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Biomedical subjects

T Nguyen

Publications and source records attributed to T Nguyen.

At least 235 records · Page 13Linked to original sources

MR artifacts, heat production, and ferromagnetism of Guglielmi detachable coils.

The Guglielmi detachable coil, a platinum microcoil used in the endovascular treatment of intracranial aneurysms, was studied in vitro for its MR imaging artifacts, heat production, and ferromagnetism. In addition, imaging artifacts were studied in vivo in eight patients who had undergone therapeutic placement of these coils. These devices displayed a very low level of MR artifact and no ferromagnetism or heat production. We conclude that the Guglielmi detachable coil is compatible with MR imaging in terms of both safety and image quality.

Aneurysm, Ruptured↗

A double-blind, randomized, controlled trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects taught the NCEP step I diet.

OBJECTIVE: We investigated the effect of egg feeding in 161 hypercholesterolemic (HC) or combined hyperlipidemic (CHL) free-living subjects taught the NCEP Step I Diet. METHODS: Subjects had LDL-C between 3.36 and 4.91 mmol/L (130 and 190 mg/dL). HC subjects had triglyceride concentrations < 75th %-ile, CHL > or = 75th %-ile. Six weeks after instituting the Step I Diet, subjects were randomized to two eggs or egg substitute daily for 12 weeks. RESULTS: Mean dietary intake (9-day food records) was within NCEP guidelines and 131 subjects finished with stable weight and adherence > 80%. Placebo group lipoprotein lipids were unchanged at study end for both HC (n = 35) and CHL (n = 21) subjects. Egg-fed HC subjects (n = 44) increased LDL-C nonsignificantly, 0.07 mmol/L (3 mg/dL) (p = 0.49). Egg-fed CHL subjects (n = 31) increased LDL-C 0.31 mmol/L (12 mg/dL) (p < 0.001). HDL-C increased significantly in both HC and CHL groups, 0.10 and 0.08 mmol/L (4 and 3 mg/dL, p = 0.003 and 0.02), respectively. HC and CHL subjects did not differ by apo E phenotype distribution. Postprandial triglyceride-rich lipoproteins and LDL subclass phenotype were unaffected by egg feeding in subsets of subjects. CONCLUSIONS: CHL subjects ingesting a Step I Diet in a free-living setting are sensitive to egg feeding and should benefit from dietary cholesterol restriction. The limited LDL-C rise in HC subjects resembles that seen in egg-fed normocholesterolemic subjects ingesting a Step I Diet, but requires confirmation.

Adult↗

Characterization of a human gene related to genes encoding somatostatin receptors.

We report the identification of a gene, named SLC-1(1), 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.

Amino Acid Sequence↗

Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists.

High-density arrays of oligonucleotide probes are proving to be powerful new tools for large-scale DNA and RNA sequence analysis. A method for constructing these arrays, using light-directed DNA synthesis with photo-activatable monomers, can currently achieve densities on the order of 10(6) sequences/cm2. One of the challenges facing this technology is to further increase the volume, complexity, and density of sequence information encoded in these arrays. Here we demonstrate a new approach for synthesizing DNA probe arrays that combines standard solid-phase oligonucleotide synthesis with polymeric photoresist films serving as the photoimageable component. This opens the way to exploiting high-resolution imaging materials and processes from the microelectronics industry for the fabrication of DNA probe arrays with substantially higher densities than are currently available.

Base Sequence↗

A novel gene codes for a putative G protein-coupled receptor with an abundant expression in brain.

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.

Amino Acid Sequence↗

Interleukin 4 inhibits hepatocyte growth factor-induced invasion and migration of colon carcinomas.

