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T Nguyen

Publications and source records attributed to T Nguyen.

At least 325 records · Page 18Linked to original sources
PubMed1993

An Alu sequence interrupts a human 5-hydroxytryptamine1D receptor pseudogene.

Molecular cloning studies have now identified six HTR genes encoding the biosynthesis of the structurally homologous human serotonin (5-hydroxytryptamine; 5-HT) receptors, namely 5-HTR1A, 5-HTR1B, 5-HTR1C, 5-HTR1D, 5-HTR2 and 5-HTRS31. Several of these receptors are encoded by intronless genes, and we now report the cloning of another intronless serotonergic HTR gene. This gene was cloned by a method using the polymerase chain reaction. The nucleotide sequence of this gene is most closely homologous to the 5-HTR1D gene; however, several stop codons, frame shifts and deletions are present in the coding region suggesting that this is a pseudogene which could not encode a functional receptor. Sequence analysis also revealed that the coding sequence of this pseudogene is disrupted by insertion of a 283-bp Alu repeat sequence.

Amino Acid Sequence↗
PubMed1993

Intracellular distribution of various boron compounds for use in boron neutron capture therapy.

The neutron capture reaction in boron (10B(n, alpha)7Li) generates two short-range particles with high linear energy transfer. The effect of neutron capture therapy depends on the selective localization of 10B atoms in target cells. The determination of the distribution of boron compounds in cancer cells at the subcellular level is required for the understanding of the effect of this treatment. The monomeric sulfhydryl borane (BSH) compound has been used clinically in Japan and preclinically in the U.S.A. Recently, new compounds have been developed: a dimeric sulfhydryl borane (BSSB), a boronophenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). This study demonstrates that the porphyrin complexes (BOPP and VCDP) are more cytotoxic than the other three compounds to the rat 9L gliosarcoma cell line. Using atomic absorption spectrophotometry to determine boron content for cellular uptake studies of these agents, we found that of the five compounds tested BOPP (25 microM) exposure resulted in the greatest boron uptake averaging 305 ng B/10(6) cells. BSSB (500 microM) was second averaging 93 ng B/10(6) cells, BSH (500 microM) third averaging 62 ng B/10(6) cells, VCDP (25 microM) fourth averaging 58 ng B/10(6) cells, and BPA (500 microM) fifth averaging 7.4 ng B/10(6) cells. Data on the distribution of boron in the nuclei, mitochondria, lysosomes, microsomes, and cytosomes of 9L cells are also presented.

Animals↗
PubMed1993

Changes in axial bone density with age: a twin study.

Bone mineral density in adult life, which is an important determinant of fracture risk, is determined by peak adult bone density, achieved in early adulthood and subsequent rates of change during adult life. Cross-sectional twin and family studies indicate that the majority of population variation in bone density may be explained by genetic factors. Although there is evidence for a genetic effect on peak bone mass, it is unknown whether there is a genetic effect on rates of changes in bone density with age. Changes in lumbar spine and femoral neck bone density determined by dual-photon absorptiometry (Lunar DP3) were examined in a cohort of monozygotic (MZ, n = 21, 3 male and 18 female pairs, median age, range, 46; 24-75 years) and dizygotic twins (DZ, n = 19; 43, 25-65 years). The median follow-up was 3 years (range 1.1-5.5 years), with each subject having at least two and up to four bone density assessments. In these twins, genetic factors determine variation in rates of change (% change/year) in lumbar spine bone density, rMZ = 0.93 and rDZ = 0.51, p < 0.02 (one tailed), and Ward's triangle, rMZ = 0.60, rDZ = 0.11, p < 0.05 (one tailed). Model-fitting analysis was also consistent with a genetic effect on rates of change in bone density at the trochanteric site, although such an effect was not shown at the femoral neck. These data demonstrate, for the first time, the possible existence of genetic determinants of rates of change in bone mineral density in adults.

Absorptiometry, Photon↗
PubMed1993

TGF-beta 1 induces bone closure of skull defects: temporal dynamics of bone formation in defects exposed to rhTGF-beta 1.

