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Biomedical subjects

T Nguyen

Publications and source records attributed to T Nguyen.

At least 109 records · Page 6Linked to original sources
PubMed2000

Serotonin transporter gene polymorphisms in alcohol dependence.

The serotonin transporter (5-HTT) gene is a candidate gene in alcohol dependence because serotonin reuptake inhibitors (SRIs) can alleviate alcohol withdrawal. Studies of the 5-HTT gene in alcohol dependence have not resulted in a consensus. Recent studies have examined the transcriptionally active promoter polymorphism, a 44-bp deletion resulting in short (S) or long (L) alleles. In this study, 131 alcohol-dependent patients of Northern and Western European descent were genotyped. Seventy of these patients were diagnosed with alcohol dependence without comorbid disorders. Sixty-one patients were diagnosed with alcohol dependence comorbid with Tourette syndrome (alcoholic-TS). We found an excess of the S allele in alcohol-dependent patients (47%) compared with 125 ethnically matched controls (39%). A similar trend was found in 150 ethnically matched TS patients without alcohol dependence comorbidity (51%). However, the statistical significance of this trend in the data was not present after Bonferroni correction. The data presented suggests a trend toward increased frequency of the S promoter allele in alcohol-dependent, alcoholic-TS and TS patients.

Adult↗
PubMed2000

Oligomerization of dopamine and serotonin receptors.

Until recently, it has largely been assumed that G protein-coupled receptors (GPCRs) function as monomeric entities. However, over the past few years, we and others have documented that GPCRs can form dimers and oligomers, leading to a re-evaluation of the mechanisms thought to mediate GPCR function. Despite the growing number of investigations into dimerization, little is known about the structural basis of receptor-receptor interactions and the functional consequences of dimer formation. Here, we present a brief review of some insights we have gained into the dimerization of dopamine and serotonin receptors. We have demonstrated that agonist-regulated trafficking is identical for receptor monomers and dimers, however, agonist treatment appears to stabilise the receptor oligomers. An investigation of the structural assembly between receptors involved in dimerization showed that there are several sites of interaction including hydrophobic transmembrane domain interactions and intermolecular disulphide bonds. We have also examined receptor hetero-oligomerization and demonstrated the potential for novel functions as a result of these associations. Finally, as a result of these observations, we have been able to present evidence that GPCRs function as oligomers in the cell.

Animals↗
PubMed2000

The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.

While CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations. Our data indicate a critical function for the third member of the CD28 family in T cell-dependent immune responses.

Abatacept↗
PubMed2000

A point mutation in beta2-microglobulin results in loss of epitope expression.

A common tool in studying the structure and function of major histocompatibility complex: (MHC) class I is the generation and analysis of beta2-microglobulin (beta2m) mutations. beta2m has been shown to affect proper class I antigen presentation at the level of structural functionality. Many studies characterizing beta2m function in class I presentation have used antibody-based assays. Monitoring the effect of beta2m mutation on antibody epitope expression, therefore, is essential in being able to truly characterize the impact of a mutant interaction between beta2m and class I. Here we describe a mutant beta2m molecule, beta2m #32, that in association with class I loses reactivity with the human beta2m-specific monoclonal antibody, BBM.1. However, the BBM.1 epitope remains intact when beta2m #32 is free from class I association.

Epitopes, B-Lymphocyte↗
PubMed2000

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration.

BACKGROUND: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1). METHOD: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis. RESULTS: Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm. CONCLUSIONS: The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.

Alveolar Process↗
PubMed2000

Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations.

The dopamine transporter (DAT) provides major regulation of the synaptic levels of dopamine and is a principal target of psychostimulant drugs. Associations between DAT gene polymorphisms and human disorders with possible links to dopaminergic neurotransmission, including attention-deficit/hyperactivity disorder (ADHD) and consequences of cocaine and alcohol administration, have been reported. We now report approximately 60000 bp of genomic sequence containing the entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons and several introns and analyze these amplification products by single-stranded sequence conformation (SSCP) and/or direct sequencing. These results define silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and 15. Rare conservative mutations are identified in amino acids encoded by DAT exons 2 and 8. Analyses of the common nucleotide variants and the previously reported VNTR in the non-coding region of exon 15 define the pattern of linkage disequilibrium across the DAT locus. These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are consistent with substantial evolutionary conservation of the DAT protein sequence. They suggest that gene variants that alter levels of DAT expression provide the best current candidate mechanism for reported associations between DAT gene markers, ADHD and other more tentatively associated neuropsychiatric disorders.

