Carey, DG, Nguyen, TV, Campbell, LV, Chisholm, DJ & Kelly, P 1996, 'Genetic influences on central abdominal fat: a twin study.', Int J Obes Relat Metab Disord, vol. 20, no. 8, pp. 722-726.
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INTRODUCTION: Recent studies of regional fat distribution have focused on the clinical importance of central abdominal obesity. Central adiposity is strongly related to insulin resistance, non-insulin dependent diabetes mellitus (NIDDM), dyslipidaemia and cardiovascular disease. While significant genetic influences on body mass index (BMI), total body and subcutaneous fat have been demonstrated, the inheritance of central abdominal obesity, has not been studied. OBJECTIVE: To assess genetic effects on regional fat distribution and associated metabolic parameters. DESIGN AND SUBJECTS: We directly measured total body, central abdominal (C-abd) and non-abdominal fat using dual energy X-ray absorptiometry in 50 monozygotic (MZ) and 36 dizygotic (DZ) female twins, of age (mean +/- SD), 44 +/- 12 and 47 +/- 14 y; BMI 24 +/- 5 and 24 +/- 3 kg/m2; C-abd fat 33 +/- 9 and 32 +/- 9%, respectively. Total variance in all parameters was independent of zygosity and genetic analyses of regional adiposity were performed before and after adjusting for age and percentage total body fat. RESULTS: A genetic influence was observed on the population variance in total fat, C-abd fat (C-abd fat rMZ = 0.66 vs rDZ = 0.20, p = 0.03) and non abdominal fat. After adjusting C-abd fat for age and total body fat there was a independent genetic influence on C-abd fat accounting for approximately 70% of the population variance (rMZ = 0.61 vs rDZ = 0.40, p = 0.001). CONCLUSION: The majority of inter-subject variance in central abdominal fat in non-obese individuals is due to genetic factors. The inheritance of abdominal obesity, with its associated metabolic consequences, may contribute to the familial aggregation of insulin resistance, diabetes and cardiovascular disease.
Heiber, M, Marchese, A, Nguyen, T, Heng, HHQ, George, SR & O'Dowd, BF 1996, 'A Novel Human Gene Encoding a G-Protein-Coupled Receptor (GPR15) Is Located on Chromosome 3', Genomics, vol. 32, no. 3, pp. 462-465.
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We used sequence similarities among G-protein-coupled receptor genes to discover a novel receptor gene. Using primers based on conserved regions of the opioid-related receptors, we isolated a PCR product that was used to locate the full-length coding region of a novel human receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor encoded by GPR15 with other receptors revealed that it shared sequence identity with the angiotensin II AT1 and AT2 receptors, the interleukin 8b receptor, and the orphan receptors GPR1 and AGTL1. GPR15 was mapped to human chromosome 3q11.2-q13.1.
Howes, LG, Nguyen, T & Jackson, B 1996, 'SAFETY AND EFFICACY OF QUINAPRIL IN HYPERTENSIVE GERIATRIC PATIENTS', Journal of the American Geriatrics Society, vol. 44, no. 9, pp. 1135-1135.
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Johnson, AG, Nguyen, TV & Day, RO 1996, 'Evaluation of the Takeda TM-2420 in the elderly.', J Hum Hypertens, vol. 10, no. 1, pp. 61-61.
Johnson, AG, Nguyen, TV, Owe-Young, R, Williamson, DJ & Day, RO 1996, 'Potential mechanisms by which nonsteroidal anti-inflammatory drugs elevate blood pressure: the role of endothelin-1.', J Hum Hypertens, vol. 10, no. 4, pp. 257-261.
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To determine whether endothelin-1 (ET-1) contributes to hypertension associated with non-steroidal anti-inflammatory drug (NSAID) usage in healthy, elderly, normotensive individuals a randomised, double-blind, placebo-controlled, crossover trial of indomethacin was undertaken in 41 healthy, elderly individuals with stable normotension or controlled hypertension (blood pressure (BP) < or = 160/90 mm Hg). The main outcome measures were systolic and diastolic BP, heart rate, cardiac output, weight, creatinine clearance, plasma renin activity, aldosterone, endothelin-1 and arginine vasopressin concentrations and 24 h urinary endothelin-1 and 6 keto prostaglandin F1 alpha outputs. Analysis of covariance was used to evaluate the effect of indomethacin on BP and related parameters. Indomethacin treatment for 1 month increased systolic (+/- s.e.m.: 4.1 +/- 2.2 mm Hg; 95% confidence interval 0 to 8.3 mm Hg) and diastolic BP (2.7 +/- 1.1 mm Hg; 0.4 to 4.9 mm Hg) without altering cardiac output (P = 0.59), implying an increase in total peripheral resistance. Indomethacin treatment produced a small increase in weight (1.4 +/- 0.4 kg; 0.6 to 2.2 kg), a small reduction in renal function (creatinine clearance: 6.8 +/- 1.8 mis/min; 3.3 to 10.3 mis/min) but a significant (83%) increase in daily urinary endothelin-1 production (13.1 +/- 3.4 ng/ml; 6.4 to 19.8 ng/ml) without altering plasma ET-1 concentration, suggesting increased renal synthesis. In conclusion, renal paracrine effects of ET-1 may contribute to NSAID-induced blood pressure elevation in humans.
Keen, RW, Nguyen, T, Sobnack, R, Perry, LA, Thompson, PW & Spector, TD 1996, 'Can biochemical markers predict bone loss at the hip and spine?: A 4-year prospective study of 141 early postmenopausal women', Osteoporosis International, vol. 6, no. 5, pp. 399-406.