The temporal dynamics of bone repair in a skull defect in rabbits was examined to characterize the in vivo cellular events occurring following a single local application of recombinant human TGF-beta 1 (rhTGF-beta 1). Rabbits received vehicle or 0.4, 1, 2, or 5 micrograms rhTGF-beta 1 applied to 12 mm defects at the time of surgery. The defect sites were subsequently evaluated by radiography and qualitative and quantitative histology at time points ranging from 1 to 180 days. Based on radiographic assessment, the defect area decreased rapidly in a dose-dependent manner through 35 days after surgery in the rhTGF-beta 1-treated groups. Minimal closure occurred in sites administered vehicle control at all time points examined. Sites treated with rhTGF-beta 1 were characterized histologically by an increase in parameters of active bone formation through 49 days, including percentage osteoid surface, percentage osteoblast/total surface, and an increase in the trabecular bone volume. Bone resorption parameters were increased at 16 and 49 days with histologic evidence of remodeling from woven to lamellar bone. By 70 days, no differences were observed among the groups for parameters of either bone formation or resorption. Bone formation rate was not altered with rhTGF-beta 1 treatment at any time point. These results indicate that exogenously applied rhTGF-beta 1 stimulated the recruitment and proliferation of osteoblasts at the defect site, resulting in a rapid deposition of bony matrix, with normal remodeling processes occurring thereafter. This study supports the hypothesis that TGF-beta 1 is a potent osteoinductive growth factor in vivo and may have potential application as a therapeutic aid to nonhealing bony defects.

Animals↗
PubMed1993

A new yeast gene with a myosin-like heptad repeat structure.

We isolated a gene encoding a 218 kDa myosin-like protein from Saccharomyces cerevisiae using a monoclonal antibody directed against human platelet myosin as a probe. The protein sequence encoded by the MLP1 gene (for myosin-like protein) contains extensive stretches of a heptad-repeat pattern suggesting that the protein can form coiled coils typical of myosins. Immunolocalization experiments using affinity-purified antibodies raised against a TrpE-MLP1 fusion protein showed a dot-like structure adjacent to the nucleus in yeast cells bearing the MLP1 gene on a multicopy plasmid. In mouse epithelial cells the yeast anti-MLP1 antibodies stained the nucleus. Mutants bearing disruptions of the MLP1 gene were viable, but more sensitive to ultraviolet light than wild-type strains, suggesting an involvement of MLP1 in DNA repair. The MLP1 gene was mapped to chromosome 11, 25 cM from met1.

Amino Acid Sequence↗
PubMed1993

Interactions of bilirubin with isolated presynaptic nerve terminals: functional effects on the uptake and release of neurotransmitters.

1. The functional effects of bilirubin:albumin solutions (10:1, mol/mol) on several synaptosomal functions were investigated using rat cortical, striatal, and hippocampal synaptosomes prepared by iso-osmotic Percoll/sucrose gradient centrifugation. 2. Bilirubin (10-80 microM) depolarized synaptosomes in a tetrodotoxin-insensitive manner as assessed by the equilibrium distribution of tetra-[3H]phenylphosphonium. Depolarization induced by bilirubin was of a lesser magnitude than that caused by KCl or veratridine. Steady-state pH gradients across the synaptosomal membrane were determined using the transmembrane distribution of [14C]methylamine. Bilirubin (20-40 microM) did not modify the intracellular pH in physiological buffers. The pigment effected a 0.14 delta pH change when the synaptosomes were suspended in a Ca2+ and Na+ free choline medium containing ouabain. 3. Bilirubin (20-80 microM) had no effect of its own on [7,8-3H] dopamine release from striatal synaptosomes. In contrast, it inhibited the initial rate of synaptosomal uptake of the catecholamine and its intrasynaptosomal content at 10 min. The pigment (20 and 40 microM) reduced the 35 mM KCl-induced release of endogenous acetylcholine from hippocampal synaptosomes by 20 and 36%, respectively. 4. The association of bilirubin with synaptic plasma membrane vesicles was characterized by a chloroform:methanol 2:1 (v/v) extraction method. At total concentrations of 10 to 80 microM bilirubin, the molar percentage of the pigment in synaptic plasma membrane phospholipids was 1-4%. 5. It is proposed that the two main functional consequences of the bilirubin-nerve ending interaction are an impairment of specific membrane-bound neurotransmitter uptake mechanisms and a reduction of the response to depolarizing stimuli. This may be the basis for rapid alterations in synaptic transmission documented in early reversible bilirubin encephalopathy.

