Biomedical subjects
Publications and source records attributed to S M Thomas.
We describe a patient with systemic lupus erythematosus who developed an unusual form of anaplastic myeloma. Possible relationships between the two disease, and the role played by immunosuppressive therapy, are discussed.
The case is described of an eight-year-old Nigerian boy who died from olfactory neuroblastoma which presented with nasal obstruction and epistaxis. Autopsy showed intracranial extension of the tumour into the frontal lobe, and histology revealed undifferentiated neuroblasts, forming rosettes in some areas and producing tangled neurofibrils in others. The histogenesis of the tumour and its diagnosis are briefly discussed.
Isoniazid (INH) was given to nine patients with Huntington disease (HD) in a double-blind, placebo-controlled crossover trial. In an earlier open trial, three of six patients had improved, and one of them remained improved after 7 years on INH. Only one patient benefited in the present trial. All patients excreted small amounts of hydrazine in their urine while taking INH, and it is this INH metabolic that elevates GABA content in brain. GABA concentrations were markedly increased in CSF during INH therapy. Lack of clinical improvement in most HD patients despite elevation of brain GABA content suggests that in the minority who are benefited, INH may be acting by some mechanism other than increase of GABAergic neuronal function.
Eight cases of multi-system amyloid have been found in 4235 autopsies (0.2%) performed at University College Hospital, Ibadan, Nigeria between 1970 and 1979. Blocks and sections of seven cases showed the organ distribution associated with secondary amyloid, involving kidney, spleen and liver. Potassium permanganate oxidation prior to Congo Red staining showed that all seven cases contained protein AA amyloid. Five patients had tuberculosis but in two patients there was no recognized cause, idiopathic AA amyloid. Patients usually presented with nephrotic syndrome or renal failure and hypertension was absent. There appears to be a low incidence of amyloidosis in Africans, despite the occurrence of a large number of potential amyloidogenic stimuli, indicating the importance of individual host reactivity and failure of amyloid degradation in the causation of amyloidosis.
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1. The aim of this work was to discover the location of the enzymes that convert phosphoenolpyruvate to fructose 6-phosphate during gluconeogenesis in fatty seeds. Cotyledons of 5-day-old dark-grown seedlings of marrow (Cucurbita pepo) were used as experimental material. 2. Cotyledons were separated into palisade and mesophyll tissue. Extracts of the two tissues had comparable activities of gluconeogenic enzymes. 3. Extracts of cotyledons were fractionated by density gradient centrifugation to yeild mitochondria and glyoxysomes, and by gel filtration to yield proplastids. The isolated organelles retained their characteristic ultrastructure and appreciable amounts of marker enzymes. The proportions of the total activities of phosphoglyceromutase and fructose-1, 6-diphosphatase recovered in the mitochondrial and glyoxysomal preparations were insignificant. The same was true for the activities of phosphoglyceromutase and phosphopyruvate hydratase found in the proplastid preparations. 4. Extracts of a number of other gluconeigenic plant tissues were centrifuged at 2500 times g to yield particulate preparations. None of these preparations contained a significant proportion of the total activity of phosphoglyceromutase. 5. It is suggested that gluconeogenesis from phosphoenolpyruvate in plants occurs in the cytoplasm.
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Among the angiotensin II (Ang II)-mediated signal events likely to be important in vascular smooth muscle cells (VSMCs) is activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). The upstream mediators by which Ang II activates ERK1/2 remain poorly defined. Recently, we showed that Ang II activated c-Src, a nonreceptor kinase, which is a candidate to mediate Ang II signal events. To determine whether c-Src is required for ERK1/2 activation by Ang II, we studied the effects of Src family-selective tyrosine kinase inhibitors on ERK1/2 activation and also studied Ang II-mediated signal events in Src-deficient and Src-overexpressing VSMCs. The tyrosine kinase inhibitors, genistein and CP-188,556, blocked Ang II-mediated ERK1/2 activation in rat VSMCs (rVSMCs). We derived Src-deficient VSMCs from the aortas of c-Src knockout mice (Src-/- mVSMCs). Basal ERK1/2 activity was lower, and activation of ERK1/2 by Ang II was significantly decreased in Src-/- mVSMCs compared with wild-type mVSMCs, whereas ERK1/2 protein expression and ERK1/2 activation by phorbol 12-myristate 13-acetate were similar. To examine the role of c-Src further, we overexpressed wild-type or dominant-negative c-Src in rVSMCs using retroviral vectors. ERK1/2 activation by Ang II was significantly increased in rVSMCs that overexpressed c-Src, whereas ERK1/2 activation by Ang II was significantly inhibited in rVSMCs that overexpressed dominant-negative c-Src compared with control rVSMCs. These findings demonstrate that c-Src activation is required for Ang II stimulation of ERK1/2 in VSMCs and suggest an important role for c-Src in Ang II-mediated signal transduction.
Abnormal serum liver enzymes are common in adults receiving total parenteral nutrition (TPN). The mechanism(s) responsible for these changes is unclear. One hypothesis is that there is overgrowth of intestinal anaerobic bacteria with subsequent toxic effects on the liver from endotoxins and/or bile acids. A retrospective survey of patients receiving TPN was undertaken. The patients were divided into two matched groups. One group had received metronidazole, a drug that suppresses anaerobic bacteria, while the other group had not. The administration of metronidazole during TPN was associated with prevention of the expected rise of serum alkaline phosphatase, gamma glutamyl transpeptidase, and aspartate amino-transferase. This study supports the concept that anerobic intestinal bacteria may be involved in the pathogenesis of liver changes commonly observed during TPN.
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BACKGROUND: Malignancies of the oral cavity and oropharynx account for 31% of all diagnosed cancers in India. In most cases, patients present with tumours that are clinically stage III/IV where surgery, radiotherapy and chemotherapy have not been very effective. Hence, there is an urgent need for alternate treatment modalities. Gene therapy is a recent development shown to be effective in various malignancies. In this study we have attempted to cause bulk reduction in tumour volume using the HSVtk/ganciclovir strategy, solely on the basis of the 'bystander' effect. METHODS: Nude mouse xenograft tumours of human head/neck cancer were engrafted with cells expressing viral thymidine kinase. After treatment with 8 mM ganciclovir for 14 days, the treatment efficacy was monitored. A novel method has been devised to evaluate cell kill microscopically in the whole tumour. RESULTS: Of the 11 mice included in the study, 9 showed a significant reduction in total tumour volume of treated versus control tumours (p = 0.015). CONCLUSIONS: Bulk reduction in tumour load can be brought about without use of viral vectors for gene transfer solely by the bystander effect.