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Biomedical subjects

V Patel

Publications and source records attributed to V Patel.

At least 163 records · Page 9Linked to original sources

TGF-beta receptor regulation mediates the response to exogenous ligand but is independent of the degree of cellular differentiation in human oral keratinocytes.

This study examined the expression of TGF-beta cell-surface receptors, the response to exogenous TGF-beta 1 and the autocrine production of TGF-beta in normal and squamous cell carcinoma-derived human oral keratinocytes with variable degrees of cellular differentiation. TGF-beta receptor expression, the response to exogenous ligand and the autocrine production of TGF-beta appeared unrelated to cellular differentiation. Cells expressed variable proportions of type-I, -II and -III TGF-beta receptors. The expression of type-III receptors correlated inversely with the expression of type-I receptors, but there was no relationship between type-II and either type-I or type-III TGF-beta receptors. Normal cells and the majority (7 of 8) of tumour-derived keratinocytes were inhibited by exogenous TGF-beta 1 and the degree of inhibition correlated with the expression of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived cell line was refractory to exogenous TGF-beta 1 although it expressed all 3 receptor types. Endogenous TGF-beta was produced by both normal and tumour-derived keratinocytes and correlated inversely to the expression of type-I, but not type-II, TGF-beta receptors. Further, cells that produced more autocrine TGF-beta had a diminished response to exogenous TGF-beta 1. The data indicate a complex interaction between the expression of TGF-beta cell-surface receptors, endogenous ligand production and the cellular response to exogenous TGF-beta 1.

3T3 Cells↗

Effect of temperature and retention time on biomethanation of cheese whey-poultry waste-cattle dung.

Various conditions, such as temperature, total solid content, cattle dung-poultry waste-cheese whey ratio, retention time and stirring, were optimized with an ultimate aim of improving anaerobic digestion. Maximum gas production (2.2 litres litre(-1) of digester day(-1)) with enriched methane content (62% CH(4)) was found with a retention time of 10 days, having a loading rate of 6.0 g total solid litre(-1) of digester day(-1) at 40 degrees C, and total solid of 6% (w/v) using a mixture of cattle dung, poultry waste and cheese whey in the ratio of 2:1:3 (w/w).

Journal Article↗

The acute effect of smoking on retinal blood flow in subjects with and without diabetes.

PURPOSE: This study investigates the effect of smoking on retinal blood flow and autoregulation in smokers with and without diabetes. METHODS: Eleven patients with diabetes mellitus and ten control subjects were investigated. Laser Doppler velocimetry and retinal photography were used to measure retinal blood flow; vascular autoregulation was assessed with 60% oxygen breathing. These procedures were performed before and after smoking. RESULTS: Both groups demonstrated a significant increase in heart rate and systolic and diastolic blood pressure (P < 0.01). In both groups, smoking caused a significant decrease in retinal blood flow: 9.6% +/- 12% in the control group (P < 0.05) and 16.4% +/- 13.8% in the diabetic group (P < 0.01). The pre-smoking oxygen reactivity was comparable in both groups (P = 0.5); 27.9% +/- 3.3% and 32.0% +/- 5.0% in the control and diabetic groups, respectively. After smoking, oxygen reactivity was reduced significantly in the control group to 9.6% +/- 4.0% (P = 0.002) and eliminated in the patients with diabetes. CONCLUSIONS: This study shows that smoking reduces retinal blood flow and the ability of the retinal vessels to autoregulate to hyperoxia; these effects are likely to be due to the vasoconstrictive effect of nicotine, which is mediated through activation of the sympathetic system. Smoking has been shown previously to increase the level of carboxyhemoglobin, thereby reducing the oxygen-carrying capacity of blood, which, when associated with the reduced blood flow shown in the current study, may reduce retinal oxygen delivery. Hypoxia is a major factor in the progression of diabetic retinopathy; therefore, smoking may exert a detrimental influence, which may be compounded further by the additional effect smoking has on autoregulation.

Adult↗

Epidermal growth factor and transforming growth factor alpha characteristics of human oral carcinoma cell lines.