Animals↗
PubMed1993

Prevention of corticosteroid bone loss.

Prolonged corticosteroid therapy is known to result in an increased risk of osteoporotic fracture, probably as a consequence of enhanced bone resorption and depressed bone formation. We examined the effects of prophylactic treatment with 1,25-dihydroxyvitamin D3 (calcitonin) and nasal salmon calcitonin on corticosteroid-induced bone loss in 103 patients being treated with long-term corticosteroids for the first time in a randomized, double-masked prospective study. Patients were randomly allocated to one of three groups receiving either calcium supplementation alone, calcium plus calcitriol, or calcium plus calcitriol and nasal salmon calcitonin. Treatment was given for 12 months. Bone mineral density (BMD) was measured every 4 months by dual-photon absorptiometry in the lumbar spine and femoral neck. Calcium supplementation alone did not prevent bone loss at either site. In the lumbar spine calcitriol, with or without nasal calcitonin, significantly reduced bone loss (p < 0.0001). Neither calcitriol alone nor calcitriol with calcitonin prevented bone loss at the femoral neck. These data suggest that treatment with calcium and calcitriol, or with calcium and intranasal calcitonin, greatly reduced or prevented corticosteroid-induced bone loss in the lumbar spine.

Adrenal Cortex Hormones↗
PubMed1993

Prevalence of HIV infection in oral and maxillofacial surgery patients.

To date there have been no systematic reports of the prevalence of HIV infection in dental surgery patients. The purpose of this study was to estimate the prevalence of (1) HIV infection and (2) the risk factors for HIV infection in a sample of patients who went an oral and maxillofacial surgery outpatient clinic in an urban hospital setting. Using a cross-sectional study design and anonymous self-administered patient questionnaires, we estimated the prevalence of HIV infection to be 4.8% (95% confidence interval = 2.3% to 9.7%) in our sample of 165 patients. Prevalence estimates for HIV risk factors were: (1) homosexual/bisexual preference (17.3%), (2) history of sexually transmitted disease (20.0%), (3) history of intravenous drug abuse (10.0%), and (4) history of blood transfusion (3.8%). In general, one might anticipate the prevalence of HIV infection in the patient sample to reflect the community prevalence of HIV infection. Consequently, the prevalence estimates of HIV infection in a sample of patients who live in San Francisco may not be applicable to the reader's local community. Given the known risk factors of HIV infection, however, a well-directed, frank patient history may be useful in identifying patients at risk for HIV infection.

Bisexuality↗
PubMed1993

Risk of abdominal septic complications after feeding jejunostomy placement in patients undergoing splenectomy for trauma.

Compared with total parenteral nutrition, enteral feeding via jejunostomy reduces septic complications in patients with severe trauma. However, violation of the bowel with insertion of a jejunostomy tube may increase the risk of intra-abdominal abscess (IAA), particularly if no simultaneous gastrointestinal tract injury exists. The records of 123 patients requiring splenectomy for trauma at a level I trauma center during a 6-year period (1986 to 1992) were reviewed to examine the incidence of IAA in patients with and without simultaneous jejunostomy placement in the presence and absence of gastrointestinal tract injuries. Thirty patients had jejunostomies placed (J), and 93 did not (NoJ). There were no significant differences between the groups in age, Abdominal Trauma Index, Injury Severity Score, or transfusion requirements. The incidence of IAA was not significantly different between the J and NoJ groups in the presence or absence of gastrointestinal tract injuries. Thus, jejunostomy placement does not increase the incidence of IAA after splenectomy regardless of the presence of a gastrointestinal tract injury.

Abdomen↗
PubMed1993

The pharmacokinetics and absorption of recombinant human relaxin in nonpregnant rabbits and rhesus monkeys after intravenous and intravaginal administration.

