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Biomedical subjects

S M Thomas

Publications and source records attributed to S M Thomas.

At least 19 recordsLinked to original sources
PubMed1999

The application of a linear algebra to the analysis of mutation rates.

Cells and bacteria growing in culture are subject to mutation, and as this mutation is the ultimate substrate for selection and evolution, the factors controlling the mutation rate are of some interest. The mutational event is not observed directly, but is inferred from the phenotype of the original mutant or of its descendants; the rate of mutation is inferred from the number of such mutant phenotypes. Such inference presumes a knowledge of the probability distribution for the size of a clone arising from a single mutation. We develop a mathematical formulation that assists in the design and analysis of experiments which investigate mutation rates and mutant clone size distribution, and we use it to analyse data for which the classical Luria-Delbrück clone-size distribution must be rejected.

Animals↗
PubMed1999

Evaluation of transcriptional fusions with green fluorescent protein versus luciferase as reporters in bacterial mutagenicity tests.

A bacterial plasmid was constructed on which the regulatory region of the umuC gene of Escherichia coli was fused to the coding sequence of the green fluorescent protein gene (gfp) from the jellyfish Aequorea victoria. Escherichia coli AB1157 strains carrying the plasmid emitted fluorescence in the presence of mutagens that induce the SOS DNA repair system. Data on tests with nitrosoguanidine, methylmethane sulphonate and UV radiation (254 nm) are presented. Although fluorescent detection using this system was not as rapid or sensitive as a similar luminescent equivalent (umuC-luxAB), the gfp reporter system was more robust. Escherichia coli umu gene induction was also analysed in Salmonella typhimurium TA1537 cells following plasmid transfer and exposure to the same range of mutagens. There was no significant difference in sensitivity between the two species. These preliminary results will provide the basis for development of mutagenicity test systems useful in the testing of complex mixtures, such as environmental samples, and the investigation of physiological parameters influencing spontaneous mutagenesis in bacteria.

Animals↗
PubMed1999

Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2.

The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2 binds to SHP substrate 1 (SHPS-1)/SIRP-1alpha, a transmembrane glycoprotein with adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887-6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223-13229). Therefore, we asked whether SHP2-SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl phosphorylation increased upon plating of murine fibroblasts onto specific extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1 tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced mitogen-activated protein kinase (MAPK) activation, and potentiation required functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we analyzed the responses of SHP-2 exon 3(-/-) and wild-type cell lines to being plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl phosphorylation of several focal adhesion proteins, MAPK activation, and the ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but were restored upon SHP-2 expression. Our data suggest a positive-feedback model in which, upon integrin engagement, basal levels of c-Src activity catalyze the tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces positive signals for downstream events such as MAPK activation and cell shape changes.

Animals↗
PubMed1999

Preponderance of hypokalaemia as a cause of acute onset quadriparesis in northern India/southern Nepal.

Of 68 patients who were admitted with acute quadriparesis to a hospital in northern India, over 70% were found to be hypokalaemic. The most common cause of hypokalaemia was that associated with gastroenteritis (54%). These patients had all received intravenous fluids previously. It is likely that their hypokalaemia was caused by gastrointestinal loss compounded by parenteral fluid replacement. The next most common group of hypokalaemia-associated quadriparesis had no obvious cause for hypokalaemia (38%). Hypokalaemia-induced quadriparesis is a potentially life-threatening illness which can be readily treated with potassium supplements. The physician should consider hypokalaemia in patients who present with acute onset quadriparesis, and even if diagnostic tests for hypokalaemia are not available, should consider a judicious trial of potassium supplementation empirically, provided that there are no contraindications.

Acute Disease↗
PubMed1999

Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin.

Paxillin is a focal adhesion scaffolding protein which was originally identified as a substrate of the oncogenic tyrosine kinase, v-src. Paxillin has been proposed to be involved in regulation of focal adhesion dynamics. Two alternatively spliced mouse paxillin cDNAs were cloned and in the process, a paxillin-related protein, Hic-5, was also identified. Cloning and characterization of Hic-5 indicates that this protein shares extensive homology with paxillin. Although Hic-5 was originally characterized as a TGF-beta-inducible gene and proposed to be a transcription factor involved in senescence, the studies here demonstrate that Hic-5 is localized to focal adhesion in REF52 cells and can interact with the focal adhesion proteins, Fak, Frnk, and vinculin. In addition, like paxillin, Hic-5 can bind to a negative regulator of Src PTKs, csk but does not bind to the adaptor protein Crk. Like paxillin, localization of this protein to focal adhesions is mediated primarily by the LIM domains; however, sequences outside the LIM domains also play a minor role in focal adhesion targeting. These results suggest that Hic-5 like paxillin could be involved in regulation of focal adhesion dynamics and raise the possibility that Hic-5 and paxillin could have overlapping or opposing functions in the overall regulation of cell growth and differentiation.