Hepatocyte growth factor (HGF) is known to have a number of biological properties including promoting tumor progression of human carcinomas. Metastasis involves a number of events that are attributed to induction by paracrine factors such as HGF. Identification of natural inhibitors of these events would allow better control of tumor progression. Recently we demonstrated that interleukin 4 (IL-4) can regulate proliferation of various human carcinoma cell lines. In the present study, we used established human colon carcinoma cell lines and primary colon carcinoma cell cultures to determine if IL-4 could regulate HGF-induced cell proliferation and other events of tumor progression such as MMP (matrix metalloproteinases)-1, -2, and -9 production, cell migration and cell-matrix invasive activity. All colon carcinoma cell lines expressed HGF and IL-4 receptors. IL-4 significantly inhibited HGF-induced proliferation of one cell line. Cell-matrix invasion was significantly enhanced by HGF (0.1-10 ng/ml); IL-4 (1-10 U/ml) significantly inhibited HGF-induced invasion in a dose-dependent manner. IL-4 also inhibited HGF-induced cell-matrix invasion of metastatic colon carcinoma cells and HGF-induced cell migration. HGF enhanced MMP-1, -2, and -9 production by cell lines. This effect could be inhibited by IL-4. These findings indicate that IL-4 is a potent inhibitor of HGF-induced invasion and metastasis-related functions of human colon carcinoma cells.

Antigens, CD↗

Specific inhibition of in vitro transcription elongation by triplex-forming oligonucleotide-intercalator conjugates targeted to HIV proviral DNA.

A 16-base pair oligo(purine)-oligo(pyrimidine) sequence present in the coding region of two HIV 1 proviral genes (pol and nef) was chosen as a target for triplex-forming oligonucleotides in in vitro transcription assays. Inhibition of transcription elongation was observed with triplex-forming oligonucleotide-acridine conjugates (Acr-15-TCG:5'-Acr-T4CT4G6-3' and Acr-9-TC:5'-Acr-T4CT4-3' where C is 5-methylcytosine) under conditions where the unsubstituted oligomers did not exhibit any inhibitory effect. Both SP6 bacteriophage RNA polymerase and eukaryotic RNA polymerase II were physically blocked by such a triplex barrier. The polymerase arrest is caused by the triple-helical complex involving the hydrogen-bonded oligonucleotide stabilized by the intercalated moiety and not solely by the acridine molecule specifically intercalated at the duplex-triplex junction. The stability of the triple-helical complex formed by the 15-mer containing thymines, cytosine, and guanines (15-TCG) and involving the formation of six contiguous C.GxG base triplets was strongly enhanced in the presence of a benzopyridoindole derivative (BePI), which intercalates in triplex structures. This improvement of the binding affinity led to an increased inhibition of transcription elongation. The present results demonstrate the necessity to use triplex-forming oligonucleotides with high binding affinity and a long residence time on their double-stranded target to efficiently inhibit transcription elongation. These data provide a rational basis for the optimization and the development of triplex-forming oligonucleotides as transcriptional blockers, even when they are targeted to the transcribed portion of a gene, downstream of the transcription initiation site.

Base Sequence↗

A novel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3.

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.

Amino Acid Sequence↗

Mechanisms for the maintenance and eventual degradation of neurofilament proteins in the distal segments of severed goldfish mauthner axons.

Cellular mechanisms that might affect the degradation of neurofilament proteins (NFPs) were examined in the distal segments of severed goldfish Mauthner axons (M-axons), which do not degenerate for more than 2 months after severance. Calpain levels, as determined by reactivity to a polyclonal antibody, remained constant for 80 d postseverance in distal segments of M-axons and then declined from 80 to 85 d postseverance. Calpain activity in rat brain, as determined by a spectrophotometric assay, was much higher than calpain activity in control and severed goldfish brain, spinal cord, muscle, or M-axons. Calpain activity was extremely low in M-axons compared with that in all other tissues and remained low for up to 80 d postseverance in distal segments of M-axons. Phosphorylated NFPs, as determined by Stains-All treatment of SDS gels, were maintained for up to 72 d postseverance and then decreased noticeably at 75 d postseverance when NFP breakdown products appeared on silver-stained gels. By 85 d post-severance, phosphorylated NFPs no longer were detected, and NFP breakdown products were the most prominent bands on silver-stained gels. These results suggest that the distal segments of M-axons survive for months after severance, because NFPs are maintained in a phosphorylated state that stabilizes and protects NFPs from degradation by low levels of calpain activity in the M-axon; the distal segments of severed M-axons degenerate eventually when NFPs no longer are maintained in a phosphorylated state and become susceptible to degradation, possibly by low levels of calpain activity in the M-axon.

