastrointestinal & Liver Dis, NL-1105 AZ Amsterdam, Netherlands. RP Bergasa, NV (reprint author), Beth Israel Med Ctr, Dept Gastroenterol & Liver Dis, 1st Ave & 16th St,18 Baird Hall, New York, NY 10003 USA. NR 18 TC 89 Z9 91 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 1999 VL 41 IS 3 BP 431 EP 434 DI 10.1016/S0190-9622(99)70117-9 PN 1 PG 4 WC Dermatology SC Dermatology GA 231WJ UT WOS:000082334200008 PM 10459118 ER PT J AU Slavkin, HC AF Slavkin, HC TI Announcing the biotechnology century SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID TRANSMISSION C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 1999 VL 130 IS 9 BP 1374 EP 1378 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 233VK UT WOS:000082447800025 PM 10492546 ER PT J AU Arseven, A McDermott, MM O'Brien, E Guralnik, JM AF Arseven, A McDermott, MM O'Brien, E Guralnik, JM TI Increased prevalence of depressive symptoms among men and women with peripheral arterial disease. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Chicago, IL USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P57 BP S26 EP S26 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000128 ER PT J AU Caplan, F Harman, SM Taub, D Pyle, R Stevens, T Christmas, C Munzer, T Clair, CS Blackman, MR AF Caplan, F Harman, SM Taub, D Pyle, R Stevens, T Christmas, C Munzer, T Clair, CS Blackman, MR TI Relationships of the GH-IGF-I axis to in vitro indices of immune function in healthy elderly men and women. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P121 BP S42 EP S42 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000189 ER PT J AU Chheda, MG Mochida, S Sheng, ZH AF Chheda, MG Mochida, S Sheng, ZH TI PKA phosphorylates snapin, a novel protein implicated in synaptic transmission. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 HHMI, NIH, Bethesda, MD USA. Tokyo Med Coll, Dept Physiol, Tokyo 160, Japan. NINDS, Synapt Funct Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P6 BP S13 EP S13 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000077 ER PT J AU Edmond, J Metz, D Harman, SM Cottrell, E Stevens, T Christman, C Munzer, T Barofsky, I Pabst, K Blackman, MR AF Edmond, J Metz, D Harman, SM Cottrell, E Stevens, T Christman, C Munzer, T Barofsky, I Pabst, K Blackman, MR TI Influences of age and self-reported physical activity on muscle strength and aerobic capacity in healthy elderly individuals. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P230 BP S69 EP S69 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000298 ER PT J AU Ling, SM Fan, MY Johnson, B Bathon, JM Guralnik, JM Fried, LP AF Ling, SM Fan, MY Johnson, B Bathon, JM Guralnik, JM Fried, LP TI Disability associated with co-morbid osteoarthritis and heart disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P368 BP S103 EP S103 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000433 ER PT J AU Vaitkevicius, P Brown, C Kurian, R Fleg, J AF Vaitkevicius, P Brown, C Kurian, R Fleg, J TI Improving congestive heart failure symptoms in older patients with exercise training SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA, Johns Hopkins Bayview Med Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P145 BP S48 EP S48 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000213 ER PT J AU Zieman, SJ Gerstenblith, G Lakatta, EG Ricker, KM Hare, JM AF Zieman, SJ Gerstenblith, G Lakatta, EG Ricker, KM Hare, JM TI Age-related increase in rat myocardial nitric oxide synthase activity and expression SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P226 BP S68 EP S68 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000294 ER PT J AU Debboun, M Strickman, D Klein, TA Glass, JA Wylie, E Laughinghouse, A Wirtz, RA Gupta, RK AF Debboun, M Strickman, D Klein, TA Glass, JA Wylie, E Laughinghouse, A Wirtz, RA Gupta, RK TI Laboratory evaluation of AI3-37220, AI3-35765, CIC-4, and deet repellents against three species of mosquitoes SO JOURNAL OF THE AMERICAN MOSQUITO CONTROL ASSOCIATION LA English DT Article DE Aedes aegypti; Anopheles stephensi; Culex quinquefasciatus; piperidines; lactone; in vitro ID FIELD-EVALUATION; N,N-DIETHYL-M-TOLUAMIDE DEET; 4 REPELLENTS; DIPTERA; CULICIDAE; FORMULATIONS; PERMETHRIN; PROTECTION; EXPOSURE; DISEASE AB Four repellents, N,N-diethyl-3-methyl-benzamide (deet), 2-hydroxy-methyl-cyclohexyl acetic acid lactone (CIC-4), and 2 piperidines (1-[3-cyclohexen-1-ylcarbonyl] piperidine [AI3-35765] and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine [AI3-37220]) were evaluated alone and in combination against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus using a modified in vitro test system. This method was a valuable tool for comparing effective concentrations of the new compounds. Because of the controlled conditions of the test, it was possible to use the results of assays that had been conducted over a 5-year period and to perform the many replications necessary to evaluate combinations of compounds. The new candidate repellents were generally as effective as deet. Although speculative at this time, there was some evidence of synergistic interaction. Repellent combinations of CIC-4/AI3-37220/AI3-35767, deet/AI3-35765, and deet/AI3-37220/AI3-35765 against An. stephensi and CIC-4/AI3-35765, deet/AI3-37220/AI3-35765, AI3-37220/AI3-35765, and CIC-4/AI3-37220 against Ae. aegypti were more effective than the component compounds alone. C1 Walter Reed Army Inst Res, Div Commun Dis & Immunol, Dept Entomol, Washington, DC 20307 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NIAID, Parasit Dis Lab, Malaria Sect, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Entomol Branch, Div Parasit Dis, Atlanta, GA 30341 USA. USA, Med Res & Mat Command, Ft Detrick, MD 21702 USA. RP Debboun, M (reprint author), Walter Reed Army Inst Res, Div Commun Dis & Immunol, Dept Entomol, Washington, DC 20307 USA. NR 41 TC 12 Z9 13 U1 1 U2 1 PU AMER MOSQUITO CONTROL ASSN INC PI LAKE CHARLES PA 2200 E PRIEN LAKE RD, LAKE CHARLES, LA 70601 USA SN 8756-971X J9 J AM MOSQUITO CONTR JI J. Am. Mosq. Control Assoc. PD SEP PY 1999 VL 15 IS 3 BP 342 EP 347 PG 6 WC Entomology SC Entomology GA 231NK UT WOS:000082316500015 PM 10480126 ER PT J AU Fernandez-Llama, P Turner, R Dibona, G Knepper, MA AF Fernandez-Llama, P Turner, R Dibona, G Knepper, MA TI Renal expression of aquaporins in liver cirrhosis induced by chronic common bile duct ligation in rats SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID WATER CHANNEL EXPRESSION; INDUCED NEPHROTIC SYNDROME; CONGESTIVE-HEART-FAILURE; INDUCED DOWN-REGULATION; COLLECTING DUCT; KIDNEY MEDULLA; UP-REGULATION; VASOPRESSIN; RETENTION; MICROPUNCTURE AB Semiquantitative immunoblotting was used to investigate the expression levels of the four major renal aquaporins, the Na-K-2Cl cotransporter of the thick ascending limb, the type 3 Na-H exchanger, and the Na-K-ATPase in kidneys from rats with cirrhosis secondary to common bile duct ligation (CBDL). These rats bad significant water retention and hyponatremia. In contrast to models of cirrhosis induced by carbon tetrachloride, aquaporin-2 expression in CBDL-induced cirrhosis was decreased. Thus, these results show that in the setting of extracellular fluid volume expansion, excessive water retention with hyponatremia can occur in the absence of increases in aquaporin-2 abundance. In addition, the expression levels of the two basolateral collecting duct aquaporins (aquaporin-3 and -4) were decreased in CBDL rats relative to sham-operated control rats. Similarly, the Na-K-2Cl cotransporter of the thick ascending limb and the type 3 Na-H exchanger showed decreases in expression. In contrast, the expression levels of aquaporin-1 and the alpha 1 subunit of the Na-K-ATPase were not decreased. Thus, dysregulation of multiple water channels and ion transporters may play a role in water balance abnormalities associated with CBDL-induced cirrhosis in rats. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Vet Adm Med Ctr, Iowa City, IA USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282-KE]; NIDDK NIH HHS [DK52617, DK15843] NR 37 TC 36 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1999 VL 10 IS 9 BP 1950 EP 1957 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 229UB UT WOS:000082213200012 PM 10477147 ER PT J AU Fleck, DE Berch, DB Shear, PK Schefft, BK Privitera, MD Strakowski, SM AF Fleck, DE Berch, DB Shear, PK Schefft, BK Privitera, MD Strakowski, SM TI Directed forgetting deficits in patients with temporal lobe epilepsy: An information processing perspective SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE intentional forgetting; seizure disorder; implicit memory; explicit memory ID MEMORY; TESTS AB Although mesial temporal lobe brain damage is frequently associated with memory loss, it is unclear whether the deficit results entirely from a disruption in the processing of relevant information or whether it also reflects interference from irrelevant information. Directed forgetting is one procedure that can be used, along with standard tests of memory, to investigate this distinction. Seventeen patients with a diagnosis of complex-partial seizures of temporal lobe origin and 17 healthy volunteers were compared on lexical decision, free recall, and recognition tests in a directed-forgetting paradigm. These tests created a memory profile to measure the influence of task relevant and irrelevant information in implicit and explicit memory. Compared with healthy volunteers, the patients were significantly impaired on the memory tasks overall [F(5,25) = 5.01, p <.01]. Specifically, directed forgetting in lexical decision and recognition both discriminated between the groups [stepdown F(1,26) = 6.84, eta(2) =.26, p <.05 and stepdown F(1,25) = 5.36, eta(2) =.13, p <.05, respectively]. The results suggest that interictal memory performance in temporal lobe epilepsy may be disrupted in part because of a deficit in the differential processing of task relevant and task irrelevant information, particularly at retrieval. C1 Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA. Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. RP Fleck, DE (reprint author), Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. NR 29 TC 10 Z9 10 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD SEP PY 1999 VL 5 IS 6 BP 549 EP 555 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 249NT UT WOS:000083339700009 PM 10561936 ER PT J AU Reitz, MS Nerurkar, LS Gallo, RC AF Reitz, MS Nerurkar, LS Gallo, RC TI Perspective on Kaposi's sarcoma: Facts, concepts, and conjectures SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; FIBROBLAST-GROWTH-FACTOR; HERPESVIRUS HUMAN HERPESVIRUS-8; PROTEIN-COUPLED RECEPTOR; HIV-INFECTED INDIVIDUALS; TYPE-1 TAT PROTEIN; EPSTEIN-BARR-VIRUS; LONG-TERM CULTURE; DNA-SEQUENCES; SPINDLE CELLS C1 Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. NCI, Int Canc Informat Ctr, Bethesda, MD 20892 USA. RP Gallo, RC (reprint author), Univ Maryland, Inst Human Virol, 725 W Lombard St,Rm S307, Baltimore, MD 21201 USA. NR 100 TC 32 Z9 33 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 1 PY 1999 VL 91 IS 17 BP 1453 EP 1458 DI 10.1093/jnci/91.17.1453 PG 6 WC Oncology SC Oncology GA 232NU UT WOS:000082377500007 PM 10469745 ER PT J AU Hewitt, M Breen, N Devesa, S AF Hewitt, M Breen, N Devesa, S TI Cancer prevalence and survivorship issues: Analyses of the 1992 National Health Interview Survey SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article AB Background/Methods: Relatively little is known about the size and makeup of the growing population of cancer survivors or about the social implications of a diagnosis of cancer. To explore these issues, we analyzed cancer survivorship information from the 1992 National Health Interview Survey (NHIS), and resulting cancer prevalence estimates were compared with those derived from cancer registry data. Results: According to the NHIS, there were an estimated 7.2 million adult survivors of cancer-excluding nonmelanoma skin cancer-in 1992, representing 3.9% of the U.S. adult population. Comparisons with prevalence estimates from cancer registry data suggest that cancer is underreported in the NHIS, Nearly three fifths (58.0%) of cancer survivors self-identified on the NHIS reported that their cancer was first detected when they noticed something wrong and went to a doctor. The majority (55.7%) of cancer survivors had obtained a second opinion or multiple opinions regarding their treatment, Most (58.0%) had received patient educational materials from a health care provider. However, relatively few had received counseling or participated in support groups (14.2%), contacted cancer organizations after their diagnosis (10.9%), or participated in a research study or clinical trial as part of their cancer treatment (4.7%). One ninth (10.7%) of the survivors had been denied health or life insurance coverage because of their cancer, Nearly one fifth (18.2%) of the cancer survivors who worked before or after their cancer was diagnosed experienced employment problems because of their cancer. Conclusions: While cancer appears to be underreported on the 1992 NHIS, the survey provides valuable information about the medical, insurance, and employment experience of cancer survivors selected from a nationally representative sample of U.S. households. C1 Natl Acad Sci, Inst Med, Washington, DC 20418 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hewitt, M (reprint author), Natl Acad Sci, Inst Med, 2101 Constitut Ave NW, Washington, DC 20418 USA. EM mhewitt@nas.edu NR 19 TC 127 Z9 133 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 1 PY 1999 VL 91 IS 17 BP 1480 EP 1486 DI 10.1093/jnci/91.17.1480 PG 7 WC Oncology SC Oncology GA 232NU UT WOS:000082377500011 PM 10469749 ER PT J AU Ambs, S Harris, CC AF Ambs, S Harris, CC TI Relationship between p53 mutations and inducible nitric oxide synthase expression in human colorectal cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID TUMOR PROGRESSION; NECK-CANCER; HEAD C1 NCI, Div Basic Sci, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NIH, Bldg 37,Rm 2C01, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 1 PY 1999 VL 91 IS 17 BP 1510 EP 1511 DI 10.1093/jnci/91.17.1510 PG 2 WC Oncology SC Oncology GA 232NU UT WOS:000082377500020 ER PT J AU Walther, MM Reiter, R Keiser, HR Choyke, PL Venzon, D Hurley, K Gnarra, JR Reynolds, JC Glenn, GM Zbar, B Linehan, WM AF Walther, MM Reiter, R Keiser, HR Choyke, PL Venzon, D Hurley, K Gnarra, JR Reynolds, JC Glenn, GM Zbar, B Linehan, WM TI Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: Comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma SO JOURNAL OF UROLOGY LA English DT Article DE pheochromocytoma; Hippel-Lindau disease; diagnosis; genetics ID MULTIPLE ENDOCRINE NEOPLASIA; TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; VONHIPPELLINDAU DISEASE; PHENOTYPE; DIAGNOSIS; TYPE-2; RET; IDENTIFICATION; ADRENALECTOMY AB Purpose: Families with von Hippel-Lindau disease have variable risk of pheochromocytoma. Patients with von Hippel-Lindau disease and pheochromocytoma identified by screening can have no characteristic signs or symptoms. Families with von Hippel-Lindau disease were screened and followed to describe the natural history of von Hippel-Lindau pheochromocytoma, and to correlate these findings with von Hippel-Lindau germline mutation. Materials and Methods: Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified (von Hippel-Lindau group). Between August 1990 and June 1997, 26 consecutive patients with sporadic pheochromocytoma were evaluated (sporadic group). Results: A total of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma, including 33 newly diagnosed during screening at the National Institutes of Health and 31 previously treated (93 adrenal and 13 extra-adrenal pheochromocytomas). Germline von Hippel-Lindau gene missense mutation was associated with extra-adrenal pheochromocytoma, younger age at presentation and the only patient with metastases. Of the 33 newly diagnosed patients with von Hippel-Lindau disease 4 had pheochromocytoma 2 times (37 pheochromocytomas) during followup. Of these pheochromocytomas 35% (13 of 37) were associated with no symptoms, normal blood pressure and normal catecholamine testing. Comparison of urinary catecholamines in the von Hippel-Lindau and sporadic groups demonstrated increased epinephrine, metanephrines and vanillylmandelic acid in the sporadic group. Analysis of urinary catecholamine excretion in the von Hippel-Lindau and sporadic groups together demonstrated a correlation between tumor size, and urinary metanephrines, vanillylmandelic acid, norepinephrine, epinephrine and dopamine. In 12 patients without signs or symptoms of pheochromocytoma 17 newly diagnosed pheochromocytomas were followed for a median of 34.5 months without morbidity. Median tumor doubling time was 17 months. Conclusions: Von Hippel-Lindau gene missense mutation correlated with the risk of pheochromocytoma in patients with von Hippel-Lindau disease. These findings support a von Hippel-Lindau disease clinical classification, wherein some families are at high risk for manifestations of pheochromocytoma. Von Hippel-Lindau disease pheochromocytomas identified by screening were smaller and less functional than sporadic pheochromocytomas. C1 NCI, Urol Oncol Branch, NHLBI, Bethesda, MD 20892 USA. NCI, Dept Diagnost Radiol & Nucl Med, Warren G Magnuson Clin Ctr,Biostat Sect,NIH, Canc Diag Branch,Div Canc Treatment Diag & Ctr, Bethesda, MD 20892 USA. NCI, Dept Diagnost Radiol & Nucl Med,NIH, Warren G Magnuson Clin Ctr,Data Management Sect, Canc Diag Branch,Div Canc Treatment Diag & Ctr, Bethesda, MD 20892 USA. NCI, Immunobiol Lab, Frederick, MD USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, NHLBI, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 32 TC 128 Z9 136 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1999 VL 162 IS 3 BP 659 EP 664 DI 10.1097/00005392-199909010-00004 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 225NE UT WOS:000081967000003 PM 10458336 ER PT J AU Afonso, A Emmert-Buck, MR Duray, PH Bostwick, DG Lineman, WM Vocke, CD AF Afonso, A Emmert-Buck, MR Duray, PH Bostwick, DG Lineman, WM Vocke, CD TI Loss of heterozygosity on chromosome 13 is associated with advanced stage prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate carcinoma; loss of heterozygosity; tumor suppressor gene; human chromosome 13; tissue microdissection ID RETINOBLASTOMA SUSCEPTIBILITY GENE; ALLELIC LOSS; HIGH-FREQUENCY; REGIONS; ADENOCARCINOMAS; MICROSATELLITES; IDENTIFICATION; INSTABILITY; CARCINOMA; DELETION AB Purpose: In order to investigate the possible involvement of a tumor suppressor gene(s) on chromosome 13 in prostatic neoplasms, we performed loss of heterozygosity (LOH) analysis on normal and tumor pairs from 36 prostate cancer patients. Materials and Methods: Pure DNA was obtained from carcinoma cells and normal epithelium by tissue microdissection. The DNA had previously been analyzed for LOH on chromosomes 8 and 16. After an initial pilot experiment to determine the region(s) of significant LOH from 9 loci on chromosome 13q, 3 loci at and near the Rbl locus (D13S153, D13S1319, and D13S1303) were chosen for further study. Results: The overall rate of LOH on chromosome 13 was 27.3%. Four tumors exhibited LOM at all 3 loci. Two tumors exhibited LOM at D13S153 but not at the other, more telomeric loci; two additional tumors had loss at D13S1303 or D13S1319 but not D13S153. These data suggest that a tumor suppressor gene involved in prostate cancer may be located just telomeric to Rbl. Analysis of clinical and pathological data from carcinomas with and without loss shows that chromosome 13q LOH is correlated with advanced stage prostate cancer. Conclusions: Our LOH data suggests that there may be a tumor suppressor gene telomeric to Rbl that is potentially involved in prostate cancer progression. Identification of this gene may be valuable in providing diagnostic and prognostic information for prostate cancer patients. C1 NCI, Urol Oncol Branch, DCS, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Mayo Clin, Dept Pathol, Rochester, MN USA. RP Vocke, CD (reprint author), NCI, Urol Oncol Branch, DCS, NIH, 10 Ctr Dr MSC 1502,Bldg 10,Room 2B43, Bethesda, MD 20892 USA. NR 16 TC 16 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1999 VL 162 IS 3 BP 922 EP 926 DI 10.1097/00005392-199909010-00091 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 225NE UT WOS:000081967000091 PM 10458409 ER PT J AU Ortiz-Conde, BA Hughes, SH AF Ortiz-Conde, BA Hughes, SH TI Studies of the genomic RNA of leukosis viruses: Implications for RNA dimerization SO JOURNAL OF VIROLOGY LA English DT Article ID MOLONEY MURINE LEUKEMIA; PRIMER-BINDING-SITE; NUCLEOCAPSID PROTEIN; DIMER FORMATION; IN-VITRO; SARCOMA VIRUSES; VIRAL-RNA; TYPE-1; REPLICATION; MATURATION AB Retroviral particles contain two positive-strand genomic RNAs linked together by noncovalent bonds that can be dissociated under mild conditions. We studied genomic RNAs of wild-type and mutant avian leukosis viruses (ALVs) in an attempt to (i) better understand the site(s) of RNA dimerization, (ii) examine whether the primer binding site (PBS) and tRNA primer are involved in dimerization, and (iii) determine the structure of genomic RNA in protease-deficient (PR-) mutants. We showed that extensively nicked wild-type ALV genomic RNAs melt cooperatively. This implies a complex secondary and/or tertiary structure for these RNAs that extends well beyond the 5' dimerization site. To investigate the role of the PBS-tRNA complex in dimerization, we analyzed genomic RNAs from mutant viruses in which the tRNA(Trp) PBS had been replaced with sequences homologous to the 3' end of six other chicken tRNAs. We found the genomic RNAs of these viruses are dimers that dissociate at the same temperature as wild-type viral RNA, which suggests that the identity of the PBS and the tRNA primer do not affect dimer stability. We studied two ALV PR- mutants: one containing a large (>1.9-kb) inversion spanning the 3' end of gag and much of pol, rendering it deficient in PR, reverse transcriptase, and integrase, and another with a point mutation in PR. In both of these mutant viruses, the genomic RNA appears to be either primarily or exclusively monomeric. These data suggest that ALV can package its RNA as monomers that subsequently dimerize. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B,Bldg 539, Frederick, MD 21702 USA. NR 50 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1999 VL 73 IS 9 BP 7165 EP 7174 PG 10 WC Virology SC Virology GA 225ME UT WOS:000081964700009 PM 10438803 ER PT J AU Hu, ZY Zhang, ZS Doo, E Coux, O Goldberg, AL Liang, TJ AF Hu, ZY Zhang, ZS Doo, E Coux, O Goldberg, AL Liang, TJ TI Hepatitis B virus X protein is both a substrate and a potential inhibitor of the proteasome complex SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; HBX PROTEIN; 20-S PROTEASOME; DNA-BINDING; IN-VIVO; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTORS; 26S PROTEASOME; DEGRADATION; SUBUNIT AB The hepatitis B virus X protein (HBX) is essential for the establishment of HBV infection in vivo and exerts a pleiotropic effect on diverse cellular functions. The yeast two-hybrid system had indicated that HBX could interact with two subunits of the 26S proteasome. Here we demonstrate an association in vivo of HBX with the 26S proteasome complex by coimmunoprecipitation and colocalization upon sucrose gradient centrifugation. Expression of HBX in HepG2 cells caused a modest decrease in the proteasome's chymotrypsin- and trypsin-like activities and in hydrolysis of ubiquitinated lysozyme, suggesting that HBX functions as an inhibitor of proteasome. In these cells, HBX is degraded with a half-life of 30 min. Proteasome inhibitors retarded this rapid degradation and caused a marked increase in the level of HBX and an accumulation of HBX in polyubiquitinated form. Thus, the low intracellular level of HBX in due to rapid proteolysis by the ubiquitin-proteasome pathway. Surprisingly, the proteasome inhibitors blocked the transactivation by HBX, and this effect was not a result of a squelching phenomenon due to HBX accumulation. Therefore, proteasome function is possibly required for the transactivation function of HBX. The inhibition of protein breakdown by proteasomes may account for the multiple actions of HBX and may be an important feature of HBV infection, possibly in helping stabilize viral gene products and suppressing antigen presentation. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. RI Coux, Olivier/B-3406-2010 OI Coux, Olivier/0000-0001-8455-3849 NR 57 TC 160 Z9 164 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1999 VL 73 IS 9 BP 7231 EP 7240 PG 10 WC Virology SC Virology GA 225ME UT WOS:000081964700016 PM 10438810 ER PT J AU Buge, SL Murty, L Arora, K Kalyanaraman, VS Markham, PD Richardson, ES Aldrich, K Patterson, LJ Miller, CJ Cheng, SM Robert-Guroff, M AF Buge, SL Murty, L Arora, K Kalyanaraman, VS Markham, PD Richardson, ES Aldrich, K Patterson, LJ Miller, CJ Cheng, SM Robert-Guroff, M TI Factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (SIV) envelope priming-gp120 boosting regimen and challenged vaginally with SIVmac251 SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODY; RHESUS MACAQUES; INTRAVAGINAL INOCULATION; SYSTEMIC INFECTION; VACCINE PROTECTION; MUCOSAL INFECTION; ATTENUATED SIV; V3 DOMAIN; T-CELLS; TYPE-1 AB Rhesus macaques were immunized with a combination vaccine regimen consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (Ad5hr-SIVenv) recombinant priming and boosting with native SIV gp120. Upon intravaginal challenge with SIVmac251, both persistently and transiently viremic animals were observed (S. L. Buge, E. Richardson, S. Alipanah, P. Markham, S. Cheng, N. Kalyan, C, J, Miller, M. Lubeck, S, Udem, J, Eldridge, and M. Robert-Guroff, J. Virol. 71:8531-8541, 1997), Long-term follow-up of the persistently viremic immunized macaques, which displayed significantly reduced viral burdens during the first 18 weeks postchallenge compared to controls, has now shown that one of four became a slow progressor, clearing virus from plasma and remaining asymptomatic with stable CD4 counts for 134 weeks postchallenge, Reboosting of the transiently viremic macaques did not reactivate latent virus. Rechallenge with two sequential SIVmac251 intravaginal exposures again resulted in partial protection of one of two immunized macaques, manifested by viral clearance and stable CD4 counts. No single immune parameter was associated with partial protection. Development of a strong antibody response capable of neutralizing a primary SIVmac251 isolate together with SIV-specific cytotoxic T lymphocytes were implicated, while CD8(+) T-cell antiviral activity and mucosal immune responses were not associated with delayed disease progression. Our data show that even a third immunization with the same Ad5hr-SIVenv recombinant can elicit significant immune responses to the inserted gene product, suggesting that preexisting Ad antibodies may not preclude effective immunization. Further, the partial protection against a virulent, pathogenic SIV challenge observed in two of six macaques immunized with a vaccine regimen based solely on the viral envelope indicates that this vectored-vaccine approach has promise and that multicomponent vaccines based in the same system merit further investigation. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. Wyeth Ayerst Res, Radnor, PA 19087 USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, Bldg 41,Room D804,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 69 TC 42 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1999 VL 73 IS 9 BP 7430 EP 7440 PG 11 WC Virology SC Virology GA 225ME UT WOS:000081964700039 PM 10438833 ER PT J AU Cohen, JI Lekstrom, K AF Cohen, JI Lekstrom, K TI Epstein-Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-KILLER-CELLS; OPEN READING FRAME; HERPESVIRUS SAIMIRI; NUCLEAR PROTEIN-2; GAMMA-INTERFERON; EXPRESSION; RECEPTOR; LYMPHOCYTES; ENCODES; GENES AB The Epstein-Barr virus (EBV) BARF1 gene encodes a soluble colony-stimulating factor 1 (CSF-1) receptor that neutralizes the effects of CSF-1 in vitro. To study the effect of BARF1 on EBV-induced transformation, we added recombinant BARF1 to B cells in the presence of EBV. BARF1 did not enhance transformation of B cells by EBV in vitro. To study the role of BARF1 in the context of EBV infection, we constructed a recombinant EBV mutant with a large deletion followed by stop codons in the BARF1 gene as well as a recombinant virus with a wild-type BARF1 gene. While BARF1 has previously been shown to act as an oncogene in several cell lines, the EBV BARF1 deletion mutant transformed B cells and initiated latent infection, and the B cells transformed with the BARF1 mutant virus induced tumors in SCID mice with an efficiency similar to that of the wild-type recombinant virus. Since human CSF-1 stimulates secretion of alpha interferon from mononuclear cells and BARF1 encodes a soluble CSF-1 receptor, we examined whether recombinant BARF1 or BARF1 derived from EBV-infected B cells could inhibit alpha interferon secretion. Recombinant BARF1 inhibited alpha interferon secretion by mononuclear cells in a dose-dependent fashion. The B cells transformed with mutant BARF1 EBV showed reduced inhibition of alpha interferon secretion by human mononuclear cells when compared with the B cells transformed with wild-type recombinant virus. These experiments indicate that BARF1 expressed from the EBV genome directly inhibits alpha interferon secretion, which may modulate the innate host response to the virus. C1 NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bldg 10,Rm 11N214, Bethesda, MD 20892 USA. NR 44 TC 70 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1999 VL 73 IS 9 BP 7627 EP 7632 PG 6 WC Virology SC Virology GA 225ME UT WOS:000081964700059 PM 10438853 ER PT J AU Beer, BE Bailes, E Goeken, R Dapolito, G Coulibaly, C Norley, SG Kurth, R Gautier, JP Gautier-Hion, A Vallet, D Sharp, PM Hirsch, VM AF Beer, BE Bailes, E Goeken, R Dapolito, G Coulibaly, C Norley, SG Kurth, R Gautier, JP Gautier-Hion, A Vallet, D Sharp, PM Hirsch, VM TI Simian immunodeficiency virus (SIV) from sun-tailed monkeys (Cercopithecus solatus): Evidence for host-dependent evolution of SIV within the C. lhoesti superspecies SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; CROSS-SPECIES TRANSMISSION; WILD-CAPTURED CHIMPANZEE; HIGHLY DIVERGENT; SOOTY MANGABEYS; MOLECULAR CHARACTERIZATION; SEROEPIDEMIOLOGIC SURVEY; PHYLOGENETIC HISTORY; SEQUENCE ALIGNMENT; PRIMATE LENTIVIRUS AB Recently we reported the characterization of simian immunodeficiency virus (SIVlhoest) from a central African l'hoest monkey (Cercopithecus lhoesti lhoesti) that revealed a distant relationship to SIV isolated from a mandrill (SIVmnd). The present report describes a novel SIV (SIVsun) isolated from a healthy, wild-caught sun-tailed monkey (Cercopithecus lhoesti solatus), another member of the l'hoest superspecies. SNsun replicated in a variety of human T-cell lines and in peripheral blood mononuclear cells of macaques (Macaca spp.) and patas monkeys (Erythrocebus patas). A full-length infectious clone of SIVsun was derived, and genetic analysis revealed that SIVsun was most closely related to SIVlhoest, with an amino acid identity of 71% in Gag, 73% in Pol, and 67% in Env. This degree of similarity is reminiscent of that observed between SIVagm isolates from vervet, grivet, and tantalus species of African green monkeys. The close relationship between SNsun and SIVlhoest, despite their geographically distinct habitats, is consistent with evolution from a common ancestor, providing further evidence for the ancient nature of the primate lentivirus family. In addition, this observation leads us to suggest that the SIVmnd lineage should be designated the SIVlhoest lineage. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2UH, England. CNRS, UMR 6552, Biol Stn, Paimpont, France. Paul Ehrlich Inst, D-63225 Langen, Germany. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Sharp, Paul/F-5783-2010 OI Sharp, Paul/0000-0001-9771-543X NR 70 TC 85 Z9 86 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1999 VL 73 IS 9 BP 7734 EP 7744 PG 11 WC Virology SC Virology GA 225ME UT WOS:000081964700069 PM 10438863 ER PT J AU Super, HJ Hasenkrug, KJ Simmons, S Brooks, DM Konzek, R Sarge, KD Morimoto, RI Jenkins, NA Gilbert, DJ Copeland, NG Frankel, W Chesebro, B AF Super, HJ Hasenkrug, KJ Simmons, S Brooks, DM Konzek, R Sarge, KD Morimoto, RI Jenkins, NA Gilbert, DJ Copeland, NG Frankel, W Chesebro, B TI Fine mapping of the friend retrovirus resistance gene, Rfv3, on mouse chromosome 15 SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-SURFACE ANTIGENS; MURINE RETROVIRUS; LINKAGE MAP; T-CELLS; VIRUS; LEUKEMIA; RECOVERY; INFECTION; ANTIBODY; MICE AB Rfv3 is a host resistance gene that operates through an unknown mechanism to control the development of the virus-neutralizing antibody response required for recovery from infection with Friend retrovirus. The Rfv3 gene was previously mapped to an approximately 20-centimorgan (cM) region of chromosome 15. More refined mapping was not possible, due to a lack of microsatellite markers and leakiness in the Rfv3 phenotype, which prevented definitive phenotyping of individual recombinant mice. In the present study, we overcame these difficulties by taking advantage of seven new microsatellite markers in the Rfv3 region and by using progeny tests to accurately determine the Rfv3 phenotype of recombinant mice. Detailed linkage analysis of relevant crossovers narrowed the location of Rfv3 to a 0.83-cM region. Mapping of closely linked genes in an interspecific backcross panel allowed us to exclude two previous candidate genes, Ly6 and Wnt7b. These studies also showed for the first time that the Hsf1 gene maps to the Rfv3-linked cluster of genes including Il2rb, Il3rb, and Pdgfb. This localization of Rfv3 to a region of less than 1 cM now makes it feasible to attempt the cloning of Rfv3 by physical methods. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Univ Kentucky, Dept Biochem, Lexington, KY 40536 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 22 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1999 VL 73 IS 9 BP 7848 EP 7852 PG 5 WC Virology SC Virology GA 225ME UT WOS:000081964700084 PM 10438878 ER PT J AU Kim, S Stern, JS Schwartz, MW McAfee, L Yanovski, S Wadden, T AF Kim, S Stern, JS Schwartz, MW McAfee, L Yanovski, S Wadden, T TI The future of weight management SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Editorial Material C1 NIH, Endocrinol & Reprod Sci Res Grp, Bethesda, MD 20892 USA. NIH, Nutr & Metab Sci Res Grp, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Washington, Seattle, WA 98195 USA. NIDDKD, Obes & Eating Disorders Program, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kim, S (reprint author), NIH, Endocrinol & Reprod Sci Res Grp, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD SEP PY 1999 VL 8 IS 7 BP 889 EP 899 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 245NU UT WOS:000083115700004 ER PT J AU Burns, DN Mofenson, LM AF Burns, DN Mofenson, LM TI Paediatric HIV-1 infection SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; ZIDOVUDINE TREATMENT; CLINICAL-TRIAL; COST-EFFECTIVENESS; WOMEN; MORTALITY; TYPE-1; RISK; PREGNANCY C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Burns, DN (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. NR 60 TC 6 Z9 6 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP PY 1999 VL 354 SU 2 BP S1 EP S6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 239QH UT WOS:000082780700001 ER PT J AU Paylor, R Hirotsune, S Gambello, MJ Yuva-Paylor, L Crawley, JN Wynshaw-Boris, A AF Paylor, R Hirotsune, S Gambello, MJ Yuva-Paylor, L Crawley, JN Wynshaw-Boris, A TI Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice SO LEARNING & MEMORY LA English DT Article ID PLATELET-ACTIVATING-FACTOR; DIEKER LISSENCEPHALY GENE; MORRIS WATER TASK; HIPPOCAMPAL-FORMATION; CORTICAL DEVELOPMENT; PREPULSE INHIBITION; WORKING MEMORY; RATS; LESIONS; FEAR AB Heterozygous mutation or deletion of Pafab1b1 (LIS1) in humans is associated with syndromes with type 1 Lissencephaly, a severe brain developmental disorder resulting from abnormal neuronal migration. We have created Lis1 heterozygous mutant mice by gene targeting. Heterozygous mutant mice are viable and fertile, but display global organizational brain defects as a result of impaired neuronal migration. To assess the functional impact of the mutation, Lis1 heterozygous mice and their wild-type littermates were evaluated on a wide variety of behavioral tests. Lis1 mutant mice displayed abnormal hindpaw clutching responses and were impaired on a rotarod test. Lis1 heterozygous mice were also impaired in the spatial learning version of the Morris water task. Impaired motor behavior and spatial learning and memory in Lis1 mutant mice indicates that impaired neuronal migration can have functional effects on complex behavioral responses. The behavioral findings also support the use of the Lis1 mutant mice as a model from human type 1 lissencephaly. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Paylor, R (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. FU NICHD NIH HHS [P30 HD024064, P30 HD24064-11] NR 42 TC 60 Z9 60 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD SEP-OCT PY 1999 VL 6 IS 5 BP 521 EP 537 DI 10.1101/lm.6.5.521 PG 17 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 247JG UT WOS:000083217200011 PM 10541472 ER PT J AU Salzmann, M Stocking, EM Silks, LA Senn, H AF Salzmann, M Stocking, EM Silks, LA Senn, H TI NMR characterization of I,I-selenocystine with 92% Se-77 enrichment SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; Se-77 NMR; H-1 NMR; Se-77 enrichment; Se-77 labeling; (Se-77)(2)-cystine; biomolecules; strong coupling ID NUCLEAR-MAGNETIC-RESONANCE; SELENOCYSTEINE; PROTEINS AB Techniques for the biosynthetic incorporation of selenomethionine into biomolecules have recently been exploited to produce both heavy-atom derivatives and NMR probes for the elucidation of local and global structures of a variety of biological macromolecules. Since the work of Bock and co-workers in 1994, also chalcogen analogue replacement of cystine by selenocystine residues in proteins can be achieved to study structural, mechanistic and functional aspects of enzymes. This paper reports the H-1 and Se-77 NMR spectroscopic characterisation of 1,1-selenocystine with 77Se at natural abundance and 92% enriched: delta(H-1), delta(Se-77); (1)J(Se-77,Se-77'), (2)J((HBbeta 1,beta 2)-H-1,Se-77), (3)J((HBbeta 1,beta 2)-H-1, 77Se'), (3)J(H-1(alpha), Se-77); T-1(Se-77), T-2(Se-77), T-1p(Se-77). The linewidth of the 77Se resonance of selenocystine is dominated by chemical shift anisotropy relaxation, as shown by its dependence on the square of the magnetic field. The reported parameters will serve as reference data for the biomolecular NMR spectroscopy of Se-77-labeled proteins where the cysteine has been replaced by selenocysteines. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 F Hoffmann La Roche AG, Pharma Res, CH-4070 Basel, Switzerland. Univ Calif Los Alamos Natl Lab, NIH Natl Stable Isotope Resource, Los Alamos, NM 87545 USA. RP Senn, H (reprint author), F Hoffmann La Roche AG, Pharma Res, PRPIS 65-512, CH-4070 Basel, Switzerland. NR 14 TC 14 Z9 14 U1 2 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD SEP PY 1999 VL 37 IS 9 BP 672 EP 675 DI 10.1002/(SICI)1097-458X(199909)37:9<672::AID-MRC514>3.0.CO;2-O PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 236AL UT WOS:000082576000010 ER PT J AU Pajevic, S Pierpaoli, C AF Pajevic, S Pierpaoli, C TI Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: Application to white matter fiber tract mapping in the human brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion; tensor; color; white matter; MRI; anisotropy; brain; human ID MAGNETIC-RESONANCE; WATER DIFFUSION; MR-IMAGES; IN-VIVO; ECHO; RAT; STROKE AB This paper investigates the use of color to represent the directional information contained in the diffusion tensor. Ideally, one wants to take into account both the properties of human color vision and of the given display hardware to produce a representation in which differences in the orientation of anisotropic structures are proportional to the perceived differences in color. It is argued here that such a goal cannot be achieved in general and therefore, empirical or heuristic schemes, which avoid some of the common artifacts of previously proposed approaches, are implemented. Directionally encoded color (DEC) maps of the human brain obtained using these schemes clearly show the main association, projection, and commissural white matter pathways. In the brainstem, motor and sensory pathways are easily identified and can be differentiated from the transverse pontine fibers and the cerebellar peduncles. DEC maps obtained from diffusion tensor imaging data provide a simple and effective way to visualize fiber direction, useful for investigating the structural anatomy of different organs. (C) 1999 Wiley-Liss, Inc. C1 NIH, Mat & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Pierpaoli, C (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, LIMB, Bldg 13,Room 3N17,13 Ctr Dr, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011 NR 34 TC 508 Z9 514 U1 0 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 1999 VL 42 IS 3 BP 526 EP 540 DI 10.1002/(SICI)1522-2594(199909)42:3<526::AID-MRM15>3.0.CO;2-J PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 232BR UT WOS:000082346300015 PM 10467297 ER PT J AU Yu, P Mosbrook, DM Tagle, DA AF Yu, P Mosbrook, DM Tagle, DA TI Genomic organization and expression analysis of mouse kynurenine aminotransferase II, a possible factor in the pathophysiology of Huntington's disease SO MAMMALIAN GENOME LA English DT Article ID ASPARTATE-AMINOTRANSFERASE; QUINOLINIC ACID; GENE PROMOTER; RAT-BRAIN; BINDING PROTEINS; TRANSAMINASE-K; C-JUN; TRANSCRIPTION; IDENTIFICATION; CLONING AB Decreased levels of the endogenous neuroprotectant kynurenic acid (KYNA) have been observed in the brain of Huntington's Disease (HD) patients and may be related to neuronal loss in this disorder. This reduction may be caused by a dysfunction of kynurenine aminotransferase II (KAT II), the major enzyme responsible for the synthesis of KYNA in the brain. Towards understanding the role of KAT II in HD, we isolated and characterized the cDNA sequence and determined the genomic organization of mouse KAT II (mKat-2). The full length mKat-2 cDNA is 1812 bp, encoding 425 amino acids, and shares 89.9% amino acid similarity with the rat Kat-2 sequence. The gene for mKat-2 is com: posed of 13 exons divided by 12 intronic sequences. Northern blot analysis demonstrated that mKat-2 mRNA is mainly expressed in kidney and liver. RT-PCR showed mKat-2 expression in the brain starting from at least d11 of embryonic development. An alternative isoform mKat-2 beta, derived from the usage of novel exons, shows a different expression pattern from mKnr-2. Western blot analysis of various mouse tissues shows a 40-kDa protein in brain, heart, kidney, and liver. In the kidney and liver an additional 45-kDa isoform was detected. Use of the BSS chromosomal mapping panel from The Jackson Laboratory indicates that the mKat-2 gene co-segregates with polymorphic markers D8Mit129 and D8Mit128 on mouse Chr 8. Knowledge of the genomic organization, the isoform tissue-specific expression patterns, the chromosomal localization of mKat-2, and the reagents generated here, will provide the tools for further studies and allow generation and characterization of mice that are nullizygous for mKat-2. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Tagle, DA (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bldg 49,Room 3A26,49 Convent Dr MSC 4442, Bethesda, MD 20892 USA. NR 52 TC 16 Z9 18 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1999 VL 10 IS 9 BP 845 EP 852 DI 10.1007/s003359901102 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 226AF UT WOS:000081997600001 PM 10441733 ER PT J AU Kozak, CA Su, Y Raj, NBK Pitha, PM AF Kozak, CA Su, Y Raj, NBK Pitha, PM TI Identification and genetic mapping of differentially expressed genes in mice differing at the If1 interferon regulatory locus SO MAMMALIAN GENOME LA English DT Article ID PRIMARY SEQUENCE; MOUSE GENOTYPE; MESSENGER-RNA; CELLS AB A subtractive cDNA library was used to identify differentially expressed genes in mouse strains that differ at ISI, a locus that regulates response to interferon induction by Newcastle Disease Virus infection. Among the isolated clones, sequence analysis identified the ribosomal proteins L37a and S8 as well as cDNAs for thymosine beta 4, the QM transcriptional factor, and a novel genetic sequence. Analysis of two multilocus mouse crosses showed that the thymosine beta 4 gene, Ptmb4, is present as a single-copy gene that maps to distal Chr X. The L37a, S8, and QM clones are all members of large multilocus families. These five clones were used to determine the map locations for 37 loci, of which 31 had not previously been described. The novel genetic sequence, D3Ppr1, mapped to distal Chr 3 near the position of the If1 locus, suggesting it may be a candidate for this regulatory gene. C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21231 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI19737] NR 18 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1999 VL 10 IS 9 BP 853 EP 857 DI 10.1007/s003359901103 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 226AF UT WOS:000081997600002 PM 10441734 ER PT J AU Lueders, KK Elliott, RW Marenholz, I Mischke, D DuPree, M Hamer, D AF Lueders, KK Elliott, RW Marenholz, I Mischke, D DuPree, M Hamer, D TI Genomic organization and mapping of the human and mouse neuronal beta 2-nicotinic acetylcholine receptor genes SO MAMMALIAN GENOME LA English DT Article ID SUBUNIT GENE; CHROMOSOMAL LOCALIZATION; EXPRESSION; BETA-2; SEQUENCE; ELEMENTS; ALPHA-2; MICE; PROMOTER; CLONING AB As a first step in determining whether there are polymorphisms in the nicotinic acetylcholine receptor (nAChR) genes that are associated with nicotine addiction, we isolated genomic clones of the beta 2-nAChR genes from human and mouse BAC libraries. Although cDNA sequences were available for the human gene, only the promoter sequence had been reported for the mouse gene. We determined the genomic structures by sequencing 12 kb of the human gene and over 7 kb of the mouse gene. While the sizes of exons in the mouse and human genes are the same, the introns differ in size. Both promoters have a high CC content (60-80%) proximal to the AUG and share a neural-restrictive silencer element (NRSE), but overall sequence identity is only 72%. Using a 6-Mb YAC contig of Chr 1, we mapped the human beta 2-nAChR gene, CHRNB2, to 1q21.3 with the order of markers cen, FLG, IVL, LORI CHRNB2, tel. The mouse gene, Acrb2, had previously been mapped to Chr 3 in a region orthologous to human Chr 1. We refined mapping of the mouse gene and other markers on a radiation hybrid panel of Chr 3 and found the order cen, Acrb2, Lor, Iv1, Flg, tel. Our results indicate that this cluster of markers on human Chr 1 is inverted with respect to its orientation on the chromosome compared with markers in the orthologous region of mouse Chr 3. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. Humboldt Univ, Inst Immunogenet, D-14050 Berlin, Germany. RP Lueders, KK (reprint author), 37 Convent Dr Bldg 37 Rm4D-14, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM33160] NR 36 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1999 VL 10 IS 9 BP 900 EP 905 DI 10.1007/s003359901111 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 226AF UT WOS:000081997600010 PM 10441742 ER PT J AU Li, HZ Wu, DK Sullivan, SL AF Li, HZ Wu, DK Sullivan, SL TI Characterization and expression of sema4g, a novel member of the semaphorin gene family SO MECHANISMS OF DEVELOPMENT LA English DT Article DE semaphorin; collapsin; axon guidance; mouse; sensory ganglion; retina; inner ear; olfactory system; vomeronasal organ; mouse chromosome 19 ID GROWTH CONE GUIDANCE; MOLECULES; COLLAPSIN; IDENTIFICATION; SYSTEM AB Semaphorins constitute a large and growing gene family, several members of which are axon guidance molecules. We report the characterization of sema4g, a novel class IV member of the semaphorin gene family, located on mouse chromosome 19. sema4g is expressed early in development in the brain, spinal cord, and several sensory organs as well as specific populations of projection neurons, compatible with the well-established function of semaphorins as axon guidance molecules. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Inst Deafness & Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Sullivan, SL (reprint author), Natl Inst Deafness & Commun Disorders, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. NR 14 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 1999 VL 87 IS 1-2 BP 169 EP 173 DI 10.1016/S0925-4773(99)00125-2 PG 5 WC Developmental Biology SC Developmental Biology GA 240LT UT WOS:000082828000016 PM 10495281 ER PT J AU Fortney, J Rost, K Zhang, ML Warren, J AF Fortney, J Rost, K Zhang, ML Warren, J TI The impact of geographic accessibility on the intensity and quality of depression treatment SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 13th NIMH International Conference on Mental Health Problems in the General Health Care Sector CY JUL, 1999 CL WASHINGTON, D.C. SP NIMH DE depression; travel time; utilization; guideline-concordance ID MENTAL-HEALTH SERVICES; PRIMARY-CARE PRACTICE; ANTIDEPRESSANT TREATMENT; MAJOR DEPRESSION; MANAGEMENT; GUIDELINES; DISORDERS; PHYSICIAN; OUTCOMES; PROGRAM AB OBJECTIVES. For depression, this research measures the impact of travel time on visit frequency and the probability of receiving treatment in concordance with AHCPR guidelines. METHODS. The medical, insurance, and pharmacy records of a community-based sample of 435 subjects with current depression were abstracted to identify those treated for depression, to determine the number of depression visits made over a 6-month period, and to ascertain whether treatment was provided in concordance with AHCPR guidelines. A Geographic Information System was used to calculate the travel time from each patient to their preferred provider. Poisson and logistic regression analyses were used to estimate the impact of travel time on visit frequency and guideline-concordance, controlling for patient casemix. RESULTS. In the community-based sample, 106 subjects were treated for depression by 105 different preferred providers. About one-third (30.7%) were treated by a mental health specialist. One average, patients made 2.8 depression visits over the 6-month period. One-third (28.9%) of the patients received guideline-concordant treatment for depression. The average number of visits for those receiving guideline-concordant care was significantly greater than for those not receiving guideline-concordant care (P < 0.01). Travel time to the preferred provider was significantly associated with making fewer visits (P < 0.0001) and having a lower likelihood of receiving guideline-concordant care (P < 0.05). DISCUSSION. For depression, both pharmacotherapy and psychotherapy treatment regimens require frequent provider contact to be effective. This study suggests that travel barriers may prevent rural patients from making a sufficient number of visits to receive effective guideline-concordant treatment. C1 Vet Adm Med Ctr, VA HSR&D, N Little Rock Div, Ctr Mental Healthcare & Outcomes Res NLR 152, Little Rock, AR 72114 USA. Univ Arkansas Med Sci, NIMH, Ctr Mental Healthcare Res, Dept Psychiat, Little Rock, AR 72205 USA. RP Fortney, J (reprint author), Vet Adm Med Ctr, VA HSR&D, N Little Rock Div, Ctr Mental Healthcare & Outcomes Res NLR 152, 2200 Ft Roots Dr, Little Rock, AR 72114 USA. FU NIMH NIH HHS [R01 MH53629, R01 MH54444, R01 MH49116] NR 29 TC 118 Z9 118 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1999 VL 37 IS 9 BP 884 EP 893 DI 10.1097/00005650-199909000-00005 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 235AA UT WOS:000082515500005 PM 10493467 ER PT J AU Chernomordik, V Gandjbakhche, AH Hebden, JC Zaccanti, G AF Chernomordik, V Gandjbakhche, AH Hebden, JC Zaccanti, G TI Effect of lateral boundaries on contrast functions in time-resolved transillumination measurements SO MEDICAL PHYSICS LA English DT Article DE time-resolved transillumination; quantitative imaging; random walk; Monte Carlo simulations; contrast functions ID PHOTON MIGRATION; LIGHT; DIFFUSION; TISSUE; MODEL; SPECTROSCOPY; TRANSPORT; DISTRIBUTIONS; REFLECTANCE; ABSORPTION AB The method of images is employed to insert the effects of the presence of a single lateral boundary on contrast functions previously derived for an infinite slab using a random walk model of photon transport. The predictions of the model for zero and extrapolated boundary conditions are compared with Monte Carlo (MC) simulations and with experimental results obtained using a homogenous phantom with tissue-like optical properties. As expected, the extrapolated boundary condition yields better agreement between the theoretical predictions and results obtained from MC and experiments. This indicates that the random walk model has potential as a forward model in iterative imaging schemes developed for optical tomography. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)01709-5]. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. UCL, Dept Med Phys, London WC1E 6JA, England. Univ Florence, Dipartimento Fis, I-50139 Florence, Italy. INFM, I-50139 Florence, Italy. RP Chernomordik, V (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 31 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 1999 VL 26 IS 9 BP 1822 EP 1831 DI 10.1118/1.598687 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 237AV UT WOS:000082632200012 PM 10505870 ER PT J AU Vortmeyer, AO Lubensky, IA Skarulis, M Li, G Moon, YW Park, WS Weil, R Barlow, C Spiegel, AM Marx, SJ Zhuang, ZP AF Vortmeyer, AO Lubensky, IA Skarulis, M Li, G Moon, YW Park, WS Weil, R Barlow, C Spiegel, AM Marx, SJ Zhuang, ZP TI Multiple endocrine neoplasia type 1: Atypical presentation, clinical course, and genetic analysis of multiple tumors SO MODERN PATHOLOGY LA English DT Article DE adrenal cortical hyperplasia; hepatic focal nodular hyperplasia; leiomyoma; loss of heterozygosity; MEN1; neuroendocrine tumors; thyroid neoplasms ID MEN1 GENE; PARATHYROID TUMORS; CHROMOSOME 11Q13; MUTATIONS; DELETION; MARKERS; LESIONS; REGION AB Multiple endocrine neoplasia type 1 (MEN1) is characterized by the development of endocrine tumors of the parathyroid and pituitary glands, pancreas, and duodenum. Less frequently occurring tumors associated with MEN1 include non-endocrine tumors such as lipomas and angiofibromas. An increased incidence of thyroid neoplasms, leiomyomas, adrenal cortical hyperplasia, hepatic focal nodular hyperplasia, and renal angiomyolipoma has been noted in the MEN1 population. The pathogenesis of non-neuroendocrine tumors in MEN1 is unknown. We report a complex clinical course and a detailed morphologic and genetic analysis of a series of tumors that developed in a patient with MEN1. All tumors were microdissected and analyzed for loss of heterozygosity of the MEN1 gene. A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's "two hit" hypothesis. Two hits of the MEN1 gene were also detected in esophageal leiomyoma tissue, suggesting that tumorigenesis was directly related to the patient's underlying MEN1. In contrast, follicular thyroid adenoma, papillary thyroid carcinoma, hepatic focal nodular hyperplasia, and adrenal cortical hyperplasia consistently showed retained heterozygosity of the MEN1 gene with flanking markers and an intragenic marker. Therefore, these tumors appear to develop along pathogenetic pathways that are different from classical MEN1-associated tumors. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Hallym Univ, Sacred Heart Hosp, Dept Orthopaed Surg, Anyang City, South Korea. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1999 VL 12 IS 9 BP 919 EP 924 PG 6 WC Pathology SC Pathology GA 238AF UT WOS:000082688200011 PM 10496602 ER PT J AU Vermaak, D Wade, PA Jones, PL Shi, YB Wolffe, AP AF Vermaak, D Wade, PA Jones, PL Shi, YB Wolffe, AP TI Functional analysis of the SIN3-Histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyte SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LINKING HISTONE ACETYLATION; CHROMATIN ASSEMBLY FACTOR-1; TRANSCRIPTIONAL REPRESSION; SACCHAROMYCES-CEREVISIAE; IN-VIVO; NEGATIVE REGULATOR; N-COR; CRYSTAL-STRUCTURE; BINDING-PROTEINS; SIN3 GENE AB We investigated the protein associations and enzymatic requirements for the Xenopus histone deacetylase catalytic subunit RPD3 to direct transcriptional repression in Xenopus oocytes. Endogenous Xenopus RPD3 is present in nuclear and cytoplasmic pools, whereas RbAp48 and SIN3 are predominantly nuclear. We cloned Xenopus RbAp48 and SIN3 and show that expression of RPD3, but not RbAp48 or SIN3, leads to an increase in nuclear and cytoplasmic histone deacetylase activity and transcriptional repression of the TR beta A promoter. This repression requires deacetylase activity and nuclear import of RPD3 mediated by a carboxy-terminal nuclear localization signal. Exogenous RPD3 is not incorporated into previously described oocyte deacetylase and ATPase complexes but cofractionates with a component of the endogenous RbAp48 in the oocyte nucleus. We show that RPD3 associates,vith RbAp48 through N- and C-terminal contacts and that RbAp48 also interacts with SIN3. Xenopus RbAp48 selectively binds to the segment of the N-terminal tail immediately proximal to the histone fold domain of histone H4 in vivo. Exogenous RPD3 may be targeted to histones through interaction with endogenous RbAp48 to direct transcriptional repression of the Xenopus TR beta A promoter in the oocyte nucleus. However, the exogenous RPD3 deacetylase functions to repress transcription in the absence of a requirement for association with SIN3 or other targeted corepressors. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NR 88 TC 59 Z9 63 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1999 VL 19 IS 9 BP 5847 EP 5860 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800003 PM 10454532 ER PT J AU Koochekpour, S Jeffers, M Wang, PH Gong, CN Taylor, GA Roessler, LM Stearman, R Vasselli, JR Stetler-Stevenson, WG Kaelin, WG Linehan, WM Klausner, RD Gnarra, JR Vande Woude, GF AF Koochekpour, S Jeffers, M Wang, PH Gong, CN Taylor, GA Roessler, LM Stearman, R Vasselli, JR Stetler-Stevenson, WG Kaelin, WG Linehan, WM Klausner, RD Gnarra, JR Vande Woude, GF TI The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR SCATTER FACTOR; MET PROTOONCOGENE; MESSENGER-RNA; MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; METASTASIS; EXPRESSION; RECEPTOR; IDENTIFICATION AB Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VEL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SP in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These studies also demonstrate a synergy between the loss of VHL function and Met signaling. C1 NCI, ABL Basic Res Program, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Off Director, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Vande Woude, GF (reprint author), NCI, ABL Basic Res Program, Div Basic Sci, Frederick Canc Res & Dev Ctr, POB B,Bldg 469, Frederick, MD 21702 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA783356] NR 59 TC 153 Z9 156 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1999 VL 19 IS 9 BP 5902 EP 5912 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800008 PM 10454537 ER PT J AU Bear, J Tan, W Zolotukhin, AS Tabernero, C Hudson, EA Felber, BK AF Bear, J Tan, W Zolotukhin, AS Tabernero, C Hudson, EA Felber, BK TI Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MESSENGER-RNA EXPORT; MEDIATED POSTTRANSCRIPTIONAL REGULATION; REV ACTIVATION DOMAIN; NUCLEAR EXPORT; LEPTOMYCIN-B; HNRNP A1; SECONDARY STRUCTURE; GENE-PRODUCT; I REX AB The nuclear export of the unspliced type D retrovirus mRNA depends on the cis-acting constitutive transport RNA element (CTE) that has been shown to interact with the human TAP (hTAP) protein promoting the export of the CTE-containing mRNAs. We report here that hTAP is a 619-amino-acid protein extending the previously identified protein by another 60 residues at the N terminus and that hTAP shares high homology with the predicted rat and mouse TAP proteins. We found that hTAP is a nuclear protein that accumulates in the nuclear rim and the nucleoplasm. We further demonstrated that hTAP is able to shuttle between the nucleus and the cytoplasm. Identification of the signals responsible for nuclear import (NLS) and export (NES) revealed that they are distinct but partially overlapping. NLS and NES of hTAP are active transferable signals that do not share similarities with known elements. The C-terminal portion contributes further to hTAP's nuclear retention and contains a signal(s) for nuclear rim association. Taken together, our data show that hTAP is a dynamic protein capable of bidirectional trafficking across the nuclear envelope. These data further support hTAP's role as an export factor of the CTE-containing mRNAs. C1 NCI, Human Retrovirus Pathogenesis Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Human Retrovirus Pathogenesis Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Bldg 535,Rm 110, Frederick, MD 21702 USA. NR 64 TC 99 Z9 102 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1999 VL 19 IS 9 BP 6306 EP 6317 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800048 PM 10454577 ER PT J AU Kawamoto, T Sueyoshi, T Zelko, I Moore, R Washburn, K Negishi, M AF Kawamoto, T Sueyoshi, T Zelko, I Moore, R Washburn, K Negishi, M TI Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GLUCOCORTICOID RECEPTORS; LIVING CELLS; OKADAIC ACID; TRANSCRIPTION; PHOSPHORYLATION; EXPRESSION; PATHWAYS; UNIT AB The constitutively active receptor (CAR) transactivates a distal enhancer called the phenobarbital (PB) responsive enhancer module (PBREM) found in PB-inducible CYP2B genes. CAR dramatically increases its binding to PBREM in livers of PB-treated mice. We have investigated the cellular mechanism of PB-induced increase of CAR binding. Western blot analyses of mouse livers revealed an extensive nuclear accumulation of CAR following PB treatment. Nuclear contents of CAR perfectly correlate with an increase of CAR binding to PBREM. PB-elicited nuclear accumulation of CAR appears to be a general step regulating the induction of CYP2B genes, since treatments with other PB-type inducers result in the same nuclear accumulation of CAR. Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Nuclear translocation of CAR also occurs in mouse primary hepatocytes but not in hepatocytes treated with the protein phosphatase inhibitor okadaic acid. Thus, the CAR-mediated transactivation of PBREM in vivo becomes PB responsive through an okadaic acid-sensitive nuclear translocation process. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Zelko, Igor/L-2673-2013; Kawamoto, Takeshi/D-7938-2015 OI Zelko, Igor/0000-0003-3976-3884; Kawamoto, Takeshi/0000-0003-3337-1775 NR 22 TC 392 Z9 405 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1999 VL 19 IS 9 BP 6318 EP 6322 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800049 PM 10454578 ER PT J AU Osada, M Tolkacheva, T Li, WQ Chan, TO Tsichlis, PN Saez, R Kimmelman, AC Chan, AML AF Osada, M Tolkacheva, T Li, WQ Chan, TO Tsichlis, PN Saez, R Kimmelman, AC Chan, AML TI Differential roles of Akt, Rac, and Ral in R-Ras-mediated cellular transformation, adhesion, and survival SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE DISSOCIATION STIMULATOR; ANCHORAGE-INDEPENDENT GROWTH; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; INTEGRIN ACTIVATION; ACTIN POLYMERIZATION; ONCOGENIC RAS; CELLS; PATHWAYS; EFFECTOR AB Multiple biological functions have been ascribed to the Ras-related G protein R-Ras. These include the ability to transform NIH 3T3 fibroblasts, the promotion of cell adhesion, and the regulation of apoptotic responses in hematopoietic cells. To investigate the signaling mechanisms responsible for these biological phenotypes, we compared three R-Ras effector loop mutants (S61, G63, and C66) for their relative biological and biochemical properties. While the S61 mutant retained the ability to cause transformation, both the G63 and the C66 mutants were defective in this biological activity. On the other hand, while both the S61 and the C66 mutants failed to promote cell adhesion and survival in 32D cells, the G63 mutant retained the ability to induce these biological activities. Thus, the ability of R-Ras to transform cells could be dissociated from its propensity to promote cell adhesion and survival. Although the transformation-competent S61 mutant bound preferentially to c-Raf, it only weakly stimulated the mitogen-activated protein kinase (MAPK) activity, and a dominant negative mutant of MEK did not significantly perturb R-Ras oncogenicity. Instead, a dominant negative mutant of phosphatidylinositol 3-kinase (PI3-K) drastically inhibited the oncogenic potential of R-Ras. Interestingly, the ability of the G63 mutant to induce cell adhesion and survival was closely associated with the PI3-K-dependent signaling cascades. To further delineate R-Ras downstream signaling events, we observed that while a dominant negative mutant of Akt/protein kinase inhibited the ability of R-Ras to promote cell survival, both dominant negative mutants of Rac and Ral suppressed cell adhesion stimulated by R-Ras. Thus, the biological actions of R-Ras are mediated by multiple effecters, with PI3-K-dependent signaling cascades being critical to its functions. C1 CUNY Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA. RP Chan, AML (reprint author), CUNY Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, 1 Gustave Levy,Box 1130, New York, NY 10029 USA. OI Chan , Tung/0000-0001-6574-9555 FU NCI NIH HHS [CA66654, CA78509] NR 57 TC 65 Z9 67 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1999 VL 19 IS 9 BP 6333 EP 6344 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800051 PM 10454580 ER PT J AU Lemkin, PF Thornwall, G AF Lemkin, PF Thornwall, G TI Flicker image comparison of 2-D gel images for putative protein identification using the 2DWG meta-database SO MOLECULAR BIOTECHNOLOGY LA English DT Review DE 2-D gel electrophoresis; databases; World Wide Web ID 2-DIMENSIONAL ELECTROPHORESIS; SWISS-2DPAGE DATABASE; COMPUTER AB With the availability of two-dimensional (2-D) gel electrophoresis databases that have many characterized proteins, it may be possible to compare a researcher's gel images with those in relevant databases. This may lead to the putative identification of unknown protein spots in a researcher's gel with those characterized in a given database, saving the researcher time and money by suggesting monoclonal antibodies to try in confirming these identifications. We have developed two tools to help with this comparison: (1) Flicker, http://www.lecb.ncifcrf.gov/flicker/, a Java applet program running in the researcher's Web browser, to visually compare their gels against gels on the Internet; and (2) the 2DWG meta-database, http://www.lecb.ncifcrf.gov/2dwgDB/, a searchable database of locations of 2-D electrophoretic gel images found on the Internet. Recent additions to Flicker allow users to click on a protein spot in a gel that is linked to a federated 2D gel database, such as SWISS-2DPAGE, and have it retrieve a report from that Web database for that protein. C1 NCI, IPS, LECB, FCRDC, Ft Detrick, MD 21702 USA. SAIC, FCRDC, Ft Detrick, MD 21702 USA. NR 29 TC 11 Z9 11 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD SEP PY 1999 VL 12 IS 2 BP 159 EP 172 DI 10.1385/MB:12:2:159 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 250TK UT WOS:000083404100004 PM 10596373 ER PT J AU Bednar, J Studitsky, VM Grigoryev, SA Felsenfeld, O Woodcock, CL AF Bednar, J Studitsky, VM Grigoryev, SA Felsenfeld, O Woodcock, CL TI The nature of the nucleosomal barrier to transcription: Direct observation of paused intermediates by electron cryomicroscopy SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE; CRYOELECTRON MICROSCOPY; TRANSCRIBING POLYMERASE; CHROMATIN; DNA; ELONGATION; MECHANISM; TEMPLATE; CORE; COMPACTION AB Transcribing SP6 RNA polymerase was arrested at unique positions in the nucleosome core, and the complexes were analyzed using biochemical methods and electron cryomicroscopy. As the polymerase enters the nucleosome, it disrupts DNA-histone interactions behind and up to similar to 20 bp ahead of the elongation complex. After the polymerase proceeds 30-40 bp into the nucleosome, two intermediates are observed. In one, only the DNA ahead of the polymerase; reassociates with the octamer. In the other, DNA both ahead of and behind the enzyme reassociates. These intermediates present a barrier to elongation. When the polymerase approaches the nucleosome dyad, it displaces the octamer, which is transferred to promoter-proximal DNA. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. RP Felsenfeld, O (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Bednar, Jan/K-2162-2012; Studitsky, Vasily/A-9382-2014 FU NIGMS NIH HHS [GM58650, GM43786, GM51352] NR 31 TC 49 Z9 51 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD SEP PY 1999 VL 4 IS 3 BP 377 EP 386 DI 10.1016/S1097-2765(00)80339-1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 241KT UT WOS:000082882800009 PM 10518218 ER PT J AU Schulte, TW Akinaga, S Murakata, T Agatsuma, T Sugimoto, S Nakano, H Lee, YS Simen, BB Argon, Y Felts, S Toft, DO Neckers, LM Sharma, SV AF Schulte, TW Akinaga, S Murakata, T Agatsuma, T Sugimoto, S Nakano, H Lee, YS Simen, BB Argon, Y Felts, S Toft, DO Neckers, LM Sharma, SV TI Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CELL-FREE SYSTEM; ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; SIGNAL-TRANSDUCTION; STEROID-RECEPTOR; TERMINAL DOMAIN; KINASE-ACTIVITY; ATP BINDING; DNA GYRASE; IN-VIVO AB The Hsp90 family of proteins in mammalian cells consists of Hsp90 alpha and beta, Grp94, and Trap-1 (Hsp75). Radicicol, an antifungal antibiotic that inhibits various signal transduction proteins such as v-src, ras, Raf-1, and mos, was found to bind to Hsp90, thus making it the prototype of a second class of Hsp90 inhibitors, distinct from the chemically unrelated benzoquinone ansamycins. We have used two novel methods to immobilize radicicol, allowing for detailed analyses of drug-protein interactions. Using these two approaches, we have studied binding of the drug to N-terminal Hsp90 point mutants expressed by in vitro translation. The results point to important drug contacts with amino acids inside the N-terminal ATP/ADP-binding pocket region and show subtle differences when compared with geldanamycin binding. Radicicol binds more strongly to Hsp90 than to Grp94, the Hsp90 homolog that resides in the endoplasmic reticulum. In contrast to Hsp90, binding of radicicol to Grp94 requires both the N-terminal ATP/ADP-binding domain as well as the adjacent negatively charged region. Radicicol also specifically binds to yeast Hsp90, Escherichia coli HtpG, and a newly described tumor necrosis factor receptor-interacting protein, Trap-1, with greater homology to bacterial HtpG than to Hsp90. Thus, the radicicol-binding site appears to be specific to and is conserved in all members of the Hsp90 family of molecular chaperones from bacteria to mammals, but is not present in other molecular chaperones with nucleotide-binding domains. C1 Natl Canc Inst, Med Branch, NIH, Rockville, MD 20850 USA. Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Shizuoka 411, Japan. Kyowa Hakko Kogyo Co Ltd, Tokyo Res Labs, Tokyo 194, Japan. NEI, Lab Ocular Therapeut, Bethesda, MD 20892 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Mayo Grad Sch, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Univ Tennessee, Dept Microbiol & Immunol, Memphis, TN 38163 USA. RP Neckers, LM (reprint author), Natl Canc Inst, Med Branch, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM len@helix.nih.gov RI Simen, Birgitte/A-3574-2010 NR 56 TC 119 Z9 122 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1999 VL 13 IS 9 BP 1435 EP 1448 DI 10.1210/me.13.9.1435 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230MZ UT WOS:000082256100001 PM 10478836 ER PT J AU Xia, J Bogardus, C Prochazka, M AF Xia, J Bogardus, C Prochazka, M TI A type 2 diabetes-associated polymorphic ARE motif affecting expression of PPP1R3 is involved in RNA-protein interactions SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE type 1 protein phosphatase; PPP1R3 gene; ARE motif polymorphism; RNA-protein binding ID SYNTHASE PHOSPHATASE-ACTIVITY; 3' UNTRANSLATED REGION; MESSENGER-RNA; 3'-UNTRANSLATED REGION; INSULIN-RESISTANCE; BINDING PROTEIN; AUUUA MOTIFS; MUSCLE; DESTABILIZATION; DEGRADATION AB We have previously described a polymorphism in the 3' untranslated region (UTR) of the PPP1R3 gene that encodes the muscle-specific glycogen-targeting regulatory PP1 subunit. This polymorphism alters the distance between two putative mRNA-destabilizing ATTTA (AUUUA) motifs and is distinguished by a 10-nucleotide (allele ARE1) vs a 2-nucleotide interval (allele ARE2). ARE2 is associated with insulin resistance as well as increased prevalence of type 2 diabetes in the Pima Indians, and correlates with reduced expression of this subunit in vivo causing a 10-fold half-life reduction of reporter mRNA in NIH3T3 cells. Gel shift assays, Northwestern blotting, and RNA-protein UV crosslinking revealed three proteins (43, 80, and 139 kDa) binding to the polymorphic ARE region in these cells. The interactions are sequence specific, and can be suppressed by an unlabeled competitor in a dose-dependent manner. The less stable ARE2 allele shows at least a-fold higher relative protein binding, indicating that the polymorphic ARE region has a mRNA-destabilizing role. We suggest that the increased protein binding to ARE2 contributes to a faster degradation of PPP1R3 mRNA carrying this allele, and the resulting lower concentration of the protein contributes to insulin resistance, thus increasing the risk for development of type 2 diabetes. C1 NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Prochazka, M (reprint author), NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 22 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP PY 1999 VL 68 IS 1 BP 48 EP 55 DI 10.1006/mgme.1999.2884 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 240XE UT WOS:000082851700006 PM 10479482 ER PT J AU Makrigiannakis, A Margioris, AN Chatzaki, E Zoumakis, E Chrousos, GP Gravanis, A AF Makrigiannakis, A Margioris, AN Chatzaki, E Zoumakis, E Chrousos, GP Gravanis, A TI The decidualizing effect of progesterone may involve direct transcriptional activation of corticotrophin-releasing hormone from human endometrial stromal cells SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE CRF; corticotrophin-releasing hormone; decidualization; endometrium; progesterone ID CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; GENE-EXPRESSION; IN-VITRO; RECEPTOR; IDENTIFICATION; HYPOTHALAMUS; MEMBRANES; MECHANISM; PROMOTER; ELEMENTS AB The hypothalamic neuropeptide corticotrophin-releasing hormone (CRH) is also produced by human endometrial cells and is directly involved in the decidualization process as a paracrine inducer. The aim of the present work was to examine the effect of progesterone, the main decidualizing factor, on endometrial CRH, in primary cultures of human endometrial stromal cells. The effect of progesterone was examined by measuring the effects of medroxyprogesterone acetate (MPA) on (i) the concentration of immunoreactive CRH in isolated human endometrial stromal cells and (ii) the activity of the CRH promoter in human endometrial stromal cells transfected with a 0.9 kb fragment of the 5'-flanking region of the human CRH gene coupled to luciferase reporter. The data show that MPA increased the production and secretion of immunoreactive CRH from stromal cells and induced the activity of the CRH promoter, both in a dose-dependent manner. These effects were partially reversed by a molar excess of the antiprogestin RU 486 and were completely abolished in the presence of 100 nmol/l of the cAMP inhibitor, Rp-cAMP. The effect of progesterone on the CRH promoter requires the existence of an intact CRH sequence since experiments carried out with a deleted palindromic cAMP response element (CRE: 5'-TGACGTCA) at -224 bp of the CRH promoter resulted in a complete loss of MPA effect. In conclusion, these data provide evidence that progesterone induces the transcription of CRH gene in human endometrial stroma. This effect coupled with the decidualizing properties of progesterone and CRH may indicate that progesterone and CRH form a decidualizing local pathway within the human endometrium. C1 Univ Crete, Sch Med, Dept Pharmacol, GR-71110 Iraklion, Greece. Univ Crete, Sch Med, Dept Clin Chem, GR-71110 Iraklion, Greece. NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Chatzaki, E (reprint author), Univ Crete, Sch Med, Dept Pharmacol, GR-71110 Iraklion, Greece. NR 40 TC 40 Z9 40 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD SEP PY 1999 VL 5 IS 9 BP 789 EP 796 DI 10.1093/molehr/5.9.789 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 232UJ UT WOS:000082388100001 PM 10460215 ER PT J AU Sueyoshi, T Yokomori, N Korach, KS Negishi, M AF Sueyoshi, T Yokomori, N Korach, KS Negishi, M TI Developmental action of estrogen receptor-alpha feminizes the growth hormone-Stat5b pathway and expression of Cyp2a4 and Cyp2d9 genes in mouse liver SO MOLECULAR PHARMACOLOGY LA English DT Article ID TESTOSTERONE 16-ALPHA-HYDROXYLASE C-P-45016-ALPHA; SEX-DEPENDENT EXPRESSION; STEROID 15-ALPHA-HYDROXYLASE; MALE-MICE; DIFFERENTIATION; TRANSCRIPTION; P-45015-ALPHA; DIMORPHISM; STAT5B; STEREOSPECIFICITY AB We have studied the roles of estrogen receptor-alpha (ER alpha) and the Stat5b form of STAT (signal transducers and activators of transcription) in sex-specific expression of Cyp2a4 (steroid 15 alpha-hydroxylase) and Cyp2d9 (steroid 16 alpha-hydroxylase) genes using ER alpha-deficient mice. ER alpha deficiency resulted in the repression of the female-specific Cyp2a4 and expression of the male-specific Cyp2d9 genes, respectively in females. In ER alpha-deficient males, the Cyp2d9 gene continued to be expressed. Nuclear localization of Stat5b occurs in both sexes of ER alpha-deficient mice, although it is normally observed in only wildtype males. Nuclear localization of Stat5b correlates with the repression of Cyp2a4 and expression of Cyp2d9, respectively. Because Stat5b was not detectable in liver nuclear extracts prepared from hypophysectomized ER alpha-deficient females, the regulation by ER alpha appeared to be mediated through a pituitary hormone (i.e., growth hormone). Thus, ER alpha appears to play a key role in the mechanism that inhibits nuclear localization of Stat5b in female mice, leading to feminization of a ER alpha-Stat5b pathway and Cyp expression. Defaulting to this ER alpha-dependent mechanism results in localization of Stat5b to nuclei, which masculinizes the expression of Cyp genes in male mice. C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 33 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1999 VL 56 IS 3 BP 473 EP 477 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230NG UT WOS:000082256800003 PM 10462534 ER PT J AU Nieves-Neira, W Rivera, MI Kohlhagen, G Hursey, ML Pourquier, P Sausville, EA Pommier, Y AF Nieves-Neira, W Rivera, MI Kohlhagen, G Hursey, ML Pourquier, P Sausville, EA Pommier, Y TI DNA protein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID ANTICANCER DRUG SCREEN; TOPOISOMERASE-I; LINES; INHIBITION; CYTOTOXICITY; CLEAVAGE; POLYMERIZATION; FEASIBILITY; APOPTOSIS; DAMAGE AB 2, 5-bis(5-Hydroxymethyl-2-thienyl)furan (NSC 652287), is a representative of a series of thiophene derivatives that exhibit potent and selective antitumor activity against several tumor cell lines in the National Cancer Institute Anticancer Drug Screen. NSC 652287 has noticeable activity for the renal cell lines and produces cures in certain corresponding xenografts. The cellular mechanisms of action of NSC 652287 were therefore investigated in this study in greater detail. The most sensitive renal carcinoma cell line, A498, exhibited cell cycle arrest in G(0)-G(1) and G(2)-M at 10 nM NSC 652287, with increased p53 and p21(WAF1) protein. At higher concentrations, NSC 652287 still induced p53 elevation but with p21(WAF1) reduction and massive apoptosis. These results collectively suggested that NSC 652287 induced DNA damage. Using alkaline elution techniques, we found that NSC 652287 induced both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks. These DNA-protein cross-links (DPC) persisted for at least 12 h after drug removal and their frequency was correlated with cytotoxicity in the renal cell lines studied. The most sensitive cells (A498) produced the highest DPC followed by the cell line with intermediate sensitivity (TK-10). DPC were minimal in the two resistant cell lines, ACHN and UO-31. Nonetheless, a similar degree of DPC occurred at doses imparting equitoxic effects. These results indicate that DNA is a primary target for the novel and potent anticancer thiophene derivative, NSC 652287. NSC 652287 did not cross-link purified DNA or mammalian topoisomerase I suggesting the importance of active metabolite(s) for the cross-linking activity. C1 NCI, Div Basic Sci, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnosis, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Frederick, MD USA. RP Pommier, Y (reprint author), NCI, Div Basic Sci, Mol Pharmacol Lab, NIH, Bldg 37,Room 5D02, Bethesda, MD 20892 USA. NR 29 TC 39 Z9 39 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1999 VL 56 IS 3 BP 478 EP 484 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230NG UT WOS:000082256800004 PM 10462535 ER PT J AU Zhou, YY Cheng, HP Song, LS Wang, DJ Lakatta, EG Xiao, RP AF Zhou, YY Cheng, HP Song, LS Wang, DJ Lakatta, EG Xiao, RP TI Spontaneous beta(2)-adrenergic signaling fails to modulate L-type Ca2+ current in mouse ventricular myocytes SO MOLECULAR PHARMACOLOGY LA English DT Article ID TRANSGENIC MICE; G-PROTEIN; CARDIAC MYOCYTES; HEART-CELLS; RECEPTOR; ACTIVATION; CAMP; OVEREXPRESSION; STIMULATION; AGONISTS AB A receptor can be activated either by specific ligand-directed changes in conformation or by intrinsic, spontaneous conformational change. In the beta(2)-adrenergic receptor (AR) overexpression transgenic (TG4) murine heart, spontaneously activated beta(2)AR (beta(2)-R*) in the absence of ligands has been evidenced by elevated basal adenylyl cyclase activity and cardiac function. In the present study, we determined whether the signaling mediated by beta(2)-R* differs from that of a ligand-elicited beta(2)AR activation (beta(2)-LR*). In ventricular myocytes from TG4 mice, the properties of L-type Ca2+ current (I-Ca), a major effector of beta(2)-LR* signaling, was unaltered, despite a 2.5-fold increase in the basal cAMP level and a 1.9-fold increase in baseline contraction amplitude as compared with that of wildtype (WT) cells. Although the contractile response to beta(2)-R* in TG4 cells was abolished by a beta(2)AR inverse agonist, ICI118,551 (5 x 10(-7) M), or an inhibitory cAMP analog, Rp-CPT-cAMPS (10(-4) M), no change was detected in the simultaneously recorded I-Ca. These results suggest that the increase in basal cAMP due to beta(2)-R*, while increasing contraction amplitude, does not affect I,, characteristics. In contrast, the beta(2)AR agonist, zinterol elicited a substantial augmentation of I-Ca in both TG4 and WT cells (pertussis toxin-treated), indicating that L-type Ca2+ channel in these cells can respond to ligand-directed signaling. Furthermore, forskolin, an adenylyl cyclase activator, elicited similar dose-dependent increase in I-Ca amplitude in WT and TG4 cells, suggesting that the sensitivity of L-type Ca2+ channel to cAMP-dependent modulation remains intact in TG4 cells. Thus, we conclude that beta(2)R* bypasses I-Ca to modulate contraction, and that beta(2)-LR* and beta(2)-R* exhibit different intracellular signaling and target protein specificity. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Xiao, RP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012; cheng, heping/A-7299-2011 NR 40 TC 34 Z9 37 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1999 VL 56 IS 3 BP 485 EP 493 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230NG UT WOS:000082256800005 PM 10462536 ER PT J AU Cihlar, T Lin, DC Pritchard, JB Fuller, MD Mendel, DB Sweet, DH AF Cihlar, T Lin, DC Pritchard, JB Fuller, MD Mendel, DB Sweet, DH TI The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1 SO MOLECULAR PHARMACOLOGY LA English DT Article ID EXPRESSION CLONING; FUNCTIONAL-CHARACTERIZATION; CLINICAL PHARMACOKINETICS; TISSUE DISTRIBUTION; INFECTED PATIENTS; P-AMINOHIPPURATE; KIDNEY; LIVER; METABOLISM; MECHANISMS AB Nephrotoxicity is the dose-limiting clinical adverse effect of cidofovir and adefovir, two potent antiviral therapeutics. Because renal uptake likely plays a role in the etiology of cidofovir- and adefovir-associated nephrotoxicity, we attempted to identify a renal transporter capable of interacting with these therapeutics. A cDNA clone was isolated from a human renal library and designated human organic anion transporter 1 (hOAT1). Northern analysis detected a specific 2.5-kilobase pair hOAT1 transcript only in human kidney. However, reverse transcription-polymerase chain reaction revealed hOATI expression in human brain and skeletal muscle, as well. Immunoblot analysis of human kidney cortex demonstrated that hOATI is an 80- to 90-kilodalton heterogeneous protein modified by abundant N-glycosylation. Xenopus laevis oocytes expressing hOATI supported probenecid-sensitive uptake of [H-3]p-aminohippurate (K-m = 4 mu M), which was trans-stimulated in oocytes preloaded with glutarate. Importantly, both hOAT1 and rat renal organic anion transporter 1 (rROAT1) mediated saturable, probenecid-sensitive uptake of cidofovir, adefovir, and other nucleoside phosphonate antivirals. The affinity of hOAT1 toward cidofovir and adefovir (K-m = 46 and 30 mu M, respectively) was 5- to g-fold higher compared with rROAT1 (K-m = 238 and 270 mu M, respectively). These data indicate that hOATI may significantly contribute to the accumulation of cidofovir and adefovir in renal proximal tubules and, thus, play an active role in the mechanism of nephrotoxicity associated with these antiviral therapeutics. C1 Gilead Sci Inc, Foster City, CA 94404 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Cihlar, T (reprint author), Gilead Sci Inc, 333 Lakeside Dr, Foster City, CA 94404 USA. RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 NR 39 TC 242 Z9 246 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1999 VL 56 IS 3 BP 570 EP 580 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230NG UT WOS:000082256800014 PM 10462545 ER PT J AU Szallasi, A Blumberg, PM Annicelli, LL Krause, JE Cortright, DN AF Szallasi, A Blumberg, PM Annicelli, LL Krause, JE Cortright, DN TI The cloned rat vanilloid receptor VR1 mediates both R-type binding and C-type calcium response in dorsal root ganglion neurons SO MOLECULAR PHARMACOLOGY LA English DT Article ID CAPSAICIN RECEPTOR; SENSORY NEURONS; INTRAVESICAL RESINIFERATOXIN; ANALOGS; CELLS; DESENSITIZATION; HYPERREFLEXIA; PHARMACOLOGY; STIMULATION; CAPSAZEPINE AB [H-3]Resiniferatoxin (RTX) binding and calcium uptake by rat dorsal root ganglion (DRG) neurons show distinct structure-activity relations, suggestive of independent vanilloid receptor (VR) subtypes. We have now characterized ligand binding to rat VR1 expressed in human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells and compared the structure-activity relations with those for calcium mobilization, Human embryonic-kidney cells (HEK293/VR1 cells) and Chinese hamster ovary cells transfected with VR1 (CHO/VR1 cells) bound [H-3]RTX with affinities of 84 and 103 pM, respectively, and positive cooperativity (Hill numbers were 2.1 and 1.8). These parameters are similar to those determined with rat DRG membranes expressing native VRs (a K-d of 70 pM acid a Hill number of 1.7). The typical vanilloid agonists olvanil and capsaicin inhibited [H-3]RTX binding to HEK293/VR1 cells with K-i values of 0.4 and 4.0 mu M, respectively. The corresponding values in DRG membranes were 0.3 and 2.5 mu M. HEK293/VR1 cells and DRG membranes also recognized the novel vanilloids isovelleral and scutigeral with similar K-i values (18 and 20 mu M in HEK293/VR1 cells; 24 and 21 mu M in DRGs). The competitive vanilloid receptor:antagonist capsazepine inhibited [H-3]RTX binding to HEK293/VR1 cells with a Ki value of 6.2 mu M and binding to DRG membranes with a K-i value of 8.6 mu M RTX and capsaicin induced calcium mobilization in HEK293/VR1 cells with EC50 values of 4.1 and 82 nM, respectively. Thus, the relative potencies of RTX (more potent for binding) and capsaicin (more potent for calcium mobilization) are similar in DRG neurons and cells transfected with VR1. We conclude that VR1 can account for both the ligand binding and calcium uptake observed in rat DRG neurons. C1 Neurogen Corp, Branford, CT USA. NCI, Bethesda, MD 20892 USA. RP Szallasi, A (reprint author), St Louis Univ, Sch Med, Dept Pathol, 1402 S Grand Blvd, St Louis, MO 63104 USA. NR 38 TC 103 Z9 106 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1999 VL 56 IS 3 BP 581 EP 587 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230NG UT WOS:000082256800015 PM 10462546 ER PT J AU Bornstein, SR Bottner, A Chrousos, GP AF Bornstein, SR Bottner, A Chrousos, GP TI Knocking out the stress response SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING FACTOR; PITUITARY-ADRENAL AXIS; GLUCOCORTICOID RECEPTOR FUNCTION; TYROSINE-HYDROXYLASE GENE; DOPAMINE-BETA-HYDROXYLASE; EXPRESSING ANTISENSE RNA; MOUSE FETAL DEVELOPMENT; FACTOR TRANSGENIC MICE; HIGH-LEVEL EXPRESSION; EMBRYONIC STEM-CELLS AB Transgenic animals and knockout mice have been generated with defined defects in various components of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. These models provide valuable and novel insights into the development, crosstalk, organization, and functioning of the stress system. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Internal Med, D-04103 Leipzig, Germany. RP Bornstein, SR (reprint author), NICHHD, Dev Endocrinol Branch, NIH, 9000 Rockville Pike,Bldg 10, Room 10N262, Bethesda, MD 20892 USA. RI Korner, Antje/B-3988-2015 OI Korner, Antje/0000-0001-6001-0356 NR 53 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 IS 5 BP 403 EP 407 DI 10.1038/sj.mp.4000602 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 245NZ UT WOS:000083116200002 PM 10523807 ER PT J AU Castellanos, FX Lau, E Tayebi, N Lee, P Long, RE Giedd, JN Sharp, WS Marsh, WL Walter, JM Hamburger, SD Ginns, EI Rapoport, JL Sidransky, E AF Castellanos, FX Lau, E Tayebi, N Lee, P Long, RE Giedd, JN Sharp, WS Marsh, WL Walter, JM Hamburger, SD Ginns, EI Rapoport, JL Sidransky, E TI Sampling and analytic considerations in molecular genetics studies of ADHD. The advantages of predicting phenotype from genotype in ADHD research - Castellanos replies SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID RECEPTOR C1 NIMH, Bethesda, MD 20892 USA. RP Castellanos, FX (reprint author), NIMH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 3 TC 0 Z9 0 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 IS 5 BP 414 EP 414 DI 10.1038/sj.mp.4000597 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 245NZ UT WOS:000083116200008 ER PT J AU Rhoads, AR Karkera, JD Detera-Wadleigh, SD AF Rhoads, AR Karkera, JD Detera-Wadleigh, SD TI Radiation hybrid mapping of genes in the lithium-sensitive Wnt signaling pathway SO MOLECULAR PSYCHIATRY LA English DT Article DE radiation hybrid mapping; Wnt pathway; lithium; bipolar disorder; susceptibility loci; chromosome localization ID INITIATIVE BIPOLAR PEDIGREES; CARDIO-FACIAL SYNDROME; BETA-CATENIN; POSSIBLE LOCUS; MOLECULAR MECHANISM; WILLIAMS-SYNDROME; LINKAGE ANALYSIS; CRITICAL REGION; POLARITY GENE; GENOME SCAN AB Lithium, an effective drug in the treatment of bipolar disorder, has been proposed to disrupt the Wnt signaling pathway. To facilitate analysis of the possible involvement of elements of the Wnt pathway in human bipolar disorder, a high resolution radiation hybrid mapping (RHM) of these genes was performed. A fine physical location has been obtained for Wnt 7A, frizzled 3, 4 and 5, dishevelled 1, 2 and 3, GSK3 beta, axin, alpha-catenin, the Armadillo repeat-containing genes (delta-catenin and ARVCF), and a frizzled-like protein (frpHE) using the Stanford Human Genome Center (SHGC) G3 panel. Most of these genes were previously mapped by fluorescence in situ hybridization (FISH). Frizzled 4, axin and frpHE did not have a previous chromosomal assignment and were linked by RHM to chromosome markers, SHGC-35131 at 11q22.1, NIB1488 at 16p13.3 and D7S2919 at 7p15.2, respectively. Interestingly, some of these genes were found to map within potential regions underlying susceptibility to bipolar disorder and schizophrenia as well as disorders of neurodevelopmental origin. This alternative approach of establishing the precise location of selected genetic components of a candidate pathway and determining if they map within previously defined susceptibility loci should help to identify plausible candidate genes that warrant further analysis through association and mutational scanning. C1 Howard Univ, Dept Biochem & Mol Biol, Washington, DC 20059 USA. NIMH, Unit Gene Mapping & Express, NIH, Bethesda, MD 20892 USA. RP Rhoads, AR (reprint author), Howard Univ, Dept Biochem & Mol Biol, Washington, DC 20059 USA. NR 51 TC 8 Z9 12 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 IS 5 BP 437 EP 442 DI 10.1038/sj.mp.4000538 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 245NZ UT WOS:000083116200013 PM 10523816 ER PT J AU Bengel, D Greenberg, BD Cora-Locatelli, G Altemus, M Heils, A Li, Q Murphy, DL AF Bengel, D Greenberg, BD Cora-Locatelli, G Altemus, M Heils, A Li, Q Murphy, DL TI Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; genetics; serotonin transporter; association study ID REUPTAKE INHIBITORS; ALLELIC VARIATION; BIPOLAR DISORDER; GENE; SUSCEPTIBILITY; PERSONALITY; EXPRESSION; DEPRESSION; TRAITS AB Although modulation of symptoms of obsessive-compulsive disorder (OCD) by serotonergic agents is well established, it is unclear whether an abnormality in the central serotonergic system is involved in its etiology. The serotonin (5-HT) transporter (5-HTT), which is the key modulator of serotonergic neurotransmission, is the target for serotonin reuptake inhibiting drugs (SRIs) that are uniquely effective in the treatment of OCD. In this preliminary study we report an association of a functional polymorphism in the 5HTT 5' regulatory-region and OCD. Seventy-five OCD Caucasian patients and 397 ethnically-matched individuals from a non-patient control group were genotyped for the 5-HTTLPR. Population-based association analysis revealed that patients with OCD were more likely to carry two copies of the long allele (I) as compared to controls (46.7% vs 32.3%: chi(2) = 5.19, P = 0.023). This finding replicates a recent family-based study of this polymorphism in OCD, and thus indicates that the 5-HTTLPR may be associated with susceptibility to OCD. C1 Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Bengel, D (reprint author), Univ Wurzburg, Dept Psychiat, Fuchsleinstr 15, D-97080 Wurzburg, Germany. NR 28 TC 115 Z9 120 U1 3 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 IS 5 BP 463 EP 466 DI 10.1038/sj.mp.4000550 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 245NZ UT WOS:000083116200016 PM 10523819 ER PT J AU Vawter, MP Howard, AL Hyde, TM Kleinman, JE Freed, WJ AF Vawter, MP Howard, AL Hyde, TM Kleinman, JE Freed, WJ TI Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; bipolar disorder; suicide; hippocampus; neural cell adhesion molecule; secreted exon; synaptophysin; actin; Western immunoblot ID CELL-ADHESION MOLECULE; LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; RECOGNITION MOLECULES; PREFRONTAL CORTEX; ALZHEIMER-DISEASE; POSTMORTEM BRAIN; CINGULATE CORTEX; VESICLE PROTEIN; NCAM AB Schizophrenia and bipolar disorder have both been linked to structural abnormalities of the hippocampus, which is consistent with a neurodevelopmental anomaly. One isoform of the neural cell adhesion molecule (N-CAM) protein, cytosolic N-CAM 105-115 kDa, was previously shown to be increased in schizophrenia in the hippocampus and prefrontal cortex. Another isoform of N-CAM, the variable alternative spliced exon of N-CAM, was also increased in the hippocampus and prefrontal cortex of bipolar disorder patients. In the present study, the secreted isoform of N-CAM (SEC N-CAM), synaptophysin, and actin proteins were measured in the hippocampus of controls, suicide victims, and patients with bipolar disorder or schizophrenia by quantitative Western immunoblotting. Previous measurements of cytosolic N-CAM (105-115 kDa) protein, from the same hippocampus samples, were used to calculate the NCAM (105-115 kDa)/synaptophysin ratio. An affinity purified antibody to SEC N-CAM recognized SEC N-CAM (108 kDa and 115 kDa) in brain but SEC N-CAM was not detectable in CSF. In bipolar disorder, but not in schizophrenia, an increased SEC N-CAM 115 kDa/108 kDa ratio was found as compared to controls (P = 0.03). The synaptophysin/actin ratio was significantly decreased in schizophrenia (P = 0.014) as compared to controls. The cytosolic N-CAM 105-115 kDa/synaptophysin ratio was increased in patients with schizophrenia (P = 0.017), but not in bipolar disorder. Thus, bipolar disorder patients show altered expression of SEC N-CAM in the hippocampus. Patients with schizophrenia show a decrease in synaptophysin and an increase in the cytosolic N-CAM 105-115 kDa/synaptophysin ratio. The results offer further evidence of differences in protein expression between bipolar disorder and schizophrenia in the hippocampus, which is consistent with a distinct neuropathology for each neuropsychiatric disorder. C1 NIDA, IRP, Baltimore, MD 21224 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Vawter, MP (reprint author), NIDA, IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224 USA. NR 59 TC 68 Z9 69 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 IS 5 BP 467 EP 475 DI 10.1038/sj.mp.4000547 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 245NZ UT WOS:000083116200017 PM 10523820 ER PT J AU Azzam, A Lerner, DM Peters, K Wiggs, E Rosenstein, DL Biesecker, L AF Azzam, A Lerner, DM Peters, K Wiggs, E Rosenstein, DL Biesecker, L TI Neuropsychiatric findings in Pallister-Hall Syndrome. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20814 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 87 BP S55 EP S55 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800187 ER PT J AU Basu, S Ashley-Koch, A Wolpert, C Menold, M Matsumoto, N Powell, C Qumsiyeh, MB Cuccaro, M Scherer, S Ledbetter, DH Green, E Vance, JM Pericak-Vance, MA Gilbert, R AF Basu, S Ashley-Koch, A Wolpert, C Menold, M Matsumoto, N Powell, C Qumsiyeh, MB Cuccaro, M Scherer, S Ledbetter, DH Green, E Vance, JM Pericak-Vance, MA Gilbert, R TI Characterization of an inversion breakpoint in a multiplex autistic disorder family: Defining the candidate region on chromosome 7q. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ S Carolina, WS Hall Psychiat Inst, Columbia, SC 29208 USA. Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 115 BP S63 EP S63 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800215 ER PT J AU Castellanos, FX Lewczyk, CM Fernandez, T Koprivica, V Kashani, A Tayebi, N Ginns, EI Rapoport, JL Sidransky, E AF Castellanos, FX Lewczyk, CM Fernandez, T Koprivica, V Kashani, A Tayebi, N Ginns, EI Rapoport, JL Sidransky, E TI Lack of an association between dopamine transporter (DAT1) & ADHD. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RI Fernandez, Thomas/D-4295-2009 OI Fernandez, Thomas/0000-0003-0830-022X NR 0 TC 2 Z9 2 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 177 BP S80 EP S80 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800277 ER PT J AU Danielyan, KG Danielyan, AK AF Danielyan, KG Danielyan, AK TI Some genealogical data of psychotic disorders with sexual content. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIH, Dept Psychiat Psychotherapy & Med Psychol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 328 BP S125 EP S126 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800427 ER PT J AU Enoch, MA Kaye, WH Harris, C Virkkunen, M Goldman, D AF Enoch, MA Kaye, WH Harris, C Virkkunen, M Goldman, D TI Personality traits associated with the 5-HT2A promoter polymorphism,-1438GA. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 208 BP S89 EP S90 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800308 ER PT J AU Feng, J Zheng, J Gelernter, J Kranzler, H Cook, E Craddock, N Goldman, D Heston, LL Bennett, WP Sommer, SS AF Feng, J Zheng, J Gelernter, J Kranzler, H Cook, E Craddock, N Goldman, D Heston, LL Bennett, WP Sommer, SS TI A common in-frame deletion in the alpha 2cadrenergic receptor (alpha 2cAR): Possible association with cocaine abuse SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 City Hope & Beckman Res Inst, Dept Human Genet, Duarte, CA USA. Yale Univ, Dept Psychiat, W Haven, CT USA. Univ Connecticut, Dept Psychiat, Storrs, CT 06269 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Birmingham, Dept Psychiat, Birmingham, W Midlands, England. NIAAA, Dept Psychiat, NIH, Bethesda, MD USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 263 BP S106 EP S106 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800363 ER PT J AU Karkera, JD Zeng, J Jacobowitz, D Leonard, S Moses, T Detera-Wadleigh, SD AF Karkera, JD Zeng, J Jacobowitz, D Leonard, S Moses, T Detera-Wadleigh, SD TI Detection of candidate genes for bipolar disorder through differential display-PCR. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Intramural Program, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver VA Med Ctr, Denver, CO 80262 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 105 BP S60 EP S60 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800205 ER PT J AU Klar, AJS AF Klar, AJS TI Two independent imprinted events regulate fission yeast mating-type switching and silencing. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract ID DNA STRANDS; INHERITANCE; CELLS C1 NCI, Frederick Canc Res & Dev Ctr, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 BP S18 EP S19 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800066 ER PT J AU Lilenfeld, LR Kaye, WH Devlin, B Bulik, CM Strober, M Berretini, W Goldman, D Halmi, K Fichter, M Kaplan, A Woodside, B Treasure, J AF Lilenfeld, LR Kaye, WH Devlin, B Bulik, CM Strober, M Berretini, W Goldman, D Halmi, K Fichter, M Kaplan, A Woodside, B Treasure, J TI Refinement of behavioral phenotypes with an international sample of eating disordered individuals. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Sch Med, Los Angeles, CA USA. Univ Penn, Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. NIAAA, Bethesda, MD USA. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp Westchester, White Plains, NY USA. Hosp Behav Med, Klin Roseneck, Munich, Germany. Toronto Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Bethlem Royal & Maudsley Hosp, Inst Psychiat, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 310 BP S120 EP S120 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800409 ER PT J AU Mazzanti, CM Malhotra, A Rotondo, A Lipsky, R Kolachana, B Bozak, D Vyas, G Goldman, D AF Mazzanti, CM Malhotra, A Rotondo, A Lipsky, R Kolachana, B Bozak, D Vyas, G Goldman, D TI The human TH01 tetra-tandem repeat and its role in schizophrenia and bipolar disorder. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIMH, Lab Behav Endocrinol, Bethesda, MD 20892 USA. Univ Pisa, Inst Psychiat, Pisa, Italy. Hillside Hosp, New York, NY 11040 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 BP S24 EP S24 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800084 ER PT J AU Mazzanti, RA Lunardi, CM Gonnelli, A Pardini, C Tiano, L Bouanani, L Bandettini, S Bozak, A Vyas, D Dell'Orso, G Cassano, L AF Mazzanti, RA Lunardi, CM Gonnelli, A Pardini, C Tiano, L Bouanani, L Bandettini, S Bozak, A Vyas, D Dell'Orso, G Cassano, L TI Evidence for association of the catechol-O-methyltransferase gene with bipolar disorder and aggressive behavior. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pisa, Dept Psychiat, Pisa, Italy. NIAAA, Rockville, MD 20852 USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 244 BP S100 EP S100 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800344 ER PT J AU Nurnberger, JI Foroud, T Flury, L Meyer, ET Edenberg, H DePaulo, JR Stine, OC Blehar, MC Detera-Wadleigh, S Gershon, ES Reich, T Goate, A AF Nurnberger, JI Foroud, T Flury, L Meyer, ET Edenberg, H DePaulo, JR Stine, OC Blehar, MC Detera-Wadleigh, S Gershon, ES Reich, T Goate, A TI New analyses of the NIMH bipolar dataset SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Gent Initiat, Rockville, MD 20857 USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Chicago, Chicago, IL 60637 USA. Washington Univ, St Louis, MO USA. RI Meyer, Eric/C-1029-2011 OI Meyer, Eric/0000-0002-1998-7162 NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 BP S19 EP S19 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800068 ER PT J AU Osher, Y Hamer, DH Benjamin, J AF Osher, Y Hamer, DH Benjamin, J TI Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene in Israeli sibling pairs. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Ben Gurion Univ Negev, Beer Sheva Mental Hlth Ctr, IL-84105 Beer Sheva, Israel. NCI, Biochem Lab, Bethesda, MD USA. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Psychiat, IL-84101 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 BP S24 EP S25 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800085 ER PT J AU Philibert, RA Cheung, D Welsh, N Damschroder-Williams, P Thiel, B Ginns, EI Gershenfeld, HK AF Philibert, RA Cheung, D Welsh, N Damschroder-Williams, P Thiel, B Ginns, EI Gershenfeld, HK TI Absence of a significant association between Na+, K+-ATPase subunit (ATP 1A3 & ATP1B3) genotypes and bipolar disorder in the Old Order Amish. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75235 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 167 BP S77 EP S78 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800267 ER PT J AU Roca, CA Harlow, BL Davis, C Schmidt, PJ Mazzanti, C Lappalainen, J Ozaki, N Goldman, D Rubinow, DR AF Roca, CA Harlow, BL Davis, C Schmidt, PJ Mazzanti, C Lappalainen, J Ozaki, N Goldman, D Rubinow, DR TI Role of three functional polymorphisms in serotonin genes in premenstrual dysphoric disorder (PMDD). SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 221 BP S93 EP S93 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800321 ER PT J AU Rudolph, JG Mazzanti, CM Lipsky, RM Ellini, A Bozak, D Vyas, G AF Rudolph, JG Mazzanti, CM Lipsky, RM Ellini, A Bozak, D Vyas, G TI Identification of four single nucleotide polymorphisms (SNPS) in muscarinic-cholinergic CHRM1 gene utilizing dHPLC large scale DNA screening SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Goldman D Lab Neurogenet, NIH, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 285 BP S112 EP S112 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800385 ER PT J AU Winterer, G Mahlberg, R Samochowiec, J Smolka, M Rommelspacher, H Schmidt, LG Sander, T AF Winterer, G Mahlberg, R Samochowiec, J Smolka, M Rommelspacher, H Schmidt, LG Sander, T TI Brain vulnerability & immaturity: Association between EEG-voltage & a GABA(B) gene polymorphism on chromosome SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Free Univ Berlin, Dept Psychiat, D-1000 Berlin, Germany. NIMH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 319 BP S122 EP S123 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800418 ER PT J AU Winterer, G Coppola, R Radler, T Weinberger, DR Egan, M AF Winterer, G Coppola, R Radler, T Weinberger, DR Egan, M TI Out-of-phase oscillations (0.5-4hz) in the temporal lobe area indicate increased genetic risk for schizophrenia. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorder Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 BP S22 EP S23 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800079 ER PT J AU Malling, HV AF Malling, HV TI Frederick J. de Serres: the years at the Research Triangle Park SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Biographical-Item C1 NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Malling, HV (reprint author), NIEHS, Toxicol Lab, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD SEP PY 1999 VL 437 IS 2 BP 69 EP 75 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 250VT UT WOS:000083410400003 PM 10610430 ER PT J AU de Serres, FJ Brockman, HE AF de Serres, FJ Brockman, HE TI Comparison of the spectra of genetic damage in formaldehyde-induced ad-3 mutations between DNA repair-proficient and -deficient heterokaryons of Neurospora crassa SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article DE formaldehyde; two-component heterokaryons; DNA repair-proficient; DNA repair-deficient; gene/point mutations; multilocus deletion mutations; ad-3 region; ad-3A locus; ad-3B locus; recessive lethal mutations; ad-3(R)/ad-3(IR) ratio; ad-3B(R-C)/ad-3B(R-NC) ratio; spontaneous mutations; chemical-induced mutations; allelic complementation; genetic risk assessment ID 2-COMPONENT HETEROKARYONS; LOCUS MUTATIONS; RISK ASSESSMENT; GENOTYPE AD-3A; REGION; INDUCTION; ASSAY AB The mutagenic effects of formaldehyde (FA) have been compared in DMA repair-proficient (heterokaryon, 12) and DNA repair-deficient (heterokaryon 59) two-component heterokaryons of Neurospora crassa. The data from forward-mutation experiments were used to compare the spectra of FA-induced specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region and on the FA-induced inactivation of heterokaryotic conidia. Previous studies have demonstrated that specific-locus mutations at these two loci result from five major genotypic classes, namely two classes of gene/point mutations (ad-3A(R) and ad-3B(R)), and three classes of multilocus deletion mutations ([ad-3A](IR), [ad-3B](IR), and [ad-3A ad-3B](IR)). Genetic analysis of ad-3 mutants recovered from both heterokaryons after FA treatment demonstrates that predominantly gene/point mutations were found in H-12 (93.2% ad-3(R), 6.8% [ad-3](IR)) and a significantly higher frequency of multilocus deletion mutations in H-59 (62.8% ad-3(R), 37.0% [ad-3](IR)). The data from our experiments with FA on H-12 demonstrate and confirm the data from other assays that EA is a weak mutagen in this DNA repair-proficient strain. However, the data from our experiments with the DNA repair-deficient strain H-59 demonstrate that comparable concentrations of FA cause more pronounced inactivation of heterokaryotic conidia and, at the highest concentration tested, about a 35-fold higher frequency of ad-3 mutations. In addition, FA induced a 5.4-fold higher frequency of ad-3 mutations resulting from multilocus deletion mutation in H-59 than in H-12. Based on our earlier studies with X-ray-induced multilocus deletion mutations, it is this class of FA-induced ad-3 mutations that might be most expected to show deleterious heterozygous effects. The implications of the present data base from our experiments with Neurospora are that the mutagenic (and possibly the carcinogenic) effect of FA exposure might well vary in different human population subgroups. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIEHS, Mammalian Mutagenesis Grp, Toxicol Lab, Syst Toxicol Branch,Environm Toxicol Program, Res Triangle Pk, NC 27703 USA. Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. RP de Serres, FJ (reprint author), NIEHS, Mammalian Mutagenesis Grp, Toxicol Lab, Syst Toxicol Branch,Environm Toxicol Program, Res Triangle Pk, NC 27703 USA. NR 20 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD SEP PY 1999 VL 437 IS 2 BP 151 EP 163 DI 10.1016/S1383-5742(99)00081-2 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 250VT UT WOS:000083410400015 PM 10556619 ER PT J AU Groll, AH Kurz, M Schneider, W Witt, V Schmidt, H Schneider, M Schwabe, D AF Groll, AH Kurz, M Schneider, W Witt, V Schmidt, H Schneider, M Schwabe, D TI Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival SO MYCOSES LA English DT Article DE aspergillosis; epidemiology; antimycotic chemotherapy; cancer; children ID BONE-MARROW TRANSPLANTATION; PRIMARY CUTANEOUS ASPERGILLOSIS; COLONY-STIMULATING FACTOR; ACUTE-LEUKEMIA PATIENTS; STEM-CELL RESCUE; PULMONARY ASPERGILLOSIS; FUNGAL-INFECTIONS; HEMATOLOGICAL MALIGNANCIES; IMMUNOCOMPROMISED PATIENTS; EARLY DIAGNOSIS AB The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n= 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups. C1 Univ Frankfurt, Dept Pediat, D-6000 Frankfurt, Germany. Univ Frankfurt, Dept Pediat Radiol, D-6000 Frankfurt, Germany. Univ Frankfurt, Dept Pathol, D-6000 Frankfurt, Germany. RP Groll, AH (reprint author), NCI, Immunocompromised Hosp Sect, Pediat Oncol Branch, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 79 TC 91 Z9 94 U1 0 U2 0 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0933-7407 J9 MYCOSES JI Mycoses PD SEP-OCT PY 1999 VL 42 IS 7-8 BP 431 EP 442 DI 10.1046/j.1439-0507.1999.00496.x PG 12 WC Dermatology; Mycology SC Dermatology; Mycology GA 241QK UT WOS:000082893900001 PM 10546484 ER PT J AU Raab, A Han, WH Badt, D Smith-Gill, SJ Lindsay, SM Schindler, H Hinterdorfer, P AF Raab, A Han, WH Badt, D Smith-Gill, SJ Lindsay, SM Schindler, H Hinterdorfer, P TI Antibody recognition imaging by force microscopy SO NATURE BIOTECHNOLOGY LA English DT Article DE force microscopy; molecular recognition; antibody-antigen; receptor-ligand; lysozyme ID DNA; RESOLUTION; BIOLOGY; EVENTS AB We have developed a method that combines dynamic force microscopy with the simultaneous molecular recognition of an antigen by an antibody, during imaging. A magnetically oscillated atomic force microscopy tip carrying a tethered antibody was scanned over a surface to which lysozyme was bound. By oscillating the probe at an amplitude of only a few nanometers, the antibody was kept in close proximity to the surface, allowing fast and efficient antigen recognition and gentle interaction between tip and sample. Antigenic sites were evident from reduction of the oscillation amplitude, as a result of antibody-antigen recognition during the lateral scan. Lysozyme molecules bound to the surface were recognized by the antibody on the scanning tip with a few nanometers lateral resolution. In principle, any ligand can be tethered to the tip; thus, this technique could potentially be used for nanometer-scale epitope mapping of biomolecules and localizing receptor sites during biological processes. C1 Univ Linz, Inst Biophys, A-4040 Linz, Austria. Mol Imaging Corp, Phoenix, AZ USA. NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. RP Hinterdorfer, P (reprint author), Univ Linz, Inst Biophys, A-4040 Linz, Austria. RI Hinterdorfer, Peter/C-4235-2013 NR 24 TC 115 Z9 117 U1 2 U2 23 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 1999 VL 17 IS 9 BP 902 EP 905 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 232HU UT WOS:000082365800034 ER PT J AU Ashcroft, GS Yang, X Glick, AB Weinstein, M Letterio, JJ Mizel, DE Anzano, M Greenwell-Wild, T Wahl, SM Deng, CX Roberts, AB AF Ashcroft, GS Yang, X Glick, AB Weinstein, M Letterio, JJ Mizel, DE Anzano, M Greenwell-Wild, T Wahl, SM Deng, CX Roberts, AB TI Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response SO NATURE CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; HUMAN-MONOCYTES; EXPRESSION; KERATINOCYTES; TGF-BETA-1; MACROPHAGE; INDUCTION; REPAIR; CELLS AB The generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor-beta (TGF-beta), has made it possible to explore the contribution of the SMAD proteins to TGF-beta activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF-beta to improve wound healing, Smad3-null (Smad3(ex8/ex8)) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, characterized by an increased rate of re-epithelialization and significantly reduced local infiltration of monocytes. Smad3(ex8/ex8) keratinocytes show altered patterns of growth and migration, and Smad3(ex8/ex8) monocytes exhibit a selectively blunted chemotactic response to TGF-beta. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of tissue repair and in the modulation of keratinocyte and monocyte function in vivo. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 33 TC 607 Z9 646 U1 3 U2 24 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 1999 VL 1 IS 5 BP 260 EP 266 PG 7 WC Cell Biology SC Cell Biology GA 246NJ UT WOS:000083169600013 PM 10559937 ER PT J AU Feliubadalo, L Font, M Purroy, J Rousaud, F Estivill, X Nunes, V Golomb, E Centola, M Aksentijevich, I Kreiss, Y Goldman, B Pras, M Kastner, DL Pras, E Gasparini, P Bisceglia, L Beccia, E Gallucci, M de Sanctis, L Ponzone, A Rizzoni, GF Zelante, L Bassi, MT George, AL Manzoni, M De Grandi, A Riboni, M Endsley, JK Ballabio, A Borsani, G Reig, N Fernandez, E Estevez, R Pineda, M Torrents, D Camps, M Lloberas, J Zorzano, A Palacin, M AF Feliubadalo, L Font, M Purroy, J Rousaud, F Estivill, X Nunes, V Golomb, E Centola, M Aksentijevich, I Kreiss, Y Goldman, B Pras, M Kastner, DL Pras, E Gasparini, P Bisceglia, L Beccia, E Gallucci, M de Sanctis, L Ponzone, A Rizzoni, GF Zelante, L Bassi, MT George, AL Manzoni, M De Grandi, A Riboni, M Endsley, JK Ballabio, A Borsani, G Reig, N Fernandez, E Estevez, R Pineda, M Torrents, D Camps, M Lloberas, J Zorzano, A Palacin, M CA Int Cystinuria Consortium TI Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b(o,+)AT) of rBAT SO NATURE GENETICS LA English DT Article ID AMINO-ACID-TRANSPORT; EXPRESSION CLONING; SLC3A1 GENE; IDENTIFICATION; LOCALIZATION; KIDNEY; SYSTEM AB Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (refs 3,4). We have identified a new transcript, encoding a protein (b(o,+)AT, for b(o,+) amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of b(o,+)AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b(o,+)AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and C295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that b(o,+)AT is the light subunit of rBAT. C1 Univ Barcelona, Dept Bioquim & Biol Mol, Fac Biol, E-08028 Barcelona, Spain. Hosp Duran & Reynals, Ctr Genet Med & Mol IRO, E-08907 Barcelona, Spain. Fdn Puigvert, Serv Nefrol IUNA, E-08025 Barcelona, Spain. Tel Aviv Univ, Sackler Sch Med, Dept Pathol, IL-69978 Tel Aviv, Israel. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Dept Med C, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Inst Human Genet, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Dept Med F, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Sci, IL-52621 Tel Hashomer, Israel. IRCCS, Med Genet Serv, Hosp CSS, San Giovanni Rotondo, Italy. IRCCS, Div Urol, Hosp CSS, San Giovanni Rotondo, Italy. Hosp Cristo Re, Div Urol, Rome, Italy. Univ Turin, Dept Pediat, I-10124 Turin, Italy. Hosp Bambino Gesu, Div Pediat Nephrol, Rome, Italy. Telethon Inst Genet & Med, I-20132 Milan, Italy. Vanderbilt Univ, Dept Med, Div Med Genet, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Med, Div Nephrol, Nashville, TN 37232 USA. Univ Barcelona, Dept Fisiol Biol Macrophage, Fac Biol, E-08028 Barcelona, Spain. RP Palacin, M (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Fac Biol, Avda Diagonal 645, E-08028 Barcelona, Spain. RI Feliubadalo, Lidia/G-4577-2016; Borsani, Giuseppe/B-1709-2010; Torrents, David/G-5785-2015; Estivill, Xavier/E-2957-2012; Bassi, Maria Teresa/A-3517-2014; Nunes, Virginia/D-4356-2014; Estivill, Xavier/A-3125-2013; Estevez, Raul/D-8610-2015; Lloberas, Jorge/D-4303-2014; Camps, Marta/F-6557-2016; Bisceglia, Luigi/B-8720-2017; Gallucci, Michele/K-9600-2016 OI Feliubadalo, Lidia/0000-0002-1736-0112; Pineda, Marta/0000-0002-5403-5845; BALLABIO, Andrea/0000-0003-1381-4604; Borsani, Giuseppe/0000-0003-0110-1148; Torrents, David/0000-0002-6086-9037; Bassi, Maria Teresa/0000-0002-8236-1197; Nunes, Virginia/0000-0002-5747-9310; Estivill, Xavier/0000-0002-0723-2256; Estevez, Raul/0000-0003-1579-650X; Lloberas, Jorge/0000-0001-7075-4201; Bisceglia, Luigi/0000-0001-5367-8518; Gallucci, Michele/0000-0002-3637-6531 FU Telethon [TGM97000, E.0556, TGM06S01] NR 29 TC 202 Z9 206 U1 2 U2 17 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1999 VL 23 IS 1 BP 52 EP 57 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 231XU UT WOS:000082337300015 PM 10471498 ER PT J AU Wade, PA Gegonne, A Jones, PL Ballestar, E Aubry, F Wolffe, AP AF Wade, PA Gegonne, A Jones, PL Ballestar, E Aubry, F Wolffe, AP TI Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation SO NATURE GENETICS LA English DT Article ID PROTEIN; GENE; IDENTIFICATION; METASTASIS; FAMILY; MTA1 AB Methylation of DNA at the dinucleotide CpG is essential for mammalian development and is correlated with stable transcriptional silencing(1-3). This transcriptional silencing has recently been linked at a molecular level to histone deacetylation MeCP2 (refs 4,5). We previously purified a histone deacetylase through the demonstration of a physical association between histone deacetylases and the methyl CpG-binding protein complex from Xenopus laevis egg extracts that consists of six subunits, including an Rpd3-like deacetylase, the RbA p48/p46 histone-binding protein and the nucleosome-stimulated ATPase Mi-2 (ref. 6). Similar species were subsequently isolated from human cell lines(7-9), implying functional conservation across evolution. This complex represents the most abundant form of deacetylase in amphibian eggs and cultured mammalian cells(6-9). Here we identify the remaining three subunits of this across enzyme complex, One of them binds specifically to methylated DNA in vitro and molecular cloning reveals a similarity to a known methyl CpG-binding protein. Our data substantiate the mechanistic link between DNA methylation, histone deacetylation and transcriptional silencing. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. INSERM, U435, F-35042 Rennes, France. RP Wade, PA (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T Room 106, Bethesda, MD 20892 USA. RI Aubry, Florence/I-2746-2015 NR 30 TC 611 Z9 626 U1 5 U2 18 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1999 VL 23 IS 1 BP 62 EP 66 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 231XU UT WOS:000082337300017 PM 10471500 ER PT J AU Harrison, KA Thaler, J Pfaff, SL Gu, H Kehrl, JH AF Harrison, KA Thaler, J Pfaff, SL Gu, H Kehrl, JH TI Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice SO NATURE GENETICS LA English DT Article ID HOMEODOMAIN TRANSCRIPTION FACTOR; HOMEOBOX GENE; BETA-CELLS; DIFFERENTIATION; REVEALS; REQUIREMENT; MESENCHYME; INTESTINE; NOTOCHORD; PDX-1 AB In most mammals the pancreas develops from the foregut endoderm as ventral and dorsal buds. These buds fuse and develop into a complex organ composed of endocrine, exocrine and ductal components(1,2). This developmental process depends upon an integrated network of transcription factors. Gene targeting experiments have revealed critical roles for Pdx1, lsl1, Pax4, Pax6 and Nkx2-2 (refs 3-10). The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas(11), although its role in pancreas development and function is unknown. To facilitate its study, we isolated the mouse HLXB9 orthologue, Hlxb9. During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9. In mice homologous for a null mutation of Hlxb9, the dorsal lobe of the pancreas fails to develop. The remnant Hlxb9(-/-) pancreas has small islets of Langerhans with reduced numbers of insulin-producing p-cells. Hlxb9(-/-) beta-cells express low levels of the glucose transporter Glut2 and homeodomain factor Nkx 6-1. Thus, Hlxb9 is key to normal pancreas development and function. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X NR 26 TC 231 Z9 239 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1999 VL 23 IS 1 BP 71 EP 75 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 231XU UT WOS:000082337300019 PM 10471502 ER PT J AU Zheng, F Kundu, GC Zhang, ZJ Ward, J DeMayo, F Mukherjee, AB AF Zheng, F Kundu, GC Zhang, ZJ Ward, J DeMayo, F Mukherjee, AB TI Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice SO NATURE MEDICINE LA English DT Article ID HUMAN MESANGIAL CELLS; A NEPHROPATHY; IGA NEPHROPATHY; GROWTH-FACTOR; BINDING PROTEINS; GENE-EXPRESSION; MESSENGER-RNA; FIBRONECTIN; REGION; PROMOTER AB The molecular mechanism(s) of immunoglobulin A (IgA) nephropathy, the most common primary renal glomerular disease worldwide, is unknown. Its pathologic features include hematuria, high levels of circulating IgA-fibronectin (Fn) complexes, and glomerular deposition of IgA, complement C3, Fn and collagen. We report here that two independent mouse models (gene knockout and antisense transgenic), both manifesting deficiency of an anti-inflammatory protein, uteroglobin (UG), develop almost all of the pathologic features of human IgA nephropathy. We further demonstrate that Fn-UG heteromerization, reported to prevent abnormal glomerular deposition of Fn and collagen, also abrogates both the formation of IgA-Fn complexes and their binding to glomerular cells. Moreover, UG prevents glomerular accumulation of exogenous IgA in UG-null mice. These results define an essential role for UG in preventing mouse IgA nephropathy and warrant further studies to determine if a similar mechanism(s) underlies the human disease. C1 NICHHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP Mukherjee, AB (reprint author), NICHHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 42 TC 72 Z9 81 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1999 VL 5 IS 9 BP 1018 EP 1025 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 231XT UT WOS:000082337200035 PM 10470078 ER PT J AU Strausbaugh, HJ Green, PG Lo, E Tangemann, K Reichling, DB Rosen, SD Levine, JD AF Strausbaugh, HJ Green, PG Lo, E Tangemann, K Reichling, DB Rosen, SD Levine, JD TI Painful stimulation suppresses joint inflammation by inducing shedding of L-selectin from neutrophils SO NATURE MEDICINE LA English DT Article ID CHEMOTACTIC FACTORS; ENDOTHELIAL-CELLS; SHEAR-FLOW; IN-VITRO; ADHESION; LEUKOCYTES; INVIVO; MAC-1; EXPRESSION; INJURY AB Although the inflammatory response is essential for protecting tissues from injury and infection(1), unrestrained inflammation can cause chronic inflammatory diseases such as arthritis, colitis and asthma. Physiological mechanisms that downregulate inflammation are poorly understood. Potent control might be achieved by regulating early stages in the inflammatory response, such as accumulation of neutrophils at the site of injury, where these cells release chemical mediators that promote inflammatory processes including plasma extravasation(2), bacteriocide and proteolysis. To access an inflammatory site, neutrophils must first adhere to the vascular endothelium in a process mediated in part by the leukocyte adhesion molecule L-selectin(3). This adhesion is prevented when L-selectin is shed from the neutrophil membrane(4,5) Although shedding of L-selectin is recognized as a potentially important mechanism for regulating neutrophilse(4,7), its physiological function has not been demonstrated. Shedding of L-selectin may mediate endogenous downregulation of inflammation by limiting neutrophil accumulation at inflammatory sites. Here we show that activation of nociceptive neurons induces shedding of L-selectin from circulating neutrophils in vivo and that this shedding suppresses an ongoing inflammatory response by inhibiting neutrophil accumulation. These findings indicate a previously unknown mechanism for endogenous feedback control of inflammation. failure of this mechanism could contribute to the etiology of chronic inflammatory disease. C1 Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Immunol, San Francisco, CA 94143 USA. RP Strausbaugh, HJ (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, 521 Parnassus Ave, San Francisco, CA 94143 USA. RI Green, Paul/C-5943-2011 FU NIADDK NIH HHS [AM32624] NR 25 TC 31 Z9 33 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1999 VL 5 IS 9 BP 1057 EP 1061 DI 10.1038/12497 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 231XT UT WOS:000082337200042 PM 10470085 ER PT J AU Yaswen, L Diehl, N Brennan, MB Hochgeschwender, U AF Yaswen, L Diehl, N Brennan, MB Hochgeschwender, U TI Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin SO NATURE MEDICINE LA English DT Article ID MELANOCYTE-STIMULATING-HORMONE; RECEPTOR; MICE; GENE; MUTATIONS; PEPTIDES; TISSUES; PROTEIN AB Pro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorticotropin, alpha-, beta- and gamma-melanocyte stimulating hormone; and the endogenous opioid beta-endorphin) have a diverse array of biological activities, including roles in pigmentation, adrenocortical function and regulation of energy stores, and in the immune system and the central and peripheral nervous systems'. We show here that mice lacking the POMC-derived peptides have obesity, defective adrenal development and altered pigmentation. This phenotype is similar to that of the recently identified human POMC-deficient patients(2). When treated with a stable alpha-melanocyte-stimulating hormone agonist, mutant mice lost more than 40% of their excess weight after 2 weeks. Our results identify the POMC-null mutant mouse as a model for studying the human POMC-null syndrome, and indicate the therapeutic use of peripheral melanocortin in the treatment of obesity. C1 Oklahoma Med Res Fdn, Dev Biol Program, Oklahoma City, OK 73104 USA. NIMH, Mol Genet Unit, Clin Neurosci Branch, Bethesda, MD 20892 USA. Eleanor Roosevelt Inst Canc Res, Denver, CO 80206 USA. RP Hochgeschwender, U (reprint author), Oklahoma Med Res Fdn, Dev Biol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. NR 25 TC 585 Z9 596 U1 1 U2 28 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1999 VL 5 IS 9 BP 1066 EP 1070 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 231XT UT WOS:000082337200044 PM 10470087 ER PT J AU Louis, JM Clore, GM Gronenborn, AM AF Louis, JM Clore, GM Gronenborn, AM TI Autoprocessing of HIV-1 protease is tightly coupled to protein folding SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN-IMMUNODEFICIENCY-VIRUS-1 PROTEASE; TRANSFRAME REGION; ESCHERICHIA-COLI; FUSION PROTEINS; INHIBITORS; PRECURSOR; KINETICS; ASSIGNMENTS; POLYPROTEIN AB In the Gag-Pol polyprotein of HIV-1, the 99-amino acid protease is flanked at its N-terminus by a transframe region (TFR) composed of the transframe octapeptide (TFP) and 48 amino acids of the p6(pol), separated by a protease cleavage site. The intact precursor (TFP-p6(pol)-PR) has very low dimer stability relative to that of the mature enzyme and exhibits negligible levels of stable tertiary structure. Thus, the TFR functions by destabilizing the native structure, unlike proregions found in zymogen forms of monomeric aspartic proteases. Cleavage at the p6(pol)-PR site to release a free N-terminus of protease is concomitant with the appearance of enzymatic activity and formation of a stable tertiary structure that is characteristic of the mature protease as demonstrated by nuclear magnetic resonance. The release of the mature protease from the precursor can either occur in two steps at pH values of 4 to 6 or in a single step above pH 6. The mature protease forms a dimer through a four-stranded beta-sheet at the interface. Residues 1-4 of the mature protease from each subunit constitute the outer strands of the beta-sheet, and are essential for maintaining the stability of the free protease but are not a prerequisite for the formation of tertiary structure and catalytic activity. Our experimental results provide the basis for the model proposed here for the regulation of the HIV-1 protease in the viral replication cycle. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gronenborn@nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 37 TC 124 Z9 124 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1999 VL 6 IS 9 BP 868 EP 875 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 231QH UT WOS:000082321000014 PM 10467100 ER PT J AU Heinz, A AF Heinz, A TI Serotonergic dysfunction after social isolation - implcations for the development of aggressiveness and alcohol dependence SO NERVENARZT LA German DT Review DE serotonin; behavior inhibition system; impulsivity; aggression; depression ID FLUID MONOAMINE METABOLITES; NONHUMAN PRIMATE MODEL; CEREBROSPINAL-FLUID; RHESUS-MONKEYS; TRYPTOPHAN DEPLETION; LEARNED HELPLESSNESS; IN-VIVO; ENVIRONMENTAL-INFLUENCES; GLUCOSE-METABOLISM; TOURETTES-SYNDROME AB Dysfunction of serotonergic neurotransmission has been associated with two different psychopathological syndromes-impulsive aggressivity resulting form a lack of stimulation of the "behavior inhibition system" on the one hand and the manifestation of clinical depression and compulsive syndromes on the other. The examination of primate behavior provides a model which may reconciliate these seemingly contradictory hypotheses. According to primate experiments, monoaminergic depletion results in anxious and desperate behavior only if the individual has previously been exposed to social isolation stress,which in turn induces a decrease in the central serotonin turnover rate. Young non-human primates who experience early social separation stress are anxious and fearful, while as adults they tend to be aggressive, consume excessive amounts of alcohol and are less intoxicated by alcohol intake. These observation indicate the importance of social separation stress in the pathogenesis of alcoholism and antisocial behavior and may point to prophylactic and pharmacological treatment strategies. C1 Zent Inst Seel Gesundheit, Klin Abhangiges Verhalten & Suchtmed, D-68159 Mannheim, Germany. NIAAA, Bethesda, MD USA. RP Heinz, A (reprint author), Zent Inst Seel Gesundheit, Klin Abhangiges Verhalten & Suchtmed, J5, D-68159 Mannheim, Germany. NR 98 TC 12 Z9 12 U1 5 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD SEP PY 1999 VL 70 IS 9 BP 780 EP 789 DI 10.1007/s001150050512 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 236RF UT WOS:000082611800002 PM 10522245 ER PT J AU Rybicki, BA Johnson, CC Peterson, EL Kortsha, GX Gorell, JM AF Rybicki, BA Johnson, CC Peterson, EL Kortsha, GX Gorell, JM TI A family history of Parkinson's disease and its effect on other PD risk factors SO NEUROEPIDEMIOLOGY LA English DT Article DE effect modification; interaction; metals; copper; iron; lead; smoking ID ALPHA-SYNUCLEIN GENE; ENVIRONMENT INTERACTION; MONOAMINE-OXIDASE; SUSCEPTIBILITY; POLYMORPHISM; ASSOCIATION; EPIDEMIOLOGY; MUTATION; EXPOSURE AB Parkinson's disease (PD) is likely a result of both inherited and exogenous factors. In a study of 144 PD cases and 464 controls, we used PD family history as a surrogate for inherited PD susceptibility. Cases were more likely to report a first- or second-degree relative with PD: 16.0 vs. 4.3%; odds ratio (OR) = 4.2; 95% confidence interval (CI) = 2.3-7.6. A PD family history was a greater risk factor for PD in subjects under age 70 (OR = 8.8; 95% CI = 3.4-22.8) compared with those over 70 (OR = 2.8; 95% CI = 1.3-6.1) and in men (OR = 8.1; 95% CI = 3.4-19.2) compared with women (OR = 2.6; 95% CI = 1.1-6.0). We also tested whether a PD family history modified the effects of other PD risk factors. In subjects with a PD family history, occupational exposure to copper, lead or iron increased the risk for PD (OR = 3.0; 95% CI = 0.7-13.3), but this was not the case for those without a family history (OR = 1.1; 95% CI = 0.7-1.6). Ever smoking cigarettes was inversely associated with PD in those without a PD family history (OR = 0.6; 95% CI = 0.4-0.9), but was positively associated with PD in those with a PD family history (OR = 1.7; 95% CI = 0.5-5.9). In summary, our results suggest that a PD family history, and perhaps, therefore, an inherited susceptibility, confers a greater risk for PD in men and individuals under 70 years of age and may modify the effects of environmental risk factors for PD. C1 Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. Henry Ford Hlth Syst, Div Movement Disorders, Detroit, MI 48202 USA. Henry Ford Hlth Syst, William T Gossett Parkinsons Dis Ctr, Dept Neurol, Detroit, MI 48202 USA. Wayne State Univ, NIEHS, Ctr Mol & Cellular Toxicol Human Applicat, Detroit, MI USA. RP Rybicki, BA (reprint author), Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, 1 Ford Pl,3E, Detroit, MI 48202 USA. OI Johnson, Christine Cole/0000-0002-6864-6604 FU NIEHS NIH HHS [ES06418] NR 44 TC 30 Z9 30 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD SEP-OCT PY 1999 VL 18 IS 5 BP 270 EP 278 DI 10.1159/000026222 PG 9 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 229QK UT WOS:000082205900008 PM 10461053 ER PT J AU Richert, ND Frank, JA AF Richert, ND Frank, JA TI Magnetization transfer imaging to monitor clinical trials in multiple sclerosis SO NEUROLOGY LA English DT Article ID APPEARING WHITE-MATTER; RESONANCE TECHNIQUES; LESION DEVELOPMENT; DISEASE BURDEN; SPIN-ECHO; MR; GADOLINIUM; PATTERNS; CONTRAST; MS AB Magnetization transfer imaging (MTI) is a sensitive magnetic resonance scanning technique for detecting disease activity and monitoring disease progression in multiple sclerosis (MS) patients. To date, MTI has not been used as an outcome measure in early phase and pivotal clinical trials. Magnetization transfer ratio, a quantitative measure of MT, can be used to follow the evolution of individual MS plaques as well as microscopic disease in normal-appearing white matter (NAWM). Volumetric whole brain NIT ratios of every voxel in the brain can be expressed as a histogram, providing an estimate of cerebral atrophy and a global disease activity including "occult" disease in NAWM, thus providing a quantitative measure of a therapeutic response. This report will briefly focus on how MTI could be used to monitor a therapeutic response in a treatment trial and address some of the pitfalls/limitations of MTI that can be encountered even in a well-designed longitudinal study. C1 Ctr Clin, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Diagnost Imaging, Washington, DC 20010 USA. RP Frank, JA (reprint author), Ctr Clin, Lab Diagnost Radiol Res, Bldg 10,Room B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA. NR 36 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1999 VL 53 IS 5 SU 3 BP S29 EP S32 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 237HN UT WOS:000082649900007 PM 10496208 ER PT J AU Reynolds, JH Desimone, R AF Reynolds, JH Desimone, R TI The role of neural mechanisms of attention in solving the binding problem SO NEURON LA English DT Article C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Reynolds, JH (reprint author), NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA. NR 0 TC 213 Z9 217 U1 5 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP PY 1999 VL 24 IS 1 BP 19 EP 29 DI 10.1016/S0896-6273(00)80819-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 241QC UT WOS:000082893200006 PM 10677024 ER PT J AU Schilling, G Wood, JD Kui, DA Slunt, HH Gonzales, V Yamada, M Cooper, JK Margolis, RL Jenkins, NA Copeland, NG Takahashi, H Tsuji, S Price, DL Borchelt, DR Ross, CA AF Schilling, G Wood, JD Kui, DA Slunt, HH Gonzales, V Yamada, M Cooper, JK Margolis, RL Jenkins, NA Copeland, NG Takahashi, H Tsuji, S Price, DL Borchelt, DR Ross, CA TI Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA SO NEURON LA English DT Article ID DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; NEURONAL INTRANUCLEAR INCLUSIONS; TRINUCLEOTIDE CAG REPEAT; HUNTINGTONS-DISEASE; TRIPLET-REPEAT; EXPANDED POLYGLUTAMINE; GENE-PRODUCT; SPINOCEREBELLAR ATAXIA; AGGREGATE FORMATION; HUMAN BRAIN AB Dentatorubral and pallidoluysian atrophy (DRPLA) is a member of a family of progressive neurodegenerative diseases caused by polyglutamine repeat expansion. Transgenic mice expressing full-length human atrophin-1 with 65 consecutive glutamines exhibit ataxia, tremors, abnormal movements, seizures, and premature death. These mice accumulate atrophin-1 immunoreactivity and inclusion bodies in the nuclei of multiple populations of neurons. Subcellular fractionation revealed 120 kDa nuclear fragments of mutant atrophin-1, whose abundance increased with age and phenotypic severity. Brains of DRPLA patients contained apparently identical 120 kDa nuclear fragments. By contrast, mice overexpressing atrophin-1 with 26 glutamines were phenotypically normal and did not accumulate the 120 kDa fragments. We conclude that the evolution of neuropathology in DRPLA involves proteolytic processing of mutant atrophin-1 and nuclear accumulation of truncated fragments. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Neuropathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21205 USA. NCI, Mammalian Genet Lab, Ctr Canc, Frederick, MD 21702 USA. Niigata Univ, Brain Res Inst, Dept Pathol, Niigata 951, Japan. Niigata Univ, Brain Res Inst, Dept Neurol, Niigata 951, Japan. RP Borchelt, DR (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RI Wood, Jonathan/A-5060-2009 FU NINDS NIH HHS [NS16375, NS34172] NR 60 TC 121 Z9 124 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP PY 1999 VL 24 IS 1 BP 275 EP 286 DI 10.1016/S0896-6273(00)80839-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 241QC UT WOS:000082893200026 PM 10677044 ER PT J AU Le, AD Poulos, CX Harding, S Watchus, J Juzytsch, W Shaham, Y AF Le, AD Poulos, CX Harding, S Watchus, J Juzytsch, W Shaham, Y TI Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcohol; drug self-administration; fluoxetine; naltrexone; opioid receptors; relapse; reinstatement; serotonin; stress ID HEROIN-SEEKING; 5-HYDROXYINDOLEACETIC ACID; BRAIN MICRODIALYSIS; UPTAKE INHIBITORS; SEROTONIN UPTAKE; INDUCED RELAPSE; ANIMAL-MODELS; ORAL ETHANOL; PREFERRING P; RATS AB We have recently shown that priming injections of alcohol and footshock stress reinstate alcohol seeking in drug-free rats. Here we tested whether naltrexone and fluoxetine, two drugs used in the treatment of alcohol dependence, would affect reinstatement of alcohol seeking induced by these events. We also determined the effects of these drugs on alcohol self-administration during the maintenance phase. rats were trained to press a lever for a 12% w/v alcohol solution. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished. Reinstatement of drug seeking tons then determined after priming injections of alcohol (0.24-0.96 g/kg) or exposure to intermittent footshock (5 and 15 min). Rats were pretreated with naltrexone (0.2-0.4 mg/kg) or fluoxetine (2.5-5 mg/kg) during maintenance or during tests for reinstatement. Both naltrexone and fluoxetine decreased lever presses for alcohol during the maintenance phase. Naltrexone blocked alcohol-induced, but not stress-induced reinstatement. In contrast, fluoxetine blocked stress-induced reinstatement, while its effect on alcohol-induced reinstatement was less consistent. The implications of these data to the understanding of relapse to alcohol are discussed. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 CAMH, Biobehav Res Dept, Toronto, ON M5S 2S1, Canada. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. NIDA, Behav Neurosci Branch, IRP, Baltimore, MD USA. RP Le, AD (reprint author), CAMH, Biobehav Res Dept, 33 Russell St, Toronto, ON M5S 2S1, Canada. RI shaham, yavin/G-1306-2014 NR 64 TC 160 Z9 161 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1999 VL 21 IS 3 BP 435 EP 444 DI 10.1016/S0893-133X(99)00024-X PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 224XZ UT WOS:000081926400012 PM 10457541 ER PT J AU Lee, SH Yajima, S Mouradian, MM AF Lee, SH Yajima, S Mouradian, MM TI Neural cell line-specific regulatory DNA cassettes harboring the murine D-1A dopamine receptor promoter SO NEUROSCIENCE RESEARCH LA English DT Article DE chloramphenicol acetyl transferase; DNA sequence; transcription; transfection ID TISSUE-SPECIFIC EXPRESSION; CENTRAL-NERVOUS-SYSTEM; TRANSGENIC MICE; GENE PROMOTER; MULTIPLE PROMOTERS; ALTERNATIVE PROMOTER; ENOLASE PROMOTER; HORMONE GENE; REGION; TRANSCRIPTION AB Transcription in the human and rat D-1A dopamine receptor genes proceeds from two distinct promoters in neuronal cells while only the downstream intronic promoter is active in renal cells. To investigate the utility of these promoters in the brain cell-specific expression of transgenes, we now studied the 5' flanking region of the murine D-1A gene. We confirmed the presence of two functional promoters utilized for the tissue-specific regulation of this gene similar to its human and rat homologues. The cloned 1.4-kb genomic fragment spans nucleotides - 967 to + 384 relative to the first ATG codon and includes intron 1 between bases - 534 to - 420. Transient expression analyses using various chroramphenicol acetyltransferase constructs revealed that the murine D-1A upstream promoter fused with the human D-1A gene activator sequence ActAR1 has potent transcriptional activity in a D-1A-expressing neuronal cell line but not in other cell lines tested including renal (OK cells), glial (C6) and hepatic (HepG2), suggesting that this hybrid construct harbors neural cell-specific elements. The availability of potent regulatory DNA cassettes harboring the murine D-1A gene promoter could aid testing the neuronal-specific expression of transgenes in vivo. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM mmm@helix.nih.gov OI Mouradian, M. Maral/0000-0002-9937-412X NR 47 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD SEP PY 1999 VL 34 IS 4 BP 225 EP 234 DI 10.1016/S0168-0102(99)00055-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 245YG UT WOS:000083135800004 PM 10576545 ER PT J AU Dudek, SM Fields, RD AF Dudek, SM Fields, RD TI Gene expression in hippocampal long-term potentiation SO NEUROSCIENTIST LA English DT Article DE LTP; gene expression; CREB; dendrites; synaptic tagging ID CAMP-RESPONSIVE ELEMENT; PROTEIN-SYNTHESIS; LATE-PHASE; MESSENGER-RNA; DENTATE GYRUS; CREB PHOSPHORYLATION; SYNAPTIC PLASTICITY; GLUTAMATE RECEPTORS; BINDING PROTEIN; REGULATED GENE AB Recent work on hippocampal LTP has focused on gene expression induced with high-frequency stimulation, as well as the signal transduction cascades responsible for the induction of these genes. Many scenarios for LTP lasting for greater than 5 hours include some or all of the following processes: 1) tagging of potentiated synapses, possibly by phosphorylation; 2) signaling to the nucleus; 3) kinase cascades and transcription factors in the nucleus; 4) expression of immediate-early genes and/or synaptic proteins; and, finally, 5) targeting of newly synthesized proteins (or RNAs) to the potentiated synapses land not to the unpotentiated synapses). Unfortunately, most scenarios proposed for the late-phase expression of LTP are still highly speculative at this time. A critical review of the literature relating to the role of gene expression in hippocampal LTP and a discussion of recent work on the subject will be presented. C1 NICHHD, Dev Neurobiol Lab, Bethesda, MD 20892 USA. OI Dudek, Serena M./0000-0003-4094-8368 NR 50 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD SEP PY 1999 VL 5 IS 5 BP 275 EP 279 DI 10.1177/107385849900500512 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 234RQ UT WOS:000082498500012 ER PT J AU Hallett, M AF Hallett, M TI Plasticity in the human motor system SO NEUROSCIENTIST LA English DT Article DE brain plasticity; brain injuries; motor representation; motor learning ID TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL BLOOD-FLOW; UPPER-LIMB AMPUTATION; ISCHEMIC NERVE BLOCK; FUNCTIONAL REORGANIZATION; HORIZONTAL CONNECTIONS; SOMATOSENSORY CORTEX; CORTICAL OUTPUTS; BRAILLE READERS; READING HAND AB The organization of motor representation in the human brain is plastic in a number of situations. Plasticity may be caused by unmasking of pre-existing connections, activity dependent synaptic changes, changes in membrane excitability, or growth of new connections. In peripheral injury, such as amputation, regions of brain no longer have a peripheral target. Neighboring motor representation areas targeting muscles ipsilateral and proximal to the amputation stump enlarge into this territory. Some changes can occur quickly, whereas others require years; this probably reflects different processes. In early brain injury, including patients with hemispherectomy, some recovery of function seems related to enhancement of ipsilateral pathways. Stroke in adult life may cause some reorganization in the lesioned hemisphere, and the role of ipsilateral pathways is not yet well established. Patterns of use and motor learning can influence brain organization. Use of a body part increases its representation, whereas disuse reduces representation. In motor learning, such as learning a finger sequence, the representation of muscles involved with the learning increases in size. Plasticity can even be cross-modal, as demonstrated by the functional role of the visual cortex when the blind read Braille. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. EM hallett@codon.nih.gov NR 61 TC 19 Z9 21 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD SEP PY 1999 VL 5 IS 5 BP 324 EP 332 DI 10.1177/107385849900500518 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 234RQ UT WOS:000082498500018 ER PT J AU Leipe, DD Aravind, L Koonin, EV AF Leipe, DD Aravind, L Koonin, EV TI Did DNA replication evolve twice independently? SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; REVERSE-TRANSCRIPTASE; PROTEIN-A; SEQUENCE DATABASES; UNIVERSAL ANCESTOR; BINDING PROTEINS; POLYMERASE-III AB DNA replication is central to all extant cellular organisms, There are substantial functional similarities between the bacterial and the archaeal/eukaryotic replication machineries, including but not limited to defined origins, replication bidirectionality, RNA primers and leading and lagging strand synthesis. However, several core components of the bacterial replication machinery are unrelated or only distantly related to the functionally equivalent components of the archaeal/eukaryotic replication apparatus. This is in sharp contrast to the principal proteins involved in transcription and translation, which are highly conserved in all divisions of life. We performed detailed sequence comparisons of the proteins that fulfill indispensable functions in DNA replication and classified them into four main categories with respect to the conservation in bacteria and archaea/eukaryotes: (i) non-homologous, such as replicative polymerases and primases; (ii) containing homologous domains but apparently non-orthologous and conceivably independently recruited to function in replication, such as the principal replicative helicases or proofreading exonucleases; (iii) apparently orthologous but poorly conserved, such as the sliding clamp proteins or DNA ligases; (iv) orthologous and highly conserved, such as clamp-loader ATPases or 5'-->3' exonucleases (FLAP nucleases), The universal conservation of some components of the DNA replication machinery and enzymes for DNA precursor biosynthesis but not the principal DNA polymerases suggests that the last common ancestor (LCA) of all modern cellular life forms possessed DNA but did not replicate it the way extant cells do. We propose that the LCA had a genetic system that contained both RNA and DNA, with the latter being produced by reverse transcription. Consequently, the modern-type system for double-stranded DNA replication likely evolved independently in the bacterial and archaeal/eukaryotic lineages. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A, Bethesda, MD 20894 USA. NR 68 TC 205 Z9 212 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1999 VL 27 IS 17 BP 3389 EP 3401 DI 10.1093/nar/27.17.3389 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234WK UT WOS:000082507200001 PM 10446225 ER PT J AU Kroutil, LC Kunkel, TA AF Kroutil, LC Kunkel, TA TI Deletion errors generated during replication of CAG repeats SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASE-BETA; NONPOLYPOSIS COLORECTAL-CANCER; MISMATCH REPAIR; MUTATIONAL SPECIFICITY; TRINUCLEOTIDE REPEATS; REPETITIVE DNA; HUMAN-DISEASE; BACTERIOPHAGE-T7; PROCESSIVITY; FIDELITY AB Triplet repeat sequence instability is associated with hereditary neurological diseases and with certain types of cancer, Here we study one form of this instability, deletion of triplet repeats during replication of template (CAG)(n) sequences by DNA polymerases. To monitor loss of triplet codons, we inserted (CAG)(g) and (CAG)(17) repeats into the lacZ sequence in M13mp2 and changed one repeat to a TAG codon to yield DNA substrates with colorless plaque phenotypes, Templates containing these inserts within gaps were copied and errors were scored as blue plaque Lac revertants whose DNA was sequenced to determine if loss of the TAG codon resulted from substitutions or deletions, DNA synthesis by either DNA polymerase beta or exonuclease-deficient T7 DNA polymerase produced deletions involving loss of from 1 to 8 of 9 or 15 of 17 repeats, Thus, these polymerases utilize misaligned template-primers containing from 3 to 45 extra template strand nucleotides, Deletion frequencies were much higher than substitution frequencies at the TAG codon in certain repeats, indicating that triplet repeats are at high risk for mutation in the absence of error correction. Proofreading-proficient T7 DNA polymerase generated deletions at 2- to 10-fold lower frequencies than did its exonuclease-deficient derivative. This suggests that misaligned triplet repeat sequences are subject to proofreading, but at reduced efficiency compared to editing of single-base mismatches. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP NIEHS, Mol Genet Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 34 TC 26 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1999 VL 27 IS 17 BP 3481 EP 3486 DI 10.1093/nar/27.17.3481 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234WK UT WOS:000082507200012 PM 10446236 ER PT J AU Orren, DK Brosh, RM Nehlin, JO Machwe, A Gray, MD Bohr, VA AF Orren, DK Brosh, RM Nehlin, JO Machwe, A Gray, MD Bohr, VA TI Enzymatic and DNA binding properties of purified WRN protein: high affinity binding to single-stranded DNA but not to DNA damage induced by 4NQO SO NUCLEIC ACIDS RESEARCH LA English DT Article ID WERNER-SYNDROME PROTEIN; PREMATURE AGING SYNDROMES; SYNDROME GENE-PRODUCT; ESCHERICHIA-COLI; HELICASE-II; WILD-TYPE; 4-NITROQUINOLINE 1-OXIDE; EXCISION-REPAIR; CELLS; EXONUCLEASE AB Mutations in the WRN gene result in Werner syndrome, an autosomal recessive disease in which many characteristics of aging are accelerated, A probable role in some aspect of DNA metabolism is suggested by the primary sequence of the WRN gene product, A recombinant His-tagged WRN protein (WRNp) was overproduced in insect cells using the baculovirus system and purified to near homogeneity by several chromatographic steps. This purification scheme removes both nuclease and topoisomerase contaminants that persist following a single Ni2+ affinity chromatography step and allows for unambiguous interpretation of WRNp enzymatic activities on DNA substrates. Purified WRNp has DNA-dependent ATPase and helicase activities consistent with its homology to the RecQ subfamily of proteins. The protein also binds with higher affinity to single-stranded DNA than to double-stranded DNA, However, WRNp has no higher affinity for various types of DNA damage, including adducts formed during 4NQO treatment, than for undamaged DNA. Our results confirm that WRNp has a role in DNA metabolism, although this role does not appear to be the specific recognition of damage in DNA. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NR 62 TC 100 Z9 100 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1999 VL 27 IS 17 BP 3557 EP 3566 DI 10.1093/nar/27.17.3557 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234WK UT WOS:000082507200023 PM 10446247 ER PT J AU Li, SS Livingstone-Zatchej, M Gupta, R Meijer, M Thoma, F Smerdon, MJ AF Li, SS Livingstone-Zatchej, M Gupta, R Meijer, M Thoma, F Smerdon, MJ TI Nucleotide excision repair in a constitutive and inducible gene of a yeast minichromosome in intact cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; DNA-REPAIR; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; TRANSCRIBED STRAND; PREFERENTIAL REPAIR; MESSENGER-RNA; NUCLEOSOME; CHROMATIN; SEQUENCES AB Repair of UV-induced cyclobutane pyrimidine dimers (CPDs) was measured in a yeast minichromosome, having a galactose-inducible GAL1:URA3 fusion gene, a constitutively expressed HIS3 gene and varied regions of chromatin structure. Transcription of GAL1:URA3 increased >150-fold, while HIS3 expression decreased <2-fold when cells were switched from glucose to galactose medium, Following galactose induction, four nucleosomes were displaced or rearranged in the GAL3-GAL10 region. However, no change in nucleosome arrangement was observed in other regions of the minichromosome following induction, indicating that only a few plasmid molecules actively transcribe at any one time, Repair at 269 cis-syn CPD sites revealed moderate preferential repair of the transcribed strand of GAL1:URA3 in galactose, consistent with transcription-coupled repair in a fraction of these genes. Many sites upstream of the transcription start site in the transcribed strand were also repaired faster upon induction. There is remarkable repair heterogeneity in the HIS3 gene and preferential repair is seen only in a short sequence immediately downstream of the transcription start site. Finally, a mild correlation of repair heterogeneity with nucleosome positions was observed in the transcribed strand of the inactive GAL1:URA3 gene and this correlation was abolished upon galactose induction. C1 Washington State Univ, Dept Biochem & Biophys, Pullman, WA 99164 USA. ETH Honggerberg, Inst Zellbiol, CH-8093 Zurich, Switzerland. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Smerdon, MJ (reprint author), Washington State Univ, Dept Biochem & Biophys, Pullman, WA 99164 USA. RI Li, Shisheng/H-9126-2012 FU NIEHS NIH HHS [ES04106] NR 46 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1999 VL 27 IS 17 BP 3610 EP 3620 DI 10.1093/nar/27.17.3610 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234WK UT WOS:000082507200030 PM 10446254 ER PT J AU Weyer, C Pratley, RE AF Weyer, C Pratley, RE TI Fasting and postprandial plasma concentrations of acylation-stimulation protein (ASP) in lean and obese Pima Indians compared to Caucasians SO OBESITY RESEARCH LA English DT Article DE complement; C3adesarg; triglyceride synthesis; ethnicity; adipose tissue ID ADIPOSE-TISSUE; TRIGLYCERIDE SYNTHESIS; DIABETES INCIDENCE; BODY-WEIGHT; METABOLISM; HUMANS; FIBROBLASTS; CHOLESTEROL; ADIPOCYTE; MELLITUS AB Objective: ASP stimulates the clearance of free fatty acids (FFA) from the circulation and the synthesis of triglycerides (TG) in adipose tissue. We tested whether fasting and postprandial plasma ASP concentrations are increased in Pima Indians, a population with a very high prevalence of obesity, but a remarkably low prevalence of dyslipidemia. Research Methods and Procedures: Plasma concentrations of ASP, TG, FFA, total cholesterol (CHOL), and insulin (INS) were measured in 15 Pima Indians (P) and 15 Caucasians (C) closely matched for age, sex, and body weight [7 lean and 8 obese subjects, body mass index (BMI) cut-off 30 kg/m(2)], before and for 4 hours after a standard mixed meal (20% of daily caloric requirements, 41% carbohydrate, 44% fat, 15% protein). Results: Fasting ASP was positively related to percent body fat (dual energy X-ray absorptiometry; r=0.49, p<0.01) and to TG and FFA, independently of percent body fat (partial r=0.42 and 0.46, respectively, both p<0.05). There were no differences in fasting TG, FFA, CHOL, INS, or ASP between lean C and lean P. In contrast, obese P had lower TG, lower CHOL, higher INS and, on average, 27% lower ASP compared to obese C. The ethnic difference in ASP remained after adjustment for TG, FFA, and percent body fat. ASP decreased in response to the meal in all four groups with no differences between groups. There was a significant inverse correlation between preprandial ASP and the change in FFA 60 minutes after the meal (r=-0.56, p<0.001). Discussion: Pima Indians do not have higher plasma ASP concentrations than Caucasians. Whether other alterations in the ASP-pathway, such as increased sensitivity of adipocytes to ASP, contribute to the high prevalence of obesity and low prevalence of dyslipidemia in Pima Indians, remains to be elucidated. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. NR 47 TC 35 Z9 36 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 1999 VL 7 IS 5 BP 444 EP 452 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 237PU UT WOS:000082665900004 PM 10509601 ER PT J AU Inskip, P AF Inskip, P TI The Neugut et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BREAST-CANCER; CONTRALATERAL BREAST; LUNG-CANCER; HODGKINS-DISEASE; RADIOTHERAPY; RISK; IRRADIATION C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Inskip, P (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD SEP PY 1999 VL 13 IS 9 BP 1261 EP + PG 3 WC Oncology SC Oncology GA 392WE UT WOS:000166434900015 ER PT J AU Ratnasinghe, D Tangrea, JA Roth, MJ Dawsey, SM Anver, M Kasprzak, BA Hu, N Wang, QH Taylor, PR AF Ratnasinghe, D Tangrea, JA Roth, MJ Dawsey, SM Anver, M Kasprzak, BA Hu, N Wang, QH Taylor, PR TI Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus SO ONCOLOGY REPORTS LA English DT Article DE immunohistochemistry; gastric cardia cancer; gastric corpus cancer; cyclooxygenase-2; NSAIDs ID CANCER; ESOPHAGEAL; ASPIRIN; RISK AB Several studies indicate that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric corpus and possibly gastric cardia cancers. The best known action of NSAIDs is to block the enzyme cyclooxygenase, the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins. We investigated the expression of cyclooxygenase-2 (Cox-2) in adenocarcinomas of the gastric cardia (N=19) and corpus (N=15) and in adjacent normal epithelium from a high risk Chinese population. Immunohistochemical detection of Cox-2 revealed positive staining in 36% of the gastric cardia cancer cases and 60% of the gastric corpus cancer cases, whereas histologically normal tissue from the same patients were negative. Smooth muscle, stroma and inflammatory cells were also positive. Our results suggest that Cox-2 is overexpressed in a large proportion of adenocarcinomas of the gastric corpus and in a smaller number of gastric cardia cancer cases. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Shanxi Canc Hosp, Dept Pathol, Taiyuan, Peoples R China. RP Ratnasinghe, D (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, NIH, 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 12 TC 24 Z9 29 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD SEP-OCT PY 1999 VL 6 IS 5 BP 965 EP 968 PG 4 WC Oncology SC Oncology GA 224JX UT WOS:000081895700004 PM 10425287 ER PT J AU Castle, JT Cardinali, M Kratochvil, FJ Abbondanzo, SL Kessler, HP Auclair, PL Yeudall, WA AF Castle, JT Cardinali, M Kratochvil, FJ Abbondanzo, SL Kessler, HP Auclair, PL Yeudall, WA TI p53 and cyclin D1 staining patterns of malignant and premalignant oral lesions in age-dependent populations SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; HUMAN HEAD; FUNCTIONAL-CHARACTERIZATION; NECK-CANCER; T-ANTIGEN; EXPRESSION; PROTEIN; OVEREXPRESSION; ALLELOTYPE; ONCOGENE AB Objective. Recent epidemiologic studies have identified a trend of increasing cancer incidence in younger patients. The purpose of this study was to determine whether this might be reflected by different molecular mechanisms for tumor development. Study design. Dysplastic and malignant oral lesions from age-distinct patient populations were immunohistochemically analyzed for expression of p53 and cyclin Dr. Chi-square analysis was used to determine statistical significance. Results. Eighty-two percent of "older" and 75%, of "younger" carcinomas stained positively with p53; 63% of carcinomas in the older population and 55% of carcinomas in the younger population showed cyclin D1 positivity. Dysplasias showed similar cyclin D1 staining in both groups, interestingly, 100% of "younger" dysplasias stained positively for p53, whereas 35.3% of "older" dysplastic lesions showed immunoreactivity. Staining of carcinomas was not statistically significant, whereas p53 staining of dysplasias proved highly significant (P < .025). Conclusions. p53 immunoreactivity is detectable at an earlier stage of carcinogenesis in younger patients than in the traditional risk population for oral cancer. C1 Natl Naval Dent Ctr, Dept Oral Pathol, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. Oregon Hlth Sci Univ, Sch Dent, Dept Oral Pathol, Portland, OR 97201 USA. Univ Florida, Coll Dent, Dept Hematol & Lymphat Pathol, Gainesville, FL USA. Univ Florida, Coll Dent, Dept Orl & Maxillofacial Pathol & Oncol, Gainesville, FL USA. RP Castle, JT (reprint author), Armed Forces Inst Pathol, Dept Otolaryngol Head & Neck Pathol, Bldg 54,Room G066-8,6825 16th St NW, Washington, DC 20306 USA. NR 37 TC 13 Z9 14 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD SEP PY 1999 VL 88 IS 3 BP 326 EP 332 DI 10.1016/S1079-2104(99)70037-5 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 235QR UT WOS:000082554500014 PM 10503863 ER PT J AU Rennert, OM Francis, GL AF Rennert, OM Francis, GL TI Diabetes mellitus: Perspectives for the future SO PEDIATRIC ANNALS LA English DT Editorial Material C1 NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Chair Res, Bethesda, MD 20814 USA. RP Rennert, OM (reprint author), NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 1999 VL 28 IS 9 BP 566 EP + PG 2 WC Pediatrics SC Pediatrics GA 249AF UT WOS:000083309000004 ER PT J AU Rennert, OM Francis, GL AF Rennert, OM Francis, GL TI Update on the genetics and pathophysiology of type I diabetes mellitus SO PEDIATRIC ANNALS LA English DT Article ID AUTOIMMUNE-DISEASE; NOD MICE; IDDM; PREVENTION; POPULATION; PREDICTION; ANTIBODIES; CHILDHOOD; EVENTS AB The authors describe the genetic, environmental, and age-dependent factors that have an impact on the risk for development of type I diabetes mellitus and review its diagnostic criteria. C1 Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Rennert, OM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pediat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 1999 VL 28 IS 9 BP 570 EP + PG 7 WC Pediatrics SC Pediatrics GA 249AF UT WOS:000083309000005 PM 10495998 ER PT J AU Gerber, MA AF Gerber, MA TI Lyme disease vaccine SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Review ID OUTER-SURFACE PROTEIN; BORRELIA-BURGDORFERI; OSPA; MICE C1 NIH, Bethesda, MD 20892 USA. RP Gerber, MA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 1999 VL 18 IS 9 BP 825 EP 826 DI 10.1097/00006454-199909000-00017 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 234NF UT WOS:000082490200014 PM 10493347 ER PT J AU Manns, A Strickler, HD Wiktor, SZ Pate, EJ Gray, R Waters, D AF Manns, A Strickler, HD Wiktor, SZ Pate, EJ Gray, R Waters, D TI Low incidence of human papillomavirus type 16 antibody seroconversion in young children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE human papillomavirus; antibodies; human papillomavirus type 16; seroconversion; vertical transmission; children ID CERVICAL-CANCER; TRANSMISSION; PREVALENCE; COHORT; DNA C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ W Indies, Kingston 7, Jamaica. Sci Applicat Int Corp, Frederick, MD USA. RP Manns, A (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8008,MSC 7248, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CP-40548] NR 11 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 1999 VL 18 IS 9 BP 833 EP 835 DI 10.1097/00006454-199909000-00020 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 234NF UT WOS:000082490200017 PM 10493350 ER PT J AU Brunell, PA AF Brunell, PA TI Possible role of varicella vaccine in preventing herpes SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter DE herpes simplex; varicella; varicella vaccine; zoster ID CHILDREN; ZOSTER C1 NIAID, Bethesda, MD 20892 USA. RP Brunell, PA (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 1999 VL 18 IS 9 BP 842 EP 843 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 234NF UT WOS:000082490200024 PM 10493357 ER PT J AU Chilton, L Bodurtha, J Butterbrodt, MP Freeland-Hyde, B Gahagan, S Grossman, D Jantz, J Allen-Davis, JT Bechtold, D Bell, JT Brenneman, G Green, WF Postl, B Zind, B Goodrich, J Mandell, F AF Chilton, L Bodurtha, J Butterbrodt, MP Freeland-Hyde, B Gahagan, S Grossman, D Jantz, J Allen-Davis, JT Bechtold, D Bell, JT Brenneman, G Green, WF Postl, B Zind, B Goodrich, J Mandell, F CA Comm Native Amer Child Hlth Comm Infect Dis TI Immunizations for Native American children SO PEDIATRICS LA English DT Article ID INVASIVE PNEUMOCOCCAL DISEASE; VACCINE EFFICACY TRIAL; B CONJUGATE VACCINES; HEPATITIS-B; VIRUS-INFECTION; ALASKA NATIVES; EPIDEMIOLOGY; POPULATION; INFANTS; INDIANS C1 Amer Coll Obstetricians & Gynecologists, Washington, DC USA. Amer Acad Child & Adolescent Psychiat, Washington, DC USA. Johns Hopkins Ctr Amer Indian & Alaskan Native Hl, Baltimore, MD USA. Canadian Paediat Soc, Ottawa, ON, Canada. Comm Infect Dis, Elk Grove Village, IL USA. Natl Vaccine Program Off, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. AAP Council Pediat Practice, Elk Grove Village, DC USA. Amer Thorac Soc, Washington, DC USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIAID, Bethesda, MD USA. NR 22 TC 5 Z9 5 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1999 VL 104 IS 3 BP 564 EP 567 PG 4 WC Pediatrics SC Pediatrics GA 240FV UT WOS:000082816000038 ER PT J AU Carlo, WA Stark, AR Bauer, C Donovan, E Oh, W Papile, LA Shankaran, S Tyson, JE Wright, LL Temprosa, E Poole, K AF Carlo, WA Stark, AR Bauer, C Donovan, E Oh, W Papile, LA Shankaran, S Tyson, JE Wright, LL Temprosa, E Poole, K CA NICHD Neonatal Res Network TI Effects of minimal ventilation in a multicenter randomized controlled trial of ventilator support and early corticosteroid therapy in extremely low birth weight infants SO PEDIATRICS LA English DT Meeting Abstract C1 NICHD, Neonatal Res Network, Bethesda, MD USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1999 VL 104 IS 3 BP 738 EP 739 PN 3 PG 2 WC Pediatrics SC Pediatrics GA 243LR UT WOS:000082999600197 ER PT J AU Stark, AR Carlo, W Bauer, C Donovan, E Oh, W Papile, L Shankaran, S Tyson, JE Wright, LL Temprosa, M Poole, K AF Stark, AR Carlo, W Bauer, C Donovan, E Oh, W Papile, L Shankaran, S Tyson, JE Wright, LL Temprosa, M Poole, K CA NICHD Neonatal Res Network TI Complications of early steroid therapy in a randomized controlled trial SO PEDIATRICS LA English DT Meeting Abstract C1 NICHD, Neonatal Res Network, Bethesda, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1999 VL 104 IS 3 BP 739 EP 739 PN 3 PG 1 WC Pediatrics SC Pediatrics GA 243LR UT WOS:000082999600198 ER PT J AU Hediger, ML Overpeck, MD McGlynn, A Kuczmarski, RJ Maurer, KR Davis, WW AF Hediger, ML Overpeck, MD McGlynn, A Kuczmarski, RJ Maurer, KR Davis, WW TI Growth and fatness at three to six years of age of children born small- or large-for-gestational age SO PEDIATRICS LA English DT Article DE blacks; birth weight; growth; large-for-gestational-age; multiple imputation; Mexican-Americans; National Health and Nutrition Examination Survey; small-for-gestational age; whites ID NUTRITION EXAMINATION SURVEY; LONG-TERM MORBIDITY; BIRTH-WEIGHT; CHILDHOOD GROWTH; NATIONAL-HEALTH; YOUNG-CHILDREN; BODY-MASS; OBESITY; SIZE; RETARDATION AB Objective. To compare young children 3 to 6 years of age who were born small-for-gestational age (SGA; <10th percentile for gestational age) or large-for-gestational age (LGA; greater than or equal to 90th percentile) with those who were born appropriate-for-gestational age (10th-89th percentile) to determine whether there are differences in growth and fatness in early childhood associated with birth weight status. Design and Methods. National sample of 3192 US-born non-Hispanic white, non-Hispanic black, and Mexican-American children 3 to 6 years of age (36-83 months) examined in the third National Health and Nutrition Examination Survey and for whom birth certificates were obtained. On the birth certificates, length of gestation from the mother's last menstrual period was examined for completeness, validity, and whether the pattern of missing (n = 141) and invalid data (n = 147) on gestation was random. Gestation was considered invalid when >44 weeks, or when at gestations of less than or equal to 35 weeks, birth weight was inconsistent with gestation. To reclaim cases with missing or invalid data on gestation for analysis, a multiple imputation (MI) procedure was used. MI procedures are recommended when, as in this case, a critical covariate (length of gestation) is not missing at random, and complete-subject analysis may be biased. Using the results of the MI procedure, children were categorized, and growth outcome was assessed by birth weight-for-gestational age status. The growth outcomes considered in these analyses were body weight (kg), height (cm), head circumference (cm), mid-upper arm circumference (MUAC; cm), and triceps and subscapular skinfold thicknesses (mm). The anthropometric outcomes first were transformed to approximate normal distributions and converted into z scores (standard deviation units [SDU]) to scale the data for comparison across ages. Outcomes at each age then were estimated using regression procedures. SUDAAN software that adjusts variance estimates to account for the sample design was used in analysis for prevalence estimates and to calculate regression coefficients (in SDU). Results. Over these ages, children born SGA remained significantly shorter and weighed less (-0.70 to -0.60 SDU). Children born LGA remained taller and weighed more (0.40-0.60 SDU). For weight and height among LGA children, there was a divergence from the mean with age compared with those born appropriate-for-gestational age (10th-89th percentile). Head circumference and MUAC followed these same patterns. The coefficients for MUAC show values for SGA children fairly consistently at about -0.50 SDU and children born LGA show increasing MUAC from +0.40 to +0.50 SDU from 36 to 83 months of age. As with weight, there is a trend toward increased MUAC coefficients with age. Measures of fatness (triceps and subscapular skinfolds), which are more prone to environmental influences, showed less association with birth weight-for-gestational age status. Only a single age group, the oldest (6 years of age) group showed a significant deficit in fatness for children born SGA. For children born LGA, there was an increase in fatness at both the triceps and subscapular sites after 3 years of age. Conclusion. These findings on a national sample of US-born non-Hispanic white, non-Hispanic black, and Mexican-American children show that children born SGA remain significantly shorter and lighter throughout early childhood and do not seem to catch up from 36 to 83 months of age. LGA infants remain longer and heavier through 83 months of age, but unlike children born SGA, children born LGA may be prone to an increasing accumulation of fat in early childhood. Thus, early childhood may be a particularly sensitive period in which there is increase in variation in levels of fatness associated with size at birth. These findings have implications for the evaluation of the growth of young children. The results indicate that intrauterine growth is associated with size in early childhood. Particularly, children born LGA may be at risk for accumulating excess fat at these ages. Birth weight status and gestational age may be useful in assembling a prognostic risk profile for children. C1 NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. PricewaterhouseCoopers, Washington, DC USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. RP Overpeck, MD (reprint author), NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Bldg 6100,Rm 7B03,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 85 Z9 87 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1999 VL 104 IS 3 BP art. no. EP e33 DI 10.1542/peds.104.3.e33 PG 6 WC Pediatrics SC Pediatrics GA 240FV UT WOS:000082816000029 PM 10469816 ER PT J AU Falloon, J Sargent, S Piscitelli, SC Bechtel, C LaFon, SW Sadler, B Walker, RE Kovacs, JA Polis, MA Davey, RT Lane, HC Masur, H AF Falloon, J Sargent, S Piscitelli, SC Bechtel, C LaFon, SW Sadler, B Walker, RE Kovacs, JA Polis, MA Davey, RT Lane, HC Masur, H TI Atovaquone suspension in HIV-infected volunteers: Pharmacokinetics, pharmacodynamics, and TMP-SMX interaction study SO PHARMACOTHERAPY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; TRIMETHOPRIM-SULFAMETHOXAZOLE; AIDS; 566C80; EFFICACY; SAFETY AB Study Objective. To evaluate the pharmacokinetics and safely of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV). Design. Open-label, nonrandomized study. Setting. Two clinical research centers. Patients. Twenty-two HIV-infected volunteers with a median CD4 cell count of 37 cells/mm(3). Interventions. Patients received atovaquone suspension fasting or fed for 2-week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long-term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim-sulfamethoxazole (TMP-SMX). Measurements and Main Results. Average steady-state atovaquone concentrations-at 500 mg were 6.7 +/- 3.2 mu g/ml fasted and 11.3 +/- 5.0 mu g/ml with food, at 750 mg, 9.9 +/- 7.1 mu g/ml fasted and 12.5 +/- 5.9 mu g/ml with food, at 1000 mg, 9.7 +/- 4.3 mu g/ml fasted and 13.6 +/- 5.0 mu g/ml with food; and at 1500 mg, 21.1 +/- 5.0 mu g/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3- to 1.7-fold increase in values. Average steady-state concentrations were less than 10 mu g/ml in 21% and more than 15 mu g/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 mu g/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP-SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%). Conclusion. Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia. C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Falloon, J (reprint author), NIAID, NIH, Bldg 10,Room 11C103,MSC 1880, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 15 TC 11 Z9 11 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP PY 1999 VL 19 IS 9 BP 1050 EP 1056 DI 10.1592/phco.19.13.1050.31598 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230ZR UT WOS:000082282000005 PM 10610011 ER PT J AU Varmus, H AF Varmus, H TI The impact of physics on biology and medicine SO PHYSICS WORLD LA English DT Article C1 NIH, Bethesda, MD 20892 USA. RP Varmus, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0953-8585 J9 PHYS WORLD JI Phys. World PD SEP PY 1999 VL 12 IS 9 BP 27 EP 31 PG 5 WC Physics, Multidisciplinary SC Physics GA 234LU UT WOS:000082486800023 ER PT J AU Stefanek, M Enger, C Benkendorf, J Honig, SF Lerman, C AF Stefanek, M Enger, C Benkendorf, J Honig, SF Lerman, C TI Bilateral prophylactic mastectomy decision making: A vignette study SO PREVENTIVE MEDICINE LA English DT Article DE bilateral prophylactic mastectomy; family history; breast cancer; worry; risk perception ID BREAST-CANCER; OVARIAN-CANCER; FAMILIES; BRCA1 AB Background Little is known about the perception of bilateral prophylactic mastectomy (BPM), and whether perceptions are influenced by a family history of breast cancer. It is also unclear what factors may play a role in selecting BPM for follow-up care. Methods, Samples of predominantly Caucasian, well-educated women with (n = 129) and without (n = 104) family histories of breast cancer were provided a vignette of a woman at increased risk. They selected one of two follow-up options: (1) clinical breast examination, breast self exam, and annual mammography or (2) BPM. Results. The samples did not differ on the decision to select BPM: (29.5% vs 22.1%). The family history sample reported worry about breast cancer as a problem (34.4%) more often than women with no history (15.7%). Multivariate analysis found worry and estimated 10-year risk of the woman in the vignette as significant predictors of selecting BPM. Conclusions. Approximately 25% of our sample selected BPM as the preferred option. The: majority supported the need to discuss BPM among women at increased risk. Finally, both factors associated with the selection of BPM (worry, risk assessment) are potentially amenable to psychosocial or educational approaches. There is a clear need far assessment of worry and risk perception prior to surgical decision making. (C) Press American Health Foundation and Academic Press. C1 NCI, Behav Res Program, Div Canc Control & Populat Serv, Bethesda, MD 20892 USA. Johns Hopkins Canc Ctr, Baltimore, MD 21287 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Stefanek, M (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Serv, 6130 Execut Blvd,EPN 211, Bethesda, MD 20892 USA. NR 17 TC 22 Z9 22 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1999 VL 29 IS 3 BP 216 EP 221 DI 10.1006/pmed.1999.0524 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 234LN UT WOS:000082486300012 PM 10479610 ER PT J AU Coe, JE Vomachka, AJ Ross, MJ AF Coe, JE Vomachka, AJ Ross, MJ TI Effect of hamster pregnancy on female protein, a homolog of serum amyloid P component SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; SYRIAN-HAMSTER; ARMENIAN HAMSTER; GENE STRUCTURE; A-PROTEIN; PENTRAXIN; CONSTITUENT; EXPRESSION; INDUCTION; MOUSE AB Pentraxins such as human serum amyloid P component (SAP) and C reactive protein (CRP) represent an ancient family of proteins that are ubiquitous in nature and have evolved with little change in structure or regulation. The pentraxin in the Syrian hamster (Mesocricetus auratus) is unique because it is preferentially expressed in the female at high constitutive levels and accordingly called female protein (FP) or FP(SAP) due to ifs close homology with human SAP. The high levels of FP in female serum (100-fold greater than male serum) suggested its role in hamster pregnancy, one of the shortest of any eutherian mammal. We determined the serum FP concentration in pregnant Syrian hamsters and found a marked decrease (>80%) at term with the nadir at parturition with subsequent increase. A similar downregulation of FP was found in the normal female Syrian hamster after injury (acute phase response), so in both cases the assumed beneficial effects were achieved with less, rather than more pentraxin, a paradoxical pentraxin response. The fall in serum FP concentration could represent a response to protect the fetus from the high and potentially toxic level of FP normally found in the female, that is harmful because of its association with amyloidosis. An FP that is 97.5% identical to Syrian hamster FP is found in the Turkish hamster (Mesocricetus brandti), although serum levels in females are much lower, and amyloid is very rare. During pregnancy/parturition of Turkish hamsters, the serum level of FP remained remarkably constant. In a more distantly related hamster, the Armenian hamster (Cricetulos migratorius), serum FP actually increased during pregnancy and at parturition in a manner similar to that found in the Armenian hamster during an acute phase response. The heterogeneity of FP kinetics during pregnancy in these three species of hamster indicates pleomorphic gene structure for regulation of their similar FPs, and suggests that this protein may have a different function in the pregnancy of each species. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Beaver Coll, Dept Biol, Glenside, PA 19038 USA. RP Coe, JE (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD SEP PY 1999 VL 221 IS 4 BP 369 EP 375 DI 10.1046/j.1525-1373.1999.d01-94.x PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 225NM UT WOS:000081967700009 PM 10460699 ER PT J AU Ma, BY Kumar, S Tsai, CJ Nussinov, R AF Ma, BY Kumar, S Tsai, CJ Nussinov, R TI Folding funnels and binding mechanisms SO PROTEIN ENGINEERING LA English DT Article DE binding; conformational ensembles; energy landscape; folding; funnels; lock-and-key vs induced fit; misfolding ID HUMAN TISSUE FACTOR; CRYSTAL-STRUCTURE; DNA-BINDING; TRP REPRESSOR; CONFORMATIONAL FLEXIBILITY; 3-DIMENSIONAL STRUCTURES; EXTRACELLULAR DOMAIN; ANGSTROM RESOLUTION; ANTIBODY D1.3; PROTEIN AB The long-held views on lock-and-key versus induced fit in binding arose from the notion that a protein exists in a single, most stable conformation, dictated by its sequence. However, in solution proteins exist in a range of conformations, which may be described by statistical mechanical laws and their populations follow statistical distributions. Upon binding, the equilibrium will shift in favor of the bound conformation from the ensemble of conformations around the bottom of the folding funnel. Hence here we extend the implications and the usefulness of the folding funnel concept to explain fundamental binding mechanisms. C1 NCI, Intramural Res Support Program, SAIC, Lab Expt & Computat Biol,FCRDC, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC, Lab Expt & Computat Biol,FCRDC, Ft Detrick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 74 TC 320 Z9 324 U1 2 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD SEP PY 1999 VL 12 IS 9 BP 713 EP 720 DI 10.1093/protein/12.9.713 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 246MN UT WOS:000083167700002 PM 10506280 ER PT J AU Zolkiewski, M Kessel, M Ginsburg, A Maurizi, MR AF Zolkiewski, M Kessel, M Ginsburg, A Maurizi, MR TI Nucleotide-dependent oligomerization of ClpB from Escherichia coli SO PROTEIN SCIENCE LA English DT Article DE electron microscopy; heat-shock proteins; nucleotide binding; protein association; sedimentation equilibrium; sedimentation velocity ID HEAT-SHOCK-PROTEIN; MOLECULAR CHAPERONE; ACTIVATED ATPASE; BINDING SITES; HSP104; COEFFICIENT; ASSAY AB Self-association of ClpB (a mixture of 95- and 80-kDa subunits) has been studied with gel filtration chromatography, analytical ultracentrifugation, and electron microscopy. Monomeric ClpB predominates at low protein concentration (0.07 mg/mL), while an oligomeric form is highly populated at >4 mg/mL. The oligomer formation is enhanced in the presence of 2 mM ATP or adenosine 5'-O-thiotriphosphate (ATP gamma S). In contrast, 2 mM ADP inhibits full oligomerization of ClpB. The apparent size of the ATP- or ATP gamma S-induced oligomer, as determined by gel filtration, sedimentation velocity and electron microscopy image averaging, and the molecular weight, as determined by sedimentation equilibrium, are consistent with those of a ClpB hexamer. These results indicate that the oligomerization reactions of ClpB are similar to those of other Hsp100 proteins. C1 Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zolkiewski, M (reprint author), Kansas State Univ, Dept Biochem, 104 Willard Hall, Manhattan, KS 66506 USA. NR 24 TC 64 Z9 64 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 1999 VL 8 IS 9 BP 1899 EP 1903 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233JR UT WOS:000082424200019 PM 10493591 ER PT J AU Caffrey, M Kaufman, J Stahl, S Wingfield, P Gronenborn, AM Clore, GM AF Caffrey, M Kaufman, J Stahl, S Wingfield, P Gronenborn, AM Clore, GM TI Monomer-trimer equilibrium of the ectodomain of SIV gp41: Insight into the mechanism of peptide inhibition of HIV infection SO PROTEIN SCIENCE LA English DT Article DE gp41; monomer; trimer; HIV; SIV; peptide inhibition ID SIMIAN IMMUNODEFICIENCY VIRUS; 44 KDA ECTODOMAIN; GLYCOPROTEIN; DOMAIN; REPLICATION; PROTEINS; CORE AB The monomer-trimer equilibrium of the ectodomain of SIV gp41 (residues 27-149, e-gp41) has been characterized by analytical ultracentrifugation, circular dichroism (CD), and NMR spectroscopy. Based on analytical ultracentrifugation experiments performed at different rotor speeds and protein concentrations, the equilibrium association constant for the STV e-gp41 trimer is 3.1 X 10(11) M-2. The presence of intermolecular nuclear Overhauser effects in a mixture of C-12 and C-13-labeled e-gp41 prepared under nondenaturing conditions unambiguously demonstrates that there is a dynamic equilibrium between the monomer and trimer. The CD spectra taken as a function of SIV e-gp41 concentration suggest that the helical content of the monomeric state does not change significantly relative to that of the trimeric state. The relevance of the monomer-trimer equilibrium is discussed with respect to gp41 function and the inhibitory properties of gp41 peptides. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 17 TC 40 Z9 40 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 1999 VL 8 IS 9 BP 1904 EP 1907 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233JR UT WOS:000082424200020 PM 10493592 ER PT J AU Angeloni, D Wei, MH Lerman, MI AF Angeloni, D Wei, MH Lerman, MI TI Two single nucleotide polymorphisms (SNPs) in the CALL gene for association studies with IQ SO PSYCHIATRIC GENETICS LA English DT Article DE CALL; CEPH; IQ; SNPs; SSCP; 3p-sundrome ID X-LINKED HYDROCEPHALUS; MENTAL-RETARDATION AB A number of genes underlie the molecular bases of intelligence. Among these is probably CALL, a novel member of the L1 gene family of neural cell adhesion molecules. By using the single strand conformation polymorphism (SSCP) protocol, we screened the regions of the CALL gene corresponding to the 5' and 3' untranslated regions (UTRs) of the CALL mRNA, searching for polymorphisms that could be useful in association studies in the field of intelligence. We report the finding of T-to-A and T-to-C single nucleotide polymorphisms (SNPs) in the 3' UTR of CALL. These SNPs have an index of heterozygosity of 0.13 and 0.10, respectively, Research is in progress to understand the association between these variants and high IQ. (C) 1999 Lippincott Williams & Wilkins. C1 NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 13 TC 10 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIATR GENET JI Psychiatr. Genet. PD SEP PY 1999 VL 9 IS 3 BP 165 EP 167 DI 10.1097/00041444-199909000-00011 PG 3 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 252MV UT WOS:000083506000011 PM 10551550 ER PT J AU Gallo, JJ Lebowitz, BD AF Gallo, JJ Lebowitz, BD TI The epidemiology of common late-life mental disorders in the community: Themes for the new century SO PSYCHIATRIC SERVICES LA English DT Article ID POPULATION-BASED SAMPLE; PRIMARY-CARE PATIENTS; APOLIPOPROTEIN-E E4; ALZHEIMERS-DISEASE; RISK-FACTORS; MAJOR DEPRESSION; ELDERLY COMMUNITY; VASCULAR DEMENTIA; UNITED-STATES; NONDEMENTED 85-YEAR-OLDS AB Objective: The prevalence and incidence of the major mental disorders of late life that are common in the community and in primary health care are reviewed. Methods: Community-based studies in English that included older adults were identified through MEDLINE searches and were reviewed. Results: As the population ages, dementia, depression, and other mental conditions of the aged will demand more attention from clinicians and investigators to minimize their effects on disability, the use of health care services, and the quality of life for older adults and caregivers. Up to 15 to 20 percent of older adults have significant depressive symptoms, and it is estimated that as many as 45 percent of persons age 85 years and older have significant cognitive impairment and dementia, Other mental-health-related conditions, such as anxiety disorders, alcohol abuse, and prescription medicine misuse, are also important considerations but have not been as web studied as depression and dementia. Because an increasing proportion of older adults are members of minority groups, clinicians need to increase their awareness of how cultural factors relate to risk for mental disorders in late life. Conclusions: Attention to three themes may help clinicians and investigators meet the challenge of treating the common mental disorders of later life: the effect of these disorders on functioning, prevention of the consequences of mental disorders, and integration of mental health care and primary health care services. C1 Univ Penn, Sch Med, Dept Family Practice & Community Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. NIMH, Adult & Geriatr Treatment & Prevent Intervent Res, Rockville, MD 20857 USA. RP Gallo, JJ (reprint author), Univ Penn, Sch Med, Dept Family Practice & Community Med, 3400 Spruce St,2 Gates, Philadelphia, PA 19104 USA. EM jjgallo@mail.med.upenn.edu NR 100 TC 147 Z9 148 U1 9 U2 17 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD SEP PY 1999 VL 50 IS 9 BP 1158 EP 1166 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 230ZY UT WOS:000082282600007 PM 10478901 ER PT J AU Yang, J McCrae, RR Costa, PT Dai, XY Yao, SQ Cai, TS Gao, BL AF Yang, J McCrae, RR Costa, PT Dai, XY Yao, SQ Cai, TS Gao, BL TI Cross-cultural personality assessment in psychiatric populations: The NEO-PI-R in the People's Republic of China SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID 5-FACTOR MODEL; INVENTORY; PSYCHOPATHOLOGY; PERSPECTIVE; DEPRESSION; STABILITY; DISORDER; MMPI-2; TRAITS; SELF AB The Revised NEO Personality Inventory (NEO-PI-R) is a measure of the 5-factor model developed on volunteer samples in the United States. To examine its validity in a non-Western, psychiatric sample, an existing Chinese translation was modified for use in the People's Republic of China (PRC). The instrument was administered to 2,000 psychiatric in- and outpatients at 13 sites throughout the PRC. Internal consistency was low for some facet scales, bur retest reliability was adequate and the hypothesized factor structure was clearly recovered. Correlations with age, California Psychological Inventory scales, and spouse ratings supported the validity of NEO-PI-R scales, and diagnostic subgroups showed meaningful personality profiles. The 5-factor model appears to be useful for the assessment of personality among Chinese psychiatric patients. C1 NIA, Gerontol Res Ctr, Personal Stress & Coping Sect, Baltimore, MD 21224 USA. Hunan Med Univ, Affiliated Hosp 2, Clin Psychol Res Ctr, Changsha, Peoples R China. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Personal Stress & Coping Sect, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Costa, Paul/0000-0003-4375-1712 NR 58 TC 74 Z9 91 U1 3 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 1999 VL 11 IS 3 BP 359 EP 368 DI 10.1037/1040-3590.11.3.359 PG 10 WC Psychology, Clinical SC Psychology GA 236NW UT WOS:000082606300012 ER PT J AU Kraemer, HC Kazdin, AE Offord, DR Kessler, RC Jensen, PS Kupfer, DJ AF Kraemer, HC Kazdin, AE Offord, DR Kessler, RC Jensen, PS Kupfer, DJ TI Measuring the potency of risk factors for clinical or policy significance SO PSYCHOLOGICAL METHODS LA English DT Article ID KAPPA-COEFFICIENTS; DISCRIMINATION; ASSOCIATION; AGREEMENT; ROCS AB For those in the prevention field who need to use risk factors to identify those at risk, mere statistical significance is not sufficient to establish clinical or policy significance. For that purpose, some measure of "potency" of risk factors is needed, that is, an effect size interpretable and meaningful in a clinical or policy context. The numerous possible candidate measures available often lead to contradictory conclusions. Which of the candidate measures is right or wrong for clinical and policy decision making depends on the fit between the trade-offs between false-positive and false-negative decisions implicit in the definition of the measure land often unknown to the user) and those related to a specific context of application. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. McMaster Univ, Fac Hlth Sci, Hamilton, ON, Canada. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NIMH, Child & Adolescent Disorders Res Branch, Rockville, MD 20857 USA. RP Kraemer, HC (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Dept Psychiat, 3811 Ohara St,Room 210, Pittsburgh, PA 15213 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 25 TC 71 Z9 71 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1082-989X J9 PSYCHOL METHODS JI Psychol. Methods PD SEP PY 1999 VL 4 IS 3 BP 257 EP 271 DI 10.1037/1082-989X.4.3.257 PG 15 WC Psychology, Multidisciplinary SC Psychology GA 238EA UT WOS:000082696900003 ER PT J AU Schooler, C Mulatu, MS Oates, G AF Schooler, C Mulatu, MS Oates, G TI The continuing effects of substantively complex work on the intellectual functioning of older workers SO PSYCHOLOGY AND AGING LA English DT Article ID LIFE-SPAN; OCCUPATIONAL CONDITIONS; INDIVIDUAL-DIFFERENCES; STRUCTURAL MODELS; UNITED-STATES; MEMORY; POLAND; JAPAN; AGE; JOB AB Using a nationally representative sample of employed men and women in this longitudinal study, the authors extended for another 20 years findings based on 1964 and 1974 data (Kohn gr Schooler, 1983) that substantively complex work improves intellectual functioning. This study provides evidence that intellectual functioning and substantive complexity of work continue to reciprocally affect each other. In addition, it shows that the intellectual flexibility measure used earlier (Kohn & Schooler, 1978, 1983) is highly correlated with more standard measures of intellectual functioning, Most importantly, it shows that, although substantively complex work significantly increased the level of intellectual functioning of both the younger and older halves of the sample, the effect is significantly greater among the older workers. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies, Room B1-A14,Fed Bldg,7550 Wisconsin Ave, Bethesda, MD 20892 USA. EM carmi.schooler@nih.gov FU NIA NIH HHS [Y02 AG-1-0168] NR 46 TC 193 Z9 193 U1 2 U2 26 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 1999 VL 14 IS 3 BP 483 EP 506 DI 10.1037/0882-7974.14.3.483 PG 24 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 239EC UT WOS:000082755000011 PM 10509702 ER PT J AU Heishman, SJ Weingartner, HJ Henningfield, JE AF Heishman, SJ Weingartner, HJ Henningfield, JE TI Selective deficits in reflective cognition of polydrug abusers: Preliminary findings SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID ATTENTION; CAPACITY; MEMORY AB The goal of this study was to determine if drug abusers exhibited specific deficits in reflective cognition similar to that observed in detoxified alcoholics who were otherwise cognitive intact. Fifteen drug abusers and 15 non-drug-abusing control participants were administered a series of cognitive tests, which assessed various learning and memory functions. Drug abusers did not differ from controls with respect to most cognitive domains. However, drug abusers exhibited selective deficits in processing unstructured information and in inhibiting intrusion errors during word recall. Such deficits in reflective functioning may play a role in the initiation of drug use or maintenance of drug dependence. C1 Natl Inst Drug Abuse, Addict Res Ctr, Clin Pharmacol Branch, Baltimore, MD 21224 USA. NIAAA, Cognit Neurosci Sect, Bethesda, MD USA. RP Heishman, SJ (reprint author), Natl Inst Drug Abuse, Addict Res Ctr, Clin Pharmacol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 1999 VL 13 IS 3 BP 227 EP 231 PG 5 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 234MH UT WOS:000082488100007 ER PT J AU Schmidt, ME Oshinsky, RJ Kim, HG Schouten, JL Folley, BS Potter, WZ AF Schmidt, ME Oshinsky, RJ Kim, HG Schouten, JL Folley, BS Potter, WZ TI Cerebral glucose metabolic and plasma catecholamine responses to the alpha(2) adrenoceptor antagonist ethoxyidazoxan given to healthy volunteers SO PSYCHOPHARMACOLOGY LA English DT Article DE alpha(2)-adrenoceptor; imidazoline; cerebral glucose metabolic rate; catecholamine ID HUMAN BRAIN; ALPHA(2)-ADRENOCEPTOR BLOCKADE; PREFRONTAL CORTEX; BINDING-SITES; TEST-RETEST; RAT-BRAIN; IDAZOXAN; ALPHA-2-ADRENOCEPTORS; LOCALIZATION; NOREPINEPHRINE AB Rationale: Methods that test for the central effects of alpha(2)-adrenoceptor antagonists can facilitate the clinical development of such compounds. Recently we evaluated the effects of idazoxan (IDX), an alpha(2)-adrenoceptor antagonist with high affinity for imidazoline sites, on a variety of measures potentially sensitive to blockade of alpha(2)-adrenoceptors including regional brain glucose metabolic rate. Objective: To test whether these effects on brain metabolic rate could have been mediated by imidazoline binding sites, single dose challenges of 9 or 12 mcg/kg ethoxyidazoxan (ETX; an alpha(2)-adrenoceptor antagonist which does not bind to imidazoline sites) were given to healthy male volunteers. Methods: The effects on brain glucose metabolism, blood pressure, catecholamines, and behavior were assessed. Results: Blood pressure increased 10-15% after both doses, Plasma catecholamines increased 2- to 2.5-fold and responses were dose dependent. There was no evidence of either dose being anxiogenic. Both doses of ETX produced diffuse increases in brain glucose metabolism. Conclusions: Brain glucose metabolic responses were more widespread and monotonic than we had observed with IDX. ETX also produced robust increases in glucose metabolism in cerebellum. While we were unable to exclude the possibility that some of the brain metabolic responses we had observed with IDX were mediated by imidazoline sites, ETX may be sufficiently distinct from IDX in alpha(2)-adrenoceptor affinity that differences in acute metabolic responses occurred. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. NIMH, Clin Pharmacol Sect, Bethesda, MD 20892 USA. Allegheny Univ Hlth Sci, Dept Neurol, Philadelphia, PA 19129 USA. Dankook Univ, Dept Pharmacol, Choongnam 330714, South Korea. NIMH, LBC, Sect Funct Brain Imaging, Bethesda, MD 20892 USA. Kennedy Krieger Inst, Neuroimaging Res Ctr, Baltimore, MD 21205 USA. RP Schmidt, ME (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC 0532, Indianapolis, IN 46285 USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 48 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1999 VL 146 IS 2 BP 119 EP 127 DI 10.1007/s002130051097 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 245GQ UT WOS:000083098300002 PM 10525746 ER PT J AU Fugh-Berman, A Cott, JM AF Fugh-Berman, A Cott, JM TI Dietary supplements and natural products as psychotherapeutic agents SO PSYCHOSOMATIC MEDICINE LA English DT Review DE Ginkgo biloba; kava; St. John's wort; vitamins; dietary supplements; omega-3 fatty acids ID GINKGO-BILOBA EXTRACT; ST-JOHNS-WORT; EOSINOPHILIA-MYALGIA-SYNDROME; SEASONAL AFFECTIVE-DISORDER; ESSENTIAL FATTY-ACIDS; DOUBLE-BLIND; ALZHEIMERS-DISEASE; L-TRYPTOPHAN; NEUROPSYCHIATRIC DISORDERS; SEROTONIN PRECURSORS AB Alternative therapies are widely used by consumers. A number of herbs and dietary supplements have demonstrable effects on mood, memory, and insomnia. There is a significant amount of evidence supporting the use of Hypericum perforatum (St. John's wort) for depression and Ginkgo biloba for dementia. Results of randomized, controlled trials also support the use of kava for anxiety and valerian for insomnia. Although evidence for the use of vitamins and amino acids as sole agents for psychiatric symptoms is not strong, there is intriguing preliminary evidence for the use of folate, tryptophan, and phenylalanine as adjuncts to enhance the effectiveness of conventional antidepressants. S-adenosylmethionine seems to have antidepressant effects, and omega-3 polyunsaturated fatty acids, particularly docosahexaenoic acid, may have mood-stabilizing effects. More research should be conducted on these and other natural products for the prevention and treatment of various psychiatric disorders. C1 NIMH, Adult Psychopharmacol Program, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Hlth Care Sci, Washington, DC 20052 USA. RP Cott, JM (reprint author), NIMH, Adult Psychopharmacol Program, 6001 Execut Blvd,Room 7157, Bethesda, MD 20892 USA. NR 174 TC 82 Z9 84 U1 5 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 1999 VL 61 IS 5 BP 712 EP 728 PG 17 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 240BN UT WOS:000082806000010 PM 10511018 ER PT J AU Lerner, DM Stoudemire, A Rosenstein, DL AF Lerner, DM Stoudemire, A Rosenstein, DL TI Neuropsychiatric toxicity associated with cytokine therapies SO PSYCHOSOMATICS LA English DT Article ID DOSE BOLUS INTERLEUKIN-2; INTERFERON-ALFA THERAPY; CLINICAL TOXICITY; ALPHA-INTERFERON; HEPATITIS; CANCER; MOOD AB The cytokines interleukin-2 and interferon-alpha are potent biological agents used to treat malignancy, infectious diseases, and neurodegenerative disorders. While these medications show substantial therapeutic promise, the neuropsychiatric toxicity associated with these agents is often treatment-limiting. The pathophysiology of this toxicity is not well delineated, and adverse effects to the central nervous system are often misdiagnosed by clinicians. This report reviews the preclinical and clinical literature describing the morbidity associated with these agents and suggests appropriate clinical management strategies and future directions for research. C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP NIMH, Expt Therapeut Branch, Bldg 10,Room 3N218,10 Ctr Dr,MSC 1274, Bethesda, MD 20892 USA. NR 29 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1999 VL 40 IS 5 BP 428 EP 435 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 231HL UT WOS:000082302200009 PM 10479948 ER PT J AU Battey, JF AF Battey, JF TI Hearing impairment data SO PUBLIC HEALTH REPORTS LA English DT Letter C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1999 VL 114 IS 5 BP 393 EP 393 DI 10.1093/phr/114.5.393 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244AY UT WOS:000083030700004 PM 10590758 ER PT J AU Teigen, PM AF Teigen, PM TI When horse walked on water: Horse-powered ferries in nineteenth-century America SO PUBLIC HISTORIAN LA English DT Book Review C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Teigen, PM (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CALIF PRESS PI BERKELEY PA JOURNALS DEPT 2120 BERKELEY WAY, BERKELEY, CA 94720 USA SN 0272-3433 J9 PUBL HISTORIAN JI Public Hist. PD FAL PY 1999 VL 21 IS 4 BP 84 EP 86 PG 3 WC History SC History GA 246ZF UT WOS:000083195600019 ER PT J AU Cragg, GM Boyd, MR Khanna, R Kneller, R Mays, TD Mazan, KD Newman, DJ Sausville, EA AF Cragg, GM Boyd, MR Khanna, R Kneller, R Mays, TD Mazan, KD Newman, DJ Sausville, EA TI International collaboration in drug discovery and development: the NCI experience SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT 2nd IUPAC International Conference on Biodiversity CY JUL 11-15, 1999 CL BELO HORIZONT, BRAZIL SP Int Union Pure & Appl Chem ID NATIONAL-CANCER-INSTITUTE; NATURAL-PRODUCTS; MICROBIAL DIVERSITY; AGENTS; EXPLORATION; ANTICANCER; PLANTS; TAXOL AB Over the millennia, natural products, mainly of plant origin, have been used for the treatment of diseases, and an impressive number of modern drugs have been isolated from natural sources based on their use in traditional medicine. The past century, however, has seen an increasing role played by micro-organisms in the production of antibiotics and other drugs for the treatment of diseases, ranging from bacterial infections to cardiovascular problems and cancer. The role of nature will continue to grow with the exploration of tropical rainforests and marine environments, as well as the huge untapped resource of micro-organisms which have, as yet, defied culture. With less than 1% of the microbial world currently known, the extraction of nucleic acids from environmental samples from soil and marine habitats, from symbiotic and endophytic microbes associated with terrestrial and marine macro-organisms, as well as from extreme habitats, such as hot springs and deep sea vents, will permit access to a vast reservoir of genetic and metabolic diversity. These resources will provide a host of novel chemical scaffolds which can be further developed by combinatorial chemical and biosynthetic approaches to yield chemotherapeutic and other bioactive agents which have been optimized on the basis of their biological activities. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Technol Dev & Commercializat Branch, Off Director, Bethesda, MD 20892 USA. RP Cragg, GM (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 50 TC 26 Z9 30 U1 2 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD SEP PY 1999 VL 71 IS 9 BP 1619 EP 1633 DI 10.1351/pac199971091619 PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 319YC UT WOS:000087372600003 ER PT J AU Amundson, SA Do, KT Fornace, AJ AF Amundson, SA Do, KT Fornace, AJ TI Induction of stress genes by low doses of gamma rays SO RADIATION RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; HUMAN-LYMPHOCYTES; ADAPTIVE RESPONSE; IONIZING-RADIATION; X-RAYS; HUMAN-LYMPHOBLASTS; G(1) ARREST; HUMAN-CELLS; IN-VIVO; P53 AB Using cells of a human myeloid tumor cell line (ML-1), we have detected induction of several stress-responsive genes by doses of gamma rays below 50 cGy, We found a linear dose-response relationship for induction of CDKN1A (formerly known as CIP1/WAF1) and GADD45 mRNA levels over the range of 2-50 cGy, with no evidence of a threshold for induction. Although exposures to 2 and 5 cGy did not result in any detectable reduction in cloning efficiency or increased apoptosis in ML-I cells, these exposures did produce a transient delay of cells in the phases of the cell cycle in addition to the observed up-regulation of CDKN1A and GADD45. The relative induction of genes such as CDKN1A by radiation doses that produce little toxicity indicates that surviving cells do contribute significantly to the observed stress responses. These studies should provi de insight into the molecular responses to physiologically relevant doses that cannot necessarily be extrapolated from high-dose studies. (C) 1999 by Radiation Research Society. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Amundson, SA (reprint author), NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 45 TC 141 Z9 154 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD SEP PY 1999 VL 152 IS 3 BP 225 EP 231 DI 10.2307/3580321 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 230YH UT WOS:000082278900001 PM 10453082 ER PT J AU Choyke, PL Doppman, JL AF Choyke, PL Doppman, JL TI Diagnosis Please - Case 18 SO RADIOLOGY LA English DT Article DE Diagnosis please C1 NIH, Ctr Clin, Dept Diagnost Radiol, Imaging Sci Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Imaging Sci Program, Bldg 10,Rm 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1999 VL 212 IS 3 BP 706 EP 707 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 229LT UT WOS:000082196600017 ER PT J AU Little, RE Gladen, BC AF Little, RE Gladen, BC TI Levels of lipid peroxides in uncomplicated pregnancy: a review of the literature SO REPRODUCTIVE TOXICOLOGY LA English DT Review ID VITAMIN-E; OXIDATIVE STRESS; INDUCED HYPERTENSION; ANTIOXIDANT ENZYMES; HUMAN PLACENTA; PREECLAMPSIA; PROSTACYCLIN; THROMBOXANE; BLOOD; WOMEN C1 NIEHS, Epidemiol Branch A305, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Little, RE (reprint author), NIEHS, Epidemiol Branch A305, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM little1@niehs.nih.gov NR 48 TC 124 Z9 126 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD SEP-OCT PY 1999 VL 13 IS 5 BP 347 EP 352 DI 10.1016/S0890-6238(99)00033-7 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 250HR UT WOS:000083383400002 PM 10560582 ER PT J AU Macaluso, M Kelaghan, J Artz, L Austin, H Fleenor, M Hook, EW Valappil, T AF Macaluso, M Kelaghan, J Artz, L Austin, H Fleenor, M Hook, EW Valappil, T TI Mechanical failure of the latex condom in a cohort of women at high STD risk SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; HIV TRANSMISSION; UNITED-STATES; BREAKAGE; SLIPPAGE; BARRIER; HERPES; USERS; MEN; INFECTION AB Background and Objectives: Mechanical failure may reduce the efficacy of condoms. Little is known about frequency and determinants of condom failure in groups at high risk of sexually transmitted diseases (STD). Goal: To measure condom breakage and slippage rates and evaluate potential determinants of failure among women attending a public STD clinic. Study Design: Women attending an STD clinic participated in a 6-month prospective study of barrier contraception fur the prevention of STD, They completed sexual diaries that were reviewed at monthly follow-up visits, No data mere collected from the male partners. Baseline characteristics of the participants and time-dependent behaviors were evaluated as potential determinants of condom failure. Results: Of 21,852 condoms used by 892 women, 500 broke during intercourse (2.3%) and 290 slipped (1.3%). Breakage was more common among young, black, single nulliparae who engaged in high-risk behavior. Slippage was more common among married women with children, Failure rates decreased with condom use, with coital frequency, and with use of spermicides. Conclusion: User characteristics and experience are determinants of breakage and slippage, which are often regarded only as the effect of product design flaws. Attention to modifiable determinants of failure may improve user counseling and product labeling. C1 Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. NICHHD, Rockville, MD USA. Emory Univ, Atlanta, GA 30322 USA. Jefferson Cty Dept Hlth, Birmingham, AL USA. RP Macaluso, M (reprint author), MJH 108,1825 Univ Blvd, Birmingham, AL 35294 USA. RI Macaluso, Maurizio/J-2076-2015 OI Macaluso, Maurizio/0000-0002-2977-9690 FU NICHD NIH HHS [N01-HD-1-3135] NR 33 TC 62 Z9 62 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP PY 1999 VL 26 IS 8 BP 450 EP 458 DI 10.1097/00007435-199909000-00006 PG 9 WC Infectious Diseases SC Infectious Diseases GA 234JR UT WOS:000082481400006 PM 10494936 ER PT J AU MacPhail, AP Mandishona, EM Bloom, PD Paterson, AC Rouault, TA Gordeuk, VR AF MacPhail, AP Mandishona, EM Bloom, PD Paterson, AC Rouault, TA Gordeuk, VR TI Measurements of iron status and survival in African iron overload SO SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID SERUM FERRITIN; IDIOPATHIC HEMOCHROMATOSIS; HEPATOCELLULAR-CARCINOMA; PATTERNS; INDEX AB Introduction. Dietary iron overload is common in southern Africa and there is a misconception that the condition is benign. Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of iron status to diagnose this form of iron overload has not been clarified. Methods. The study involved 22 black subjects found to have iron overload on liver biopsy. Fourteen subjects presented to hospital with liver disease and were found to have iron overload on percutaneous liver biopsy. Eight subjects, drawn from a family study, underwent liver biopsy because of elevated serum ferritin concentrations suggestive of iron overload, indirect measurements of iron status (transferrin saturation, serum ferritin) were performed on all subjects. Histological iron grade and hepatic iron concentration were used as direct measures of iron status. Results. There were no significant differences in either direct or indirect measurements of iron status between the two groups. In 75% of these subjects the hepatic iron concentration was greater than 350 mu g/g dry weight, an extreme elevation associated with a high risk of fibrosis and cirrhosis. Serum ferritin was elevated in all subjects and the transferrin saturation was greater than 60% in 93% of the subjects. Hepatomegaly was present in 20 of the 22 cases and there was only a moderate derangement in liver enzymes except for a tenfold increase in the median gamma-glutamyl transpeptidase concentration. There was a strong correlation between serum ferritin and hepatic iron concentrations (r = 0.71, P = 0.006). After a median follow-up of 19 months, 6 (26%) of the subjects had died. The risk of mortality correlated significantly with both the hepatic iron concentration and the serum ferritin concentration Conclusions. Indirect measurements of iron status (serum ferritin concentration and transferrin saturation) are useful in the diagnosis of African dietary iron overload. When dietary iron overload becomes symptomatic it has a high mortality. Measures to prevent and treat this condition are needed. C1 Univ Witwatersrand, Dept Anat Pathol, Johannesburg, South Africa. S African Inst Med Res, Johannesburg, South Africa. Natl Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, Bethesda, MD USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. RP MacPhail, AP (reprint author), Univ Witwatersrand, Dept Anat Pathol, Johannesburg, South Africa. NR 36 TC 11 Z9 11 U1 0 U2 0 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS PRIV BAG X1, JOHANNESBURG, SOUTH AFRICA SN 0038-2469 J9 S AFR MED J JI S. Afr. Med. J. PD SEP PY 1999 VL 89 IS 9 BP 966 EP 972 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 252XC UT WOS:000083526700036 PM 10554633 ER PT J AU Montague, JW Bortner, CD Hughes, FM Cidlowski, JA AF Montague, JW Bortner, CD Hughes, FM Cidlowski, JA TI A necessary role for reduced intracellular potassium during the DNA degradation phase of apoptosis SO STEROIDS LA English DT Article; Proceedings Paper CT Symposium on Reproductive Biology and Hormone Action in Honor of Virendra B Mahesh CY OCT 02-03, 1998 CL AUGUSTA, GEORGIA DE apoptosis; potassium; DNA degradation ID RAT THYMIC LYMPHOCYTES; CELL-DEATH; CALCIUM; FRAGMENTATION; ACTIVATION; THYMOCYTES; GLUCOCORTICOIDS; ENDONUCLEASE; CHROMATIN; K+ AB Apoptosis is a highly organized mechanism that allows specific cells to die in a controlled manner. Apoptosis can be induced by a variety of agents in a great number of cell types, but cell shrinkage and discrete chromatin cleavage remain common components of apoptosis that is manifested by constitutive enzymes. Despite intensive investigation, the actual event or events that signal this cell death process have not been completely identified. Because of their ability to effect a great number of cellular enzymes simultaneously, we have hypothesized that ions in high concentration (150 mM) in living cells may act as a repressor of apoptotic effecters. In this manuscript we review data that shows that DNA degradation only occurs in the shrunken population of lymphocytes treated with glucocorticoid, shrunken cells loose K+ and become hypotonic, and physiological concentrations on K+ inhibit nuclease activity irrespective of proteins. Together, these data suggest that the reduction in potassium levels appears necessary for the DNA degradation that occurs during apoptosis. (C) 1999 Published by Elsevier Science Inc. All rights reserved. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 TW Alexander Dr,POB 12233,MD E2-02, Res Triangle Pk, NC 27709 USA. NR 35 TC 53 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-128X J9 STEROIDS JI Steroids PD SEP PY 1999 VL 64 IS 9 BP 563 EP 569 DI 10.1016/S0039-128X(99)00034-3 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 237QZ UT WOS:000082668700002 PM 10503710 ER PT J AU Yeh, SY Dersch, C Rothman, R Cadet, JL AF Yeh, SY Dersch, C Rothman, R Cadet, JL TI Effects of antihistamines on 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats SO SYNAPSE LA English DT Article DE MDMA; neurotoxicity; hyperthermia; antihistamine; chlorpheniramine; diphenhydramine; tripelennamine; pyrilamine ID TRYPTOPHAN-HYDROXYLASE ACTIVITY; BODY-TEMPERATURE; METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUBSTITUTED AMPHETAMINES; P-CHLOROAMPHETAMINE; TRANSGENIC MICE; BRAIN; NEUROTOXICITY; FENFLURAMINE; ECSTASY AB This study investigated the effects of chlorpheniramine (CPA, 10-25 mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and pyrilamine (PYRI, 20 mg/kg) on 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg x 2)-induced hyperthermia and depletion of indoles in rat brains, on the uptake of serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP, PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injections for 13 h. As compared to saline controls, MDMA increased body temperature and decreased levels of indoles, measured by HPLC, in several brain regions of rats. CPA attenuated and DIPH had no effect on MDMA-induced hyperthermia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated these effects. CPA inhibited the binding of [H-3]paroxetine and [H-3]nisoxetine to the synaptosomes of cerebral cortex and of [H-3]win 35,428 to the synaptosomes of striatum. CPA, DIPH, TRIP, and PYRI inhibited [3H]serotonin uptake. CPA, PYRI, and TRIP, but not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the antihistamines on MDMA-induced hyperthermia and depletion of serotonin are discussed. Published 1999 Wiley-Liss, Inc.dagger. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, Addict Res Ctr,NIH, Baltimore, MD 21224 USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Yeh, SY (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, Addict Res Ctr,NIH, POB 5180, Baltimore, MD 21224 USA. NR 46 TC 13 Z9 13 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP 1 PY 1999 VL 33 IS 3 BP 207 EP 217 DI 10.1002/(SICI)1098-2396(19990901)33:3<207::AID-SYN5>3.0.CO;2-8 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 221VL UT WOS:000081747600005 PM 10420168 ER PT J AU Rothman, RB Baumann, MH Dersch, CM Appel, J Houghten, RA AF Rothman, RB Baumann, MH Dersch, CM Appel, J Houghten, RA TI Discovery of novel peptidic dopamine transporter ligands by screening a positional scanning combinatorial hexapeptide library SO SYNAPSE LA English DT Article DE transporters; dopamine; serotonin; combinatorial chemistry; cocaine ID BIOGENIC-AMINE TRANSPORTERS; POTENTIAL COCAINE ANTAGONISTS; NONHUMAN-PRIMATES; SCHIZOPHRENIC-PATIENTS; SEROTONIN-TRANSPORTER; BINDING-SITES; I-125 RTI-55; DRUGS; IDENTIFICATION; CAUDATE AB The acute reinforcing effects of cocaine are thought by some to result from cocaine binding to the dopamine (DA) transporter, which inhibits DA uptake and increases synaptic DA levels in the mesolimbic system. Other data suggest that neurotransmitters other than DA contribute to cocaine reinforcement and addiction. These considerations illustrate the need to have additional research tools with which to test the "DA hypothesis." One strategy is to identify drugs which bind to the DA transporter (DAT ligands) but which do not inhibit DA uptake as effectively as cocaine. The purpose of the present study was to identify members of a novel structural class of DAT ligands and to characterize their interactions at the DA transporter. A positional scanning hexapeptide D-amino acid library was screened for inhibition of [I-125]RTI-55 binding to rat caudate DA transporters. Based on the results, 12 peptides were synthesized. All 12 peptides inhibited [I-125]RTI-55 binding to DA transporters with IC50 values, which ranged from 1.8 mu M to 12 mu M The two most potent peptides (TPI-669-1 and TPI-669-4) were prepared in larger quantities and were characterized further for activity at the DAT and 5-HT transporter. Both peptides inhibited DA and 5-HT uptake and transporter binding with IC50/K-i values in the low micromolar range. In vivo microdialysis studies demonstrated that both peptides increase extracellular DA and 5-HT in the nucleus accumbens of rats. These data demonstrate that peptides can function as inhibitors of biogenic amine transport. Future work will focus on developing more potent and selective peptides. Published 1999 Wiley-Liss, Inc.dagger. C1 NIDA, CPS, DIR, NIH, Baltimore, MD 21224 USA. Torrey Pines Inst Mol Studies, San Diego, CA USA. RP Rothman, RB (reprint author), NIDA, CPS, DIR, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 9 Z9 9 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP 1 PY 1999 VL 33 IS 3 BP 239 EP 246 DI 10.1002/(SICI)1098-2396(19990901)33:3<239::AID-SYN8>3.0.CO;2-R PG 8 WC Neurosciences SC Neurosciences & Neurology GA 221VL UT WOS:000081747600008 PM 10420171 ER PT J AU Seetharamaiah, GS Zhuang, J Huang, J Patibandla, SA Kaithamana, S Tahara, K Kohn, LD Prabhakar, BS AF Seetharamaiah, GS Zhuang, J Huang, J Patibandla, SA Kaithamana, S Tahara, K Kohn, LD Prabhakar, BS TI Selective binding of thyrotropin receptor autoantibodies to recombinant extracellular domain of thyrotropin/lutropin-chorionic gonadotropin receptor chimeric proteins SO THYROID LA English DT Article ID THYROID-STIMULATING ANTIBODIES; TSH RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; DIFFERENT SITES; DISEASE; EPITOPES; PATIENT; SERA; GLYCOSYLATION AB The extracellular domain of the glycosylated human thyrotropin receptor (ET-gp) contains epitopes that can adsorb pathogenic antibodies from sera of patients with Graves' disease (GD). In an attempt to define the regions within the ETSHR with which autoantibodies interact, we expressed extracellular domains of eight thyrotropin receptor/chorionic gonadotropin receptor (TSHR/LH-CGR) chimeric proteins in insect cells. The levels of expression were high and chimeric proteins were glycosylated. Chimeric proteins designated as EMc2+4 and EMc2+3+4, in which amino acids (aa) 90-165 and 261-370, and aa 90-370, respectively, of TSHR were replaced with corresponding aa of LH-CGR, partially reversed the thyrotropin binding inhibitory immunoglobulin (TBII) activity of experimental anti-TSHR antisera (anti-ET-gp). The other six chimeras almost completely reversed the TBII activity of these anti-ET-GP antisera. Next, we tested the ability of these chimeric proteins to reverse the TBII: activity of GD patients' sera. Similar to our earlier study, ET-gp protein reversed the TBII activity of all eight GD patients' sera tested. Chimera EMc2, in which aa 90-165 of TSHR has been replaced with corresponding aa of LH-CGR, and EMc2+4 partially reversed the TBII activity of only three of the eight GD patients' sera. However, the other six chimeric proteins failed to neutralize the TBII activity of any of GD patients' sera. These data showed the following: (1) There is considerable heterogeneity amongst autoantibodies in GD patients' sera, (2) The TBII activity of some, but not others, is dependent on aa 90-165 and 261-370, and (3) Most Graves' sera, with TBII activity, failed to react with chimeric proteins in which either N-terminal or C-terminal regions of the extra cellular domain of the TSHR were replaced with corresponding regions of LH-CGR. These results suggest that the TBII activity of GD patients' sera is dependent on conformational epitopes and replacement of certain regions of TSHR with homologous regions of LH-CGR results in sufficient alteration in the conformation of the protein leading to loss of reactivity. C1 Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA. Natl Inst Diabet & Digest Dis, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD USA. RP Prabhakar, BS (reprint author), Univ Illinois, Dept Microbiol & Immunol, 835 S Wolcott,M-C 790, Chicago, IL 60612 USA. NR 35 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD SEP PY 1999 VL 9 IS 9 BP 879 EP 886 DI 10.1089/thy.1999.9.879 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 242LY UT WOS:000082943600005 PM 10524566 ER PT J AU Sills, RC Hailey, JR Neal, J Boorman, GA Haseman, JK Melnick, RL AF Sills, RC Hailey, JR Neal, J Boorman, GA Haseman, JK Melnick, RL TI Examination of low-incidence brain tumor responses in F344 rats following chemical exposures in national toxicology program carcinogenicity studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE brain tumors; Fischer 344 rat; chemical carcinogenicity studies; bromoethane; chloroethane; 3,3 '-dimethylbenzidine dihydrochloride; 3,3 '-dimethoxybenzidine dihydrochloride; furosemide; C.I direct blue 15; diphenhydramine hydrochloride; 1-H-benzotriazole; isoprene; 1,3-butadiene; glycidol ID ETHYLENE-OXIDE; FISCHER-344 RATS; UNITED-STATES; HUMAN GLIOMAS; GENE; MICE; PROGRESSION; INDUCTION; TOXICITY; P53 AB Neoplasms in the brain are uncommon in control Fischer 344 (F344) rats; they occur at a rate of less than 1% in 2-yr toxicity/carcinogenicity studies. Furthermore, only 10 of nearly 500 studies conducted by the National Toxicology Program (NTP) showed any evidence of chemically related neoplastic effects in the brain. Generally, the brain tumor responses were considered equivocal, because the characteristics of potential neurocarcinogenic agents (such as statistically significant increased incidences, decreased latency and/or survival, and demonstration of dose-response relationships) were not observed. A thorough examination, including comparisons with a well-established historical database, is often critical in evaluating rare brain tumors. Chemicals that gave equivocal evidence of brain tumor responses were generally associated with carcinogenicity at other sites, and many chemicals were mutagenic when incubated with metabolic activating enzymes. Other factors that were supportive of the theory that marginal increases in brain tumor incidence were related to chemical exposure were that (a) some of the tumors were malignant, (b) no brain neoplasms were observed in concurrent controls from some studies, and/or (c) brain tumors were also seen following exposure to structurally related chemicals. In 2-yr studies in F344 rats (studies conducted by the NTP), equivocal evidence of carcinogenicity was observed for the following 9 chemicals: isoprene, bromoethane, chloroethane, 3,3'-dimethylbenzidine dihydrochloride, 3,3'-dimethoxybenzidine dihydrochloride, furosemide, C.I. direct blue 15, diphenhydramine hydrochloride, and l-H-benzotriazole. Glycidol was the only chemical evaluated by the NTP with which there was clear evidence of brain tumor induction in F344 rats. Clarification of the potential neurocarcinogenic risks of chemicals that produce equivocal evidence of a brain tumor response in conventional 2-yr rodent studies may be aided by the use of transgenic mouse models that exhibit genetic alterations that reflect those present in human brain tumors as well as by the use of in utero exposures. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Sills, RC (reprint author), NIEHS, MD B3-08,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 50 TC 24 Z9 25 U1 1 U2 5 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1999 VL 27 IS 5 BP 589 EP 599 DI 10.1177/019262339902700513 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 240WY UT WOS:000082851100013 PM 10528639 ER PT J AU Chun, H Cipolone, K Procter, J Stroncek, DF AF Chun, H Cipolone, K Procter, J Stroncek, DF TI Granulocyte storage and antigen stability SO TRANSFUSION LA English DT Article ID ISOIMMUNE NEONATAL NEUTROPENIA; AUTOIMMUNE NEUTROPENIA; MONOCLONAL-ANTIBODIES; IMMUNOFLUORESCENCE; INFANCY; HISTORY; NB1 AB BACKGROUND: Current methods for the detection of granulocyte antibodies require panels of freshly isolated cells. This makes these assays time-consuming, costly, and technically difficult. STUDY DESIGN AND METHODS: The immunofluorescence method of detecting the binding of antibodies to granulocytes was modified for use with a flow cytometer, and methods were tested to store granulocytes for use in that assay. Granulocytes were stored at 4 degrees C for 7 days under three conditions: I-percent formaldehyde-fixed cells were stored in Hanks' balanced salt solution (HBSS); untreated cells were stored in tissue culture medium (RPMI-1640); and cells were fixed and stored with a commercial white cell-storage solution (Cyto-Chex Reagent). Antigen stability was evaluated by using monoclonal antibodies (MoAbs) and alloantibodies. Serologic studies were done by an indirect immunofluorescence assay and assessed by flow cytometric analysis. RESULTS: On Day 2, only 2 to 7 percent of granulocytes stored in RPMI-1640 remained. On Day 7, 67 to 76 percent of granulocytes fixed in formaldehyde and stored in HBSS remained, and 47 to 87 percent of granulocytes stored in a white cell-storage solution remained. All antigens were detectable by the MoAbs and alloantisera on Day 7. However, nonspecific staining by the fluorescein isothiocyanate (FITC)-conjugated secondary antibody hindered interpretation of test results on Day 4. Nonspecific staining occurred over time and was associated with increased cell permeability during storage. Two sources of nonspecific staining were identified. The first source was the FITC-conjugated secondary antibody; it was eliminated by switching to a phycoerythrin conjugate. The second source was factors in human serum; it was resolved by examining only viable, impermeable cells identified by using 7-aminoactinomycin-D. CONCLUSION: Granulocytes and their antigens can be preserved for at least 7 days, but evaluation of antibody reactions was possible for only 4 days as a result of nonspecific staining due to enhanced membrane permeability of dying cells. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Chun, H (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C711,10 Ctr Dr MSC1184, Bethesda, MD 20892 USA. NR 19 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1999 VL 39 IS 9 BP 983 EP 990 DI 10.1046/j.1537-2995.1999.39090983.x PG 8 WC Hematology SC Hematology GA 235XY UT WOS:000082570200012 PM 10533825 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI G-patch: a new conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID BINDING PROTEIN; NUCLEIC-ACID; CLONING; GENE; IDENTIFICATION; RECOGNITION; SPLICEOSOME; MOTIF; LOCUS; SET C1 Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NR 22 TC 95 Z9 98 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD SEP PY 1999 VL 24 IS 9 BP 342 EP 344 DI 10.1016/S0968-0004(99)01437-1 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233ZK UT WOS:000082456900005 PM 10470032 ER PT J AU Vercelli, M Quaglia, A Parodi, S Crosignani, P AF Vercelli, M Quaglia, A Parodi, S Crosignani, P CA ITAPREVAL Working Grp TI Cancer prevalence in the elderly SO TUMORI LA English DT Article DE prevalence; cancer registries; elderly; aging; age distribution; elderly/young ratios ID POPULATION; DIAGNOSIS; MORTALITY; REGISTRY AB Aims and background: To describe the cancer prevalence in elderly Italian people and analyze the differences, if any, with the prevalence among younger subjects. Methods & study design: The cancer prevalence among elderly patients (65 years and over), the three age classes encompassing elderly age (65-74 years, 75-84 years, 85 years and over) and younger patients (0-64 years) was computed using the PREVAL method on the basis of the incident cases over the period 1976-1992 followed up to 31 December 1992 (prevalence reference date). Data were collected by 11 Italian cancer registries. Results: The observed prevalence figures for all cancers (except skin epitheliomas), both sexes combined and considering the whole elderly group, were 1,090 and 3,601 cases per 100,000 one and five years since diagnosis, respectively; the prevalence increased up to the 75-84 age group and showed a slight decrease after age 85. With regard to specific cancer sites, in men bladder and prostate had the highest prevalence 5 years from diagnosis (more than 800 cases per 100,000), followed by colon and lung (about 500 cases per 100,000) stomach and rectum (about 300 cases per 100,000); in women breast cancer ranked first (more than 1,000 cases per 100,000), followed by colon (about 350 cases per 100,000), corpus uteri, stomach and rectum cancers (between 150 and 200 cases per 100,000). For all malignancies and the two sexes combined the prevalence figures were about six times higher in the older than in the younger age group. Conclusions: These figures confirm the important role of aging in determining the increase in cancer prevalence. The resulting prevalence figures clearly indicate the cancer burden placed on health care services; moreover, the figures will probably increase in the next decades due to a possible improvement in survival and to the dramatic aging of the population, assuming a stable trend for incidence rates. This picture will represent a major challenge for politicians and those dealing with health care planning and social policies in general, especially in the light of the reduction of the available financial resources and the specific features of medical and social needs in the elderly. C1 Univ Genoa, Oncol Biol & Genet Dept, I-16126 Genoa, Italy. Natl Canc Inst, Tumor Registry Sect, Ligurian Canc Registry, Genoa, Italy. Natl Canc Inst, Dept Epidemiol, Lombardy Canc Registry, I-20133 Milan, Italy. ISS, Rome, Italy. Latina Canc Registry, Latina, Italy. Modena Canc Registry, Modena, Italy. Parma Canc Registry, Parma, Italy. Univ Genoa, IST, Liguria Canc Registry, I-16126 Genoa, Italy. Ragusa Canc Registry, Ragusa, Italy. RP Vercelli, M (reprint author), Ist Nazl Ric Canc, Registro Tumori Liguria, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. RI Federico, Massimo/J-5984-2014; Gatta, Gemma/B-8627-2017; Tagliabue, Giovanna /D-4194-2017; FEDERICO, Massimo/A-6801-2012; Ponz de Leon, Maurizio/A-9356-2015; OI Vercelli, Marina/0000-0002-9757-2616; Sant, Milena/0000-0002-4148-8597; Federico, Massimo/0000-0002-5074-3262; Gatta, Gemma/0000-0003-4160-6458; Tagliabue, Giovanna /0000-0001-8165-5524; Roncucci, Luca/0000-0002-0410-1760; Micheli, Andrea/0000-0002-4558-4754; FEDERICO, Massimo/0000-0002-9889-3796; Ponz de Leon, Maurizio/0000-0003-4465-1043; guzzinati, stefano/0000-0002-4908-5506 NR 28 TC 15 Z9 15 U1 3 U2 4 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD SEP-OCT PY 1999 VL 85 IS 5 BP 391 EP 399 PG 9 WC Oncology SC Oncology GA 273QY UT WOS:000084719400006 PM 10665856 ER PT J AU Blackshear, P Mahler, J Bennett, LM McAllister, KA Forsythe, D Davis, BJ AF Blackshear, P Mahler, J Bennett, LM McAllister, KA Forsythe, D Davis, BJ TI Extragonadal teratocarcinoma in chimeric mice SO VETERINARY PATHOLOGY LA English DT Article DE chimera; embryonic stem cells; extragonadal teratocarcinoma; mice AB Chimeric mice often are created through the genetic manipulation of the mouse embryo in the process of developing animal models of disease. These mice have variable percentages of their somatic and germ cells derived from the donor embryonic stem cells and host blastocysts. In the development of mouse models deficient in the breast cancer susceptibility gene 2 (Brca2) or the 70-kd heat shock protein (Hsp70-2), 3-4-week-old chimeras developed single or multiple masses composed of both well-differentiated and poorly differentiated tissues derived from all three germ layers. These cases of extragonadal teratocarcinoma, a rarely reported tumor, may be related to the genetic predisposition of the 129/O1a mouse strain used to generate the embryonic stem cells. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Blackshear, P (reprint author), NIEHS, POB 12233,MD C2-09, Res Triangle Pk, NC 27709 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 1999 VL 36 IS 5 BP 457 EP 460 DI 10.1354/vp.36-5-457 PG 4 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 257XL UT WOS:000083808000013 PM 10490215 ER PT J AU Durbin, AP McAuliffe, JM Collins, PL Murphy, BR AF Durbin, AP McAuliffe, JM Collins, PL Murphy, BR TI Mutations in the C, D, and V open reading frames of human parainfluenza virus type 3 attenuate replication in rodents and primates SO VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; MESSENGER-RNA SYNTHESIS; SENDAI-VIRUS; MEASLES-VIRUS; P-GENE; CLONED CDNA; VACCINE DEVELOPMENT; SEQUENCE-ANALYSIS; RHESUS-MONKEYS; PROTEIN AB Human parainfluenza virus type 3 (HPIV3) is a single-stranded negative-sense RNA virus belonging to the Respirovirus genus of the Paramyxoviridae family in the order Mononegavirales. The P gene encodes at least four proteins, including the C protein, which is expressed from an open reading frame (ORF) that overlaps the P ORF, and the D protein, which is encoded when the P ORF is fused to the D ORF by transcriptional editing. The P mRNA also contains a third ORF for the V protein, although it is unclear how or whether this ORF is accessed. We have used recombinant DNA technology to recover five mutant viruses that either interrupt or alter the C, D, and V ORFs. In one mutant virus, rC-KO, expression of the C protein was abrogated by changing the start codon from methionine to threonine and introducing two stop codons at amino acid positions 7 and 26 of the C ORF. Tn a second mutant virus, rF164S, a point mutation was introduced into the C ORF changing amino acid position 164 from phenylalanine (F) to serine (S), which corresponds to the F170S mutation described in the C protein of Sendai virus (Itoh et ai., J. Gen. Virol. 78, 3207-3215). rC-KO was significantly attenuated in vitro and in vivo (rodents and primates), whereas rF164S was attenuated only in vivo. Interestingly, the rF164S mutant was more attenuated in the upper than in the lower respiratory tract of hamsters and monkeys. This pattern is the converse of that seen with temperature-sensitive attenuating mutations, and thus inclusion of this novel mutation in a recombinant live-attenuated vaccine candidate might prove useful in reducing residual virulence in the upper respiratory tract. Both rC-KO and rF164S conferred protection against challenge with wild-type HPIV3. In three other viruses, the D and V ORFs were interrupted singly or in combination. Although interruption of the D and V ORFs individually did not affect virus replication in vitro or in vivo, interruption of both together attenuated replication in vivo. These results indicate that the C, D, and V proteins of HPIV3 each has a role in virus replication in vitro, in vivo, or both, and define mutations that might be useful for the development of a vaccine against HPIV3. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), 7 Ctr Dr,MSC 0720, Bethesda, MD 20814 USA. NR 53 TC 75 Z9 76 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1999 VL 261 IS 2 BP 319 EP 330 DI 10.1006/viro.1999.9878 PG 12 WC Virology SC Virology GA 234KW UT WOS:000082484700017 PM 10497117 ER PT J AU Betakova, T Wolffe, EJ Moss, B AF Betakova, T Wolffe, EJ Moss, B TI Membrane topology of the vaccinia virus A17L envelope protein SO VIROLOGY LA English DT Article ID ACTIN-CONTAINING MICROVILLI; OPEN READING FRAME; TO-CELL SPREAD; INTERMEDIATE COMPARTMENT; ENDOPLASMIC-RETICULUM; VIRION MORPHOGENESIS; STRUCTURAL PROTEINS; P-GLYCOPROTEIN; GENE; BIOGENESIS AB The formation of a lipoprotein membrane within specialized areas of the cytoplasm is the first visible step in poxvirus morphogenesis. The A17L viral protein, an essential nonglycosylated membrane component, was predicted to have four centrally located alpha-helical membrane-spanning domains. The gene was expressed as a 23-kDa protein in a cell-free transcriplion/translation system containing canine pancreatic microsomes. The N- and C-terminal ends of the membrane-associated protein were susceptible to proteinase digestion, whereas the central region was resistant, consistent with a model in which the first and fourth hydrophobic domains are membrane spanning. This topology was supported by the sizes of the major proteinase-resistant membrane-associated products of genes containing one or more deleted hydrophobic domains and by evidence that the C-terminus was intraluminal and glycosylated on deletion of the second, third, and fourth domains, the third and fourth domains, or just the fourth domain. Moreover, glycosylation also occurred when an N-glycosylation site was introduced into the second hydrophobic domain of the full-length A17L protein. The data indicated a predominant topology in which the N- and C-termini are cytoplasmic, the first and fourth hydrophobic domains span the microsomal membrane, and the second and third hydrophobic domains are intraluminal. This arrangement has important implications for interactions of the A17L protein with other membrane components. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NR 42 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1999 VL 261 IS 2 BP 347 EP 356 DI 10.1006/viro.1999.9870 PG 10 WC Virology SC Virology GA 234KW UT WOS:000082484700020 PM 10497120 ER PT J AU Lamirande, EW Nichols, DK Owens, JW Gaskin, JM Jacobson, ER AF Lamirande, EW Nichols, DK Owens, JW Gaskin, JM Jacobson, ER TI Isolation and experimental transmission of a reovirus pathogenic in ratsnakes (Elaphe species) SO VIRUS RESEARCH LA English DT Article; Proceedings Paper CT 4th International Symposium on Viruses of Lower Vertebrates CY MAY 12-15, 1998 CL WEYMOUTH LAB, WEYMOUTH, ENGLAND HO WEYMOUTH LAB DE Elaphe sp.; pneumonia; reovirus; snake; tracheitis ID VIRUS; PNEUMONIA; SNAKE AB A reovirus was isolated from juvenile Moellendorff's ratsnakes (Elaphe moellendorffi) and beauty snakes (Elaphe taenuris) that died soon after importation into the USA. Viper heart (VH2) cells inoculated with tissue homogenates showed cytopathic effects consisting of large syncytia formation followed by cell detachment from the monolayer. Tissue culture supernatants failed to hemagglutinate guinea pig and chicken erythrocytes at room temperature. Electron microscopy of purified virions revealed spherical to icosahedral particles measuring 70-85 nm in diameter with a double capsid layer. Preparations of the viral genome contained ten segments of dsRNA when analyzed by polyacrylamide gel electrophoresis. A juvenile black ratsnake (Elaphe obsoleta obsaleta) was experimentally inoculated with the isolate and was found dead 26 days post inoculation. Necropsy revealed diffuse subacute interstitial pneumonia with respiratory epithelial cell hyperplasia and syncytia. Reovirus isolated from this snake was used to inoculate another juvenile black ratsnake which was euthanized 40 days post inoculation. Pneumonia and multifocal subacute proliferative tracheitis were found on necropsy. Reovirus was isolated from the lung of this snake and was demonstrated by transmission electron microscopy. This is the first documentation of a pathogenic reptile reovirus and the first report of experimental transmission of a reovirus in snakes. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Smithsonian Inst, Natl Zool Pk, Dept Pathol, Washington, DC 20008 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32610 USA. Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32610 USA. RP Lamirande, EW (reprint author), Smithsonian Inst, Natl Zool Pk, Dept Pathol, Washington, DC 20008 USA. NR 14 TC 31 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD SEP PY 1999 VL 63 IS 1-2 BP 135 EP 141 DI 10.1016/S0168-1702(99)00067-2 PG 7 WC Virology SC Virology GA 238PB UT WOS:000082717700017 PM 10509725 ER PT J AU Kelley, MW AF Kelley, MW TI Genetics and hearing loss SO VOLTA REVIEW LA English DT Book Review C1 NIDCD, Unit Dev Neurosci, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20057 USA. RP Kelley, MW (reprint author), NIDCD, Unit Dev Neurosci, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ALEXANDER GRAHAM BELL ASSOC FOR THE DEAF PI WASHINGTON PA 3417 VOLTA PLACE NW, WASHINGTON, DC 20007 USA SN 0042-8639 J9 VOLTA REV JI Volta Rev. PD FAL PY 1999 VL 101 IS 4 BP 223 EP 224 PG 2 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 402BH UT WOS:000166965800004 ER PT J AU Kip, KE Bourassa, MG Jacobs, AK Schwartz, L Feit, F Alderman, EL Weiner, BH Weiss, MB Kellett, MA Sharaf, BL Dimas, AP Jones, RH Sopko, G Detre, KM AF Kip, KE Bourassa, MG Jacobs, AK Schwartz, L Feit, F Alderman, EL Weiner, BH Weiss, MB Kellett, MA Sharaf, BL Dimas, AP Jones, RH Sopko, G Detre, KM CA BARI Investigators TI Influence of Pre-PTCA strategy and initial PTCA result in patients with multivessel disease - The Bypass Angioplasty Revascularization Investigation (BARI) SO CIRCULATION LA English DT Article DE angioplasty; coronary disease; revascularization ID LUMINAL CORONARY ANGIOPLASTY; ANGIOGRAPHIC FOLLOW-UP; MYOCARDIAL-INFARCTION; COMPLETENESS; REGISTRY; 2-VESSEL; TRIAL AB Background-In PTCA patients with multivessel coronary artery disease, incomplete revascularization (IR) is the result of both pre-PTCA strategy and initial lesion outcome. The unique contribution of these components on long-term patient outcome is uncertain. Methods and Results-From the Bypass Angioplasty Revascularization Investigation (BARI), 2047 patients who underwent first-time PTCA were evaluated. Before enrollment, all significant lesions were assessed by the PTCA operator for clinical importance and intention to dilate. Complete revascularization (CR) was defined as successful dilatation of all clinically relevant lesions. Planned CR was indicated in 65% of all patients. More lesions were intended for PTCA in these patients compared with those with planned IR (2.8 versus 2.1). Successful dilatation of all intended lesions occurred in 45% of patients with planned CR versus 56% with planned IR (P<0.001). In multivariable analysis, planned IR (versus planned CR), initial lesions attempted (not all versus all intended lesions attempted), and initial lesion outcome (not all versus all attempted lesions successful) were unrelated to 5-year risk of cardiac death or death/myocardial infarction but were all independently related to risk of CABG. Conclusions-Overall, a pre-PTCA strategy of IR in BARI-like patients appears comparable to a strategy of CR except for a higher need for CABG. Whether the use of new devices may attenuate the elevated risk of CABG in patients with multivessel disease and planned IR remains to be determined. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Boston Med Ctr, Boston, MA USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. NYU Med Ctr, New York, NY 10016 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. New York Med Coll, Valhalla, NY 10595 USA. Maine Med Ctr, Portland, ME 04102 USA. Rhode Isl Hosp, Providence, RI USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Med Ctr, Durham, NC USA. NHLBI, Bethesda, MD 20892 USA. RP Kip, KE (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St,127 Parran Hall, Pittsburgh, PA 15261 USA. OI Bourassa, Martial G./0000-0002-4439-8650 NR 24 TC 16 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 31 PY 1999 VL 100 IS 9 BP 910 EP 917 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 232DZ UT WOS:000082353000005 PM 10468520 ER PT J AU Tsai, CJ Ma, BY Nussinov, R AF Tsai, CJ Ma, BY Nussinov, R TI Folding and binding cascades: Shifts in energy landscapes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID PROTEIN; LEVINTHAL; MODEL C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Tsai, CJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 21 TC 230 Z9 230 U1 1 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 9970 EP 9972 DI 10.1073/pnas.96.18.9970 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100002 PM 10468538 ER PT J AU Sarafianos, SG Das, K Clark, AD Ding, JP Boyer, PL Hughes, SH Arnold, E AF Sarafianos, SG Das, K Clark, AD Ding, JP Boyer, PL Hughes, SH Arnold, E TI Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TEMPLATE-PRIMER UTILIZATION; HIGH-LEVEL RESISTANCE; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; CONFERS RESISTANCE; CRYSTAL-STRUCTURE; YMDD MOTIF; INHIBITION; POLYMERASE AB An important component of triple-drug anti-AIDS therapy is 2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine). Single mutations at residue 184 of the reverse transcriptase (RT) in HIV cause high-level resistance to 3TC and contribute to the failure of anti-AIDS combination therapy. We have determined crystal structures of the 3TC-resistant mutant HIV-1 RT (M184I) in both the presence and absence of a DNA/DNA template-primer, In the absence of a DNA substrate, the wild-type and mutant structures are very similar. However, comparison of crystal structures of M184I mutant and wild-type HIV-1 RT with and without DNA reveals repositioning of the template-primer in the M184I/DNA binary complex and other smaller changes in residues in the dNTP-binding site. On the basis of these structural results, we developed a model that explains the ability of the 3TC-resistant mutant M184I to incorporate dNTPs but not the nucleotide analog 3TCTP. In this model, steric hindrance is expected for NRTIs with beta- or L- ring configurations, as with the enantiomer of 3TC that is used in therapy. Steric conflict between the oxathiolane ring of 3TCTP and the side chain of P-branched amino acids (Val, Ile, Thr) at position 184 perturbs inhibitor binding, leading to a reduction in incorporation of the analog. The model can also explain the 3TC resistance of analogous hepatitis B polymerase mutants. Repositioning of the template-primer as observed in the binary complex (M184I/DNA) may also occur in the catalytic ternary complex (M184I/DNA/3TCTP) and contribute to 3TC resistance by interfering with the formation of a catalytically competent closed complex. C1 Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program, Frederick, MD 21702 USA. RP Arnold, E (reprint author), Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA. OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [AI 36144, AI 09578, F32 AI009578] NR 55 TC 215 Z9 223 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10027 EP 10032 DI 10.1073/pnas.96.18.10027 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100020 PM 10468556 ER PT J AU Lee, JS Lee, CH Chung, JH AF Lee, JS Lee, CH Chung, JH TI The beta-globin promoter is important for recruitment of erythroid Kruppel-like factor to the locus control region in erythroid cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOMINANT CONTROL REGION; GENE-EXPRESSION; CHROMATIN STRUCTURE; FACTOR EKLF; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; TRANSGENIC MICE; 5' HS-2; DELETION; DOMAIN AB Erythroid Kruppel-like factor (EKLF), which binds to the CACCC box in the beta-globin promoter, is required for the expression of the beta-globin gene in adult erythroid cells, It was recently demonstrated that EKLF is also required for the activity of the beta-globin locus control region (LCR) 5'HS3. Some evidence suggests that the LCR and the beta-globin promoter interact in adult erythroid cells, and the network of protein-protein interactions that exists between these two elements may regulate how EKLF is recruited to the LCR, In this report, we use the PIN*POINT assay to study the role of the promoter on the recruitment of EKLF to 5'HS2 and 5'HS3 of the LCR. We find that recruitment of EKLF to 5'HS2 requires the TATA box, but recruitment to 5'HS3 depends on the CACCC and TATA boxes of the beta-globin promoter. Furthermore, recruitment of EKLF to 5'HS3 only occurred in beta-globin-expressing murine erythroid leukemia cells, whereas recruitment of EKLF to 5'HS2 occurred in both gamma-globin-expressing K562 cells and murine erythroid leukemia cells. Unlike EKLF, Spl, which also binds to CACCC boxes, is not recruited to 5'HS3, We have also examined how one 5'HS affects the recruitment of EKLF to another 5'HS. We have found that the recruitment of EKLF to 5'HS3 depends on the presence of 5'HS2 in cis, but the recruitment to 5'HS2 does not depend on 5'HS3. Based on these results, we present a model that illustrates how EKLF may be recruited to the beta-globin locus. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Chung, JH (reprint author), NHLBI, Mol Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 40 TC 21 Z9 21 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10051 EP 10055 DI 10.1073/pnas.96.18.10051 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100024 PM 10468560 ER PT J AU Kim, MK Lee, JS Chung, JH AF Kim, MK Lee, JS Chung, JH TI In vivo transcription factor recruitment during thyroid hormone receptor-mediated activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION; N-COR; HISTONE DEACETYLASE; RESPONSE ELEMENTS; V-ERBA; REPRESSION; COACTIVATOR; COMPLEX; BETA; SUPERFAMILY AB Thyroid hormone receptor (TR) can act as both a transcriptional activator and a silencer. Optimal activation by TR requires synergism with activator(s) bound to the promoter (promoter proximal activator). It is thought that liganded TR either helps to recruit preinitiation complexes (PIC) to the promoter or activates the PIC already recruited. However, the studies analyzing the Tn action on the PIC formation were done in vitro and, therefore, it is not clear how relevant they are to the in vivo TR action. For example, in vivo, the TR can act from distances equal to or greater than a kilobase from the promoter, but such distant effect is not reproducible in vitro. In this study, we used the PIN*POINT (ProteIN POsition Identification with Nuclease Tail) assay to define the molecular mechanism of TR action on transcription from the thymidine kinase promoter in the cellular context. We demonstrate that the recruitment of promoter-proximal activator Spl, and the components of the basal transcription factors such as TBP, TFIIB, and Cdk7, is enhanced with thyroid hormone activation. Our results suggest that DNA forms a loop with TR-mediated activation to accommodate interactions between the liganded TR complex and the complex formed on the promoter. We also show that Spl bound to the promoter is essential for the DNA looping and recruitment of basal transcription factors such as TFIIB and Cdk7 but not for recruitment of TBP. On the basis of these findings, we present a model that illustrates the molecular mechanism of TR-mediated activation in vivo. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kim, MK (reprint author), NHLBI, Mol Hematol Branch, NIH, Bldg 10,Room 7D11,10 Ctr Dr, Bethesda, MD 20892 USA. NR 46 TC 21 Z9 22 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10092 EP 10097 DI 10.1073/pnas.96.18.10092 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100031 PM 10468567 ER PT J AU Pollack, L Tate, MW Darnton, NC Knight, JB Gruner, SM Eaton, WA Austin, RH AF Pollack, L Tate, MW Darnton, NC Knight, JB Gruner, SM Eaton, WA Austin, RH TI Compactness of the denatured state of a fast-folding protein measured by submillisecond small-angle x-ray scattering SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOCHROME-C; LANDSCAPE PERSPECTIVE; KINETICS; INTERMEDIATE; LIGANDS AB Time-resolved small-angle x-ray scattering was used to measure the radius of gyration of cytochrome c after initiation of folding by a pH jump. Submillisecond time resolution was obtained with a microfabricated diffusional mixer and synchrotron radiation. The results show that the protein first collapses to compact denatured structures before folding very fast to the native state. C1 Cornell Univ, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA. Princeton Univ, Dept Phys, Princeton, NJ 08544 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Pollack, L (reprint author), Cornell Univ, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA. RI Gruner, Sol/G-2924-2010 OI Gruner, Sol/0000-0002-1171-4426 NR 30 TC 223 Z9 225 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10115 EP 10117 DI 10.1073/pnas.96.18.10115 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100035 PM 10468571 ER PT J AU Hammad, SM Stefansson, S Twal, WO Drake, CJ Fleming, P Remaley, A Brewer, HB Argraves, WS AF Hammad, SM Stefansson, S Twal, WO Drake, CJ Fleming, P Remaley, A Brewer, HB Argraves, WS TI Cubilin, the endocytic receptor for intrinsic factor-vitamin B-12 complex, mediates high-density lipoprotein holoparticle endocytosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID APOLIPOPROTEIN-A-I; GOLDEN SYRIAN-HAMSTER; CHOLESTEROL LEVELS; SR-BI; ALPHA-2-MACROGLOBULIN RECEPTOR; LDL RECEPTOR; PLASMA; METABOLISM; PROTEIN; CELLS AB Receptors that endocytose high-density lipoproteins (HDL) have been elusive. Here yolk-sac endoderm-like cells were used to identify an endocytic receptor for HDL. The receptor was isolated by HDL affinity chromatography and identified as cubilin, the recently described endocytic receptor for intrinsic factor-vitamin B-12. Cubilin antibodies inhibit HDL endocytosis by the endoderm-like cells and in mouse embryo yolk-sec endoderm, a prominent site of cubilin expression. Cubilin-mediated HDL endocytosis is inhibitable by HDL2, HDL3, apolipoprotein (apo)A-I, apoA-II, apoE, and RAP, but not by low-density lipoprotein (LDL), oxidized LDL, VLDL, apoC-I, apoC-III,or heparin. These findings, coupled with the fact that cubilin is expressed in kidney proximal tubules, suggest a role for this receptor in embryonic acquisition of maternal HDL and renal catabolism of filterable forms of HDL. C1 Med Univ S Carolina, Dept Cell Biol, Charleston, SC 29425 USA. Amer Red Cross, Jerome H Holland Lab, Dept Biochem, Rockville, MD 20855 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Argraves, WS (reprint author), Med Univ S Carolina, Dept Cell Biol, Charleston, SC 29425 USA. NR 47 TC 119 Z9 121 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10158 EP 10163 DI 10.1073/pnas.96.18.10158 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100043 PM 10468579 ER PT J AU Engels, FHC Koski, GK Bedrosian, I Xu, SW Luger, S Nowell, PC Cohen, PA Czerniecki, BJ AF Engels, FHC Koski, GK Bedrosian, I Xu, SW Luger, S Nowell, PC Cohen, PA Czerniecki, BJ TI Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PERIPHERAL-BLOOD MONOCYTES; VERSUS-HOST DISEASE; MARROW TRANSPLANTATION; T-LYMPHOCYTES; ANTIGEN; DONOR; IMMUNOTHERAPY; GENERATION; INDUCTION; RESPOND AB Effective host T lymphocyte sensitization to malignant cells depends on successful antigen presentation. In this study, me examined the capacity of malignant myeloid progenitor cells of patients in the chronic phase of chronic myelogenous leukemia (CML) to acquire characteristics of activated dendritic cells (DCs) after intracellular calcium mobilization, thereby bypassing a need for third-party antigen-presenting cells. Treatment of purified CD33(+) CML cells from 15 patients with calcium ionophore (CI) consistently resulted in de novo expression of the costimulatory molecules CD80 (B7.1) and CD86 (B7.2), CD40 and the DC-specific activation marker CD83, as well as marked up-regulation of MHC class I and II molecules and the adhesion molecule CD54. Most of these changes occurred within 24 hr of treatment, Morphologically, CI-treated CML cells developed long dendritic projections similar to those seen in mature DCs, Functionally, CI-treated CML cells provided stimulation of allogeneic T lymphocytes 10- to 20-fold that of untreated CML cells or untreated monocytes, Fluorescent in situ hybridization of CI-activated CML cells confirmed their leukemic origin by displaying the typical bcr/abl fusion signal. No difference in bcr/abl translocation percentages between untreated and CI-treated CML nuclei was observed. These observations indicate that calcium mobilization may constitute a valuable approach for rapidly and reliably generating CML-derived DCs for immunotherapy of CML. C1 Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. RP Czerniecki, BJ (reprint author), Univ Penn, Med Ctr, Dept Surg, 4 Silverstein Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA-42232] NR 25 TC 31 Z9 34 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10332 EP 10337 DI 10.1073/pnas.96.18.10332 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100072 PM 10468608 ER PT J AU Ginsberg, HS Moldawer, LL Prince, GA AF Ginsberg, HS Moldawer, LL Prince, GA TI Role of the type 5 adenovirus gene encoding the early region 1B 55-kDa protein in pulmonary pathogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokines ID RESPIRATORY-TRACT; PNEUMONIA; DISEASE; MODEL AB Comparison of the inflammatory response of Sigmodon hispidus cotton rats to pulmonary infection with wild-type 5 adenovirus (Ad5) or with a viral mutant, in which the early region 1B gene encoding a 55-kDa protein, Ad5dl110 (dl110), was deleted, indicated that the inflammation in animals infected with dl110 was markedly reduced compared with the inflammation in animals infected with wild-type Ad5, although both viruses replicated to the same extent. Comparable experiments done with C57BL/6 mice yielded identical results, even though only the early phase of gene expression essential for viral replication occurs in mice, Cytokine analysis of infected mouse lungs indicated that tumor necrosis factor-cw and IL-6 were produced in relatively large quantities in wild-type Ad5-infected mice and at significantly lower levels in dl110-infected mice during the early stages of infection. C1 NIAID, Rockville, MD 20852 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Univ Florida, Sch Med, Dept Surg, Gainesville, FL 32610 USA. Virion Syst, Rockville, MD 20850 USA. RP Ginsberg, HS (reprint author), NIAID, Rockville, MD 20852 USA. FU NIAID NIH HHS [AI12052] NR 14 TC 9 Z9 9 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10409 EP 10411 DI 10.1073/pnas.96.18.10409 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100085 PM 10468621 ER PT J AU Gomeza, J Zhang, L Kostenis, E Felder, C Bymaster, F Brodkin, J Shannon, H Xia, B Deng, CX Wess, J AF Gomeza, J Zhang, L Kostenis, E Felder, C Bymaster, F Brodkin, J Shannon, H Xia, B Deng, CX Wess, J TI Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M-4 muscarinic acetylcholine receptor knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SUBTYPE-SPECIFIC ANTIBODIES; ADENYLYL-CYCLASE ACTIVITY; PHENOTYPICAL CHARACTERIZATION; CHOLINERGIC RECEPTORS; MOLECULAR-BIOLOGY; GENE-EXPRESSION; RAT; NEURONS; ANTAGONISTS; BRAIN AB Muscarinic acetylcholine receptors (M-1-M-5) regulate many key functions of the central and peripheral nervous system. Primarily because of the lack of receptor subtype-selective ligands, the precise physiological roles of the individual muscarinic receptor subtypes remain to be elucidated; Interestingly, the M-4 receptor subtype is expressed abundantly in the striatum and various other forebrain regions. To study its potential role in the regulation of locomotor activity and other central functions, we used gene-targeting technology to create mice that lack functional M-4 receptors. Pharmacologic analysis of M-4 receptor-deficient mice indicated that M-4 receptors are not required for muscarinic receptor-mediated analgesia, tremor, hypothermia, and salivation. Strikingly, M-4 receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses (as compared with their wild-type littermates) after activation of D1 dopamine receptors. These results indicate that M-4 receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels. Our findings offer new perspectives for the treatment of Parkinson's disease and other movement disorders that are characterized by an imbalance between muscarinic cholinergic and dopaminergic neurotransmission. C1 NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Wess, J (reprint author), NIDDKD, Bioorgan Chem Lab, Bldg 8A,Room B1A-05, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 41 TC 203 Z9 208 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10483 EP 10488 DI 10.1073/pnas.96.18.10483 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100099 PM 10468635 ER PT J AU Garruto, RM Little, MA James, GD Brown, DE AF Garruto, RM Little, MA James, GD Brown, DE TI Natural experimental models: The global search for biomedical paradigms among traditional, modernizing, and modern populations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review ID NOMADIC TURKANA PASTORALISTS; CATECHOLAMINE EXCRETION RATES; WESTERN SAMOAN MEN; BLOOD-PRESSURE; VILIUISK ENCEPHALOMYELITIS; STRESS; GROWTH; WOMEN; LIFESTYLE; PACIFIC AB During the past four decades, biomedical scientists have slowly begun to recognize the unique opportunities for studying biomedical processes, disease etiology, and mechanisms of pathogenesis in populations with unusual genetic structures, physiological characteristics, focal endemic disease, or special circumstances. Such populations greatly extend our research capabilities and provide a natural laboratory for studying relationships among biobehavioral, genetic, and ecological processes that are involved in the development of disease. The models presented illustrate three different types of natural experiments: those occurring in traditionally living, modernizing, and modern populations. The examples are drawn from current research that involves population mechanisms of adaptation among East African Turkana pastoralists; a search for etiology and mechanisms of pathogenesis of an emerging disease among the Yakut people of Siberia; and psychosocial stress, hypertension, and cardiovascular disease in women working outside the home in New York City and among subpopulations in Hawaii. The models in general, and the examples in specific, represent natural laboratories in which relatively small intrapopulation differences and large interpopulation differences can be used to evaluate health and disease outcomes. C1 SUNY Binghamton, Dept Anthropol, Binghamton, NY 13902 USA. SUNY Binghamton, Dept Biol Sci, Binghamton, NY 13902 USA. SUNY Binghamton, Decker Sch Nursing, Binghamton, NY 13902 USA. SUNY Binghamton, Inst Primary & Preventat Hlth Care, Binghamton, NY 13902 USA. NIH, Bethesda, MD 20892 USA. Univ Hawaii, Dept Anthropol, Hilo, HI 96720 USA. RP Garruto, RM (reprint author), SUNY Binghamton, Dept Anthropol, Sci 1,Room 11,POB 6000, Binghamton, NY 13902 USA. FU NHLBI NIH HHS [HL 47540, HL37054, P01 HL047540]; NIGMS NIH HHS [GM 08073, S06 GM008073] NR 104 TC 23 Z9 25 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 31 PY 1999 VL 96 IS 18 BP 10536 EP 10543 DI 10.1073/pnas.96.18.10536 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233JQ UT WOS:000082424100108 PM 10468644 ER PT J AU Kohn, MC Melnick, RL AF Kohn, MC Melnick, RL TI A physiological model for ligand-induced accumulation of alpha(2u) globulin in male rat kidney - Roles of protein synthesis and lysosomal degradation in the renal dosimetry of 2,4,4-trimethyl-2-pentanol SO TOXICOLOGY LA English DT Article DE alpha(2u)-globulin; PBPK modeling; cathepsins; 2,4,4-trimethyl-2-pentanol ID MALE FISCHER-344 RATS; ADULT MALE-RATS; ALPHA-2U-GLOBULIN NEPHROPATHY; UNLEADED GASOLINE; CELL-PROLIFERATION; PROXIMAL TUBULE; EXCRETION; CANCER; EXPOSURE; AGENTS AB A physiologically based pharmacokinetic (PBPK) model was constructed for the disposition of 2,4,4-trimethyl-2-pentanol (TMP-2-OH) in male rats and its induction of accumulation of renal alpha(2u)-globulin (alpha 2u). The model included diffusion-restricted delivery of TMP-2-OH to compartments representing liver, lung, fat, kidney, GI tract, aggregated rapidly perfused tissues, and aggregated slowly perfused tissues. Metabolism by oxidation and glucuronidation was included for liver and kidneys. Rates of hepatic alpha 2u production and resorption by renal proximal tubules were taken from the literature. Degradation of liganded alpha 2u by renal lysosomal cathepsins was modeled with a K-m value corresponding to the measured 30% reduction in proteolytic efficiency and with free and bound forms of alpha 2u competing for access to the enzymes. Increased pinocytotic uptake of alpha 2u into the kidney induces cathepsin activity. A model that ascribed renal alpha 2u accumulation solely to reduced lysosomal proteolysis failed to reproduce the observed accumulation. The model could reproduce experimental observations if a transient increase in hepatic synthesis of alpha 2u, stimulated by the presence of liganded alpha 2u in the blood, and accelerated secretion of the protein from the liver were assumed. This model reproduces time course data of blood and kidney TMP-2-OH and renal alpha 2u concentrations, suggesting that renal accumulation of alpha 2u is not simply a consequence of reduced proteolytic degradation but may also involve a transient increase in hepatic alpha 2u production. The model predicts increased delivery of TMP-2-OH to the kidney and consequent increased renal production of potentially toxic TMP-2-OH metabolites than would be the case if no alpha 2u were present. Induced lysosomal activity and increased production of toxic metabolites may both contribute to the nephrotoxicity observed in male rats exposed to an alpha 2u ligand or its precursor. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Anal, POB 12233,Mail Drip A3-06, Res Triangle Pk, NC 27709 USA. NR 65 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD AUG 31 PY 1999 VL 136 IS 2-3 BP 89 EP 105 DI 10.1016/S0300-483X(99)00063-3 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 240XA UT WOS:000082851300003 PM 10514002 ER PT J AU Levin, I Leapman, RD Kaiser, DL van Buskirk, PC Bilodeau, S Carl, R AF Levin, I Leapman, RD Kaiser, DL van Buskirk, PC Bilodeau, S Carl, R TI Accommodation of excess Ti in a (Ba, Sr)TiO3 thin film with 53.4% Ti grown on Pt/SiO2/Si by metalorganic chemical-vapor deposition SO APPLIED PHYSICS LETTERS LA English DT Article ID DIELECTRIC-PROPERTIES; (BA,SR)TIO3 AB The microstructure and chemistry of a Ti-rich (Ba, Sr)TiO3 film with 53.4% Ti deposited on a Pt/SiO2/Si substrate by metallorganic chemical-vapor deposition was studied using high-resolution transmission electron microscopy and elemental mapping in electron energy-loss spectroscopy. We established that the Ti/Ba ratio at all the grain boundaries in this film is significantly higher than that in the grain interiors. Structural images revealed the presence of disordered amorphous-like regions at some of the grain boundaries and triple junctions; these regions were tentatively identified as those having the highest Ti/Ba ratio in the chemical maps. Analysis of the electron energy-loss near-edge structure for the O-K edge indicated an increased titanium-to-oxygen coordination at the grain boundaries. No second phase was detected at the (Ba, Sr)TiO3/Pt interface. (C) 1999 American Institute of Physics. [S0003-6951(99)01735-0]. C1 Natl Inst Stand & Technol, Div Ceram, Gaithersburg, MD 20899 USA. NIH, ORS, Bethesda, MD 20892 USA. Appl Technol Mat Inc, Danbury, CT 06810 USA. RP Levin, I (reprint author), Natl Inst Stand & Technol, Div Ceram, Gaithersburg, MD 20899 USA. RI Levin, Igor/F-8588-2010 NR 13 TC 19 Z9 21 U1 0 U2 4 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD AUG 30 PY 1999 VL 75 IS 9 BP 1299 EP 1301 DI 10.1063/1.124674 PG 3 WC Physics, Applied SC Physics GA 228BV UT WOS:000082117000038 ER PT J AU Hadar, M McGowan, JJ AF Hadar, M McGowan, JJ TI Taking the sting out of applying for NIH grants SO SCIENTIST LA English DT Editorial Material C1 NIAID, Div Extramural Activities, Bethesda, MD 20892 USA. RP Hadar, M (reprint author), NIAID, Div Extramural Activities, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD AUG 30 PY 1999 VL 13 IS 17 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 243MJ UT WOS:000083001600019 ER PT J AU Cohen, OJ Fauci, AS AF Cohen, OJ Fauci, AS TI Transmission of drug-resistant strains of HIV-1: unfortunate, but inevitable SO LANCET LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; INFECTION; INHIBITOR C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, OJ (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 15 Z9 15 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 28 PY 1999 VL 354 IS 9180 BP 697 EP 698 DI 10.1016/S0140-6736(99)90106-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 230BY UT WOS:000082233000004 PM 10475176 ER PT J AU Sinha, A Sazawal, S Kumar, R Sood, S Reddaiah, VP Singh, B Rao, M Naficy, A Clemens, JD Bhan, MK AF Sinha, A Sazawal, S Kumar, R Sood, S Reddaiah, VP Singh, B Rao, M Naficy, A Clemens, JD Bhan, MK TI Typhoid fever in children aged less than 5 years SO LANCET LA English DT Article ID VI-CAPSULAR POLYSACCHARIDE; SALMONELLA-TYPHI; VACCINE; YOUNGER AB Background Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. Methods A baseline census was undertaken in 1995, Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin, Findings 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. Interpretation Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed. C1 All India Inst Med Sci, Dept Pediat, Div Paediat Gastroenterol, Adv Ctr Diarrhoeal Dis Res,Indian Council Med Res, New Delhi 110029, India. All India Inst Med Sci, Dept Microbiol, New Delhi 110029, India. All India Inst Med Sci, Ctr Community Med, New Delhi 110029, India. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD USA. NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bhan, MK (reprint author), All India Inst Med Sci, Dept Pediat, Div Paediat Gastroenterol, Adv Ctr Diarrhoeal Dis Res,Indian Council Med Res, New Delhi 110029, India. NR 22 TC 203 Z9 207 U1 1 U2 9 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 28 PY 1999 VL 354 IS 9180 BP 734 EP 737 DI 10.1016/S0140-6736(98)09001-1 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 230BY UT WOS:000082233000013 PM 10475185 ER PT J AU Deere, M Sanford, T Francomano, CA Daniels, K Hecht, JT AF Deere, M Sanford, T Francomano, CA Daniels, K Hecht, JT TI Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE cartilage oligomeric matrix; protein; COMP; pseudoachondroplasia; PSACH; multiple epiphyseal dysplasia; EDM1; mutation; dwarfism ID COMP; GENE; MOSAICISM; TENDON AB Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are allelic disorders caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP), PSACH is a dominant condition characterized by disproportionate short stature; joint laxity, and early-onset osteoarthritis. EDM1 is a less severe skeletal dysplasia associated with average to mild short stature, joint pain, and early-onset osteoarthritis, COMP is an extracellular matrix protein present in cartilage, ligament, and tendon tissues. Here, we report on nine novel mutations in COMP causing PSACH and EDM1, Four of these mutations are in exons 13C and 14 where no previous mutations had been reported. One of those mutations was identified in two separate EDM1 families. In addition, we have identified the first case of PSACH resulting from an expansion of the five aspartates in exon 17B, We are also reporting a mutation in a third PSACH family with somatic/germline mosaicism, Therefore, this report increases the range of mutations that cause PSACH and EDM1 and provides additional regions to target for mutational analysis. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, Sch Med, Dept Pediat, Houston, TX 77225 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Univ Iowa, Dept Biol Sci, Iowa City, IA USA. RP Hecht, JT (reprint author), Univ Texas, Sch Med, Dept Pediat, POB 20708, Houston, TX 77225 USA. FU NCI NIH HHS [CA16672] NR 24 TC 43 Z9 45 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 27 PY 1999 VL 85 IS 5 BP 486 EP 490 DI 10.1002/(SICI)1096-8628(19990827)85:5<486::AID-AJMG10>3.0.CO;2-O PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 218BT UT WOS:000081533900010 PM 10405447 ER PT J AU Neyns, B Teugels, E Bourgain, C Birrer, M De Greve, J AF Neyns, B Teugels, E Bourgain, C Birrer, M De Greve, J TI Alteration of jun proto-oncogene status by plasmid transfection affects growth of human ovarian cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID WILD-TYPE P53; C-JUN; DELETION MUTANT; AP-1 COMPLEX; HUMAN-BREAST; GENE; TRANSFORMATION; EXPRESSION; MUTATIONS; RAS AB The AP-1 transcription factor (the Jun and Fos proteins) is suspected of playing an important role in the biology of human cancer. Human epithelial ovarian tumors and cancer cell lines express the c-jun and jun-B proto-oncogenes at a high level, in contrast with the jun-D gene, We have investigated here the functional relevance of these observations for the growth of ovarian cancer cells, Transient constitutive expression of a dominant negative c-jun mutant (TAM67) in human AZ224, SKOV3 and OVCAR3 ovarian cancer cells inhibited the outgrowth of selection marker-resistant colonies by at least 75% as opposed to a control plasmid, Transfection of jun-B did not affect these cell lines, while jun-D transfection had a cell line-specific effect. In comparison, transfection of the tumor-suppressor gene p53 had a less important inhibitory effect on OVCAR3 cells and no effect on SKOV3 and AZ224 cells when compared to TAM67, Regulated TAM67 expression in AZ224 cells, from plasmids containing the mouse metallothionein or the MMTV promoter, suppressed cancer cell growth in vitro and in nude mice without evidence of increased cell death. Our observations support a role for the c-jun proto-oncogene as a positive mediator of human ovarian cancer cell growth and make it a potential therapeutic target. Int. J. Cancer 82:687-693, 1999, (C) 1999 Wiley-Liss, Inc. C1 Free Univ Brussels, Akad Ziekenhuis, Mol Oncol Lab, B-1090 Brussels, Belgium. Free Univ Brussels, Akad Ziekenhuis, Ctr Oncol, B-1090 Brussels, Belgium. Free Univ Brussels, Akad Ziekenhuis, Lab Expt Pathol, B-1090 Brussels, Belgium. Natl Canc Inst, Div Canc Prevent & Control, Biomarkers & Prevent Res Branch, Rockville, MD USA. RP De Greve, J (reprint author), Free Univ Brussels, Akad Ziekenhuis, Mol Oncol Lab, Laarbeeklaan 101, B-1090 Brussels, Belgium. RI De Greve, Jacques/J-4939-2012 OI De Greve, Jacques/0000-0002-2389-0742 NR 34 TC 12 Z9 13 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 27 PY 1999 VL 82 IS 5 BP 687 EP 693 PG 7 WC Oncology SC Oncology GA 222AQ UT WOS:000081760400011 PM 10417766 ER PT J AU Sun, QA Wu, YL Zappacosta, F Jeang, KT Lee, BJ Hatfield, DL Gladyshev, VN AF Sun, QA Wu, YL Zappacosta, F Jeang, KT Lee, BJ Hatfield, DL Gladyshev, VN TI Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HYDROGEN-PEROXIDE; HUMAN PLACENTA; PROTEIN; PURIFICATION; ACTIVATION; REDUCTION; GENE; SELENOPROTEIN; INVOLVEMENT AB The intracellular generation of reactive oxygen species, together with the thioredoxin and glutathione systems, is thought to participate in redox signaling in mammalian cells. The activity of thioredoxin is dependent on the redox status of thioredoxin reductase (TR), the activity of which in turn is dependent on a selenocysteine residue. Two mammalian TR isozymes (TR2 and TR3), in addition to that previously characterized (TR1), have now been identified in humans and mice. All three TR isozymes contain a selenocysteine residue that is located in the penultimate position at the carboxyl terminus and which is encoded by a UGA codon. The generation of reactive oxygen species in a human carcinoma cell line was shown to result in both the oxidation of the selenocysteine in TR1 and a subsequent increase in the expression of this enzyme. These observations identify the carboxyl-terminal selenocysteine of TR1 as a cellular redox sensor and support an essential role for mammalian TR isozymes in redox-regulated cell signaling. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Struct Lab, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Inst Mol Biol & Genet, Mol Genet Lab, Seoul 151742, South Korea. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Jeang, Kuan-Teh/A-2424-2008; Gladyshev, Vadim/A-9894-2013 NR 48 TC 211 Z9 223 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 24522 EP 24530 DI 10.1074/jbc.274.35.24522 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400014 PM 10455115 ER PT J AU Chen, YR Sturgeon, BE Gunther, MR Mason, RP AF Chen, YR Sturgeon, BE Gunther, MR Mason, RP TI Electron spin resonance investigation of the cyanyl and azidyl radical formation by cytochrome c oxidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; SODIUM-AZIDE; CHEMICAL ISCHEMIA; HORSERADISH-PEROXIDASE; NITRIC-OXIDE; IN-VITRO; CYANIDE; ACTIVATION; MECHANISM; RAMAN AB Cyanide (CN-) is a frequently used inhibitor of mitochondrial respiration due to its binding to the ferric heme a(3) of cytochrome c oxidase (CcO), As-isolated CcO oxidized cyanide to the cyanyl radical ((CN)-C-.) that was detected, using the ESR spin-trapping technique, as the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/(CN)-C-. radical adduct, The enzymatic conversion of cyanide to the cyanyl radical by CcO was time-dependent but not affected by azide (N-3(-)), The small but variable amounts of compound P present in the as-isolated CcO accounted for this one-electron oxidation of cyanide to the cyanyl radical, In contrast, as-isolated CcO exhibited little ability to catalyze the oxidation of azide, presumably because of azide's lower affinity for the CcO. However, the DMPO/N-.(3) radical adduct was readily detected when H2O2 was included in the system. The results presented here indicate the need to re-evaluate oxidative stress in mitochondria "chemical hypoxia" induced by cyanide or azide to account for the presence of highly reactive free radicals. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chen, YR (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 55 TC 22 Z9 22 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 24611 EP 24616 DI 10.1074/jbc.274.35.24611 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400025 PM 10455126 ER PT J AU Bing, ZY Reddy, SAG Ren, YS Qin, J Liao, WSL AF Bing, ZY Reddy, SAG Ren, YS Qin, J Liao, WSL TI Purification and characterization of the serum amyloid A3 enhancer factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACUTE-PHASE RESPONSE; RAT ALPHA-2-MACROGLOBULIN GENE; POLYMERASE-II TRANSCRIPTION; DNA-BINDING; NUCLEAR FACTOR; HEPATOMA-CELLS; FACTOR LSF; C/EBP-LIKE; PROTEIN AB Serum amyloid A (SAA) is a major acute-phase protein synthesized and secreted mainly by the liver. In response to acute inflammation, its expression may be induced up to 1000-fold, primarily as a result of a 200-fold increase in the rate of SAA gene transcription. We showed previously that cytokine-induced transcription of the SAA3 gene promoter requires a transcriptional enhancer that contains three functional elements: two CCAAT/enhancer-binding protein (C/EBP)-binding sites and a third site that interacts with a constitutively expressed transcription factor, SAA3 enhancer factor (SEF), Each of these binding sites as well as cooperation among their binding factors is necessary for maximum transcription activation by inflammatory cytokines. Deletion or site-specific mutations in the SEF-binding site drastically reduced SAA3 promoter activity, strongly suggesting that SEF is important in SAA3 promoter function. To further elucidate its role in the regulation of the SAA3 gene, we purified SEF from HeLa nuclear extracts to near homogeneity by using conventional liquid chromatography and DNA affinity chromatography, Ultraviolet cross-linking and Southwestern experiments indicated that SEF consisted of a single polypeptide with an apparent molecular mass of 65 kDa, Protein sequencing and antibody supershift experiments identified SEF as transcription factor LBP-1c/CP2/LSF. Cotransfection of SEF expression vector with SAA3-luciferase reporter resulted in approximately a 5-fold increase in luciferase activity. Interestingly, interleukin-1 treatment of SEF-transfected cells caused dramatic synergistic activation (31-fold) of the SAA3 promoter. In addition to its role in regulating SAA3 gene expression, we provide evidence that SEF could also bind in a sequence-specific manner to the promoters of the alpha(2)-macroglobulin and A alpha-fibrinogen genes and to an intronic enhancer of the human Wilm's tumor 1 gene, suggesting a functional role in the regulation of these genes. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Liao, WSL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Box 117, Houston, TX 77030 USA. FU NIAMS NIH HHS [AR 38858] NR 45 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 24649 EP 24656 DI 10.1074/jbc.274.35.24649 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400030 PM 10455131 ER PT J AU Reif, A Frohlich, LG Kotsonis, P Frey, A Bommel, HM Wink, DA Pfleiderer, W Schmidt, HHHW AF Reif, A Frohlich, LG Kotsonis, P Frey, A Bommel, HM Wink, DA Pfleiderer, W Schmidt, HHHW TI Tetrahydrobiopterin inhibits monomerization and is consumed during catalysis in neuronal NO synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; L-ARGININE; PROTEIN INHIBITOR; OXYGENASE DOMAIN; ESCHERICHIA-COLI; PROSTHETIC GROUP; BINDING-SITES; CENTER-DOT; ENZYME; HEME AB The biosynthesis of nitric oxide (NO) is catalyzed by homodimeric NO synthases (NOS), For unknown reasons, all NOS co-purify with substoichiometric amounts of (6R)-5,6,7,8-tetrahydrobiopterin (H(4)Bip) and require additional H(4)Bip for maximal activity. We examined the effects of H(4)Bip and pterin-derived inhibitors (antipterins) on purified neuronal NOS-I quaternary structure and H(4)Bip content. During L-arginine turnover, NOS-I dimers time dependently dissociated into inactive monomers, paralleled by a loss of enzyme-associated pterin. Dimer dissociation was inhibited when saturating levels of H(4)Bip were added during catalysis, Similar results were obtained with pterin-free NOS-I expressed in Escherichia coli. This stabilizing effect of H(4)Bip was mimicked by the anti-pterin 2-amino-4,6-dioxo-3,4,5,6,8,8a,9, 10-octahydro-oxazolo [1,2f]-pteridine (PHS-32), which also displaced NOS-associated H(4)Bip in a competitive manner. Surprisingly, H(4)Bip not only dissociated from NOS during catalysis, but was only partially recovered in the solute (50.0 +/- 16.5% of control at 20 min). NOS-associated H(4)Bip appeared to react with a NOS catalysis product to a derivative distinct from dihydrobiopterin or biopterin. Under identical conditions, reagent H(4)Bip was chemically stable and fully recovered (95.5 +/- 3.4% of control). A similar loss of both reagent and enzyme-bound H(4)Bip and dimer content was observed by NO generated from spermine NONO-ate. In conclusion, we propose a role for H(4)Bip as a dimer-stabilizing factor of neuronal NOS during catalysis, possibly by interfering with enzyme destabilizing products. C1 Univ Wurzburg, Dept Pharmacol & Toxicol, D-97078 Wurzburg, Germany. NCI, Bethesda, MD 20892 USA. Univ Konstanz, Fac Chem, D-78434 Constance, Germany. RP Reif, A (reprint author), Univ Wurzburg, Dept Pharmacol & Toxicol, Versbacher Str 9, D-97078 Wurzburg, Germany. RI Schmidt, Harald H. H. W./B-1549-2008 OI Schmidt, Harald H. H. W./0000-0003-0419-5549 NR 59 TC 90 Z9 92 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 24921 EP 24929 DI 10.1074/jbc.274.35.24921 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400066 PM 10455167 ER PT J AU Mueller, SC Ghersi, G Akiyama, SK Sang, QXA Howard, L Pineiro-Sanchez, M Nakahara, H Yeh, Y Chen, WT AF Mueller, SC Ghersi, G Akiyama, SK Sang, QXA Howard, L Pineiro-Sanchez, M Nakahara, H Yeh, Y Chen, WT TI A novel protease-docking function of integrin at invadopodia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MALIGNANT MELANOMA-CELLS; FIBRONECTIN RECEPTOR; MOLECULAR-CLONING; TYROSINE PHOSPHORYLATION; ONCOGENIC TRANSFORMATION; MONOCLONAL-ANTIBODIES; MEMBRANE GLYCOPROTEIN; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; ADHESION RECEPTORS AB Invadopodia are membrane extensions of aggressive tumor cells that function in the activation of membrane-bound proteases occurring during tumor cell invasion. We explore a novel and provocative activity of integrins in docking proteases to sites of invasion, termed invadopodia. In the absence of collagen, alpha(3)beta(1) integrin and the gelatinolytic enzyme, seprase, exist as nonassociating membrane proteins. Type I collagen substratum induces the association of alpha(3)beta(1) integrin with seprase as a complex on invadopodia. The results show that alpha(3)beta(1) integrin is a docking protein for seprase to form functional invadopodia, In addition, alpha(5)beta(1) integrin may participate in the adhesion process necessary for invadopodial formation. Thus, alpha(3)beta(1) and alpha(5)beta(1) integrins play major organizational roles in the adhesion and formation of invadopodia, promoting invasive cell behavior. C1 SUNY Stony Brook, Dept Med, Div Med Oncol, Stony Brook, NY 11794 USA. Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Florida State Univ, Dept Chem, Tallahassee, FL 32306 USA. RP Chen, WT (reprint author), SUNY Stony Brook, Dept Med, Div Med Oncol, HSC T-17,Rm 080, Stony Brook, NY 11794 USA. RI Howard, Linda/B-2463-2009; OI HOWARD, LINDA/0000-0003-4760-7996; Ghersi, Giulio/0000-0001-7250-9808 FU NCI NIH HHS [R21CA62232, R01CA61273, R01CA39077] NR 28 TC 143 Z9 149 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 24947 EP 24952 DI 10.1074/jbc.274.35.24947 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400070 PM 10455171 ER PT J AU Ulianich, L Suzuki, K Mori, A Nakazato, M Pietrarelli, M Goldsmith, P Pacifico, F Consiglio, E Formisano, S Kohn, LD AF Ulianich, L Suzuki, K Mori, A Nakazato, M Pietrarelli, M Goldsmith, P Pacifico, F Consiglio, E Formisano, S Kohn, LD TI Follicular thyroglobulin (TG) suppression of thyroid-restricted genes involves the apical membrane asialoglycoprotein receptor and TG phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-I; HEPATIC LECTIN-1 SUBUNIT; PROMOTER OKADAIC ACID; GROWTH-FACTOR-I; THYROTROPIN RECEPTOR; TUMOR PROMOTER; RAT; EXPRESSION; PROTEIN; CELLS AB Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes (Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D. S., Kimura, S., Katoh, R., Kawaoi, A., and Kohn, L, D. (1997) Proc. Natl. Acad. Sci. U. S. A. 95, 8251-8256). The ability of highly purified 27, 19, or 12 S follicular TG to suppress thyroid-restricted gene expression correlates with their ability to bind to FRTL-5 thyrocytes and is inhibited by a specific antibody to the thyroid apical membrane asialoglycoprotein receptor (ASGPR), which is related to the ASGPR of liver cells. Phosphorylating serine/threonine residues of TG, by autophosphorylation or protein kinase A, eliminates TG suppression and enhances transcript levels of the thyroid-restricted genes 2-fold in the absence of a change in TG binding to the ASGPR. Follicular TG suppression of thyroid-restricted genes is thus mediated by the ASPGR on the thyrocyte apical membrane and regulated by a signal system wherein phosphorylation of serine/threonine residues on the bound ligand is an important component. These data provide a hitherto unsuspected role for the ASGPR in transcriptional signaling, aside from its role in endocytosis. They establish a functional role for phosphorylated serine/threonine residues on the TG molecule. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Federico II Med Sch, CNR, Ctr Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy. Federico II Med Sch, Dipartimento Biol & Patol Cellulare & Mol L Calif, I-80131 Naples, Italy. RP Kohn, LD (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 9C101B, Bethesda, MD 20892 USA. OI Pacifico, Francesco Maria/0000-0001-9563-3596 NR 59 TC 42 Z9 42 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 25099 EP 25107 DI 10.1074/jbc.274.35.25099 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400089 PM 10455190 ER PT J AU Liu, XB Singh, BB Ambudkar, IS AF Liu, XB Singh, BB Ambudkar, IS TI ATP-dependent activation of K-Ca and ROMK-type K-ATP channels in human submandibular gland ductal cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PAROTID ACINAR-CELLS; TRANSMEMBRANE CONDUCTANCE REGULATOR; EXTRACELLULAR ATP; SMOOTH-MUSCLE; HSG-PA; RAT; RECEPTORS; LINE; PURINOCEPTORS; LOCALIZATION AB [Ca2+](i) and membrane current were measured in human submandibular gland ductal (HSG) cells to determine the regulation of salivary cell function by ATP, 1-10 mu M ATP activated internal Ca2+ release, outward Ca2+-dependent K+ channel (K-Ca), and inward store-operated Ca2+ current (I-SOC). The subsequent addition of 100 mu M ATP activated an inwardly rectifying K+ current, without increasing [Ca2+](i). The K+ current was also stimulated by ATP in cells treated with thapsigargin in a Ca2+-free medium and was blocked by glibenclamide and tolbutamide, but not by charybdotoxin, This suggests the involvement of a Ca2+-independent, sulfonylurea-sensitive K+ channel (K-ATP). UTP mimicked the low [ATP] effects, while benzoyl-ATP activated internal Ca2+ release, a Ca2+ influx pathway, and K-Ca. Thus, ATP acts via P-2U (P2Y(2)) and P-2Z (P2X(7)) receptors to increase [Ca2+](i) and activate K-Ca, but not K-ATP. Importantly, (i) ROMK1 and the cystic fibrosis transmembrane regulator protein (but not SUR1, SUR2A, or SUR2B) and (ii) cAMP-stimulated Cl- and K+ currents were detected in HSG cells. These data demonstrate for the first time that a ROMK-type K-ATP channel is present in salivary gland duct cells that is regulated by extracellular ATP and possibly by the cystic fibrosis transmembrane regulator. This reveals a potentially novel mechanism for K+ secretion in these cells. C1 NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1N-113, Bethesda, MD 20892 USA. OI Singh, Brij/0000-0003-0535-5997 NR 36 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 25121 EP 25129 DI 10.1074/jbc.274.35.25121 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400092 PM 10455193 ER PT J AU Williamson, LC Bateman, KE Clifford, JCM Neale, EA AF Williamson, LC Bateman, KE Clifford, JCM Neale, EA TI Neuronal sensitivity to tetanus toxin requires gangliosides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL-CORD NEURONS; RAT-BRAIN; SPHINGOLIPID BIOSYNTHESIS; NEUROTRANSMITTER RELEASE; PC12 CELLS; BOTULINUM; BINDING; NEUROTOXINS; INHIBITION; MEMBRANES AB Tetanus toxin produces spastic paralysis in situ by blocking inhibitory neurotransmitter release in the spinal cord. Although di- and trisialogangliosides bind tetanus toxin, their role as productive toxin receptors remains unclear. We examined toxin binding and action in spinal cord cell cultures grown in the presence of fumonisin B-1, an inhibitor of ganglioside synthesis. Mouse spinal cord neurons grown for 3 weeks in culture in 20 mu M fumonisin B-1 develop dendrites, axons, and synaptic terminals similar to untreated neurons, even though thin layer chromatography shows a greater than 90% inhibition of ganglioside synthesis. Absence of tetanus and cholera toxin binding by toxin-horseradish peroxidase conjugates or immunofluorescence further indicates loss of mono- and polysialogangliosides. In contrast to control cultures, tetanus toxin added to fumonisin B-1-treated cultures does not block potassium-stimulated glycine release, inhibit activity-dependent uptake of FM1-43, or abolish immunoreactivity for vesicle-associated membrane protein, the toxin substrate. Supplementing fumonisin B-1-treated cultures with mixed brain gangliosides completely restores the ability of tetanus toxin to bind to the neuronal surface and to block neurotransmitter release. These data demonstrate that fumonisin B-1 protects against toxin-induced synaptic blockade and that gangliosides are a necessary component of the receptor mechanism for tetanus toxin. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Neale, EA (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 44 TC 38 Z9 39 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 27 PY 1999 VL 274 IS 35 BP 25173 EP 25180 DI 10.1074/jbc.274.35.25173 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400099 PM 10455200 ER PT J AU Borchers, C Parker, CE Deterding, LJ Tomer, KB AF Borchers, C Parker, CE Deterding, LJ Tomer, KB TI Preliminary comparison of precursor scans and liquid chromatography-tandem mass spectrometry on a hybrid quadrupole time-of-flight mass spectrometer SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 15th Montreux Symposium on LC-MS, SFC-MS, CE-MS and MS-MS CY NOV 11-13, 1998 CL MONTREUX, FRANCE DE mass spectrometry; peptides; substance P; HIV-p24 ID SELECTIVE DETECTION; COMPLEX-MIXTURES; IDENTIFICATION; PEPTIDES AB Recent mass spectrometry instrumentation developments include the appearance of novel hybrid tandem instrumentation, Q-TOF, consisting of a quadrupole mass analyzer (MS1) and a time-of-flight (TOF) analyzer. The TOF analyzer is not scanned, but collects all fragment ions entering the analyzer at a given time. Thus, the typical precursor scan experiment cannot be performed. Instead, a full MS-MS spectrum can be acquired for each mass passed by MS1. Appropriate data manipulation, i.e. extracted ion current chromatograms, can correlate specific fragment ion formation to the parent ion. Precursor scanning and LC-MS-MS are compared on a Q-TOF instrument for the determination of protein modifications, including acetylation and phosphorylation. Model peptides used for phosphopeptide detection were generated from a mixture of p-casein. Model acetylated peptides were generated from a mixture of acetylated substance P1-9 and substance P1-11. The results were then applied to a more complex mixture, a digest of HIV-p24. Results indicate that precursor scanning is useful for screening, but that LC-MS-MS has a sensitivity advantage and is less susceptible to suppression effects. LC-MS-MS, therefore, appears to be better for the detection of trace components in complex mixtures. (C) 1999 Elsevier Science BN. All rights reserved. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 13 TC 59 Z9 60 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 27 PY 1999 VL 854 IS 1-2 BP 119 EP 130 DI 10.1016/S0021-9673(99)00479-3 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 233UG UT WOS:000082445200012 PM 10497933 ER PT J AU de Alba, E De Vries, L Farquhar, MG Tjandra, N AF de Alba, E De Vries, L Farquhar, MG Tjandra, N TI Solution structure of human GAIP (G alpha interacting protein): A regulator of G protein signaling SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE GAIP; G protein; NMR; dipolar couplings; signaling pathway ID GTPASE-ACTIVATING PROTEIN; RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE MEDIUM; HETEROTRIMERIC G-PROTEINS; TRIPLE-RESONANCE NMR; ACTIVITY IN-VITRO; ORIENTED MACROMOLECULES; CORE DOMAIN; RGS PROTEIN; TRANSITION-STATE AB The solution structure of the human protein GAIP (G alpha interacting protein), a regulator of G protein signaling, has been determined by NMR techniques. Dipolar couplings of the oriented protein in two different liquid crystal media have been used in the structure calculation. The solution structure of GAIP is compared to the crystal structure of an homologous protein from rat (RGS4) complexed to the alpha-subunit of a G protein. Some of RGS4 residues involved in the G alpha-RGS binding interface have similar orientations in GAIP (free form), indicating that upon binding these residues do not suffer conformational rearrangements, and therefore, their role does not seem to be restricted to G alpha interaction but also to RGS folding and stability. We suggest that other structural differences between the two proteins may be related to the process of binding as well as to a distinct efficiency in their respective GTPase activating function. (C) 1999 Academic Press. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Div Cellular & Mol Med, La Jolla, CA 92093 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 56 TC 56 Z9 57 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 27 PY 1999 VL 291 IS 4 BP 927 EP 939 DI 10.1006/jmbi.1999.2989 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 230FM UT WOS:000082241200013 PM 10452897 ER PT J AU Drotschmann, K Clark, AB Kunkel, TA AF Drotschmann, K Clark, AB Kunkel, TA TI Mutator phenotypes of common polymorphisms and missense mutations in MSH2 SO CURRENT BIOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; GERMLINE MUTATIONS; CELL-LINES; HMLH1 GENES; HMSH2; HNPCC; DEFECTS; MLH1; RISK AB Hereditary non-polyposis colorectal cancer (HNPCC) is associated with germline mutations in the DNA mismatch repair gene hMSH2 [1], the human homologue of the Escherichia coli MutS gene. These are mostly nonsense, frameshift or deletion mutations that result in loss of intact protein and complete inactivation of DNA mismatch repair. However, cancer is also associated with hMSH2 missense mutations that are merely inferred to be deleterious because they result in non-conservative substitutions of amino acids that are highly conserved among MutS family proteins. Moreover, sequence polymorphisms exist in hMSH2 that also change conserved amino acids but whose functional consequences and relationship to cancer are uncertain. Here, we show that yeast strains harboring putative equivalents of three hMSH2 polymorphisms have elevated mutation rates. Mutator effects were also observed for yeast equivalents of hMSH2 missense mutations found in HNPCC families and in an early onset colon tumor. Several distinct phenotypes were observed, indicating that these missense mutations have differential effects on MSH2 function(s). The results suggest that cancer may be associated with even partial loss of hMSH2 function and they are consistent with the hypothesis that polymorphisms in hMSH2 might predispose humans to disease. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 23 TC 45 Z9 49 U1 0 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 26 PY 1999 VL 9 IS 16 BP 907 EP 910 DI 10.1016/S0960-9822(99)80396-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 230UJ UT WOS:000082268500023 PM 10469597 ER PT J AU Ponting, CP Hofmann, K Bork, P AF Ponting, CP Hofmann, K Bork, P TI A latrophilin/CL-1-like GPS domain in polycystin-1 SO CURRENT BIOLOGY LA English DT Letter ID KIDNEY-DISEASE; PSI-BLAST; PROTEIN; PKD1; RECEPTOR; GENE; EXOCYTOSIS; REVEALS; ENCODES; FAMILY C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. MEMOREC Stoffel GmbH, D-50829 Cologne, Germany. European Mol Biol Lab, D-69012 Heidelberg, Germany. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. RP Ponting, CP (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Hofmann, Kay/D-6714-2011; Bork, Peer/F-1813-2013 OI Hofmann, Kay/0000-0002-2289-9083; Bork, Peer/0000-0002-2627-833X NR 25 TC 81 Z9 83 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 26 PY 1999 VL 9 IS 16 BP R585 EP R588 DI 10.1016/S0960-9822(99)80379-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 230UJ UT WOS:000082268500006 PM 10469603 ER PT J AU Neamati, N Turpin, JA Winslow, HE Christensen, JL Williamson, K Orr, A Rice, WG Pommier, Y Garofalo, A Brizzi, A Campiani, G Fiorini, I Nacci, V AF Neamati, N Turpin, JA Winslow, HE Christensen, JL Williamson, K Orr, A Rice, WG Pommier, Y Garofalo, A Brizzi, A Campiani, G Fiorini, I Nacci, V TI Thiazolothiazepine inhibitors of HIV-1 integrase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYCONDENSED HETEROCYCLES; TYPE-1 INTEGRASE; ACTIVE-SITE; ZINC FINGERS; DIVALENT-CATIONS; CATALYTIC DOMAIN; REPLICATION; DERIVATIVES; DISCOVERY AB A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purified IN than those containing only one carbonyl group. Substitution with electron-donating or -withdrawing groups did not enhance nor abolish potency against purified IN. By contrast, compounds with a naphthalene ring system showed enhanced potency, suggesting that a hydrophobic pocket in the IN active site might accommodate an aromatic system rather than a halogen. The position of sulfur in the thiazole ring appears important for potency against IN, as its replacement with an oxygen or carbon abolished activity. Further extension of the thiazole ring diminished potency. Compounds 1, 19, and 20 showed antiviral activity and inhibited IN within similar concentrations. These compounds inhibited IN when Mn2+ or Mg2+ was used as cofactor. None of these compounds showed detectable activities against HIV-1 reverse transcriptase, protease, virus attachment, or nucleocapsid protein zinc fingers. Therefore, thiazolothiazepines are potentially important lead compounds for development as inhibitors of IN and HIV replication. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD 21701 USA. Achill Pharmaceut, Frederick, MD 21701 USA. Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy. RP Neamati, N (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RI garofalo, antonio/E-9964-2011; OI garofalo, antonio/0000-0003-1337-5509 NR 42 TC 76 Z9 78 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 26 PY 1999 VL 42 IS 17 BP 3334 EP 3341 DI 10.1021/jm990047z PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 230FN UT WOS:000082241300016 PM 10464020 ER PT J AU Norton, JA Fraker, DL Alexander, HR Venzon, DJ Doppman, JL Serrano, J Goebel, SU Peghini, PL Roy, PK Gibril, F Jensen, RT AF Norton, JA Fraker, DL Alexander, HR Venzon, DJ Doppman, JL Serrano, J Goebel, SU Peghini, PL Roy, PK Gibril, F Jensen, RT TI Surgery to cure the Zollinger-Ellison syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ENDOCRINE NEOPLASIA TYPE-1; DUODENAL GASTRINOMAS; SURGICAL-MANAGEMENT; PROVOCATIVE TESTS; LONG-TERM; RESECTION; LOCALIZATION; SECRETIN; EXCISION AB Background and Methods The role of surgery in patients with the Zollinger-Ellison syndrome is controversial. To determine the efficacy of surgery in patients with this syndrome, we followed 151 consecutive patients who underwent laparotomy between 1981 and 1998. Of these patients, 123 had sporadic gastrinomas and 28 had multiple endocrine neoplasia type 1 with an imaged tumor of at least 3 cm in diameter. Tumor-localization studies and functional localization studies were performed routinely. All patients underwent surgery according to a similar operative protocol, and all patients who had surgery after 1986 underwent duodenotomy. Results The 151 patients underwent 180 exploratory operations. The mean (+/-SD) follow-up after the first operation was 8+/-4 years. Gastrinomas were found in 140 of the patients (93 percent), including all of the last 81 patients to undergo surgery. The tumors were located in the duodenum in 74 patients (49 percent) and in the pancreas in 36 patients (24 percent); however, primary tumors were found in lymph nodes in 17 patients (11 percent) and in another location in 13 patients (9 percent). The primary location was unknown in 24 patients (16 percent). Among the patients with sporadic gastrinomas, 34 percent were free of disease at 10 years, as compared with none of the patients with multiple endocrine neoplasia type 1. The overall 10-year survival rate was 94 percent. Conclusions All patients with the Zollinger-Ellison syndrome who do not have multiple endocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure. (N Engl J Med 1999;341:635-44.) (C) 1999, Massachusetts Medical Society. C1 NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. NCI, Surg Metab Sect, Surg Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, Digest Dis Branch, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 40 TC 273 Z9 281 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 26 PY 1999 VL 341 IS 9 BP 635 EP 644 DI 10.1056/NEJM199908263410902 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 229JY UT WOS:000082192500002 PM 10460814 ER PT J AU Ferris, FL Davis, MD Aiello, LM AF Ferris, FL Davis, MD Aiello, LM TI Treatment of diabetic retinopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RETINAL MICROANEURYSM COUNTS; ALDOSE REDUCTASE INHIBITORS; GALACTOSE-FED DOGS; EYE-CARE; MICROVASCULAR COMPLICATIONS; VITREOUS SURGERY; COST-EFFECTIVENESS; INSULIN INFUSION; HARD EXUDATE; RISK-FACTORS C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Ferris, FL (reprint author), Div Biometry & Epidemiol, 31 Ctr Dr,MSC 2510,Bldg 31,Rm 6A52, Bethesda, MD 20892 USA. EM rickferris@nei.nih.gov NR 132 TC 101 Z9 107 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 26 PY 1999 VL 341 IS 9 BP 667 EP 678 DI 10.1056/NEJM199908263410907 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 229JY UT WOS:000082192500007 PM 10460819 ER PT J AU Abati, A Merino, M AF Abati, A Merino, M TI Loss of heterozygosity analysis to diagnose adrenal cortical carcinoma - Are we there yet? Reply SO CANCER CYTOPATHOLOGY LA English DT Editorial Material C1 NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, Bldg 10,Room 2A19,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 1999 VL 87 IS 4 BP 176 EP 177 DI 10.1002/(SICI)1097-0142(19990825)87:4<176::AID-CNCR2>3.0.CO;2-6 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 226UP UT WOS:000082041000002 ER PT J AU Abati, A Sanjuan, X Wilder, A Linehan, WM Hewitt, SM Merino, MJ AF Abati, A Sanjuan, X Wilder, A Linehan, WM Hewitt, SM Merino, MJ TI Utilization of microdissection and the polymerase chain reaction for the diagnosis of adrenal cortical carcinoma in fine-needle aspiration cytology SO CANCER CYTOPATHOLOGY LA English DT Article DE loss of heterozygosity; microdissection; p53; 1p; von Hippel-Lindau; adrenal cortical carcinoma; adrenal cortical lesions ID ADRENOCORTICAL CARCINOMA; GENE DELETION; SPECIMENS AB BACKGROUND, Loss of heterozygosity (LOH) for several tumor suppressor genes (including loci on 3p, 1, and 17p,) has been documented in surgical specimens of adrenal cortical carcinomas (ACCA) without accompanying losses in benign hyperplastic and adenomatous adrenal cortical lesions (ACL). This disparate pattern of LOH raises the possibility of exploitation of these differences for diagnostic utilization. Cytologic differentiation of benign versus malignant ACL may be impossible based solely on fine-needle aspiration (FNA) material. The authors attempted to extrapolate the genetic findings on surgical specimens to FNA specimens of ACL to determine whether LOH studies could be utilized as a definitive diagnostic tool. METHODS. Microdissection of archival material was performed on FNAs of ten ACCAs (stained with the Papanicolaou and Diff-Quik stains) with corresponding histologic material (stained with hematoxylin and eosin), one FNA of a benign ACL, and three touch preparations of benign adrenal cortex. LOH analysis was performed by polymerase chain reaction (PCR) with flanking markers for the following putative tumor suppressor genes: p53 (17p13; TP53), 1p (1p36; D1S165), and the von Hippel-Lindau gene at 3p25 (D3S1038 and D3S1110). RESULTS. Similar results were obtained with cytologic and histologic material. As expected, benign ACL showed no LOH for the markers examined. Of the informative ACCA cases, 70% showed LOH for at least 1 of the 3 markers tested on both FNA and histologic samples. For all cases with amplifiable DNA, there was a 100% concordance rate for LOH between cytologic and histologic material, with at least 7 of the 10 cytologic samples originating from metastatic lesions and all of the surgical material originating from the primary adrenal neoplasm. CONCLUSIONS. The results of this study suggest that the combination of microdissection and PCR for LOH of p5, 1p, and 3p25 from FNA material has the potential to be utilized to distinguish ACCA from benign ACL in informative cases. It also shows a 100% concordance rate between metastatic and primary ACCAs for the losses observed, a finding that can be extremely useful for the definitive identification of metastatic lesions. Archival cytologic preparations of ACCA are a reliable source of DNA for LOH studies. [See editorial counterpoint on pages 173-5 and reply to counterpoint on pages 176-7, this issue.] (C) 1999 American Cancer Society. C1 NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, Bldg 10,Room 2A19,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 17 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 1999 VL 87 IS 4 BP 231 EP 237 DI 10.1002/(SICI)1097-0142(19990825)87:4<231::AID-CNCR11>3.0.CO;2-A PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 226UP UT WOS:000082041000011 PM 10455212 ER PT J AU Filie, AC Chiesa, A Bryant, BR Merino, MJ Sobel, ME Abati, A AF Filie, AC Chiesa, A Bryant, BR Merino, MJ Sobel, ME Abati, A TI The tall cell variant of papillary carcinoma of the thyroid - Cytologic features and loss of heterozygosity of metastatic and/or recurrent neoplasms and primary neoplasms SO CANCER CYTOPATHOLOGY LA English DT Article DE thyroid; papillary carcinoma; tall cell variant; loss of heterozygosity; cytology; metastasis; recurrence; p53; chromosome 1 ID POLYMERASE-CHAIN-REACTION; FINE-NEEDLE ASPIRATION; MICRODISSECTION; CYTOPATHOLOGY; CANCER AB BACKGROUND. The Tall cell variant of papillary carcinoma of the thyroid (TCV) is characterized by the proliferation of oxyphilic, tall, columnar cells with a height-to-width ratio of at least 2:1. TCV exhibits more aggressive clinical behavior than conventional thyroid papillary carcinoma (CPC). Cytologic features suggestive of TCV have been described in fine-needle aspiration material from primary tumors. Similarly, loss of heterozygosity (LOH) for chromosome 1 (D1S243) and the p53 gene (TP53) have been reported in TCV but not in CPC, thus making exploitation of this genetic feature a potential tool for molecular discrimination between these two neoplasms. METHODS. Cytology samples of metastatic and/or recurrent neoplasms (M/R) (12 cases) and 7 cases of primary TCV obtained from 12 patients were evaluated. The cytologic findings of these cases were compared with previously published findings. Microdissection and polymerase chain reaction for LOH for chromosome 1 and p53 (D1S243 and TP53 markers) were performed on cytologic smears from 6 cases of MIR tumors and 3 cases of primary tumors. RESULTS. More then 50% of M/R showed atypical follicular cells with enlarged nuclei, granular chromatin, nuclear grooves, pseudoinclusions, and abundant finely granular cytoplasm. Cells were disposed in monolayers (58%) and papillary clusters (50%). Similar findings were present in cases of primary TCV. LOH studies showed that 4 of 6 M/R were noninformative and 2 of 3 cases of primary TCV were informative for the D1S243 marker; however, in contrast with previously published reports, no LOH was detected for the markers evaluated. CONCLUSIONS. MIR and primary TCV have similar cytologic features. Additional studies of larger series of M/R and primary TCV should be performed to delineate further any potential application of LOH for chromosome 1 and the p53 gene as a tool for diagnosing TCV with cytologic preparations. (C) 1999 American Cancer Society. C1 NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Mol Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Filie, AC (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, 10 Ctr Dr,Bldg 10,R2A19, Bethesda, MD 20892 USA. NR 18 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 1999 VL 87 IS 4 BP 238 EP 242 DI 10.1002/(SICI)1097-0142(19990825)87:4<238::AID-CNCR12>3.0.CO;2-N PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 226UP UT WOS:000082041000012 PM 10455213 ER PT J AU Miotti, PG Taha, TET Kumwenda, NI Broadhead, R Mtimavalye, LAR Van der Hoeven, L Chiphangwi, JD Liomba, G Biggar, RJ AF Miotti, PG Taha, TET Kumwenda, NI Broadhead, R Mtimavalye, LAR Van der Hoeven, L Chiphangwi, JD Liomba, G Biggar, RJ TI HIV transmission through breastfeeding - A study in Malawi SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; BREAST-MILK; POSTNATAL TRANSMISSION; HIV-1-INFECTED WOMEN; P24 ANTIGEN; MOTHER; TYPE-1; INFECTION; COHORT AB Context Understanding the risk of human immunodeficiency virus (HIV) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations. Objective To measure the frequency, timing, and risk factors of HIV transmission through breast milk. Design Prospective cohort study conducted between 1994 and 1997, with follow-up of infants through 24 months of age. Setting Postnatal clinic of tertiary care hospital, Blantyre, Malawi. Participants A total of 672 infants (HIV-negative at birth) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy. Main Outcome Measure Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission, using proportional hazard models to derive risk ratios (RRs) and 95% confidence intervals (Cls). Results Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped. The cumulative infection rate while breastfeeding, from month 1 to the end of months 5, 11, 17, and 23, was 3.5%, 7.0%, 8.9%, and 10.3 %, respectively. Incidence per month was 0.7% during age 1 to 5 months, 0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P = .01 for trend). The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR, 0.44; 95% CI, 0.23-0.84), Conclusions Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding, which should be considered in formulating breastfeeding policy recommendations. C1 Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Malawi Coll Med, Blantyre, Malawi. NCI, NIH, Bethesda, MD USA. RP Miotti, PG (reprint author), NIAID, Div Aids, NIH, Room 4109,6700 B Rockledge Dr,MSC 7626, Bethesda, MD 20892 USA. FU NIAID NIH HHS [N01-AI-35173-117] NR 33 TC 218 Z9 227 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 25 PY 1999 VL 282 IS 8 BP 744 EP 749 DI 10.1001/jama.282.8.744 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 228CJ UT WOS:000082118800025 PM 10463709 ER PT J AU Itokawa, K Sora, I Schindler, CW Itokawa, M Takahashi, N Uhl, GR AF Itokawa, K Sora, I Schindler, CW Itokawa, M Takahashi, N Uhl, GR TI Heterozygous VMAT2 knockout mice display prolonged QT intervals: possible contributions to sudden death SO MOLECULAR BRAIN RESEARCH LA English DT Article DE vesicular monoamine transporter 2; transgenic mouse; electrocardiogram; telemetry; prolonged QT ID VESICULAR MONOAMINE TRANSPORTER-2; AMPHETAMINE; TOXICITY AB Heterozygous knockout (KO) mice with half of wild-type levels of expression of the vesicular monoamine transporter (VMAT2) can suddenly die in midlife. To seek mechanisms for this sudden death, we have examined electrocardiogram (ECG) data telemetered from freely-moving heterozygote and wild-type littermate mice. Many ECG parameters were indistinguishable in mice of these two strains. However, heterozygous mice displayed prolonged QT intervals. These findings provide likely contributions to differences in vulnerability to lethal arrhythmias in these animals, and a candidate gene for contributions to human interindividual differences in vulnerability to cardiac arrhythmias. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Preclin Pharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA. Osaka Univ, Grad Sch Med, Dept Neurol, Suita, Osaka 5650871, Japan. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. NR 14 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG 25 PY 1999 VL 71 IS 2 BP 354 EP 357 DI 10.1016/S0169-328X(99)00194-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 239KF UT WOS:000082766700024 ER PT J AU Dianov, GL Jensen, BR Kenny, MK Bohr, VA AF Dianov, GL Jensen, BR Kenny, MK Bohr, VA TI Replication protein A stimulates proliferating cell nuclear antigen-dependent repair of abasic sites in DNA by human cell extracts SO BIOCHEMISTRY LA English DT Article ID BASE EXCISION-REPAIR; BINDING-PROTEIN; SACCHAROMYCES-CEREVISIAE; POLYMERASE-DELTA; PCNA; REQUIREMENT; FEN-1; IDENTIFICATION; RECONSTITUTION; SEQUENCE AB Base excision repair (BER) pathway is the major cellular process for removal of endogenous base lesions and apurinic/apyrimidinic (AP) sites in DNA. There are two base excision repair subpathways in mammalian cells, characterized by the number of nucleotides synthesized into the excision patch. They are the "single-nucleotide'' (one nucleotide incorporated) and the "long-patch" (several nucleotides incorporated) BER pathways. Proliferating cell nuclear antigen (PCNA) is known to be an essential factor in long-patch base excision repair. We have studied the role of replication protein A (RPA) in PCNA-dependent, long-patch BER of AP sites in human cell extracts. PCNA and RPA were separated from the other BER proteins by fractionation of human whole-cell extract on a phosphocellulose column. The protein fraction PC-FII (phosphocellulose fraction II), which does not contain RPA and PCNA but otherwise contains all core BER proteins required for PCNA-dependent EER (AP endonuclease, DNA polymerases delta, beta and DNA ligase, and FEN1 endonuclease), had reduced ability to repair plasmid DNA containing AP sites. Purified PCNA or RPA, when added separately, could only partially restore the PC-FII repair activity of AP sites. However, additions of both proteins together greatly stimulated AP site repair by PC-FII. These results demonstrate a role for RPA in PCNA-dependent EER of AP sites. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10467 USA. RP Dianov, GL (reprint author), NIA, Mol Genet Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NCI NIH HHS [CA71612] NR 35 TC 45 Z9 46 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 24 PY 1999 VL 38 IS 34 BP 11021 EP 11025 DI 10.1021/bi9908890 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 232AB UT WOS:000082342600013 PM 10460157 ER PT J AU Vaisman, A Lim, SE Patrick, SM Copeland, WC Hinkle, DC Turchi, JJ Chaney, SG AF Vaisman, A Lim, SE Patrick, SM Copeland, WC Hinkle, DC Turchi, JJ Chaney, SG TI Effect of DNA polymerases and high mobility group protein 1 on the carrier ligand specificity for translesion synthesis past platinum-DNA adducts SO BIOCHEMISTRY LA English DT Article ID ANTICANCER DRUG CISPLATIN; INTRASTRAND CROSS-LINK; MAMMALIAN-CELLS; IN-VITRO; REVERSE-TRANSCRIPTASE; BYPASS REPLICATION; CATALYTIC SUBUNIT; MITOCHONDRIAL-DNA; CRYSTAL-STRUCTURE; NUCLEAR PROTEINS AB Translesion synthesis past Pt-DNA adducts can affect both the cytotoxicity and mutagenicity of the platinum adducts, We have shown previously that the extent of replicative bypass in vivo is influenced by the carrier ligand of platinum adducts. The specificity of replicative bypass may be determined by the DNA polymerase complexes that catalyze translesion synthesis past Pt-DNA adducts and/or by DNA damage-recognition proteins that bind to the Pt-DNA adducts and block translesion replication. In the present study, primer extension on DNA templates containing site-specifically placed cisplatin. oxaliplatin. JM216; or chlorodiethylenetriamine-Pt adducts revealed that the eukaryotic DNA polymerases beta, zeta, gamma, and human immunodeficiency virus type I reverse transcriptase (HIV-I RT) had a similar specificity for translesion synthesis past Pt-DNA adducts (dien much greater than oxaliplatin greater than or equal to cisplatin > JM316). Primer extension assays performed in the presence of high mobility group protein 1 (HMG 1), which is known to recognize cisplatin-damaged DNA, revealed that inhibition of translesion synthesis by HMG1 also depended on the carrier ligand of the Pt-DNA adduct (cisplatin > oxaliplarin = JM216 much greater than dien), These data were consistent with the results of gel-shift experiments showing similar differences in the affinity of HMG1 For DNA modified with the different platinum adducts. Our studies show that both DNA polymerases and damage recognition proteins can impart specificity to replicative bypass of Pt-DNA adducts. This information may serve as a model for further studies of translesion synthesis. C1 Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. Wright State Univ, Sch Med, Dept Biochem & Mol Biol, Dayton, OH 45435 USA. RP Chaney, SG (reprint author), Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. RI Vaisman, Alexandra/C-3766-2013; Turchi, John/B-5807-2015 OI Vaisman, Alexandra/0000-0002-2521-1467; Turchi, John/0000-0001-5375-2992 FU NCI NIH HHS [CA64374]; NIGMS NIH HHS [GM55826] NR 50 TC 106 Z9 109 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 24 PY 1999 VL 38 IS 34 BP 11026 EP 11039 DI 10.1021/bi9909187 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 232AB UT WOS:000082342600014 PM 10460158 ER PT J AU Valenzuela, JG Francischetti, IMB Ribeiro, JMC AF Valenzuela, JG Francischetti, IMB Ribeiro, JMC TI Purification, cloning, and synthesis of a novel salivary anti-thrombin from the mosquito Anopheles albimanus SO BIOCHEMISTRY LA English DT Article ID BLOOD; INHIBITORS; PROTEINS; ANIMALS; GENERATION; PEPTIDES; ENZYMES; APYRASE; MOTIF AB An anti-thrombin peptide (anophelin) was isolated from the salivary glands of the mosquito Anopheles albimanus through molecular sieving and reverse-phase high-performance liquid chromatography. The purified peptide inhibited thrombin-induced platelet aggregation, thrombin esterolytic activity on a synthetic substrate, and thrombin cleavage of fibrinogen. The purified anti-thrombin had a molecular mass of 6342.4 Da. Its amino terminus was blocked, but internal sequence yielded three peptide sequences, which were used to design oligonucleotide probes for polymerase chain reaction amplification of salivary gland cDNA and isolation of the full-length clone. Analysis of the sequence of anophelin shows no similarities to any other anti-thrombin peptides. Anophelin was successfully synthesized and characterized to be a tight-binding, specific, and novel inhibitor of thrombin. C1 NIAID, Parasit Dis Lab, Sect Med Entomol, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Parasit Dis Lab, Sect Med Entomol, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 23 TC 67 Z9 73 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 24 PY 1999 VL 38 IS 34 BP 11209 EP 11215 DI 10.1021/bi990761i PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 232AB UT WOS:000082342600034 PM 10460178 ER PT J AU Cardillo, C Nambi, SS Kilcoyne, CM Choucair, WK Katz, A Quon, MJ Panza, JA AF Cardillo, C Nambi, SS Kilcoyne, CM Choucair, WK Katz, A Quon, MJ Panza, JA TI Insulin stimulates both endothelin and nitric oxide activity in the human forearm SO CIRCULATION LA English DT Article DE insulin; endothelin; nitric oxide; vasodilation; receptors ID SKELETAL-MUSCLE VASODILATION; IN-VIVO; RECEPTOR ANTAGONIST; BLOOD-PRESSURE; RELEASE; CELLS; POTENT; HYPERINSULINEMIA; SENSITIVITY; EXPRESSION AB Background-The mechanism of the hemodynamic effect of insulin in the skeletal muscle circulation has not been fully elucidated. The purpose of this study was to assess whether the hemodynamic response to insulin involves the concurrent release of endothelin (ET-1) and nitric oxide (NO), 2 substances with opposing vasoactive properties, Methods and Results-Bioactivity of ET-1 and NO was assessed without insulin and during insulin infusion in the forearm circulation of healthy subjects by use of blockers of ET-I receptors and by NO synthesis inhibition, In the absence of hyperinsulinemia, ET-1 receptor blockade did not result in any significant change in forearm blood flow from baseline (P=0.29). Intra-arterial insulin administration did not significantly modify forearm blood flow (P=0.88). However, in the presence of hyperinsulinemia, ET-1 receptor antagonism was associated with a significant vasodilator response (P<0.001). In the presence of ET-1 receptor blockade, the vasoconstrictor response to NO inhibition by N-G-monomethyl-L-arginine was significantly higher after insulin infusion than in the absence of hyperinsulinemia (P=0.006). Conclusions-These findings suggest that in the skeletal muscle circulation, insulin stimulates both ET-I and NO activity. An imbalance between the release of these 2 substances may be involved in the pathophysiology of hypertension and atherosclerosis in insulin-resistant states associated with endothelial dysfunction. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 32 TC 188 Z9 198 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 24 PY 1999 VL 100 IS 8 BP 820 EP 825 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 229AG UT WOS:000082170200010 PM 10458717 ER PT J AU Rothman, RB Ayestas, MA Dersch, CM Baumann, MH AF Rothman, RB Ayestas, MA Dersch, CM Baumann, MH TI Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates - Implications for primary pulmonary hypertension SO CIRCULATION LA English DT Article DE pulmonary heart disease; hypertension; drugs; obesity ID BIOGENIC-AMINE TRANSPORTERS; RAT STRIATAL MEMBRANES; DOPAMINE TRANSPORTER; PARA-CHLOROAMPHETAMINE; MESOLIMBIC DOPAMINE; SMOOTH-MUSCLE; BINDING-SITES; COCAINE; AMPHETAMINE; PHENTERMINE AB Background-Coadministration of phentermine and fenfluramine (phen/fen) effectively treats obesity and possibly addictive disorders. The association of fenfluramine and certain ther anorexic agents with serious side effects, such as cardiac valvulopathy and primary pulmonary hypertension (PPH), limits the clinical utility of these drugs. Development of new medications that produce neurochemical effects like phen/fen without causing unwanted side effects would be a significant therapeutic breakthrough. Methods and Results-We tested the hypothesis that fenfluramine (and other anorexic agents) might increase the risk of PPH through interactions with serotonin (5-HT) transporters. Because 5-HT transporter proteins in the lung and brain are identical, we examined, in rat brain, the effects of selected drugs on 5-HT efflux in vivo and monoamine transporters in vitro as a generalized index of transporter function. Our data show that drugs known or suspected to increase the risk of PPH (eg, aminorex; fenfluramine, and chlorphentermine) are 5-HT transporter substrates, whereas drugs that have not been shown to increase the risk of PPH are less potent in this regard. Conclusions-We speculate that medications that are 5-HT transporter substrates get translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic drug toxicity, and individual susceptibility, PPH could develop as a response to high levels of these drugs or metabolites. Emerging evidence suggests that it is possible to develop transporter substrates devoid of adverse side effects. Such medications could have therapeutic application in the management of obesity, drug dependence, depression, and other disorders. C1 NIDA, Intramural Res Program, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Intramural Res Program, Clin Psychopharmacol Sect, NIH, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. NR 46 TC 136 Z9 143 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 24 PY 1999 VL 100 IS 8 BP 869 EP 875 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 229AG UT WOS:000082170200018 PM 10458725 ER PT J AU Wyatt, RJ AF Wyatt, RJ TI Soares & McGrath - The treatment of tardive dyskinesia: a systematic review and meta-analysis SO SCHIZOPHRENIA RESEARCH LA English DT Editorial Material C1 NIMH, Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Wyatt, RJ (reprint author), NIMH, Neuropsychiat Branch, 15 North Dr,MSC 2668,Suite 203, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG 23 PY 1999 VL 39 IS 1 BP 17 EP 18 DI 10.1016/S0920-9964(99)00022-5 PG 2 WC Psychiatry SC Psychiatry GA 230TF UT WOS:000082265900002 ER PT J AU Ananthan, S Saini, SK Kezar, HS Davis, P Porreca, F Dersch, CM Rothman, RB AF Ananthan, S Saini, SK Kezar, HS Davis, P Porreca, F Dersch, CM Rothman, RB TI Synthesis, opioid receptor binding, and activity profiles of novel pyrido- and thienomorphinans. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Arizona, Dept Pharmacol, Tucson, AZ 85724 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. So Res Inst, Birmingham, AL 35255 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 270-MEDI BP U1007 EP U1007 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033903017 ER PT J AU Barchi, JJ Ford, H Dai, F Mu, L Siddiqui, M Nicklaus, M Marquez, VE Anderson, L AF Barchi, JJ Ford, H Dai, F Mu, L Siddiqui, M Nicklaus, M Marquez, VE Anderson, L TI Adenosine deaminase binds substrates with a distinct sugar conformation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 71-MEDI BP U934 EP U934 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902822 ER PT J AU Brechbiel, MW Deal, KA Chappell, LL Dadachova, E Davis, I Mirzadeh, S Kennel, SJ AF Brechbiel, MW Deal, KA Chappell, LL Dadachova, E Davis, I Mirzadeh, S Kennel, SJ TI Development of a bifunctional chelating agent suitable for radioimmunotherapy using actinium-225. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Oak Ridge Natl Lab, Oak Ridge, TN USA. RI Dadachova, Ekaterina/I-7838-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 173-MEDI BP U970 EP U970 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902921 ER PT J AU Brechbiel, MW Yordanov, AT Garmestani, K Phillips, K Herring, B Horak, E Beitzel, M Schwarz, UP Gansow, OA Waldmann, TA AF Brechbiel, MW Yordanov, AT Garmestani, K Phillips, K Herring, B Horak, E Beitzel, M Schwarz, UP Gansow, OA Waldmann, TA TI Preparation and in vivo stability evaluation of linkers for At-211 labeling of humanized antitac. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 419-INOR BP U836 EP U836 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902533 ER PT J AU Brechbiel, MW Deal, KA Stein, W Degraff, B Mitchell, J Planalp, RP AF Brechbiel, MW Deal, KA Stein, W Degraff, B Mitchell, J Planalp, RP TI Evaluation of the biological end cytotoxic properties of CIS,CIS-1,3,5-triaminocyclohexane Cu(II) complexes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Univ New Hampshire, Dept Chem, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 415-INOR BP U834 EP U835 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902526 ER PT J AU Coxon, B Sari, N Pozsgay, V AF Coxon, B Sari, N Pozsgay, V TI NMR spectroscopy end molecular dynamics of a synthetic octasaccharide fragment of the O-polysaccharide of Shigella dysenteriae type 1. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 65-CARB BP U200 EP U200 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900545 ER PT J AU Dadachova, E Chappell, LL Brechbiel, MW AF Dadachova, E Chappell, LL Brechbiel, MW TI Spectrophotometric assay for determination of polyazacarboxylate-macrocyclic ligands in ligand-protein conjugates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Dadachova, Ekaterina/I-7838-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 40-ANYL BP U139 EP U139 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900359 ER PT J AU Furness, MS Dersch, CM Horel, R Rothman, RB Rice, KC AF Furness, MS Dersch, CM Horel, R Rothman, RB Rice, KC TI delta opioid selectivity of N-substituted SNC80 analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 269-MEDI BP U1006 EP U1007 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033903016 ER PT J AU Gabrielsen, BJ AF Gabrielsen, BJ TI Role of the National Cancer Institute: Technology development and commercialization branch in commercializing biotechnology. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Fairview Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 16-CHAL BP U388 EP U388 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901166 ER PT J AU Kim, YC Ji, XD Linden, J Jacobson, KA AF Kim, YC Ji, XD Linden, J Jacobson, KA TI Selective and potent antagonists for adenosine A(2B) receptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Internal Med & Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 144-MEDI BP U960 EP U960 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902892 ER PT J AU Lee, JW Lee, JY Kim, JY Oh, U Park, YH Marquez, VE Blumberg, PM AF Lee, JW Lee, JY Kim, JY Oh, U Park, YH Marquez, VE Blumberg, PM TI N-(3-acyloxy-2-benzylpropyl)-N '-(4-hydroxy-3-methoxybenzyl)thiourea derivatives as potent vanilloid receptor agonists and analgesics. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Seoul 151742, South Korea. Seoul Natl Univ, Coll Pharm, Physiol Lab, Yongin Si 449900, Kyounggi Do, South Korea. Pacific R&D Ctr, Yongin Si 449900, Kyounggi Do, South Korea. NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 274-MEDI BP U1009 EP U1009 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033903021 ER PT J AU Lee, YS Sugiyama, K Kador, PF AF Lee, YS Sugiyama, K Kador, PF TI Effect of charge state of HIS110 and NADPH at the active site of aldose reductase on the binding affinity of tight-binding inhibitor tolrestat. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 194-COMP BP U531 EP U531 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901624 ER PT J AU Liwanag, PM Hudson, VW Hazard, GF AF Liwanag, PM Hudson, VW Hazard, GF TI ChemIDplus: An experimental public chemical information and structure search system. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Lib Med, Div Specialized Informat Serv, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 38-CINF BP U361 EP U362 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901075 ER PT J AU Long, YQ Lung, FDT Yao, ZJ Voigt, JH King, CR Burke, TR Roller, PP AF Long, YQ Lung, FDT Yao, ZJ Voigt, JH King, CR Burke, TR Roller, PP TI Overlapping function of amino acids in position-2 and Y-0 leading to high-affinity nonphosphorylated peptide ligands of GRB2-SH2 domain. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RI Yao, Zhu-Jun/E-7635-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 227-MEDI BP U990 EP U990 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902975 ER PT J AU Lu, RJ Eissenstat, MA AF Lu, RJ Eissenstat, MA TI Novel protection of carbonyl compounds: Scandium triflate catalyzed efficient, selective cleavage of ketals ano acetals. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SAIC, Frederick Natl Canc Inst, Struct Biochem Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 516-ORGN BP U171 EP U172 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226RA UT WOS:000082034000516 ER PT J AU Luzzio, FA Thomas, EM Figg, WD AF Luzzio, FA Thomas, EM Figg, WD TI Stereoselective synthesis of thalidomide analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Louisville, Louisville, KY 40292 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 164-ORGN BP U58 EP U58 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226RA UT WOS:000082034000165 ER PT J AU Marquez, VE Marchi, JJ Anderson, L Knispel, T Meier, C AF Marquez, VE Marchi, JJ Anderson, L Knispel, T Meier, C TI What changes in conformational parameters can be induced by phosphorylation in conformationally biased nucleosides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Div Basic Sci, Bethesda, MD 20982 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 60-CARB BP U198 EP U198 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900540 ER PT J AU Ogunbadeniyi, A Shen, J Bowen, W Mattson, M Adejare, A AF Ogunbadeniyi, A Shen, J Bowen, W Mattson, M Adejare, A TI Ligands for characterizing PCP binding sites on the NMDA receptor complex. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Kansas City, MO 64110 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 98-MEDI BP U944 EP U944 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902849 ER PT J AU Planalp, RP Park, G Brechbiel, MW Torti, SV AF Planalp, RP Park, G Brechbiel, MW Torti, SV TI Metal complexation behavior and cytotoxicity of novel hexadentate chelators. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Chem Sect, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 231-MEDI BP U991 EP U991 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902979 ER PT J AU Planalp, RP Park, GS Rogers, RD Brechbiel, MW AF Planalp, RP Park, GS Rogers, RD Brechbiel, MW TI Synthesis and chracterization of dicationic metal complexes of tachpyr and tach-6-Mepyr ligands derived from the cis-1,3,5-triaminocyclohexane framework. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. NIH, Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 516-INOR BP U868 EP U868 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902627 ER PT J AU Pozsgay, V Robbins, JB Schneerson, R AF Pozsgay, V Robbins, JB Schneerson, R TI Synthetic oligosaccharide-based conjugate vaccine against shigella dysenteriae type SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 12-CARB BP U183 EP U184 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900493 ER PT J AU Pradhan, P Liu, XH Jerina, DM Sayer, J Shah, JH Lakshman, MK Yeh, HJC AF Pradhan, P Liu, XH Jerina, DM Sayer, J Shah, JH Lakshman, MK Yeh, HJC TI NMR solution structures of undecanucleotide duplexes containing N,6-deoxyadenosine adducts derived from a 9,10-epoxide and 7,8-diol-9,10-epoxide of 7,8,9,10-tetrahydrobenzo[a]pyrene. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 248-PHYS BP U344 EP U344 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226RA UT WOS:000082034000973 ER PT J AU Rick, SW Cachau, RE AF Rick, SW Cachau, RE TI Protein folding and the influence of secondary structure on hydrogen bond energies and peptide group planarity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 188-COMP BP U529 EP U529 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901618 ER PT J AU Robarge, MJ Agoston, GE Izenwasser, S Kopajtic, T George, C Newman, AH AF Robarge, MJ Agoston, GE Izenwasser, S Kopajtic, T George, C Newman, AH TI Highly selective chiral N-substituted 3 alpha-[bis(4 '-fluorophenyl)methoxy]tropane analogs for the dopamine transporter: Synthesis and comparative molecular field analysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA, NIH, Baltimore, MD 21224 USA. Entremed Inc, Rockville, MD 20850 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 122-MEDI BP U952 EP U952 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902870 ER PT J AU Rogan, WJ AF Rogan, WJ TI Environmental chemicals and brain development in young children: Lead, PCBs, PCDFs, and other adventures in subtle outcomes and low-level exposures. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 42-ENVR BP U555 EP U556 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901683 ER PT J AU Todebush, PM Ma, BY Lii, JH Bowen, JP Allinger, NL AF Todebush, PM Ma, BY Lii, JH Bowen, JP Allinger, NL TI Comparative study of dipole moments. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Georgia, Dept Chem, Computat Ctr Mol Struct & Design, Athens, GA 30602 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 140-COMP BP U517 EP U517 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901575 ER PT J AU Voigt, JH Androphy, EJ Chen, JJ Nicklaus, MC Baleja, JD AF Voigt, JH Androphy, EJ Chen, JJ Nicklaus, MC Baleja, JD TI Discovery of hovel inhibitors of the papillomavirus E6 protein mediated P53 degradation by 3-D database searching. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. New England Med Ctr, Dept Dermatol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 89-COMP BP U502 EP U503 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033901530 ER PT J AU Yau, WM Gawrisch, K AF Yau, WM Gawrisch, K TI Deuteration of indole and 1-methylindole by Raney nickel catalysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract DE deuterium; Raney nickel; deuteration; indole; N-methylindole; solid-state NMR C1 NIAAA, Lab Membrane Biophys & Biochem, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 4-CATL BP U703 EP U703 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226RA UT WOS:000082034002134 ER PT J AU Yu, H Wang, LJ Flippen-Anderson, J Rice, KC AF Yu, H Wang, LJ Flippen-Anderson, J Rice, KC TI Synthesis of a novel 7,14-ethano-bridged opiate. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD, LMC, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Washington, DC 20375 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 271-MEDI BP U1007 EP U1008 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033903018 ER PT J AU Zhang, SX Bastow, KF Tachibana, Y Kuo, SC Hamel, E Mauger, A Narayanan, VL Lee, KH AF Zhang, SX Bastow, KF Tachibana, Y Kuo, SC Hamel, E Mauger, A Narayanan, VL Lee, KH TI Substituted 2-thienyl-1,8-naphthyridin-4-ones: Their synthesis, cytotoxicity, and inhibition of tubulin polymerization. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. China Med Coll, Grad Inst Pharmaceut Chem, Taichung 400, Taiwan. NCI, Lab Drug Discovery Res & Dev, Div Canc Treatment & Diagnosis, NIH, Frederick, MD 21702 USA. NCI, Drug Synth & Chem Branch, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 171-MEDI BP U969 EP U969 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902919 ER PT J AU Kustova, Y Grinberg, A Basile, AS AF Kustova, Y Grinberg, A Basile, AS TI Increased blood-brain barrier permeability in LP-BM5 infected mice is mediated by neuroexcitatory mechanisms SO BRAIN RESEARCH LA English DT Article DE IgG; blood-brain barrier; LP-BM5; mouse; serum protein; MK-801; immunodeficiency ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CENTRAL-NERVOUS-SYSTEM; CAPILLARY ENDOTHELIAL-CELLS; GLUTAMATE RECEPTORS; IMMUNOHISTOCHEMICAL LOCALIZATION; SERUM-PROTEINS; LEUKEMIA-VIRUS; SPINAL-CORD; RAT; RETROVIRUS AB Serum protein levels in LP-BM5 infected mouse brains were investigated to gain insight into the contribution of blood-brain barrier (BBB) patency to the pathogenesis of retroviral encephalopathy. Evens blue uptake by the forebrain and cerebellum was significantly increased between 8-12 weeks post inoculation. Immunohistochemistry revealed foci of albumin, transferrin, alpha(2)-macroglobulin and IgG transudation around blood vessels particularly in the cerebral cortex and cerebellar vermis. These leaks were often associated with astrocytosis and apoptotic cells. Unlike the other serum proteins, IgG immunoreactivity extended from the circumventricular organs and disseminated throughout the brain parenchyma, accumulating on the plasma membranes of hippocampal and cortical neurons. Consistent with the chronic elevation of free glutamate levels in LP-BM5 infected mice, the increase in Evans blue uptake into the forebrain was completely reversed following dizocilpine administration. Thus, the chronic increase in free glutamate levels in LP-BM5 infected mouse brain contributes to BBB disruption. Furthermore, the CNS accumulation of serum proteins, particularly IgG, observed in these mice may increase osmotic load, impair neuronal function, and cause white matter pallor. Administration of NMDA receptor antagonists may prove useful in managing BBB permeability in those neuropathologies, such as HIV-associated dementia/cognitive/motor complex, having a glutamatergic component. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NICHD, NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Basile, AS (reprint author), NICHD, NIDDK, Bioorgan Chem Lab, NIH, Bldg 8,Room 1A15,, Bethesda, MD 20892 USA. EM asbasile@helix.nih.gov NR 51 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 21 PY 1999 VL 839 IS 1 BP 153 EP 163 DI 10.1016/S0006-8993(99)01734-5 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 227TU UT WOS:000082096700016 PM 10482808 ER PT J AU Barzilay, JI Spiekerman, CF Wahl, PW Kuller, LH Cushman, M Furberg, CD Dobs, A Polak, JF Savage, PJ AF Barzilay, JI Spiekerman, CF Wahl, PW Kuller, LH Cushman, M Furberg, CD Dobs, A Polak, JF Savage, PJ TI Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria SO LANCET LA English DT Article ID HEALTH AB Background The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cutoff value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly. Methods We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8-year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria. Findings There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose stales was a third of that attributable by the WHO criteria (53 vs 159 cases per 10 000), For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%), Interpretation The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly. C1 Kaiser Permanente Georgia, Div Endocrinol, Tucker, GA 30084 USA. Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Vermont, Sch Med, Dept Med, Colchester, VT USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Johns Hopkins Univ, Sch Med, Div Endocrinol, Baltimore, MD USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Barzilay, JI (reprint author), Kaiser Permanente Georgia, Div Endocrinol, 200 Crescent Ctr Pkwy, Tucker, GA 30084 USA. FU NHLBI NIH HHS [N01-HC-97079] NR 13 TC 132 Z9 137 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 21 PY 1999 VL 354 IS 9179 BP 622 EP 625 DI 10.1016/S0140-6736(98)12030-5 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 229UQ UT WOS:000082214500009 PM 10466662 ER PT J AU Schachter, J West, SK Mabey, D Dawson, CR Bobo, L Bailey, R Vitale, S Quinn, TC Sheta, A Sallam, S Mkocha, H Mabey, D Faal, H AF Schachter, J West, SK Mabey, D Dawson, CR Bobo, L Bailey, R Vitale, S Quinn, TC Sheta, A Sallam, S Mkocha, H Mabey, D Faal, H TI Azithromycin in control of trachoma SO LANCET LA English DT Article ID SINGLE-DOSE AZITHROMYCIN; CONTROLLED TRIAL; CHAIN-REACTION; INFECTION; TANZANIA; CHILDREN AB Background Trachoma is the leading cause of preventable blindness. Programmes to prevent blindness due to trachoma are based on community-wide treatment with topical tetracycline. We assessed the potential of community-wide azithromycin treatment for trachoma control. Methods Pairs of villages in trachoma endemic areas of Egypt, The Gambia, and Tanzania were matched on trachoma rates in 1-10-year-old children. Villages were randomly assigned community-wide oral azithromycin treatment (three doses with intervals of 1 week) or treatment with 1% topical tetracycline (once daily for 6 weeks). Clinical examinations were done at baseline, 2-4.5 months, and 12-14 months after treatment. Chlamydia trachomatitis was identified by ligase chain reaction (LCR). Analyses were by intention to treat. Univariate comparisons and multivariate analyses were used to compare outcomes. Findings LCR positivity was correlated with clinical severity, but about 30% of Egyptian and Gambian villagers with no active disease were LCR positive. Village-wide LCR positivity ranged from 16.5% (Tanzania) to 43.6% (Egypt). Treatment compliance was over 90% except in the tetracycline treatment village in Egypt. Of the participants initially LCR positive, 866 (95%) of 924 who received at least one azithromycin dose and 482 (82%) of 587 who received 28 days or more topical tetracycline, were negative at follow-up. At 1 year, village-wide LCR positivity rates were substantially lower than at baseline with both treatments; the decreases were greater with azithromycin than with tetracycline (93% vs 77% in Egypt, 78 vs 66% in The Gambia, 64 vs 55% in Tanzania). Similarly, greater reduction in clinical activity occurred after azithromycin. In multivariate analyses, factors associated with being LCR positive at 1 year were: not receiving azithromycin; age under 10 years; and LCR positivity at baseline. Interpretation Community-wide treatment with oral azithromycin markedly reduces C trachomatis infection and clinical trachoma in endemic areas and may be an important approach to control of trachoma. C1 Univ Calif San Francisco, Dept Lab Med, Chlamydia Res Lab, San Francisco, CA 94143 USA. Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. Wilmer Eye Inst, Baltimore, MD USA. Johns Hopkins Univ, Dept Paediat Infect Dis, Baltimore, MD USA. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. Univ Alexandria, Fac Med, Dept Ophthalmol, Alexandria, Egypt. Univ Alexandria, High Inst Publ Hlth, Dept Epidemiol, Alexandria, Egypt. NIAID, Bethesda, MD 20892 USA. Cent Eye Hlth Fdn, Kongwa Trachoma Project, Kongwa, Tanzania. Minist Hlth, Natl Eye Care Programme, Banjul, Gambia. RP Schachter, J (reprint author), Univ Calif San Francisco, Dept Lab Med, Chlamydia Res Lab, Box 0842, San Francisco, CA 94143 USA. RI Quinn, Thomas/A-2494-2010 FU PHS HHS [P01 A135682] NR 17 TC 173 Z9 175 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 21 PY 1999 VL 354 IS 9179 BP 630 EP 635 DI 10.1016/S0140-6736(98)12387-5 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 229UQ UT WOS:000082214500011 PM 10466664 ER PT J AU Zimmerberg, J Chernomordik, LV AF Zimmerberg, J Chernomordik, LV TI Membrane fusion SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE exocytosis; viral fusion; fusion pathway; membrane curvature; hemifusion ID PHOSPHOLIPID-BILAYER MEMBRANES; INFLUENZA HEMAGGLUTININ; CA2+-ACTIVATED SECRETION; ELECTRICAL BREAKDOWN; MOLECULAR MECHANISMS; PLANAR MEMBRANE; LIPID BILAYERS; PORE FORMATION; PROTEIN; EXOCYTOSIS AB Although catalyzed by different proteins, the energy barriers for lipid bilayer fusion in exocytosis, viral fusion, and trafficking seem to be the same as those for the fusion of protein-free phospholipid membranes. To minimize this energy, fusion will proceed through a minimal number of lipid molecules, probably localized in bent non-bilayer intermediates. Experiments on phospholipid bilayer membrane fusion show the pathway of contact, hemifusion, flickering fusion pore formation, and fusion pore enlargement caused by swelling of the vesicle. Lipid curvature determines the barriers to hemifusion and fusion pore formation, while swelling-induced membrane tension drives fusion pore enlargement. Experiments on viral protein-induced cell-cell fusion and exocytosis show the same pathway with the same fundamental effects of lipid curvature and membrane tension. Thus while proteins control these reactions, lipid energetics determine the basic reaction scheme for membrane fusion. Published by Elsevier Science B.V. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 68 TC 95 Z9 97 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD AUG 20 PY 1999 VL 38 IS 3 BP 197 EP 205 DI 10.1016/S0169-409X(99)00029-0 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 232LB UT WOS:000082371300002 ER PT J AU Martinez, M Goldin, LR Cao, QH Zhang, J Sanders, AR Nancarrow, DJ Taylor, JM Levinson, DF Kirby, A Crowe, RR Andreasen, NC Black, DW Silverman, JM Lennon, DP Nertney, DA Brown, DM Mowry, BJ Gershon, ES Gejman, PV AF Martinez, M Goldin, LR Cao, QH Zhang, J Sanders, AR Nancarrow, DJ Taylor, JM Levinson, DF Kirby, A Crowe, RR Andreasen, NC Black, DW Silverman, JM Lennon, DP Nertney, DA Brown, DM Mowry, BJ Gershon, ES Gejman, PV TI Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; linkage; genome scan ID DIAGNOSTIC INTERVIEW; LINKAGE ANALYSIS; COMPLEX TRAITS; GENETIC DISSECTION; NUCLEAR FAMILIES; LOD SCORES; DISORDER; MODELS; TESTS AB Evidence for suggestive linkage to schizophrenia with chromosome 6q markers was previously reported from a two-stage approach. Using nonparametric affected sib pairs (ASP) methods, nominal p-values of 0.00018 and 0.00095 were obtained in the screening (81 ASPs; 63 independent) and the replication (109 ASPs; 87 independent) data sets, respectively. Here, we report a follow-up study of this 50cM 6q region using 12 microsatellite markers to test for linkage to schizophrenia. We increased the replication sample size by adding an independent sample of 43 multiplex pedigrees (66 ASPs; 54 independent). Pairwise and multipoint nonparametric linkage analyses conducted in this third data set showed evidence consistent with excess sharing in this 6q region, though the statistical level is weaker (p=0.013). When combining both replication data sets (total of 141 independent ASPs), an overall nominal p-value=0.000014 (LOD=3.82) was obtained. The sibling recurrence risk (hs) attributed to this putative 6q susceptibility locus is estimated to be 1.92. The linkage region could not be narrowed down since LOD score values greater than three were observed within a 13cM region. The length of this region was only slightly reduced (12cM) when using the total sample of independent ASPs (204) obtained from all three data sets. This suggests that very large sample sizes may be needed to narrow down this region by ASP linkage methods. Study of the etiological candidate genes in this region is ongoing. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:337-343, 1999. (C) 1994 Wiley-Liss, Inc. C1 Hop St Louis, INSERM, U358, F-75010 Paris, France. NIMH, Clin Neurogenet Branch, Bethesda, MD 20892 USA. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Univ Queensland, Dept Psychiat, Brisbane, Qld, Australia. Wolston Park Hosp, Queensland Ctr Schizophrenia Res, Brisbane, Qld, Australia. Allegheny Univ Hlth Sci, Dept Psychiat, Philadelphia, PA USA. Univ Iowa Coll Med, Mental Hlth Clin Res Ctr, Iowa City, IA USA. Univ Iowa Coll Med, Dept Psychiat, Iowa City, IA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Res Genet Inc, Huntsville, AL USA. RP Martinez, M (reprint author), Hop St Louis, INSERM, U358, 1 Ave Claude Vellefaux, F-75010 Paris, France. RI Taylor, Jennifer/A-1686-2010; Martinez, Maria/B-3111-2013 OI Taylor, Jennifer/0000-0003-4231-0181; Martinez, Maria/0000-0003-2180-4537 NR 26 TC 84 Z9 85 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 20 PY 1999 VL 88 IS 4 BP 337 EP 343 DI 10.1002/(SICI)1096-8628(19990820)88:4<337::AID-AJMG9>3.0.CO;2-A PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 218YW UT WOS:000081581400009 PM 10402499 ER PT J AU Goldman, D Urbanek, MK Guenther, D Robin, R Long, J AF Goldman, D Urbanek, MK Guenther, D Robin, R Long, J TI Association between a functional polymorphism at the DRD2 gene and the liability to substance abuse SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 20 PY 1999 VL 88 IS 4 BP 447 EP 447 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 218YW UT WOS:000081581400026 ER PT J AU Li, AE Ito, H Rovira, II Kim, KS Takeda, K Yu, ZY Ferrans, VJ Finkel, T AF Li, AE Ito, H Rovira, II Kim, KS Takeda, K Yu, ZY Ferrans, VJ Finkel, T TI A role for reactive oxygen species in endothelial cell anoikis SO CIRCULATION RESEARCH LA English DT Article DE JNK; caspase; hydrogen peroxide; mitochondria ID EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; APOPTOSIS; ACTIVATION; SURVIVAL; GENERATION; PATHWAY; KINASE; DEATH AB When adherent cells, such as epithelial or endothelial cells, are detached and continuously maintained in suspension, they undergo a form of programmed cell death termed anoikis. We demonstrate that coincident with endothelial cell detachment, there is a dramatic rise in the intracellular level of reactive oxygen species (ROS). Reattachment to a solid surface rapidly attenuates the level of ROS. The mitochondria appear to be the major source of the detachment-induced risen ROS. The change in the intracellular redox state appears to contribute to endothelial anoikis, because treatment with either the cell-permeant antioxidant N-acetylcysteine or the flavin protein inhibitor diphenylene iodonium is demonstrated to reduce oxidant levels and protect against subsequent cell death. Similarly, the endogenous intracellular level of ROS is shown to correlate with the extent of cell death. Finally, we demonstrate that the activities of both caspases and of the c-Jun N-terminal kinases are modulated by the rise in intracellular ROS levels. These results suggest that oxidants serve as signaling molecules and regulators of anoikis. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, 10 Ctr Dr,MSC 1650,Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 33 TC 114 Z9 122 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 20 PY 1999 VL 85 IS 4 BP 304 EP 310 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 228KY UT WOS:000082136700002 PM 10455058 ER PT J AU Miyata, M Kudo, G Lee, YH Yang, TJ Gelboin, HV Fernandez-Salguero, P Kimura, S Gonzalez, FJ AF Miyata, M Kudo, G Lee, YH Yang, TJ Gelboin, HV Fernandez-Salguero, P Kimura, S Gonzalez, FJ TI Targeted disruption of the microsomal epoxide hydrolase gene - Microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADULT HUMAN-LIVER; COMPLEMENTARY-DNA; MESSENGER-RNA; DIOL-EPOXIDE; EXPRESSION; CELLS; MICE; SUSCEPTIBILITY; 7,12-DIMETHYLBENZ(A)ANTHRACENE; METABOLISM AB Microsomal epoxide hydrolase (mEH) is a conserved enzyme that is known to hydrolyze many drugs and carcinogens, and a few endogenous steroids and bile acids. mEH-null mice were produced and found to be fertile and have no phenotypic abnormalities thus indicating that mEH is not critical for reproduction and physiological homeostasis, mEH has also been implicated in participating in the metabolic activation of polycyclic aromatic hydrocarbon carcinogens, Embryonic fibroblast derived from the mEH-null mice were unable to produce the proximate carcinogenic metabolite of 7,12-dimethylbenz[a]anthracene (DMBA), a widely studied experimental prototype for the polycylic aromatic hydrocarbon class of chemical carcinogens, They were also resistant to DMBA-mediated toxicity. Using the two-stage initiation-promotion skin cancer bioassay, the mEH-null mice were found to be highly resistant to DMBA-induced carcinogenesis. In a complete carcinogenesis bioassay, the mEH mice were totally resistant to tumorigenesis, These data establish in an intact animal model that mEH is a key genetic determinant in DMBA carcinogenesis through its role in production of the ultimate carcinogenic metabolite of DMBA, the 3,4-diol-1,2-epoxide. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3E-24, Bethesda, MD 20892 USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 46 TC 144 Z9 148 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 20 PY 1999 VL 274 IS 34 BP 23963 EP 23968 DI 10.1074/jbc.274.34.23963 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 227ZV UT WOS:000082110900043 PM 10446164 ER PT J AU Passer, BJ Pellegrini, L Vito, P Ganjei, JK D'Adamio, L AF Passer, BJ Pellegrini, L Vito, P Ganjei, JK D'Adamio, L TI Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X-L - A potential role in modulating the threshold of cell death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISEASE-ASSOCIATED PRESENILINS; AMYLOID BETA-PEPTIDE; CYTOCHROME-C; IN-VIVO; ISOLATED-MITOCHONDRIA; MISSENSE MUTATIONS; APOPTOSIS; GENE; PROTEINS; EXPRESSION AB The familial Alzheimer's disease gene products, presenilin-1 and presenilin-2, have been reported to be functionally involved in amyloid precursor protein processing, notch receptor signaling, and programmed cell death or apoptosis. However, the molecular mechanisms by which presenilins regulate these processes remain unknown. With regard to the latter, we describe a molecular link between presenilins and the apoptotic pathway. Bcl-X-L, an anti-apoptotic member of the Bcl-2 family was shown to interact with the carboxyl-terminal fragments of PS1 and PS2 by the yeast two-hybrid system. In vivo interaction analysis revealed that both PS2 and its naturally occurring carboxyl-terminal products, PS2short and PS2Ccas, associated with Bcl-X-L, whereas the caspase-3-generated amino-terminal PS2Ncas fragment did not. This interaction was corroborated by demonstrating that Bcl-X-L and PS2 partially co-localized to sites of the vesicular transport system. Functional analysis revealed that presenilins can influence mitochondrial-dependent apoptotic activities, such as cytochrome c release and Bar-mediated apoptosis. Together, these data support a possible role of the Alzheimer's presenilins in modulating the anti-apoptotic effects of Bcl-X-L. C1 NIAID, Cellular & Mol Immunol Lab, T Cell Apoptosis Unit, NIH, Bethesda, MD 20892 USA. Basel Inst Immunol, CH-4005 Basel, Switzerland. RP D'Adamio, L (reprint author), NIAID, Cellular & Mol Immunol Lab, T Cell Apoptosis Unit, NIH, Bldg 4,Rm 431, Bethesda, MD 20892 USA. NR 45 TC 84 Z9 85 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 20 PY 1999 VL 274 IS 34 BP 24007 EP 24013 DI 10.1074/jbc.274.34.24007 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 227ZV UT WOS:000082110900048 PM 10446169 ER PT J AU Krutzsch, HC Choe, BJ Sipes, JM Guo, NH Roberts, DD AF Krutzsch, HC Choe, BJ Sipes, JM Guo, NH Roberts, DD TI Identification of an alpha(3)beta(1) integrin recognition sequence in thrombospondin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARIN-BINDING PEPTIDES; MELANOMA CELL-ADHESION; I REPEATS; MULTIPLE ALIGNMENT; TERMINAL DOMAIN; LAMININ-5; RECEPTOR; PROTEIN; VLA-3; CHAIN AB A synthetic peptide containing amino acid residues 190-201 of thrombospondin-l (TSP1) promoted adhesion of MDA-MB-435 breast carcinoma cells when immobilized and inhibited adhesion of the same cells to TSP1 when added in solution. Adhesion to this peptide was enhanced by a beta(1) integrin-activating antibody, Mn2+, and insulin-like growth factor I and was inhibited by an alpha(3)beta(1) integrin function-blocking antibody. The soluble peptide inhibited adhesion of cells to the immobilized TSP1 peptide or spreading on intact TSP1 but at the same concentrations did not inhibit attachment or spreading on type Iv collagen or fibronectin, Substitution of several residues in the TSP1 peptide with Ala residues abolished or diminished the inhibitory activity of the peptide in solution, but only substitution of Arg-198 completely inactivated the adhesive activity of the immobilized peptide. The essential residues for activity of the peptide as a soluble inhibitor are Asn-196, Val-197, and Arg-198, but flanking residues enhance the inhibitory activity of this core sequence, either by altering the conformation of the active sequence or by interacting with the integrin, This functional sequence is conserved in all known mammalian TSP1 sequences and in TSP1 from Xenopus laevis, The TSP1 peptide also inhibited adhesion of MDA-MB-435 cells to the laminin-l peptide GD6, which contains a potential integrin-recognition sequence Asn-Leu-Arg and is derived from a similar position in a pentraxin module. Adhesion studies using recombinant TSP1 fragments also localized beta 1 integrin-dependent adhesion to residues 175-242 of this region, which contain the active sequence. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 41 TC 62 Z9 62 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 20 PY 1999 VL 274 IS 34 BP 24080 EP 24086 DI 10.1074/jbc.274.34.24080 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 227ZV UT WOS:000082110900058 PM 10446179 ER PT J AU Jain, N Zhang, T Kee, WH Li, WQ Cao, XM AF Jain, N Zhang, T Kee, WH Li, WQ Cao, XM TI Protein kinase C delta associates with and phosphorylates Stat3 in an interleukin-6-dependent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; TRANSCRIPTION FACTOR APRF; TYROSINE PHOSPHORYLATION; SERINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CYTOKINE RECEPTORS; GENE-REGULATION; V-SRC; ACTIVATION; PATHWAY AB Stat3 is activated by phosphorylation on Tyr-705, which leads to dimer formation, nuclear translocation, and regulation of gene expression. Serine phosphorylation of Stat3 by mitogen-activated protein kinase has also been observed in cells responding to epidermal growth factor and shown to affect its tyrosine phosphorylation and transcriptional activity. Serine phosphorylation of Stat3 is also induced by interleukin-6 (IL-6) stimulation, which is shown to be independent of mitogen activated protein kinase and sensitive to the Ser/ Thr kinase inhibitor H7. In this study, we investigated whether protein kinase C (PKC) is the kinase that is induced and responsible for Stat3 serine phosphorylation by IL-6 stimulation and which isoform of PKCs is likely to be involved. Here, we report that Stat3 was specifically associated with PKC delta in vivo in an IL-6-dependent manner in several cell types. Furthermore, Stat3 was phosphorylated by PKC delta in vivo on Ser-727, which could be inhibited either by a specific PKC delta inhibitor or by a dominant-negative mutant of PKC delta. Finally, we showed that the phosphorylation of Stat3 by PKC delta led to a negative regulation of Stat3 DNA binding and transcriptional activity. These results indicate that PKC delta is likely to be the kinase that phosphorylates Stat3 in response to IL-6 stimulation and suggest a possible regulatory role of PKC delta on Stats function. C1 Natl Univ Singapore, Signal Transduct Lab, Inst Mol & Cell Biol, Singapore 117609, Singapore. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cao, XM (reprint author), Natl Univ Singapore, Signal Transduct Lab, Inst Mol & Cell Biol, 30 Med Dr, Singapore 117609, Singapore. RI ASTAR, IMCB/E-2320-2012 NR 47 TC 135 Z9 135 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 20 PY 1999 VL 274 IS 34 BP 24392 EP 24400 DI 10.1074/jbc.274.34.24392 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 227ZV UT WOS:000082110900098 PM 10446219 ER PT J AU Ptitsyn, OB Ting, KLH AF Ptitsyn, OB Ting, KLH TI Non-functional conserved residues in globins and their possible role as a folding nucleus SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE conserved protein residues; protein folding; folding nucleation; molten globule; globins ID TRANSITION-STATE; CHYMOTRYPSIN INHIBITOR-2; ANGSTROM RESOLUTION; CYTOCHROME-C; STRUCTURAL CHARACTERIZATION; CRYSTALLOGRAPHIC ANALYSIS; CRYSTAL-STRUCTURE; MOLTEN GLOBULE; PROTEIN; HEMOGLOBIN AB Structure-based sequence alignment of 728 sequences of different globin subfamilies shows that in each subfamily there are two clusters of consensually conserved residues. The first is the well-known "functional" cluster which includes six heme-binding conserved residues (Phe CD1, His F8; aliphatic Ell, FG5; hydrophobic F4, G5) and seven other conserved residues (Pro C2; aliphatic H19; hydrophobic B10, B13, B14, CD4, E4) that do not bind the heme but belong to its immediate neighborhood. The second cluster revealed here (aliphatic A8, G16, G12; aromatic A12; hydrophobic H8 and possibly H12) is distant from the heme. It is entirely non-polar and includes one turn (i, i+4 positions) from each of helices A, G, and H. It is known that A, G, and H helices formed at the earliest stage of apomyoglobin folding remain relatively stable in the equilibrium molten globule state, and are likely to be tightly packed with each other in this state. We have shown the existence of two similar conserved clusters in c-type cytochromes, heme-binding and distal from the heme. The second cluster in c-cytochromes includes one turn from each of the N and C-terminal a-helices. These N and C-terminal helices in cytochrome c are formed at the earliest stage of protein folding, remain relatively stable in the molten globule state, and are tightly packed with each other in this state, similar to the observed behavior of the globins. At least these two large protein families (c-type cytochromes and globins) have a close similarity in the existence and mutual positions of non-functional conserved residues. We assume that non-functional conserved residues are requisite for the fast and correct folding of both of these protein families into their stable 3D structures. C1 NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20891 USA. Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. RP Ting, KLH (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20891 USA. NR 42 TC 91 Z9 93 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 20 PY 1999 VL 291 IS 3 BP 671 EP 682 DI 10.1006/jmbi.1999.2920 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 228EE UT WOS:000082123500014 PM 10448045 ER PT J AU Ma, DW Tang, TJ Kozikowski, AP Lewin, NE Blumberg, PM AF Ma, DW Tang, TJ Kozikowski, AP Lewin, NE Blumberg, PM TI General and stereospecific route to 9-substituted, 8,9-disubstituted, and 9,10-disubstituted analogues of benzolactam-V8 SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; AMINO-ACIDS; STRUCTURAL BASIS; TUMOR PROMOTERS; ARYL HALIDES; INDOLACTAM-V; L-TYROSINE; MODULATORS; (-)-INDOLACTAM-V; TELEOCIDINS AB Nitration of the L-tyrosine derivative 9 provides the S-nitro compound 13', which is converted into amide 15 by reduction and protection. Nitration of 15 either ortho or para to the acetamido group gives 16 and 17. After reduction of the nitro group, the anilines 21b and 29b are coupled with triflate 22a, and then cyclized to afford lactams 24 and 31, respectively. By means of a Pd-catalyzed coupling reaction, 8-acetamido-4-decynylbenzolactam-V8 (26) and 9-decyny-10-acctamidobenzolactam-V8 (33) are obtained. The regioisomers 16 and 17 are transformed into a single isomer, 34, which is converted into 9-decynylbenzolactam-V8 (4). The K-i values for 4, 26, and 33 to displace PDBU binding from recombinant PKC alpha (PKC = protein kinase C) art! about 6, 173, and 16 nM. These results demonstrate that while the introduction of a substituent at; either the 8- or 10-position of the 9-substituted benzolactam-V8s lowers their binding affinity, these newly generated analogues still retain reasonably good potency for PKC. C1 Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China. Georgetown Univ, Med Ctr, Drug Discovery Program, Inst Cognit & Computat Sci, Washington, DC 20007 USA. NCI, Bethesda, MD 20892 USA. RP Ma, DW (reprint author), Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, 354 Fenglin Lu, Shanghai 200032, Peoples R China. OI Tang, Wenjun/0000-0002-8209-4156 NR 54 TC 19 Z9 20 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 20 PY 1999 VL 64 IS 17 BP 6366 EP 6373 DI 10.1021/jo990605h PG 8 WC Chemistry, Organic SC Chemistry GA 230GN UT WOS:000082243600033 ER PT J AU Corthout, E Uttl, B Walsh, V Hallett, M Cowey, A AF Corthout, E Uttl, B Walsh, V Hallett, M Cowey, A TI Timing of activity in early visual cortex as revealed by transcranial magnetic stimulation SO NEUROREPORT LA English DT Article DE transcranial magnetic stimulation (TMS); visual cortex; visual perception ID MACAQUE MONKEY; AREAS V1; RESPONSE LATENCIES; SUPPRESSION; PERCEPTION; V5; ORIENTATION; PRIMATE; MASKING; NEURONS AB To determine the timing of visual processing in the early visual cortex, we applied single pulse transcranial magnetic stimulation to the occipital pole of healthy subjects while they were engaged in a forced-choice visual letter-identification task. We found two separate periods of activity, the first ranging from 20 to 60 ms after the onset of the visual stimulus, and the second ranging from 100 to 140 ms after the onset of the visual stimulus. We suggest that these two periods reflect necessary activity in V1, before and after re-entry. (C) 1999 Lippincott Williams & Wilkins. C1 Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Corthout, E (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. NR 22 TC 94 Z9 95 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 20 PY 1999 VL 10 IS 12 BP 2631 EP 2634 DI 10.1097/00001756-199908200-00035 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 228BN UT WOS:000082116100036 PM 10574382 ER PT J AU Node, K Huo, YQ Ruan, XL Yang, BC Spiecker, M Ley, K Zeldin, DC Liao, JK AF Node, K Huo, YQ Ruan, XL Yang, BC Spiecker, M Ley, K Zeldin, DC Liao, JK TI Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids SO SCIENCE LA English DT Article ID EPOXYEICOSATRIENOIC ACIDS; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; EXPRESSION; HEART AB The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxy-genases that have vasodilatory properties similar to that of endothelium-derived hyperpolarizing factor. The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytokine-induced endothelial cell adhesion molecule expression, and EETs prevented leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-kappa B and I kappa B kinase. The inhibitory effects of EETs were independent of their membrane-hyperpolarizing effects, suggesting that these molecules play an important nonvasodilatory role in vascular inflammation. C1 Brigham & Womens Hosp, Div Cardiovasc, Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Virginia, Ctr Hlth Sci, Dept Biomed Engn, Charlottesville, VA 22908 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Vasc Med & Atherosclerosis Unit, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL052233-05, HL-52233, HL-58108, P01 HL048743, P01 HL048743-080008, P01 HL048743-090008, R01 HL052233, R01 HL052233-06] NR 20 TC 684 Z9 715 U1 0 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 20 PY 1999 VL 285 IS 5431 BP 1276 EP 1279 DI 10.1126/science.285.5431.1276 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228HC UT WOS:000082130200046 PM 10455056 ER PT J AU Mason, RP Mak, IT Trumbore, MW Mason, PE AF Mason, RP Mak, IT Trumbore, MW Mason, PE TI Antioxidant properties of calcium antagonists related to membrane biophysical interactions SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Can Physicians Always Explain the results of Clinical Trials - A Case Study of Amlodipine in Heart Failure CY SEP, 1997 CL PHOENIX, ARIZONA ID LIPID-PEROXIDATION; CHANNEL BLOCKERS; CARDIAC MEMBRANES; ENDOTHELIAL-CELLS; NIFEDIPINE; BINDING; ATHEROSCLEROSIS; PROTECTION; AMLODIPINE; VERAPAMIL AB The antioxidant activities of representative calcium antagonists, including amlodipine, verapamil, and diltiazem, were measured in hepatic microsomal membranes by the Fe-catalyzed, hydroxyl radical-producing system (dihydroxyfumarate + Fe3+) and assessed by malondialdehyde (MDA) formation. Despite the absence of L-type calcium channels in this membrane preparation, the calcium antagonists showed dose-dependent antioxidant activity. The biophysical mechanism for calcium-antagonist antioxidant activity was evaluated using radioligand binding assays, high-resolution differential scanning calorimetry, and small-angle x-ray diffraction approaches. These analyses demonstrated that calcium-antagonist antioxidant potency correlated directly with the compounds' relative affinity for the membrane lipid bilayer and ability to modulate membrane thermodynamic properties (amlodipine much greater than verapamil > diltiazem). The charged 1,4-dihydropyridine calcium antagonist, amlodipine, had the highest affinity for the membrane lipid bilayer (K-p >10(4)) and produced the largest changes in membrane thermodynamic properties, including a reduction in thermal phase transition temperature (- 11%), enthalpy (- 14%), and cooperative unit size (-59%), relative to control phosphatidylcholine liposomes. Electron density profiles generated from xray diffraction data demonstrated that amlodipine effected a broad and dose-dependent increase in molecular volume associated with the membrane hydrocarbon core. These data indicate that lipophilic calcium antagonists inhibit lipid peroxidation in cellular membranes as a result of modulating physicochemical properties of the membrane lipid bilayer, independently of calcium channel inhibition. Amlodipine had the most potent antioxidant activity as a result of distinct biophysical interactions with the membrane lipid bilayer. The nonreceptor-mediated antioxidant activity of calcium antagonists may contribute to cytoprotective mechanisms of action in cardiovascular diseases. (C) 1999 by Excerpta Medico, Inc. C1 Med Coll Penn & Hahnemann Univ, Sch Med, Dept Biochem & Med, Pittsburgh, PA USA. George Washington Univ, Med Ctr, Dept Med, Div Expt Med, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Physiol, Washington, DC 20037 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Mason, RP (reprint author), Allegheny Gen Hosp, 320 E 9th Ave, Pittsburgh, PA 15212 USA. NR 24 TC 55 Z9 58 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 19 PY 1999 VL 84 IS 4A SI SI BP 16L EP 22L PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231BD UT WOS:000082285400003 PM 10480441 ER PT J AU Alter, MJ Kruszon-Moran, D Nainan, OV McQuillan, GM Gao, FX Moyer, LA Kaslow, RA Margolis, HS AF Alter, MJ Kruszon-Moran, D Nainan, OV McQuillan, GM Gao, FX Moyer, LA Kaslow, RA Margolis, HS TI The prevalence of hepatitis C virus infection in the United States, 1988 through 1994 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT IX Triennial International Symposium on Viral Hepatitis and Liver Disease CY APR 21-25, 1996 CL ROME, ITALY ID NON-B-HEPATITIS; SEXUALLY-TRANSMITTED DISEASES; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-A; RISK-FACTORS; VIRAL-HEPATITIS; LIVER-DISEASE; BLOOD-DONORS; EPIDEMIOLOGY; TRANSFUSION AB Background Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. Methods We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. Results The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype la, and 17.0 percent with genotype Ib). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. Conclusions In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection. (N Engl J Med 1999;341:556-62.) (C)1999, Massachusetts Medical Society. C1 Ctr Dis Control & Prevent, Hepatitis Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NIAID, Bethesda, MD 20892 USA. RP Alter, MJ (reprint author), Ctr Dis Control & Prevent, Hepatitis Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Mailstop G37, Atlanta, GA 30333 USA. NR 41 TC 1916 Z9 1953 U1 10 U2 46 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 19 PY 1999 VL 341 IS 8 BP 556 EP 562 DI 10.1056/NEJM199908193410802 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 227CV UT WOS:000082061500002 PM 10451460 ER PT J AU Robles, AI Wang, XW Harris, CC AF Robles, AI Wang, XW Harris, CC TI Drug-induced apoptosis is delayed and reduced in XPD lymphoblastoid cell lines: possible role of TFIIH in p53-mediated apoptotic cell death SO ONCOGENE LA English DT Article DE DNA helicase; doxorubicin; DNA repair; programmed cell death ID NUCLEOTIDE EXCISION-REPAIR; DNA-DAMAGE; XERODERMA-PIGMENTOSUM; IONIZING-RADIATION; POLY(ADP-RIBOSE) POLYMERASE; GAMMA-RADIATION; P53; PHOSPHORYLATION; TRANSCRIPTION; ACTIVATION AB The tumor suppressor gene product p53 can bind to and inhibit the helicase activity of the multisubunit transcription-repair factor TFIIH, We previously reported that p53-mediated apoptosis is attenuated in primary human fibroblasts from individuals with Xeroderma Pigmentosum (XP) that harbor mutations in the TFIIH DNA helicases XPD or XPB, In this study we show that apoptosis is reduced and delayed in three XPD Iymphoblastoid cell lines (LCLs), but not in an XPD heterozygote LCL, after exposure to doxorubicin, a DNA-damaging agent and topoisomerase II inhibitor frequently used in cancer therapy. Apoptosis was assessed by quantitation of Annexin V binding to exposed phosphatidylserine residues and by caspase-mediated cleavage of Poly(ADP)Ribose Polymerase (PARP). Apoptosis induced by doxorubicin was suppressed in LCLs retrovirally transduced with the Human Papillomavirus 16 E6 oncoprotein, consistent with the hypothesis that this is a p53-dependent process. PARP cleavage was not delayed in XPD LCLs in response to anti-Fas (CD95) antibody-mediated apoptosis, thus, the defect in the apoptotic pathway in these cells lies upstream of caspase activation. Similar changes in the expression of apoptosis-effector genes, p53, and p53-responsive genes p21(cip/WAF-1/Sid1) p21), gadd45, bcl-2 and bar were observed in normal and XPD LCLs after treatment with doxorubicin, indicating that delayed apoptosis was not a consequence of defective transcription of these genes. Thus, our studies provide further support to the hypothesis that XPD and p53 can functionally interact in a p53-mediated apoptotic pathway. C1 NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bldg 37 Rm 2C05, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 41 TC 43 Z9 46 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 19 PY 1999 VL 18 IS 33 BP 4681 EP 4688 DI 10.1038/sj.onc.1202862 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 228UQ UT WOS:000082154400005 PM 10467415 ER PT J AU Devereux, TR Anna, CH Foley, JF White, CM Sills, RC Barrett, JC AF Devereux, TR Anna, CH Foley, JF White, CM Sills, RC Barrett, JC TI Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis SO ONCOGENE LA English DT Article DE beta-catenin mutations; chemical carcinogenesis; mouse liver tumors; beta-catenin expression; H-ras ID TUMOR-SUPPRESSOR PROTEIN; LIVER-TUMORS; SOMATIC MUTATIONS; RAS PROTOONCOGENE; B6C3F1 MICE; METHYLENE-CHLORIDE; COLON TUMORS; APC; CANCER; ACTIVATION AB beta-catenin activation, and subsequent upregulation of Wnt-signaling, is an important event in the development of certain human and rodent cancers. Recently, mutations in the beta-catenin gene in the region of the serine-threonine glycogen kinase (GSK)-3 beta phosphorylation target sites have been identified in hepatocellular neoplasms from humans and transgenic mice. In this study we: examined 152 hepatocellular neoplasms from B6C3F1 mice included in five chemical treatment groups and controls for mutations in the beta-catenin gene. Twenty of 29 hepatocellular neoplasms from mice treated with methyleugenol had point mutations at codons 32, 33, 33 or 41. sites which are mutated in colon and other cancers. Likewise, nine of 24 methylene chloride-induced hepatocellular neoplasms and 18 of 42 oxazepam-induced neoplasms exhibited similar mutations. In contrast,only three of 18 vinyl carbamate-induced liver tumors, one of 18 TCDD-induced liver tumors, and two of 22 spontaneous liver neoplasms had mutations in beta-catenin. Thus. there appears to be a chemical specific involvement of beta-catenin activation in mouse hepatocellular carcinogenesis. Expression analyses using Western blot and immunohistochemisty indicate that beta-catenin protein accumulates along cell membranes following mutation. The finding of mutations in both adenomas and carcinomas from diverse chemical treatment groups and the immunostaining of beta-catenin protein in an altered hepatocellular focus suggest that these alterations are early events in mouse hepatocellular carcinogenesis. C1 NIEHS, Mol Carcinogenesis Lab, Mol Toxicol Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Devereux, TR (reprint author), NIEHS, Mol Carcinogenesis Lab, Mol Toxicol Grp, MD D4-04,POB 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 94 Z9 96 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 19 PY 1999 VL 18 IS 33 BP 4726 EP 4733 DI 10.1038/sj.onc.1202858 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 228UQ UT WOS:000082154400010 PM 10467420 ER PT J AU Lorenzi, MV Castagnino, P Chen, Q Hori, Y Miki, T AF Lorenzi, MV Castagnino, P Chen, Q Hori, Y Miki, T TI Distinct expression patterns and transforming properties of multiple isoforms of Ost, an exchange factor for RhoA and Cdc42 SO ONCOGENE LA English DT Article DE expression cloning; cell cycle; alternative splicing; embryogenesis ID CELL-CYCLE PROGRESSION; ACTIN STRESS FIBERS; PROTEIN-KINASE-C; RAS TRANSFORMATION; ACTIVATION; GTPASES; ONCOGENE; RAC1; FAMILY; GENE AB A search for transforming genes expressed in brain led to the identification of a no, el isoform of Ost. an exchange factor for RhoA and Cdc42, In addition to the Dbl-homology (DH) and pleckstrin-homology (PH) domains identified in the original Ost, this isoform contained a SH3 domain and a novel) HIV-Tat related (TR) domain. The presence or absence of these domains in Ost defined multiple isoforms of the protein. RT-PCR and in situ hybridization analysis revealed that these isoforms were generated by tissue-specific and developmentally restricted alternative splicing events. Whereas deletion of the N-terminus activated the transforming properties of Ost, the presence of the SH3 domain reduced the transforming activity of the protein. This inhibition mas relieved by the presence of a TR domain, which contained a potential SH3 ligand sequence. The transforming activity of all Ost isoforms was inhibited by dominant negative forms of the Rho family proteins. Expression of Ost isoforms potently induced the formation of actin stress fibers and filopodia as well as JNK activity and AP1- and SRF-regulated transcriptional pathways. Ost transfectants also displayed elevated levels of cyclins A and D1, suggesting that the de-regulation of these cyclins is linked to Oat-mediated transformation. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37 Room 1E24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 35 TC 20 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 19 PY 1999 VL 18 IS 33 BP 4742 EP 4755 DI 10.1038/sj.onc.1202851 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 228UQ UT WOS:000082154400012 PM 10467422 ER PT J AU DerSimonian, R Levine, RJ AF DerSimonian, R Levine, RJ TI Resolving discrepancies between a meta-analysis and a subsequent large controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PREGNANCY-INDUCED HYPERTENSION; ACUTE MYOCARDIAL-INFARCTION; CALCIUM SUPPLEMENTATION; CLINICAL-TRIALS; METAANALYSIS; PREECLAMPSIA; PREVENTION; RISK; DESIGN AB Context A recent mete-analysis found calcium supplementation to be highly effective in preventing preeclampsia but a large National Institutes of Health trial (Calcium for Preeclampsia Prevention [CPEP]) found no risk reduction due to calcium in healthy nulliparous women. Objectives To resolve discrepancies between the results of the meta-analysis and the CPEP trial and to assess the role of effect heterogeneity in the discrepancies. Data Sources Literature search of English-language articles published prior to July 10, 1997, the date of publication of the CPEP trial, using MEDLINE and by a manual search of bibliographies of published articles. Study Selection Trials were included if they reported data on preeclampsia and calcium supplementation. Fourteen trials were systematically evaluated for differences in study design and patient populations. One trial was excluded because its results were reported after publication of the major CPEP results. Data Extraction The sample size and number of subjects who developed preeclampsia in the calcium supplementation group vs a control group were recorded and analyzed on an intent-to-treat basis. Each author independently extracted the data. Data Synthesis Substantial heterogeneity existed across trials (P = .001). After stratifying studies by the presence of a placebo-controlled group and by high-risk and low-risk populations, the conclusions of the meta-analysis of placebo-controlled trials enrolling a low-risk population (relative risk, 0.79; 99% confidence interval, 0.44-1.42; P = .30) were compatible with the conclusions of the CPEP trial that calcium supplementation does not prevent preeclampsia in healthy nulliparous women. In contrast, the data implied a strong beneficial calcium effect (relative risk, 0.19; 99% confidence interval, 0.08-0.46; P = .001) in healthy high-risk subject populations. However, only 225 women were analyzed and because of inconsistent data, these results remain equivocal. Conclusions Further studies are needed to establish the efficacy of calcium for preeclampsia prevention in healthy high-risk populations. A single summary measure does not adequately describe the findings of a meta-analysis when the observed effects in individual studies differ substantially. In such settings the primary focus should be to identify and incorporate pertinent covariates that reduce heterogeneity and allow for optimum treatment strategies. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP DerSimonian, R (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. NR 47 TC 50 Z9 53 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 18 PY 1999 VL 282 IS 7 BP 664 EP 670 DI 10.1001/jama.282.7.664 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 226QY UT WOS:000082033700026 PM 10517720 ER PT J AU Bergen, AW Caporaso, N AF Bergen, AW Caporaso, N TI Cigarette smoking SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID HUMAN LIVER-MICROSOMES; SUBSTANCE USE DISORDERS; FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINIC ACETYLCHOLINE-RECEPTORS; UNITED-STATES; TOBACCO DEPENDENCE; MAJOR DEPRESSION; LUNG-CANCER; RACIAL-DIFFERENCES; YOUNG-ADULTS AB Cigarette smoking is the largest preventable risk factor for morbidity and mortality in developed countries. Dramatic changes in the prevalence of cigarette smoking in the second half of this century in the United States (i.e., a reduction among men and an increase among women) have reduced current smoking levels to approximately one quarter of the adult population and have reduced differences in smoking prevalence and smoking-attributable diseases between the sexes, Current smoking in the United States is positively associated with younger age, lower income, reduced educational achievement, and disadvantaged neighborhood environment. Daily smokers smoke cigarettes to maintain nicotine levels in the brain, primarily to avoid the negative effects of nicotine withdrawal, but also to modulate mood. Regular smokers exhibit higher and lower levels of stress and arousal, respectively, than nonsmokers, as well as higher impulsivity and neuroticism trait values. Nicotine dependence is the single most common psychiatric diagnosis in the United States, and substance abuse, major depression, and anxiety disorders are the most prevalent psychiatric comorbid conditions associated with nicotine dependence. Studies in twins have implicated genetic factors that explain most of the variability in vulnerability to smoking and in persistence of the smoking phenotype, Future research into the causes of smoking must take into account these associated demographics, social factors, comorbid psychiatric conditions, and genetic factors to understand this complex human behavior. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Bergen, AW (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Rm 7110, Bethesda, MD 20892 USA. EM Bergena@epndce.nci.nih.gov OI Bergen, Andrew/0000-0002-1237-7644 NR 185 TC 127 Z9 130 U1 7 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD AUG 18 PY 1999 VL 91 IS 16 BP 1365 EP 1375 DI 10.1093/jnci/91.16.1365 PG 11 WC Oncology SC Oncology GA 227EG UT WOS:000082064900010 PM 10451441 ER PT J AU Magrath, I Bhatia, K AF Magrath, I Bhatia, K TI Breast cancer: a new Epstein-Barr virus-associated disease? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID IN-SITU HYBRIDIZATION; MEDULLARY CARCINOMA; CELL TUMORS; INFECTION; EPITHELIUM; ABSENCE C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Magrath, I (reprint author), NCI, Div Clin Sci, NIH, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 20 TC 21 Z9 21 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 18 PY 1999 VL 91 IS 16 BP 1349 EP 1350 DI 10.1093/jnci/91.16.1349 PG 2 WC Oncology SC Oncology GA 227EG UT WOS:000082064900001 PM 10451431 ER PT J AU Legler, JM Ries, LAG Smith, MA Warren, JL Heineman, EF Kaplan, RS Linet, MS AF Legler, JM Ries, LAG Smith, MA Warren, JL Heineman, EF Kaplan, RS Linet, MS TI Brain and other central nervous system cancers: Recent trends in incidence and mortality SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ELECTRIC UTILITY WORKERS; ONSET AQUEDUCTAL STENOSIS; NESTED CASE-CONTROL; UNITED-STATES; OCCUPATIONAL EXPOSURE; MAGNETIC-FIELDS; MATERNAL DIET; STEM GLIOMAS; TUMORS; CHILDHOOD AB Background: During the 1980s, the incidence of primary malignant brain and other central nervous system tumors (hereafter called brain cancer) was reported to be increasing among all age groups in the United States, while mortality was declining for persons younger than 65 years. We analyzed these data to provide updates on incidence and mortality trends for brain cancer in the United States and to examine these patterns in search of their causes. Methods: Data on incidence, overall and according to histology and anatomic site, and on relative survival were obtained from the Surveillance, Epidemiologyl and End Results (SEER) Program of the National Cancer Institute for 1975 through 1995, Mortality data were obtained from the National Center for Health Statistics. Medicare procedure claims from the National Cancer Institute's SEER-Medicare database were used for imaging trends. Statistically significant changes in incidence trends were identified, and annual percent changes mere computed for log linear models. Results/Conclusions: Rates stabilized for all age groups during the most recent period for which SEER data were available, except for the group containing individuals 85 years of age or older, Mortality trends continued to decline for the younger age groups, and the steep increases in mortality seen in the past for the elderly slowed substantially, Patterns differed by age group according to the site and grade of tumors between younger and older patients. During the last decade, use of computed tomography scans was relatively stable for those 65-74 years old but increased among those 85 years old or older. Implications: Improvements in diagnosis and changes in the diagnosis and treatment of elderly patients provide likely explanations for the observed patterns in brain cancer trends. C1 NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Etiol, NIH, Bethesda, MD 20892 USA. RP Legler, JM (reprint author), NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Execut Plaza N,Suite 313, Bethesda, MD 20892 USA. NR 64 TC 293 Z9 302 U1 1 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 18 PY 1999 VL 91 IS 16 BP 1382 EP 1390 DI 10.1093/jnci/91.16.1382 PG 9 WC Oncology SC Oncology GA 227EG UT WOS:000082064900012 PM 10451443 ER PT J AU Gilbert, ES Tarone, R Bouville, A Ron, E AF Gilbert, ES Tarone, R Bouville, A Ron, E TI Thyroid cancer rates and I-131 doses from Nevada atmospheric nuclear bomb tests - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Biol, Bethesda, MD 20892 USA. RP Gilbert, ES (reprint author), NIH, Execut Plaza N,Rm 408, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 18 PY 1999 VL 91 IS 16 BP 1424 EP 1425 DI 10.1093/jnci/91.16.1424 PG 2 WC Oncology SC Oncology GA 227EG UT WOS:000082064900025 ER PT J AU Engels, EA Rosenberg, PS O'Brien, TR Goedert, JJ AF Engels, EA Rosenberg, PS O'Brien, TR Goedert, JJ CA Multicenter Hemophilia Cohort Study TI Plasma HIV viral load in patients with hemophilia and late-stage HIV disease: A measure of current immune suppression SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA LEVELS; ANTIRETROVIRAL THERAPY; LYMPHOCYTE COUNTS; TYPE-1 INFECTION; PROGNOSTIC VALUE; IN-VIVO; AIDS; MACROPHAGES; PROGRESSION AB Background: For patients infected with HIV, plasma HIV viral load in early disease predicts long-term prognosis. However, the implications of viral load measurements late in HIV disease are uncertain. Objective: To evaluate the relation between plasma HIV viral load and subsequent risk for disease progression in patients with late-stage HIV disease. Design: Retrospective cohort study. Setting: 16 treatment centers for patients with hemophilia. Patients: 389 patients with hemophilia and late-stage HIV disease (CD4 count < 200 cells/mm(3)). Measurements: Plasma HIV viral load was measured at baseline. Patients were followed for AIDS-related illnesses (primary outcome) and, specifically, Pneumocystis carinii pneumonia (secondary outcome). Results: HIV viral load strongly predicted AIDS-related illness. For patients with viral loads less than 4.00 log(10) copies/mL, the 1-year actuarial risk was 0% and the 5-year risk was 25%. For patients with viral loads of at least 6.00 log(10) copies/mL, the 1-year actuarial risk was 42% and the 5-year risk was 78%. A linear relation existed between viral load a nd risk for AIDS-related illness (hazard ratio, 2.37 per log(10) copies/mL; P < 0.001). In addition, viral load most strongly predicted risk for illness immediately after viral load testing; this predictive relation attenuated over time (P = 0.002). These findings changed little after adjustment for CD4 cell counts that were updated during follow-up. In the first year after viral load was measured, it predicted occurrence of P, carinii pneumonia (hazard ratio, 4.69 per log(10) copies/mL; P < 0.001). Conclusions: In patients with hemophilia and late-stage HIV disease, viral load predicts disease progression independently of CD4 cell counts. Because viral load most strongly predicts progression immediately after load is measured, it seems to reflect the current level of immunosuppression. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20822 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20822 USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8005, Rockville, MD 20822 USA. FU NCI NIH HHS [N01-CP-33002] NR 36 TC 15 Z9 15 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 17 PY 1999 VL 131 IS 4 BP 256 EP + PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 226GR UT WOS:000082012500003 PM 10454946 ER PT J AU Folsom, AR Rosamond, WD Shahar, E Cooper, LS Aleksic, N Nieto, FJ Rasmussen, ML Wu, KK AF Folsom, AR Rosamond, WD Shahar, E Cooper, LS Aleksic, N Nieto, FJ Rasmussen, ML Wu, KK CA ARIC Study Investigators TI Prospective study of markers of hemostatic function with risk of ischemic stroke SO CIRCULATION LA English DT Article DE stroke; ischemia; hemostasis ID VON-WILLEBRAND-FACTOR; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; BLOOD-CELL COUNT; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; CEREBROVASCULAR-DISEASE; FACTOR-VIII; FIBRINOGEN; DEATH AB Background-Several markers of hemostatic function and inflammation have been associated with increased risk of coronary heart disease, but prospective evidence for their role in ischemic stroke is scant. Methods and Results-The Atherosclerosis Risk in Communities (ARIC) Study measured several of these markers in more than 14 700 participants 45 to 64 years old who were free of cardiovascular disease and were followed up for 6 to 9 years for occurrence of ischemic stroke (n=191), There was no apparent association between ischemic stroke incidence and factor VIIc, antithrombin III. platelet count, or activated partial thromboplastin time. After adjustment for multiple cardiovascular risk factors, von Willebrand factor, factor VIIIc, fibrinogen, and white blood cell count were positively associated and protein C was negatively but nonsignificantly associated with ischemic stroke incidence in regression analyses based on either continuous variables or fourths of the variable distributions. The adjusted relative risk land 95% CI) for ischemic stroke in those in the highest versus lowest fourth were: von Willebrand factor, 1.71 (1.1 to 2.7); factor VIIIc, 1.93 (1.2 to 3.1); white blood cell count, 1.50 (0.9 to 2.4), fibrinogen. 1.26 (0.8 to 2.0); and protein C, 0.65 (0.4 to 1.0), Conclusions-This study offers modest support for the hypothesis that some markers of hemostatic function and inflammation can identify groups of middle-aged adults at increased risk of stroke. These factors may play a role in the pathogenesis of ischemic stroke. C1 Univ Texas, Sch Med, Div Hematol, Houston, TX 77030 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Wu, KK (reprint author), Univ Texas, Sch Med, Div Hematol, 6431 Fannin,MSB 5-234, Houston, TX 77030 USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 31 TC 288 Z9 300 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 17 PY 1999 VL 100 IS 7 BP 736 EP 742 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 227LY UT WOS:000082082900010 PM 10449696 ER PT J AU Pause, A Peterson, B Schaffar, G Stearman, R Klausner, RD AF Pause, A Peterson, B Schaffar, G Stearman, R Klausner, RD TI Studying interactions of four proteins in the yeast two-hybrid system: Structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; ENDOTHELIAL GROWTH-FACTOR; F-BOX PROTEIN; HIPPEL-LINDAU-DISEASE; CELL-CYCLE EXIT; GENE-PRODUCT; HUMAN CUL-1; ELONGIN-C; PROTEOLYSIS; DEGRADATION AB The yeast two hybrid system is a powerful technique that detects interactions between two proteins and has been useful in identifying new binding partners. However, the system fails to detect protein-protein interactions that require the presence of additional components of a multisubunit complex. Here we demonstrate that the vector YIpDCE1 can be used to express elongins B and C in yeast, and that these proteins form a stable complex that interacts with the von Hippel-Lindau tumor-suppressor gene product (pVHL). Only when pVHL and elongins B and C (VBC) are present does an interaction with the cullin family member, hCUL-2, occur, forming the heterotetrameric pVHL/elongin BC/hCUL-2 complex. This system was then used to map the binding region of hCUL-2 for the VBC complex, The first amino-terminal 108 aa of hCUL-2 are necessary for interaction with the VBC complex. The elongin BC dimer acts as a bridge between pVHL and hCUL-2 because pVHL and hCUL-2 can form distinct complexes with elongins B and C. These results reveal a striking structural resemblance of pVHL/elongin BC/hCUL-2 complex with the E3-like ubiquitin ligase complex SKP1/Cullin/F-box protein with respect to protein composition and sites of interactions. Thus, it seems possible that pVHL/elongin BC/hCUL-2 complex will possess ubiquitin ligase activity targeting specific proteins for degradation by the proteasome. C1 Max Planck Inst Biochem, Mol Oncol Grp, D-82152 Martinsried, Germany. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Stearman, R (reprint author), Bldg 18T Room 101,MSC5430,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 73 Z9 75 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9533 EP 9538 DI 10.1073/pnas.96.17.9533 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500018 PM 10449727 ER PT J AU Liu, XH Castelli, JC Youle, RJ AF Liu, XH Castelli, JC Youle, RJ TI Receptor-mediated uptake of an extracellular Bcl-x(L) fusion protein inhibits apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diphtheria toxin; Bax; Bcl-2; immunotoxin; endocytosis ID CELL-DEATH PATHWAY; DIPHTHERIA-TOXIN; ION-CHANNEL; BCL-2; BAX; CYTOSOL; MEMBRANES; ACTIVATION; PROTEASES; FORMS AB Bcl-x(L), a member of the Bcl-2 family, inhibits many pathways of apoptosis when overexpressed in the cell cytosol. We examined the capacity of Bcl-x(L) fusion proteins to bind cells from the outside and block apoptosis. Full-length Bcl-x(L) protein at micromolar concentrations did not affect apoptosis when added to cell media. To increase uptake by cells, Bcl-x(L) was fused to the receptor-binding domain of diphtheria toxin (DTR), The Bcl-x(L)-DTR fusion protein blocked apoptosis induced by staurosporine, gamma-irradiation, and poliovirus in a variety of cell types when added to media, The potency of inhibition of poliovirus-induced apoptosis by Bcl-x(L)-DTR was greater than that of strong caspase inhibitors. Brefeldin A, an inhibitor of vesicular traffic between the endoplasmic reticulum and Golgi apparatus, prevented the Bcl-x(L)-DTR blockade of apoptosis induced by staurosporine, suggesting that Bcl-x(L)-DTR must be endocytosed and reach intracellular compartments for activity, Many diseases are caused by overexpression or underexpression of Bcl-x(L) homologues, Extracellular delivery of Bcl-2 family member proteins may have a wide range of uses in promoting or preventing cell death. C1 NIH, Biochem Sect, Surg Neurol Branch, NINDS, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NIH, Biochem Sect, Surg Neurol Branch, NINDS, Bldg 10,Room 5D-37,MSC 1414,10 Ctr Dr, Bethesda, MD 20892 USA. NR 36 TC 21 Z9 24 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9563 EP 9567 DI 10.1073/pnas.96.17.9563 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500023 PM 10449732 ER PT J AU Linder, S Nelson, D Weiss, M Aepfelbacher, M AF Linder, S Nelson, D Weiss, M Aepfelbacher, M TI Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS-TRANSFORMED FIBROBLASTS; ACTIN-DEPOLYMERIZING PROTEIN; N-WASP; GTPASE CDC42HS; CELLS; RHO; POLYMERIZATION; EXPRESSION; MEMBRANE; BINDING AB Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC 42Bs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages, Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes, Conversely, macrophages from patients expressing truncated forms of WASp completely lacked po dosomes, These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages. C1 Max von Pettenkofer Inst Med Mikrobiol, D-80336 Munich, Germany. Univ Munich, Inst Prophylaxe & Epidemiol Kreislaufkrankheiten, D-80336 Munich, Germany. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Munich, Dr Von Haunerschen Kinderspital, Klinikum Innenstadt, D-80337 Munich, Germany. RP Linder, S (reprint author), Max von Pettenkofer Inst Med Mikrobiol, Pettenkoferstr 9A, D-80336 Munich, Germany. NR 38 TC 279 Z9 282 U1 3 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9648 EP 9653 DI 10.1073/pnas.96.17.9648 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500039 PM 10449748 ER PT J AU Everett, LA Morsli, H Wu, DK Green, ED AF Everett, LA Morsli, H Wu, DK Green, ED TI Expression pattern of the mouse ortholog of the Pendred's syndrome gene (Pds) suggests a key role for pendrin in the inner ear SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SENSORINEURAL HEARING-LOSS; VESTIBULAR AQUEDUCT; MUTATIONS; COCHLEA; LOCALIZATION AB Pendred's syndrome is an autosomal-recessive disorder characterized by deafness and goiter. After our recent identification of the human gene mutated in Pendred's syndrome (PDS), we sought to investigate in greater detail the expression of the gene and the function of its encoded protein (pendrin), Toward that end,,ve isolated the corresponding mouse ortholog (Pds) and performed RNA in situ hybridization on mouse inner ears (from 8 days postcoitum to postnatal day 5) to establish the expression pattern of Pds in the developing auditory and vestibular systems. Pds expression was detected throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea, This highly discrete expression pattern is unlike that of any other known gene and involves several regions thought to be important for endolymphatic fluid resorption in the inner ear, consistent with the putative functioning of pendrin as an anion transporter, These studies provide key first steps toward defining the precise role of pendrin in inner ear development and elucidating the pathogenic mechanism for the deafness seen in Pendred's syndrome. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Green, ED (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, 49 Convent Dr,Bldg 49,Room 2A08, Bethesda, MD 20892 USA. NR 45 TC 193 Z9 206 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9727 EP 9732 DI 10.1073/pnas.96.17.9727 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500053 PM 10449762 ER PT J AU Hukriede, NA Joly, L Tsang, M Miles, J Tellis, P Epstein, JA Barbazuk, WB Li, FN Paw, B Postlethwait, JH Hudson, TJ Zon, LI McPherson, JD Chevrette, M Dawid, IB Johnson, SL Ekker, M AF Hukriede, NA Joly, L Tsang, M Miles, J Tellis, P Epstein, JA Barbazuk, WB Li, FN Paw, B Postlethwait, JH Hudson, TJ Zon, LI McPherson, JD Chevrette, M Dawid, IB Johnson, SL Ekker, M TI Radiation hybrid mapping of the zebrafish genome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENETIC-LINKAGE MAP; DANIO-RERIO; IDENTIFICATION; CHROMOSOMES; IRRADIATION AB The zebrafish is an excellent genetic system for the study of vertebrate development and disease. In an effort to provide a rapid and robust tool for zebrafish gene mapping, a panel of radiation hybrids (RH) was produced by fusion of irradiated zebrafish AB9 cells with mouse B78 cells. The overall retention of zebrafish sequences in the 93 RH cell lines that constitute the LN54 panel is 22%. Characterization of the LN54 panel with 849 simple sequence length polymorphism markers, 84 cloned genes and 122 expressed sequence tags allowed the production of an RH map whose total size was 11,501 centiRays. From this value, we estimated the average breakpoint frequency of the LN54 RH panel to correspond to 1 centiRay = 148 kilobase. Placement of a group of 235 unbiased markers on the RH map suggests that the map generated for the LN54 panel, at present, covers 88% of the zebrafish genome. Comparison of marker positions in RH and meiotic maps indicated a 96% concordance. Mapping expressed sequence tags and cloned genes by using the LN54 panel should prove to be a valuable method for the identification of candidate genes for specific mutations in zebrafish. C1 Univ Ottawa, Loeb Hlth Res Inst, Ottawa Hosp, Dept Med, Ottawa, ON K1Y 4E9, Canada. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Biol Computat, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. McGill Univ, Dept Surg, Montreal, PQ H3G 1A4, Canada. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. RP Ekker, M (reprint author), Univ Ottawa, Loeb Hlth Res Inst, Ottawa Hosp, Dept Med, 725 Parkdale Ave, Ottawa, ON K1Y 4E9, Canada. RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 FU NCRR NIH HHS [R01-RR10715, R01 RR010715]; NIDDK NIH HHS [R01 DK055381, R01 DK55379, R01 DK55381] NR 25 TC 247 Z9 248 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9745 EP 9750 DI 10.1073/pnas.96.17.9745 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500056 PM 10449765 ER PT J AU Young, MR Li, JJ Rincon, M Flavell, RA Sathyanarayana, BK Hunziker, R Colburn, N AF Young, MR Li, JJ Rincon, M Flavell, RA Sathyanarayana, BK Hunziker, R Colburn, N TI Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYPE-16 E7 ONCOGENE; MOUSE SKIN; GENE-EXPRESSION; INDUCED TRANSFORMATION; C-JUN; DELETION MUTANT; PHORBOL ESTERS; FOS; CARCINOGENESIS; CELLS AB Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer, Transactivation of AP-1 is required for tumor promoter-induced transformation in mouse epidermal JB6 cells and for progression in mouse and human keratinocytes, Until now, the question of whether AP-1 transactivation is required for carcinogenesis in vivo has remained unanswered, as has the issue of functionally significant target genes. To address these issues we have generated a transgenic mouse in which transactivation mutant c-jun (TAM67), under the control of the human keratin-14 promoter, is expressed specifically in the basal cells of the epidermis where tumor induction is initiated. The keratin-14-TAM67 transgene was expressed in the epidermis, tongue, and cervix, with no apparent abnormalities in any tissue or organ, TAM67 expression blocked 12-O-tetradecanoylphorbol 13-acetate (TPA, phorbol 12-tetradecanoate 13-acetate) induction of the AP-1-regulated luciferase in AP-1 luciferase/TAM67 mice, but did not inhibit induction of candidate AP-1 target genes, collagenase-1 or stromelysin-3, More interestingly, TAM67 expression did not inhibit TPA-induced hyperproliferation. In two-stage skin carcinogenesis experiments, the transgenic animals showed a dramatic inhibition of papilloma induction. We conclude that transactivation of a subset of AP-l-dependent genes is required for tumor promotion and may be targeted for cancer prevention. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. NCI, Adv Biosci Labs, Basic Res Program, Frederick, MD 21702 USA. NIAID, Transgen Mouse Facil, Frederick, MD 21702 USA. Univ Vermont, Dept Med, Program Immunobiol, Burlington, VT 05405 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA. RP Young, MR (reprint author), NCI, Basic Res Lab, Frederick, MD 21702 USA. NR 52 TC 324 Z9 330 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9827 EP 9832 DI 10.1073/pnas.96.17.9827 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500070 PM 10449779 ER PT J AU Barlow, C Dennery, PA Shigenaga, MK Smith, MA Morrow, JD Roberts, LJ Wynshaw-Boris, A Levine, RL AF Barlow, C Dennery, PA Shigenaga, MK Smith, MA Morrow, JD Roberts, LJ Wynshaw-Boris, A Levine, RL TI Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATM-DEFICIENT MICE; HEME OXYGENASE; LIPID-PEROXIDATION; P53; KINASE; TOXICITY; PHOSPHORYLATION; RESISTANCE; INDUCTION; RADIATION AB Ataxia-telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of cancer, and neurodegeneration, especially of the cerebellar Purkinje cells. Ionizing radiation oxidizes macromolecules and causes tissue damage through the generation of reactive oxygen species (ROS), We therefore hypothesized that A-T is due to oxidative damage resulting from loss of function of the A-T gene product. To assess this hypothesis, we employed an animal model of A-T, the mouse with a disrupted Atm gene, We show that organs which develop pathologic changes in the Atm-deficient mice are targets of oxidative damage, and that cerebellar Purkinje cells are particularly affected. These observations provide a mechanistic basis for the A-T phenotype and lay a rational foundation for therapeutic intervention. C1 Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. NIH, Natl Ctr Human Genome Res, Lab Genet Dis Res, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94035 USA. Univ Calif Berkeley, Dept Biochem & Mol Biol, Berkeley, CA 94720 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Nashville, TN 37232 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Barlow, C (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Smith, Mark/A-9053-2009; Levine, Rodney/D-9885-2011; OI Dennery, Phyllis/0000-0001-5745-1855 FU NHLBI NIH HHS [HL58782]; NIDDK NIH HHS [DK48831, R01 DK048831]; NIGMS NIH HHS [GM42056, P01 GM015431, P50 GM015431, R01 GM042056, R37 GM042056] NR 32 TC 165 Z9 169 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 17 PY 1999 VL 96 IS 17 BP 9915 EP 9919 DI 10.1073/pnas.96.17.9915 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500085 PM 10449794 ER PT J AU Zhang, XP Morham, SG Langenbach, R Young, DA AF Zhang, XP Morham, SG Langenbach, R Young, DA TI Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cyclooxygenase; nonsteroidal antiinflammatory drugs; neoplastic transformation; transgenic knockout cells; ras ID CARCINOMA CELL-LINES; COLON-CANCER CELLS; ARACHIDONIC-ACID; SULINDAC SULFIDE; EPITHELIAL-CELLS; GENE DISRUPTION; MESSENGER-RNA; APOPTOSIS; EXPRESSION; INDUCTION AB In this study, we use primary embryonic fibroblasts derived from cyclooxygenase-deficient transgenic embryos to further investigate the role of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), in the process of neoplastic transformation. Cells with either, neither, or both of the cyclooxygenases were transformed by Ha-ras and/or SV40. Our results show that when a cyclooxygenase enzyme is present, the transformed cells have marked increases in COX-2 and/or COX-1 expression. Nevertheless, each type of cell, deficient in either or both cyclooxygenases, can be readily transformed at almost equal efficiency. Different nonsteroidal antiinflammatory drugs (NSAIDs) were used to examine their possible antineoplastic effects on the transformed cells, which have various levels of expression of COX-1 or COX-2. Our results show that NSAIDs suppress the colony formation in soft agar in a dosage-dependent manner in the absence of the cyclooxygenase(s). Thymidine incorporation and apoptosis analyses further demonstrate that the NSAIDs are effective in the cyclooxygenase-null cells. Our findings with cyclooxygenase knockout cells confirm recent reports that some of the antiproliferative and antineoplastic effects of NSAIDs are independent of the inhibition of either COX-1 or COX-2. They also show that transformation is independent of the status of cyclooxygenase expression, suggesting that the involvement of the cyclooxygenases in tumorigenesis may occur at later steps. C1 Univ Rochester, Med Ctr, Dept Med, Div Endocrinol & Metab,Sch Med & Dent, Rochester, NY 14642 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Young, DA (reprint author), Univ Rochester, Med Ctr, Dept Med, Div Endocrinol & Metab,Sch Med & Dent, Box 693,601 Elmwood Ave, Rochester, NY 14642 USA. FU NIADDK NIH HHS [R01AM-16177] NR 46 TC 228 Z9 234 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 16 PY 1999 VL 190 IS 4 BP 451 EP 459 DI 10.1084/jem.190.4.451 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 228VR UT WOS:000082156800002 PM 10449516 ER PT J AU Song, XY Zeng, L Jin, WW Thompson, J Mizel, DE Lei, KJ Billinghurst, RC Poole, AR Wahl, SM AF Song, XY Zeng, L Jin, WW Thompson, J Mizel, DE Lei, KJ Billinghurst, RC Poole, AR Wahl, SM TI Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE inflammation; cartilage resorption; serine protease inhibitor ID HUMAN ARTICULAR-CARTILAGE; PROTEINASE-INHIBITOR; NEUTROPHIL ELASTASE; HUMAN-MONOCYTES; II COLLAGEN; CATHEPSIN-G; DEGRADATION; MATRIX; LIPOPOLYSACCHARIDE; ANTILEUKOPROTEASE AB Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor alpha and nuclear factor kappa B activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generate cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Joint Dis Lab, Shriners Hosp Children, Div Surg Res,Dept Surg, Montreal, PQ H3G 1A6, Canada. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 332,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 45 TC 117 Z9 122 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 16 PY 1999 VL 190 IS 4 BP 535 EP 542 DI 10.1084/jem.190.4.535 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 228VR UT WOS:000082156800010 PM 10449524 ER PT J AU Bicout, DJ Berezhkovskii, AM Szabo, A Weiss, GH AF Bicout, DJ Berezhkovskii, AM Szabo, A Weiss, GH TI Kramers-like turnover in activationless rate processes SO PHYSICAL REVIEW LETTERS LA English DT Article AB The activationless escape of a free Brownian particle from a unit interval is analyzed over the entire range of friction coefficient gamma. Approximate analytic expressions that compare favorably with simulations are derived for the effective and asymptotic rate constants k and Gamma that describe the escape kinetics. Both rate constants show a turnover behavior as functions of gamma, qualitatively similar to the rate constant in the Kramers theory of activated rate processes. It is found that k similar to 1/ln(1/gamma) and Gamma similar to gamma(1/3) as gamma --> 0 while both rate constants vanish as gamma(-1) as gamma --> infinity. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM bicout@speck.niddk.nih.gov RI Szabo, Attila/H-3867-2012 NR 9 TC 6 Z9 6 U1 0 U2 3 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 EI 1079-7114 J9 PHYS REV LETT JI Phys. Rev. Lett. PD AUG 16 PY 1999 VL 83 IS 7 BP 1279 EP 1282 DI 10.1103/PhysRevLett.83.1279 PG 4 WC Physics, Multidisciplinary SC Physics GA 227EY UT WOS:000082066600002 ER PT J AU Aamodt, R AF Aamodt, R TI On Harvey, Sulstan, and Darwin SO SCIENTIST LA English DT Letter C1 NCI, Resources Dev Branch, Canc Diagnosis Program, DCTD, Bethesda, MD 20892 USA. RP Aamodt, R (reprint author), NCI, Resources Dev Branch, Canc Diagnosis Program, DCTD, 6130 Execut Blvd,EPN 700, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD AUG 16 PY 1999 VL 13 IS 16 BP 12 EP 12 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 243MH UT WOS:000083001500009 ER PT J AU Alter, HJ AF Alter, HJ TI Hot papers - Virology - The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease by H. J. Alter, Y. Nakatsuji, J. Melpolder, J. Wages, R. Wesley, J.W.K. Shih, J.P. Kim - Comments SO SCIENTIST LA English DT Editorial Material AB Miriam J. Alter of the Centers for Disease Control and Prevention and Harvey J. Alter of the National Institutes of Health discuss the hepatitis G virus. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Alter, HJ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD AUG 16 PY 1999 VL 13 IS 16 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 243MH UT WOS:000083001500013 ER PT J AU Weinberg, CR Wilcox, AJ AF Weinberg, CR Wilcox, AJ TI "Distinguishing the effects of maternal and offspring genes through studies of 'case-parent triads' " and "a new method for estimating the risk ratio in studies using case-parental control design" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 5 TC 10 Z9 10 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1999 VL 150 IS 4 BP 428 EP 429 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 225NL UT WOS:000081967600014 PM 10453820 ER PT J AU Longnecker, MP Michalek, JE AF Longnecker, MP Michalek, JE TI Weight history, glucose intolerance, and insulin levels in middle-aged Swedish men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID VETERANS C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. USAF, Res Lab, Brooks AFB, TX 78235 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 3 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1999 VL 150 IS 4 BP 430 EP 431 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 225NL UT WOS:000081967600017 PM 10453822 ER PT J AU Vance, BA Bennett, MJ Ward, Y Gress, RG Kearse, KP AF Vance, BA Bennett, MJ Ward, Y Gress, RG Kearse, KP TI Distinct but dispensable N-glycosylation of human CD69 proteins SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE CD69; glycosylation; asparagine; posttranslational modification ID ACTIVATION ANTIGEN CD69; ENDOPLASMIC-RETICULUM; EXPRESSION; RECEPTOR; CELLS; AIM/CD69; CLONING; DOMAIN; SITES AB Human CD69 is uniquely glycosylated at typical (Asn-X-Ser/Thr) and atypical (Asn-X-Cys) motifs, which represents the molecular basis for the formation of CD69 homodimers and heterodimers. Here we examined the importance of N-glycosylation for the assembly and intracellular transport of CD69 proteins using mutant CD69 molecules that specifically lack typical and atypical N-glycan attachment motifs. These studies verify the importance of Cys residues in atypical triplet sequences for N-glycan addition to human CD69 proteins in the endoplasmic reticulum (ER). In addition, these data demonstrate that monoglycosylated CD69 proteins (bearing N-glycans exclusively at atypical or typical sites) and aglycosylated CD69 molecules (lacking N-glycans) efficiently dimerize in the ER and have similar stability as wild-type CD69 molecules. Finally, these results show that CD69 proteins lacking atypical or typical N-glycan addition sites are transported to the plasma membrane. (C) 1999 Academic Press. C1 E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. NCI, Transplantat Therapy Sect, NIH, Bethesda, MD 20892 USA. NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. RP Kearse, KP (reprint author), E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 15 PY 1999 VL 368 IS 2 BP 214 EP 220 DI 10.1006/abbi.1999.1322 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 230LM UT WOS:000082252700002 PM 10441371 ER PT J AU Mou, S Linnekin, D AF Mou, S Linnekin, D TI Lyn is activated during late G(1) of stem-cell-factor-induced cell cycle progression in haemopoietic cells SO BIOCHEMICAL JOURNAL LA English DT Article DE growth factors; haematopoiesis; receptor tyrosine kinase; signal transduction; Src family members ID COLONY-STIMULATING FACTOR; C-KIT LIGAND; GROWTH-FACTOR; TYROSINE KINASE; PROTEIN-KINASE; DEPENDENT KINASE-2; PHOSPHORYLATION; MITOSIS; INTERLEUKIN-3; ASSOCIATION AB Stem cell factor (SCF) binds the receptor tyrosine kinase c-Kit and is critical in haemopoiesis. Recently we found that the Src family member Lyn is highly expressed in SCF-responsive cells, associates with c-Kit and is activated within minutes of the addition of SCF. Here we show that SCF activates Lyn a second time, hours later, during SCF-induced cell cycle progression. In cells arrested at specific phases of the cell cycle with the drugs mimosine, aphidicolin and nocodazole, maximal Lyn kinase activity occurred in late G(1) and through the G(1)/S transition. Similarly, kinetic studies of SCF-induced cell cycle progression found that activation of Lyn preceded the G(1)/S transition and was maintained into early S-phase. Activation of Lyn was paralleled by two events critical for the G(1)/S transition, increases in cyclin-dependent kinase 2 (Cdk2) activity and phosphorylation of the retinoblastoma gene product (Rb), Lyn was associated with Cdk2; Cdk2-associated Lyn was heavily phosphorylated on serine and threonine residues both in vitro and in situ during S-phase. Inhibition of Lyn activity with PP1 disrupted association with Cdk2 and decreased the numbers of cells entering S-phase. The degree of phosphorylation of Rb in PP1-treated cells suggested an increased number of cells arrested in the middle of G(1). These findings demonstrate that SCF activates the Src family member Lyn before the G(1)/S transition of the cell cycle and suggest that Lyn is involved in SCF-induced cell cycle progression. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res & Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Linnekin, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Div Basic Sci, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 42 TC 11 Z9 12 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 15 PY 1999 VL 342 BP 163 EP 170 DI 10.1042/0264-6021:3420163 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 230QE UT WOS:000082261200022 PM 10432313 ER PT J AU Sharom, FJ Yu, XH Lu, PH Liu, RH Chu, JWK Szabo, K Muller, M Hose, CD Monks, A Varadi, A Seprodi, J Sarkadi, B AF Sharom, FJ Yu, XH Lu, PH Liu, RH Chu, JWK Szabo, K Muller, M Hose, CD Monks, A Varadi, A Seprodi, J Sarkadi, B TI Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE peptide derivatives; azidopine photolabeling; ATPase activity; drug binding; drug transport; proteoliposomes; fluorescent dye transport; daunorubicin transport ID HAMSTER OVARY CELLS; ANTICANCER DRUG SCREEN; ATPASE ACTIVITY; FUNCTIONAL RECONSTITUTION; HYDROPHOBIC PEPTIDES; RESISTANCE PROTEIN; CLINICAL REVERSAL; INSECT CELLS; ACCUMULATION; BINDING AB P-Glycoprotein-mediated multidrug resistance can be reversed by the action of a group of compounds known as chemosensitizers. The interactions with P-glycoprotein of two novel hydrophobic peptide chemosensitizers (reversins 121 and 205) have been studied in model systems in vitro, and in a variety of MDR1-expressing intact tumor cells. The reversins bound to purified P-glycoprotein with high affinity (77-154 nM), as assessed by a quenching assay using fluorescently labeled purified protein. The peptides modulated P-glycoprotein ATPase activity in Sf9 insect fell membranes expressing human MDR1, plasma membrane vesicles from multidrug-resistant cells, and reconstituted proteoliposomes. Both peptides induced a large stimulation of ATPase activity; however, higher concentrations, especially of reversin 205, led to inhibition. This pattern was different from that of simple linear peptides, and resembled that of chemosensitizers such as verapamil. In both membrane vesicles and reconstituted proteoliposomes, 1-2 mu M reversins were more effective than cyclosporin A at blocking colchicine transport. Reversin 121 and reversin 205 restored the uptake of [H-3]daunorubicin and rhodamine 123 in MDR1-expressing cells to the level observed in the drug-sensitive parent cell lines, and also effectively inhibited the extrusion of calcein acetoxymethyl ester from intact cells. In cytotoxicity assays, reversin 121 and reversin 205 eliminated the resistance of MDR1-expressing tumor cells against MDR1-substrate anticancer drugs, and they had no toxic effects in MDR1-negative control cells. Me suggest that peptides of the reversin type interact with the MDR1 protein with high affinity and specificity, and thus they may be good candidates for the development of MDR1-modulating agents to sensitize drug resistance in cancer. (C) 1999 Elsevier Science Inc. C1 Univ Guelph, Guelph Waterloo Ctr Grad Work Chem & Biochem, Dept Chem & Biochem, Guelph, ON N1G 2W1, Canada. Hungarian Acad Sci, Inst Enzymol, Biol Res Ctr, Budapest, Hungary. Hungarian Acad Sci, Res Grp, Natl Inst Haematol & Immunol, Budapest, Hungary. NCI, Frederick Canc Res Facil, Frederick, MD 21702 USA. Semmelweis Univ Med, Dept Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. RP Sharom, FJ (reprint author), Univ Guelph, Guelph Waterloo Ctr Grad Work Chem & Biochem, Dept Chem & Biochem, Guelph, ON N1G 2W1, Canada. RI Varadi, Andras/A-2055-2012; Sarkadi, Balazs/I-5024-2013; Sharom, Frances/A-1613-2010 OI Sharom, Frances/0000-0002-9521-5367 NR 58 TC 88 Z9 89 U1 0 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 15 PY 1999 VL 58 IS 4 BP 571 EP 586 DI 10.1016/S0006-2952(99)00139-2 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 215TV UT WOS:000081400200004 PM 10413294 ER PT J AU Horton, JK Roy, G Piper, JT Van Houten, B Awasthi, YC Mitra, S Alaoui-Jamali, MA Boldogh, I Singhal, SS AF Horton, JK Roy, G Piper, JT Van Houten, B Awasthi, YC Mitra, S Alaoui-Jamali, MA Boldogh, I Singhal, SS TI Characterization of a chlorambucil-resistant human ovarian carcinoma cell line overexpressing glutathione S-transferase mu. SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE glutathione S-transferase; chlorambucil; ovarian carcinoma; drug resistance ID DNA CROSS-LINKING; BREAST-CANCER CELLS; DRUG-RESISTANCE; COMPLEMENTARY-DNA; ALKYLATING-AGENTS; HUMAN LUNG; EXPRESSION; MELPHALAN; SENSITIVITY; CISPLATIN AB Ovarian carcinoma cells 10-fold resistant to the alkylating agent chlorambucil (CBL) were isolated after repeated exposure of the parent cells to gradually escalating concentrations of the drug. The resistant variant, A2780(100), was highly cross-resistant (9-fold) to melphalan and showed lower-level resistance to other cross-linking agents. The resistant A2780(100) cells had almost 5-fold higher glutathione S-transferase (GST) activity than the parental A2780 cells with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. The pi-class GST(s) was the major isoform(s) in both cell lines. However, the resistant A2780(100) cells had at least 11-fold higher GST mu as compared with the parental cells, in which this isoform was barely detectable. A significant induction of GST mu was observed in A2780 cells, but not in the resistant cells, 18 hr after a single exposure to 100 mu M CBL. The induction of GST mu by CBL was both time and concentration-dependent. Assays of the conjugation of CBL with GSH showed that the human CL-class GST had 3.6- and 5.2-fold higher catalytic efficiency relative to the pi- and alpha-class GSTs, respectively. This difference was reflected in the relatively higher (about 6-fold) efficiency of CBL conjugation in A2780(100) cells as compared with the parental cells. These results have demonstrated for the first time a near-linear correlation between CBL resistance and overexpression of mu-class GSTs and suggest that this overexpression maybe responsible, at least in part, for the acquired resistance of ovarian carcinoma cells to CBL, and possibly the other bifunctional alkylating agents. Consistent with this hypothesis, we found evidence for decreased formation of DNA lesions in A2780(100) compared with the drug sensitive A2780 cells after exposure to CBL. (C) 1999 Elsevier Science Inc. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77550 USA. Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77550 USA. McGill Univ, Dept Med, Lady Davis Inst, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Lady Davis Inst, Montreal, PQ, Canada. McGill Univ, Translat Ctr Res Canc, Montreal, PQ, Canada. RP Horton, JK (reprint author), NIEHS, Struct Biol Lab, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES 07572, ES 70218]; NIGMS NIH HHS [GM 32304] NR 42 TC 41 Z9 42 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 15 PY 1999 VL 58 IS 4 BP 693 EP 702 DI 10.1016/S0006-2952(99)00142-2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 215TV UT WOS:000081400200018 PM 10413308 ER PT J AU Kimbrell, TA George, MS Parekh, PI Ketter, TA Podell, DM Danielson, AL Repella, JD Benson, BE Willis, MW Herscovitch, P Post, RM AF Kimbrell, TA George, MS Parekh, PI Ketter, TA Podell, DM Danielson, AL Repella, JD Benson, BE Willis, MW Herscovitch, P Post, RM TI Regional brain activity during transient self-induced anxiety and anger in healthy adults SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-21, 1995 CL MIAMI, FL SP Soc Biol Psychiat DE anger; anxiety; PET; gender; induction; emotion ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; PET IMAGES; FUNCTIONAL NEUROANATOMY; SYMPTOM PROVOCATION; FACIAL EXPRESSIONS; ACTIVATION; EMOTION AB Background: Several studies have demonstrated that transient self-induced sadness activates anterior paralimbic structures. To further examine the specificity of these findings and the neural substrates involved in anger and anxiety, we studied the neural correlates of the induction of anxiety and anger in healthy adults, Methods: We used H(2)(15)O and positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in 16 healthy adults during the induction of transient anxiety, anger, and neutral emotions. Subjects achieved differential emotions by recalling prior life events while viewing affect-appropriate faces. Results: Both the anxiety and anger conditions were associated with increased normalized rCBF in left inferior frontal and left temporal pole regions and decreased rCBF in right posterior temporal/parietal and right superior frontal cortex, compared to the neutral induction. Additionally, compared to neutral induction, anxiety was associated with increased rCBF in the left anterior cingulate and cuneus and decreased rCBF in right medial frontal cortex while the anger induction was uniquely associated with increased rCBF in right temporal pot and thalamus, Conclusions: Self-generated transient states of anxiety and anger are associated with both overlapping and distinct regional brain activity patterns and provide a template far further dissection of specific components of normal and pathologic emotions. Biol Psychiatry 1999; 46:454-465 (C) 1999 Society of Biological Psychiatry. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Dept Nucl Med, Positron Emiss Tomog Sect, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 73 TC 158 Z9 165 U1 11 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1999 VL 46 IS 4 BP 454 EP 465 DI 10.1016/S0006-3223(99)00103-1 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 226TA UT WOS:000082036700002 PM 10459394 ER PT J AU Roca, CA Su, TP Elpern, S McFarland, H Rubinow, DR AF Roca, CA Su, TP Elpern, S McFarland, H Rubinow, DR TI Cerebrospinal fluid somatostatin, mood, and cognition in multiple sclerosis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE multiple sclerosis; somatostatin; cerebrospinal fluid; neuropsychological testing; mood ID ALZHEIMERS-DISEASE; CSF SOMATOSTATIN; ILLNESS; IMMUNOREACTIVITY; METABOLITES; DEPRESSION; CORTEX; SCALE AB Background: Cerebrospinal fluid (CSF) somatostatin (SS) levels have been shown to be decreased in multiple sclerosis (MS) during relapse as well as in disorders characterized by depression or cognitive impairment. Since MS is often associated with depression and cognitive impairment, we examined both the effect of course of illness on CSF SS as well as the variance in SS attributable to associated features (e.g., depression or cognitive impairment). Methods: Fifteen patients with chronic progressive MS participating in a 2-year cyclosporine trial underwent lumbar punctures for CSF SS at baseline and at 12 and 24 months. Additionally, patients were evaluated by neuropsychological testing, and physical disability and mood ratings. Baseline CSF SS levels were also obtained in a group of control subjects (n = 10). Results: At baseline, CSF SS levels were lower in MS patients than control subjects (p <.001). Decreaed CSF SS at 24 months was correlated with decreased cognitive performance on several measures and was best and significantly predicted by cognitive deterioration at 24 months. Conclusions: Our data support those from previous studies that found lower levels of CSF SS in MS during relapse and suggest that changes in CSF SS are related to the process responsible for diminished cognitive function in MS. Biol Psychiatry 1999;46:551-556 (C) 1999 Society of Biological Psychiatry. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Roca, CA (reprint author), Bldg 10,Room 3N238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. NR 33 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1999 VL 46 IS 4 BP 551 EP 556 DI 10.1016/S0006-3223(99)00006-2 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 226TA UT WOS:000082036700014 PM 10459406 ER PT J AU Lindell, SG Suomi, SJ Shoaf, S Linnoila, M Higley, JD AF Lindell, SG Suomi, SJ Shoaf, S Linnoila, M Higley, JD TI Salivary prolactin as a marker for central serotonin turnover SO BIOLOGICAL PSYCHIATRY LA English DT Article DE serotonin; prolactin; saliva; fenfluramine; aggression; CSF 5-hydroxyindoleacetic acid ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID; D-FENFLURAMINE; CSF 5-HIAA; ELECTROCHEMICAL DETECTION; NONHUMAN-PRIMATES; SEVERE AGGRESSION; RHESUS-MONKEYS; DISORDER; METABOLITES AB Central nervous system (CNS) serotonin deficits have been linked to many pathological behaviors in both human and nonhuman primates, The plasma prolactin response to fenfluramine has been widely used to assess CNS seratonin functioning in humans, Prolactin is also found as an integrated measure in saliva. We hypothesized that salivary prolactin concentrations would correlate positively with cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) in rhesus monkeys. Twenty-seven adult male and female rhesus macaques (Macaca mulatta) were sampled for concurrent saliva, blood, and CSF, Saliva and blood serum were assayed for prolactin concentrations, and CSF was assayed for 5-HIAA, homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). Salivary prolactin concentrations were positively correlated with CSF 5-HIAA concentrations. Na other relationships between any of the measures, including that between salivary prolactin and serum prolactin, were found to be statistically significant. These findings suggest the possibility of using salivary prolactin concentrations as an index of CNS serotonin turnover in humans, Biol Psychiatry 1999;46: 568-572 (C) 1999 Society of Biological Psychiatry. C1 NIAAA, Clin Studies Lab, Primate Unit, NIHAC, Poolesville, MD 20837 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. NIAAA, Div Intramural Clin & Biol Res, Clin Studies Lab, Bethesda, MD 20892 USA. RP Higley, JD (reprint author), NIAAA, Clin Studies Lab, Primate Unit, NIHAC, POB 529,, Poolesville, MD 20837 USA. NR 31 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1999 VL 46 IS 4 BP 568 EP 572 DI 10.1016/S0006-3223(99)00037-2 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 226TA UT WOS:000082036700016 PM 10459408 ER PT J AU Leibenluft, E Ashman, SB Feldman-Naim, S Yonkers, KA AF Leibenluft, E Ashman, SB Feldman-Naim, S Yonkers, KA TI Lack of relationship between menstrual cycle phase and mood in a sample of women with rapid cycling bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE menstrual cycle; bipolar disorder; rapid cycling ID ILLNESS AB Background: Women are overrepresented in samples of patients with rapid cycling bipolar disorder (RCBD), To explore whether menstrually related mood changes might account for this gender difference, we studied the relationship between menstrual cycle phase and mood in a sample of premenopausal women with rapid cycling bipolar disorder (RCBD), Methods: Twenty-five women with RCBD completed daily self-rating forms indicating their mood and days of menstruation for a minimum of three months, The data were analyzed for each individual and for the group as a whole, categorically (depression, euthymia, and hypomania) and ordinally (0-100, with 0 being "most depressed ever felt" and 100 being "most manic"), with and without normalization of the menstrual cycle to a 28-day cycle. Results: None of the group analyses showed a significant effect of menstrual cycle on mood. Although some women did exhibit significant relationships between menstrual cycle phase and categorical mood state, there was no consistent pattern to the relationship. Conclusions: There was no systematic relationship between menstrual cycle and mood in a sample of women with RCBD. Biol Psychiatry 1999;46:577-580 (C) 1999 Society of Biological Psychiatry. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX USA. RP Leibenluft, E (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, 10-4N-208,10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA. NR 11 TC 45 Z9 45 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1999 VL 46 IS 4 BP 577 EP 580 DI 10.1016/S0006-3223(99)00023-2 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 226TA UT WOS:000082036700018 PM 10459410 ER PT J AU Deng, XY Ueda, H Su, SB Gong, WH Dunlop, NM Gao, JL Murphy, PM Wang, JM AF Deng, XY Ueda, H Su, SB Gong, WH Dunlop, NM Gao, JL Murphy, PM Wang, JM TI A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R SO BLOOD LA English DT Article ID LIPOXIN A(4) RECEPTOR; MULTIPLE LEUKOCYTE RECEPTORS; SERUM AMYLOID-A; CHEMOATTRACTANT RECEPTORS; MCP3 INTERACTS; STABLE ANALOGS; HIV-1; FORMYLPEPTIDE; NEUTROPHILS; CHEMOTAXIS AB Because envelope gp120 of various strains of human immunodeficiency virus type 1 (HIV-1) downregulates the expression and function of a variety of chemoattractant receptors through a process of heterologous desensitization, we investigated whether epitopes derived from gp120 could mimic the effect. A synthetic peptide domain, designated F peptide, corresponding to amino acid residues 414-434 in the V4-C4 region of gp120 of the HIV-1 Bru strain, potently reduced monocyte binding and chemotaxis response to macrophage inflammatory protein 1 beta (MIP-1 beta) and stromal cell-derived factor 1 alpha (SDF-1 alpha), chemokines that use the receptors CCR5 and CXCR4, respectively. Further study showed that F peptide by itself is an inducer of chemotaxis and calcium mobilization in human monocytes and neutrophils. In cross-desensitization experiments, among the numerous chemoattractants tested, only the bacterial chemotactic peptide fMLF, when used at high concentrations, partially attenuated calcium mobilization induced by F peptide in phagocytes, suggesting that this peptide domain might share a 7-transmembrane, G-protein-coupled receptor with fMLF By using cells transfected with cDNAs encoding receptors that interact with fMLF, we found that F peptide uses an fMLF receptor variant, FPRL1, as a functional receptor. The activation of monocytes by F peptide resulted in downregulation of the cell surface expression of CCR5 and CXCR4 in a protein kinase C-dependent manner. These results demonstrate that activation of FPRL1 on human moncytes by a peptide domain derived from HIV-1 gp120 could lead to desensitization of cell response to other chemoattractants. This may explain, at least in part, the initial activation of innate immune responses in HIV-1-infected patients followed by immune suppression. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 31-40, Frederick, MD 21702 USA. NR 42 TC 92 Z9 97 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1165 EP 1173 PG 9 WC Hematology SC Hematology GA 225FE UT WOS:000081947100003 PM 10438703 ER PT J AU Koski, GK Schwartz, GN Weng, DE Gress, RE Engels, FHC Tsokos, M Czerniecki, BJ Cohen, PA AF Koski, GK Schwartz, GN Weng, DE Gress, RE Engels, FHC Tsokos, M Czerniecki, BJ Cohen, PA TI Calcium ionophore-treated myeloid cells acquire many dendritic cell characteristics independent of prior differentiation state, transformation status, or sensitivity to biologic agents SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN-BONE-MARROW; PROMYELOCYTIC LEUKEMIA-CELLS; PERIPHERAL-BLOOD MONOCYTES; TUMOR-NECROSIS-FACTOR; GM-CSF; TNF-ALPHA; HEMATOPOIETIC PROGENITORS; MYELOGENOUS LEUKEMIA; EXPRESSION AB We previously reported that treatment of human peripheral blood monocytes or dendritic cells (DC) with calcium ionophore (CI) led to the rapid (18 hour) acquisition of many characteristics of mature DC, including CD83 expression. We therefore investigated whether less-mature myeloid cells were similarly susceptible to rapid CI activation. Although the promyelocytic leukemia line HL-60 was refractory to cytokine differentiation, CI treatment induced near-uniform overnight expression of CD83, CD80 (B7.1), and CD86 (87.2), as well as additional characteristics of mature DC. Several cytokines that alone had restricted impact on HL-50 could enhance CI-induced differentiation and resultant T-cell sensitizing capacity, In parallel studies, CD34(pos) cells cultured from normal donor bone marrow developed marked DC-like morphology after overnight treatment with either rhCD40L or CI, but only CI simultaneously induced upregulation of CD83, CD80, and CD86, This contrasted to peripheral blood monocytes, in which such upregulation could be induced with either CI or rhCD40L treatment. We conclude that normal and transformed myeloid cells at many stages of ontogeny possess the capacity to rapidly acquire many properties of mature DC in response to CI treatment. This apparent ability to respond to calcium mobilization, even when putative signal-transducing agents are inoperative, suggests strategies for implementing host antileukemic immune responses. C1 NCI, Med Branch, Pathol Lab, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. RP Cohen, PA (reprint author), Cleveland Clin Fdn, Surg Res Ctr, FF-50,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 57 TC 54 Z9 68 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1359 EP 1371 PG 13 WC Hematology SC Hematology GA 225FE UT WOS:000081947100024 PM 10438724 ER PT J AU Tuscano, JM Riva, A Toscano, SN Tedder, TF Kehrl, JH AF Tuscano, JM Riva, A Toscano, SN Tedder, TF Kehrl, JH TI CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade SO BLOOD LA English DT Article ID GERMINAL CENTER KINASE; TYROSINE-PHOSPHATASE 1C; FAS-MEDIATED APOPTOSIS; N-TERMINAL KINASE; PROTEIN-KINASE; BCL-X; CD22-DEFICIENT MICE; NEGATIVE REGULATOR; LYMPHOMA-CELLS; SURFACE IGM AB CD22 is a B-cell-specific adhesion molecule that modulates BCR-mediated signal transduction. Ligation of human CD22 with monoclonal antibodies (MoAbs) that block the ligand binding site triggers rapid tyrosine phosphorylation of CD22 and primary B-cell proliferation. Because extracellular signal-regulated kinases (ERKs) couple upstream signaling pathways to gene activation and are activated by B-cell antigen receptor (BCR) signaling, we examined whether CD22 ligation also activated ERKs and/or modified BCR-induced ERK activation. Ligation of CD22 on either primary B cells or B-cell lines failed to significantly activate the mitogen activated protein kinase (MAPK) ERK-2, but did activate the stress-activated protein kinases (SAPKs; c-jun NH2-terminal kinases or JNKs). In contrast, BCR ligation resulted in ERK-5 activation without significant SAPK activation. Concurrent ligation of CD22 and BCR enhanced BCR-mediated ERK-2 activation without appreciably modulating CD22-induced SAPK activation. Consistent with its induction of SAPK activity, there was a marked increase in nuclear extracts of activator protein-1 (AP-1) and c-jun levels within 2 hours of exposure of primary B cells to the CD22 MoAb. Despite their differences in ERK activation, both CD22 and BCR ligation triggered several Burkitt lymphoma cell lines to undergo apoptosis, and the 2 stimuli together induced greater cell death than either signal alone. The pro-apoptotic effects were CD22-blocking MoAb-specific and dose-dependent. Examination of expression levels of Bcl-2 protoncogene family members (Bcl-2, Bcl-x(L), Mcl-1, and Bar) showed a downregulation of Bcl-x(L) and Mcl-1 after CD22 ligation. This study provides a plausible mechanism to explain how CD22 and BCR signaling can costimulate B-cell proliferation and induce apoptosis in Burkitt lymphoma cell lines. C1 Univ Calif Davis, UC Davis Canc Ctr, Dept Med, Sacramento, CA USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, B Cell Mol Immunol Sect, NIH, Bldg 10,Room 11B08, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X FU NCI NIH HHS [CA-54464]; NIAID NIH HHS [AI-26872]; PHS HHS [AL50985] NR 58 TC 60 Z9 61 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1382 EP 1392 PG 11 WC Hematology SC Hematology GA 225FE UT WOS:000081947100026 PM 10438726 ER PT J AU Munoz, SJ Alter, HJ Nakatsuji, Y Shih, JWK Reddy, RK Jeffers, L Schiff, ER Reid, AE Marrone, A Rothstein, K Manzarbeitia, C Liang, TJ AF Munoz, SJ Alter, HJ Nakatsuji, Y Shih, JWK Reddy, RK Jeffers, L Schiff, ER Reid, AE Marrone, A Rothstein, K Manzarbeitia, C Liang, TJ TI The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology SO BLOOD LA English DT Article ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; GBV-C; NON-A; LIVER-FAILURE; INFECTION; JAPAN; RNA; IDENTIFICATION; ASSOCIATION AB Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients, There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis, Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P < .02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis. (C) 1999 by The American Society of Hematology. C1 Albert Einstein Med Ctr, Ctr Liver Dis, Philadelphia, PA 19141 USA. NIDDK, NIH, Liver Dis Sect, Ctr Clin, Bethesda, MD USA. NIDDK, NIH, Dept Transfus Med, Bethesda, MD USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Miami, Ctr Liver Dis, Miami, FL USA. RP Munoz, SJ (reprint author), Albert Einstein Med Ctr, Ctr Liver Dis, 5401 Old York Rd,Klein Bldg,Suite 509, Philadelphia, PA 19141 USA. NR 42 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1460 EP 1464 PG 5 WC Hematology SC Hematology GA 225FE UT WOS:000081947100034 PM 10438734 ER PT J AU Ishikawa, Y Sugano, H Miller, RW Goto, M AF Ishikawa, Y Sugano, H Miller, RW Goto, M TI Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome and possible genotype-phenotype relations to cell type and race - Reply SO CANCER LA English DT Letter C1 Japanese Fdn Canc Res, Inst Canc, Dept Pathol, Tokyo 170, Japan. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Tokyo Metropolitan Otsuka Hosp, Tokyo, Japan. RP Ishikawa, Y (reprint author), Japanese Fdn Canc Res, Inst Canc, Dept Pathol, Tokyo 170, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1999 VL 86 IS 4 BP 729 EP 729 PG 1 WC Oncology SC Oncology GA 223YA UT WOS:000081868100024 ER PT J AU Bera, TK Viner, J Brinkmann, M Pastan, I AF Bera, TK Viner, J Brinkmann, M Pastan, I TI Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2 SO CANCER RESEARCH LA English DT Article ID RECOMBINANT IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; HUMAN-BREAST; CANCER; CARCINOMA; PROTEINS; FRAGMENT; TOXINS; CELLS; MICE AB We have generated a stable bivalent Fv molecule [(dsFv)(2)] of the anti-erbB2 monoclonal antibody e23 in which the V-H and V-L domains of the Fv are linked to each other by a disulfide bond and the two Pvs are connected by a 15-amino acid Linker (T. K. Bera et al.t, J. Mol. Biol., 281: 475-483, 1998). The e23 (dsFv)(2) molecule is linked to a truncated form of Pseudomonas exotoxin (PE38) to generate a bivalent disulfide-stabilized immunotoxin e23 (dsFv)(2)-PE38. Compared to the monovalent immunotoxin, the (dsFv)(2) immunotoxin showed greatly Increased cytotoxicity to four cancer cell lines expressing low levels of erbB2 but not to four other cell lines with high erbB2 expression. e23 (dsFv)(2)-PE38 was administered i.v. to mice, and its half-life was determined. The t(1/2)alpha and t(1/2)beta were 20 and 325 min, respectively, whereas the corresponding values for the monovalent dsFv immunotoxin were shorter, 6 and 52 min. The antitumor activities of the monovalent and bivalent immunotoxin were compared using mice bearing A431 tumors. Despite the fact that e23 (dsFv)(2)-PE38 was 13-fold more active than e23 dsFv-PE38 on A431 cells in cell culture, its antitumor activity in mice was <2-fold that of the monovalent immunotoxin. These data show that a large increase in avidity does not always lead to an increase in cytotoxic activity. Furthermore, in one of the cases in which cytotoxic activity in vitro was greatly enhanced, there was only a small increase in antitumor activity. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 24 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1999 VL 59 IS 16 BP 4018 EP 4022 PG 5 WC Oncology SC Oncology GA 228KJ UT WOS:000082135400034 PM 10463601 ER PT J AU Feledy, JA Beanan, MJ Sandoval, JJ Goodrich, JS Lim, JH Matsuo-Takasaki, M Sato, SM Sargent, TD AF Feledy, JA Beanan, MJ Sandoval, JJ Goodrich, JS Lim, JH Matsuo-Takasaki, M Sato, SM Sargent, TD TI Inhibitory patterning of the anterior neural plate in Xenopus by homeodomain factors Dlx3 and Msx1 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Msx1; Dlx3; Xenopus; antineural patterning ID HOMEOBOX GENE; MESODERM INDUCTION; LAEVIS; EMBRYOS; EXPRESSION; ECTODERM; DIFFERENTIATION; PROTEIN; SIGNALS; HOMOLOG AB Patterning of the embryonic ectoderm is dependent upon the action of negative (antineural) and positive (neurogenic) transcriptional regulators. Msx1 and Dlx3 are two antineural genes for which the anterior epidermal-neural boundaries of expression differ, probably due to differential sensitivity to BMP signaling in the ectoderm. In the extreme anterior neural plate, Dlx3 is strongly expressed while Msx1 is silent. While both of these factors prevent the activation of genes specific to the nascent central nervous system, Msx1 inhibits anterior markers, including Otx2 and cement gland-specific genes. Dlx3 has little, if any, effect on these anterior neural plate genes, instead providing a permissive environment for their expression while repressing more panneural markers, including prepattern genes belonging to the Zic family and BF-1. These properties define a molecular mechanism for translating the organizer-dependent morphogenic gradient of BMP activity into spatially restricted gene expression in the prospective anterior neural plate. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Genet Mol Lab, NIH, Bldg 6B,Room 412,MSC 2790,6 Ctr Dr, Bethesda, MD 20892 USA. NR 47 TC 88 Z9 88 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 15 PY 1999 VL 212 IS 2 BP 455 EP 464 DI 10.1006/dbio.1999.9374 PG 10 WC Developmental Biology SC Developmental Biology GA 228EJ UT WOS:000082123900016 PM 10433834 ER PT J AU McDonald, JP Rapic-Otrin, V Epstein, JA Broughton, BC Wang, XY Lehmann, AR Wolgemuth, DJ Woodgate, R AF McDonald, JP Rapic-Otrin, V Epstein, JA Broughton, BC Wang, XY Lehmann, AR Wolgemuth, DJ Woodgate, R TI Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta SO GENOMICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; XERODERMA-PIGMENTOSUM VARIANT; SOS-INDUCED MUTAGENESIS; ESCHERICHIA-COLI DINB; GERM-CELLS; COLORECTAL CANCERS; UV MUTAGENESIS; THYMINE DIMER; RECA PROTEIN; MALE MICE AB The Saccharomyces cerevisiae RAD30 gene encodes a novel eukaryotic DNA polymerase, poi eta that is able to replicate across cis-syn cyclobutane pyrimidine dimers both accurately and efficiently. Very recently, a human homolog of RAD30 was identified, mutations in which result in the sunlight-sensitive, cancer-prone, Xeroderma pigmentosum variant group phenotype. We report here the cloning and localization of a second human homolog of RAD30. Interestingly, RAD30B is localized on chromosome 18q21.1 in a region that is often implicated in the etiology of many human cancers. The mouse homolog (Rad30b) is located on chromosome 18E2. The human RAD30B and mouse Rad30b mRNA transcripts, Like many repair proteins, are highly expressed in the testis. In situ hybridization analysis indicates that expression of mouse Rad30b occurs predominantly in postmeiotic round spermatids. Database searches revealed genomic and EST sequences from other eukaryotes such as Aspergillus nidulans, Schizosaccharomyces pombe, Brugia malayi, Caenorhabditis elegans, Trypanosoma cruzi, Arabidopsis thaliana and Drosophila melanogaster that also encode putative homologs of RAD30, thereby suggesting that Rad30-dependent translesion DNA synthesis is conserved within the eukaryotic kingdom. (C) 1999 Academic Press. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Biol Computat, NIH, Bethesda, MD 20892 USA. Univ Sussex, MRC, Cell Mutat Unit, Brighton BN1 9RR, E Sussex, England. Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [R01HD34915] NR 59 TC 162 Z9 172 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1999 VL 60 IS 1 BP 20 EP 30 DI 10.1006/geno.1999.5906 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 231TU UT WOS:000082327000003 PM 10458907 ER PT J AU Morgan, RO Jenkins, NA Gilbert, DJ Copeland, NG Balsara, BR Testa, JR Fernandez, MP AF Morgan, RO Jenkins, NA Gilbert, DJ Copeland, NG Balsara, BR Testa, JR Fernandez, MP TI Novel human and mouse annexin A10 are linked to the genome duplications during early chordate evolution SO GENOMICS LA English DT Article ID DNA-SEQUENCES; CHROMOSOMAL LOCALIZATION; GENE; PROTEIN; DIVERGENCE; EXPRESSION; FAMILIES; BINDING; CDNA; MAP AB me have identified and characterized a 12th subfamily of vertebrate annexins by systematic analysis of the primary structure, chromosomal mapping, and molecular evolution of unique cDNA and protein sequences from human and mouse. Distinctive features included rare expression, a codon deletion in conserved repeat 3, and an unusual ablation of the type II calcium-binding sites in tetrad core repeats 1, 3, and 4. The paralogy of novel annexin A10 (following revised nomenclature) was confirmed by FISH-mapping human ANXA10 to chromosome 4q33 and genetic linkage mapping mouse Anxa10 to midchromosome 8. Phylogenetic analysis established that the 5' and 3' halves of the annexin A6 octad are more closely related 60 annexins A5 and A10, respectively, than they are to each other. Molecular date estimates, paralogy Linkage maps between human chromosomes 4 and 5, and annexin structural considerations led to the proposal that annexins A5 and A10 may have been the direct progenitors of annexin A6 octad formation via chromosomal duplication during the genome expansion in early chordates. (C) 1999 Academic Press. C1 Univ Oviedo, Dept Biochem & Mol Biol, Fac Med, E-33006 Oviedo, Spain. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Fernandez, MP (reprint author), Univ Oviedo, Dept Biochem & Mol Biol, Fac Med, E-33006 Oviedo, Spain. OI Fernandez-Fernandez, Maria Pilar/0000-0001-6552-409X FU NCI NIH HHS [CA-06927]; PHS HHS [PM95-0152] NR 39 TC 46 Z9 49 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1999 VL 60 IS 1 BP 40 EP 49 DI 10.1006/geno.1999.5895 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 231TU UT WOS:000082327000005 PM 10458909 ER PT J AU Yang, D Howard, OMZ Chen, QQ Oppenheim, JJ AF Yang, D Howard, OMZ Chen, QQ Oppenheim, JJ TI Cutting edge: Immature dendritic cells generated from monocytes in the presence of TGP-beta 1 express functional C-C chemokine receptor 6 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY RESPONSE; TNF-ALPHA; IN-VITRO; MATURATION; MIGRATION; RECRUITMENT; TRAFFICKING; INTERACTS; PROTEIN; MODEL AB Although CD34(+) progenitor-derived immature dendritic cells (DCs) express CCR6, several recent studies reported that monocyte-derived immature DCs do not do so. We observed that DCs generated from monocytes in the presence of GM-CSF, IL-4, and TGF-beta 1 consistently responded to liver and activation-regulated chemokine (LARC, also known as macrophage inflammatory protein-3 alpha). These immature DCs expressed one class of high-affinity binding sites for LARC, and expressed both CCR6 mRNA and protein. Therefore, LARC-CCR6 interaction presumably also contributes to the regulation of trafficking of monocyte-derived DCs, and utilization of TGF-beta can potentially provide a ready source of CCR6(+) monocyte-derived DCs for therapeutic purposes. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Room 21-89, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000] NR 25 TC 91 Z9 94 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 1737 EP 1741 PG 5 WC Immunology SC Immunology GA 224LH UT WOS:000081900200005 PM 10438902 ER PT J AU George, TC Ortaldo, JR Lemieux, S Kumar, V Bennett, M AF George, TC Ortaldo, JR Lemieux, S Kumar, V Bennett, M TI Tolerance and alloreactivity of the Ly49D subset of murine NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BONE-MARROW ALLOGRAFTS; I-DEFICIENT MICE; HYBRID RESISTANCE; GRAFT-REJECTION; INHIBITORY RECEPTORS; SIGNAL-TRANSDUCTION; SELF-TOLERANCE; MHC; EXPRESSION AB Class I-specific stimulatory and inhibitory receptors expressed by NK cell subsets contribute to the alloreactive potential of the self-tolerant murine NK cell repertoire. In this report, we have studied potential mechanisms of tolerance to the function of the positive signaling Ly49D receptor in mice that express one of its ligands, H2-D-d. Our results demonstrate that H2-D-d-expressing mice possess a large Ly49D(+) subset of NK cells that is functionally capable of rejecting bone marrow cell (BMC) allografts in vivo and lysing allogeneic Con A lymphoblasts in vitro. Also, we show that the Ly49D receptor is responsible for the ability of H2(b/d) F-1 hybrid mice to reject H2(d/d) parental BMC (hybrid resistance). Thus, deletion or anergy of Ly49D(+) cells in H2-Dd+ hosts cannot explain self tolerance. Our functional studies revealed that coexpression of the D-d-specific Ly49A or Ly49G2 inhibitory receptors by Ly49D(+) cells resulted in tolerance to Dd+ targets, while coexpression of K-b-specific inhibitory receptors Ly49C/I resulted in tolerance to Kb+ targets. Only in H2(d/d) cells did Ly49C/I dominantly inhibit Ly49D-D-d stimulation. This correlated with an increased mean fluorescence intensity of Ly49C expression, as well as an increased percentage of Ly49C(+) cells in the Ly49D(+)A/ G2(-) compartment. Therefore, we conclude that self tolerance of the Ly49D subset can be achieved through coexpression of a sufficient level of self-specific inhibitory receptors. C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA. NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Quebec, Inst Armand Frappier, Inst Natl Res Sci, Human Hlth Res Ctr, Laval, PQ, Canada. RP Bennett, M (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, 6000 Harry Hines Blvd, Dallas, TX 75235 USA. FU NCI NIH HHS [CA36921]; NIAID NIH HHS [AI25401, AI38938] NR 59 TC 70 Z9 70 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 1859 EP 1867 PG 9 WC Immunology SC Immunology GA 224LH UT WOS:000081900200023 PM 10438920 ER PT J AU Watanabe, M Fenton, RG Wigginton, JM McCormick, KL Volker, KF Fogler, WE Roessler, PG Wiltrout, RH AF Watanabe, M Fenton, RG Wigginton, JM McCormick, KL Volker, KF Fogler, WE Roessler, PG Wiltrout, RH TI Intradermal delivery of IL-12 naked DNA induces systemic NK cell activation and Th1 response in vivo that is independent of endogenous IL-12 production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYPE-1 CYTOKINE RESPONSES; MURINE RENAL-CARCINOMA; IFN-GAMMA PRODUCTION; STIMULATORY FACTOR; IMMUNOREGULATORY FUNCTIONS; GENE-EXPRESSION; T-CELLS; IN-VIVO; PROINFLAMMATORY CYTOKINE; IL-12-DEFICIENT MICE AB In this study four murine IL-12 naked DNA expression plasmids (pIL-12), containing both the p35 and p40 subunits, were shown to induce systemic biological effects in vivo after intradermal injection. Three of the four IL-12 expression vectors augmented NK activity and induced expression of the IFN-gamma and IFN-gamma-inducible Mig genes. Both IL-12 p70 heterodimer and IFN-gamma proteins were documented in the Serum within 24 h after intradermal injection of the pIL-12o(-) plasmid, which also induced the highest level of NK activity in the spleen and liver among the IL-12 constructs. Interestingly, both p40 mRNA expression at the injection site and serum protein levels followed a biphasic pattern of expression, with peaks on days 1 and 5, Subsequent studies revealed that the ability of intradermally injected pIL-12o(-) to augment NK lytic activity was prevented by administration of a neutralizing anti-IL-12 mAb, Finally, injection of the pIL-12o(-) into BALB/c IL-12 p40(-/-) mice also resulted in a biphasic pattern of IL-12 p70 appearance in the serum, and induced IFN-gamma protein and activated NK lytic activity in liver and spleen. These results demonstrate that injection of delivered naked DNA encoding the IL-12 gene mediates the biphasic systemic production of IL-12-inducible genes and augments the cytotoxic function of NK cells in lymphoid and parenchymal organs as a direct result of transgene expression. The results also suggest that these naked DNA plasmids may be useful adjuvants for vaccines against infectious and neoplastic diseases. C1 NCI, Expt Therapeut Sect, Expt Immunol Lab, Div Basic Sci,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Dept Expt Transplantat & Immunol, Div Clin Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. Entremed Inc, Rockville, MD 20850 USA. RP Wiltrout, RH (reprint author), NCI, Expt Therapeut Sect, Expt Immunol Lab, Div Basic Sci,Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 54 TC 38 Z9 39 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 1943 EP 1950 PG 8 WC Immunology SC Immunology GA 224LH UT WOS:000081900200033 PM 10438930 ER PT J AU van Ginkel, FW Wahl, SM Kearney, JF Kweon, MN Fujihashi, K Burrows, PD Kiyono, H McGhee, JR AF van Ginkel, FW Wahl, SM Kearney, JF Kweon, MN Fujihashi, K Burrows, PD Kiyono, H McGhee, JR TI Partial IgA-deficiency with increased Th2-type cytokines in TGF-beta 1 knockout mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA-1 NULL MICE; HUMAN SERUM IGA; HUMAN B-CELLS; ANTIBODY-RESPONSES; IMMUNOGLOBULIN-A; FACTOR-ALPHA; T-CELLS; LYMPHOID-TISSUE AB Though it has been shown that TGF-beta 1 directs B cells to switch to IgA in vitro, no studies have assessed TGF-beta 1 effects on mucosal vs systemic immunity in vivo. When the B cell functions of TGF-beta 1 gene-disrupted (TGF-beta 1(-/-)) mice were analyzed, significantly decreased IgA levels and increased IgG and IgM levels in serum and external secretions were observed. Further, analysis of Ab forming cells (AFC) isolated from both mucosal and systemic lymphoid tissue showed elevated IgM, IgG, and IgE, with decreased IBA AFC, A lack of IgA-committed B cells was seen in TGF-beta 1(-/-) mice, especially in the gastrointestinal (GI) tract. Splenic T cells triggered via the TCR expressed elevated Th2-type cytokines and, consistent with this observation, a 31-fold increase in serum IgE was seen in TGF-beta 1(-/-) mice. Thus, uncontrolled B cell responses, which include elevated IgE levels, a lack of antiinflammatory IgA, and an excess of complement-binding IgG and IgM Abs, will promote inflammation at mucosal surfaces in TGF-beta 1(-/-) mice acid likely contribute to pulmonary and GI tract lesions, ultimately leading to the early death of these mice. C1 Univ Alabama, Dept Microbiol, Immunobiol Vaccine Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Oral Biol, Birmingham, AL 35294 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Microbial Dis Res Inst, Dept Mucosal Immunol, Osaka, Japan. RP van Ginkel, FW (reprint author), Univ Alabama, Dept Microbiol, Immunobiol Vaccine Ctr, BBRB Room 775,845 19th St S, Birmingham, AL 35294 USA. FU NIAID NIH HHS [AI18958, R01 AI014782, AI43197]; NIDCR NIH HHS [DE12242] NR 51 TC 87 Z9 88 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 1951 EP 1957 PG 7 WC Immunology SC Immunology GA 224LH UT WOS:000081900200034 PM 10438931 ER PT J AU Dent, AL Doherty, TM Paul, WE Sher, A Staudt, LM AF Dent, AL Doherty, TM Paul, WE Sher, A Staudt, LM TI BCL-6-deficient mice reveal an IL-4-independent, STAT-6-dependent pathway that controls susceptibility to infection by Leishmania major SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GERMINAL-CENTER FORMATION; CD4(+) T-CELLS; HUMAN B-CELLS; INTERFERON-GAMMA; BALB/C MICE; TRANSCRIPTION FACTOR; IMMUNE-RESPONSES; BCL-6 PROTEIN; TH2 RESPONSE; IL-13 AB The BCL-6 gene negatively regulates Th2 responses as shown by the finding that BCL-6-deficient (BCL-6(-/-)) mice develop a lethal Th2-type inflammatory disease. The response of inbred mouse strains to infection with Leishmania major is under genetic control; BALB/c mice are susceptible and develop a progressive parasite burden, whereas most other common laboratory strains of mice are resistant to infection. We found that BCL-6-/- mice on a resistant genetic background (C57BL/6 x 129 intercrossed mice) were highly susceptible to L, major infection; they resembled BALB/c mice in terms of lesion size, parasite load, and the production of Th2 cytokines, BCL-6(-/-)IL-4(-/-) double-mutant mice mere also susceptible to L, major infection and produced 10-fold higher levels of the Th2 cytokine IL-13 than IL-4(-/-) littermate controls. By contrast, BCL-6(-/-)STAT6(-/-) double mutant mice were resistant to L, major infection despite also producing elevated levels of IL-13. These results show that STAT6 is required for susceptibility to L. major infection and suggest that IL-13 signaling through STAT6 may contribute to a nonhealing, exacerbated L, major infection. C1 NCI, Metab Branch, NIH, Silver Spring, MD 20910 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N114,9000 Rockville Pike, Silver Spring, MD 20910 USA. NR 36 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 2098 EP 2103 PG 6 WC Immunology SC Immunology GA 224LH UT WOS:000081900200052 PM 10438949 ER PT J AU Kuroiwa, T Lee, EG Danning, CL Illei, GG McInnes, IB Boumpas, DT AF Kuroiwa, T Lee, EG Danning, CL Illei, GG McInnes, IB Boumpas, DT TI CD40 ligand-activated human monocytes amplify glomerular inflammatory responses through soluble and cell-to-cell contact-dependent mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; HUMAN MESANGIAL CELLS; TUBULAR EPITHELIAL-CELLS; CRESCENTIC GLOMERULONEPHRITIS; CHEMOATTRACTANT PROTEIN-1; LUPUS NEPHRITIS; MONOCLONAL-ANTIBODIES; ICAM-1 EXPRESSION; MURINE LUPUS; TNF-ALPHA AB Monocytes/macrophages play a critical role in the initiation and progression of a variety of glomerulonephritides. We sought to define the interactions between physiologically activated human monocytes and glomerular mesangial cells (MC) by employing a cell culture system that permits the accurate assessment of the contribution of soluble factors and cell-to-cell contact. Human peripheral blood monocytes, primed with IFN-gamma and GM-CSF, were activated with CD40 ligand (CD40L) or TNF-alpha and cocultured with MC. CD40L-activated monocytes induced higher levels of IL-6, monocyte chemoattractant protein-1 (MCP-1) and ICAM-1 synthesis by MC. Separation of CD40L-activated monocytes from MC by a porous membrane decreased the mesangial synthesis of IL-6 by 80% and ICAM-1 by 45%, but had no effect on MCP-1. Neutralizing Abs against the beta(2) integrins, LFA-1 and Mac-1, decreased IL-6 production by 40 and 50%, respectively. Ligation of mesangial surface ICAM-1 directly enhanced IL-6, but not MCP-1, production. Simultaneous neutralization of soluble TNF-alpha and IL-1 beta decreased MCP-1 production by 55% in membrane-separated cocultures of MC/CD40L-activated monocytes, Paraformaldehyde-fixed CD40L-activated monocytes (to preserve membrane integrity but prevent secretory activity), cocultured with MC at various ratios, induced IL-6, MCP-1, and ICAM-1 synthesis by MC, Plasma membrane preparations from activated monocytes also induced mesangial IL-6 and MCP-1 synthesis. The addition of plasma membrane enhanced TNF-alpha-induced mesangial IL-6 production by similar to 4-fold. Together, these data suggest that the CD40/CD40L is essential for optimal effector function of monocytes, that CD40L-activated monocytes stimulate MC through both soluble factors and cell-to-cell contact mediated pathways, and that both pathways are essential for maximum stimulation of MC. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Kuroiwa, T (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N218,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. NR 54 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 2168 EP 2175 PG 8 WC Immunology SC Immunology GA 224LH UT WOS:000081900200061 PM 10438958 ER PT J AU Mammano, F Frolenkov, GI Lagostena, L Belyantseva, IA Kurc, M Dodane, V Colavita, A Kachar, B AF Mammano, F Frolenkov, GI Lagostena, L Belyantseva, IA Kurc, M Dodane, V Colavita, A Kachar, B TI ATP-induced Ca2+ release in cochlear outer hair cells: Localization of an inositol triphosphate-gated Ca2+ store to the base of the sensory hair bundle SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sensory transduction; cochlea; purinergic receptors; InsP(3); endoplasmic reticulum; mitochondria; G-proteins; electromotility; patch-clamp; calcium imaging; organ of Corti; Hensen's body ID GUINEA-PIG COCHLEA; NONSELECTIVE CATION CHANNELS; INTRACELLULAR CALCIUM; MECHANOELECTRICAL-TRANSDUCTION; EXTRACELLULAR ATP; P2X RECEPTORS; ORGAN; CORTI; INNER; EXPRESSION AB We used a high-performance fluorescence imaging system to visualize rapid changes in intracellular free Ca2+ concentration ([Ca2+](i)) evoked by focal applications of extracellular ATP to the hair bundle of outer hair cells (OHCs): the sensory-motor receptors of the cochlea. Simultaneous recordings of the whole-cell current and Calcium Green-1 fluorescence showed a two-component increase in [Ca2+](i). After an initial entry of Ca2+ through the apical membrane, a second and larger, inositol triphosphate (InsP(3))-gated, [Ca2+](i) surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca2+ release site showed that it coincides with the localization of a unique system of endoplasmic reticulum (ER) membranes and mitochondria known as Hensen's body. Using confocal immunofluorescence microscopy, we showed that InsP(3) receptors share this location. Consistent with a Ca2+-mobilizing second messenger system linked to ATP-P2 receptors, we also determined that an isoform of G-proteins is present in the stereocilia. Voltage-driven cell shape changes and nonlinear capacitance were monitored before and after ATP application, showing that the ATP-evoked [Ca2+](i) rise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca2+-clearance power of the stereocilia and transiently elevates [Ca2+](i) at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and potentially influence mechanotransduction. C1 Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Int Sch Adv Studies, Biophys Sector, I-34014 Trieste, Italy. Int Sch Adv Studies, Ist Nazl Fis Mat Unit, I-34014 Trieste, Italy. Abdus Salam Ctr Theoret Phys, Microprocessor Lab, I-34014 Trieste, Italy. Ist Nazl Fis Nucl, I-34014 Trieste, Italy. RP Kachar, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bldg 36,Room 5D-15, Bethesda, MD 20892 USA. RI Mammano, Fabio/I-5064-2012 OI Mammano, Fabio/0000-0003-3751-1691 NR 72 TC 62 Z9 65 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 1999 VL 19 IS 16 BP 6918 EP 6929 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 224LP UT WOS:000081900800021 PM 10436049 ER PT J AU Dong, HL Zhang, PS Song, IS Petralia, RS Liao, DZ Huganir, RL AF Dong, HL Zhang, PS Song, IS Petralia, RS Liao, DZ Huganir, RL TI Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GRIP1; GRIP2; AMPA receptor; neuronal synapses; GAD; postsynaptic density; vesicle; development ID POSTSYNAPTIC DENSITY; RAT-BRAIN; HIPPOCAMPAL-NEURONS; AMPA RECEPTORS; SYNAPSES; LOCALIZATION; ASSOCIATION; CHANNELS; SUBUNITS; BINDING AB The molecular mechanisms underlying the targeting and localization of glutamate receptors at postsynaptic sites is poorly understood. Recently, we have identified a PDZ domain-containing protein, glutamate receptor-interacting protein 1 (GRIP1), which specifically binds to the C termini of AMPA receptor subunits and may be involved in the synaptic targeting of these receptors. Here, we report the cloning of GRIP2, a homolog of GRIP1, and the characterization of the GRIP1 and GRIP2 proteins in the rat CNS. GRIP1 and GRIP2 are similar to 130 kDa proteins that are highly enriched in brain. GRIP1 and GRIP2 are widely expressed in brain, with the highest levels found in the cerebral cortex, hippocampus, and olfactory bulb. Biochemical studies show that GRIP1 and GRIP2 are enriched in synaptic plasma membrane and postsynaptic density fractions. GRIP1 is expressed early in embryonic development before the expression of AMPA receptors and peaks in expression at postnatal day 8-10. In contrast, GRIP2 is expressed relatively late in development and parallels the expression of AMPA receptors. Immunohistochemistry using the GRIP1 antibodies demonstrated that GRIP1 is expressed in neurons in a somatodendritic staining pattern. At the ultrastructural level, DAB and immunogold electromicroscopy studies showed that GRIP1 was enriched in dendritic spines near the postsynaptic density and was expressed in dendritic shafts and in peri-Golgi regions in the neuronal soma. GRIP1 appeared to be clustered at both glutamatergic and GABAergic synapses. These results suggest that GRIP1 and GRIP2 are AMPA receptor binding proteins potentially involved in the targeting of AMPA receptors to synapses. GRIP1 also may play functional roles at both excitatory and inhibitory synapses, as well as in early neuronal development. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Huganir, RL (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Howard Hughes Med Inst, 725 N Wolfe St,PCTB 904, Baltimore, MD 21205 USA. NR 38 TC 166 Z9 173 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 1999 VL 19 IS 16 BP 6930 EP 6941 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 224LP UT WOS:000081900800022 PM 10436050 ER PT J AU Lins, U Kachar, B Farina, M AF Lins, U Kachar, B Farina, M TI Imaging faces of shadowed magnetite (Fe3O4) crystals from magnetotactic bacteria with energy-filtering transmission electron microscopy SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE magnetotactic bacteria; bacterial magnetite; energy filtering transmission electron microscopy; biomineralization ID FORCE MICROSCOPY; MAGNETOSOMES; REPLICATION; PARTICLES; FREEZE AB We used energy-filtering transmission electron microscopy to image magnetite crystals isolated from uncultured magnetotactic bacteria. These magnetite crystals were shadowed in high vacuum with platinum at 45 degrees. The shadowed crystals were observed in a Zeiss (Thornwood, NY) CEM902 transmission electron microscope. Imaging shadowed crystals with inelastically scattered electrons provided information of the decoration pattern of small platinum particles over crystal surfaces, and thus information an surface characteristics of crystals. Results were comparable to those obtained from scanning electron microscopy using a field emitter gun. Electron energy loss spectra of the crystals as well as of the supporting film were recorded to evaluate variations of image contrast with energy losses. Results indicated that the contrast is attenuated with inelastic imaging and that the effect of contrast tuning caused a contrast inversion at a given point between 100 and 150 eV. We believe this approach can be useful for studying multilayered materials by transmission electron microscopy. (C) 1999 Wiley-Liss, Inc. C1 Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Dept Anat, Lab Biomineralizacao, BR-21941590 Rio De Janeiro, Brazil. Natl Inst Deafness & Other Commun Disorders, Biol Cellulaire Lab, NIH, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Inst Microbiol Professor Paulo de Goes, Setor Microscopia Eletron, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Inst Microbiol Professor Paulo de Goes, Dept Microbiol Geral, Rio De Janeiro, Brazil. RP Farina, M (reprint author), Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Dept Anat, Lab Biomineralizacao, CCS,Bl F, BR-21941590 Rio De Janeiro, Brazil. RI Farina, Marcos/I-3744-2014; Lins, Ulysses/N-7282-2015 OI Lins, Ulysses/0000-0002-1786-1144 NR 18 TC 1 Z9 2 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD AUG 15 PY 1999 VL 46 IS 4-5 BP 319 EP 324 DI 10.1002/(SICI)1097-0029(19990815/01)46:4/5<319::AID-JEMT9>3.0.CO;2-N PG 6 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 232TU UT WOS:000082386700009 PM 10469468 ER PT J AU Norel, R Petrey, D Wolfson, HJ Nussinov, R AF Norel, R Petrey, D Wolfson, HJ Nussinov, R TI Examination of shape complementarity in docking of unbound proteins SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE docking; protein-protein recognition; molecular surface complementarity; shape complementarity; rigid-body matching; surface normals ID MOLECULAR-SURFACE RECOGNITION; AUTOMATED DOCKING; INTERFACES; ALGORITHM; BINDING; SEARCH AB Here we carry out an examination of shape complementarity as a criterion in protein-protein docking and binding, Specifically, we examine the quality of shape complementarity as a critical determinant not only in the docking of 26 protein-protein "bound" complexed cases, but in particular, of 19 "unbound" protein-protein cases, where the structures have been determined separately. In all cases, entire molecular surfaces are utilized in the docking, with no consideration of the location of the active site, or of particular residues/atoms in either the receptor or the ligand that participate in the binding. To evaluate the goodness of the strictly geometry-based shape complementarity in the docking process as compared to the main favorable and unfavorable energy components, we study systematically a potential correlation between each of these components and the root mean square deviation (RMSD) of the "unbound" protein-protein cases, Specifically, we examine the non-polar buried surface area, polar buried surface area, buried surface area relating to groups bearing unsatisfied buried charges, and the number of hydrogen bonds in all docked protein-protein interfaces, For these cases, where the two proteins have been crystallized separately, and where entire molecular surfaces are considered without a predefinition of the binding site, no correlation is observed, None of these parameters appears to consistently improve on shape complementarity in the docking of unbound molecules, These findings argue that simplicity in the docking process, utilizing geometrical shape criteria may capture many of the essential features in protein-protein docking. In particular, they further reinforce the long held notion of the importance of molecular surface shape complementarity in the binding, and hence in docking. This is particularly interesting in light of the fact that the structures of the docked pairs have been determined separately, allowing side chains on the surface of the proteins to move relatively freely. This study has been enabled by our efficient, computer vision-based docking algorithms. The fast CPU matching times, on the order of minutes on a PC, allow such large-scale docking experiments of large molecules, which may not be feasible by other techniques, (C) 1999 Wiley-Liss, Inc. C1 NCI, Frederick Canc Res Facil, Lab Expt & Computat Biol, SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res Facil, Lab Expt & Computat Biol, SAIC, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011; OI Norel, Raquel/0000-0001-7737-4172 FU NCI NIH HHS [1-CO-74102]; NIGMS NIH HHS [2RO1-GM41371, 5-T32-GM08281] NR 31 TC 90 Z9 91 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD AUG 15 PY 1999 VL 36 IS 3 BP 307 EP 317 DI 10.1002/(SICI)1097-0134(19990815)36:3<307::AID-PROT5>3.0.CO;2-R PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220HD UT WOS:000081658200005 PM 10409824 ER PT J AU Miyazawa, S Jernigan, RL AF Miyazawa, S Jernigan, RL TI Evaluation of short-range interactions as secondary structure energies for protein fold and sequence recognition SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE empirical potentials; protein inverse folding; protein sequence threading; statistical potentials ID GLOBULAR-PROTEINS; LATTICE MODEL; 3-DIMENSIONAL STRUCTURE; STRUCTURE PREDICTION; STRUCTURE MATCHES; MEAN FORCE; POTENTIALS; BINDING; REPRESENTATION; IDENTIFICATION AB Short-range interactions for secondary structures of proteins are evaluated as potentials of mean force from the observed frequencies of secondary structures in known protein structures which are assumed to have an equilibrium distribution with the Boltzmann factor of secondary structure energies. A secondary conformation at each residue position in a protein is described by a tripeptide, including one nearest neighbor on each side. The secondary structure potentials are approximated as additive contributions from neighboring residues along the sequence. These are part of an empirical potential to provide a crude estimate of protein conformational energy at a residue level. Unlike previous works, interactions are decoupled into intrinsic potentials of residues, potentials of backbone-backbone interactions, and of side chain-backbone interactions. Also interactions are decoupled into one-body, two-body, and higher order interactions between peptide backbone and side chain and between backbones. These decouplings are essential to correctly evaluate the total secondary structure energy of a protein structure without over-counting interactions. Each interaction potential is evaluated separately by taking account of the correlation in the amino acid order of protein sequences, Interactions among side chains are neglected, because of the relatively limited number of protein structures. Published 1999 Wiley-Liss, Inc. C1 Gunma Univ, Fac Technol, Kiryu, Gumma 3768515, Japan. NCI, Lab Expt & Computat Biol, DBS, NIH, Bethesda, MD 20892 USA. RP Miyazawa, S (reprint author), Gunma Univ, Fac Technol, Kiryu, Gumma 3768515, Japan. RI Jernigan, Robert/A-5421-2012 NR 50 TC 31 Z9 32 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD AUG 15 PY 1999 VL 36 IS 3 BP 347 EP 356 DI 10.1002/(SICI)1097-0134(19990815)36:3<347::AID-PROT9>3.0.CO;2-3 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220HD UT WOS:000081658200009 PM 10409828 ER PT J AU Miyazawa, S Jernigan, RL AF Miyazawa, S Jernigan, RL TI An empirical energy potential with a reference state for protein fold and sequence recognition SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE optimal protein sequence; protein inverse folding; protein sequence threading; scoring function; protein sequence design; sequence-structure compatibility; statistical potentials; 3D-1D ID 3-DIMENSIONAL STRUCTURE; GLOBULAR-PROTEINS; MEAN FORCE; MODELS; DESIGN; CONFORMATIONS; DISCRIMINATE; IDENTIFICATION; COMPATIBILITY; PREDICTION AB We consider modifications of an empirical energy potential for fold and sequence recognition to represent approximately the stabilities of proteins in various environments. A potential used here includes a secondary structure potential representing short-range interactions for secondary structures of proteins, and a tertiary structure potential consisting of a long-range, pairwise contact potential and a repulsive packing potential. This potential is devised to evaluate together the total conformational energy of a protein at the coarse grained residue level. It was previously estimated from the observed frequencies of secondary structures, from contact frequencies between residues, and from the distributions of the number of residues in contact in known protein structures by regarding those distributions as the equilibrium distributions with the Boltzmann factor of these interaction energies. The stability of native structures is assumed as a primary requirement for proteins to fold into their native structures. A collapse energy is subtracted from the contact energies to remove the protein size dependence and to represent protein stabilities for monomeric and multimeric states. The free energy of the whole ensemble of protein conformations that is subtracted from the conformational energy to represent protein stability is approximated as the average energy expected for a typical native structure with the same amino acid composition. This term may be constant in fold recognition but essentially varies in sequence recognition. A simple test of threading sequences into structures without gaps is employed to demonstrate the importance of the present modifications that permit the same potential to be utilized for both fold and sequence recognition. Published 1999 Wiley-Liss, Inc. C1 Gunma Univ, Fac Technol, Kiryu, Gumma 3768515, Japan. NCI, Lab Expt & Computat Biol, DBS, NIH, Bethesda, MD 20892 USA. RP Miyazawa, S (reprint author), Gunma Univ, Fac Technol, Kiryu, Gumma 3768515, Japan. RI Jernigan, Robert/A-5421-2012 NR 41 TC 70 Z9 70 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD AUG 15 PY 1999 VL 36 IS 3 BP 357 EP 369 DI 10.1002/(SICI)1097-0134(19990815)36:3<357::AID-PROT10>3.0.CO;2-U PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220HD UT WOS:000081658200010 PM 10409829 ER PT J AU Brenneman, DE Hauser, J Spong, CY Phillips, TM Pert, CB Ruff, M AF Brenneman, DE Hauser, J Spong, CY Phillips, TM Pert, CB Ruff, M TI VIP and D-ala-peptide T-amide release chemokines which prevent HIV-1 GP120-induced neuronal death SO BRAIN RESEARCH LA English DT Article DE vasoactive intestinal peptide; peptide T; chemokine; gp120; acquired immunodeficiency syndrome; secretion ID VASOACTIVE-INTESTINAL-PEPTIDE; HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE PROTEIN GP120; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; RECEPTOR-BINDING; CEREBRAL-CORTEX; AIDS DEMENTIA; COAT PROTEIN; BRAIN INJURY AB Vasoactive intestinal peptide (VIP) and DAPTA (D-ala(1)-peptide T-amide, a gp120-derived octapeptide homologous to VIP) prevent neuronal cell death produced by five variants of HIV-1 (human immunodeficiency virus) envelope protein (gp120). VIP or DAPTA treatment of astrocyte cultures resulted in the release of macrophage inflammatory protein-1 alpha (MIP-1 alpha) and RANTES, beta chemokines known to block gp120 interactions with microglial chemokine receptors. In rat cerebral cortical cultures, gp120-induced neuronal killing was partially or completely prevented by chemokines that stimulate the CXCR4, CCR3 or CCR5 chemokine receptors. Chemokines exhibited marked differences in potency and efficacy in preventing toxicity associated with five gp120 variants (LAV/BRU, CM243, RF, SF2, and MN). RANTES had the broadest and most potent inhibition (IC50 <3 pM for RF isolate). An octapeptide derived from RANTES also exhibited neuroprotection from gp120 (RF isolate) toxicity (IC50 = 0.3 mu M). Treatment with chemokines alone had no delectable effect on neuronal cell number. However, antiserum to MTP-la produced neuronal cell death that was prevented by co-treatment with MIP-1 alpha, suggesting that this endogenous chemokine exerts a tonic regulation important to neuronal survival. The neuroprotective action of VIP on gp120 was attenuated by co-treatment with anti-MIP-1 alpha. These studies suggest that the neuroprotective action of VIP is linked in part to its release of MIP-1 alpha. Furthermore, neuroprotection produced by chemokines is dependent on both the type of chemokine and the variant structure of gp120 and may be relevant to drug strategies for the treatment of AIDS dementia. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NICHHD, Sect Dev & Mol Pharmacol, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Immunochem Lab, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20037 USA. RP Brenneman, DE (reprint author), NICHHD, Sect Dev & Mol Pharmacol, NIH, Bethesda, MD 20892 USA. NR 54 TC 39 Z9 41 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 14 PY 1999 VL 838 IS 1-2 BP 27 EP 36 DI 10.1016/S0006-8993(99)01644-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 227TR UT WOS:000082096500004 PM 10446313 ER PT J AU Swann, PG Odom, S Zhou, YJ Szallasi, Z Blumberg, PM Draber, P Rivera, J AF Swann, PG Odom, S Zhou, YJ Szallasi, Z Blumberg, PM Draber, P Rivera, J TI Requirement for a negative charge at threonine 60 of the FcR gamma for complete activation of Syk SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY RECEPTOR; IMMUNOGLOBULIN-E RECEPTOR; EPSILON-RI; MAST-CELL; IGE RECEPTOR; C-DELTA; SIGNAL-TRANSDUCTION; SH2 DOMAINS AB Aggregation of Fc epsilon RI on mast cells results in the phosphorylation of the Fc epsilon RI gamma chain on tyrosine and threonine residues within the immunoreceptor tyrosine-based activation motif, In the present study we sought to identify the site of threonine phosphorylation in Fc epsilon RI gamma and investigate its functional importance. We found that threonine 60 was phosphorylated in vitro and in vivo. Expression of a mutated Fc epsilon RI gamma (T60A), in either Fc epsilon RI gamma-deficient or gamma-null mast cells, resulted in a delay of Fc epsilon RI endocytosis, inhibition of TNF-alpha mRNA production, and inhibition of degranulation but did not affect Fc epsilon RI-induced cell adhesion. Tyrosine phosphorylation of the T60A mutant gamma chain was normal, but Syk phosphorylation was dramatically reduced in these transfectents, This correlated with reduced co-immunoprecipitation of Fc epsilon RI gamma with Syk. Substitution of an aspartic residue for threonine 60 of the Fc epsilon RI gamma reconstituted complete activation of Syk and co-immunoprecipitation of Fc epsilon RI gamma with Syk. We conclude that the negative charge provided by phosphorylation of threonine 60 of the Fc epsilon RI gamma is required for the appropriate interaction and activation of Syk, This is a likely requirement for immunoreceptor tyrosine-based activation motifs involved in Syk activation. C1 NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. NIAMSD, Sect Lymphocyte Activat, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. Acad Sci Czech Republic, Inst Mol Genet, CR-14220 Prague 4, Czech Republic. RP Bldg 10,Rm 9N228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. EM Juan_Rivera@nih.gov RI Draber, Petr/G-3412-2014 OI Draber, Petr/0000-0002-3986-2025 NR 61 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23068 EP 23077 DI 10.1074/jbc.274.33.23068 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800025 PM 10438475 ER PT J AU Silvente-Poirot, S Escrieut, C Gales, C Fehrentz, JA Escherich, A Wank, SA Martinez, J Moroder, L Maigret, B Bouisson, M Vaysse, N Fourmy, D AF Silvente-Poirot, S Escrieut, C Gales, C Fehrentz, JA Escherich, A Wank, SA Martinez, J Moroder, L Maigret, B Bouisson, M Vaysse, N Fourmy, D TI Evidence for a direct interaction between the penultimate aspartic acid of cholecystokinin and histidine 207, located in the second extracellular loop of the cholecystokinin B receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; FUNCTIONAL EXPRESSION; ANGIOTENSIN-II; MUTANT CYCLES; A RECEPTOR; ANTAGONISTS; BINDING; SELECTIVITY; ACTIVATION; RESIDUE AB Recently, we reported that the mutation of His(207) to Phe located in the second extracellular loop of the cholecystokinin B receptor strongly affected cholecystokinin (CCK) binding (Silvente-Poirot, S., Escrieut, C., and Wank, S. A. (1998) Mol. Pharmacol. 54, 364-371), To characterize the functional group in CCK that interacts with His(207), we first substituted His(207) to Ala. This mutation decreased the affinity and the potency of CCK to produce total inositol phosphates 302-fold and 456-fold without affecting the expression of the mutant receptor. The screening of L-alanine-modified CCK peptides to bind and activate the wild type and mutant receptors allowed the identification of the interaction of the C-terminal Asp(8) of CCK with His(207). The H207A-CCKBR mutant, unlike the wild type receptor, was insensitive to substitution of Asp(8) of CCK to other amino acid residues. This interaction was further confirmed by mutating His(207) to Asp, The affinity of CCK for the H207D-CCKBR mutant was 100-fold lower than for the H207ACCKBR mutant, consistent with an electrostatic repulsion between the negative charges of the two interacting aspartic acids. Peptides with neutral amino acids in position eight of CCK reversed this effect and displayed a gain of affinity for the H207D mutant compared with CCK. To date, this is the first report concerning the identification of a direct contact point between the CCKB receptor and CCK. C1 CHU Rangueil, INSERM U151, Inst Louis Bugnart, F-31403 Toulouse, France. Univ Nancy, Chim Theor Lab, F-54506 Vandoeuvre Nancy, France. NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Max Planck Inst Biochem, D-82143 Martinsried, Germany. RP Silvente-Poirot, S (reprint author), CHU Rangueil, INSERM U151, Inst Louis Bugnart, Bat L3, F-31403 Toulouse, France. RI Poirot, Sandrine/D-5448-2017; OI Martinez, Jean/0000-0002-9267-4621 NR 39 TC 38 Z9 39 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23191 EP 23197 DI 10.1074/jbc.274.33.23191 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800040 PM 10438490 ER PT J AU Rumsey, SC Welch, RW Garraffo, HM Ge, P Lu, SF Crossman, AT Kirk, KL Levine, M AF Rumsey, SC Welch, RW Garraffo, HM Ge, P Lu, SF Crossman, AT Kirk, KL Levine, M TI Specificity of ascorbate analogs for ascorbate transport - Synthesis and detection of [I-125]-6-deoxy-6-iodo-1-ascorbic acid and characterization of its ascorbate-specific transport properties SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEHYDROASCORBIC ACID; VITAMIN-C; LIQUID-CHROMATOGRAPHY; HUMAN NEUTROPHILS; GLUCOSE; CELLS; ACCUMULATION; MECHANISMS; PLASMA AB Cellular ascorbic acid accumulation occurs in vitro by two distinct mechanisms: transport of ascorbate itself or transport and subsequent intracellular reduction of its oxidized product, dehydroascorbic acid. It is unclear which mechanism predominates in vivo, An easily detectable compound resembling ascorbate but not dehydroascorbic acid could be a powerful tool to distinguish the two transport activities. To identify compounds, 21 ascorbate analogs were tested for inhibition of ascorbate or dehydroascorbic acid transport in human fibroblasts. The most effective analogs, competitive inhibitors of ascorbate transport with K-i values of 3 mu M, were 6-deoxy-6-bromo-, 6-deoxy-6-chloro-, and 6-deoxy-6-iodo-L-ascorbate, No analog inhibited dehydroascorbic acid transport. Using substitution chemistry, [I-125]6-deoxy-6-iodo-L-ascorbate (1.4 x 10(4) mCi/mmol) was synthesized. HPLC detection methods were developed for radiolabeled and nonradiolabeled compounds, and transport kinetics of both compounds were characterized. Transport was sodium-dependent, inhibited by excess ascorbate, and similar to that of ascorbate, Transport of oxidized ascorbate and oxidized 6-deoxy-6-iodo-L-ascorbate was investigated using Xenopus laevis oocytes expressing glucose transporter isoform GLUT1 or GLUT3, Oxidation of ascorbate or its analog in media increased uptake of ascorbate in oocytes by 6-13-fold compared with control but not that of 6-deoxy-6-iodo-L-ascorbate. Therefore, 6-deoxy-6-iodo-L-ascorbate, although an effective inhibitor of ascorbate transport, either in its reduced or oxidized form was not a substrate for dehydroascorbic acid transport. Thus, radiolabeled and nonradiolabeled 6-deoxy-6-iodo-L-ascorbate provide a new means for discriminating dehydroascorbic acid and ascorbate transport in ascorbate recycling. C1 NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10,Rm 4D52,MSC 1372, Bethesda, MD 20892 USA. NR 25 TC 34 Z9 35 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23215 EP 23222 DI 10.1074/jbc.274.33.23215 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800044 PM 10438494 ER PT J AU Louis, JM Wondrak, EM Kimmel, AR Wingfield, PT Nashed, NT AF Louis, JM Wondrak, EM Kimmel, AR Wingfield, PT Nashed, NT TI Proteolytic processing of HIV-1 protease precursor, kinetics and mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GAG-POL POLYPROTEIN; PARTICLE MATURATION; TRANSFRAME REGION; VIRAL INFECTIVITY; PROTEINASE; CLEAVAGE; ACTIVATION; INHIBITION; SEQUENCES AB Previously it was demonstrated using a model precursor that processing at the N terminus of the HIV-1 protease (PR) precedes processing at its C terminus. We now show the expression, purification, and kinetics of the autoprocessing reaction of a PR precursor linked to 53 amino acids of the native flanking transframe region (Delta TFP-p6(pol)) of Gag-Pol and containing its two native cleavage sites. The PR contains the two cysteine residues exchanged to alanines, mutations that do not alter the kinetics or the structural stability of the mature PR. Delta TFP-p6(pol)-PR, which encompasses the known PR inhibitor sequence Glu-Asp-Leu within Delta TFP, undergoes cleavage at the Delta TFP/p6(pol) and p6(pol)/PR sites in two consecutive steps to produce the mature PR. Both Delta TFP-p6(pol)-PR and p6(pol)-PR exhibit low intrinsic enzymatic activity. The appearance of the mature PR is accompanied by a large increase in catalytic activity, It follows first-order kinetics in protein concentration with a rate constant of 0.13 +/- 0.01 min(-1) in 0.1 ar acetate at pH 4.8, The pH-rate profile for the observed first-order rate constant is bell-shaped with two ionizable groups of pK(a) 4.9 and 5.1. The rate constant also exhibits approximately 7-fold higher sensitivity to urea denaturation as compared with that of the mature PR, suggesting that the cleavage at the N terminus of the PR domain from the precursor leads to the stabilization of the dimeric structure. C1 NIH, Phys Chem Lab, NIDDK, Bethesda, MD 20892 USA. NIH, Cellular & Dev Biol Lab, NIDDK, Bethesda, MD 20892 USA. NIH, Lab Protein Express, NIAMS, Bethesda, MD 20892 USA. NIH, NIDDK, Lab Bioorg Chem, Bethesda, MD 20892 USA. RP Louis, JM (reprint author), NIH, Phys Chem Lab, NIDDK, Bldg 5,Room 411, Bethesda, MD 20892 USA. EM jmlouis@helix.nih.gov NR 37 TC 53 Z9 53 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23437 EP 23442 DI 10.1074/jbc.274.33.23437 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800071 PM 10438521 ER PT J AU Sinclair, C Borchers, C Parker, C Tomer, K Charbonneau, H Rossie, S AF Sinclair, C Borchers, C Parker, C Tomer, K Charbonneau, H Rossie, S TI The tetratricopeptide repeat domain and a C-terminal region control the activity of Ser/Thr protein phosphatase 5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE/THREONINE PHOSPHATASE; CATALYTIC SUBUNIT; CELL-CYCLE; TYROSINE PHOSPHORYLATION; LIMITED PROTEOLYSIS; TPR; CALCINEURIN; RECEPTOR; KINASE; IDENTIFICATION AB Protein Ser/Thr phosphatase 5 is a 58-kDa protein containing a catalytic domain structurally related to the catalytic subunits of protein phosphatases 1, 2A, and 2B and an extended N-terminal domain with three tetratricopeptide repeats. The activity of this enzyme is stimulated 4-14-fold in vitro by polyunsaturated fatty acids and anionic phospholipids. The structural basis for lipid activation of protein phosphatase 5 was examined by limited proteolysis and site-directed mutagenesis. Trypsinolysis removed the tetratricopeptide repeat domain and increased activity to approximately half that of lipid-stimulated, full-length enzyme. Subtilisin re moved the tetratricopeptide repeat domain and 10 residues from the C terminus, creating a catalytic fragment with activity that was equal to or greater than that of lipid-stimulated, full-length enzyme. Catalytic fragments generated by proteolysis were no longer stimulated by lipid, and degradation of the tetratricopeptide repeat domain was decreased by association with lipid. A truncated mutant missing 13 C-terminal residues was also insensitive to lipid and was as active as full-length, lipid-stimulated enzyme. These results suggest that the C-terminal and N-terminal domain act in a coordinated manner to suppress the activity of protein phosphatase 5 and mediate its activation by lipid. These regions may be targets for the regulation of protein phosphatase 5 activity in vivo. C1 Purdue Univ, Dept Biochem 1153, W Lafayette, IN 47907 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Rossie, S (reprint author), Purdue Univ, Dept Biochem 1153, W Lafayette, IN 47907 USA. RI Tomer, Kenneth/E-8018-2013 FU NCI NIH HHS [CA59935]; NIDDK NIH HHS [DK20542]; NINDS NIH HHS [NS31221] NR 37 TC 60 Z9 62 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23666 EP 23672 DI 10.1074/jbc.274.33.23666 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800100 PM 10438550 ER PT J AU Biswas, I Ban, C Fleming, KG Qin, J Lary, JW Yphantis, DA Yang, W Hsieh, P AF Biswas, I Ban, C Fleming, KG Qin, J Lary, JW Yphantis, DA Yang, W Hsieh, P TI Oligomerization of a MutS mismatch repair protein from Thermus aquaticus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BASE PAIRS; HETERODUPLEX DNA; TRANSLOCATION MECHANISM; GENETIC-RECOMBINATION; REPLICATION FIDELITY; CANCER-CELLS; BINDS; HETERODIMER; BETA; ULTRACENTRIFUGE AB The MutS DNA mismatch protein recognizes heteroduplex DNAs containing mispaired or unpaired bases. We have examined the oligomerization of a MutS protein from Thermus aquaticus that binds to heteroduplex DNAs at elevated temperatures. Analytical gel filtration, cross-linking of MutS protein with disuccinimidyl suberate, light scattering, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry establish that the Tag protein is largely a dimer in free solution, Analytical equilibrium sedimentation showed that the oligomerization of Tag MutS involves a dimer-tetramer equilibrium in which dimer predominates at concentrations below 10 mu M. The Delta G(2-4)(0) for the dimer to tetramer transition is approximately -6.9 +/- 0.1 kcal/mol of tetramer, Analytical gel filtration of native complexes and gel mobility shift assays of an maltose-binding protein-MutS fusion protein bound to a short, 37-base pair heteroduplex DNA reveal that the protein binds to DNA as a dimer with no change in oligomerization upon DNA binding. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. Univ Connecticut, Natl Analyt Ultracentrifuge Facil, Storrs, CT 06269 USA. Univ Crete, Dept Biol, Heraklion 71409, Crete, Greece. Univ Crete, Inst Mol Biol & Biotechnol, Heraklion 71409, Crete, Greece. RP Hsieh, P (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 10,Rm 9D04,10 Ctr Dr,MSC 1810, Bethesda, MD 20892 USA. RI Yang, Wei/D-4926-2011; Fleming, Karen/E-7892-2011; Ban, Changill/F-5426-2013 OI Yang, Wei/0000-0002-3591-2195; NR 32 TC 47 Z9 49 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23673 EP 23678 DI 10.1074/jbc.274.33.23673 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800101 PM 10438551 ER PT J AU Grishin, NV AF Grishin, NV TI Phosphatidylinositol phosphate kinase: A link between protein kinase and glutathione synthase folds SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein kinase; lipid kinase; ATP-grasp fold; fold evolution; SAICAR synthase ID CRYSTAL-STRUCTURE; CATALYTIC SUBUNIT; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; BINDING; CLASSIFICATION; RESISTANCE; SYNTHETASE; DATABASE; COMPLEX AB Comparisons of serine/threonine protein kinase (PK) and type II beta phosphatidylinositol phosphate kinase (PIPK) structures with each other and also with other proteins reveal structural and functional similarity between the two kinases and proteins of the glutathione synthase fold (ATP-grasp). This suggests that these enzymes are evolutionarily related. The structure of PIPK, which clearly resembles both PK and ATP-grasp, provides a link between the two proteins and establishes that the C-terminal domains of PK, PIPK and ATP-grasp share the same fold. The functional implications of the proposed homology are discussed. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Grishin, NV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A, Bethesda, MD 20894 USA. NR 31 TC 35 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 13 PY 1999 VL 291 IS 2 BP 239 EP 247 DI 10.1006/jmbi.1999.2973 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226EA UT WOS:000082006300001 PM 10438618 ER PT J AU Gawley, RE Zhang, QH Higgs, PI Wang, SP Leblanc, RM AF Gawley, RE Zhang, QH Higgs, PI Wang, SP Leblanc, RM TI Anthracylmethyl crown ethers as fluorescence sensors of saxitoxin (vol 40, pg 5461, 1999) SO TETRAHEDRON LETTERS LA English DT Correction C1 Univ Miami, Dept Chem, Coral Gables, FL 33124 USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Coral Gables, FL 33124 USA. RP Gawley, RE (reprint author), Univ Miami, Dept Chem, POB 249118, Coral Gables, FL 33124 USA. NR 1 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD AUG 13 PY 1999 VL 40 IS 33 BP 6135 EP 6135 PG 1 WC Chemistry, Organic SC Chemistry GA 223DC UT WOS:000081824100048 ER PT J AU Jiang, JL Li, AH Jang, SY Chang, L Melman, N Moro, S Ji, XD Lobkovsky, EB Clardy, JC Jacobson, KA AF Jiang, JL Li, AH Jang, SY Chang, L Melman, N Moro, S Ji, XD Lobkovsky, EB Clardy, JC Jacobson, KA TI Chiral resolution and stereospecificity of 6-phenyl-4-phenylethynyl-1,4-dihydropyridines as selective A(3) adenosine receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CALCIUM-CHANNEL; RAT-BRAIN; DERIVATIVES; AFFINITY; AGONIST; 1,4-DIHYDROPYRIDINE; STIMULATION; BLOCKERS; LIGANDS; ACIDS AB Racemic 6-phenyl-4-phenylethynyl-1,4-dihydropyridine derivatives have been shown to be highly selective A(3) adenosine receptor antagonists (Jiang et al. J. Med. Chem. 1997, 40, 2596-2608). Methods for resolving the optical isomers at the C4 position, involving selective crystallization or chromatographic separation of diastereomeric ester derivatives, have been developed. Optically pure glycerol and threitol derivatives were used as chiral auxiliary groups for ester formation at the 3-position, resulting in diastereomeric mixtures of dihydropyridines. Esterification of a 6-phenyl-4-phenylethynyl-1,4-dihydropyridine derivative at the S-position with a chiral, protected glycerol moiety, (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol, allowed the selective crystallization of a pure diastereomer, 9. The H-1 NMR spectrum of 9 using the lanthanide shift reagent Eu(fod)(3) indicated optical purity, and the (4S,2'R)-configuration was assigned using X-ray crystallography. The noncrystalline (4R,2'R)-isomer 10 was also isolated and shown to be 3-fold more potent than the (4S,2'R)-isomer in binding to A(3) receptors. The 2,2-dimethyl-1,3-dioxolane moiety also served as a protected form of a diol, which showed selective reactivity versus a 5-ethyl ester in basic transesterification reactions. A racemic 5-carboxylic acid derivative could not be resolved through crystallization of diastereomeric salts. Enantiomers of 5-benzyl 3-ethyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-dihydropyridine-3,5-dicarboxylate (2) were obtained via an ester derived from (4R,5R)-(-)-2,3-O-isopropylidene-D-threitol at the 3-position, which was resolved using HPLC, and each diastereomer was subsequently deprotected in acidic conditions. The resulting diols were exchanged for ethyl ester groups by base-catalyzed transesterification. The binding of pure enantiomers of 2 at A(3) adenosine receptors indicated a 35-fold stereoselectivity for the (4S)-isomer 21. A receptor docking hypothesis, using a previously derived human A(3) receptor model, shows the bulkier of the two ester groups (5-Bn) of 21 oriented toward the exofacial side and the 4-position phenylethynyl group situated between transmembrane helical domain TM6 and TM7. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Baker Lab, Dept Chem, Ithaca, NY 14853 USA. RP Jacobson, KA (reprint author), NIDDK, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 36 TC 44 Z9 44 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 12 PY 1999 VL 42 IS 16 BP 3055 EP 3065 DI 10.1021/jm980688e PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 226TU UT WOS:000082038700008 PM 10447949 ER PT J AU Ashcroft, M Stephens, RM Hallberg, B Downward, J Kaplan, DR AF Ashcroft, M Stephens, RM Hallberg, B Downward, J Kaplan, DR TI The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth SO ONCOGENE LA English DT Article DE Trk; PC12; NGF; phosphatidylinositol 3-kinase; differentiation; survival ID NERVE-GROWTH-FACTOR; TRK TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; PHEOCHROMOCYTOMA CELLS; SIGNAL-TRANSDUCTION; NEURONAL DIFFERENTIATION; PHOSPHOINOSITIDE 3-KINASE; AKT PROTOONCOGENE; FACTOR RECEPTORS AB The Trk/Nerve Growth Factor receptor mediates the rapid activation of a number of intracellular signaling proteins, including phosphatidylinositol 3-kinase (PI 3-kinase). Here, we describe a novel, NGF-inducible system that we used to specifically address the signaling potential of endogenous PI 3-kinase in NGF-mediated neuronal survival and differentiation processes. This system utilizes a Trk receptor mutant (Trk(def)) lacking sequences Y490, Y785 and KFG important for the activation of the major Trk targets; SHC, PLC-gamma I, Ras, PI 3-kinase and SNT. TrKdef was kinase active but defective for NGF-induced responses when stably expressed in PC12nnr5 cells (which lack detectable levels of TrkA and are non-responsive to NGF). The PI 3-kinase consensus binding site, YxxM (YYPM), was introduced into the insert region within the kinase domain of Trk(def). NGF-stimulated tyrosine phosphorylation of the Trk(def)+PI 3-kinase addback receptor, resulted in the direct association and selective activation ;of PI 3-kinase in vitro and the production of PI(3,4)P-2 and PI(3,4,5)P-3 in rivo (comparable to wild-type). PC12nnr5 cells stably expressing Trk(def)+PI 3-kinase, initiated neurite outgrowth but failed to stably extend and maintain these neurites in response to NGF as compared to PC12 parental cells, or PC12nnr5 cells overexpressing wild-type Trk. However, Trk(def)+PI 3-kinase was fully competent in mediating NGF-induced survival processes. We propose that while endogenous PI 3-kinase can contribute in part to neurite initiation professes, its selective activation and subsequent signaling to downstream effecters such as Akt, functions mainly to promote cell survival in the PC12 system. C1 NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. Imperial Canc Res Fund, London WC2A 3PX, England. RP Ashcroft, M (reprint author), NCI, ABL Basic Res Program, FCRDC, W 7th St, Frederick, MD 21702 USA. NR 65 TC 72 Z9 72 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 12 PY 1999 VL 18 IS 32 BP 4586 EP 4597 DI 10.1038/sj.onc.1202814 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 226KF UT WOS:000082018600008 PM 10467403 ER PT J AU Ariumi, Y Masutani, M Copeland, TD Mimori, T Sugimura, T Shimotohno, K Ueda, K Hatanaka, M Noda, M AF Ariumi, Y Masutani, M Copeland, TD Mimori, T Sugimura, T Shimotohno, K Ueda, K Hatanaka, M Noda, M TI Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro SO ONCOGENE LA English DT Article DE DNA-PK; PARP; Ku; poly(ADP-ribosyl)ation; dsDNA break ID HUMAN-IMMUNODEFICIENCY-VIRUS; ABL TYROSINE KINASE; C-ABL; V(D)J RECOMBINATION; DAMAGE; REPAIR; CELLS; P53; ACTIVATION; ANTIGEN AB It has been suggested that DNA-dependent protein kinase (DNA-PK) is a central component of DNA double-strand-break repair. The mechanism of DNA-PK action, however, has not been fully understood. Poly(ADP-ribose) polymerase (PARP) is another nuclear enzyme which has high affinity to DNA ends. In this study, we analysed the interaction between these tao enzymes. First, DNA-PK was found to suppress the PARP activity and alters the pattern of poly(ADP-ribosyl)ation. Although DNA-PK phosphorylates PARP in a DNA-dependent manner, this modification is unlikely to be responsible for the suppression of PARP activity, since this suppression occurs even in the absence of ATP. Conversely, PARP was found to ADP-ribosylate DNA-PK in vitro. However, the autophosphorylation activity of DNA-PK was not influenced by this modification. In a competitive electrophoretic mobility shift assay, Ku 70/80 complex, the DNA binding component of DNA-PK, was found to have higher affinity to a short fragment of DNA than does PARP. Furthermore, co-immunoprecipitation analysis suggested direct or close association between Ku and PARP. Thus, DNA-PK suppresses PARP activity, probably through direct binding and/or sequestration of DNA-ends which serve as an important stimulator for both enzymes. C1 Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. Natl Canc Ctr, Res Inst, Div Biochem, Tokyo 1040045, Japan. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Keio Univ, Sch Med, Tokyo 1600016, Japan. Kyoto Univ, Chem Res Inst, Kyoto 6110011, Japan. Kyoto Univ, Grad Sch Med, Dept Mol Oncol, Kyoto 6068501, Japan. RP Ariumi, Y (reprint author), Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. RI Ariumi, Yasuo/F-5804-2013 NR 49 TC 93 Z9 95 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 12 PY 1999 VL 18 IS 32 BP 4616 EP 4625 DI 10.1038/sj.onc.1202823 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 226KF UT WOS:000082018600011 PM 10467406 ER PT J AU Pozsgay, V AF Pozsgay, V TI A new, lipophilic p-alkoxybenzyl ether protecting group and its use in the synthesis of a disaccharide SO ORGANIC LETTERS LA English DT Article ID STRATEGY AB [GRAPHICS] In contrast to major advances in the chemical synthesis of oligosaccharides, the methods of purification of the intermediates are essentially the same as they were decades ago, Here, the synthesis of p-(dodecyloxy)benzyl chloride is described and it is demonstrated that the new p-(dodecyloxy)benzyl ether protecting group can render a protected disaccharide sufficiently lipophilic for selective adsorption on C-18 silica, thus sidestepping the expensive silica gel chromatography traditionally used for the isolation of protected oligosaccharides. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 11 TC 19 Z9 19 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD AUG 12 PY 1999 VL 1 IS 3 BP 477 EP 479 DI 10.1021/ol990670d PG 3 WC Chemistry, Organic SC Chemistry GA 256AD UT WOS:000083701600032 PM 10822587 ER PT J AU Osipovich, O Duhe, RJ Hasty, P Durum, SK Muegge, K AF Osipovich, O Duhe, RJ Hasty, P Durum, SK Muegge, K TI Defining functional domains of Ku80: DNA end binding and survival after radiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BIOCHEMICAL-CHARACTERIZATION; KU70; AUTOANTIGEN; DEFICIENT; ANTIGEN; CELLS AB The Ku heterodimeric protein (Ku80/Ku70) is an essential component of the double-strand break DNA repair pathway in mammalian cells, We have recently defined a central region within Ku80 that is required for heterodimerization with Ku70, We now identified a core region within Ku80 (amino acids 210 to 531) that is necessary for binding of Ku to DNA ends, Interaction with Ku70 and DNA end binding are important for Ru80 function in vivo since Ku80 mutants lacking DNA end binding activity were unable to restore radiation resistance in Ku80 deficient fibroblast cell lines. However, Ku80 mutants were identified that retained DNA end binding activity but were unable to restore radiation survival, thus pointing to additional functional properties of Ku80. An N-terminal deletional mutant of Ku80 was able to suppress wild type Ku80 function for radiation survival in several cell lines, thus demonstrating dominant negative function. (C) 1999 Academic Press. C1 NCI, Mol Immunoregulat Lab, SAIC, Frederick, MD 21702 USA. Lexicon Genet Inc, The Woodlands, TX 77382 USA. RP Osipovich, O (reprint author), NCI, Mol Immunoregulat Lab, SAIC, Frederick, MD 21702 USA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 11 PY 1999 VL 261 IS 3 BP 802 EP 807 DI 10.1006/bbrc.1999.1118 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 226HQ UT WOS:000082014900043 PM 10441505 ER PT J AU Culnane, M Fowler, MG Oleske, J AF Culnane, M Fowler, MG Oleske, J TI Infant growth after in utero exposure to zidovudine - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID UNINFECTED CHILDREN; IMMUNODEFICIENCY C1 NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Culnane, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1999 VL 282 IS 6 BP 528 EP 529 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 224UV UT WOS:000081919100023 ER PT J AU Yu, KF Zhang, J AF Yu, KF Zhang, J TI Correcting the odds ratio in cohort studies of common outcomes - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Yu, KF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1999 VL 282 IS 6 BP 529 EP 529 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 224UV UT WOS:000081919100025 ER PT J AU Udey, MC Stanley, JR AF Udey, MC Stanley, JR TI Pemphigus - Diseases of antidesmosomal autoimmunity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PARANEOPLASTIC PEMPHIGUS; VULGARIS ANTIGEN; FOGO-SELVAGEM; PATHOGENIC AUTOANTIBODIES; PASSIVE TRANSFER; NEONATAL MICE; FOLIACEUS; SUSCEPTIBILITY; BACULOVIRUS; ANTIBODIES C1 NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Div Clin Sci, NIH, Bldg 10,Room 12B238, Bethesda, MD 20892 USA. NR 33 TC 58 Z9 62 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1999 VL 282 IS 6 BP 572 EP 576 DI 10.1001/jama.282.6.572 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 224UV UT WOS:000081919100032 PM 10450720 ER PT J AU Mofenson, LM AF Mofenson, LM TI Can perinatal HIV infection be eliminated in the United States? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE TREATMENT; CHANGING PATTERN; PRENATAL-CARE; WOMEN; TRANSMISSION; AIDS; PREVALENCE; REDUCTION; COHORT C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20852 USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 31 TC 28 Z9 28 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1999 VL 282 IS 6 BP 577 EP 579 DI 10.1001/jama.282.6.577 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 224UV UT WOS:000081919100033 PM 10450721 ER PT J AU Fazekas, F Barkhof, F Filippi, M Grossman, RI Li, DKB McDonald, WI McFarland, HF Paty, DW Simon, JH Wolinsky, JS Miller, DH AF Fazekas, F Barkhof, F Filippi, M Grossman, RI Li, DKB McDonald, WI McFarland, HF Paty, DW Simon, JH Wolinsky, JS Miller, DH TI The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis SO NEUROLOGY LA English DT Review ID FAST SPIN-ECHO; CLINICALLY ISOLATED SYNDROMES; ACUTE DISSEMINATED ENCEPHALOMYELITIS; GADOLINIUM-ENHANCED MRI; FOLLOW-UP; BRAIN MRI; OPTIC-NERVE; LESION LOAD; FAST-FLAIR; CORD MRI AB MRI is very sensitive in showing MS lesions throughout the CNS, Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS. C1 Graz Univ, Dept Neurol, A-8036 Graz, Austria. Graz Univ, MRI Ctr, A-8036 Graz, Austria. Vrije Univ Hosp, Amsterdam, Netherlands. Univ Milan, Dept Neurosci, Neuroimaging Res Unit, Sci Inst Osped San Raffaele, I-20122 Milan, Italy. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Inst Neurol, London WC1N 3BG, England. NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Texas, Sch Med, Houston, TX USA. RP Graz Univ, Dept Neurol, Auenbruggerpl 22, A-8036 Graz, Austria. EM franz.fazekase@kfunigraz.ac.at FU Multiple Sclerosis Society [491] NR 71 TC 165 Z9 172 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 11 PY 1999 VL 53 IS 3 BP 448 EP 456 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 224PA UT WOS:000081906400003 PM 10449103 ER PT J AU Launer, LJ Terwindt, GM Ferrari, MD AF Launer, LJ Terwindt, GM Ferrari, MD TI The prevalence and characteristics of migraine in a population-based cohort - The GEM Study SO NEUROLOGY LA English DT Article ID TENSION-TYPE HEADACHE; GENERAL-POPULATION; NATIONWIDE SURVEY; AURA; EPIDEMIOLOGY; DISORDERS; ADULTS; LIFE; RACE AB Objective: To describe the distribution of migraine and its subtypes in the general population. Background: Previous population-based studies are limited by small samples or a narrow age range, do not provide prevalence estimates of migraine with and without aura, or underestimate prevalence by not accounting for patients missed as a result of using imperfect screening instruments. Methods: The participants in the Genetic Epidemiology of Migraine Study were comprised of 6,491 adults, age 20 to 65 years, selected randomly from two county population registries in the Netherlands to participate in a general health survey (52.7% response). Migraineurs were identified as follows: All participants were screened on headache history. Those meeting screen-positive criteria were given a detailed questionnaire on headache. A total of 1,292 randomly selected screen-positives (83% of screen-positives) and 197 randomly selected screen-negatives (5% of screen-negatives) were administered a semistructured clinical interview by telephone. Final diagnosis met 1988 International Headache Society criteria. Prevalence of migraine was estimated for sex and 5-year age strata. Results: The lifetime prevalence of migraine in women was 33% and the 1-year prevalence of migraine in women was 25%. In men, the lifetime prevalence was 13.3% and the 1-year prevalence was 7.5%. Among patients with migraine in the past year, 63.9% had migraine without aura, 17.9% had migraine with aura, and 13.1% had migraine both with and without aura. The prevalence of migraine was significantly higher in women and not associated with socioeconomic status. Migraineurs suffered a median of 12 migraine attacks per year; 25% had at least two attacks per month. Conclusions: The prevalence of migraine is higher then previously reported. The coexistence of migraine with and without aura occurs frequently and has implications for future studies on the genetics of migraine. C1 Natl Inst Publ Hlth & Environm, Dept Chron Dis Epidemiol, NL-3720 BA Bilthoven, Netherlands. Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, Netherlands. RP Launer, LJ (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Gateway Bldg 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 22 TC 328 Z9 333 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 11 PY 1999 VL 53 IS 3 BP 537 EP 542 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 224PA UT WOS:000081906400017 PM 10449117 ER PT J AU Levy, LM Reis, IL Grafman, J AF Levy, LM Reis, IL Grafman, J TI Metabolic abnormalities detected by H-1-MRS in dyscalculia and dysgraphia SO NEUROLOGY LA English DT Article ID DEVELOPMENTAL DYSLEXIA; BRAIN AB Proton MRS was performed in a patient with developmental acalculia. The results indicated a focal, wedge-shaped defect in the left temporoparietal brain region near the angular gyrus, with differential decreases in N-acetyl-aspartate, creatine, and choline, These results support the hypothesis that developmental acalculia, like acquired acalculia, is associated with left posterior hemisphere lesions. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 10 TC 34 Z9 36 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 11 PY 1999 VL 53 IS 3 BP 639 EP 641 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 224PA UT WOS:000081906400037 PM 10449137 ER PT J AU Ji, XH Blaszczyk, J Xiao, B O'Donnell, R Hu, X Herzog, C Singh, SV Zimniak, P AF Ji, XH Blaszczyk, J Xiao, B O'Donnell, R Hu, X Herzog, C Singh, SV Zimniak, P TI Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1 SO BIOCHEMISTRY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CATALYTIC EFFICIENCY; HUMAN PLACENTA; OPTICAL ENANTIOMERS; POLYMORPHIC FORMS; HIGH-RESOLUTION; DIOL EPOXIDES; PI; CONJUGATION; COMPLEX AB Two variants of human class pi glutathione (GSH) S-transferase 1-1 with either isoleucine or valine in position 104 (hGSTP1-1[I104] and hGSTP1-1[V104]) have distinct activity toward (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. To elucidate their structure-function relationship, we determined the crystal structures of the two variants in complex with GSBpd, the GSH conjugate of (+)-anti-BPDE, at 2.1 and 2.0 Angstrom resolution, respectively. The crystal structures reveal that residue 104 in the xenobiotic substrate-binding site (H-site) dictates the binding modes of the product molecule GSBpd with the following three consequences. First, the distance between the hydroxyl group of Y7 and the sulfur atom of GSBpd is 5.9 Angstrom in the hGSTP1-1[I104].GSBpd complex versus 3.2 Angstrom in the V104 variant. Second, one of the hydroxyl groups of GSBpd forms a direct hydrogen bond with R13 in hGSTP1-1[V104].GSBpd; in contrast, this hydrogen bond is not observed in the I104 complex. Third, in the hydrophilic portion of the H-site of the I104 complex, five H-site water molecules [Ji, X., et al. (1997) Biochemistry 36, 9690-9702] are observed, whereas in the V104 complex, two of the five have been displaced by the Bpd moiety of GSBpd. Although there is no direct hydrogen bond between Y108 (OH) and the hydroxyl groups of GSBpd, indirect hydrogen bonds mediated by water molecules are observed in both complexes, supporting the previously suggested role of the hydroxyl group of Y108 as an electrophilic participant in the addition of GSH to epoxides. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. John L McClellan Mem Vet Hosp, Little Rock, AR 72205 USA. Mercy Hosp, Canc Res Lab, Pittsburgh, PA 15219 USA. RP Ji, XH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIEHS NIH HHS [ES09140, ES07804] NR 35 TC 33 Z9 34 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 10 PY 1999 VL 38 IS 32 BP 10231 EP 10238 DI 10.1021/bi990668u PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226HL UT WOS:000082014500003 PM 10441116 ER PT J AU Takenaka, T Qin, GJ Brady, RO Medin, JA AF Takenaka, T Qin, GJ Brady, RO Medin, JA TI Circulating alpha-galactosidase A derived from transduced bone marrow cells: Relevance for corrective gene transfer for Fabry disease SO HUMAN GENE THERAPY LA English DT Article ID ENDOTHELIAL-CELLS; THERAPY; PURIFICATION; EXPRESSION; PLACENTA; SAFE; LINE AB Fabry disease is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A), We previously engineered a retrovirus encoding human alpha-gal A and demonstrated enzymatic correction of patient cells. Further, we demonstrated metabolic cooperativity, in that corrected cells secrete alpha-gal A that can be taken up and utilized by bystander cells in vitro, In the present study, we created a system to examine and quantitate this phenomenon in vivo, To differentiate from endogenous alpha-gal A, we constructed a retroviral vector (pUMFG/alpha-gal A/FLAG) containing a fusion form of alpha-gal A with a specific tag sequence at the carboxy terminus. The catalytic activity of the fusion protein was identical to wild-type alpha-gal A, The fusion protein was overexpressed in and secreted by transduced patient cells. In uptake studies, the fusion protein was detected in the lysosome-enriched fraction of recipient cells, We then examined the effectiveness of the pUMFG/alpha-g A/FLAG retroviral vector in vivo. Murine bone marrow (BM) cells were transduced and transplanted into irradiated hosts, After 9 weeks, proviral DNA was detected by PCR in peripheral blood and BM mononuclear cells, More importantly, specific fusion protein enzymatic activity could be demonstrated in those cells and in plasma, Thus, we have demonstrated that overexpressed alpha-gal A enters the circulation from transduced BM cells and is stable over a significant period of time. C1 Univ Illinois, Hematol Oncol Sect, Dept Med, Chicago, IL 60607 USA. Univ Illinois, Dept Biochem & Mol Biol, Chicago, IL 60607 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Univ Illinois, Hematol Oncol Sect, Dept Med, Mol Biol Res Bldg,Room 3150,900 S Ashland Ave, Chicago, IL 60607 USA. EM jmedin@uic.edu NR 26 TC 29 Z9 34 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG 10 PY 1999 VL 10 IS 12 BP 1931 EP 1939 DI 10.1089/10430349950017293 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 227DK UT WOS:000082062900004 PM 10466627 ER PT J AU Stewart, AK Sutherland, DR Nanji, S Zhao, Y Lutzko, C Nayar, R Peck, B Ruedy, C McGarrity, G Tisdale, J Dube, ID AF Stewart, AK Sutherland, DR Nanji, S Zhao, Y Lutzko, C Nayar, R Peck, B Ruedy, C McGarrity, G Tisdale, J Dube, ID TI Engraftment of gene-marked hematopoietic progenitors in myeloma patients after transplant of autologous long-term marrow cultures SO HUMAN GENE THERAPY LA English DT Article ID HUMAN ADENOSINE-DEAMINASE; APE LEUKEMIA-VIRUS; CELL-CYCLE STATUS; BONE-MARROW; STEM-CELLS; RETROVIRAL VECTORS; REPOPULATING CELLS; RECOMBINANT RETROVIRUSES; PERIPHERAL-BLOOD; INITIATING CELLS AB We conducted a phase I hematopoietic stem cell (HSC) gene-marking trial in patients undergoing autologous blood or marrow stem cell transplant for the treatment of multiple myeloma, Between 500 and 1000 ml of bone marrow was harvested from each of 14 myeloma patients and 1 syngeneic donor, A mean of 3.3 x 10(9) cells per patient were plated in 20 to 50 long-term marrow culture (LTMC) flasks and maintained for 3 weeks. LTMCs were exposed on days 8 and 15 to clinical-grade neo(r)-containing retrovirus supernatant (G1Na). A mean of 8.23 x 10(8) day-21 LTMC cells containing 5.2 x 10(4) gene-marked granulocyte-macrophage progenitor cells (CFU-GM) were infused along with an unmanipulated peripheral blood stem cell graft into each patient after myeloablative therapy. Proviral DNA was detected in 71% of 68 tested blood and bone marrow samples and 150 of 2936 (5.1%) CFU-GM derived from patient bone marrow samples after transplant. The proportion of proviral DNA-positive CFU-GM declined from a mean of 9.8% at 3 months to a mean of 2.3% at 24 months postinfusion. Southern blots of 26 marrow and blood samples were negative. Semiquantitative PCR analysis indicated that gene transfer was achieved in 0.01-1% of total bone marrow and blood mononuclear cells (MNCs). Proviral DNA was also observed in EBV-transformed B lymphocytes, in CD34(+)-enriched bone marrow cells, and in CFUs derived from the latter progenitors. Gene-modified cells were detected by PCR in peripheral blood and bone marrow for 24 months after infusion of LTMC cells. Sensitivity and specificity of the PCR assays were independently validated in four laboratories. Our data confirm that HSCs may be successfully transduced in stromal based culture systems. The major obstacle to therapeutic application of this approach remains the overall low level of genetically modified cells among the total hematopoietic cell pool in vivo. C1 Toronto Hosp, Dept Med, Toronto, ON M5T 2S8, Canada. Univ Toronto, Fac Med, Toronto, ON, Canada. Sunnybrook & Womens Coll Hlth Sci, Dept Lab Med, Toronto, ON, Canada. Genet Therapy Inc, Gaithersburg, MD USA. NIH, Bethesda, MD 20892 USA. RP Stewart, AK (reprint author), Princess Margaret Hosp, 5th Floor,Room 126,610 Univ Ave, Toronto, ON M5G 2M9, Canada. NR 51 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG 10 PY 1999 VL 10 IS 12 BP 1953 EP 1964 DI 10.1089/10430349950017310 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 227DK UT WOS:000082062900006 PM 10466629 ER PT J AU Stewart, AK Lassam, NJ Graham, FL Gauldi, J Wollenberg, B Habib, NA AF Stewart, AK Lassam, NJ Graham, FL Gauldi, J Wollenberg, B Habib, NA TI Human gene marker/therapy clinical protocols (complete updated listings) SO HUMAN GENE THERAPY LA English DT Article C1 NIH, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Royal Brompton Hosp, London SW3 6LY, England. UCL, Sch Med, London W1N 8AA, England. Hammersmith Hosp, London, England. Univ Wales Coll Cardiff, Cardiff CF1 3NS, S Glam, Wales. Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Univ London Imperial Coll Sci Technol & Med, London, England. RP Stewart, AK (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Wollenberg, Barbara/E-7435-2010 NR 0 TC 12 Z9 12 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG 10 PY 1999 VL 10 IS 12 BP 2037 EP 2088 PG 52 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 227DK UT WOS:000082062900014 ER PT J AU Grundy, SM Cleeman, JI Rifkind, BM Kuller, LH AF Grundy, SM Cleeman, JI Rifkind, BM Kuller, LH CA Natl Cholesterol Educ Program TI Cholesterol lowering in the elderly population SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; BEAM COMPUTED-TOMOGRAPHY; SERUM-CHOLESTEROL; RISK-FACTORS; MYOCARDIAL-INFARCTION; ARTERY DISEASE; CARDIOVASCULAR-DISEASE; SYSTOLIC HYPERTENSION; PRIMARY-PREVENTION; BLOOD CHOLESTEROL AB The incidence of coronary heart disease (CHD) peaks in the elderly population. In secondary and primary prevention trials, cholesterol-lowering therapy reduces risk for CHD in both older and younger participants. This benefit, therefore, can be extended to the elderly. C1 NHLBI, Natl Cholesterol Educ Program, Bethesda, MD 20892 USA. RP Cleeman, JI (reprint author), NHLBI, Natl Cholesterol Educ Program, 31 Ctr Dr,Bldg 31,Room 4A16, Bethesda, MD 20892 USA. NR 64 TC 78 Z9 84 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 9 PY 1999 VL 159 IS 15 BP 1670 EP 1678 DI 10.1001/archinte.159.15.1670 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 224MR UT WOS:000081903300004 PM 10448768 ER PT J AU Culleton, BF Larson, MG Evans, JC Wilson, PWF Barrett, BJ Parfrey, PS Levy, D AF Culleton, BF Larson, MG Evans, JC Wilson, PWF Barrett, BJ Parfrey, PS Levy, D TI Prevalence and correlates of elevated serum creatinine levels - The Framingham heart study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; STAGE RENAL-DISEASE; URINARY ALBUMIN EXCRETION; BLOOD-PRESSURE; BODY-COMPOSITION; AGE; FAILURE; CLEARANCE; RISK; MICROALBUMINURIA AB Background: Elevated serum creatinine (SCr) levels are a predictor of end-stage renal disease, but little is known about the prevalence of elevated SCr levels and their correlates in the community. Methods: In this cross-sectional, community-based sample, SCr levels were measured in 6233 adults (mean age, 54 years; 54% women) who composed the "broad sample" of this investigation. A subset, consisting of 3241 individuals who were free of known renal disease, cardiovascular disease, hypertension, and diabetes, constituted the healthy reference sample. In this latter sample, sex-specific 95th percentiles for SCr levels (men, 136 mu mol/L [1.5 mg/dL]; women, 120 mu mol/L [1.4 mg/dL]) were labeled cutpoints. These cutpoints were applied to the broad sample in a logistic regression model to identify prevalence and correlates of elevated SCr levels. Results: The prevalence of elevated SCr levels was 8.9% in men and 8.0% in women. Logistic regression in men identified age, treatment for hypertension (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.27-2.42), and body mass index (OR, 1.08; 95% CI, 1.01-1.15) as correlates of elevated SCr levels. Additionally, men with diabetes who were receiving antihypertensive medication were more likely to have raised SCr values (OR, 2.94, 95% CI, 1.60-5.39). In women, age, use of cardiac medications (OR, 1.58; 95% CI, 1.10-2.96), and treatment for hypertension (OR, 1.42; 95% CI, 1.07-1.87) were associated with elevated SCr levels. Conclusions: Elevated SCr levels are common in the community and are strongly associated with older age, treatment for hypertension, and diabetes. Longitudinal studies are warranted to determine the clinical outcomes of individuals with elevated levels of SCr and to examine factors related to the progression of renal disease in the community. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Mem Univ Newfoundland, Div Nephrol, St Johns, NF, Canada. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 45 TC 138 Z9 146 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 9 PY 1999 VL 159 IS 15 BP 1785 EP 1790 DI 10.1001/archinte.159.15.1785 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 224MR UT WOS:000081903300019 PM 10448783 ER PT J AU Valtschanoff, JG Burette, A Wenthold, RJ Weinberg, RJ AF Valtschanoff, JG Burette, A Wenthold, RJ Weinberg, RJ TI Expression of NR2 receptor subunit in rat somatic sensory cortex: Synaptic distribution and colocalization with NR1 and PSD-95 SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NMDA; glutamate; postsynaptic density; postembedding immunocytochemistry; anchoring proteins; scaffold ID CENTRAL-NERVOUS-SYSTEM; LONG-TERM POTENTIATION; DENSITY PROTEIN PSD-95; NMDA RECEPTOR; GLUTAMATE-RECEPTORS; POSTSYNAPTIC DENSITY; SPLICE VARIANTS; CEREBRAL-CORTEX; IMMUNOCYTOCHEMICAL LOCALIZATION; ULTRASTRUCTURAL-LOCALIZATION AB Functional N-methyl-D-aspartate (NMDA) receptors comprise heteromeric combinations of NR1 and NR2 subunits. In the present study we employed light and electron microscopic immunocytochemistry to study the expression of NR2A and NR2B (NR2A/B) protein in somatic sensory cortex of adult rats. To relate this distribution to that of NR1 and to the NMDA receptor anchoring protein PSD-95, we documented extensive cellular colocalization of NR2A/B with NR1 at the light microscopic level. In contrast, PSD-95 exhibited little somatic staining, being restricted mainly to dendrites and neuropil. We employed postembedding immunocytochemistry to study the ultrastructural expression of NR2A/B. Labeling in neuronal perikarya was associated with rough endoplasmic reticulum and Golgi apparatus; in dendrites, gold particles labeled microtubules. The preponderance of labeling was associated with asymmetric synapses. Double immunolabeling revealed that NR2 colocalized in many synapses with NR1 and with PSD-95. Quantitative measurements revealed that density of gold particles coding for both NR2 and PSD-95 was highest just inside the postsynaptic membrane. Tangentially along the membrane, gold particles were concentrated at the synaptic specialization. These data provide structural evidence in neocortex for heteromeric NMDA receptors anchored at the postsynaptic membrane. (C) 1999 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Valtschanoff, JG (reprint author), Univ N Carolina, Dept Cell Biol & Anat, CB 7090, Chapel Hill, NC 27599 USA. FU NINDS NIH HHS [NS29879] NR 81 TC 40 Z9 43 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 9 PY 1999 VL 410 IS 4 BP 599 EP 611 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 212LH UT WOS:000081217800007 PM 10398051 ER PT J AU Pollin, TI Dobyns, WB Crowe, CA Ledbetter, DH Bailey-Wilson, JE Smith, ACM AF Pollin, TI Dobyns, WB Crowe, CA Ledbetter, DH Bailey-Wilson, JE Smith, ACM TI Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome (MDS) critical region in chromosome 17p13.3 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT International Symposium on Mosaicism in Human Skin CY MAY 22-23, 1998 CL MARBURG, GERMANY DE chromosome 17; lissencephaly; Miller-Dieker syndrome; genetic counseling; chromosome translocations ID IN-SITU HYBRIDIZATION; DIAGNOSIS; INVERSION; FAMILY AB We studied the pedigrees of 14 families segregating a reciprocal translocation with one breakpoint in chromosome 17p13 and the other in the distal region of another autosome. All 14 were ascertained on the basis of an affected index case: 13 had Miller-Dieker syndrome (MDS) and one had dup(17p). In these 14 families, 38 balanced translocation carriers had 127 pregnancies, corrected for ascertainment bias by the exclusion of all index cases and carriers in the line of descent to the index cases. An abnormal phentotype, unbalanced chromosome constitution, or both, were found in 33 of 127 (26%) pregnancies: 15 of 127 (12%) had MDS and an unbalanced karyotype with del (17p); 9 of 127 (7%) had a less severe phenotype with dup(17p); and 9 were unstudied, although MDS with der(17) was usually suspected based on early death and multiple congenital anomalies. When unexplained pregnancy losses, including miscarriages and stillbirths; were excluded from the total, 33 of 99 (33%) pregnancies were phenotypically or genotypically abnormal. The overall risk of abnormal pregnancy outcome of 26% is in the upper range of the reported risk for unbalanced offspring of carrier parents assessed through liveborn aneuploid offspring [Gardner and Sutherland (1996), Oxford Univ, Press], The risk increases to 33% when unexplained pregnancy losses are excluded from the total. These results are consistent with Daniel's model of risk based on the size of the unbalanced fragments [Daniel (1985) Clin Genet 28:216-224, Daniel et al, (1989) Am J Med Genet 31:14-53], Pregnancy losses included 26 miscarriages (20%) and two stillbirths (2%) among the 127 pregnancies, similar to the respective population frequencies of 10-20% and 1%. (C) 1999 Wiley-Liss, Inc. C1 Univ Maryland, Sch Med, Div Diabet Obes & Nutr, Baltimore, MD 21201 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC USA. RP Pollin, TI (reprint author), Univ Maryland, Sch Med, Div Diabet Obes & Nutr, 725 W Lombard St, Baltimore, MD 21201 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920; Dobyns, William/0000-0002-7681-2844 NR 28 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 6 PY 1999 VL 85 IS 4 BP 369 EP 375 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 216VK UT WOS:000081465000013 PM 10398263 ER PT J AU Bell, AC West, AG Felsenfeld, G AF Bell, AC West, AG Felsenfeld, G TI The protein CTCF is required for the enhancer blocking activity of vertebrate insulators SO CELL LA English DT Article ID DNA-BINDING PROTEIN; ZINC-FINGER PROTEIN; HAIRY-WING PROTEIN; BETA-GLOBIN LOCUS; C-MYC GENE; DROSOPHILA-MELANOGASTER; CHROMATIN INSULATOR; TRANSCRIPTIONAL ACTIVITY; CHROMOSOMAL DOMAINS; PROMOTER AB An insulator is a DNA sequence that can act as a barrier to the influences of neighboring cis-acting elements, preventing gene activation, for example, when located between an enhancer and a promoter. We have identified a 42 bp fragment of the chicken beta-globin insulator that is both necessary and sufficient for enhancer blocking activity in human cells. We show that this sequence is the binding site for CTCF, a previously identified eleven-zinc finger DNA-binding protein that is highly conserved in vertebrates. CTCF sites are present in all of the vertebrate enhancer-blocking elements we have examined. We suggest that directional enhancer blocking by CTCF is a conserved component of gene regulation in vertebrates. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI West, Adam/0000-0003-3502-7804 NR 38 TC 655 Z9 672 U1 3 U2 33 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 6 PY 1999 VL 98 IS 3 BP 387 EP 396 DI 10.1016/S0092-8674(00)81967-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 225GP UT WOS:000081950300013 PM 10458613 ER PT J AU Brocke, L Chiang, LW Wagner, PD Schulman, H AF Brocke, L Chiang, LW Wagner, PD Schulman, H TI Functional implications of the subunit composition of neuronal CaM kinase II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; ALTERNATIVELY SPLICED ISOFORMS; HAMSTER OVARY CELLS; MOLECULAR-CLONING; CALCIUM SIGNALS; BETA-SUBUNIT; CALMODULIN; EXPRESSION; AUTOPHOSPHORYLATION; BRAIN AB The assembly of 6-12 subunits of Ca2+/calmodulin-dependent kinase II (CaM kinase II) into holoenzymes is an important structural feature of the enzyme and its postulated role as a molecular detector of Ca2+ oscillations. Using single cell reverse transcriptase-polymerase chain reaction, we show that alpha- and beta-CaM kinase II mRNAs are simultaneously present in the majority of hippocampal neurons examined and that co-assembly of their protein products into heteromers is therefore possible. The subunit composition of CaM kinase II holoenzymes was analyzed by immunoprecipitation with subunit-specific monoclonal antibodies. Rat forebrain CaM kinase II consists of heteromers composed of alpha and beta subunits at a ratio of 2:1 and homomers composed of only alpha subunits, We examined the functional effect of the heteromeric assembly by analyzing the calmodulin dependence of autophosphorylation, Recombinant homomers of alpha- or beta-CaM kinase II, as well as of alternatively spliced beta isoforms, have distinct calmodulin dependences for autophosphorylation based on differences in their calmodulin affinities. Half-maximal autophosphorylation of alpha is achieved at 130 nM calmodulin, while that for beta occurs at 15 nM calmodulin, In CaM kinase II isolated from rat forebrain, however, the calmodulin dependence for autophosphorylation of the beta subunits is shifted toward that of alpha homomers, This suggests that Thr(287) in beta subunits is phosphorylated by a subunits present in the same holoenzyme, Once autophosphorylated, beta-CaM kinase II traps calmodulin by reducing the rate of calmodulin dissociation. C1 Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Schulman, H (reprint author), Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA. FU NIGMS NIH HHS [GM30179]; NIMH NIH HHS [MH48108] NR 51 TC 92 Z9 94 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 6 PY 1999 VL 274 IS 32 BP 22713 EP 22722 DI 10.1074/jbc.274.32.22713 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 223YD UT WOS:000081868400084 PM 10428854 ER PT J AU Sipes, JM Krutzsch, HC Lawler, J Roberts, DD AF Sipes, JM Krutzsch, HC Lawler, J Roberts, DD TI Cooperation between thrombospondin-1 type 1 repeat peptides and alpha(v)beta(3) integrin ligands to promote melanoma cell spreading and focal adhesion kinase phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; HEPARIN-BINDING PEPTIDES; ENDOTHELIAL-CELLS; I REPEATS; ALPHA-2-BETA-1 INTEGRIN; TERMINAL DOMAIN; PROTEIN; RECEPTOR; MOTILITY; GROWTH AB CD47-binding sequences from the carboxyl-terminal domain of thrombospondin-1 (TSP1) are known to regulate activity of the alpha(v)beta(3) integrin (Gao, G., Lindberg, F. P., Dimitry, J. M., Brown, E. J., and Frazier, W. A. (1996) J. Cell Biol. 135, 533-544). Here we show that peptides from the type 1 repeats of TSP1 also stimulate alpha(v)beta(3) integrin function in melanoma cells. Addition of soluble peptide 246 (KRFKQDGGWSHWSPWSS) enhances spreading of A2058 melanoma cells on several gp, integrin ligands, including vitronectin, recombinant TSP1 fragments containing the Arg-Gly-Asp sequence, and native TSP1. This activity requires the Trp residues and is independent of CD36-binding sequences in the type 1 repeats. Recombinant type 1 repeats expressed as a glutathione S-transferase fusion protein also enhance spreading on vitronectin and TSP1, Activation of alpha(v)beta(3) integrin by the soluble peptide 246 stimulates organization of F-actin and increases tyrosine phosphorylation of focal adhesion kinase, In contrast, direct adhesion of melanoma cells on immobilized peptide 246 inhibits tyrosine phosphorylation of focal adhesion kinase, Stimulation of alpha(v)beta(3) integrin function by the type 1 repeat peptide differs from that induced by CD47-binding TSP1 peptides in that heparan sulfate proteoglycans are required and pertussis toxin does not inhibit the former activity. Thus, the type I repeats contain a second sequence of TSP1 that can enhance alpha(v)beta(3) integrin signaling, and these two sequences stimulate recognition of both vitronectin and TSP1 by the alpha(v)beta(3) integrin. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NHLBI NIH HHS [HL28749] NR 50 TC 45 Z9 45 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 6 PY 1999 VL 274 IS 32 BP 22755 EP 22762 DI 10.1074/jbc.274.32.22755 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 223YD UT WOS:000081868400089 PM 10428859 ER PT J AU Yuan, HQ Kingston, DGI Sackett, DL Hamel, E AF Yuan, HQ Kingston, DGI Sackett, DL Hamel, E TI Synthesis and biological activity of a novel C4-C6 bridged paclitaxel analog SO TETRAHEDRON LA English DT Article DE taxoids; macrocycles; lactonization; biologically active compounds ID BETA-TUBULIN; ANTICANCER AGENT; BACCATIN-III; AMINO-ACIDS; RING-C; TAXOL; CHEMISTRY; MICROTUBULE; PHOTOLABELS; TAXOTERE AB The novel paclitaxel analog 15 with a bridge between the C-4 and C-6 positions was synthesized and was found to be less active than paclitaxel in in vitro tubulin assembly and cytotoxicity assays. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kingston, DGI (reprint author), Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. OI Kingston, David/0000-0001-8944-246X NR 25 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD AUG 6 PY 1999 VL 55 IS 32 BP 9707 EP 9716 DI 10.1016/S0040-4020(99)00552-9 PG 10 WC Chemistry, Organic SC Chemistry GA 223CV UT WOS:000081823300005 ER PT J AU Parascandola, M AF Parascandola, M TI One renegade cell - The quest for the origins of cancer SO TLS-THE TIMES LITERARY SUPPLEMENT LA English DT Book Review C1 NIH, Bethesda, MD USA. RP Parascandola, M (reprint author), NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TIMES SUPPLEMENTS LIMITED PI MARKET HARBOROUGH PA TOWER HOUSE, SOVEREIGN PARK, MARKET HARBOROUGH LE87 4JJ, ENGLAND SN 0307-661X J9 TLS-TIMES LIT SUPPL JI TLS-Times Lit. Suppl. PD AUG 6 PY 1999 IS 5027 BP 27 EP 27 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 225KH UT WOS:000081958100048 ER PT J AU Parascandola, M AF Parascandola, M TI Living downstream - An ecologist looks at cancer and the environment SO TLS-THE TIMES LITERARY SUPPLEMENT LA English DT Book Review C1 NIH, Bethesda, MD USA. RP Parascandola, M (reprint author), NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TIMES SUPPLEMENTS LIMITED PI MARKET HARBOROUGH PA TOWER HOUSE, SOVEREIGN PARK, MARKET HARBOROUGH LE87 4JJ, ENGLAND SN 0307-661X J9 TLS-TIMES LIT SUPPL JI TLS-Times Lit. Suppl. PD AUG 6 PY 1999 IS 5027 BP 27 EP 27 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 225KH UT WOS:000081958100047 ER PT J AU Frey, A Mantis, N Kozlowski, PA Quayle, AJ Bajardi, A Perdomo, JJ Robey, FA Neutra, MR AF Frey, A Mantis, N Kozlowski, PA Quayle, AJ Bajardi, A Perdomo, JJ Robey, FA Neutra, MR TI Immunization of mice with peptomers covalently coupled to aluminum oxide nanoparticles SO VACCINE LA English DT Article DE adjuvant; antibodies; vaccine ID IMMUNODEFICIENCY-VIRUS ENVELOPE; MUCOSAL IMMUNE-RESPONSES; T-CELL; PEPTIDE VACCINE; CHOLERA-TOXIN; TYPE-1 GP120; C4 DOMAIN; MONOCLONAL-ANTIBODIES; SYNTHETIC PEPTIDES; CD4-BINDING DOMAIN AB Subunit vaccines generally require adjuvants to elicit immune responses, but adjuvants may alter the conformation of critical epitopes and reduce vaccine efficacy. We therefore tested an immunization strategy in which antigen is covalently coupled to aluminum oxide nanoparticles using a method that favors preservation of the native conformation. The test antigen consisted of "peptomers" (head-to-tail-linked peptide homopolymers) derived from the 4th conserved region (C4) of HIV-1 gp120 which is believed to be in an alpha-helical conformation prior to binding to CD4, Immune responses in mice to peptomer-nanoparticle conjugates were compared to responses elicited by free C4 peptide and C4 peptomers, with and without the hydrophilic adjuvant muramyl dipeptide (MDP). Highest peptomer-specific serum antibody responses were induced by peptomer-particles without MDP. Serum antibodies induced by peptomer-particles also showed highest reactivity towards recombinant, glycosylated gp120 and HIV-1 infected T cells. The results suggest that this novel vaccine approach could be useful for induction of immune responses against conformation-sensitive viral antigens without the need for additional adjuvants. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Childrens Hosp, GI Cell Biol Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Fearing Res Lab, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Neutra, MR (reprint author), Childrens Hosp, GI Cell Biol Res Lab, 300 Longwood Ave,Enders 1220, Boston, MA 02115 USA. OI Mantis, Nicholas/0000-0002-5083-8640 FU NIAID NIH HHS [AI34757]; NICHD NIH HHS [HD17557]; NIDDK NIH HHS [DK34854] NR 47 TC 26 Z9 27 U1 2 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 6 PY 1999 VL 17 IS 23-24 BP 3007 EP 3019 DI 10.1016/S0264-410X(99)00163-2 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 225KD UT WOS:000081957300010 PM 10462236 ER PT J AU Hu, GJ Wang, RYH Han, DS Alter, HJ Shih, JWK AF Hu, GJ Wang, RYH Han, DS Alter, HJ Shih, JWK TI Characterization of the humoral and cellular immune responses against hepatitis C virus core induced by DNA-based immunization SO VACCINE LA English DT Article DE HCV; DNA vaccine; antibodies; CTL ID NON-B-HEPATITIS; NON-A-HEPATITIS; T-LYMPHOCYTES; ANTIGEN; ANTIBODIES; CHIMPANZEES; INDUCTION; INFECTION; EPITOPES; PROTEIN AB Hepatitis C Virus (HCV) causes most cases of posttransfusion hepatitis. Chronic HCV infection is highly related to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Current therapies are only minimally effective and no vaccine has been developed. DNA-based immunization could be of prophylactic and therapeutic value for HCV infection. By intramuscular inoculation in BALB/c mice with an HCV recombinant plasmid pCI-HCV-C, we found significant levels of IgM antibody, but no significant IgG rise. After boost the immunized mice with recombinant HCV-core protein (cD1-10; 1-164aa), the anticore IgG, verified by Western-blotting? rose rapidly, which was two weeks earlier than that with control plasmid. Spleen cells from pCI-HCV-C immunized mice gave higher proliferation index (PI) than control (P < 0.05). The PI of cp1-10 boosted mice was even higher. Proliferation blocking assay with mAb proved the responding cell to be of CD4(+)CD8(-) phenotype, supporting specific priming of T helper cells. A S Cr-51-releasing CTL assay specific for HCV-core was developed, and a specific CTL response against HCV-core was demonstrated in both pCI-HCV-C immunized mice and mice boosted with cp1-10. Strong cytotoxic activity against peptide-pulsed p815 cells (H-2(d)), but not EL-4 cells (H-2(b)), suggested MHC class I restriction of the CTL activity. Blocking of CTL with mAb proved the effector cells to be of CD4(-)CD8(+). Three CTL epitopes in HCV-core protein were demonstrated. We failed to detect CTL when immunized only with core protein. The results suggested that vaccination with HCV-core derived DNA sequences could be an effective method to induce humoral and cellular immune responses to HCV. Published by Elsevier Science Ltd. All rights reserved. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Shih, JWK (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NR 39 TC 37 Z9 44 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 6 PY 1999 VL 17 IS 23-24 BP 3160 EP 3170 DI 10.1016/S0264-410X(99)00130-9 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 225KD UT WOS:000081957300026 PM 10462252 ER PT J AU Prasad, NB Uma, B Bhatt, SKG Gowda, VT AF Prasad, NB Uma, B Bhatt, SKG Gowda, VT TI Comparative characterisation of Russell's viper (Daboia/Vipera russelli) venoms from different regions of the Indian peninsula SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE venom variation; phospholipase A(2); polyclonal antiserum; Daboial Vipera russelli ID CROTALUS-SCUTULATUS-SCUTULATUS; NAJA-NAJA-NAJA; SNAKE-VENOMS; GEOGRAPHICAL VARIATION; MONOCLONAL-ANTIBODIES; PHOSPHOLIPASE-A(2); NEUROTOXICITY; PURIFICATION; NECROSIS; ARIZONA AB Russell's viper (Daboia/Vipera russelli) venom from different regions of India was subjected to chromatographic, electrophoretic, biochemical and immunological analysis. The elution profiles from ion-exchange chromatography and protein banding pattern from SDS-PAGE showed a significant variation in the constituents of venoms. The acidic proteins are found to be predominant in the venoms of eastern and western regions while basic proteins are the major contributors of the northern and southern regional venoms. The major variation of phospholipases A(2) in the venom samples of India may be described as: southern regional venom is rich in basic, toxic PLA(2) while this activity showed a dramatic decrease as one moves towards west, north and eastern regions of India. In addition, the caseinolytic, TAME-hydrolytic, anticoagulant, oedema-inducing and haemorrhagic activities of the venoms have also varied from one region to another. The muscle specimens of mice injected with venoms of different regions showed variable change in the muscle fibre damage and cell morphology. The eastern regional venom is most lethal among all the venoms. The lethal potencies for four regional venoms vary as: eastern > western > southern > northern. The polyclonal antibodies prepared against the venom of southern region showed cross-reaction with the venoms of other regions, but the extent of cross-reaction and diffusion patterns are different. However, the polyclonal antibodies prepared against southern regional venom showed no protection against lethal toxicity of other regional venoms. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Mysore, Dept Studies Biochem, Mysore 570006, Karnataka, India. RP Prasad, NB (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 9000 Rockville Pike,49 Convent Dr, Bethesda, MD 20892 USA. NR 59 TC 41 Z9 42 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD AUG 5 PY 1999 VL 1428 IS 2-3 BP 121 EP 136 DI 10.1016/S0304-4165(99)00053-7 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 228NH UT WOS:000082142200001 PM 10434030 ER PT J AU Mueller, SO Stopper, H AF Mueller, SO Stopper, H TI Characterization of the genotoxicity of anthraquinones in mammalian cells SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE anthraquinone; L5178Y mouse lymphoma cell; topoisomerase II; loss of heterozygosity ID TOPOISOMERASE-II; INTRACELLULAR ACCUMULATION; DNA; MUTAGENICITY; ENZYMES; DRUGS; CARCINOGENICITY; ANTHRACYCLINES; MECHANISMS; EXPRESSION AB Naturally occurring 1,8-dihydroxyanthraquinones are under consideration as possible carcinogens. Here we wanted to elucidate a possible mechanism of their genotoxicity. All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine. In a cell-free decatenation assay, emodin exerted a stronger, danthron a similar and aloe-emodin a weaker inhibition of topoisomerase II activity than m-amsacrine. Analysis of the chromosomal extent of DNA damage induced by these anthraquinones was performed in mouse lymphoma L5178Y cells. Anthraquinone-induced mutant cell clones showed similar chromosomal lesions when compared to the topoisomerase II inhibitors etoposide and m-amsacrine, but were different from mutants induced by the DNA alkylator ethyl methanesulfonate. These data support the idea that inhibition of the catalytic activity of topoisomerase II contributes to anthraquinone-induced genotoxicity and mutagenicity. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Wurzburg, Dept Toxicol, D-97078 Wurzburg, Germany. RP Mueller, SO (reprint author), NIEHS, POB 12233,MD E4-01, Res Triangle Pk, NC 27709 USA. NR 24 TC 44 Z9 48 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD AUG 5 PY 1999 VL 1428 IS 2-3 BP 406 EP 414 DI 10.1016/S0304-4165(99)00064-1 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 228NH UT WOS:000082142200031 PM 10434060 ER PT J AU Miyazaki, Y Geber, A Miyazaki, H Falconer, D Parkinson, T Hitchcock, C Grimberg, B Nyswaner, K Bennett, JE AF Miyazaki, Y Geber, A Miyazaki, H Falconer, D Parkinson, T Hitchcock, C Grimberg, B Nyswaner, K Bennett, JE TI Cloning, sequencing, expression and allelic sequence diversity of ERG3 (C-5 sterol desaturase gene) in Candida albicans SO GENE LA English DT Article DE Darlington; ergosterol; GAL1; heterozygosity; yeast ID SACCHAROMYCES-CEREVISIAE; YEAST; MUTANTS; ERGOSTEROL; DNA; COMPLEMENTATION; DISRUPTION; VIABILITY; STRAINS AB The C-5 sterol desaturase gene (ERG3), essential for yeast ergosterol biosynthesis, was cloned and sequenced from Candida albicans by homology with the Saccharomyces cerevisiae ERG3. The ERG3 ORF contained 1158 bp and encoded 386 deduced amino acids. The clone was used to transform a gall mutant derived from the Darlington strain of C. albicans, using galactose selection. The Darlington strain is known to lack Delta(5,6) sterols, i.e. to have an erg3 phenotype (Howell, S.A., et al., 1990. J. Appl. Bacteriol. 69, 692-696). The transformant (CDTR1) contained six tandem integrated ERG3GAL1 repeats, had double the abundance of ERG3 transcript found in the host strain, and synthesized ergosterol, a Delta(5,6) sterol. The Darlington strain was noted to have an abundance of ERG3 transcript. Both ERG3 alleles in Darlington were cloned and sequenced in order to look for changes that might explain the erg3 phenotype. One allele, called Dar-2, contained a stop codon in place of tryptophan-292. The other ERG3 allele, called Dar-l, had changes in three amino acids, two of which were conserved in three fungal and one plant species. EcoRI genomic fragments containing ERG3 from the Dar-l allele and from B311, the wildtype strain, were inserted into the plasmid pRS316 and used to transform a Saccharomyces cerevisiae erg3,ura3 mutant using uracil selection. The 4.1 kb ERG3 fragments from the B311 and Dar-l both contained 1.4 kb 5' and 1.5 kb 3' flanking sequences around the coding region. Transformants with ERG3 from B311 but not from Dar-l showed restored ergosterol synthesis. One or more of these three deduced amino acids in the Dar-l allele of ERG3 appeared critical for function. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Pfizer Cent Res, Dept Discovery Biol, Sandwich, Kent, England. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Grimberg, Brian/I-1251-2013 OI Grimberg, Brian/0000-0002-6015-4912 NR 32 TC 38 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 5 PY 1999 VL 236 IS 1 BP 43 EP 51 DI 10.1016/S0378-1119(99)00263-2 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 225QF UT WOS:000081971700006 PM 10433965 ER PT J AU Mofenson, LM Lambert, JS Stiehm, ER Bethel, J Meyer, WA Whitehouse, J Moye, J Reichelderfer, P Harris, DR Fowler, MG Mathieson, BJ Nemo, GJ AF Mofenson, LM Lambert, JS Stiehm, ER Bethel, J Meyer, WA Whitehouse, J Moye, J Reichelderfer, P Harris, DR Fowler, MG Mathieson, BJ Nemo, GJ CA Pediat AIDS Clin Trials Grp Study 185 Team TI Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND ID MOTHER-TO-CHILD; CLINICAL-TRIALS GROUP; MATERNAL VIRAL LOAD; VERTICAL TRANSMISSION; HIV-1 TRANSMISSION; INFECTION; INFANT; PREGNANCY; AIDS; PREDICTORS AB Background Maternal, obstetrical, and infant-related factors associated with the risk of perinatal transmission of human immunodeficiency virus type 1 (HIV-1) were identified before the widespread use of zidovudine therapy in pregnant women. The risk factors for transmission when women and infants receive zidovudine are not well characterized. Methods We examined the effects of maternal, obstetrical, and infant-related characteristics and maternal virologic and immunologic variables on the risk of perinatal transmission of HIV-1 among 480 women and their infants, all of whom received zidovudine. The women and infants were participating in a phase 3 trial of passive immunoprophylaxis for the prevention of perinatal transmission. Results In univariate analyses, the risk of perinatal transmission was associated with each of the following: decreased maternal CD4+ lymphocyte counts at base line; decreased maternal HIV-1 p24 antibody levels at base line and delivery; increased maternal HIV-1 titer at base line and delivery; increased maternal HIV-1 RNA levels at base line and delivery; and the presence of chorioamnionitis at delivery. In multivariate analyses, the only independent risk factor was the maternal HIV-1 RNA level at base line (odds ratio for transmission, 2.4 per log increase in the number of copies; 95 percent confidence interval, 1.2 to 4.7; P = 0.02) and at delivery (odds ratio, 3.4; 95 percent confidence interval, 1.7 to 6.8; P = 0.001). There was no perinatal transmission of HIV-1 among the 84 women who had HIV-1 levels below the limit of detection (500 copies per milliliter) at base line or the 107 women who had undetectable levels at delivery. Conclusions Among pregnant women and their infants, all treated with zidovudine, the maternal plasma HIV-1 RNA level was the best predictor of the risk of perinatal transmission of HIV-1. Antiretroviral therapy that reduces the HIV-1 RNA level to below 500 copies per milliliter appears to minimize the risk of perinatal transmission as well as improve the health of the women. (N Engl J Med 1999;341:385-93.) (C) 1999, Massachusetts Medical Society. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Contracept & Reprod Hlth Branch, NIH, Bethesda, MD 20892 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. WESTAT Corp, Rockville, MD 20850 USA. Quest Diagnost, Baltimore, MD USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Rm 4B11, Rockville, MD 20852 USA. OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 NR 43 TC 318 Z9 331 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 5 PY 1999 VL 341 IS 6 BP 385 EP 393 DI 10.1056/NEJM199908053410601 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 223UN UT WOS:000081860100001 PM 10432323 ER PT J AU Garcia, PM Kalish, LA Pitt, J Minkoff, H Quinn, TC Burchett, SK Kornegay, J Jackson, B Moye, J Hanson, C Zorrilla, C Lew, JF AF Garcia, PM Kalish, LA Pitt, J Minkoff, H Quinn, TC Burchett, SK Kornegay, J Jackson, B Moye, J Hanson, C Zorrilla, C Lew, JF CA Women Infants Transmision Study Grp TI Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 02-07, 1998 CL MIAMI, FLORIDA SP Soc Perinatal Obstetricians ID TO-CHILD TRANSMISSION; VIRAL LOAD; VERTICAL TRANSMISSION; ZIDOVUDINE TREATMENT; HIV TRANSMISSION; PREGNANCY; INFECTION; INFANT; AIDS; REDUCTION AB Background The importance of plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA in pregnant women in relation to the other factors known to influence the risk of transmission of infection to their infants is incompletely defined. We studied the relation of maternal plasma HIV-1 RNA levels to the risk of perinatal transmission and the timing of transmission. Methods We measured plasma HIV-1 RNA serially in 552 women with HIV-1 infection who had singleton pregnancies. The status of infection in their infants was assessed by culture of blood and further classified as early (if a culture of blood obtained within the first two days of life was positive) or late (if a culture of blood obtained in the first seven days of life was negative but subsequent cultures were positive). The rates of transmission at various levels of maternal plasma HIV-1 RNA were analyzed by tests for trend, with adjustment for covariates by stratification and logistic regression. Results Increasing geometric mean levels of plasma HIV-1 RNA were associated with increasing rates of transmission: the rate was 0 percent among women with less than 1000 copies per milliliter (0 of 57), 16.6 percent among women with 1000 to 10,000 copies per milliliter (32 of 193), 21.3 percent among women with 10,001 to 50,000 copies per milliliter (39 of 183), 30.9 percent among women with 50,001 to 100,000 copies per milliliter (17 of 54), and 40.6 percent among women with more than 100,000 copies per milliliter (26 of 64, P<0.001). The treatment status of one woman was unknown. The highest rate of transmission was among women whose plasma HIV-1 RNA levels exceeded 100,000 copies per milliliter and who had not received zidovudine (19 of 30 women, 63.3 percent). Neither higher HIV-1 RNA levels early in pregnancy nor higher levels late in pregnancy were associated with the timing of infection in the infants. Conclusions In pregnant women with HIV-1 infection, the level of plasma HIV-1 RNA predicts the risk but not the timing of transmission of HIV-1 to their infants. (N Engl J Med 1999;341:394-402.) (C) 1999, Massachusetts Medical Society. C1 Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. New England Res Inst, Watertown, MA 02172 USA. Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. Johns Hopkins Univ, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Roche Mol Syst, Alameda, CA USA. NICHHD, Bethesda, MD 20892 USA. Baylor Coll Med, Sect Allergy & Immunol, Houston, TX 77030 USA. Univ Puerto Rico, Dept Obstet & Gynecol, San Juan, PR 00936 USA. RP Garcia, PM (reprint author), Northwestern Univ, Prentice Womens Hosp, Rm 410,333 E Super St, Chicago, IL 60611 USA. RI Quinn, Thomas/A-2494-2010; OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [U01 AI 34840, U01 AI 34841, U01 AI 34842] NR 28 TC 434 Z9 454 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 5 PY 1999 VL 341 IS 6 BP 394 EP 402 DI 10.1056/NEJM199908053410602 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 223UN UT WOS:000081860100002 PM 10432324 ER PT J AU Carome, MA AF Carome, MA TI Is informed consent always necessary for randomized, controlled trials? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Carome, MA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 5 PY 1999 VL 341 IS 6 BP 448 EP 449 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 223UN UT WOS:000081860100012 PM 10438260 ER PT J AU Ciminale, V Zotti, L D'Agostino, DM Ferro, T Casareto, L Franchini, G Bernardi, P Chieco-Bianchi, L AF Ciminale, V Zotti, L D'Agostino, DM Ferro, T Casareto, L Franchini, G Bernardi, P Chieco-Bianchi, L TI Mitochondrial targeting of the p13(II) protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I) SO ONCOGENE LA English DT Article DE HTLV; X region; p13(II); mitochondria; Delta psi ID GREEN-FLUORESCENT PROTEIN; CYTOCHROME-C; CYCLOSPORINE-A; MESSENGER-RNA; BCL-2; APOPTOSIS; RELEASE; LOCALIZATION; INFECTIVITY; EXPRESSION AB The X region of the HTLV-I genome contains four major open reading frames (ORFs), two of which, termed x-I and x-II, are of still undefined biological significance. By indirect immunofluorescence and dual labeling with marker proteins, we demonstrate that p13(II), an 87-amino acid protein coded by the x-II ORF, is selectively targeted to mitochondria, Mutational analysis revealed that mitochondrial targeting of p13(II) is directed by an atypical 10-amino acid signal sequence that is not cleaved upon import and is able to target the Green Fluorescent Protein to mitochondria, Expression of p13(II) results in specific alterations of mitochondrial morphology and distribution from a typical string-like, dispersed network to round-shaped clusters, suggesting that p13(II) might interfere with processes relying on an intact mitochondrial architecture. Functional studies of mitochondria with the cationic fluorochrome tetramethylrhodamine revealed that a subpopulation of the cells with p13(II)-positive mitochondria show a disruption in the mitochondrial inner membrane potential (Delta psi), an early event observed in cells committed to apoptosis, Taken together, these results suggest novel virus-cell interactions that might be important in HTLV-I replication and/or pathogenicity. C1 Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy. RP Ciminale, V (reprint author), Univ Padua, Dept Oncol & Surg Sci, Via Gattamelata 64, I-35128 Padua, Italy. RI Bernardi, Paolo/C-3656-2008 OI Bernardi, Paolo/0000-0001-9187-3736 NR 42 TC 69 Z9 70 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 5 PY 1999 VL 18 IS 31 BP 4505 EP 4514 DI 10.1038/sj.onc.1203047 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 222YT UT WOS:000081813500012 PM 10442641 ER PT J AU Furlong, MT Hough, CD Sherman-Baust, CA Pizer, ES Morin, PJ AF Furlong, MT Hough, CD Sherman-Baust, CA Pizer, ES Morin, PJ TI Evidence for the colonic origin of ovarian cancer cell line SW626 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BETA-CATENIN; CARCINOMA; GENE; MUTATIONS; EXPRESSION; ACTIVATION; APC C1 NIA, Gerontol Res Ctr, Biol Chem Lab, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Morin, PJ (reprint author), NIA, Gerontol Res Ctr, Biol Chem Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 14 TC 18 Z9 18 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 4 PY 1999 VL 91 IS 15 BP 1327 EP 1328 DI 10.1093/jnci/91.15.1327 PG 2 WC Oncology SC Oncology GA 223HZ UT WOS:000081836800016 PM 10433623 ER PT J AU Mahoney, AB Sacks, DL Saraiva, E Modi, G Turco, SJ AF Mahoney, AB Sacks, DL Saraiva, E Modi, G Turco, SJ TI Intra-species and stage-specific polymorphisms in lipophosphoglycan structure control Leishmania donovani-sand fly interactions SO BIOCHEMISTRY LA English DT Article ID DEVELOPMENTAL MODIFICATION; SURFACE LIPOPHOSPHOGLYCAN; MAJOR PROMASTIGOTES; GLYCOPROTEIN; CARBOHYDRATE; METACYCLOGENESIS; CHROMATOGRAPHY; MIDGUT AB The Leishmania lipophosphoglycan conveys the ability for the parasites to avoid destruction in diverse host environments. During its life cycle within the sand fly vector, the parasite differentiates from a dividing procyclic promastigote stage that avoids expulsion from the midgut by attaching to the gut wall, to a nondividing metacyclic promastigote stage that is unable to attach to the midgut and migrates to the mouth parts for reinfection of a mammalian host. Lipophosphoglycan plays an integral role during this transition. Structurally, lipophosphoglycan is a multidomain glycoconjugate whose polymorphisms among species lie in the backbone Gal(beta 1,4)Man(alpha 1)-PO4 repeating units and the oligosaccharide cap. We have characterized the lipophosphoglycan from an Indian L. donovani isolate. Unlike East African isolates, which express unsubstituted repeats and a galactose- and mannose-terminating cap, procyclic lipophosphoglycan from the Indian isolate consists of beta 1,3-linked glucose residues that branch off the backbone repeats (n similar to 17) and also terminate the cap. Of biological significance, metacyclic lipophosphoglycan lacks the glucose residues while doubling the number of repeats. The importance of these developmental modifications in lipophosphoglycan structure was determined using binding experiments to Phlebotomus argentypes mid,outs. Procyclic promastigotes and procyclic LPG were able to bind to sand fly midguts in vitro whereas metacyclic parasites and LPG lost this capacity. These results demonstrate that the Leishmania adapts the synthesis of terminally exposed sugars of its LPG to manipulate parasite-sand fly interactions. C1 Univ Kentucky, Med Ctr, Dept Biochem, Lexington, KY 40536 USA. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Turco, SJ (reprint author), Univ Kentucky, Med Ctr, Dept Biochem, Lexington, KY 40536 USA. FU NIAID NIH HHS [AI20941] NR 25 TC 50 Z9 52 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 3 PY 1999 VL 38 IS 31 BP 9813 EP 9823 DI 10.1021/bi990741g PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226HG UT WOS:000082014100004 PM 10433687 ER PT J AU Xia, H Gu, YJ Pan, SS Ji, XH Singh, SV AF Xia, H Gu, YJ Pan, SS Ji, XH Singh, SV TI Amino acid substitutions at positions 207 and 221 contribute to catalytic differences between murine glutathione S-transferase Al-1 and A2-2 toward (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene SO BIOCHEMISTRY LA English DT Article ID A/J MOUSE; ANTICARCINOGENIC ORGANOSULFIDES; EXCEPTIONAL ACTIVITY; OPTICAL ENANTIOMERS; PROTEIN-STRUCTURE; HUMAN-LIVER; RAT-LIVER; MU-CLASS; BENZOPYRENE; CONJUGATION AB We have previously identified a novel Alpha class murine glutathione (GSH) S-transferase isoenzyme (designated mGSTA1-2) which is exceptionally efficient in catalyzing the GSH conjugation of (+)-anti-7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyre [(+)-anti-BPDE], the ultimate carcinogen of widespread environmental pollutant benzo[a]pyrene. Furthermore, we have demonstrated that the AZ-type subunit of this isoenzyme is significantly more active toward (+)-anti-BPDE than the other subunit (mGSTA2). To establish the basis for catalytic differences between mGSTA1 and mGSTA2, which differ in their primary structures by 10 amino acids [distributed in three sections (I-III) as clusters of two (residues 65 and 95), three (residues 157, 162, and 169), and five (residues 207, 213, 218, 221, and 222) amino acids], three chimeric enzymes were expressed and tested for their activity toward (+)anti-BPDE. These studies revealed that amino acid substitution(s) in section III determined the high catalytic activity of mGSTA1. Molecular modeling studies suggested that amino acid substitutions at positions 207 and/or 221, but not at positions 213, 218, and 222, may be responsible for such a difference. To test this possibility, amino acids at positions 207 and 221 of mGSTA1 were mutated with the equivalent residues of mGSTA2. Kinetic analysis of the wild type and the mutant enzymes revealed that both methionine-207 and isoleucine-221 are critical for higher activity of mGSTA1-1 toward (+)-anti-BPDE compared with that of mGSTA2-2. C1 Mercy Hosp, Canc Res Lab, Pittsburgh, PA 15219 USA. Univ Pittsburgh, Med Ctr, Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Singh, SV (reprint author), Mercy Hosp, Canc Res Lab, Pittsburgh, PA 15219 USA. RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [R01 CA76348] NR 45 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 3 PY 1999 VL 38 IS 31 BP 9824 EP 9830 DI 10.1021/bi9908078 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226HG UT WOS:000082014100005 PM 10433688 ER PT J AU Pette, M Muraro, PA Pette, DF Dinter, H McFarland, HF Martin, R AF Pette, M Muraro, PA Pette, DF Dinter, H McFarland, HF Martin, R TI Differential effects of phosphodiesterase type 4-specific inhibition on human autoreactive myelin-specific T cell clones SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE rolipram; phosphodiesterase inhibition; multiple sclerosis; T lymphocytes ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROTEIN-KINASE-A; NF-KAPPA-B; CYCLIC-AMP; BASIC-PROTEIN; LYMPHOCYTE ACTIVATION; CYTOKINE PRODUCTION; MULTIPLE-SCLEROSIS; T-HELPER-2 CELLS; GENE-EXPRESSION AB Proinflammatory cytokines, secreted by autoreactive CD4 + T lymphocytes may contribute to the pathogenesis of several human autoimmune diseases, including multiple sclerosis (MS). Since the antigen specificities of these T cells are not known at present, therapeutic strategies aiming at common effector pathways, in particular cytokine secretion, may be more feasible in the near future. We have studied the influence of the isoenzyme-specific phosphodiesterase inhibitor rolipram on the proliferation and cytokine secretion of human myelin basic protein-specific T cell clones. The inhibition of proliferation correlated with interference with the IL-2/IL-2 receptor system, while the effects of rolipram on several T helper 1-(TNF-alpha, TNF-beta, IFN-gamma) and T helper 2-like cytokines (IL-4, IL-13) as well as IL-10 revealed an interesting drug profile, with preferential inhibition of TNF-beta, TNF-alpha and IL-10. This profile suggest that rolipram differs from other currently used immunomodulatory drugs. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Neurol Klin, D-01307 Dresden, Germany. Univ G DAnnunzio, Sch Med, Dept Oncol & Neurosci, Neurol Clin, I-66100 Chieti, Italy. Berlex Biosci, Dept Immunol, Richmond, CA 94804 USA. RP Pette, M (reprint author), NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 38 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD AUG 3 PY 1999 VL 98 IS 2 BP 147 EP 156 DI 10.1016/S0165-5728(99)00088-0 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 218LX UT WOS:000081555000009 PM 10430048 ER PT J AU Wandinger, KP Hagenah, JM Kluter, H Rothermundt, M Peters, M Vieregge, P AF Wandinger, KP Hagenah, JM Kluter, H Rothermundt, M Peters, M Vieregge, P TI Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson's disease SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Parkinson's disease; interleukin-2; interferon-gamma; amantadine treatment; T cell function; neuropharmacology ID RHEUMATOID-ARTHRITIS; CEREBROSPINAL-FLUID; DIABETES-MELLITUS; PERIPHERAL-BLOOD; SUBSTANTIA-NIGRA; GROWTH-FACTOR; T-CELLS; HLA-DR; LYMPHOCYTES; EXPRESSION AB An involvement of immunological events in the process of neurodegeneration has frequently been reported. We investigated the cytokine producing capacity for interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in whole blood cultures of de-novo patients with idiopathic Parkinson's disease (PD) at the time of first diagnosis and after oral amantadine treatment. Before treatment, productions of IL-2 and IFN-gamma were markedly decreased in PD patients compared to patients with major depressive disorder and healthy controls. After amantadine treatment, the in vitro IL-2 secretion defect was corrected to normal levels in half of the patients, and the increase in IL-2 production was correlated with an increase in IFN-gamma secretion. Our findings suggest that immunological abnormalities occur in the course of PD and that a formerly unappreciated therapeutic potential of amantadine may arise from its immunomodulatory effects on altered T cell function in patients with PD. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Lubeck, Sch Med, Inst Immunol & Transfus Med, D-2400 Lubeck, Germany. Univ Lubeck, Sch Med, Dept Neurol, D-2400 Lubeck, Germany. Univ Lubeck, Sch Med, Dept Psychiat, D-2400 Lubeck, Germany. RP Wandinger, KP (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10 room 5B-16,10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. NR 42 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD AUG 3 PY 1999 VL 98 IS 2 BP 214 EP 220 DI 10.1016/S0165-5728(99)00093-4 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 218LX UT WOS:000081555000016 PM 10430055 ER PT J AU Tanimura, Y Yamashita, K Anfinrud, PA AF Tanimura, Y Yamashita, K Anfinrud, PA TI Femtochemistry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 1st Japanese-American Frontiers of Science Symposium CY AUG 21-23, 1998 CL NATL ACAD SCI & ENGN, IRVINE, CALIFORNIA HO NATL ACAD SCI & ENGN ID ULTRAFAST ELECTRON-DIFFRACTION; RESONANCE RAMAN-SPECTROSCOPY; RETINAL CHROMOPHORE; BACTERIORHODOPSIN MUTANTS; VIBRATIONAL SPECTROSCOPY; MOLECULAR-DYNAMICS; FEMTOSECOND; PHOTOISOMERIZATION; PULSES AB The topic of femtochemistry is surveyed from both theoretical and experimental points of view. A time-dependent wave packet description of the photodissociation of the O-C-S molecule reveals vibrational motion in the transition-state region and suggests targets for direct experimental observation. Theoretical approaches for treating femtosecond chemical phenomena in condensed phases are featured along with prospects for laser-controlled chemical reactions by using tailored ultrashort chirped pulses. An experimental study of the photoisomerization of retinal in the protein bacteriorhodopsin is discussed with an aim to gain insight into the potential energy surfaces on which this remarkably efficient and selective reactions proceeds. Finally, a prospective view of new frontiers in femtochemistry is given. C1 Inst Mol Sci, Aichi 4448585, Japan. Univ Tokyo, Grad Sch Engn, Dept Chem Syst Engn, Tokyo 1138656, Japan. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tanimura, Y (reprint author), Inst Mol Sci, Aichi 4448585, Japan. RI TANIMURA, YOSHITAKA/E-2050-2011 OI TANIMURA, YOSHITAKA/0000-0002-7913-054X NR 28 TC 5 Z9 5 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 8823 EP 8824 DI 10.1073/pnas.96.16.8823 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500010 PM 10430852 ER PT J AU Smith, JS Keller, JR Lohrey, NC McCauslin, CS Ortiz, M Cowan, K Spence, SE AF Smith, JS Keller, JR Lohrey, NC McCauslin, CS Ortiz, M Cowan, K Spence, SE TI Redirected infection of directly biotinylated recombinant adenovirus vectors through cell surface receptors and antigens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TARGETED GENE DELIVERY; RETROVIRAL VECTORS; MYELOGENOUS LEUKEMIA; T-LYMPHOCYTES; PROTEIN-A; BINDING; LINE; COMPLEX; LIGAND; EXPRESSION AB The inability of adenovirus to infect primitive hematopoietic cells presents an obstacle to the use of adenovirus vectors for gene transfer to these cell types. Therefore, expanding the tropism of adenovirus vectors to unique cell surface antigens would be an important development for gene therapy protocols, In this study, we sought to redirect infection of adenovirus vectors to primitive human hematopoietic cells that universally express the c-Kit receptor on their cell surface. To accomplish this, a vector was constructed by covalently linking biotin molecules to recombinant adenovirus, followed by addition of the biotinylated ligand for the c-Kit receptor, stem cell factor (SCF), through an avidin bridge. Gene transfer was directed specifically to c-Kit-positive hematopoietic cell lines, resulting in up to a 2,440 fold increase in luciferase expression with frequencies equivalent to recombinant virus infection of permissive cells. Substitution of biotinylated antibodies directed against c-Kit, CD34 (binds L-selectin), and CD44 (hyaluronate receptor) receptors for biotinylated SCP resulted in 50-, 8-, and 260-fold increases in reporter gene expression, respectively, demonstrating that infection also could be redirected through antibody-antigen interactions and through antigens other than growth factor receptors, The versatility of this vector was demonstrated further by infection of primary T cells with vectors targeted with antibodies to CD44 (resting and activated T cells) and biotinylated IL-2 (activated T cells only). Taken together, directly biotinylated adenovirus vectors represent a versatile and efficient method for redirection of virus infection to specific cells. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Lab Leukocyte Biol, Frederick, MD 21702 USA. NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. RP Spence, SE (reprint author), NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Intramural Res Support Program, Bldg 560,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 36 TC 46 Z9 47 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 8855 EP 8860 DI 10.1073/pnas.96.16.8855 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500018 PM 10430860 ER PT J AU Amalfitano, A McVie-Wylie, AJ Hu, H Dawson, TL Raben, N Plotz, P Chen, YT AF Amalfitano, A McVie-Wylie, AJ Hu, H Dawson, TL Raben, N Plotz, P Chen, YT TI Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Pompe; gene therapy ID MEDIATED GENE-TRANSFER; HIGH-LEVEL PRODUCTION; PACKAGING CELL-LINES; POMPE-DISEASE; ENZYME DEFICIENCY; SKELETAL-MUSCLE; THERAPY; ACCUMULATION; FIBROBLASTS; EXPRESSION AB This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals, We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid alpha-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies. C1 Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Amalfitano, A (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Box 2618 Med Sci Res Bldg,Room 101B, Durham, NC 27710 USA. OI Dawson, Thomas/0000-0003-3878-1722 NR 24 TC 100 Z9 102 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 8861 EP 8866 DI 10.1073/pnas.96.16.8861 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500019 PM 10430861 ER PT J AU Tang, MJ Shen, X Frank, EG O'Donnell, M Woodgate, R Goodman, MF AF Tang, MJ Shen, X Frank, EG O'Donnell, M Woodgate, R Goodman, MF TI UmuD ' C-2 is an error-prone DNA polymerase, Escherichia coli pol V SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECA PROTEIN; MUTAGENESIS PROTEINS; SOS MUTAGENESIS; ULTRAVIOLET-LIGHT; UV MUTAGENESIS; MUTANTS; REPAIR; UMUC; CLEAVAGE; BYPASS AB The damage-inducible UmuD' and UmuC proteins are required for most SOS mutagenesis in Escherichia coli, Our recent assay to reconstitute this process in vitro, using a native UmuD'C-2 complex, revealed that the highly purified preparation contained DNA polymerase activity. Here we eliminate the possibility that this activity is caused by a contaminating DNA polymerase and show that it is intrinsic to UmuD'C-2. E. coli dinB has recently been shown to have DNA polymerase activity (pol IV). We suggest that UmuD'2C, the fifth DNA polymerase discovered in E, coli, be designated as E. coli pol V. In the presence of RecA, beta sliding clamp, gamma clamp loading complex, and E. coli single-stranded binding protein (SSB), pol V's polymerase activity is highly "error prone" at both damaged and undamaged DNA template sites, catalyzing efficient bypass of abasic lesions that mould otherwise severely inhibit replication by pol III holoenzyme complex (HE), Pol V bypasses a site-directed abasic lesion with an efficiency about 100- to 150-fold higher than pol III HE. In accordance with the "A-rule," dAMP is preferentially incorporated opposite the lesion. A pol V mutant, UmuD'(2)C104 (D101N), has no measurable lesion bypass activity, A kinetic analysis shows that addition of increasing amounts of pol III to a fixed level of pol V inhibits lesion bypass, demonstrating that both enzymes compete for free 3'-OH template-primer ends. We show however, that despite competition for primer-3'-ends, pol V and pol III HE can nevertheless interact synergistically to stimulate synthesis downstream from a template lesion. C1 Univ So Calif, Dept Biol Sci, Hedco Mol Biol Labs, Los Angeles, CA 90089 USA. Rockefeller Univ, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY 10021 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci, Hedco Mol Biol Labs, SHS Room 172,Univ Pk, Los Angeles, CA 90089 USA. EM mgoodman@mizar.usc.edu FU NIGMS NIH HHS [GM38839, GM42554, R01 GM038839, R37 GM038839] NR 37 TC 410 Z9 416 U1 3 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 8919 EP 8924 DI 10.1073/pnas.96.16.8919 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500029 PM 10430871 ER PT J AU Yamashita, T Wada, R Sasaki, T Deng, CX Bierfreund, U Sandhoff, K Proia, RL AF Yamashita, T Wada, R Sasaki, T Deng, CX Bierfreund, U Sandhoff, K Proia, RL TI A vital role for glycosphingolipid synthesis during development and differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EMBRYONIC STEM-CELLS; VISCERAL ENDODERM; NEURONAL DIFFERENTIATION; GENE; MEMBRANE; GLUCOSYLCERAMIDE; GASTRULATION; EXPRESSION; ADHESION; SURFACE AB Glycosphingolipids (GSLs) are believed to be integral for the dynamics of many cell membrane events, including cellular interactions, signaling, and trafficking. We have investigated their roles in development and differentiation by eliminating the major synthesis pathway of GSLs through targeted disruption of the Ugcg gene encoding glucosylceramide synthase, In the absence of GSL synthesis, embryogenesis proceeded well into gastrulation with differentiation into primitive germ layers and patterning of the embryo but was abruptly halted bg a major apoptotic process. In vivo, embryonic stem cells deficient in GSL synthesis were again able to differentiate into endodermal, mesodermal, and ectodermal derivatives but were strikingly deficient in their ability to form well differentiated tissues. In vitro, however, hematopoietic and neuronal differentiation could be induced. The results demonstrate that the synthesis of GSL structures is essential for embryonic development and for the differentiation of some tissues and support the concept that GSLs are involved in crucial cell interactions mediating these processes. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg 10,Room 9D-20,10 Ctr Dr,MSC 1810, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012; deng, chuxia/N-6713-2016 NR 48 TC 292 Z9 297 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9142 EP 9147 DI 10.1073/pnas.96.16.9142 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500067 PM 10430909 ER PT J AU Rangarajan, S Woodgate, R Goodman, MF AF Rangarajan, S Woodgate, R Goodman, MF TI A phenotype for enigmatic DNA polymerase II: A pivotal role for pol II in replication restart in UV-irradiated Escherichia coli SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADAPTIVE MUTATION; ULTRAVIOLET-LIGHT; RECA PROTEIN; GENE; MUTAGENESIS; MUTANTS; DAMAGE; REPAIR; PURIFICATION; RESISTANCE AB DNA synthesis in Escherichia coli is inhibited transiently after UV irradiation, Induced replisome reactivation or "replication restart" occurs shortly thereafter, allowing cells to complete replication of damaged genomes, At the present time, the molecular mechanism underlying replication restart is not understood. DNA polymerase II (pol II), encoded by the dinA (polB) gene, is induced as part of the global SOS response to DNA damage. Here we show that pol II plays a pivotal role in resuming DNA replication in tells exposed to UV irradiation, There is a 50-min delay in replication restart in mutant cells lacking pol II. Although replication restart appears normal in Delta umuDC strains containing pol II, the restart process is delayed for >90 min in cells lacking both pol LT and UmuD'C-2, Because of the presence of pol II, a transient replication-restart burst is observed in a "quick-stop" temperature-sensitive pol III mutant (dnaE486) at nonpermissive temperature. However, complete recovery of DNA synthesis requires the concerted action of both pol II and pol III. Our data demonstrate that pol II and UmuD'C-2 act in independent pathways of replication restart, thereby providing a phenotype for pol II in the repair of UV-damaged DNA. C1 Univ So Calif, Dept Sci Biol, Hedco Mol Biol Labs, Los Angeles, CA 90089 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Sci Biol, Hedco Mol Biol Labs, SHS Room 172, Los Angeles, CA 90089 USA. FU NIGMS NIH HHS [GM42554] NR 41 TC 105 Z9 108 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9224 EP 9229 DI 10.1073/pnas.96.16.9224 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500082 PM 10430924 ER PT J AU Loftus, SK Chen, Y Gooden, G Ryan, JF Birznieks, G Hilliard, M Baxevanis, AD Bittner, M Meltzer, P Trent, J Pavan, W AF Loftus, SK Chen, Y Gooden, G Ryan, JF Birznieks, G Hilliard, M Baxevanis, AD Bittner, M Meltzer, P Trent, J Pavan, W TI Informatic selection of a neural crest-melanocyte cDNA set for microarray analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-GENOME; GENE AB With cDNA microarrays, it is now possible to compare the expression of many genes simultaneously. To maximize the likelihood of finding genes whose expression is altered under the experimental conditions, it would be advantageous to be able to select clones for tissue-appropriate cDNA sets. We have taken advantage of the extensive sequence information in the dbEST expressed sequence tag (EST) database to identify a neural crest-derived melanocyte cDNA set for microarray analysis. Analysis of characterized genes with dbEST identified one library that contained ESTs representing 21 neural crest-expressed genes (library 198). The distribution of the ESTs corresponding to these genes was biased toward being derived from library 198. This is in contrast to the EST distribution profile for a set of control genes, characterized to be more ubiquitously expressed in multiple tissues (P < 1 x 10(-9)). From library 198, a subset of 852 clustered ESTs were selected that have a library distribution profile similar to that of the 21 neural crest-expressed genes. Microarray analysis demonstrated the majority of the neural crest-selected 852 ESTs (Mel1 array) were differentially expressed in melanoma cell lines compared with a non-neural crest kidney epithelial cell line (P < 1 x 10(-8)). This was net observed with an array of 1,238 ESTs that was selected without library origin bias (P = 0.204). This study presents an approach for selecting tissue-appropriate cDNAs that can be used to examine the expression profiles of developmental processes and diseases. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Pavan, W (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 18 TC 51 Z9 56 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9277 EP 9280 DI 10.1073/pnas.96.16.9277 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500091 PM 10430933 ER PT J AU Essand, M Vasmatzis, G Brinkmann, U Duray, P Lee, B Pastan, I AF Essand, M Vasmatzis, G Brinkmann, U Duray, P Lee, B Pastan, I TI High expression of a specific T-cell receptor gamma transcript in epithelial cells of the prostate SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GERM-LINE TRANSCRIPTION; GENES; LOCUS; REARRANGEMENT AB We have identified expression of T-cell receptor gamma chain (TCR gamma) mRNA in human prostate and have shown that it originates from epithelial cells of the prostate and not from infiltrating T-lymphocytes. In contrast, the T-cell receptor delta chain (TCR delta) gene is silent in human prostate. The major TCR gamma transcript in prostate has a different size than the transcript expressed in thymus, spleen, and blood leukocytes. It is expressed in normal prostate epithelium, adenocarcinoma of the prostate, and the prostatic adenocarcinoma cell line LNCaP, The RNA originates from an unrearranged TCR gamma locus, and it is initiated within the intronic sequence directly upstream of the J gamma 1.2 gene segment. The prostate-specific TCR gamma transcript consists of the J gamma 1,2 and C gamma 1 gene segments, and it has an untranslated sequence including a polyadenylation signal and poly(A) sequence at the 3'end, The finding that prostate epithelial cells express a high level of a transcript from a gene that was thought to by exclusively expressed by T-lymphocytes is highly unexpected. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16, Bethesda, MD 20892 USA. NR 18 TC 55 Z9 55 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9287 EP 9292 DI 10.1073/pnas.96.16.9287 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500093 PM 10430935 ER PT J AU Ehrenshaft, M Bilski, P Li, MY Chignell, CF Daub, ME AF Ehrenshaft, M Bilski, P Li, MY Chignell, CF Daub, ME TI A highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SOR1; PDX1; photosensitizer; cercosporin ID ESCHERICHIA-COLI K-12; SINGLET MOLECULAR-OXYGEN; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; CERCOSPORIN; RESISTANCE; PYRIDOXINE; OPERON; TRANSCRIPTION; ASPERGILLUS AB The Cercospora nicotianae SOR1 (singlet oxygen resistance) gene was identified previously as a gene involved in resistance of this fungus to singlet-oxygen-generating phototoxins. Although homologues to SOR1 occur in organisms in four kingdoms and encode one of the most highly conserved proteins get identified, the precise function of this protein has, until now, remained unknown. We show that SOR1 is essential in pyridoxine (vitamin B6) synthesis in C. nicotianae and Aspergillus flavus, although it shows no homology to previously identified pyridoxine synthesis genes identified in Escherichia coli. Sequence database analysis demonstrated that organisms encode either SOR1 or E. coli pyridoxine biosynthesis genes, but not both, suggesting that there are two divergent pathways for de novo pyridoxine biosynthesis in nature. pathway divergence appears to have occurred during the evolution of the eubacteria, We also present data showing that pyridoxine quenches singlet oxygen at a rate comparable to that of vitamins C and E, two of the most highly efficient biological antioxidants, suggesting a previously unknown role for pyridoxine in active oxygen resistance. C1 N Carolina State Univ, Dept Plant Pathol, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Ehrenshaft, M (reprint author), N Carolina State Univ, Dept Plant Pathol, Box 7616, Raleigh, NC 27695 USA. NR 41 TC 198 Z9 204 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9374 EP 9378 DI 10.1073/pnas.96.16.9374 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500108 PM 10430950 ER PT J AU Ishai, A Ungerleider, LG Martin, A Schouten, HL Haxby, JV AF Ishai, A Ungerleider, LG Martin, A Schouten, HL Haxby, JV TI Distributed representation of objects in the human ventral visual pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE face perception; functional MRI; object recognition ID TEMPORAL CORTEX; RECOGNITION; MECHANISMS; FACES AB Brain imaging and electrophysiological recording studies in humans have reported discrete cortical regions in posterior ventral temporal cortex that respond preferentially to faces, buildings, and letters. These findings suggest a category-specific anatomically segregated modular organization of the object vision pathway. Here we present data from a functional MRI study in which we found three distinct regions of ventral temporal cortex that responded preferentially to faces and two categories of other objects, namely houses and chairs, and had a highly consistent topological arrangement. Although the data could be interpreted as evidence for separate modules, we found that each category also evoked significant responses in the regions that responded maximally to other stimuli. Moreover, each category was associated with its oven differential pattern of response across ventral temporal cortex. These results indicate that the representation of an object is not restricted to a region that responds maximally to that object, but rather is distributed across a broader expanse of cortex. We propose that the functional architecture of the ventral visual pathway is not a mosaic of category-specific modules but instead is a continuous representation of information about object form that has a highly consistent and orderly topological arrangement. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Ishai, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C104,MSC-1366, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 23 TC 565 Z9 571 U1 3 U2 33 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9379 EP 9384 DI 10.1073/pnas.96.16.9379 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500109 PM 10430951 ER PT J AU Maier, DL Mani, S Donovan, SL Soppet, D Tessarollo, L McCasland, JS Meiri, KF AF Maier, DL Mani, S Donovan, SL Soppet, D Tessarollo, L McCasland, JS Meiri, KF TI Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SOMATOSENSORY CORTEX; CEREBRAL-CORTEX; CRITICAL PERIOD; NERVOUS-SYSTEM; LAYER-IV; MOUSE; GAP-43; SEROTONIN; NEURONS; EXPRESSION AB There is strong evidence that growth-associated protein (GAP-43), a protein found only in the nervous system, regulates the response of neurons to axonal guidance signals. However, its role in complex spatial patterning in cerebral cortex has not been explored. We show that mice lacking GAP-43 expression (-/-) fail to establish the ordered whisker representation (barrel array) normally found in layer IV of rodent primary somatosensory cortex. Thalamocortical afferents to -/- cortex form irregular patches in layer IV within a poorly defined cortical field, which varies between hemispheres, rather than the stereotypic, whisker-specific, segregated map seen in normal animals. Furthermore, many thalamocortical afferents project abnormally to widely separated cortical targets. Taken together, our findings indicate a loss of identifiable whisker territories in the GAP-43 -/- mouse cortex, Here, we present a disrupted somatotopic map phenotype in cortex, in clear contrast to the blurring of boundaries within an ordered whisker map in other barrelless mutants. Our results indicate that GAP-43 expression is critical for the normal establishment of ordered topography in barrel cortex. C1 SUNY Hlth Sci Ctr, Dept Pharmacol, Syracuse, NY 13210 USA. SUNY Hlth Sci Ctr, Dept Anat & Cell Biol, Syracuse, NY 13210 USA. NCI, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Human Genome Sci, Rockville, MD 20850 USA. RP Meiri, KF (reprint author), SUNY Hlth Sci Ctr, Dept Pharmacol, Syracuse, NY 13210 USA. FU NINDS NIH HHS [NS31829, NS33118, R01 NS033118] NR 32 TC 112 Z9 117 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9397 EP 9402 DI 10.1073/pnas.96.16.9397 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500112 PM 10430954 ER PT J AU Bettelheim, FA Ansari, R Cheng, QF Zigler, JS AF Bettelheim, FA Ansari, R Cheng, QF Zigler, JS TI The mode of chaperoning of dithiothreitol-denatured alpha-lactalbumin by alpha-crystallin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEAT-SHOCK PROTEINS; QUATERNARY STRUCTURE; MOLECULAR CHAPERONE; LENS CRYSTALLINS; SPECTROSCOPY; EXPRESSION; EVOLUTION; EXCHANGE AB Molecular chaperones prevent the aggregation of partially folded or misfolded forms of protein. alpha-crystallin performs such a function in the ocular lens. To gain insight into the mechanism of the anti-aggregation activity of alpha-crystallin, we performed dynamic light scattering(DLS) measurements investigating its interaction with partially denatured alpha-lactalbumin over a 24 hr period. Analyses were conducted as a function of the concentration of alpha-lactalbumin as well, as the bovine alpha-crystallin/alpha-lactalbumin ratio. Additional studies of the systems were performed by HPLC and SDS gel electrophoresis. The particle distribution patterns derived from the DLS data indicated that the chaperoned complex (lactalbumin plus crystallin) is a loose fluffy globular entity. After the complex becomes saturated with lactalbumin, it appears to release the partially denatured lactalbumin which may aggregate into high molecular weight moieties. These eventually may precipitate out of solution. On longer standing, 24hr and over, the chaperoned complex as well as the lactalbumin aggregates become more compact. The chaperoned complex (alpha-crystallin plus alpha-lactalbumin) is in dynamic equilibrium both with the monomeric and the aggregated alpha-lactalbumin population. (C) 1999 Academic Press. C1 Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NASA, Lewis Res Ctr, Cleveland, OH 44135 USA. RP Bettelheim, FA (reprint author), Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. FU NEI NIH HHS [EY-12496-01] NR 34 TC 33 Z9 33 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 2 PY 1999 VL 261 IS 2 BP 292 EP 297 DI 10.1006/bbrc.1999.1031 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 226TC UT WOS:000082036900012 PM 10425180 ER PT J AU Morris, JA Zhang, D Coleman, KG Nagle, J Pentchev, PG Carstea, ED AF Morris, JA Zhang, D Coleman, KG Nagle, J Pentchev, PG Carstea, ED TI The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CPG ISLANDS; CHOLESTEROL HOMEOSTASIS; NUCLEOTIDE-SEQUENCE; DISEASE; MUTATION; STORAGE; LESION; CELLS AB Niemann-Pick C (NP-C) is a fatal autosomal recessive storage disorder characterized by progressive neurodegeneration and variable hepatosplenomegaly. At the cellular level, cells derived from an affected individual accumulate unesterified cholesterol in lysosomes when cultured with low-density lipoprotein. The NP-C gene was identified at 18q11. The transcript is 4.9 kb encoding a 1278-amino-acid protein. We have defined the genomic structure of NPC1 along with the 5' flanking sequence. The NPC1 gene spans greater than 47 kb and contains 25 exons. Exons range in size from 74 to 788 bp with introns ranging in size from 0.097 to 7 kb. All intron/exon boundaries follow the GT/AG rule. The 5' flanking sequence has a CpG island containing multiple Spl sites indicative of a promoter region. The CpG; island is located in the 5' flanking sequence, exon 1 and the 5' end of intron 1, We have also identified multiple single nucleotide polymorphisms in the coding and intronic sequences. (C) 1999 Academic Press. C1 NINDS, NIH, Bethesda, MD 20892 USA. St Marys Hosp & Med Ctr, Saccomanno Res Inst, Grand Junction, CO 81502 USA. RP Morris, JA (reprint author), Merck Res Labs, Dept Human Genet, WP26A-3000,POB 4, W Point, PA 19486 USA. NR 25 TC 50 Z9 53 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 2 PY 1999 VL 261 IS 2 BP 493 EP 498 DI 10.1006/bbrc.1999.1070 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 226TC UT WOS:000082036900045 PM 10425213 ER PT J AU Long, YQ Voigt, JH Lung, FDT King, CR Roller, PP AF Long, YQ Voigt, JH Lung, FDT King, CR Roller, PP TI Significant compensatory role of position Y-2 conferring high affinity to non-phosphorylated inhibitors of GRB2-SH2 domain SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID STRUCTURAL BASIS; SH2 DOMAIN; BINDING; LIGANDS AB Systematic modification of amino acid at position Y-2 of a library-derived non-phosporylated thioether-cyclized peptide, cyclo(CH2CO-Glu(-2)-Leu-Tyr(0)-Glu-Asn-Val-Gly-Met-Tyr-Cys)-amide, aided by molecular modeling, demonstrates that the Glu(-2) sidechain compensates for the absence of Tyr phosphorylation in retaining effective binding to Grb2-SH2 domain. Replacement of Glu(-2) with gamma-carboxyglutamic acid produced a high affinity inhibitor, the first example with submicromolar affinity (IC50 = 640 nM). (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Roller, PP (reprint author), NCI, Div Basic Sci, Med Chem Lab, NIH, 37-5C02, Bethesda, MD 20892 USA. NR 15 TC 32 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 2 PY 1999 VL 9 IS 15 BP 2267 EP 2272 DI 10.1016/S0960-894X(99)00379-0 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 225DW UT WOS:000081944000031 PM 10465559 ER PT J AU Dunson, WA Dunson, DB AF Dunson, WA Dunson, DB TI Factors influencing growth and survival of the killifish, Rivulus marmoratus, held inside enclosures in mangrove swamps SO COPEIA LA English DT Article ID HERMAPHRODITIC FISH; ASSEMBLAGE; ESTUARINE; SALINITY AB We measured growth and survival in field enclosures of juvenile Rivulus marmoratus under a variety of biotic (effects of body mass and intraspecific density) and abiotic conditions (seasonal climatic changes, site-specific hypoxia). We also tested three different enclosure types, surface-floating buckets (0.021 m(3)), and tubes (0.006 m(3)) positioned at the surface or on the bottom. Growth rate was inversely correlated with wet body mass (between 6 and 42 mg) and density (1-16 fish/0.021 m(3) enclosure). However, density did not affect survival. Growth was significantly lower in tubes placed on the bottom than at the surface. There were considerable differences in growth and survival among sites. This likely is due to differences in occurrence and persistence of hypoxic events. At the Catfish Creek location (a pool surrounded by black mangroves), the bottom was routinely hypoxic. At a shallow bay site, hypoxia was episodic: on the bottom at dawn (O-2) < 2 mg/l occurred on nine of 48 days, with values < I mg/l on two of 48 days. Maximum growth rates (3.5-4%/day) were recorded in February to May, in comparison with lower values in December to January. However, low growth rates also occurred in the spring, probably caused by episodic hypoxia. C1 Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, WA (reprint author), Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA. NR 22 TC 19 Z9 19 U1 1 U2 4 PU AMER SOC ICHTHYOLOGISTS HERPETOLOGISTS PI CHARLESTON PA UNIV CHARLESTON, GRICE MARINE LABORATORY, 205 FORT JOHNSON RD, CHARLESTON, SC 29412 USA SN 0045-8511 J9 COPEIA JI Copeia PD AUG 2 PY 1999 IS 3 BP 661 EP 668 PG 8 WC Zoology SC Zoology GA 227HR UT WOS:000082075500010 ER PT J AU Bos, MP Hogan, D Belland, RJ AF Bos, MP Hogan, D Belland, RJ TI Homologue scanning mutagenesis reveals CD66 receptor residues required for neisserial Opa protein binding SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Neisseria gonorrhoeae; carcinoembryonic antigen; bacterial adhesion; opacity protein; mutagenesis ID CARCINOEMBRYONIC ANTIGEN CEA; GONOCOCCAL OPACITY PROTEINS; EPITHELIAL-CELLS; INTERCELLULAR-ADHESION; GENE FAMILY; PATHOGENIC NEISSERIAE; GONORRHOEAE; VARIANTS; EXPRESSION; SEQUENCE AB The immunoglobulin-like family of CD66 antigens, present on human neutrophils and epithelial cells, are used as receptors for adhesins expressed by the pathogenic Neisseriae. N. gonorrhoeae strain MS11 can express 11 isoforms of these adhesins, called opacity-related (Opa) proteins. Each MS11 Opa protein recognizes a distinct spectrum of CD66 receptors. CD66-Opa binding is mediated by the NH2-terminal domain of the receptor and occurs through protein-protein interactions. In this report, we have investigated the molecular basis for the binding between the CD66 and Opa protein families by mapping amino acids in CD66 receptors that determine Opa protein binding. Wi performed homologue scanning mutagenesis between CD66e, which binds multiple Opa variants, and CD66b, which binds none, and tested both loss-of-function by CD66e and gain-of-function by CD66b in solution assays and in assays involving full-length receptors expressed by epithelial cells. We found that three residues in the CD66e N-domain are required for maximal Opa protein receptor activity. Opa proteins that recognize the same spectrum of native CD66 molecules showed differential binding of receptors with submaximal activity, indicating that the binding characteristics of these Opa proteins are actually slightly different. These data provide a first step toward resolving the structural requirements for Opa-CD66 interaction. C1 NIAID, Rocky Mt Labs, NIH, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. RP Bos, MP (reprint author), NIAID, Rocky Mt Labs, NIH, Microbial Struct & Funct Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 47 TC 41 Z9 43 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 2 PY 1999 VL 190 IS 3 BP 331 EP 340 DI 10.1084/jem.190.3.331 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 224LT UT WOS:000081901100005 PM 10430622 ER PT J AU Gabriele, L Phung, J Fukumoto, J Segal, D Wang, IM Giannakakou, P Giese, N Ozata, K Morse, HC AF Gabriele, L Phung, J Fukumoto, J Segal, D Wang, IM Giannakakou, P Giese, N Ozata, K Morse, HC TI Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE apoptosis; caspase; chronic myelogenous leukemia; interferon; interferon consensus sequence-binding protein ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; BCL-X GENE; T-LYMPHOCYTES; IN-VITRO; FACTOR FAMILY; ICE FAMILY; HEMATOPOIETIC PROGENITORS; TUMOR-SUPPRESSOR; IFN-GAMMA; ANTI-FAS AB Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a disease with marked expansion of granulocytes and macrophages that frequently progresses to a fatal blast crisis, thus resembling human chronic myelogenous leukemia (CML). One important feature of CML is decreased responsiveness of myeloid cells to apoptotic stimuli. Here we show that myeloid cells from mice deficient in ICSBP exhibit reduced spontaneous apoptosis and a significant decrease in sensitivity to apoptosis induced by DNA damage. In contrast, apoptosis in thymocytes from ICSBP-deficient mice is unaffected. We also show that overexpression of ICSBP in the human U937 monocytic cell line enhances the rate of spontaneous apoptosis and the sensitivity to apoptosis induced by etoposide, lipopolysaccharide plus ATP, or rapamycin. Programmed cell death induced by etoposide was specifically blocked by peptides inhibitory for the caspase-1 or caspase-3 subfamilies of caspases. Studies of proapoptotic genes showed that cells overexpressing ICSBP have enhanced expression of caspase-3 precursor protein. In addition, analyses of antiapoptotic genes showed that overexpression of ICSBP results in decreased expression of Bcl-X-L. These data suggest that ICSBP modulates survival of myeloid cells by regulating expression of apoptosis-related genes. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Gabriele, L (reprint author), NIAID, Immunopathol Lab, NIH, Bldg 7,Rm 309,7 Ctr Dr,MSC 0760, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 73 TC 89 Z9 89 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 2 PY 1999 VL 190 IS 3 BP 411 EP 421 DI 10.1084/jem.190.3.411 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 224LT UT WOS:000081901100012 PM 10430629 ER PT J AU Miyaguchi, K Maeda, Y Kojima, T Setoguchi, Y Mori, N AF Miyaguchi, K Maeda, Y Kojima, T Setoguchi, Y Mori, N TI Neuron-targeted gene transfer by adenovirus carrying neural-restrictive silencer element SO NEUROREPORT LA English DT Article DE brain; gene expression; gene therapy; hippocampus; neuron; slice culture; silencer; transfection ID ACETYLCHOLINE-RECEPTOR GENE; CELL-ADHESION MOLECULE; SODIUM-CHANNEL GENE; FACTOR REST; SYNAPSIN-I; EXPRESSION; VECTOR; BRAIN; IDENTIFICATION; REPRESSOR AB ADENOVIRUS transfers genes to a wide range of cell types, but its application to neurons has been hampered by its reduced efficiency of infection as compared with that for glia. To achieve neuron-targeted gene transfer, we have produced an adenovirus carrying the reporter lacZ gene driven by the SCG10 minimum promoter containing the neural-restrictive silencer element (NRSE), which element selectively represses the transcription of genes in non-neuronal cells. When rat hippocampal slice cultures were infected with NRSE-bearing adenovirus, beta-galactosidase-positive cells were mostly pyramidal and granular neurons, whereas infection with virus carrying a mutated NRSE resulted in beta-galactosidase expression in both neurons and glia. The results suggest that the adenovirus carrying NRSE to be a useful tool for neurontargeted gene transfer. NeuroReport 10:2349-2353 (C) 1999 Lippincott Williams & Wilkins. C1 Natl Inst Longev Sci, Dept Mol Genet, Aichi 4748522, Japan. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Kumamoto Univ, Fac Med, Dept Neurol, Kumamoto 860, Japan. Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, Tokyo 113, Japan. RP Mori, N (reprint author), Natl Inst Longev Sci, Dept Mol Genet, Gengo 36-3, Aichi 4748522, Japan. NR 25 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 2 PY 1999 VL 10 IS 11 BP 2349 EP 2353 DI 10.1097/00001756-199908020-00024 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 221AC UT WOS:000081701200026 PM 10439462 ER PT J AU Perry, G Roder, H Nunomura, A Takeda, A Friedlich, AL Zhu, XW Raina, AK Holbrook, N Siedlak, SL Harris, PLR Smith, MA AF Perry, G Roder, H Nunomura, A Takeda, A Friedlich, AL Zhu, XW Raina, AK Holbrook, N Siedlak, SL Harris, PLR Smith, MA TI Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation SO NEUROREPORT LA English DT Article DE Alzheimer disease; ERK2; MAP kinase; PHF-tau; phosphorylation ID PROTEIN-KINASE; TAU; LOCALIZATION AB RESPONSES to increased oxidative stress may be the common mechanism responsible for the varied cytopathology of Alzheimer disease (AD). A possible link in support of this hypothesis is that one of the most striking features of AD, the abnormal accumulation of highly phosphorylated tau and neurofilament proteins, may be brought about by extracellular receptor kinase (ERK) whose activation is a common response to oxidative stress. In this study, we demonstrate that activated ERK is specifically increased in the same vulnerable neurons in AD that are the site of oxidative damage and abnormal phosphorylation. These findings suggest that ERK dysregulation, likely resulting from oxidative stress, could play an important role in the increased phosphorylation of cytoskeletal proteins observed in AD. NeuroReport 10:2411-2415 (C) 1999 Lippincott Williams & Wilkins. C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. NAP AG, D-80339 Munich, Germany. Asahikawa Med Coll, Dept Psychiat & Neurol, Asahikawa, Hokkaido 0788510, Japan. NIA, Gerontol Res Ctr, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Perry, G (reprint author), Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. RI Smith, Mark/A-9053-2009; Zhu, Xiongwei/A-9629-2009; Perry, George/A-8611-2009 OI Perry, George/0000-0002-6547-0172 FU NIA NIH HHS [AG09287, AG14249]; NINDS NIH HHS [NS38648] NR 19 TC 208 Z9 209 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 2 PY 1999 VL 10 IS 11 BP 2411 EP 2415 DI 10.1097/00001756-199908020-00035 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 221AC UT WOS:000081701200037 PM 10439473 ER PT J AU Hirsch, R Guralnik, JM Leveille, SG Simonsick, EM Ling, S Bandeen-Roche, K Rantanen, T Pahor, M Fried, LP Hochberg, MC AF Hirsch, R Guralnik, JM Leveille, SG Simonsick, EM Ling, S Bandeen-Roche, K Rantanen, T Pahor, M Fried, LP Hochberg, MC TI Severity of hand osteoarthritis and its association with upper extremity impairment in a population of disabled older women: The Women's Health and Aging Study SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE disabled; elderly; hand osteoarthritis; muscle strength; severity ID OSTEO-ARTHRITIS; PHYSICAL-DISABILITY; KNEE; STRENGTH; PEOPLE; ADULTS; INDEX AB Most severity indices of osteoarthritis (OA) include measures of physical function which render them unsuitable for assessing the impact of OA on disability. Data from 1002 moderate to severely disabled community-dwelling women greater than or equal to 65 years were used to develop hand OA severity indices which are independent of functional status. Baseline exams and strength tests were conducted by trained nurse examiners. Each distal and proximal interphalangeal joint, and first carpometacarpal joint (20 joints in all) was scored for the presence of a) bony enlargement or deformity, and b) pain on motion or tenderness on palpation. Severity indices were then created. Deformity index (DEF) = sum of joints with bony changes (0-20); Pain/Tenderness index (PT) = sum of joints with pain or tenderness (0-20); and Combined Deformity/Pain index = sum of DEF and PT (0-40). These indices were then validated against grip and pinch strength. All three indices showed a significant trend for weaker grip strength as severity index scores increased. When the 25(th), 50(th) and 75(th) percentiles were used to divide each severity index into levels Of involvement, a threshold effect was observed with significantly poorer grip strength performance above the 75(th) percentile for each index. Similar results were seen for pinch strength. In conclusion, these hand OA severity indices, based on examination findings alone, help distinguish disease status, and may provide a valuable research tool for investigating the role of hand OA in impairment and disability. (C) 1999, Editrice Kurtis. C1 NIA, Bethesda, MD 20892 USA. RP Hirsch, R (reprint author), Natl Ctr Hlth Stat, DHES, Presidential Bldg Room 900,6525 Belcrest Rd, Hyattsville, MD 20782 USA. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 25 TC 13 Z9 13 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD AUG PY 1999 VL 11 IS 4 BP 253 EP 261 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 256GW UT WOS:000083718400006 PM 10605614 ER PT J AU Enoch, MA White, KV Harris, CR Robin, RW Ross, J Rohrbaugh, JW Goldman, D AF Enoch, MA White, KV Harris, CR Robin, RW Ross, J Rohrbaugh, JW Goldman, D TI Association of low-voltage alpha EEG with a subtype of alcohol use disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE EEG; alpha; alcoholism; anxiety ID ANXIETY DISORDERS; PANIC DISORDER; ELECTROENCEPHALOGRAM; DEPRESSION; WOMEN; SONS; MEN AB Background: Neurophysiological traits may identify more homogeneous subgroups of alcoholics. Such discoveries could yield information regarding pathophysiological development, leading to more specific preventive measures and treatments. In an earlier study of 127 individuals, 59 of whom were unrelated, we found that a heritable resting Electroencephalographic (EEG) phenotype, i.e., the low-voltage alpha (LVA) trait, was associated with alcohol use disorders and anxiety disorders. Methods: We evaluated these findings using an independent, similarly established, dataset of 120 subjects. We also extended the study to a larger set of 149 unrelated individuals from a total sample of 247 subjects for whom psychiatric diagnoses and resting EEG phenotypes were available. Blind-rated psychiatric diagnoses were formulated according to DSM-III-R criteria. Results: In the replication sample, the LVA trait was again more common among subjects with anxiety disorders than among those without. In the total group of unrelated individuals, alcoholics were significantly (3 times) more likely to show the LVA trait than were nonalcoholics. Again, individuals with anxiety disorders were significantly (3 limes) more likely to exhibit the LVA trait than were those without anxiety disorders. Of 11 unrelated alcoholics with anxiety disorders, seven showed the LVA trait. It was specifically the LVA trait and not low amplitude alpha activity that was associated with alcohol use disorders. Conclusions: The results of this replication study and the analysis of the total sample of unrelated individuals support an association between LVA EEG and the subtype of alcohol use disorders associated with anxiety disorders. The LVA phenotype may be a vulnerability factor for alcohol use disorders and anxiety disorders. C1 Ross Ctr Anxiety & Related Disorders, Washington, DC USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 12420 Parklawn Dr,Pk 5 Bldg,Room 451,MSC 8110, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 44 TC 57 Z9 57 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1999 VL 23 IS 8 BP 1312 EP 1319 DI 10.1097/00000374-199908000-00004 PG 8 WC Substance Abuse SC Substance Abuse GA 228GV UT WOS:000082129500005 PM 10470973 ER PT J AU Vivian, JA Higley, JD Linnoila, M Woods, JH AF Vivian, JA Higley, JD Linnoila, M Woods, JH TI Oral ethanol self-administration in rhesus monkeys: Behavioral and neurochemical correlates SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; preferences; self-administration; serotonin ID ALCOHOL-PREFERRING P; NONHUMAN PRIMATE MODEL; NONPREFERRING NP LINES; 5-HYDROXYINDOLEACETIC ACID; REINFORCING PROPERTY; CEREBROSPINAL-FLUID; VERVET MONKEYS; RATS; CONSUMPTION; SEROTONIN AB Background: Previous research has revealed that orally administered ethanol serves as a reinforcer in nonhuman primates. The purposes of the present study were to examine the relationship between ethanol preferences and intakes in two distinct self-administration contexts and to reveal some of the behavioral and neurochemical correlates of oral ethanol self-administration in monkeys. Methods: Three cohorts of 13 to 29 rhesus monkeys (Macaca mulatta) were socially housed and given daily, l-hr, one-spout access to an ethanol solution (8.4%, w/v) sweetened with aspartame. Twelve of these monkeys were subsequently selected, individually housed, and given daily, 2-hr, two-spout access to a range of ethanol concentrations (0.25-16%, w/v) concurrently with water. Results: These monkeys (National Institute on Alcohol Abuse and Alcoholism group) showed a marked preference for ethanol (0.5-4%, w/v) over water, and ethanol preferences were 3-fold greater than those of a second group of 12 monkeys (University of Michigan group) purchased from a commercial vendor. Ethanol consumption was consistent across the self-administration paradigms. Monkeys that consumed large quantities of ethanol under the one-spout, social-housing conditions continued to drink large quantities of ethanol under the two-spout, individual-housing conditions (r = 0.86). An association between ethanol preferences and intakes was also demonstrated. Monkeys with the greatest preferences for ethanol over water under the two-spout choice conditions consumed the largest quantities of ethanol (r = 0.82). Finally, cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations were inversely related to ethanol preference but not to ethanol intake. Conclusions: These results indicate that ethanol consumption is stable across contexts and is positively correlated with the preference for ethanol over water. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIAAA, Clin Studies Lab, Bethesda, MD USA. RP Vivian, JA (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB III, Ann Arbor, MI 48109 USA. FU NIAAA NIH HHS [AA11424]; NIDA NIH HHS [DA00254, DA05773] NR 55 TC 22 Z9 22 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1999 VL 23 IS 8 BP 1352 EP 1361 DI 10.1097/00000374-199908000-00009 PG 10 WC Substance Abuse SC Substance Abuse GA 228GV UT WOS:000082129500010 PM 10470978 ER PT J AU Cooper, HA Exner, DV Waclawiw, MA Domanski, MJ AF Cooper, HA Exner, DV Waclawiw, MA Domanski, MJ TI White blood cell count and mortality in patients with ischemic and nonischemic left ventricular systolic dysfunction (an analysis of the studies of left ventricular dysfunction [SOLVD]) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; LEUKOCYTE COUNT; CARDIOVASCULAR-DISEASE; FIBRINOGEN; RISK; ASSOCIATION; PREDICTOR; FAILURE; MEN AB We conducted a retrospective analysis of the Studies OF Left Ventricular Dysfunction (SOLVD) trials to assess the predictive value of the baseline white blood cell (WBC) count on mortality, Mortality was higher in participants with a baseline WBC count >7,000 compared to those with a baseline WBC less than or equal to 7,000 (27% vs 21%, p <0.0001), After controlling for important covariates, each increase in WBC count of 1,000/mm(3) was significantly associated with an increased risk of: all-cause mortality (relative risk [RR] 1.05, p <0.001). Overall, compared with a baseline W8C count less than or equal to 7,000, a baseline WBC count >7,000 was significantly associated with an increased risk of all-cause mortality (RR 1.22, p = 0.001), In participants with ischemic left ventricular (LV) dysfunction, a WBC count >7,000 remained significantly associated with an increased risk of all-cause mortality (RR 1.26, p <0.001), whereas in participants with nonischemic LV dysfunction there was no relation between WBC count and mortality (RR 1.08, p = 0.5). Thus, baseline WBC is an independent predictor of mortality in patients with LV dysfunction, specifically in those with ischemic cardiomyopathy. (C) 1999 by Excerpta Medica, Inc. C1 NHLBI, Clin Trials Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Cardiol, Washington, DC 20007 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Cooper, HA (reprint author), NHLBI, Clin Trials Sci Res Grp, Div Epidemiol & Clin Applicat, 2 Rockledge Ctr,Room 8149,6701 Rockledge Dr,MSC 7, Bethesda, MD 20892 USA. NR 17 TC 40 Z9 42 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1999 VL 84 IS 3 BP 252 EP 257 DI 10.1016/S0002-9149(99)00272-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 220RE UT WOS:000081680600002 PM 10496431 ER PT J AU Rashid, H Exner, DV Mirsky, I Cooper, HA Waclawiw, MA Domanski, MJ AF Rashid, H Exner, DV Mirsky, I Cooper, HA Waclawiw, MA Domanski, MJ TI Comparison of echocardiography and radionuclide angiography as predictors of mortality in patients with left ventricular dysfunction (studies of left ventricular dysfunction) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; EJECTION FRACTION; THROMBOLYTIC THERAPY; SURVIVAL; TRIAL AB Left ventricular (LV) systolic dysfunction, as indicated by a reduced LV ejection fraction (EF) is a potent predictor of cardiovascular mortality. Radionuclide angiography accurately and reproducibly assesses LVEF; however, echocardiography is used more frequently in clinical practice. Whether these methods predict similar mortality has not been fully investigated. We performed a retrospective analysis of patients with baseline radionuclide angiographic (RNA; n = 4,330) and echocardiographic (echo; n = 1,376) based EFs less than or equal to 0.35 who were enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to address this hypothesis. After adjusting for important prognostic variables, the risk of death (RR 1.15; 95% confidence interval 1.01 to 1.30; p = 0.03) and of cardiovascular death (RR 1.15; 95% confidence interval 1.01 to 1.32; p = 0.04) was higher for patients with EGG-based EFs, To compare the 2 techniques across a range of IEF values, we divided the cohort into tertiles of EF, The adjusted risk estimates for all-cause and cardiovascular mortality were similar within each tertile. Of note, the mortality difference in patients with echo-versus RNA-based EFs was most prominent in women. Further, patients with echo-based EFs had significantly higher mortality at sites where this technique was less frequently used to assess the EF. Thus, for a given EF less than or equal to 0.35, an echo-based value was associated with a higher risk of death compared with the RNA-based method of measurement, These data suggest that EF wolves determined by echocardiography and radionuclide angiography predict different mortality and this may, in part, be related to technical proficiency as well as patient characteristics. (C) 1999 by Excerpta Medica, Inc. C1 NHLBI, Clin Trials Res Grp, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Div Cardiol, Washington, DC USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Rashid, H (reprint author), NHLBI, Clin Trials Res Grp, 2 Rockledge Ctr,6701 Rockledge Dr,Room 8149, Bethesda, MD 20892 USA. NR 24 TC 20 Z9 22 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1999 VL 84 IS 3 BP 299 EP 303 DI 10.1016/S0002-9149(99)00280-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 220RE UT WOS:000081680600010 PM 10496439 ER PT J AU Andrews, NP Goldstein, DS Quyyumi, AA AF Andrews, NP Goldstein, DS Quyyumi, AA TI Effect of systemic alpha(-2) adrenergic blockade on the morning increase in platelet aggregation in normal subjects SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; 2 HYDROXYLATED METABOLITES; CORONARY-ARTERY DISEASE; CIRCADIAN VARIATION; STRENUOUS EXERCISE; PHYSICAL EXERTION; IN-VIVO; ACTIVATION; CATECHOLAMINES AB To assess whether activation of platelets by catecholamines contributes to the increase in platelet aggregation associated with either the assumption of upright posture or exercise, we studied the effect of oral yohimbine on these phenomena. Whole blood platelet aggregation and plasma catecholamine levels were measured before and after standing and at peak exercise in untreated normal subjects and after oral yohimbine. Neurochemical indexes indicated systemic alpha(2)-receptor blockade by yohimbine. Yohimbine reduced the ortho-static increase in platelet aggregation response by 63 +/- 11%, but exercise-induced increase in aggregation was unaffected, Thus, alpha(2)-adrenergic blockade attenuates the orthostatic increase in platelet aggregation. Agents designed to inhibit the morning surge in catecholamine levels or block platelet alpha(2) adrenoceptors may reduce the risk of thrombotic vascular events in atherosclerosis. (C) 1999 by Excerpta Medico, Inc. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 17 Z9 19 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1999 VL 84 IS 3 BP 316 EP 320 DI 10.1016/S0002-9149(99)00283-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 220RE UT WOS:000081680600013 PM 10496442 ER PT J AU Kellam, SG Koretz, D Moscicki, EK AF Kellam, SG Koretz, D Moscicki, EK TI Core elements of developmental epidemiologically based prevention research SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE development; epidemiology; prevention research ID DEPRESSIVE SYMPTOMS; MENTAL-HEALTH; CHILDREN; CHILDHOOD; 1ST-GRADE; BEHAVIOR; SCHOOL; TRIALS AB In the early 1990's, important progress was documented in prevention research on mental and behavioral disorders, with recommendations for a prevention research agenda. One of the earliest implementation efforts was the workshop, "A Scientific Structure for the Emerging Field of Prevention Research," sponsored by the National Institute of Mental Health and The Johns Hopkins University Prevention Research Center, and held in Baltimore, Maryland, in December of 1994. The purpose of the workshop was to merge three perspectives from the traditionally disparate areas of epidemiology, life course development, and intervention trials technology into an integrated interdisciplinary effort that would define a scientific structure enabling rapid advancement in prevention science. As a consequence of that workshop, the papers were written that are contained in this and the next special issue on prevention of the American Journal of Community Psychology. This first paper is a description of the salient features of developmental epidemiologically-based prevention research. Beyond the above three perspectives. we discuss the role of development mental and intervention theories; measurement of implementation, mediators, and moderators, including multi-stage sampling and measurement; the central role of multilevel growth modeling; concepts of attributable risk and prevented fraction; proximal/distal modeling and effect sites; and partnerships between researchers and communities. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. NIMH, Rockville, MD USA. RP Kellam, SG (reprint author), Johns Hopkins Univ, Prevent Res Ctr, 5200 Eastern Ave,Mason F Lord Bldg,Suite 500 W, Baltimore, MD 21224 USA. NR 64 TC 73 Z9 74 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD AUG PY 1999 VL 27 IS 4 BP 463 EP 482 DI 10.1023/A:1022129127298 PG 20 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 254ZJ UT WOS:000083644000002 PM 10573831 ER PT J AU Sharrett, AR Hubbard, LD Cooper, LS Sorlie, PD Brothers, RJ Nieto, FJ Pinsky, JL Klein, R AF Sharrett, AR Hubbard, LD Cooper, LS Sorlie, PD Brothers, RJ Nieto, FJ Pinsky, JL Klein, R TI Retinal arteriolar diameters and elevated blood pressure - The atherosclerosis risk in communities study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arterioles; arteriosclerosis; blood pressure; cardiovascular diseases; microcirculation; retinal artery AB Narrowing and other changes in retinal arterioles may reflect damage due to hypertension, which may predict stroke and other cardiovascular diseases independently of blood pressure level, Newly developed quantitative methods of assessing retinal narrowing are used to determine whether this sign is related only to current blood pressure or whether it also independently reflects the effects of previous blood pressure. Retinal photography was performed at the third examination of Atherosclerosis Risk in Communities (ARIC) Study in 1993-1995, and results are presented for the 9,300 nondiabetic participants aged 50-71 years. Generalized narrowing of smaller arterioles was strongly and monotonically related to current blood pressure in men and women, whether they were taking antihypertensive medications or not, and, independent of current blood pressure, was consistently and monotonically related to blood pressure levels measured 3 and 6 years before the retinal assessment. Arteriovenous nicking was also independently related to both current and previous blood pressures. The patterns of association suggested that these signs reflect both transient and persisting structural effects of elevated blood pressure, in agreement with the scant pathologic literature available. The findings suggest that retinal assessment may be useful for research on the microvascular contributions to clinical cardiovascular diseases. C1 NHLBI, Div Epidemiol Clin Applicat, Clin Applicat & Epidemiol Program, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Sharrett, AR (reprint author), NHLBI, Div Epidemiol Clin Applicat, Clin Applicat & Epidemiol Program, 2 Rockledge Ctr,6701 Rockledge Dr,MSC 7934, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC55018, N01-HC55015, N01-HC55019] NR 9 TC 206 Z9 211 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 1999 VL 150 IS 3 BP 263 EP 270 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 221AZ UT WOS:000081703200007 PM 10430230 ER PT J AU Athanassiadou, A Voutsinas, G Psiouri, L Leroy, E Polymeropoulos, MH Ilias, A Maniatis, GM Papapetropoulos, T AF Athanassiadou, A Voutsinas, G Psiouri, L Leroy, E Polymeropoulos, MH Ilias, A Maniatis, GM Papapetropoulos, T TI Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding alpha-synuclein SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID ALZHEIMER-DISEASE; G209A MUTATION; LEWY BODIES; ASSIGNMENT; COMPONENT; ABSENCE C1 Univ Patras, Fac Med, Dept Biol, Patras, Greece. Univ Patras, Fac Med, Dept Neurol, Patras, Greece. Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD USA. Novartis Pharmaceut Corp, Pharmacogenet, Gaithersburg, MD USA. Univ Athens, Eginit Hosp, Athens, Greece. RP Athanassiadou, A (reprint author), Univ Patras, Fac Med, Dept Biol, Patras, Greece. NR 21 TC 80 Z9 84 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1999 VL 65 IS 2 BP 555 EP 558 DI 10.1086/302486 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 223JA UT WOS:000081836900030 PM 10417297 ER PT J AU Cantor, KP Silberman, W AF Cantor, KP Silberman, W TI Mortality among aerial pesticide applicators and flight instructors: Follow-up from 1965-1988 SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE pesticides; cancer; leukemia; prostate cancer; retrospective cohort; pesticide applicators ID NATIONAL-DEATH-INDEX; VITAL STATUS; PROPORTIONAL MORTALITY; PANCREATIC-CANCER; RISK; PILOTS; LEUKEMIA; WORKERS; FARMERS; COHORT AB Background Vital status followup for a retrospective cohort mortality study of 9,961 male aerial pesticide applicators was extended beyond a previous study (1965-1979) (Cantor et al. 1991), through December 31, 1988. Methods Rate ratios (RR) were used to compare directly adjusted mortality rates between applicators and a comparison cohort of 9,969 flight instructors. Standardized mortality ratios (SMR) were calculated for comparisons with the U.S. white male population. Results Among applicator pilots, there were 1,441 deaths, and among instructors, 1,045. In both groups, aircraft accidents were the major cause of death (446 applicators; 234 instructors). Compared with flight instructors, aerial applicator pilots were at significantly elevated risk for all causes of death (risk ratio = 1.34) and for malignant neoplasms (1.18), non-motor vehicle accidents (1.71), motor vehicle accidents (1.69), and stroke (1.91), Pancreatic cancer (2.71) and leukemia (3.35) were significantly elevated. Applicators were at lower risk of colon cancer (0.51) and multiple myeloma (0.23) mortality Based on U.S. rates, the SMR for an causes of death among applicators was 111 (95% confidence interval (CI) = 105-117) and among instructors, 81 (CI = 76-85), Conclusions Aircraft accidents were a major cause of mortality in both applicator and flight instructor cohorts. Several other causes of death, some possibly related to pesticide exposure, were also elevated among pesticide applicator pilots. Am. J. Ind, Med, 36: 239-247, 1999, Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fed Aviat Adm, Aeromed Certificat Div, Civil Aeromed Inst, Oklahoma City, OK 73126 USA. RP Cantor, KP (reprint author), 6120 Execut Blvd,EPS-8106, Bethesda, MD 20892 USA. NR 42 TC 40 Z9 40 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 1999 VL 36 IS 2 BP 239 EP 247 DI 10.1002/(SICI)1097-0274(199908)36:2<239::AID-AJIM3>3.0.CO;2-V PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 214GD UT WOS:000081319500003 PM 10398932 ER PT J AU Kernan, GJ Ji, BT Dosemeci, M Silverman, DT Balbus, J Zahm, SH AF Kernan, GJ Ji, BT Dosemeci, M Silverman, DT Balbus, J Zahm, SH TI Occupational risk factors for pancreatic cancer: A case-control study based on death certificates from 24 US States SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE case-control study; formaldehyde; industry; occupation; pancreatic cancer; solvents; job-exposure matrix ID FORMALDEHYDE EXPOSURE; EPIDEMIOLOGIC EVIDENCE; METHYLENE-CHLORIDE; UNITED-STATES; NASAL CAVITY; MORTALITY; WORKERS; ASSOCIATIONS; LOUISIANA; PATTERNS AB Background The relation between occupational exposure and pancreatic cancer is not well established. A population-based case-control study based on death certificates from 24 U.S. states was conducted to determine if occupations/industries or work-related exposures to solvents were associated with pancreatic cancer death. Methods The cases were 63,097 persons who died from pancreatic cancer occurring in the period 1984-1993. The controls were 252,386 persons who died from causes other than cancer in the same time period. Results Industries associated with significantly increased risk of pancreatic cancer included printing and paper manufacturing; chemical, petroleum, and related processing; transport, communication, and public service; wholesale and retail trades; and medical and other health-related services. Occupations associated with significantly increased risk included managerial, administrative, and other professional occupations; technical occupations; and sales, clerical, and other administrative support occupations. Potential exposures to formaldehyde and other solvents were assessed by using a job exposure matrix developed for this study. Occupational exposure to formaldehyde was associated with a moderately increased risk of pancreatic cancer; with ORs of 1.2, 1.2, 1.4 for subjects with low, medium, and high probabilities of exposure and 1.2, 1.2, and 1.1 for subjects with low, medium, and high intensity of exposure, respectively. Conclusions The findings of this study did not suggest that industrial or occupational exposure is a major contributor to the etiology of pancreatic cancer. Further study may be needed to confirm the positive association between formaldehyde Exposure and pancreatic cancer. Am. J. Ind. Med. 36:260-270, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. WS Atkins Polska Ltd, Warsaw, Poland. George Washington Univ, Dept Environm & Occupat Hlth, Washington, DC USA. RP Ji, BT (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8120, Rockville, MD 20852 USA. RI Zahm, Shelia/B-5025-2015 NR 50 TC 24 Z9 26 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 1999 VL 36 IS 2 BP 260 EP 270 DI 10.1002/(SICI)1097-0274(199908)36:2<260::AID-AJIM5>3.0.CO;2-P PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 214GD UT WOS:000081319500005 PM 10398934 ER PT J AU Petronis, JD Regan, F Briefel, G Simpson, PM Hess, JM Contoreggi, CS AF Petronis, JD Regan, F Briefel, G Simpson, PM Hess, JM Contoreggi, CS TI Ventilation-perfusion scintigraphic evaluation of pulmonary clot burden after percutaneous thrombolysis of clotted hemodialysis access grafts SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE pulmonary embolism; interventional procedure grafts; dialysis; shunts ID PHARMACOMECHANICAL THROMBOLYSIS; EMBOLISM; FISTULA; THERAPY AB The objective of this study is to determine, by using rigorous methods, if pulmonary perfusion defects were detectable by ventilation-perfusion scintigraphy after percutaneous thrombolysis of clotted hemodialysis access grafts, Thirteen patients were studied. Four patients underwent pharmacomechanical thrombolysis with urokinase and the remainder had mechanical thrombolysis alone. Pre- and postthrombolysis scintigraphic studies were performed on all patients. Perfusion defects were described as vascular (well-defined borders confined to segmental boundaries) or nonvascular, Vascular defects were graded by severity (0 to 3) and area (0 to 3) for each involved segment, Nonvascular defects were graded by severity (0 to 1)and area (0 to 1). Two experienced readers evaluated the scans blinded to each other's results and all other clinical data, including thrombolysis outcomes. Twelve patients did not have any significant worsening of their perfusion defect scores postthrombolysis, In only one patient did a study show a new nonvascular perfusion defect with a matching ventilation abnormality. The defect was believed to be caused by mucus plugging, The patient had no evidence of pulmonary embolism. Our study suggests emboli that resulted from the pharmacomechanical or mechanical thrombolysis procedure were either small, underwent lysis before impacting the lung, or were below the limit of detection of ventilation-perfusion scintigraphy, (C) 1999 by the National Kidney Foundation, Inc. C1 Johns Hopkins Bayview Med Ctr, Div Nucl Med, Dept Radiol, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Nephrol, Baltimore, MD 21224 USA. NIDA, NIH, Intramural Res Program, Baltimore, MD USA. Univ Arkansas Med Sci, Ctr Appl Res, Dept Pediat, Little Rock, AR 72205 USA. RP Petronis, JD (reprint author), Johns Hopkins Bayview Med Ctr, Div Nucl Med, Dept Radiol, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 20 TC 18 Z9 19 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 1999 VL 34 IS 2 BP 207 EP 211 DI 10.1016/S0272-6386(99)70344-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 225JY UT WOS:000081955600002 PM 10430963 ER PT J AU Bryan, RN McLaughlin, A AF Bryan, RN McLaughlin, A TI MR perfusion imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RI Bryan, R. Nick/P-1661-2014 NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 1999 VL 20 IS 7 BP 1192 EP 1193 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 232CY UT WOS:000082349200002 PM 10472969 ER PT J AU Bryan, RN Cai, JW Burke, G Hutchinson, RG Liao, DP Toole, JF Dagher, AP Cooper, L AF Bryan, RN Cai, JW Burke, G Hutchinson, RG Liao, DP Toole, JF Dagher, AP Cooper, L TI Prevalence and anatomic characteristics of infarct-like lesions on MR images of middle-aged adults: The atherosclerosis risk in communities study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CARDIOVASCULAR HEALTH; AGING BRAIN; LACUNAR INFARCTION; OLDER ADULTS; STROKE; POPULATION; DISEASE; ABNORMALITIES; DEMENTIA; SPACES AB BACKGROUND AND PURPOSE: MR imaging has revealed putative evidence of subclinical cerebrovascular disease (CVD) as reflected by white matter signal changes and infarct-like lesions (ILLs), Nonetheless, the prevalence of this condition in the general population has been defined only to a limited extent, We herein report the prevalence and anatomic characteristics of ILLs seen on cranial MR images obtained as part of a population-based study of cardiovascular disease in middle-aged adults, These results are contrasted to those of previous similar studies, particularly those of an elderly population in the Cardiovascular Health Study (CHS), METHODS: This Atherosclerosis Risk in Communities (ARIC) cohort consists of a probability sample of community-living persons who were 55 to 72 years old at the time of MR examination, MR imaging of 1890 participants was performed at two ARIC field centers, based on a common protocol. MR studies were evaluated by trained readers at the MR Reading Center using original digital data displayed on a high-resolution workstation, The measures of lesion size, anatomic location, and signal intensity were collected, The definition for an ILL was a non-mass, hyperintense region with an arterial vascular distribution on spin-density and T2-weighted images, RESULTS: Two hundred ninety participants had ILLs, for an overall prevalence of 15.3%, Eighty-two percent of participants with ILLs had lesions that were 3 mm or larger in maximal dimension, although 87% of these lesions were 20 mm or smaller in maximal dimension, The prevalence of ILLs increased with age, from 7.9% in the 55- to 59-year-old age group to 22.9% in the 65- to 72-year-old age group (P < .001). Lesion prevalence was greater in black (20.7%) than in white persons (10.2% [P < .0001]), but did not differ significantly between male and female participants, The basal ganglia and thalamic region was the most commonly affected anatomic site, accounting for 78.9% of the lesions, CONCLUSION: Considering that the prevalence of self-reported stroke or transient ischemic attack in ARIC participants is 1.5%, these results suggest that there is significantly more subclinical than clinical CVD in the general population, Furthermore, the prevalence of this subclinical disease increases with age, and is greater in black persons, ILLs are dominated by "lacunae" in the basal ganglia and thalamus, These results are, in general, similar to those of a comparable study of elderly participants in the CHS, except for a 60% lower prevalence of ILLs in this younger population. C1 Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Bryan, RN (reprint author), Dept Diagnost Radiol, Bldg 10,Room 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. RI Bryan, R. Nick/P-1661-2014 FU NHLBI NIH HHS [N01-HC-35126, N01-HC-55015, N01-HC-55016] NR 31 TC 62 Z9 63 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 1999 VL 20 IS 7 BP 1273 EP 1280 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 232CY UT WOS:000082349200018 PM 10472985 ER PT J AU Belt, AR Baldassare, JJ Molnar, M Romero, R Hertelendy, F AF Belt, AR Baldassare, JJ Molnar, M Romero, R Hertelendy, F TI The nuclear transcription factor NF-kappa B mediates interleukin-1 beta-induced expression of cyclooxygenase-2 in human myometrial cells SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 18-22, 1997 CL SAN DIEGO, CALIFORNIA SP Soc Gynecol Invest DE prostaglandins; cyclooxygenase 2 expression; myometrium; immortalized myometrial cells; NF-kappa B activation; interleukin 1 ID GENE-EXPRESSION; PRETERM LABOR; WOMEN; ACTIVATION; INFECTION; PROTEINS; FLUID AB OBJECTIVE: Up-regulation of prostaglandin production by gestational tissues in the setting of intrauterine infection has been implicated as an important contributor to preterm labor and parturition. In this study we investigated the possible role of the nuclear transcription factor NF-kappa B in interleukin-1 signaling, leading to the expression of cyclooxygenase 2 and prostaglandin production in human myometrial cell cultures. STUDY DESIGN: Human myometrial smooth muscle cells from an immortalized line were used as a model system between passages 20 and 35. Growth-arrested cell cultures were stimulated with human recombinant interleukin 1, and the activation of NF-kappa B was assessed by the degradation of the inhibitory protein I kappa B alpha (Western analysis), as well as by nuclear binding of NF-kappa B by using an electrophoretic mobility shift assay. The abundance of cyclooxygenase-2 messenger ribonucleic acid and protein was measured by Northern and Western analyses, whereas prostaglandin (prostaglandin I-2 and prostaglandin E-2) production was determined by specific radioimmunoassays. RESULTS: Within 15 minutes of stimulation with interleukin 1, 90% of I kappa B-alpha was degraded. This was temporally associated with nuclear translocation and binding of NF-kappa B. Within 30 minutes, cyclooxygenase 2 messenger ribonucleic acid appeared, with steady-state levels increasing up to 4 hours. This was followed by an up to 80-fold increase in cyclooxygenase 2 protein and a corresponding time-dependent increase in prostaglandin production. When I kappa B-alpha degradation was blocked with calpain I inhibitor, NF-kappa B translocation, cyclooxygenase 2 messenger ribonucleic acid and protein expression, and prostaglandin synthesis were also inhibited. CONCLUSION: Stimulation of human myometrial cells with interleukin 1 leads to rapid activation of the transcription factor NF-kappa B, which is functionally linked to the expression of cyclooxygenase 2 messenger ribonucleic acid, protein, and prostaglandin synthesis. C1 St Louis Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63117 USA. St Louis Univ, Dept Pharmacol & Physiol Sci, St Louis, MO 63117 USA. St Marys Hlth Ctr, St Louis, MO USA. Semmelweis Univ Med, Inst Pathophysiol, H-1085 Budapest, Hungary. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, Perinatol Res Branch, Bethesda, MD USA. RP Hertelendy, F (reprint author), St Louis Univ, Sch Med, Dept Obstet & Gynecol, St Marys W Pavil,1027 Bellevue Ave, St Louis, MO 63117 USA. OI Molnar, Miklos/0000-0001-9231-782X NR 27 TC 130 Z9 132 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1999 VL 181 IS 2 BP 359 EP 366 DI 10.1016/S0002-9378(99)70562-4 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 228WZ UT WOS:000082161300036 PM 10454683 ER PT J AU Huntsman, D Resau, JH Klineberg, E Auersperg, N AF Huntsman, D Resau, JH Klineberg, E Auersperg, N TI Comparison of c-met expression in ovarian epithelial tumors and normal epithelia of the female reproductive tract by quantitative laser scan microscopy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; E-CADHERIN EXPRESSION; SURFACE EPITHELIUM; HGF RECEPTOR; LUMEN FORMATION; CELLS; CARCINOMA; CANCER; OVEREXPRESSION AB The transmembrane tyrosine kinase receptor c-met with its Ligand, hepatocyte growth factor/scatter factor (HGF/SF), acts as a mitogen, motogen, and morphogen in many normal epithelia, HGF/SF-met signaling has also been implicated in neoplastic progression and metastasis, In this study, immunofluorescence staining and quantitative laser scanning confocal microscopy were used to measure c-met expression in ovarian surface epithelial tumors from 17 oophorectomy specimens. These specimens were from patients aged 25 to 81 (mean age, 52) and included 10 malignant tumors, 4 borderline tumors, and five benign tumors including a Brenner tumor. For comparison, c-met expression was measured in normal tissues from the same patients, including 4 ovarian surface epithelia, 4 fallopian tube epithelia, 2 endometria, and 3 endocervical epithelia, as well as 3 cases of endometriosis, Relative pixel intensity values of c-met expression ranged from 0.4 in a normal ovarian surface epithelium to 22.3 in a borderline serous tumor. Malignant tumors (mean, 9.6) and borderline tumors (mean, 12.9) had higher average c-met expression levels than normal tissues (mean, 3.6) and endometriosis (mean, 1.8). The expression levels of benign tumors were intermediate (mean, 7.9), Among the normal tissues, c-met expression in fallopian tubes (mean, 8.2; range, 3.4-12.9) was higher than that of the other normal epithelia (mean, 1.6; range, 0.4-4.3). in eight cases where both normal and malignant tissues were sampled, c-met expression was significantly greater in malignant than in normal epithelia (P = 0.01). These findings indicate that c-met plays a role in the biology of the normal tissues examined. They confirm that its expression increases in the malignant progression of ovarian surface epithelial tumors, and suggest that increases comparable to those in frankly malignant carcinomas have already been reached in borderline lesions, ie, early in the neoplastic process. C1 Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Auersperg, N (reprint author), Univ British Columbia, BC Womens Hosp 2H30, Dept Obstet & Gynecol, 4490 Oak St, Vancouver, BC V6H 3V5, Canada. NR 21 TC 63 Z9 65 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1999 VL 155 IS 2 BP 343 EP 348 DI 10.1016/S0002-9440(10)65130-9 PG 6 WC Pathology SC Pathology GA 224LY UT WOS:000081901600004 PM 10433927 ER PT J AU Murata, K Dalakas, MC AF Murata, K Dalakas, MC TI Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MHC CLASS-II; T-CELL; DUCHENNE DYSTROPHY; MUSCLE; ACTIVATION; DISEASES; ANTIGEN; CD80; GENE; B7 AB To examine if the muscle fibers in patients with inflammatory myopathies have the potential to behave as antigen presenting cells (APCs), we investigated the expression of costimulatory molecules BB-1, B7-1 (CD80), and B7-2 (CD86), and their counterreceptors, CD28 or CTLA-4 (CD152), in the muscle biopsies of patients with polymyositis (PM), PM associated with human immunodeficiency virus infection (HIV-PM), sporadic inclusion body myositis (s-IBM), dermatomyositis (DM), and normal or disease controls. The expression of the B7 family of molecules on the muscle fibers was limited to BB-1, In PM, HN-PM, and s-IBM, but not the disease controls, the nonnecrotic, MHC-class I-expressing muscle fibers, invaded or not by CD8+ T cells, had prominent membrane expression of BB-1, Several of the BB-1-positive fibers bound strongly in a cell-to-cell contact with their CD28 or CTLA-4 ligands on the autoinvasive CD8+ T cells, as confirmed by confocal microscopy. By reverse transcription-polymerase chain reaction, the expression of CD28 and CTLA-4 was up-regulated in PM, HIV-PILI, and s-IBM, but not the controls, Because the BB-1-positive fibers expressed MHC-class I antigen and bound to up-regulated counterreceptors CD28 and CTLA-4 on the autoinvasive CD8+ T cells only in Phl, HIV-PM, and s-IBM, the BB-1 molecule in these diseases should have a functional role in antigen presentation and T cell differentiation. These findings complement recent studies and suggest that in PM, HIV-PM, and s-IBM the muscle fibers are not only targets of CD8+ cytotoxic T cells but may also behave as "professional" APC. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Rm 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 25 TC 73 Z9 79 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1999 VL 155 IS 2 BP 453 EP 460 DI 10.1016/S0002-9440(10)65141-3 PG 8 WC Pathology SC Pathology GA 224LY UT WOS:000081901600015 PM 10433938 ER PT J AU Lubensky, IA Schmidt, L Zhuang, ZP Weirich, G Pack, S Zambrano, N Walther, MM Choyke, P Linehan, WM Zbar, B AF Lubensky, IA Schmidt, L Zhuang, ZP Weirich, G Pack, S Zambrano, N Walther, MM Choyke, P Linehan, WM Zbar, B TI Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FACTOR SCATTER FACTOR; CELL-CARCINOMA; METANEPHRIC ADENOMA; PROTOONCOGENE; GENE; TUMORS; RECEPTOR; CLASSIFICATION; FAMILIES; KIDNEY AB Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described, We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of rectal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma Clear cells with intracytoplasmic Lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal. cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Lubensky, IA (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [N01-CO-56000] NR 41 TC 126 Z9 130 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1999 VL 155 IS 2 BP 517 EP 526 DI 10.1016/S0002-9440(10)65147-4 PG 10 WC Pathology SC Pathology GA 224LY UT WOS:000081901600021 PM 10433944 ER PT J AU Arai, AE Kasserra, CE Territo, PR Gandjbakhche, AH Balaban, RS AF Arai, AE Kasserra, CE Territo, PR Gandjbakhche, AH Balaban, RS TI Myocardial oxygenation in vivo: optical spectroscopy of cytoplasmic myoglobin and mitochondrial cytochromes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE oxygen; mitochondria; oxygen consumption; facilitated diffusion; pig; dog; cytochrome b; cytochrome c; diffusion; computer simulation; hemoglobin ID CORONARY-ARTERY OCCLUSION; CANINE HEART; RABBIT HEART; VENTRICULAR MYOCARDIUM; OXIDATIVE-METABOLISM; CARDIAC OXYGENATION; MUSCLE; ISCHEMIA; FLOW; REPERFUSION AB The oxygenation state of myoglobin and the redox state of cytochrome c provide information on the Po, in the cytosol and mitochondria, respectively. An optical "window" from similar to 540 to 585 nm was found in the pig heart in vivo that permitted the monitoring of myoglobin and cytochrome c without interference from Hb oxygenation or blood volume. Scanning reflectance spectroscopy was performed on the surgically exposed left ventricle of pigs. Difference spectra between control and a total left anterior descending coronary artery occlusion revealed maxima and minima in this spectral region consistent with myoglobin deoxygenation and cytochrome c and b reduction. Comparison of in vivo data with in vitro fractions of the heart, including Hb-free tissue whole heart and homogenates, mitochondria, myoglobin, and pig red blood cells, reveals minimal contributions of Hb in vivo. This conclusion was confirmed by expanding the blood volume of the myocardium and increasing mean Hb O-2 saturation with an intracoronary infusion of adenosine (20 mu g.kg(-1).min(-1)), which had no significant effect on the 540- to 585-nm region. These results also suggested that myoglobin O-2 saturation was not blood flow limited under these conditions in vivo. Work jump studies with phenylephrine also failed to change cytochrome c redox state or myoglobin oxygenation. Computer simulations using recent physical data are consistent with the notion that myoglobin O-2 saturation is >92% under basal conditions and does not change significantly with moderate workloads. These studies show that reflectance spectroscopy can assess myocardial oxygenation in vivo. Myoglobin O-2 saturation is very high and is not labile to moderate changes in cardiac workload in the open-chest pig model. These findings indicate that myoglobin does not contribute significantly to O-2 transport via facilitated diffusion under these conditions. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D416,MS 1016, Bethesda, MD 20892 USA. EM rsb@zeus.nhlbi.nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 49 TC 55 Z9 55 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1999 VL 277 IS 2 BP H683 EP H697 PG 15 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 223XA UT WOS:000081865800031 PM 10444495 ER PT J AU Gandjbakhche, AH Bonner, RF Arai, AE Balaban, RS AF Gandjbakhche, AH Bonner, RF Arai, AE Balaban, RS TI Visible-light photon migration through myocardium in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myoglobin; hemoglobin; cytochromes; hematocrit; pig; oxygen; Monte Carlo simulations; photon migration ID OPTICAL-PROPERTIES; TISSUE; OXYGENATION; REFLECTANCE; MYOGLOBIN; HEART; STATE AB Empirical data between 510 and 590 nm of diffuse reflected light from the pig heart in vivo have shown that myoglobin and cytochrome c absorption peaks with little apparent contribution of red blood cell (RBC) Hb. Monte Carlo simulations of photon migration in tissue were performed to compare the effects of myoglobin and cytochromes with those of blood Hb on photon pathlengths and diffuse reflectance of visible wavelengths (450-600 nm) from the pig heart in vivo. Wavelength dependence of the input parameters, including the transport-corrected scattering coefficients (1.1-1.2 mm(-1)) and the absorption coefficients of blood-free solubilized heart tissue (0.43-1.47 mm(-1)), as well as the absorption coefficients of Hb, were determined by an integrating sphere method and standard spectrophotometry, respectively. The Monte Carlo simulations indicate that in the 510- to 590-nm range the mean path length within the myocardium for diffusely reflected light varies from 1.4 to 1.2 mm, whereas their mean penetration depth within the epicardium is only 330-400 mu m for blood-free heart tissue. Analysis shows that; the blood Hb absorption extrema are only observable between 510 and 590 nm when REC concentration in tissue is >0.5%. Blood within vessels much larger than capillaries does not contribute significantly to the spectral features, because virtually all light; in this spectral range is absorbed during transit through large vessels (>100 mu m). This analysis suggests that diffuse reflected light in the 510- to 590-nm region will show spectral features uniquely associated with myoglobin and cytochrome c oxygenation states within 400 mu m of the surface of the heart in situ as long as the capillary RBC concentration remains <0.5%. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D416,MS 1016, Bethesda, MD 20892 USA. EM rsb@zeus.nhlbi.nih.gov RI Balaban, Robert/A-7459-2009; Bonner, Robert/C-6783-2015 OI Balaban, Robert/0000-0003-4086-0948; NR 17 TC 38 Z9 38 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1999 VL 277 IS 2 BP H698 EP H704 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 223XA UT WOS:000081865800032 PM 10444496 ER PT J AU Duan, YF Kopin, IJ Goldstein, DS AF Duan, YF Kopin, IJ Goldstein, DS TI Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hypothalamus; medulla; electrophysiology; baroreflex; cardiovascular function ID BARORECEPTOR REFLEX; CARDIOVASCULAR REGULATION; ELECTRICAL-STIMULATION; HYPOTHALAMIC DEFENSE; SUPRAOPTIC NUCLEI; VIGILANCE AREAS; VASOPRESSIN; RABBITS; RATS; MEDULLA AB The present study assessed whether the baroreflex inhibition elicited by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) involves altered activity in the nucleus of the solitary tract (NTS). Unit recordings were made from 107 neurons in the NTS in anesthetized rabbits, Intravenous phenylephrine was used to induce a presser response and to activate baroreflexes. Of the neurons that responded to presser responses, two-thirds were excited and one-third was inhibited. Stimulation of the PVN inhibited 70% of the phenylephrine-responsive NTS neurons, with or without concurrent baroreceptor stimulation. When PVN stimulation was delivered concurrently with phenylephrine injection, more NTS neuronal inhibition and less excitation occurred than with phenylephrine alone. Usually PVN stimulation inhibited NTS neurons that were excited by presser responses; less commonly, PVN stimulation excited NTS neurons that were inhibited by presser responses. The findings are consistent with the view that PVN activation during the defense reaction inhibits baroreflexes by altering firing of NTS neurons. C1 NINDS, Clin Neurochem Sect, NIH, Bethesda, MD 20892 USA. RP Duan, YF (reprint author), Univ Maryland, Dept Psychiat, 701 W Pratt St,4th Floor, Baltimore, MD 21201 USA. EM yduan001@umaryland.edu NR 31 TC 29 Z9 33 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 1999 VL 277 IS 2 BP R403 EP R411 PG 9 WC Physiology SC Physiology GA 224WT UT WOS:000081923500009 PM 10444546 ER PT J AU Ecelbarger, CA Yu, SH Lee, AJ Weinstein, LS Knepper, MA AF Ecelbarger, CA Yu, SH Lee, AJ Weinstein, LS Knepper, MA TI Decreased renal Na-K-2Cl cotransporter abundance in mice with heterozygous disruption of the G(s)alpha gene SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE vasopressin; urinary concentrating mechanism; adenosine 3 ',5 '-cyclic monophosphate; sodium-potassium-adenosinetriphosphatase; aquaporins ID THICK ASCENDING LIMB; DEPENDENT ADENYLATE-CYCLASE; RAT-KIDNEY; ARGININE VASOPRESSIN; BRATTLEBORO RAT; COLLECTING DUCT; TUBULE; LOCALIZATION; EXPRESSION; ADH AB Transport processes along the nephron are regulated in part by hormone stimulation of adenylyl cyclases mediated by the heterotrimeric G protein G(s). To assess the role of this pathway in the regulation of Na-K-2Cl cotransporter abundance in the renal thick ascending limb (TAL), we studied mice with heterozygous disruption of the Gnas gene, which codes for the alpha-subunit of G(s). Outer medullary G(s)alpha protein abundance (as assessed by semiquantitative immunoblotting) and glucagon-stimulated cAMP production were significantly reduced in the heterozygous G(s)alpha knockout mice (GSKO) relative to their wild-type (WT) littermates. Furthermore, Na-K-2Cl cotransporter protein abundance in the outer medulla was significantly reduced (band density, 48% of WT). In addition, GSKO mice had a significantly reduced (72% of WT) urinary osmolality in response to a single injection of 1-deamino-[8-D-arginine]vasopressin (DDAVP), a vasopressin analog. In contrast, outer medullary protein expression of the type 3 Na/H exchanger (NHE-3) or Tamm-Horsfall protein did not differ between the GSKO mice and their WT littermates. However, abundance of type VI adenylyl cyclase was markedly decreased in the outer medullas of GSKO mice, suggesting a novel feed-forward regulatory mechanism. We conclude that expression of the Na-K-2Cl cotransporter of the TAL is dependent on G(s)alpha-mediated hormone stimulation, most likely due to long-term changes in cellular cAMP levels. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NIH, Bldg 10,10 Ctr Dr,MSC 1603,Rm 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [K01 DK002672] NR 36 TC 32 Z9 32 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 1999 VL 277 IS 2 BP F235 EP F244 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 224WR UT WOS:000081923400010 PM 10444578 ER PT J AU Fernandez-Llama, P Ecelbarger, CA Ware, JA Andrews, P Lee, AJ Turner, R Nielsen, S Knepper, MA AF Fernandez-Llama, P Ecelbarger, CA Ware, JA Andrews, P Lee, AJ Turner, R Nielsen, S Knepper, MA TI Cyclooxygenase inhibitors increase Na-K-2Cl cotransporter abundance in thick ascending limb of Henle's loop SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE urinary concentration mechanism; prostaglandins; indomethacin; diclofenac ID MOLECULAR-CLONING; COLLECTING DUCT; RABBIT KIDNEY; NEPHRON SEGMENTS; BRATTLEBORO RAT; VASOPRESSIN; PROSTAGLANDIN-E2; TRANSPORT; EXPRESSION; EXCRETION AB Cyclooxygenase inhibitors, such as indomethacin and diclofenac, have well-described effects to enhance renal water reabsorption and urinary concentrating ability. Concentrating ability is regulated in part at the level of the thick ascending limb of Henle's loop, where active NaCl absorption drives the countercurrent multiplication mechanism. We used semiquantitative immunoblotting to test the effects of indomethacin and diclofenac, given over a 48-h period, on the expression levels of the ion transporters responsible for active NaCl transport in the thick ascending limb. Both agents strongly increased the expression level of the apical Na-K-2Cl cotransporter in both outer medulla and cortex. Neither agent significantly altered outer medullary expression levels of other thick ascending limb proteins, namely, the type 3 Na/H exchanger (NHE-3), Tamm-Horsfall protein, or alpha 1- or beta 1-subunits of the Na-K-ATPase. Administration of the EP3-selective PGE(2) analog, misoprostol, to indomethacin-treated rats reversed the stimulatory effect of indomethacin on Na-K-2Cl cotransporter expression. We conclude that cyclooxygenase inhibitors enhance urinary concentrating ability in part through effects to increase Na-K-2Cl cotransporter expression in the thick ascending limb of Henle's loop. This action is most likely due to elimination of an EP3-receptor-mediated tonic inhibitory effect of PGE(2) on cAMP production. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Cell Biol, Washington, DC 20007 USA. Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. RP Knepper, MA (reprint author), NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282] NR 39 TC 48 Z9 48 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 1999 VL 277 IS 2 BP F219 EP F226 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 224WR UT WOS:000081923400008 PM 10444576 ER PT J AU Kwon, TH Frokiaer, J Fernandez-Llama, P Maunsbach, AB Knepper, MA Nielsen, S AF Kwon, TH Frokiaer, J Fernandez-Llama, P Maunsbach, AB Knepper, MA Nielsen, S TI Altered expression of Na transporters NHE-3, NaPi-II, Na-K-ATPase, BSC-1, and TSC in CRF rat kidneys SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE fractional excretion of sodium; renal hypertrophy; glomerulotubular imbalance ID THICK ASCENDING LIMB; ISOLATED UREMIC NEPHRON; CL COTRANSPORTER; REMNANT KIDNEY; RENAL-INSUFFICIENCY; FUNCTIONAL PROFILE; MOLECULAR-CLONING; PROXIMAL TUBULE; SODIUM; REABSORPTION AB In chronic renal failure (CRF), reduction in renal mass leads to an increase in the filtration rates of the remaining nephrons and increased excretion of sodium per nephron. To address the mechanisms involved in the increased sodium excretion, we determined the total kidney levels and the densities per nephron of the major renal NaCl transporters in rats with experimental CRF. Two weeks after 5/6 nephrectomy (reducing the total number of nephrons to similar to 24 +/- 8%), the rats were azotemic and displayed increased Na excretion. Semiquantitative immunoblotting revealed significant reduction in the total kidney levels of the proximal tubule Na transporters NHE-3 (48% of control), NaPi-II (13%), and Na-K-ATPase (30%). However, the densities per nephron of NHE-3, NaPi-II, and Na-K-ATPase were not significantly altered in remnant kidneys, despite the extensive hypertrophy of remaining nephrons. Immunocytochemistry confirmed the reduction in NHE-3 and Na-K-ATPase labeling densities in the proximal tubule. In contrast, there was no significant reduction in the total kidney levels of the thick ascending limb and distal convoluted tubule NaCl transporters BSC-1 and TSC, respectively. This corresponded to a 3.6 and 2.5-fold increase in densities per nephron, respectively (confirmed by immunocytochemistry). In conclusion, in this rat CRF model: 1) increased fractional sodium excretion is associated with altered expression of proximal tubule Na transporter expression (NHE-3, NaPi-II, and Na-K-ATPase), consistent with glomerulotubular imbalance in the face of increased single-nephron glomerular filtration rate; and 2) compensatory increases in BSC-1 and TSC expression per nephron occur in distal segments. C1 Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Aarhus Univ Hosp, Dept Clin Physiol, DK-8000 Aarhus, Denmark. Inst Expt Clin Res, DK-8000 Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 56 TC 55 Z9 55 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 1999 VL 277 IS 2 BP F257 EP F270 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 224WR UT WOS:000081923400013 PM 10444581 ER PT J AU Ernst, M Zametkin, AJ Matochik, JA Pascualvaca, D Jons, PH Cohen, RM AF Ernst, M Zametkin, AJ Matochik, JA Pascualvaca, D Jons, PH Cohen, RM TI High midbrain [F-18]DOPA accumulation in children with attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; AMINO-ACID DECARBOXYLASE; FLUID HOMOVANILLIC-ACID; BRAIN METABOLISM; INTRAVENOUS DEXTROAMPHETAMINE; 5-HYDROXYINDOLEACETIC ACID; MONOAMINE METABOLITES; DOPAMINE-RECEPTORS; ADULTS; STRIATUM AB Objective: Attention deficit hyperactivity disorder (ADHD) is a highly prevalent childhood psychiatric disorder characterized by impaired attention, excessive motor activity, and impulsivity. Despite extensive investigation of the neuropathophysiology of ADHD by a wide array of methodologies, the neurobiochemical substrate of this disorder is still unknown. Converging evidence, however, suggests a primary role of the dopaminergic system. Method: This study examined the integrity of presynaptic dopaminergic function in children with ADHD through use of positron emission tomography and the tracer [F-18]fluorodopa ([F-18]DOPA). Accumulation of [F-18]DOPA in synaptic terminals, a measure of dopa decarboxylase activity, was quantified in regions rich in dopaminergic innervation, including caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). Results: Accumulation of [F-18]DOPA in the right midbrain was higher by 48% in 10 children with ADHD than in 10 normal children. Despite its magnitude, this difference would not have reached statistical significance if corrected by the Bonferroni test for multiple comparisons. However, [F-18]DOPA in the right midbrain was correlated with symptom severity. No other dopamine-rich regions significantly differed between groups. Conclusions: These findings are suggestive of dopaminergic dysfunction at the level of the dopaminergic nuclei in children with ADHD. Abnormality in dopa decarboxylase activity may be primary or secondary to deficits in other functional units of the dopamine pathway (e.g., receptor, uptake transporter, vesicular transporter, degradation enzymes). Efforts toward defining the origin of this abnormality should help delineate mechanisms of midbrain control of attention and motor behavior important for the understanding of the causes and treatment of ADHD. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIMH, Psychol & Psychopathol Lab, Bethesda, MD 20892 USA. Natl Inst Drug Abuse, Neuroimaging Branch, Baltimore, MD USA. RP Ernst, M (reprint author), NIH, Bldg 36,Rm 1A05,36 Convent Dr,MSC 4030, Bethesda, MD 20892 USA. NR 53 TC 165 Z9 167 U1 1 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1999 VL 156 IS 8 BP 1209 EP 1215 PG 7 WC Psychiatry SC Psychiatry GA 224WQ UT WOS:000081923300013 PM 10450262 ER PT J AU Mills, JL AF Mills, JL TI Heinz Berendes, 1925-1999 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 NICHHD, Pediat Epidemiol Sect, NIH, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NICHHD, Pediat Epidemiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1999 VL 89 IS 8 BP 1156 EP 1157 DI 10.2105/AJPH.89.8.1156 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 220CL UT WOS:000081646900003 ER PT J AU Marcus, PM Baird, DD Millikan, RC Moorman, PG Qaqish, B Newman, B AF Marcus, PM Baird, DD Millikan, RC Moorman, PG Qaqish, B Newman, B TI Adolescent reproductive events and subsequent breast cancer risk SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INDUCED-ABORTION; EPIDEMIOLOGY; INVOLUTION; APOPTOSIS; PATHWAYS; WOMEN AB Objectives rs. This study investigated the relationship between reproductive events during adolescence and subsequent breast cancer risk. Methods. Logistic regression models used self-reported data from 862 case patients slid 790 controls in the Carolina Breast Cancer Study. Results. Miscarriage induced abortion, and full-term pregnancy before 20 years of age were not associated with breast cancer. Among premenopausal women breast-feeding before 20 years of age was inversely associated with disease. Oral contraceptive rase before 18 years of age was positively associated with disease risk among African American women only. Conclusions. Pregnancy during adolescence does not appear to influence breast cancer risk, but breast-feeding may. A possible increased breast cancer risk; among Africas American women who used oral contraceptives as adolescents warrants further study. C1 NCI, Div Canc Prevent, Biometry Branch, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Marcus, PM (reprint author), NCI, Div Canc Prevent, Biometry Branch, Execut Plaza N,Suite 344,6130 Execut Blvd,MSC 735, Bethesda, MD 20892 USA. OI Baird, Donna/0000-0002-5544-2653 FU NCI NIH HHS [P50-CA58223, R25-CA57726, T32-CA09330] NR 23 TC 20 Z9 21 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1999 VL 89 IS 8 BP 1244 EP 1247 DI 10.2105/AJPH.89.8.1244 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 220CL UT WOS:000081646900022 PM 10432916 ER PT J AU Beaty, MW Kumar, S Sorbara, L Miller, K Raffeld, M Jaffe, ES AF Beaty, MW Kumar, S Sorbara, L Miller, K Raffeld, M Jaffe, ES TI A biphenotypic human herpesvirus 8-associated primary bowel lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID AIDS-RELATED LYMPHOMAS; T-CELL C1 NIAID, Pathol Lab, NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Beaty, MW (reprint author), NIAID, Pathol Lab, NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 36 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1999 VL 23 IS 8 BP 992 EP 994 DI 10.1097/00000478-199908000-00023 PG 3 WC Pathology; Surgery SC Pathology; Surgery GA 221RQ UT WOS:000081740400021 PM 10435572 ER PT J AU Kabrane-Lazizi, Y Fine, JB Elm, J Glass, GE Higa, H Diwan, A Gibbs, CJ Meng, XJ Emerson, SU Purcell, RH AF Kabrane-Lazizi, Y Fine, JB Elm, J Glass, GE Higa, H Diwan, A Gibbs, CJ Meng, XJ Emerson, SU Purcell, RH TI Evidence for widespread infection of wild rats with hepatitis E virus in the United States SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NON-B HEPATITIS; RHESUS-MONKEYS; NON-A; ANTIBODY; SWINE; HEV; SEROREACTIVITY; PREVALENCE; DISEASE; PIGS AB Hepatitis E is an important medical pathogen in many developing countries but is rarely reported from the United States, although antibody to hepatitis E virus (anti-HEV) is found in > 1% of U.S. citizens. Zoonotic spread of the virus is suspected. Sera obtained from 239 wild rats trapped in widely separated regions of the United States were tested for anti-HEV. Seventy-seven percent of rats from Maryland, 90% from Hawaii, and 44% from Louisiana were seropositive for anti-HEV. Rats from urban as well as rural areas were seropositive and the prevalence of anti-HEV Ige increased in parallel with the estimated age of the rats, leading to speculation that they might be involved in the puzzling high prevalence of anti-HEV among some U.S. city dwellers. The discovery of anti-HEV in rats in the United States and the recently reported discovery that HEV is endemic in U.S. swine raise many questions about transmission, reservoirs, and strains of HEV in developed countries. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. John A Burns Sch Med, Dept Trop Med, Honolulu, HI USA. Dept Hlth, Honolulu, HI USA. NINDS, Lab Cent Nervous Syst Disorders, NIH, Bethesda, MD 20892 USA. Virginia Polytech Inst & State Univ, Ctr Mol Med & Infect Dis, Dept Biochem Sci & Pathobiol, Blacksburg, VA 24061 USA. RP Kabrane-Lazizi, Y (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 26 TC 159 Z9 169 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD AUG PY 1999 VL 61 IS 2 BP 331 EP 335 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 227VQ UT WOS:000082101000028 PM 10463689 ER PT J AU Schuck, P AF Schuck, P TI Sedimentation equilibrium analysis of interference optical data by systematic noise decomposition SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE sedimentation velocity; Lamm equation; hydrodynamics; time-invariant noise; analytical ultracentrifugation; molecular interactions ID RAPID PRECISION INTERFEROMETRY; ANALYTICAL ULTRACENTRIFUGATION; RECEPTOR; TIME AB An analytical method is described for removal of systematic signal offsets from interference optical data of sedimentation equilibrium gradients. It is demonstrated that the time-invariant signal contributions can be extracted from hydrodynamic modeling of interference profiles acquired during the approach to sedimentation equilibrium. This method is based on a technique for the explicit algebraic calculation of time-invariant noise components from sedimentation data, recently described for the direct modeling of sedimentation velocity experiments (P. Schuck and B. Demeler, Biophys. J. 76, 2288-2296, 1999). The calculated systematic signal offset is very well defined by the experimental data, stable over time, and its calculation is robust and to a large extent independent of the hydrodynamic model. The calculated time-invariant signal can be used to reduce the systematic errors in the measured sedimentation equilibrium profiles by more than an order of magnitude. It is shown that the resulting net equilibrium fringe profiles after subtraction of the time-invariant noise component allow equilibrium analyses consistent with those obtained from absorbance profiles. However, due to a higher dynamic range and the higher number of data points, the parameters derived from the net interference analysis can exhibit significantly improved precision. The presented study demonstrates the feasibility and potential of this analytical method for full exploitation of the remarkable precision of the interference optical data acquisition system, allowing sedimentation equilibrium experiments at loading concentrations below 0.05 mg/ml. C1 NIH, Bioengn & Phys Sci Program, ORS, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, Bioengn & Phys Sci Program, ORS, Bldg 10, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 35 TC 22 Z9 23 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 1999 VL 272 IS 2 BP 199 EP 208 DI 10.1006/abio.1999.4172 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 222CX UT WOS:000081766800011 PM 10415089 ER PT J AU Rezende, MM Herbert, B Kirk, KL Gong, YF Kimoto, H AF Rezende, MM Herbert, B Kirk, KL Gong, YF Kimoto, H TI Crystal structure of 9-benzyl-2-fluoroadenine SO ANALYTICAL SCIENCES LA English DT Article ID PURINE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Natl Ind Res Inst Nagoya, Kita Ku, Nagoya, Aichi 4628510, Japan. RP Rezende, MM (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU JAPAN SOC ANALYTICAL CHEM PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO, 141, JAPAN SN 0910-6340 J9 ANAL SCI JI Anal. Sci. PD AUG PY 1999 VL 15 IS 8 BP 819 EP 820 DI 10.2116/analsci.15.819 PG 2 WC Chemistry, Analytical SC Chemistry GA 223XM UT WOS:000081866900022 ER PT J AU Sun, HS Yerle, M Pinton, P Chardon, P Rogel-Gaillard, C Lyons, LA Laughlin, TF Tuggle, CK AF Sun, HS Yerle, M Pinton, P Chardon, P Rogel-Gaillard, C Lyons, LA Laughlin, TF Tuggle, CK TI Physical assignments of human chromosome 13 genes on pig chromosome 11 demonstrate extensive synteny and gene order conservation between pig and human SO ANIMAL GENETICS LA English DT Article DE pig; comparative map; physical mapping; SSC11 ID CELL HYBRID PANEL; INSITU HYBRIDIZATION; BOVINE CHROMOSOME-12; HUMAN GENOMES; LINKAGE MAP; ZOO-FISH; PORCINE; SEQUENCES; PROGRAM; REVEALS AB Previous mapping between the human and pig genomes suggested extensive conservation of human chromosome 13 (HSA13) to pig chromosome 11 (SSC11). The objectives of this study were comparative gene mapping of pig homologs of HSA13 genes and examining gene order within this conserved synteny group by physical assignment of each locus. A detailed HSA13 to SSC11 comparison was chosen since the comparative gene map is not well developed for these chromosomes and a rearranged gene order within conserved synteny groups was observed from the comparison between HSA13 and bovine chromosome 12 (BTA12). Heterologous primers for PCR were designed and used to amplify pig homologous fragments. The pig fragments were sequenced to confirm the homology. Six pig STSs (FLT1, ESD, RB1, HTR2A, EDNRB, and F10) were physically mapped using a somatic cell hybrid panel to Department of Animal SSC11, and fluorescent in situ hybridization (FISH) mapping was also applied to improve map resolution and determine gene order. Results from this study increase the comparative information available on SSC11 and suggest a conserved gene order on SSC11 and HSA13, in Department of Animal contrast to human:bovine comparisons of this syntenic group. C1 Iowa State Univ, Dept Anim Sci, Ames, IA 50011 USA. INRA, Lab Genet Cellulaire, F-31326 Castanet Tolosan, France. NCI, Lab Genomic Divers, Bethesda, MD 20892 USA. NCI, FCRDC, Biol Carcinogenesis & Dev Program, SAIC Frederick, Bethesda, MD 20892 USA. RP Tuggle, CK (reprint author), Iowa State Univ, Dept Anim Sci, Ames, IA 50011 USA. NR 28 TC 10 Z9 13 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD AUG PY 1999 VL 30 IS 4 BP 304 EP 308 DI 10.1046/j.1365-2052.1999.00474.x PG 5 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA 230KY UT WOS:000082251400009 PM 10467706 ER PT J AU Brooks, EA AF Brooks, EA TI Probabilistic methods for a linear reaction-hyperbolic system with constant coefficients SO ANNALS OF APPLIED PROBABILITY LA English DT Article DE hyperbolic equations; stochastic processes; traveling waves; renewal theory; central limit theorem ID FAST AXONAL-TRANSPORT; EQUATIONS AB Linear reaction-hyperbolic systems of partial differential equations in one space dimension arise in the study of the physiological process by which materials are transported in nerve cell axons. Probabilistic methods are developed to derive a closed form approximate solution for an initial-boundary value problem of such a system. The approximate solution obtained is a translating solution of a heat equation. An estimate is proved giving the deviation of this approximate traveling wave solution from the exact solution. C1 Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Brooks, EA (reprint author), Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Anal, POB 12233, Res Triangle Pk, NC 27709 USA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 7, 3401 INVESTMENT BLVD, HAYWARD, CA 94545 USA SN 1050-5164 J9 ANN APPL PROBAB JI Ann. Appl. Probab. PD AUG PY 1999 VL 9 IS 3 BP 719 EP 731 PG 13 WC Statistics & Probability SC Mathematics GA 264CJ UT WOS:000084162200008 ER PT J AU McFarland, HF AF McFarland, HF TI The path to damage in multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID DEMYELINATION; ANTIBODY C1 NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), NIH, Neuroimmunol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1999 VL 46 IS 2 BP 141 EP 142 DI 10.1002/1531-8249(199908)46:2<141::AID-ANA1>3.0.CO;2-Z PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 224BU UT WOS:000081876900001 PM 10443877 ER PT J AU Parchi, P Giese, A Capellari, S Brown, P Schulz-Schaeffer, W Windl, O Zerr, I Budka, H Kopp, N Piccardo, P Poser, S Rojiani, A Streichemberger, N Julien, J Vital, C Ghetti, B Gambetti, P Kretzschmar, H AF Parchi, P Giese, A Capellari, S Brown, P Schulz-Schaeffer, W Windl, O Zerr, I Budka, H Kopp, N Piccardo, P Poser, S Rojiani, A Streichemberger, N Julien, J Vital, C Ghetti, B Gambetti, P Kretzschmar, H TI Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects SO ANNALS OF NEUROLOGY LA English DT Article ID PRION PROTEIN GENE; SPONGIFORM ENCEPHALOPATHY; DIAGNOSTIC-CRITERIA; STRAIN VARIATION; NERVOUS-SYSTEM; SCRAPIE PRION; VARIANT CJD; PRP 27-30; AGENT; POLYMORPHISM AB Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrPSc) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrPSc properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrPSc deposition. Seventy percent of subjects showed the classic CJD phenotype, PrPSc type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrPSc type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were Linked to PrPSc type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrPSc type 1 and valine homozygosity, The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrPSc in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants. C1 Case Western Reserve Univ, Inst Pathol, Div Neuropathol, Cleveland, OH 44106 USA. Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany. Univ Gottingen, Dept Neuropathol, D-3400 Gottingen, Germany. NINDS, Lab CNS Studies, NIH, Bethesda, MD 20892 USA. Univ Vienna, Inst Neurol, Vienna, Austria. Austrian Reference Ctr Human Prion Dis, Vienna, Austria. Hop Neurol Pierre Wertheimer, Lyon, France. CHU Bordeaux, Dept Neurol, Pessac, France. CHU Bordeaux, Dept Pathol, Pessac, France. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. Univ S Florida, Dept Pathol, Tampa, FL USA. RP Parchi, P (reprint author), Case Western Reserve Univ, Inst Pathol, Div Neuropathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. RI Giese, Armin/F-3271-2010; Windl, Otto/C-6760-2011; capellari, sabina/F-5545-2012; Parchi, Piero/L-9833-2015; OI Giese, Armin/0000-0002-8238-4102; Parchi, Piero/0000-0002-9444-9524; Budka, Herbert/0000-0002-1933-1577 FU NIA NIH HHS [AG08992, AG08155, AG10133] NR 44 TC 758 Z9 779 U1 2 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1999 VL 46 IS 2 BP 224 EP 233 DI 10.1002/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 224BU UT WOS:000081876900012 PM 10443888 ER PT J AU Lieberman, AP Trojanowski, JQ Leonard, DGB Chen, KL Barnett, JL Leverenz, JB Bird, TD Robitaille, Y Malandrini, A Fischbeck, KH AF Lieberman, AP Trojanowski, JQ Leonard, DGB Chen, KL Barnett, JL Leverenz, JB Bird, TD Robitaille, Y Malandrini, A Fischbeck, KH TI Ataxin 1 and ataxin 3 in neuronal intranuclear inclusion disease SO ANNALS OF NEUROLOGY LA English DT Article ID MACHADO-JOSEPH-DISEASE; SPINOCEREBELLAR ATAXIA; TRANSGENIC MICE; RECTAL BIOPSY; PROTEIN; LOCALIZATION; GENE; ABNORMALITIES; AGGREGATION; EXPANSIONS AB Neuronal intranuclear inclusion disease (NIID) Is a multisystem neurodegenerative disorder characterized by large intranuclear aggregates in neurons of the central and peripheral nervous system. These ubiquitinated intranuclear inclusions are morphologically similar to the intraneuronal aggregates that have been identified in the CAG/polyglutamine expansion diseases. As rare aggregates in NIID contain a polyglutamine epitope, we further investigated the relationship between this disease and the CAG/polyglutamine expansion diseases. Here, we show that ataxin 1 and ataxin 3 proteins are recruited into aggregates in NIID in the absence of a CAG expansion in the SCA1 and SCA3 genes. These data support an association of NIID with the polyglutamine disorders and provide evidence of in vivo recruitment of proteins with polyglutamine tracts into intraneuronal aggregates. C1 NINDS, Neurogenet Branch, DIR, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Michigan Hosp, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. Univ Washington, Sch Med, Dept Behav Sci, Seattle, WA USA. Vet Affairs Med Ctr, Geriatr Res Serv, Seattle, WA 98108 USA. Univ Montreal, Dept Pathol, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Neurosurg, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Neurol, Montreal, PQ H3A 2T5, Canada. Univ Siena, Inst Neurol Sci, I-53100 Siena, Italy. RP Lieberman, AP (reprint author), NINDS, Neurogenet Branch, DIR, NIH, Bldg 10,Room 3B14,10 Ctr Dr,MSC 1250, Bethesda, MD 20892 USA. NR 17 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1999 VL 46 IS 2 BP 271 EP 273 DI 10.1002/1531-8249(199908)46:2<271::AID-ANA21>3.0.CO;2-M PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 224BU UT WOS:000081876900021 PM 10443897 ER PT J AU Dosemeci, M AF Dosemeci, M TI Retrospective exposure assessment in large occupational cohort studies in China: Advantages and concerns SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Editorial Material ID WORKERS; SILICA; BENZENE C1 NCI, Occupat Epidemiol Branch, Rockville, MD 20852 USA. RP Dosemeci, M (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd, Rockville, MD 20852 USA. NR 14 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD AUG PY 1999 VL 43 IS 6 BP 377 EP 379 PG 3 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 241RU UT WOS:000082897000001 PM 10518463 ER PT J AU Izbicka, E Nishioka, D Marcell, V Raymond, E Davidson, KK Lawrence, RA Wheelhouse, RT Hurley, LH Wu, RS Von Hoff, DD AF Izbicka, E Nishioka, D Marcell, V Raymond, E Davidson, KK Lawrence, RA Wheelhouse, RT Hurley, LH Wu, RS Von Hoff, DD TI Telomere-interactive agents affect proliferation rates and induce chromosomal destabilization in sea urchin embryos SO ANTI-CANCER DRUG DESIGN LA English DT Article DE G quadruplex; porphyrin; sea urchin; telomerase; telomere ID QUADRUPLEX DNA; CELLS; INHIBITION; CANCER; TARGET; APHIDICOLIN; SEPARATION; EGGS AB Cationic porphyrins, which interact with guanine quadruplex (G4) telomeric folds, inhibit telomerase activity in human tumor cells. In this study, we have further examined effects of porphyrins and other telomere- and telomerase-interactive agents on proliferation rates and chromosome stability in a novel in vivo model, developing sea urchin embryos. We studied two porphyrins: (i) TMPyP4, a potent telomerase inhibitor;. and (ii) TMPyP2, an isomer of TMPyP4 and an inefficient telomerase inhibitor, azidothymine (AZT), the reverse transcriptase inhibitor antisense phosphorothioate oligonucleotide to telomerase RNA (TAG6) and a control scrambled sequence (ODN). TMPyP4, AZT and TAG6 (but not TMPyP2 or ODN) decreased the rates of cell proliferation and increased the percentage of cells trapped in mitosis. Nuclear localization of TAG6, but not of ODN, was demonstrated with 5'-fluoresceinated analogs of TAG6 and ODN, Formation of elongated chromosomes incapable of separating in anaphase, induced by TMPyP4, AZT and TAG6, closely resembled phenotypes resulting from telomerase template mutation or dominant negative TRF2 allele, Our data suggest that G4-interactive agents exert their antiproliferative effects via chromosomal destabilization and warrant their further development as valuable anticancer tools. C1 Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Univ Texas, Coll Pharm, Drug Dynam Inst, Austin, TX 78712 USA. NIH, Bethesda, MD 20892 USA. RP Izbicka, E (reprint author), Inst Drug Dev, Canc Therapy & Res Ctr, 7979 Wurzbach Rd,Suite 337, San Antonio, TX 78229 USA. RI Wheelhouse, Richard/B-2519-2009 OI Wheelhouse, Richard/0000-0002-2250-3384 FU NCI NIH HHS [CA67760] NR 36 TC 61 Z9 64 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD AUG PY 1999 VL 14 IS 4 BP 355 EP 365 PG 11 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA 264CF UT WOS:000084161900006 PM 10625928 ER PT J AU Buckheit, RW White, EL Fliakas-Boltz, V Russell, J Stup, TL Kinjerski, TL Osterling, MC Weigand, A Bader, JP AF Buckheit, RW White, EL Fliakas-Boltz, V Russell, J Stup, TL Kinjerski, TL Osterling, MC Weigand, A Bader, JP TI Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID OXATHIIN CARBOXANILIDE; NUCLEOSIDE ANALOGS; ANTIVIRAL ACTIVITY; TYPE-1; RESISTANCE; DRUG; DERIVATIVES; 5'-TRIPHOSPHATES; COMBINATIONS; SENSITIVITY AB (+)-Calanolide A (NSC 650886) has previously been reported to be a unique and specific nonnucleoside inhibitor of the reverse transcriptase (RT) of human immunodeficiency virus (HIV) type 1 (HIV-1) (M. J. Currens et al., J. Pharmacol. Exp. Ther., 279:645-651, 1996). Two isomers of calanolide A, (-)-calanolide B (NSC 661122; costatolide) and (-)-dihydrocalanolide B (NSC 661123; dihydrocostatolide), possess antiviral properties similar to those of calanolide A. Each of these three compounds possesses the phenotypic properties ascribed to the pharmacologic class of nonnucleoside RT inhibitors (NNRTIs). The calanolide analogs, however, exhibit 10-fold enhanced antiviral activity against drug-resistant viruses that bear the most prevalent NNRTI resistance that is engendered by amino acid change Y181C in the RT. Further enhancement of activity is observed with RTs that possess the Y181C change together with mutations that yield resistance to AZT. In addition, enzymatic inhibition assays have demonstrated that the compounds inhibit RT through a mechanism that affects both the K-m for dTTP and the V-max, i.e., mixed-type inhibition. In fresh human cells, costatolide and dihydrocostatolide are highly effective inhibitors of low-passage clinical virus strains, including those representative of the various HIV-1 clade strains, syncytium-inducing and non-syncytium-inducing isolates, and T-tropic and monocyte-tropic isolates. Similar to calanolide A, decreased activities of the two isomers were observed against viruses and RTs with amino acid changes at residues L100, K103, T139, and Y188 in the RT, although costatolide exhibited a smaller loss of activity against many of these NNRTI-resistant isolates. Comparison of cross-resistance data obtained with a panel of NNRTI-resistant virus strains suggests that each of the three stereoisomers may interact differently with the RT, despite their high degree of structural similarity. Selection of viruses resistant to each of the three compounds in a variety of cell lines yielded viruses with T139I, L100I, Y188H, or L187F amino acid changes in the RT. Similarly, a variety of resistant virus strains with different amino acid changes were selected in cell culture when the calanolide analogs were used in combination with other active anti-HIV agents, including nucleoside and nonnucleoside RT and protease inhibitors. In assays with combinations of anti-HIV agents, costatolide exhibited synergy with these anti-HIV agents. The calanolide isomers represent a novel and distinct subgroup of the NNRTI family, and these data suggest that a compound of the calanolide A series, such as costatolide, should be evaluated further for therapeutic use in combination with other anti-HIV agents. C1 Serquest So Res Inst, Infect Dis Res Dept, Frederick, MD 21701 USA. So Res Inst, Dept Biochem, Birmingham, AL 35205 USA. NCI, Dev Therapeut Program, Div Canc Treatment Diag & Ctr, Bethesda, MD 20892 USA. RP Buckheit, RW (reprint author), Serquest So Res Inst, Infect Dis Res Dept, 431 Aviat Way, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CM-37818] NR 31 TC 38 Z9 40 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1999 VL 43 IS 8 BP 1827 EP 1834 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 222MK UT WOS:000081789200002 PM 10428899 ER PT J AU Mondon, P Petter, R Amalfitano, G Luzzati, R Concia, E Polacheck, I Kwon-Chung, KJ AF Mondon, P Petter, R Amalfitano, G Luzzati, R Concia, E Polacheck, I Kwon-Chung, KJ TI Heteroresistance to fluconazole and voriconazole in Cryptococcus neoformans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; METHICILLIN RESISTANCE; CANDIDA-ALBICANS; DRUG-RESISTANCE; AIDS PATIENTS; MENINGITIS; SUSCEPTIBILITY; GENE; PERSISTENCE; STRAINS AB Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates fi om an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, greater than or equal to 64 mu g/ml) were recovered at a variable frequency (7 x 10(-3) to 4.6 x 10(-2)), Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point, For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 mu g/ml) and voriconazole (1 mu g/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 mu g/ml) and moderately resistant to voriconazole (1 mu g/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35 degrees C and was completely abolished at 40 degrees C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens. C1 NIAID, Clin Invest Lab, MMS, NIH, Bethesda, MD 20892 USA. Univ Hosp Verona, Verona, Italy. Hadassah Med Ctr, IL-91120 Jerusalem, Israel. RP Kwon-Chung, KJ (reprint author), NIAID, Clin Invest Lab, MMS, NIH, Bldg 10,11C304, Bethesda, MD 20892 USA. NR 34 TC 58 Z9 61 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1999 VL 43 IS 8 BP 1856 EP 1861 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 222MK UT WOS:000081789200005 PM 10428902 ER PT J AU Cho-Chung, YS Beaucag, S Marquez, V Neckers, L Torrence, PF AF Cho-Chung, YS Beaucag, S Marquez, V Neckers, L Torrence, PF TI Abstracts from the Third Annual NIH Symposium on Therapeutic Oligonucleotides: Discovery and Milestone Achievements - December 4, 1998 - Bethesda, Maryland SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Editorial Material C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Med Chem Lab, DBS, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Sect, Med Branch, DCS, Rockville, MD 20850 USA. NIDDK, Biomed Chem Sect, Med Chem Lab, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bldg 10,Room 5B05,10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 1999 VL 9 IS 4 BP 359 EP 359 DI 10.1089/oli.1.1999.9.359 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 226RR UT WOS:000082035800005 ER PT J AU Cho-Chung, YS Nesterova, M Park, YG Lee, YN AF Cho-Chung, YS Nesterova, M Park, YG Lee, YN TI Protein kinase A-RI alpha antisense: Antitumor mechanism of action SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 3rd Annual NIH Symposium on Therapeutic Oligonucleotides - Discovery and Milestone Achievements CY DEC 04, 1998 CL BETHESDA, MARYLAND SP NIH ID RII(BETA) REGULATORY SUBUNIT; HL-60 LEUKEMIA-CELLS; CATALYTIC SUBUNIT; CYCLIC-AMP; MOLECULAR-CLONING; GROWTH-INHIBITION; MESSENGER-RNA; HUMAN TESTIS; DIFFERENTIATION; OLIGODEOXYNUCLEOTIDE C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 1999 VL 9 IS 4 BP 383 EP 388 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 226RR UT WOS:000082035800011 ER PT J AU Silverman, RH Cowell, JK Torrence, PF AF Silverman, RH Cowell, JK Torrence, PF TI 2 ',5 '-oligoadenylate-antisense chimeras as experimental therapeutic agents for cancer and viral infections SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 3rd Annual NIH Symposium on Therapeutic Oligonucleotides - Discovery and Milestone Achievements CY DEC 04, 1998 CL BETHESDA, MARYLAND SP NIH ID RESPIRATORY SYNCYTIAL VIRUS; TARGETING RNA; MESSENGER-RNA; ANTISENSE; 2-5A; TELOMERASE; CELLS; DEGRADATION C1 Cleveland Clin Fdn, Dept Canc Biol, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Ctr Mol Genet, Lerner Res Inst, Cleveland, OH 44195 USA. NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Silverman, RH (reprint author), Cleveland Clin Fdn, Dept Canc Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. OI Cowell, John/0000-0002-2079-5950 NR 22 TC 1 Z9 1 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 1999 VL 9 IS 4 BP 409 EP 414 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 226RR UT WOS:000082035800016 ER PT J AU Marquez, VE Goddard, A Alvarez, E Ford, H Christman, JK Sheikhnejad, G Brank, A Marasco, CJ Suffrin, JR O'Gara, M Cheng, X AF Marquez, VE Goddard, A Alvarez, E Ford, H Christman, JK Sheikhnejad, G Brank, A Marasco, CJ Suffrin, JR O'Gara, M Cheng, X TI Oligonucleotides containing 5,6-dihydro-5-azacytosine at CpG sites can produce potent inhibition of DNA cytosine-C5-methyltransferase without covalently binding to the enzyme SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 3rd Annual NIH Symposium on Therapeutic Oligonucleotides - Discovery and Milestone Achievements CY DEC 04, 1998 CL BETHESDA, MARYLAND SP NIH ID CYTOSINE METHYLTRANSFERASES; CYTIDINE DEAMINASE; TRANSITION-STATE; MAMMALIAN-CELLS; METHYLATION; 5-AZA-2'-DEOXYCYTIDINE; 5-AZACYTIDINE; CANCER; BASE; DIFFERENTIATION C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Roswell Pk Canc Inst, Grace Canc Drug Ctr, Buffalo, NY 14263 USA. Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30329 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C-02,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 1999 VL 9 IS 4 BP 415 EP 421 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 226RR UT WOS:000082035800017 ER PT J AU Kamitani, H Ikawa, H Hsi, LC Watanabe, T DuBois, RN Eling, TE AF Kamitani, H Ikawa, H Hsi, LC Watanabe, T DuBois, RN Eling, TE TI Regulation of 12-lipoxygenase in rat intestinal epithelial cells during differentiation and apoptosis induced by sodium butyrate SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE 12-lipoxygenase; cell differentiation; NDGA; sodium butyrate; alkaline phosphatase ID POLYUNSATURATED FATTY-ACIDS; ARACHIDONATE 12-LIPOXYGENASE; COLON-CANCER; PPAR-GAMMA; EXPRESSION; RECEPTOR; LINE; CDNA; 15-LIPOXYGENASE; METABOLITE AB We evaluated the expression and activity of rat 12-lipoxygenase (LO) in rat intestinal epithelial (RIE) cells during apoptosis and cell differentiation. Sodium butyrate (NaBT) treatment induced wildtype RIE (W-RIE) cells to undergo differentiation and apoptosis. Alkaline phosphatase (ALP) activity, a marker of cell differentiation, and DNA fragmentation, an index of apoptosis, were increased by NaBT treatment. Arachidonic acid was metabolized primarily to 12-hydroxyeicosatetraenoic acid (HETE) suggesting induction of 12-LO activity. In contrast, sense-RIE (S-RIE) cells engineered to overexpress COX-2 were resistant to apoptosis by treatment with 5 mM NaBT and NaBT did not induce 12-LO activity, The upregulation of 12-LO expression by NaBT in W-RIE cells was confirmed at both the transcriptional and translational level but 12-LO was undetectable in S-RIE cells following NaBT treatment. The expression of 12-LO mRNA in W-RIE cells occurs as early as 6 h after treatment and reaches maximum expression at 24 h following treatment. This inducible 12-LO was isolated by RT-PCR and identified as rat "leukocyte-type" 12-LO. The level of 12-LO expression in W-RIE cells was dependent on the concentration of NaBT and appears to reflect the extent of cell differentiation. NDGA, a lipoxygenase inhibitor, attenuated induction of ALP activity by NaBT treatment of W-RIE cells. These observations suggested that 12-LO is regulated by treatment with NaBT and is associated with cell differentiation in rat intestinal epithelial cells. (C) 1999 Academic Press. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Tottori Univ, Sch Med, Inst Neurol Sci, Div Neurosurg, Yonago, Tottori 683, Japan. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vet Affairs Med Ctr, Nashville, TN 37232 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 40 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 1999 VL 368 IS 1 BP 45 EP 55 DI 10.1006/abbi.1999.1284 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 223JK UT WOS:000081837800007 PM 10415110 ER PT J AU Luke, MC Darling, TN Hsu, R Summers, RM Smith, JA Solomon, BI Thomas, GR Yancey, KB AF Luke, MC Darling, TN Hsu, R Summers, RM Smith, JA Solomon, BI Thomas, GR Yancey, KB TI Mucosal morbidity in patients with epidermolysis bullosa acquisita SO ARCHIVES OF DERMATOLOGY LA English DT Article ID VII-COLLAGEN; UPPER AIRWAY; VIRTUAL BRONCHOSCOPY; CLINICAL-ASSESSMENT; SKIN; DISEASE; AUTOANTIBODIES; IDENTIFICATION; ANTIGEN; PEROXIDASE AB Background: Epidermolysis bullosa acquisita is an acquired inflammatory and/or dermolytic subepidermal blistering disease characterized by IgG autoantibodies to type VII collagen. Four patients with documented epidermolysis bullosa acquisita were evaluated by a multidisciplinary team of care providers (4 dermatologists, an ophthalmologist, a radiologist, a voice and speech specialist, and an otolaryngologist) for 1 to 5 years to characterize mucosal involvement and its complications and response to treatment. Patients were evaluated clinically and by slitlamp examinations, endoscopies, computed tomographic scans, and videofluorographic swallowing studies. Spiral computed tomographic scans for virtual endoscopy were used for the nontraumatic evaluation of airways in 2 patients with respiratory tract compromise. Observations: Involvement of 5 or more mucosal sites-mouth, nose, conjunctiva, pharynx, and larynx-was documented in all patients. Complications included ankyloglossia, periodontal disease, scarring and crusting of nasal mucosa, symblepharon formation, obstruction of nasolacrimal ducts, deformation of the epiglottis, impaired phonation, dysphagia, esophageal strictures, and supraglottic stenosis requiring emergency tracheostomy. Conclusions: Epidermolysis bullosa acquisita may extensively (or predominantly) affect mucosal epithelia in a manner resembling cicatricial pemphigoid. Mucosal disease in these patients is often subclinical, can lead to serious complications, and is best managed using a multidisciplinary approach. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NEI, Dept Diagnost Radiol, Ctr Clin, NIH, Bethesda, MD 20892 USA. NEI, Dept Rehabil Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Neck Surg Branch, Tumor Biol Sect, NIH, Bethesda, MD USA. RP Yancey, KB (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. OI Darling, Thomas/0000-0002-5161-1974 NR 28 TC 32 Z9 32 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 1999 VL 135 IS 8 BP 954 EP 959 DI 10.1001/archderm.135.8.954 PG 6 WC Dermatology SC Dermatology GA 225VR UT WOS:000081987100011 PM 10456345 ER PT J AU Miller, FG Pickar, D Rosenstein, DL AF Miller, FG Pickar, D Rosenstein, DL TI Addressing ethical issues in the psychiatric research literature SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter C1 Univ Virginia, Charlottesville, VA 22903 USA. NIMH, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), Univ Virginia, Charlottesville, VA 22903 USA. NR 11 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1999 VL 56 IS 8 BP 763 EP 764 DI 10.1001/archpsyc.56.8.763 PG 2 WC Psychiatry SC Psychiatry GA 221JX UT WOS:000081724900015 PM 10435612 ER PT J AU Tomaski, SM Zalzal, GH AF Tomaski, SM Zalzal, GH TI In vitro regulation of expression of cartilage-derived morphogenetic proteins by growth hormone and insulinlike growth factor 1 in the bovine cricoid chondrocyte SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 14-16, 1997 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediat Otolaryngol ID FACTOR-BETA SUPERFAMILY; FACTOR-I; LARYNGOTRACHEAL RECONSTRUCTION; BONE DIFFERENTIATION; OSTEOGENIN; MEMBERS; GRAFTS AB Objectives: To delineate the endogenous growth factors that regulate cricoid cartilage growth at the molecular level. Specifically, to attempt to establish the presence of cartilage-derived morphogenetic proteins (CDMPs), cartilage-specific members of the bone morphogenetic protein family, in newborn bovine cricoid chondrocytes and to assess the expression of these endogenous growth factors with the addition of exogenous growth hormone or insulinlike growth factor 1 in an in vitro chondrocyte culture model. Methods and Design: Basic science molecular biologic research methods, including high-density monolayer and explant chondrocyte cultures with extraction of messenger RNA and quantitation via Northern blot hybridization via radiolabeled complementary DNA probes. Setting: Intramural basic science research laboratory. Results: Both CDMP-1 and CDMP-2 were found in newborn cricoid chondrocytes. Addition of exogenous growth hormone did not appear to influence the expression of CDMP-1 or CDMP-2. Addition of exogenous insulinlike growth factor 1 appeared to down-regulate the expression of CDMP-1 but had no effect on the expression of CDMP-2. No major differences in CDMP level of expression were no ted between high-density monolayer cultures vs explant cultures. No tissue specificity differences were noted in regulation of CDMPs between cricoid and articular chondrocytes. Conclusions: Our preliminary studies indicate the presence of endogenous morphogenetic proteins in newborn bovine cricoid chondrocytes. These novel polypeptide hormones (CDMP-1 and CDMP-2) have not been previously reported in laryngeal cartilage chondrocytes. Change in level of transcription of these morphogenetic proteins under various in vitro conditions suggests that these proteins are subject to regulation and/or play a regulatory role in cricoid chondrocyte growth and differentiation. Further experimentation is needed to confirm these findings. C1 Childrens Natl Med Ctr, Dept Pediat Otolaryngol, Washington, DC 20010 USA. NIDR, Craniofacial & Skeletal Res Branch, NIH, Bethesda, MD 20892 USA. RP Zalzal, GH (reprint author), Childrens Natl Med Ctr, Dept Pediat Otolaryngol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 34 TC 5 Z9 7 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 1999 VL 125 IS 8 BP 901 EP 906 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 224LV UT WOS:000081901300011 PM 10448738 ER PT J AU El-Gabalawy, HS Goldbach-Mansky, R Smith, D Arayssi, T Bale, S Gulko, P Yarboro, C Wilder, RL Klippel, JH Schumacher, HR AF El-Gabalawy, HS Goldbach-Mansky, R Smith, D Arayssi, T Bale, S Gulko, P Yarboro, C Wilder, RL Klippel, JH Schumacher, HR TI Association of HLA alleles and clinical features in patients with synovitis of recent onset SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SYSTEMIC LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; EARLY RHEUMATOID-ARTHRITIS; SHARED EPITOPE HYPOTHESIS; LINKAGE DISEQUILIBRIUM; AUTOIMMUNE-DISEASES; REACTIVE ARTHRITIS; AMERICAN PATIENTS; TRANSGENIC MICE AB Objective. To determine how HLA alleles are associated with the clinical disease patterns of patients with synovitis of recent onset. Methods. The HLA alleles A, B, C, DR beta 1, and DQ beta 1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints, At a mean disease duration of 33 weeks, 98 patients (46%) met the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Controls were racially matched healthy individuals (n = 244). Results. Shared epitope (SE) alleles were significantly more common in rheumatoid factor-positive (RFS) patients fulfilling the ACR RA criteria than in other patients with early arthritis (65% versus 35%; P < 0.001). In addition, the RA patients had by far the highest frequency of radiographic erosions (52% and 39% in RF+ and RF- RA, respectively, versus 3% and 9% in SpA and UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF- RA patients (odds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45), The presence of 2 SE alleles or an associated DQ beta 1*0301 (DQ7) or DQ beta 1*0302 (DQ8) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequilibrium with DR beta 1*0401, both in the patient and in the control populations. B27 was linked with the presence of SE alleles in the patients, including those patients fulfilling the RA criteria, but not in the controls (12%, versus 3%; P < 0.001). Enthesitis was present in 23 (11%) of 211 patients, was highly associated with B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature specific only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear. Conclusion. This study of HLA associations in a diverse cohort of early synovitis patients emphasizes the complex degree of genetic interaction between alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patients to characteristic clinical syndromes, had an unexpected degree of association in this cohort, perhaps explaining the overlap in clinical features in many patients. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. RP El-Gabalawy, HS (reprint author), NIAMSD, NIH, Bldg 10,Room 9S205, Bethesda, MD 20892 USA. OI Arayssi, Thurayya/0000-0003-2469-0272 NR 46 TC 76 Z9 76 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1999 VL 42 IS 8 BP 1696 EP 1705 DI 10.1002/1529-0131(199908)42:8<1696::AID-ANR19>3.0.CO;2-K PG 10 WC Rheumatology SC Rheumatology GA 224AU UT WOS:000081874400019 PM 10446870 ER PT J AU Miller, RV Jeffrey, W Mitchell, D Elasri, M AF Miller, RV Jeffrey, W Mitchell, D Elasri, M TI Bacterial responses to ultraviolet light SO ASM NEWS LA English DT Article ID ESCHERICHIA-COLI; MUTAGENESIS; DAMAGE; RECA C1 Oklahoma State Univ, Dept Microbiol & Mol Genet, Stillwater, OK 74078 USA. Univ W Florida, Ctr Environm Diagnost & Bioremediat, Pensacola, FL 32514 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. NR 11 TC 72 Z9 73 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD AUG PY 1999 VL 65 IS 8 BP 535 EP 541 PG 7 WC Microbiology SC Microbiology GA 225XR UT WOS:000081991700013 ER EF