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Biomedical subjects

S Thomas

Publications and source records attributed to S Thomas.

At least 469 records · Page 26Linked to original sources
PubMed1994

A large duplicated area in the polycystic kidney disease 1 (PKD1) region of chromosome 16 is prone to rearrangement.

An area of 500 kb at the proximal end of the polycystic kidney disease 1 (PKD1) region has been mapped in detail, with 260 kb cloned in cosmids. The area cloned from normal individuals contains two homologous but divergent regions each of 75 kb, including the previously described marker 26-6. Pulsed-field gel electrophoresis identified a duplication of 75 kb of this region, referred to as the OX duplication (OXdup), in three patients with PKD1. The OXdup probably arose by an unequal exchange promoted by misalignment of partially homologous areas. Study of the OXdup in a large PKD1 family showed that it segregated with PKD1 in just one-half of the family, indicating that a recent crossover had occurred between the OXdup and PKD1 and showing that it was not a PKD1 mutation. Further analysis identified an OXdup breakpoint fragment: the OXdup was subsequently identified in 2 normal individuals of 110 assayed. The finding of the OXdup and in other individuals an 11-kb deletion (OXdel) at a similar point within this duplicated area indicates that this is an unusually unstable genomic region.

Chromosome Mapping↗
PubMed1994

Mutations in the conserved regions of p53 are infrequent in betel-associated oral cancers from Papua New Guinea.

Seventy-five % of the world's oral cancers arise in developing countries. In high incidence areas of Southeast Asia such as Papua New Guinea (PNG) the major region-specific risk exposure is betel quid chewing. While it has been shown that p53 gene mutations in the conserved midregion (exons 5-9) are a common feature of oral cancers in the developed world, there is no information on this type of genetic lesion in betel quid-associated oral cancers. We examined 50 oral squamous cell carcinomas, 20 from Baltimore, MD and 30 from PNG, for mutations in exons 5-9 of the p53 gene. DNA extracted from frozen biopsies was amplified by polymerase chain reaction, the purified product was sequenced directly, and mutations were confirmed by repeating the entire procedure. Mutations were found in 3 of 30 tumors from PNG (10%), whereas 9 mutations were detected among the 20 tumors (45%) from Baltimore, MD. This difference in frequency is statistically significant (P < 0.01) by chi 2 analysis. Nuclear accumulation of p53 protein, determined by immunohistochemistry with the CM-1 antiserum, was observed in the PNG cases harboring a missense mutation of the p53 gene. In agreement with the low number of PNG cancers with mutations, only 17% of the cases from PNG were immunostain positive. To explore whether less conserved regions of the gene are preferential targets for alterations in this patient group, sequence analysis in tumors from PNG was extended to outlying regions of the gene (all of exons 4 and 10, and splice sites), but mutations in only two additional tumors were identified. The presence of human papillomavirus DNA in PNG cases was examined with a polymerase chain reaction-based procedure, and viral sequences (human papillomavirus strains 11/16) were detected in two tumors. Human papillomavirus-triggered degradation of the tumor suppressor protein is thus unlikely to be a typical pathway to p53 dysfunction in tumors from PNG.

Adult↗
PubMed1994

Bicycle incidents in children--abdominal trauma and handlebars.

OBJECTIVES: To investigate the frequency and causes of bicycle related abdominal injuries in children and to examine the pattern of presentation. DESIGN: The study was a prospective study of bicycle related injury in children less than 15 years of age presenting to two paediatric hospitals (15 April-30 June 1992) and three general hospitals (1 August 1991-30 June 1992). RESULTS: In a series of 813 children, 41 sustained non-penetrating abdominal trauma due to a bicycle incident. In 21 cases, handlebar trauma was responsible. Ten of these children suffered life-threatening intra-abdominal injury. Handlebars with no plastic or foam covering of the metal ends were involved in all ten cases. In several of these cases, presentation to hospital was delayed and in others confirmation of the extent of injury took up to 48 hours. The length of hospital stay for those with significant intra-abdominal organ damage ranged from two to 156 days. CONCLUSIONS: Intra-abdominal trauma must be considered when dealing with children who are victims of bicycle trauma. Impact with handlebars may have occurred and some form of padded protection of handlebar ends is recommended unless their design can be suitably modified.

Abdominal Injuries↗
PubMed1994

[3H]A-81988, a potent, selective, competitive antagonist radioligand for angiotensin AT1 receptors.