Adolescent↗
PubMed2000

Prediction of angiographic carotid artery stenosis indexes by colour Doppler-assisted duplex imaging. A critical appraisal of the parameters used.

The aim of our study was to establish colour Doppler-assisted duplex imaging (CDDI)-criteria to predict an angiographic internal carotid artery (ICA) stenosis of at least 70%, according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trialists (ECST) methods of measurement. In the following, we describe the findings in 79 patients who were screened for carotid endarterectomy by CDDI and further evaluated by digital subtraction angiography (DSA). In 158 carotid arteries, 107 stenoses of > 30% and nine occlusions were found. Receiver operator characteristic graphs were constructed in order to calculate sensitivities and specificities of the assessment by CDDI in the prediction of high-grade stenoses determined by angiography. Optimal cut-off points were defined by highest accuracy which reflects the combination of high sensitivity and specificity. The critical index of a high-grade ICA stenosis according to the ECST method could be predicted with an accuracy greater than 90% by a systolic peak velocitiy of 1.25 m/s or an area reduction by CDDI of 70%. Corresponding values, 1.6 m/s and 80% area reduction, predicted the stenosis indexes according to the NASCET method less reliably, with accuracies of between 80% and 90%. Flow velocity criterion was slightly less accurate than the area reduction criterion by CDDI. Finally, double-blind evaluation performed by two readers per examination modality showed that the measurement of area reduction in CDDI is at least as reliable as stenosis indexes according to ECST and NASCET methods.

Adult↗
PubMed2000

Characterization of apelin, the ligand for the APJ receptor.

The apelin peptide was recently discovered and demonstrated to be the endogenous ligand for the G protein-coupled receptor, APJ. A search of the GenBank databases retrieved a rat expressed sequence tag partially encoding the preproapelin sequence. The GenBank search also revealed a human sequence on chromosome Xq25-26.1, containing the gene encoding preproapelin. We have used the rat sequence to screen a rat brain cDNA library to obtain a cDNA encoding the full-length open reading frame of rat preproapelin. This cDNA encoded a protein of 77 amino acids, sharing an identity of 82% with human preproapelin. Northern and in situ hybridization analyses revealed both human and rat apelin and APJ to be expressed in the brain and periphery. Both sequence and mRNA expression distribution analyses revealed similarities between apelin and angiotensin II, suggesting they that share related physiological roles. A synthetic apelin peptide was injected intravenously into male Wistar rats, resulting in immediate lowering of both systolic and diastolic blood pressure, which persisted for several minutes. Intraperitoneal apelin injections induced an increase in drinking behavior within the first 30 min after injection, with a return to baseline within 1 h.

Amino Acid Sequence↗
PubMed2000

Maternal deaths in an urban perinatal network, 1992-1998.

OBJECTIVE: The object of this study was to use an in-depth peer-review process to determine the maternal mortality ratio at a single urban perinatal center and to identify factors associated with fatal outcomes to elucidate opportunities for preventive measures to reduce the maternal mortality ratio. STUDY DESIGN: Between 1992 and 1998 all maternal deaths occurring within our perinatal network were identified. A peer-review committee was established to review all available data for each death to determine the underlying cause of death, whether it was related to pregnancy, and whether the death was potentially preventable. RESULTS: There were 131,500 births and 42 maternal deaths, for a maternal mortality ratio of 31.9 maternal deaths per 100,000 live births. The adjusted pregnancy-related maternal mortality ratio was 22.8 maternal deaths per 100,000 live births, with 37% of those deaths (11/30) deemed potentially preventable and a provider factor cited in >80% of these. Pulmonary embolus and cardiac disease together accounted for 40% of the pregnancy-related deaths. CONCLUSION: Local maternal mortality ratios identified through a peer-review process indicate that the magnitude of the problem is much greater than is recognized through national death certificate data. The high proportion of potentially preventable maternal deaths indicates the need for improvement in both patient and provider education if we are to reduce the maternal mortality ratio to 3.3 maternal deaths per 100,000 live births, the stated national health goal of Healthy People 2000.