Animals↗

A serotonin receptor gene (5HT1A) variant found in a Tourette's syndrome patient.

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 (Arg(219) 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 (Asn(417) 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.

Alcoholism↗

Structures, alternative splicing, and neurexin binding of multiple neuroligins.

Neuroligin 1 is a neuronal cell surface protein that binds to a subset of neurexins, polymorphic cell surface proteins that are also localized on neurons (Ichtchenko, K., Hata, Y., Nguyen, T., Ullrich, B., Missler, M., Moomaw, C., and Südhof, T. C. (1995) Cell 81, 435-443). We now describe two novel neuroligins called neuroligins 2 and 3 that are similar in structure and sequence to neuroligin 1. All neuroligins contain an N-terminal hydrophobic sequence with the characteristics of a cleaved signal peptide followed by a large esterase homology domain, a highly conserved single transmembrane region, and a short cytoplasmic domain. The three neuroligins are alternatively spliced at the same position and are expressed at high levels only in brain. Binding studies demonstrate that all three neuroligins bind to beta-neurexins both as native brain proteins and as recombinant proteins. Tight binding of the three neuroligins to beta-neurexins is observed only for beta-neurexins lacking an insert in splice site 4. Thus, neuroligins constitute a multigene family of brain-specific proteins with distinct isoforms that may have overlapping functions in mediating recognition processes between neurons.

Alternative Splicing↗

Transforming growth factor beta 1 improves wound healing and random flap survival in normal and irradiated rats.

OBJECTIVES: To evaluate the effect of chronic irradiation on wound healing and random flap survival (FV), and the effect of transforming growth factor beta 1 (TGF-beta 1) in this setting using an animal model. DESIGN: A randomized, controlled study with four groups of rats to study the effect of irradiation 4 months before surgical intervention. The effect of TGF-beta 1 on FV and wound healing also was evaluated in the irradiated and nonirradiated groups. SUBJECTS: Ninety-five rats were available for evaluation. Group 1 (n = 10) was the control; group 2 (n = 28) received TGF-beta 1; group 3 (n = 28) received radiation therapy; and group 4 (n = 29) received radiation therapy and TGF-beta 1. INTERVENTION: The irradiated groups received 15 Gy to their dorsal skin. Four months later all received McFarlane skin flaps. Groups 2 and 4 received topical TGF-beta 1, 4 micrograms, to the bed of the flap; groups 1 and 3 received saline. On postoperative day 7 all rats were evaluated for tensile strength and FV, and histologic staining with hematoxylin-eosin for collagen and TGF-beta 1 was done. The slides were evaluated in a "blinded" fashion. RESULTS: Irradiation decreased tensile strength and FV, but not to a notable degree. Transforming growth factor beta 1 improved tensile strength in the irradiated (P = .04, Student's t test) and nonirradiated groups (P = .05, Student's t test). Transforming growth factor beta 1 also improved FV in all groups, but significantly in the irradiation plus TGF-beta 1 group (P = .001, Student's t test). The TGF-beta 1 group had the most mature collagen present at the wound edge. No qualitative difference was seen in the immunohistochemical staining for the four groups. CONCLUSIONS: Transforming growth factor beta 1 improves wound healing and random FV in radiated and nonirradiated rat skin. Further study is needed to determine the radiation dose necessary to create an "impaired wound-healing model" in rats, and the optimum dose of TGF-beta 1 in this setting.

Administration, Topical↗

Transforming growth factor-beta 1 enhances bone healing to unloaded tricalcium phosphate coated implants: an experimental study in dogs.