Recombinant human relaxin (rhRlx) is being developed as a potential cervical ripening agent to be applied intravaginally or intracervically prior to parturition. The pharmacokinetics and absorption of rhRlx were determined in nonpregnant female rabbits and rhesus monkeys after intravenous bolus (iv) and intravaginal administration of 0.1 mg/kg; additionally, rabbits were dosed with 0.5 mg/kg intravaginally. In rabbits (n = 6), mean (+/- SD) peak concentrations following iv bolus administration were 1554 +/- 296 ng/mL. The weight-normalized clearance (CL/W) was 5.9 +/- 0.4 mL/min/kg, initial volume of distribution (V1/W) was 57 +/- 9 mL/kg, and volume of distribution at steady state (Vss/W), assuming central compartment elimination, was 240 +/- 20 mL/kg. Vss/W could be as large as 2000 +/- 400 mL/kg without this assumption. The estimated amounts of rhRlx absorbed in rabbits following intravaginal administration of 0.1 and 0.5 mg/kg (n = 5/dose) were 3.1 +/- 1.4 and 0.7 +/- 0.3%, respectively; peak concentrations were 600 +/- 297 and 1066 +/- 584 pg/mL, respectively. In rhesus monkeys (n = 5) after iv administration, peak concentrations were 971 +/- 277 ng/mL; CL/W was 4.1 +/- 0.6 mL/min/kg, V1/W was 78 +/- 25 mL/kg, and Vss/W, assuming central compartment elimination, was 690 +/- 220 mL/kg. The upper limit for Vss/W was 1600 +/- 200 mL/kg when no assumptions were made regarding site (compartment) of elimination. After intravaginal administration (n = 6), two monkeys had undetectable rhRlx concentrations throughout the 48-hr sampling interval; one monkey had only one sample containing measurable rhRlx (51 pg/mL) at 24 hr; and three monkeys absorbed < 2% of the 0.1 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

A single-site mutation in the XPAC gene alters photoproduct recognition.

The XPAC (xeroderma pigmentosum group A complementing) gene, which is located on chromosome 9, carries a variety of point mutations in XP group A patients. We investigated the role of the XPAC gene product in excision repair by generating revertants of an XP group A cell line (XP12RO) that have increased resistance to ultraviolet light. One of these cell lines, XP129, can repair (6-4) pyrimidine-pyrimidone photoproducts normally but has reduced repair of cyclobutane dimers, as in XP12RO. Sequence analysis of cDNA from the XPAC gene indicated that XP12RO contains a termination codon at amino acid position 207, resulting in a reduced amount of mRNA and no detectable protein. In the revertant XP129 line, this termination codon has been mutated further and now encodes glycine in one allele instead of the wild-type arginine. The mRNA level detected by allele-specific polymerase chain reaction amplification was greater for the reverted sequence than for the chain-terminating sequence. These observations indicated that a point mutation resulting in a mis-sense mutation in the XPAC gene and altered expression of the XPAC protein can alter the substrate specificity of the excision repair system, and imply that the XPAC gene product plays an important role in photoproduct recognition.

Amino Acid Sequence↗
PubMed1993

The effect of ibuprofen on microvascular thrombosis in an experimental rabbit model.

The efficacy of ibuprofen in reducing microvascular thrombosis in a well-established experimental model was studied. Bilateral 2-mm arterial inversion grafts were constructed in the femoral arteries of New Zealand White rabbits. The experimental group (n = 40 grafts) received subcutaneous injections of ibuprofen 15 mg/kg t.i.d. beginning 1 day preoperatively and continued for 7 days postoperatively. The control group (n = 42 grafts) received injections of an equivalent volume of saline three times per day. Patency was evaluated at 7 days by the distal milking test. Seventy-three percent of the ibuprofen grafts were patent at 7 days, whereas 57% of the control grafts remained open. This difference in microvascular patency was not statistically significant. Representative scanning electron micrographs revealed a moderate reduction in aggregated platelets and overall clot density in the patent ibuprofen arterial inversion grafts compared with the patent control specimens. Although the use of ibuprofen as a sole antithrombotic agent cannot be recommended as the result of this study, it may be efficacious when used in conjunction with other agents such as dextran 40.

Anastomosis, Surgical↗
PubMed1993

Restoration of T-cell function in HIV infection by reduction of intracellular cAMP levels with adenosine analogues.