Female↗
PubMed2000

Laser lithotripsy and cyanide.

BACKGROUND AND PURPOSE: Holmium:YAG lithotripsy of uric acid calculi produces cyanide. The laser and stone parameters required to produce cyanide are poorly defined. In this study, we tested the hypotheses that cyanide production: (1) varies with holmium:YAG power settings; (2) varies among holmium:YAG, pulsed-dye, and alexandrite lasers; and (3) occurs during holmium:YAG lithotripsy of all purine calculi. MATERIALS AND METHODS: Holmium:YAG lithotripsy of uric acid calculi was done using various optical fiber diameters (272-940 microm) and pulse energies (0.5-1.5 J) for constant irradiation (0.25 kJ). Fragmentation and cyanide were quantified. Cyanide values were divided by fragmentation values, and fragment sizes were characterized. To test the second hypothesis, uric acid calculi were irradiated with Ho:YAG, pulsed-dye, and alexandrite lasers. Fragmentation and cyanide were measured, and cyanide per fragmentation was calculated. Fragment sizes were characterized. Finally, Ho:YAG lithotripsy (0.25 kJ) of purine and nonpurine calculi was done, and cyanide production was measured. RESULTS: Fragmentation increased as pulse energy increased for the 550- and 940-microm optical fibers (P < 0.05). Cyanide increased as pulse energy increased for all optical fibers (P < 0.002). Cyanide per fragmentation increased as pulse energy increased for the 272-microm optical fiber (P = 0.03). Fragment size increased as pulse energy increased for the 272-microm, 550-microm, and 940-microm optical fibers (P < 0.001). The mean cyanide production from 0.25 kJ of optical energy was Ho:YAG laser 106 microg, pulsed-dye 55 microm, and alexandrite 1 microg (P < 0.001). The mean cyanide normalized for fragmentation (microg/mg) was 1.18, 0.85, and 0.02, respectively (P < 0.001). The mean fragment size was 0.6, 1.1, and 1.9 mm, respectively (P < 0.001). After 0.25 kJ, the mean amount of cyanide produced was monosodium urate stones 85 microg, uric acid 78 microg, xanthine 17 microg, ammonium acid urate 16 microg, calcium phosphate 8 microg, cystine 7 microg, and struvite 4 microg (P < 0.001). CONCLUSIONS: Cyanide production varies with Ho:YAG pulse energy. To minimize cyanide and fragment size, Ho:YAG lasertripsy is best done at a pulse energy < or = 1.0 J. Cyanide production from laser lithotripsy of uric acid calculi varies among Ho:YAG, pulsed-dye, and alexandrite lasers and is related to pulse duration. Cyanide is produced by Ho:YAG lasertripsy of all purine calculi.

Cyanides↗
PubMed2000

Fat and carbohydrate balances during adaptation to a high-fat.

BACKGROUND: Dietary fat contents are highly variable. Failure to compensate for the positive fat balance that occurs during the shift to a high-fat, low-carbohydrate diet by increasing energy expenditure or by decreasing food intake may result in the gain of fat mass. OBJECTIVE: The objective of this study was to investigate the time course of fat oxidation during adaptation to an isoenergetic high-fat, low-carbohydrate diet. DESIGN: After a 5-d control diet, dietary fat was increased from 37% of energy to 50% of energy for 4 d in 6 healthy, young lean men. Respiratory quotient and substrate macronutrient oxidation and balance were measured in a respiratory chamber. Fasting concentrations of insulin, glucose, and triacylglycerol; maximal oxygen consumption (f1.gif" BORDER="0">O(2)max) during treadmill exercise; and free-living energy expenditure were determined. Body fat was measured by dual-energy X-ray absorptiometry and visceral adipose tissue by computerized tomography. RESULTS: Compared with the baseline diet, the high-fat, low-carbohydrate diet resulted in positive fat and protein balances and a negative carbohydrate balance. Insulin concentration and the postabsorptive respiratory quotient were positively correlated with the fat balance during the high-fat, low-carbohydrate diet, whereas f1.gif" BORDER="0">O(2)max during treadmill exercise was negatively related to fat balance. With use of stepwise regression, f1.gif" BORDER="0">O(2)max was the best predictor of fat balance. There was a negative correlation between fat balance and carbohydrate balance (r(2) = 0.88). CONCLUSION: Both baseline insulin concentration and f1.gif" BORDER="0">O(2)max during treadmill exercise predict fat balance during the shift to a high-fat diet under isoenergetic conditions.