Abbott-81988 (A-81988), 2-(N-n-Propyl-N-[(2'-[1H-tetrazol-5-yl]biphenyl-4- yl)methyl]amino)pyridine-3-carboxylic acid is a potent, competitive, non-peptidic antagonist of angiotensin AT1 receptors. A-81988 was labeled with tritium to high specific activity (16 Ci/mmol) and radioligand binding assays performed in rat liver membranes. [3H]A-81988 bound with high affinity (KD = 0.57 nM) and the KD determined from kinetics assays was similar. Non-specific binding (defined with 10(-6) M angiotensin-II) was very low (< 6% at the KD). The binding of [3H]A-81988 was competitive and exhibited appropriate pharmacological specificity for compounds acting at angiotensin AT1 receptors. These properties demonstrate that [3H]A-81988 will be a useful radioligand for studies of angiotensin AT1 receptors in various tissues.

Angiotensin II↗
PubMed1994

Effectiveness of bicycle helmets in preventing head injury in children: case-control study.

OBJECTIVE: To examine the risk of injury to the head and the effect of wearing helmets in bicycle accidents among children. DESIGN: Case-control study by questionnaire completed by the children and their carers. SETTING: Two large children's hospitals in Brisbane, Australia. SUBJECT: 445 children presenting with bicycle related injuries during 15 April 1991 to 30 June 1992. The cases comprised 102 children who had sustained injury to the upper head including the skull, forehead and scalp or loss of consciousness. The controls were 278 cyclists presenting with injuries other than to the head or face. A further 65 children with injuries to the face were considered as an extra comparison group. MAIN OUTCOME MEASURES: Cause and type of injury, wearing of helmet. RESULTS: Most children (230) were injured after losing control and falling from their bicycle. Only 31 had contact with another moving vehicle. Children with head injury were significantly more likely to have made contact with a moving vehicle than control children (19 (19%) v 12 (4%), P < 0.001). Head injuries were more likely to occur on paved surfaces than on grass, gravel, or dirt. Wearing a helmet reduced the risk of head injury by 63% (95% confidence interval 34% to 80%) and of loss of consciousness by 86% (62% to 95%). CONCLUSIONS: The risk of head injury in bicycle accidents is reduced among children wearing a helmet. Current helmet design maximises protection in the type of accident most commonly occurring in this study. Legislation enforcing helmet use among children should be considered.

Accidents, Traffic↗
PubMed1994

Isolation and sequence of a full length cDNA encoding a novel rat inositol 1,4,5-trisphosphate 3-kinase.

Immunoscreening a rat liver cDNA expression library has led to the isolation of a full-length cDNA clone encoding a novel isoform of rat inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase). Sequence comparison shows it (i) to be 93% identical to human hippocampus IP3 3-kinase B over 468 residues at the protein level, and (ii) to encode a protein 204 amino acids larger than the published sequence of its human homologue.

Amino Acid Sequence↗
PubMed1994

Recombinant vaccinia viruses expressing interleukin-5 stimulate an earlier appearance of antibody-secreting cells in the lung.

Interleukin-5 (IL-5) is a cytokine that participates in the regulation of antibody secretion, in particular promoting the secretion of IgA at mucosal sites. In this report, recombinant vaccinia viruses expressing IL-5 have been inoculated into mice and the appearance of antibody-secreting cells in the spleen and lungs investigated. Although vaccinia virus-expressed IL-5 did not increase the level of IgA in serum, antibody-secreting cells, measured in an enzyme-linked immunosorbent spot assay, appeared earlier in lungs when the immunizing virus expressed IL-5. These early B cells secreted either IgM or IgG1.

Animals↗
PubMed1994

PBDX is the XG blood group gene.

We have identified the Xga antigen, encoded by the XG blood group gene, by employing rabbit polyclonal and mouse monoclonal antibodies raised against a peptide derived from the N-terminal domain of a candidate gene, referred to earlier as PBDX. In indirect haemagglutination assays, these anti-peptide antibodies react with Xg(a+) but not Xg(a-) erythrocytes. In antibody-specific immobilization of antigen (ASIA) and immunoblot assays, the anti-peptide antibodies react with the same molecule as does human anti-Xga. Therefore, by its identity with PBDX, Xga is identified as a cell-surface protein that is 48% homologous to CD99 (previously designated the 12E7 antigen), the product of MIC2 which is tightly linked to XG. PBDX is renamed here XG.