OBJECTIVE AND DESIGN: The impaired function of T cells is characteristic of HIV infection. It contributes to disease pathogenesis and is associated with disease prognosis. Our aim was to describe a biochemical basis for this impairment and a pharmacological way of restoring function. METHODS: Measurement of intracellular cAMP, protein kinase A (PKA) activity and proliferative capacity of T cells to recall antigens. RESULTS: HIV-seropositive individuals without AIDS showed significant increases in intracellular cAMP levels and PKA activity (inhibitors of lymphocyte function). The proliferative capacity of T cells to recall antigens correlated inversely with initial cAMP levels: poor proliferation was associated with high cAMP level in HIV infection. Moreover, drugs that reduced intracellular cAMP levels led to significant restoration of specific T-cell proliferation and cytotoxicity. CONCLUSIONS: Our findings indicate that high intracellular cAMP concentrations contribute to pathogenesis of T-cell anergy in HIV infection and that drugs that decrease intracellular cAMP levels may be beneficial in the treatment of AIDS.

Adenosine↗
PubMed1993

Analgesic efficacy of non-steroidal anti-inflammatory drugs in experimental pain in humans.

1. The aim of this study was to establish a simple and reliable experimental pain model that could distinguish the analgesic effects of non-steroidal anti-inflammatory drug (NSAID) treatment from placebo in human volunteers. 2. The reproducibility and reliability over time of subject pain ratings was compared using cutaneous electrical stimuli applied to either the thenar eminence or the ear lobe at varying intensities and modes. Subjects were asked to respond firstly, when the stimulus became clearly sharp and painful ('first pain') and secondly, when the sensation became deep and burning and no further increase in stimulus intensity could be tolerated ('second pain'). 3. Constant voltage stimuli were found to be more reproducible than constant current stimuli. Both phasic (intermittent) and tonic (continuous) stimulation modalities produced 'first' and 'second pain' sensations. The latter sensation was more reproducible, and was perceived as a burning pain which is akin to clinical pain. 4. Analgesics from the NSAID class were found to attenuate reliably only 'second pain' sensations. The analgesic effects of ibuprofen (ibuprofen vs placebo: 0.12 +/- 0.09 vs 0.02 +/- 0.07 volt h(-1), P = 0.03; 95% confidence interval for differences (CI): 0.03-0.18) and diflunisal (diflunisal vs placebo: 0.29 +/- 0.40 vs 0.005 +/- 0.27 volt h(-1), P = 0.0001; CI: 0.168-0.407), respectively, could be distinguished from placebo.

Adult↗
PubMed1993

Subcellular distribution of various boron compounds and implications for their efficacy in boron neutron capture therapy by Monte Carlo simulations.

Neutron capture therapy has a promising role in cancer treatment since it can achieve selectivity at the cellular level. The effect of this therapy depends on the subcellular localization of boron atoms in the target cell. Five boron compounds were investigated in this study: the monomeric and dimeric sulfhydryl boranes (BSH and BSSB), a boronated phenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). The study shows that when exponentially growing rat 9L gliosarcoma cells are exposed to an isoeffective concentration of each of the five compounds for 1 h, BOPP produces a much higher intracellular level of boron than the other four compounds; BSSB produces the second highest level, while exposure to BSH, VCDP, and BPA resulted in lower intracellular boron levels. Subcellular fractionation studies showed that most of the boron localized in the cytoplasm of the cells with all five compounds. A significantly higher boron concentration was found in the lysosomes of the cells, but the nuclei contained only minimal concentrations of boron. Computer simulations of neutron capture reactions with boron using a Monte Carlo simulation code indicated that BOPP would yield the highest potential effectiveness, followed by BSSB, BSH, VCDP, and BPA, in that order.

Animals↗
PubMed1992

Isolation and characterization of the human glutathione S-transferase A2 subunit gene.

We have isolated and characterized a second human liver glutathione S-transferase (GST) subunit gene. The nucleotide sequence of this gene indicates that it encodes the alpha class subunit A2, with a coding region of about 13 kb. Using reverse transcription assays it could be shown that the A2 subunit gene is expressed in human liver and HepG2 cells. The transcription initiation site has been determined by primer extension analysis. A "TATA"-sequence was found 26 nucleotides upstream from the transcription start site. A comparison of the structure of the A2 subunit gene with that of the A1 subunit gene shows significant sequence identity between the two genes. Southern blot analysis of restriction endonuclease digests of human DNA indicates that there may be several more human alpha class GST genes.

Amino Acid Sequence↗