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Biomedical subjects

T M Williams

Publications and source records attributed to T M Williams.

At least 91 records · Page 5Linked to original sources
PubMed1996

Strategy for distinguishing a new DQB1 allele (DQB1*0611) from the closely related DQB1*0602 allele via sequence specific PCR or direct DNA sequencing.

A novel DQ6 allele (DQB1*0611) was identified via direct DNA sequencing in an African-American donor for bone marrow transplantation. The allele was not suspected on the basis of a sequence specific PCR assay which instead indicated the presence of DQB1*0602. DQB1*0602 and DQB1*0611 differ in exon 2 only at codon 9 resulting in a tyrosine substitution for phenylalanine. A modification of current DQB1 sequence specific PCR assays was devised which allows distinction between the closely related DQB1*0602 and DQB1*0611 alleles. Preliminary allele frequency studies suggest that DQB1*0611 is rare both in a non-African American sample and in American of African descent carrying DR11, DQ6 haplotypes. The selection of various DQB1*0611 detection methods is discussed.

Alleles↗
PubMed1995

Peptidyl dipeptidase A-catalyzed metabolism of delta sleep-inducing peptide in bovine brain microvessel endothelial cells: a cell culture model of the blood brain barrier.

Previous studies have shown that the metabolism of delta sleep-inducing peptide (DSIP) in the blood-brain barrier (BBB) is catalyzed by amino-peptidases. In this study, we have shown that peptidyl dipeptidase A in cultured bovine brain microvessel endothelial cells (BBMEC), a model of the BBB, and a purified form of this enzyme can also metabolize DSIP by sequential hydrolyses of dipeptides or tripeptides from the carboxyl terminus of this nonapeptide. Both the dipeptidase and tripeptidase activity associated with peptidyl dipeptidase A can be inhibited by captopril. Total stabilization of DSIP to metabolism in BBMEC could be achieved by inclusion of an inhibitor of peptidyl dipeptidase A (e.g., captopril) and an inhibitor of aminopeptidases (e.g., bestatin).

Amino Acid Sequence↗
PubMed1995

EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomen.

Chromosome translocations found in neoplasms often result in the creation of hybrid genes encoding chimeric proteins. This case study describes a patient with desmoplastic small round cell tumor (DSRCT) of the abdomen, an aggressive neoplasm characterized by translocation of chromosomes 11 and 22. Southern hybridization showed that the Ewing sarcoma gene (EWS) gene was rearranged in the DSRCT. Reverse transcriptase-polymerase chain reaction analysis of tumor cell RNA revealed that exons 1 to 7 of the EWS gene were joined to exons 8 to 10 of the Wilms' Tumor-1 (WT-1) gene resulting in the production of a chimeric message. The WT-1 and EWS genes encode DNA and RNA binding proteins involved in Wilms' tumor and Ewing sarcoma pathogenesis, respectively. The fusion of these two genes in DSRCT results in the production of a putatively oncogenic protein composed of the zinc finger DNA binding domains of WT-1 linked to potential transcriptional regulatory domains of EWS. DNA sequencing revealed the genomic breakpoints of translocation on chromosomes 11 and 22. The genomic breakpoint on chromosome 22 occurred in EWS intron 7 just 2 nucleotides 3' of exon 7. Polymerase chain reaction-based assays were developed that could detect the fused genes in the DSRCT tumor using either RNA or genomic DNA. The potential diagnostic use of these assays is discussed.

Abdominal Neoplasms↗
PubMed1995

Thermoregulation of the intra-abdominal testes of the bottlenose dolphin (Tursiops truncatus) during exercise.

Dolphins possess a vascular countercurrent heat exchanger (CCHE) that functions to cool their intra-abdominal testes. Spermatic arteries in the posterior abdomen are juxtaposed to veins returning cooled blood from the surfaces of the dorsal fin and tail flukes. In this study, we investigated the effect of exercise on CCHE function in the bottlenose dolphin. The CCHE flanks a region of the bowel in the posterior abdomen and influences colonic temperatures. A rectal probe housing a linear array of seven copper-constantan thermocouples was designed to measure colonic temperatures simultaneously at positions anterior to, within and posterior to the region of the colon flanked by the CCHE. Immediately after vigorous swimming, temperatures at the CCHE decreased relative to resting and pre-swim values: post-swim temperatures at the CCHE were maximally 0.5 degrees C cooler than pre-swim temperatures. These data suggest that the CCHE has an increased ability to cool the arterial blood supply to the testes when the dolphin is swimming. This ability could offset the increased thermal load on the testes is an exercising dolphin. To the best of our knowledge, this is the first report of deep body cooling in an exercising mammal that is not undertaking a dive.

Animals↗
PubMed1995

Modeling of natural organic matter transport processes in groundwater.

A forced-gradient tracer test was conducted at the Georgetown site to study the transport of natural organic matter (NOM) in groundwater. In particular, the goal of this experiment was to investigate the interactions between NOM and the aquifer matrix. A detailed three-dimensional characterization of the hydrologic conductivity heterogeneity of the site was obtained using slug tests. The transport of a conservative tracer (chloride) was successfully reproduced using these conductivity data. Despite the good simulation of the flow field, NOM breakthrough curves could not be reproduced using a two-site sorption model with spatially constant parameters. Preliminary results suggest that different mechanisms for the adsorption/desorption processes, as well as their spatial variability, may significantly affect the transport and fate of NOM.