12E7 Antigen↗
PubMed1994

Malignant transformation of human bronchial epithelial cells by radon-simulated alpha-particles.

Epidemiological studies have shown that inhalation of radon is associated with an increased risk for bronchogenic carcinoma in uranium miners. These alpha-emitting radon daughters also represent the largest component of background radiation to the general public. In the present study, the oncogenic transforming effects of single versus multiple doses of radon-simulated alpha-particles were examined using human papillomavirus-immortalized human bronchial epithelial cells. Endpoints such as growth kinetics, resistance to serum and 12-O-tetradecanoylphorbol-13-acetate-induced terminal differentiation, anchorage-independent growth and tumorigenicity in nude mice were used to assess the various stages of transformation in the bronchial epithelial cells. We show here, for the first time, that immortalized human cells in culture can be malignantly transformed by a single 30 cGy dose of alpha-particles. Transformed cells produced progressively growing subcutaneous tumors upon inoculation into athymic nude mice. Immunofluorescent staining of keratin and isozyme analysis of the cell lines subsequently generated from these tumors indicated that the cells were of human epithelial origin. Analysis of genomic DNA from the tumorigenic cell lines using PCR amplification and restriction enzyme analysis demonstrated no point mutation at either codon 12/13 or 61 in any of the ras oncogenes examined (K-, N- and H-ras). This system provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.

Animals↗
PubMed1994

The G-C specific DNA binding drug, mithramycin, selectively inhibits transcription of the C-MYC and C-HA-RAS genes in regenerating liver.

Expression of the c-myc and c-Ha-ras protooncogenes is dramatically increased in regenerating rat liver as an early response to partial hepatectomy. Nuclear runon transcription studies confirm that the increased c-myc and c-Ha-ras mRNA levels in regenerating livers reflect transcriptional activation of these genes. Mithramycin, a G-C specific DNA binding drug, prevents the increased transcriptional activity of c-myc and c-Ha-ras genes after hepatectomy but does not alter the transcriptional activity of the beta-actin gene. Continuous exposure of rats to mithramycin after hepatectomy prevents the increase in both c-myc and c-Ha-ras expression and blocks the increased cellular proliferation characteristic of regeneration. The delayed increase in c-myc and c-Ha-ras gene expression is associated with a delay in cellular proliferation. The inhibition of c-myc and c-Ha-ras transcription by mithramycin, the delay in cellular proliferation, and the ability of mithramycin to prevent protein binding to the c-myc promoter, suggest that the increased expression of these genes is a necessary component of liver regeneration.

Animals↗
PubMed1994

The use of percutaneous transluminal angioplasty in hepatic artery stenosis after transplantation.

Graft ischemia following liver transplantation is associated with a high incidence of morbidity and mortality. The present report concerns a group of seven patients in whom an anastomotic stenosis of the hepatic artery was identified. Three patients had unexplained allograft dysfunction at a median time of 28 days (range 13-64 days), and 3 had a biliary leak at a median time of 42 days after liver transplantation (range 35-270 days). In one patient the stenosis was diagnosed by routine Doppler ultrasound one week after transplant. Management was by percutaneous transluminal angioplasty at a median time of 35 days (range 13-270 days) after transplantation. After angioplasty there was a marked improvement in clinical appearance, liver function, and liver histology in 5 of the 7 patients. Those patients who had a biliary leak subsequently developed strictures that eventually required biliary tract reconstruction (hepaticojejunostomy) in two and retransplantation in one. Percutaneous transluminal angioplasty is an effective way of improving arterial blood flow in cases of anastomotic stenosis, reducing the likelihood of complete occlusion by thrombosis. If recognized early and treated promptly ischemic changes in the graft can resolve and the development of biliary strictures may be avoided.

Adult↗
PubMed1994

Positive selection for resistance to 2-deoxyglucose gives rise, in Streptococcus salivarius, to seven classes of pleiotropic mutants, including ptsH and ptsI missense mutants.