Adipose Tissue↗
PubMed2000

Concurrent physical activity increases fat oxidation during the shift to a high-fat diet.

BACKGROUND: It takes several days to adapt to a high-fat diet. In an earlier study, we observed a large degree of interindividual variation in the capacity to adapt to a high-fat diet. We hypothesized that concurrent physical activity would accelerate fat oxidation during an isoenergetic high-fat diet. OBJECTIVE: The objective of this study was to determine the effect of increased physical activity on the ability of young healthy men to increase fat oxidation during the shift to a high-fat diet. DESIGN: Six young healthy men participated in a randomized, single-blind crossover study. The volunteers consumed a diet contributing 37% of energy as fat, 14% as protein, and 49% as carbohydrate for 4 d. Energy expenditure and macronutrient balance were then measured in a respiration chamber as the energy content of the isoenergetic diet was changed to 50% fat, 14% protein, and 36% carbohydrate. Treadmill walking, as the physical activity, was used to increase total daily energy expenditure to 1.8 times the resting metabolic rate during 1 of 2 stays in the metabolic chamber. Total daily energy expenditure was maintained at 1.4 times the resting metabolic rate for the other stay. RESULTS: Energy balance was not significantly different between the 2 conditions. The 24-h respiratory quotient decreased more rapidly and to a greater extent under conditions of increased energy expenditure. Further, there was a decrease in the interindividual variability in the response of the respiratory quotient to a high-fat diet with increased energy expenditure (physical activity). Cumulative carbohydrate and protein balances were greater under conditions of increased physical activity. Conversely, cumulative fat balance was greater under sedentary conditions. CONCLUSION: Concurrent physical activity increases fat oxidation during the shift to a high-fat diet.

Adaptation, Physiological↗
PubMed2000

Growth and function of isolated canine pancreatic ductal cells.

These studies investigated the growth characteristics and functional properties of isolated canine pancreatic ductal epithelial cells. Cells were isolated from the accessory pancreatic duct and cultured by using three conditions: on vitrogen-coated petri dishes with fibroblast conditioned medium (nonpolarized); in vitrogen-coated Transwells above a fibroblast feeder layer (polarized); or as organotypic rafts above a fibroblast-embedded collagen layer (polarized). Growth characteristics, transepithelial resistances, and carbonic anhydrase and cyclic adenosine monophosphate (AMP) responses were evaluated. Under polarized conditions, the cells grew as monolayers with columnar epithelial characteristics. The monolayers developed high transepithelial resistance and became impervious to the passage of horseradish peroxidase. Epithelial growth factor (EGF) (2 ng/ml) stimulated ductal cell growth and accelerated the formation of a high-resistance monolayer. Forskolin (10 microM) rapidly decreased transepithelial resistance. Carbonic anhydrase activity, which was lower in nonpolarized compared with polarized conditions, was stimulated by carbachol (175 microM). Secretin, however, did not stimulate carbonic anhydrase activity in these cells. Although secretin stimulated adenylyl cyclase activity in early-passage cells, this response was lost in later-passage cells. Both vasoactive intestinal polypeptide (VIP; 1 microM) and forskolin (10 microM) consistently increased adenylyl cyclase activity. Isolated canine pancreatic ductal epithelial cells proliferate in vitro, develop high-resistance epithelial monolayers, and respond to stimuli that activate adenylyl cyclase. These cells should provide a useful model for regulatory studies of ductal cell functions.

Adenylyl Cyclases↗
PubMed2000

A discrepancy between gestational age estimated by last menstrual period and biparietal diameter may indicate an increased risk of fetal death and adverse pregnancy outcome.