Adsorption↗
PubMed1995

Osteogenic sarcoma metastatic to the kidney: spontaneous subcapsular hemorrhage with renal artery thrombosis.

The authors describe an occult metastatic deposit in the kidney of a 22-year-old woman; such lesions are not usually detected until autopsy. They postulate that after the development of acute subcapsular hematoma, a "renal compartmental syndrome" occurred, leading to renal artery thrombosis. Primary vascular involvement by the metastatic osteosarcoma, which was remote from the renal hilus, was not identified pathologically.

Adult↗
PubMed1995

Histologic evaluation of alveolar bone following CO2 laser removal of connective tissue from periodontal defects.

This study was undertaken to examine histologically the healing response of alveolar bone following removal of granulation and/or connective tissues from interproximal craters by manual curettage or ablation by carbon dioxide laser. The time required to complete each type of degranulation procedure was also compared. Four interproximal treatment sites in each quadrant of two dogs were randomly assigned to each treatment modality. Neither treatment modality was totally effective in removing all suprabony connective tissue. Healing was clinically uneventful and histologically similar for both treatment groups at all time intervals. Laser-treated specimens exhibited little or no inflammatory cell infiltrate, areas of heat-induced tissue necrosis, accumulations of carbonized debris that initially was surrounded by macrophages and eventually phagocytized by multi-nucleated giant cells, and spicules of nonvital bone that exhibited a surface layer of osteoid. Although manual curettage was found to be statistically significantly faster, the difference between mean times was roughly 55 seconds and therefore unlikely to be clinically significant.

Alveolar Bone Loss↗
PubMed1994

Temperature regulation of the testes of the bottlenose dolphin (Tursiops truncatus): evidence from colonic temperatures.

Dolphins possess a countercurrent heat exchanger that functions to cool their intra-abdominal testes. Spermatic arteries in the posterior abdomen are juxtaposed to veins returning cooled blood from the surfaces of the dorsal fin and flukes. A rectal probe housing a linear array of five copper-constantan thermocouples was designed to measure colonic temperatures simultaneously at positions anterior to, within, and posterior to the region of the colon flanked by the countercurrent heat exchanger. Colonic temperatures adjacent to the countercurrent heat exchanger were maximally 1.3 degrees C cooler than temperatures measured outside this region. Temporary heating and cooling of the dorsal fin and flukes affected temperatures at the countercurrent heat exchanger, but had little or no effect on temperatures posterior to its position. These measurements support the hypothesis that cooled blood is introduced into the deep abdominal cavity and functions specifically to regulate the temperature of arterial blood flow to the dolphin testes.

Animals↗
PubMed1993

5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.

A series of highly potent, structurally novel, non-nucleoside RT inhibitors has been described. Low nanomolar concentrations of 5-chloro-3-(phenylsulfonyl)-indole-2-carboxamide (1) inhibit the HIV-1 RT enzyme in vitro and HTLVIIIb viral spread in MT-4 human T-lymphoid cells. Good oral bioavailability was observed in rhesus monkeys upon oral dosing of 1 as a suspension in methocel. When compared to other non-nucleoside inhibitors (e.g. 15-18), 1 possesses improved inhibitory potency with respect to the wild-type RT, as well as the K103N and Y181C mutant enzymes. Additional studies within this class of inhibitors are in progress.

Animals↗
PubMed1993

Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogues.

A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalmido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB. One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by > 95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent.

Antiviral Agents↗
PubMed1993

Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1H)-one.

In an ongoing effort to develop novel nonnucleoside, specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors, a series of 3-[(pyridylmethyl)amino]- and 3-[(phenylmethyl)amino]-2-pyridinone derivatives was synthesized and tested for HIV-1 RT inhibitory activity. The more potent compounds have a 2'-methoxy group and 4'- and/or 5'-aliphatic substituents on the pyridyl and phenyl rings. Several of the more potent compounds were also evaluated for antiviral activity in MT-4 cell culture. From this series of compounds, 3-[N-[(5-ethyl-2-methoxy-6-methyl-3-pyridyl)methyl]amino]-5-ethyl-6- methylpyridin-2(1H)-one (6) was selected for clinical evaluation.

Aminopyridines↗
PubMed1993

Cognitive dysfunction in adults with type 1 (insulin-dependent) diabetes mellitus of long duration: effects of recurrent hypoglycaemia and other chronic complications.

To examine the long-term effects of recurrent severe hypoglycaemia and other biomedical complications on mental efficiency, a battery of cognitive tests was administered to 142 Type 1 (insulin-dependent) diabetic adult patients (age 33.5 +/- 5.6 years; mean +/- SD) and 100 demographically similar non-diabetic control subjects. All diabetic subjects had been diagnosed before the age of 17 years. Diabetic subjects with one or more complications (distal symmetrical polyneuropathy; advanced background or proliferative retinopathy; overt nephropathy; one or more episodes of severe hypoglycaemia) performed significantly (p < 0.001) more poorly than non-diabetic control subjects on tests requiring sustained attention, rapid analysis of visuospatial detail, and hand eye co-ordination. Regression analyses indicated that the best biomedical predictor of cognitive test performance was a diagnosis of polyneuropathy. Although severe recurrent hypoglycaemia was not associated with performance on any test, the neuropathy x recurrent hypoglycaemia interaction term was significant. These results suggest that in adults with Type 1 diabetes of long duration, recurrent hypoglycaemia does not appear to influence cognitive performance directly, but may interact with neuropathy to exaggerate or otherwise magnify the extent of neurobehavioural dysfunction.

Adult↗