Growth of bone into cementless prosthetic components is compromised after revision of failed joint prostheses and by osteoporosis, gaps, and micromotion. We studied the effects of recombinant human transforming growth factor-beta 1 adsorbed on ceramic coated implants on the improvement of mechanical fixation and bone growth on the implant. Unloaded cylindrical grit-blasted titanium alloy implants were inserted bilaterally into both the medial and lateral femoral condyles of 10 skeletally mature mongrel dogs. The implants measured 10 mm in length and 6 mm in diameter and were initially surrounded by a 2 mm gap. One implant had an uncoated titanium surface and three implants were coated with tricalcium phosphate and 0, 0.3, or 3.0 micrograms of recombinant human transforming growth factor-beta 1. The dogs were killed at 6 weeks. Mechanical testing showed a 3-fold increase in fixation for the 0.3 microgram dose of recombinant human transforming growth factor-beta 1 and a 2-fold increase for the 3.0 micrograms dose. Histological analysis of bone growth on the implant demonstrated that maximal stimulation occurred with the 0.3 microgram dose, but bone volume in the gap was maximally stimulated by the 3.0 micrograms dose and increased 2-fold over control values. The majority of tricalcium phosphate was resorbed after the 6-week observation period. This study suggests that recombinant human transforming growth factor-beta 1 adsorbed onto implants coated with tricalcium phosphate ceramic can enhance mechanical fixation and bone growth on the implant. The use of transforming growth factor-beta 1 on ceramic coated prosthetic components may help to improve the functional outcome of cementless total joint replacements.

Animals↗

Prevalent vertebral deformities: relationship to bone mineral density and spinal osteophytosis in elderly men and women.

The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density (BMD) at the lumbar spine and femoral neck, severity of spinal degenerative disease and vertebral deformity prevalence. We performed standardized spinal radiographs in a random sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study, a population-based study of fracture risk factors. Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis. BMD was measured by dual-energy X-ray absorptiometry. The prevalence of vertebral deformities was critically dependent on the criterion used. The less strict criteria seemed to overestimate deformities at either end of the spine region analysed. However, irrespective of the criterion used, prevalence of deformity was higher in men than in women (25% vs 20% for the 3 SD criterion, 17% vs 12% for the 4 SD criterion and 27% vs 25% for the 25% criterion). Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25% criterion (OR/SD change in BMD 1.39 (p = 0.02) vs 1.20 (p = 0.19)), 3 SD criterion (OR/SD change in BMD 1.45 (p = 0.01) vs 1.10 (p = 0.34)) and 4 SD criterion (OR/SD change in BMD 1.98 (p = 0.0002) vs 1.68 (p = 0.008)). BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women. Severity of spinal osteophytosis was not associated with vertebral deformity. In conclusion, femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures. Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk, indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis. These findings support the use of femoral neck bone densitometry in older men and women. Moreover, these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly, with important implications for the design of clinical trials. However, irrespective of the criterion used, vertebral deformities in men are at least as common, if not more so, than in women, suggesting that vertebral osteoporotic fractures are overlooked in men.

Absorptiometry, Photon↗

Can biochemical markers predict bone loss at the hip and spine?: a 4-year prospective study of 141 early postmenopausal women.

A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0 +/- 3.3 years, mean menopause duration 20.4 +/- 5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at -20 degrees C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was -1.41% (0.18) at the lumbar spine and -0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.

Absorptiometry, Photon↗

Spatial and temporal distribution of Indian hedgehog mRNA in the embryonic mouse mandible.

Hedgehog genes are involved in pattern formation during embryonic development. A recent report showed that Sonic hedgehog is expressed in the mouse mandible in the presumptive incisor region. In the present study, Indian hedgehog (Ihh) transcripts were present from gestational day 9 to 14 in the mouse mandible (reverse transcription/polymerase chain reaction analysis). Ihh mRNA was present in the dental lamina in both incisor and molar regions and in the developing whiskers (in-situ hybridization). Ihh may be involved in the site-specific proliferation of mandibular epithelium during the formation of the dental lamina. This is consistent with the observation that endogenous synthesis of retinoic acid is necessary for the initiation of odontogenesis and that retinoic acid induces hedgehog expression.

Animals↗