OBJECTIVE: To determine if the discrepancy between gestational age estimated by last menstrual period and by biparietal diameter (GALMP - GABPD) is associated with adverse pregnancy outcome. DESIGN: Population-based follow up study. POPULATION: Singleton pregnancies were studied when a reliable date of last menstrual period and biparietal diameter measured between 12 and 22 weeks of gestation was available (n = 16,469). METHODS: Logistic regression analysis and Kaplan-Meier survival analysis were used to analyse the association between GALMP - GABPD and adverse pregnancy outcome. MAIN OUTCOME MEASURES: Adverse outcome was defined as abortion after 12 weeks of gestation, still-birth or postnatal death within one year of birth, delivery < 37 weeks of gestation, a birthweight < 2,500 g or a sex-specific birthweight lower than 22% below the expected. RESULTS: The risk of death was more than doubled if GALMP - GABPD of > or = 8 days was compared with GALMP - GABPD of < 8 days (OR 2.2; 95% CI 1.6-3.1). The risk of death was a factor of 6.1 higher if GALMP - GABPD of > or = 8 days was combined with increased (> 2 x multiple of median) maternal alpha-fetoprotein measured in the 2nd trimester. CONCLUSIONS: A discrepancy between GALMP and GABPD generally reflects the precision of the two methods used to predict term pregnancy. However, a positive discrepancy of more than seven days, particularly with high maternal alpha-fetoprotein, might indicate intrauterine growth retardation and an increased risk of adverse perinatal outcome.

Abortion, Spontaneous↗
PubMed2000

Prognostic value of 12-lead electrocardiogram during dobutamine stress echocardiography.

The aim of this study was to assess the prognostic value of the 12-lead electrocardiogram (ECG) obtained during dobutamine stress echocardiography (DSE) in predicting subsequent cardiac events. We retrospectively analyzed 345 patients undergoing DSE in 1992-1994 and selected those patients with negative echo results for ischemia. Of the 200 patients with negative DSE results, a separate analysis of their ECG data was performed with results reported as either positive, negative, or nondiagnostic for ischemia. Follow-up was performed through a physician chart review and direct telephone contact. Event rates were determined for hard (myocardial infarction or cardiac death) and soft (hospitalization for angina and/or congestive heart failure, coronary angioplasty, or coronary artery bypass graft surgery) cardiac events occurring after the negative DSE for up to 6 years after the test. Death was also determined by referencing the patients' data with mortality data available on the Internet. There were 143 patients with ECG data reported as negative and 40 patients with ECG data reported as positive for ischemia. The hard and soft event rates were 1.5% and 9% per patient per year in the ECG negative group and 2% and 11% in the ECG positive group. There were no statistical differences in event rates between the two groups during the 5-year follow-up period. Our results suggest that the ECG result obtained during DSE does not confer any incremental prognostic value over the echo result.

Angina Pectoris↗
PubMed2000

Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases.

OBJECTIVE: Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls. METHODS: A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays. RESULTS: Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94-97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48-86%, p = 0.02) and GERD (69%, CI: 39-91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81-98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10-56%) versus 80% (CI: 59-93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies. CONCLUSIONS: The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.

Antigens, Bacterial↗
PubMed2000

Secretory lipophilins: a tale of two species.

Secretory lipophilins are "lipid-loving" proteins that are major constituents of several mammalian secretions, including the prostatic fluid of rats and the tears of humans and rabbits. These proteins form covalent heterodimers that are stabilized by three intramolecular cystine disulfide bonds. The heterodimers, some of which are glycosylated, may undergo additional non-covalent assembly to form tetramers. The peptide components found in secretory lipophilins are from two subfamilies: lipophilins A/B and lipophilin C. The C subfamily members described in this report are three rabbit and one human lipophilin, plus human mammaglobin and the C3 subunit of rat prostatein. Human A/B and C lipophilins are expressed by many tissues and are especially prominent in endocrine-responsive organs. The gene for human lipophilin B resides at chromosome 10q22-23. This region harbors the PTEN/MMAC1 gene and is believed to contain additional tumor suppressor genes. Although the functions of secretory lipophilins are imperfectly understood, their abundance in glandular secretions and in hormone-responsive tissues suggests that they deserve considerably more attention than they have received to date.

Animals↗