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Kolakowski, LF, Jung, BP, Nguyen, T, Johnson, MP, Lynch, KR, Cheng, R, Heng, HHQ, George, SR & O'Dowd, BF 1996, 'Characterization of a human gene related to genes encoding somatostatin receptors', FEBS Letters, vol. 398, no. 2-3, pp. 253-258.
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We report the identification of a gene, named SLC‐11, encoding a novel G protein‐coupled receptor (GPCR). A customized search procedure of a database of expressed sequence tags (dbEST) retrieved a human cDNA sequence that partially encoded a GPCR. A genomic DNA fragment identical to the cDNA was obtained and used to screen a library to isolate the full‐length coding region of the gene. This gene was intronless in its open reading frame, and encoded a receptor of 402 amino acids, and shared −40% amino acid identity in the transmembrane (TM) regions to the five known human somatostatin receptors. Northern blot analysis revealed that SLC‐1 is expressed in human brain regions, including the forebrain and hypothalamus. Expression in the rat was highest in brain, followed by heart, kidney, and ovary. Expression of SLC‐1 in COS‐7 cells failed to show specific binding to radiolabelled Tyr1‐somatostatin‐14, naloxone, bremazocine, 1,3‐di(2‐tolyl)‐guanidine (DTG), or haloperidol. A repeat polymorphism of the form (CA)n was discovered in the 5′‐untranslated region (UTR) of the gene and SLC‐1 was mapped to chromosome 22, q13.3.
Lam, S, Shen, Y, Nguyen, T, Messier, TL, Brann, M, Comings, D, George, SR & O'Dowd, BF 1996, 'A Serotonin Receptor Gene (5HT1A) Variant Found in a Tourette's Syndrome Patient', Biochemical and Biophysical Research Communications, vol. 219, no. 3, pp. 853-858.
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Serotonergic pathway disturbances have been implicated in neuropsychiatric disorders such as Tourette's syndrome (TS), substance abuse, and depression. In order to search for the presence of an association between these neuropsychiatric disorders and particular serotonin receptors isolated from these patients, we have started to analyze the structure of these receptor genes. We now report that a missense nucleotide change in the 5HT1A receptor gene produces a variant form of the 5HT1A receptor (Arg219 to Leu) identified in DNA extracted from a TS patient. Also, in several DNA samples examined, both in controls and in the patients, we found a second missense nucleotide change which resulted in an amino acid change (Asn417 to Lys) located in the carboxyl tail of the receptor. Several other polymorphic changes have been reported previously in the human 5HT1A receptor and we have also confirmed these findings in our samples.
Nguyen, TV, Morrison, NA, Sambrook, PN, Kelly, PJ & Eisman, JA 1996, 'Vitamin D receptor gene and osteoporosis.', J Clin Endocrinol Metab, vol. 81, no. 4, pp. 1674-1675.
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O'Dowd, BF, Nguyen, T, Lynch, KR, Kolakowski, LF, Thompson, M, Cheng, R, Marchese, A, Ng, G, Heng, HHQ & George, SR 1996, 'A novel gene codes for a putative G protein‐coupled receptor with an abundant expression in brain', FEBS Letters, vol. 394, no. 3, pp. 325-329.
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Following the cloning of the dopamine receptors we continued a search of the human genome for related genes. We searched an EST data base and discovered cDNA fragments encoding novel G protein‐coupled receptor genes. The available GenBank sequence of one of these EST fragments showed that it encoded a receptor with closest similarity to the D2 dopamine and adrenergic receptors. This cDNA was used to isolate the gene (GPR19), and the encoded receptor also demonstrated similarity with the neuropeptide Y receptor. The gene was mapped to chromosome 12, in region p13.2–12.3. Northern blot analysis revealed expression of GPR19 in peripheral regions, and brain regions significantly overlapping with the D2 receptor gene expression. A sequence of the rat orthologue of GPR19 was obtained and in situ hybridization analysis demonstrated a very abundant expression in rat brain.
Pocock, NA, Noakes, KA, Howard, GM, Nguyen, TV, Kelly, PJ, Sambrook, PN, Eisman, JA & Freund, J 1996, 'Screening for osteoporosis: what is the role of heel ultrasound?', Medical Journal of Australia, vol. 164, no. 6, pp. 367-370.
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Vinh, H, Wain, J, Vo, TN, Cao, NN, Mai, TC, Bethell, D, Nguyen, TT, Tu, SD, Nguyen, MD & White, NJ 1996, 'Two or three days of ofloxacin treatment for uncomplicated multidrug-resistant typhoid fever in children', Antimicrobial Agents and Chemotherapy, vol. 40, no. 4, pp. 958-961.
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An open randomized comparison of 2 days (Ofx2) versus 3 days (Ofx3) of oral ofloxacin treatment (15 mg/kg/day) was conducted with Vietnamese children between 1 and 15 years of age with suspected typhoid fever. Of 108 children enrolled, 100 were blood culture positive for Salmonella typhi, and 86% of the isolates were multidrug resistant. There were no significant adverse effects. The therapeutic responses were similar in both groups, with mean (+/- standard deviation) fever clearances of 107 +/- 60 h in the Ofx3 group and 100 +/- 64 h in the Ofx2 group (P > 0.2). There were six 'clinical' failures in the Ofx2 group and two clinical failures in the Ofx3 group (P > 0.2), in which fever and symptoms persisted for more than 1 week after the start of treatment, but only one of these was culture positive (Ofx3). There was one suspected relapse, and one carrier was identified. Short courses of ofloxacin are simple, inexpensive, safe, and effective for the treatment of uncomplicated multidrug-resistant typhoid fever.