Amino Acid Sequence↗
PubMed1999

Perceptions of cancer and its causes among "Industrial Corridor" residents: the LMRICS Planning Project. Lower Mississippi River Interagency Cancer Study.

The Industrial Corridor is composed of 11 parishes heavily concentrated with petrochemical facilities along the Mississippi River from Baton Rouge to the mouth of the river. There exists a generalized belief that the proximity of these waste-emitting industries to residential areas has adversely impacted the health of the residents including increasing the rates of cancer. At the same time, Louisiana Tumor Registry data do not support the widely held belief of excess cancer rates in the corridor. A community in the corridor was chosen to explore the issues of health beliefs, health-seeking behavior, and perceived quality of life. An extensive questionnaire was developed and administered to a sample of community residents. The results of the questionnaire suggest there may be multiple factors that influence the perceived well-being and preventive health practices of corridor residents.

Black or African American↗
PubMed1998

Continuous culture dynamics for aniline metabolism by Pseudomonas sp. CIT1.

Inhibition by toxic substrates enables multiple steady states to arise in biodegradation systems. This phenomenon was investigated for the continuous metabolism of aniline by Pseudomonas sp. CIT1. Differences of various metabolic parameters between the two growth regimes (uninhibited and inhibited) and the transient response to a step-up in dilution rate were determined. Regulatory mechanisms consistent with the experimental evidence are proposed. Aniline is the transcriptional inducer of a metabolic pathway that converts aniline to TCA cycle intermediates. The suite of enzymes is coordinately expressed from a single promoter. We followed the level of the pathway mRNA using a fragment containing the catechol 2,3 dioxygenase gene (andioxB) and monitored the pathway enzyme activity using catechol 2,3 dioxygenase (C23D). The inhibited regime resulted in a 60% lower growth yield, near constant levels of C23D monomer, but a 50% reduction in the specific activity of C23D, increased RNA synthesis rates (total and aniline pathway mRNA), and elevated RNA decay rates. Elucidation of regulatory mechanisms indicates that C23D is noncompetitively inhibited by aniline and subject to feedback inhibition by 2-hydroxymuconic semialdehyde (HMS). During uninhibited growth regime operation, metabolism of HMS is the rate-limiting step; in contrast, conversion of aniline to catechol limits growth in the inhibited regime.

Aniline Compounds↗
PubMed1998

Construction of a umuC'-luxAB plasmid for the detection of mutagenic DNA repair via luminescence.

This paper describes a novel system for the detection of mutagenic DNA repair in Escherichia coli. The DNA damage inducible umuC gene of Escherichia coli has been fused to the luxAB genes from Vibrio harvleyi that encode the enzyme luciferase. Mutagenicity has been assessed semi-quantitatively by the induction of bioluminescence. This system is simple, rapid and equivalent in sensitivity to other currently available test procedures. Its use in the detection of known SOS mutagens MMS, MNNG and UV is described.

Artificial Gene Fusion↗
PubMed1998

Trends in the use of pelvimetry techniques.

Assessment of maternal pelvic dimensions is usually considered necessary where vaginal delivery is contemplated in a breech presentation or if reduced pelvic dimensions are suspected in a current or previous pregnancy. Pelvimetry techniques include computed tomography (CT), conventional radiography, digital fluorography and magnetic resonance imaging (MRI). The first three techniques result in a radiation dose to mother and fetus which, depending on how the technique is performed, can vary by up to 40-fold. Of the techniques using X-rays, CT pelvimetry with a lateral scanogram generally gives the lowest radiation dose and conventional radiography using an air gap technique with a single lateral view is a relatively low-dose alternative where CT is not available. A questionnaire was sent to 227 hospitals during 1993 and 1996 to assess whether there was a move towards lower dose techniques of pelvimetry. The results show a trend away from conventional pelvimetry (48.4% in 1993 to 28% in 1996) with a small proportion of centres using MRI (4%) in 1996. Of the centres still using conventional pelvimetry, relatively few were using a low-dose air-gap technique (2.1% in 1993 to 10.9% in 1996). An increasing majority of centres were using one-view CT (69.3% in 1993 and 80.4% in 1996) but a significant proportion were still performing more than one view. This study shows that there was a move towards lower dose techniques of pelvimetry but that there were still many hospitals that had not implemented a policy of reducing radiation exposure in these patients.

Female↗
PubMed1998

Update on endovascular management of arterial occlusive disease.