We have used the toxic non-metabolizable glucose/mannose analogue 2-deoxyglucose to isolate a comprehensive collection of mutants of the phosphoenolpyruvate:sugar phosphotransferase system from Streptococcus salivarius. To increase the range of possible mutations, we isolated spontaneous mutants on different media containing 2-deoxyglucose and various metabolizable sugars, either lactose, melibiose, galactose or fructose. We found that the frequency at which 2-deoxyglucose-resistant mutants were isolated varied according to the growth substrate. The highest frequency was obtained with the combination galactose and 2-deoxyglucose and was 15-fold higher than the rate observed with the mixture melibiose and 2-deoxyglucose, the combination that gave the lowest frequency. By combining results from: (i) Western blot analysis of IIIMan, a specific component of the phosphoenolpyruvate:mannose phosphotransferase system in S. salivarius; (ii) rocket immunoelectrophoresis of HPr and EI, the two general energy-coupling proteins of the phosphotransferase system; and (iii) from gene sequencing, mutants could be assigned to seven classes.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗
PubMed1994

A randomised comparison of the Omniflex and Magnarail systems in recanalisation of coronary occlusions.

OBJECTIVE: The reported success rates for angioplasty of occluded coronary arteries fall some way short of the success rates for angioplasty of sub-occlusive stenoses. Two angioplasty systems used in this setting were compared. DESIGN: A prospective randomised open study comparing the Magnarail system (Schneider) and the Omniflex system (Medtronic). SETTING: A regional cardiothoracic centre performing over 300 angioplasty procedures a year. PATIENTS AND METHODS: 50 consecutive patients with occluded (thrombolysis in myocardial infarction study (TIMI) grade 0 or 1) arteries thought to be suitable for recanalisation were assigned to undergo angioplasty with either the Magnarail or Omniflex as the primary system. Twenty minutes of fluoroscopic screening was allowed with the primary randomised system before it was considered a failure. The other non-randomised system could then be used at the operators' discretion, and a further 20 minutes' screening was permitted. MAIN OUTCOME MEASURES: A patent coronary artery with a residual stenosis of < 50% with prompt distal opacification (TIMI grade 3 flow) and a reduction in collateral supply to the index artery. RESULTS: The overall success rate in recanalising occluded vessels was 72%-64% for the Magnarail system used as the primary system and 51.7% for the Omniflex (NS). The Magnarail was more successful in angioplasties of the right coronary artery (11/14 v 3/10, p = 0.02) and in mid and distal sites of occlusion (11/17 v 4/14, p < 0.05). There was a trend in favour of the Omniflex in the left anterior descending coronary artery. CONCLUSION: Both systems would seem to be suitable for angioplasty of occluded coronary arteries. The improved steerability of the Magnarail may be advantageous in distal occlusions and lesions in tortuous arteries. The relatively stiffer Omniflex may be superior for proximal occlusions. The study group was too small to confirm this unequivocally.

Angioplasty, Balloon, Coronary↗
PubMed1994

UREA TRANSPORT BY HEPATOCYTES AND RED BLOOD CELLS OF SELECTED ELASMOBRANCH AND TELEOST FISHES

Although urea transport is receiving increased attention in mammalian systems, very little is known about urea transport in fish tissues. This study examined mechanisms of urea transport in red blood cells and hepatocytes from the lesser spotted dogfish (Scyliorhinus canicula), Atlantic stingray (Dasyatis sabina), turbot (Scopthalmus maximus), redfish (Scianops ocellatus), gulf toadfish (Opsanus beta) and oyster toadfish (Opsanus tau). Urea appeared to be passively distributed in both tissues (i.e. there was no difference between plasma and tissue urea concentrations). Additionally, a number of in vitro experiments examining [14C]urea flux were performed. In red blood cells from all species except redfish, urea transport occurred via simple passive diffusion, but redfish red blood cells showed a small (25 %) phloretin-sensitive uptake component. In hepatocytes of the two elasmobranch species (dogfish and stingray), urea efflux was also by simple passive diffusion. However, urea efflux in toadfish (both O. beta and O. tau) hepatocytes exhibited a marked phloretin-sensitivity, and O. beta hepatocytes were used in further experiments with other inhibitors and treatments. Urea transport in O. beta had a relatively high specificity for urea compared with the urea analogues acetamide, thiourea and N-methylurea, was unaffected by phloridzin and extracellular Na+ removal, and was not inhibited by physiological levels of glucose (0.5&shy;10 mmol l-1). A phloretin-sensitive glucose transport, that was not inhibited by physiological levels of urea, was discovered in O. beta hepatocytes. The results are discussed in terms of patterns of species distribution and similarities between urea and glucose transport.

Journal Article↗