Although balloon angioplasty is the most widely used technique for treating peripheral vascular disease, developments in endovascular therapies have extended methods of percutaneous vascular intervention. Lasers have been used to recanalize occluded arteries. Mechanical devices can remove obstructions and metallic stents can be placed to keep a vessel open with good long-term patency.

Angiography, Digital Subtraction↗
PubMed1997

Establishment of a human squamous cell carcinoma cell line of the upper aero-digestive tract.

A human squamous cell carcinoma (SCC) cell line has been established from the surgical specimen of an untreated, upper aero-digestive tract tumour, diagnosed as a squamous carcinoma, grade III, of the pyriform fossa. The tumour tissue was grown as a xenograft in an athymic nude mouse and was designated as NT-8. Histological examination of the surgical specimen and the nude mouse tumour showed that the two were identical. NT-8 was subsequently passed by subcutaneous injections into nude mice. After the 6th passage in nude mouse, the tumour was cultured in vitro where it grew as an epithelial cell line, with a typical cobblestone appearance. This cell line was designated as NT-8e. Both the primary tumour as well as xenograft and the cells in culture have retained several common morphological and biochemical characteristics. Immunological markers for epithelial cells including epithelial membrane antigen and cytokeratins were seen in all three, confirming the epithelial lineage. Characterization of the NT-8e cell line including growth parameters, anchorage-independent growth and tumorigenicity in nude mice, chromosome counts and DNA content by flow cytometry have been carried out.

Animals↗
PubMed1997

X-ray pelvimetry--which is the best technique?

AIM: To provide definitive data on the radiation doses given to both mother and fetus using different pelvimetry techniques at a number of centres. This data was combined with an assessment of image quality, to determine the optimum technique. PATIENTS AND METHODS: Multiple thermoluminescent dosimeters (TLDs) were used to measure patient and fetal doses inside an anthropomorphic phantom of a pregnant women at full term. Measurements were made at twenty hospitals that routinely perform pelvimetry using techniques including computed tomography (CT), conventional radiography, conventional radiography using an air-gap technique, and digital fluorography. To assess image quality the images obtained by the different techniques were reviewed by a panel of two radiologists and a senior radiographer. RESULTS: A wide range of absorbed doses and relative risks to mother and fetus was observed. The largest and smallest doses encountered in the study differed by a factor of approximately forty. CT pelvimetry was seen to give an average of 25% of the dose of conventional pelvimetry, and at some centres dose savings of over 90% would be possible by performing lateral CT scanograms in preference to plain film pelvimetry. However, a surprisingly wide variation in doses was observed between centres performing CT pelvimetry, and in some cases the potential dose saving would be small. An air-gap technique practised by one of the centres in the survey was found to give absorbed doses and relative risks comparable to average CT scanograms. A digital fluorography technique also gave a very low dose at one centre. However, a similar technique performed at another of the centres conferred little benefit over conventional pelvimetry. There was no observable correlation between the dose administered to the patient and image quality for any of the techniques, and CT and conventional pelvimetry both gave similar image quality. CONCLUSION: While CT deserves its reputation as a low dose technique for pelvimetry, in some cases there may be little dose saving over conventional techniques. The total mAs from the CT examination should be kept as low as possible. Low absorbed doses with good image quality may also be achieved without specialized equipment using an air gap technique. This method is highly recommended as an alternative to CT, for example if no CT scanner is available.

Female↗
PubMed1997

Intravascular contrast media: can we justify the continued use of ionic contrast agents?

Cost has been the major factor preventing the universal conversion to non-ionic contrast agents. We assessed the costs and potential benefits of making this change in our department. During a 10-month-period the use of all intravascular contrast agents and reaction rates were audited prospectively. One thousand three hundred and ninety-four examinations were included. A local protocol for the use of ionic and non-ionic contrast media was already in place, based on the Royal College of Radiologists Guidelines. For each patient the contrast agent used, risk factors, and presence or absence of a contrast reaction were recorded. Non-ionic contrast agent usage exceeded ionic by a factor of 10. Patients receiving ionic agents intravenously had a reaction rate of 16.8% compared with 2.7% for non-ionic contrast media. The use of ionic contrast media was subsequently suspended and the effect of this on overall costs assessed by retrospectively and prospectively analysing hospital expenditure on contrast agents. No increase in costs was found. The reasons for this are two-fold. Firstly in our institution the protocol in place and the nature of the workload resulted in relatively small volumes of ionic contrast media being used compared with non-ionic agents. Secondly, since our department is a bulk purchaser of non-ionic agents, substantial discounts could be negotiated. The benefits of non-ionic contrast media are well recognized and our experience suggests that cost may no longer be a barrier to conversion to these lower risk agents.

Contrast Media↗