This study examined the expression of epidermal growth factor (EGF) cell-surface receptors, the response to exogenous ligand and the autocrine production of transforming growth factor alpha (TGF-alpha) in normal and carcinoma-derived human oral keratinocytes. One of eight malignant cell lines overexpressed EGF receptors, while the remainder expressed receptor numbers similar to normal cells. Exogenous EGF stimulated incorporation of tritiated thymidine in a dose-dependent manner. In keratinocytes expressing normal numbers of EGF receptors, the cellular response to exogenous EGF correlated positively with total EGF receptor number. SCC-derived keratinocytes produced more TGF-alpha than normal cells. There was no statistical correlation between the autocrine production of TGF-alpha, EGF cell-surface receptor expression and cellular response to exogenous EGF. While the growth-stimulatory effects of exogenous TGF-alpha were inhibited by the addition of a neutralising antibody, the presence of this antibody in conditioned medium failed to produce a similar decrease in growth. The results indicate that overexpression of EGF receptors is not an invariable characteristic of human oral squamous carcinoma-derived cell lines. Further, the contribution of TGF-alpha to the growth of normal and carcinoma-derived human oral keratinocytes in vitro may be less significant than previously documented.

Adult↗

Vessel diameter changes during the cardiac cycle.

Retinal vessel diameter, which is an important parameter in blood flow measurement, is affected by pulsation during the cardiac cycle and by vasomotion. This project studied these changes by analysing three monochromatic fundus photographs taken in eight arbitrary parts of the cardiac cycle of 10 healthy subjects. It was found that the venous diameter decreased in early systole, increasing thereafter to a maximum level in early diastole and then declined towards end diastole. The maximum change of 4.82% (between early systole and early diastole) (p = 0.03) represents a 9.83% change in volumetric blood flow. The arterial diameter peaked in mid-late systole, increasing by 3.46% (p = 0.01); this represents a blood flow increase of 7.04%. Vasomotion led to changes of 3.71% and 2.61% in arteries and veins respectively. It is concluded that for accurate measurement of retinal blood flow, fundus photographs should be taken synchronised with the electrocardiogram.

Adult↗

Oxygen reactivity in diabetes mellitus: effect of hypertension and hyperglycaemia.

1. Laser Doppler velocimetry and computerized image analysis of retinal photographs were used to define retinal vascular autoregulation to 60% oxygen breathing. This normally causes vasoconstriction in the retinal circulation. Normotensive and hypertensive diabetic subjects were studied under conditions of relative normoglycaemia (< 10 mmol) and hyperglycaemia (> 15 mmol) together with control subjects. 2. Retinal blood flow was significantly higher in diabetic subjects when hypertensive and hyperglycaemic than in the same diabetic subjects when normotensive. 3. In the normotensive non-diabetic subjects the oxygen reactivity was 41.16 +/- 14.09%. It was significantly reduced in normotensive 'hyperglycaemic' diabetic subjects (21.75 +/- 15.56%), hypertensive diabetic subjects with controlled blood pressure and 'normoglycaemia' (30.49 +/- 14.20%), hypertensive diabetic subjects with controlled blood pressure and 'hyperglycaemia' (18.36 +/- 11.42%), hypertensive diabetic subjects with uncontrolled blood pressure and 'normoglycaemia' (26.91 +/- 13.43%) and hypertensive diabetic subjects with uncontrolled blood pressure and 'hyperglycaemia' (17.17 +/- 13.24%) (mean +/- SD, all P values < 0.05). 4. In conclusion, retinal vascular reactivity is impaired in diabetic subjects both when they are normotensive and when they are hypertensive. Hyperglycaemia, to a degree commonly encountered in clinical practice, impairs retinal vascular auto-regulation even further.

Adult↗

Accurate vessel width measurement from fundus photographs: a new concept.

Accurate determination of retinal vessel width measurement is important in the study of the haemodynamic changes that accompany various physiological and pathological states. Currently the width at the half height of the transmittance and densitometry profiles are used as a measure of retinal vessel width. A consistent phenomenon of two 'kick points' on the slopes of the transmittance and densitometry profiles near the base, has been observed. In this study, mathematical models have been formulated to describe the characteristic curves of the transmittance and the densitometry profiles. They demonstrate the kick points being coincident with the edges of the blood column. The horizontal distance across the kick points would therefore indicate the actual blood column width. To evaluate this hypothesis, blood was infused through two lengths of plastic tubing of known diameters, and photographed. In comparison with the known diameters, the half height underestimated the blood column width by 7.33% and 6.46%, while the kick point method slightly overestimated it by 1.40% and 0.34%. These techniques were applied to monochromatic fundus photographs. In comparison with the kick point method, the half height underestimated the blood column width in veins by 16.67% and in arteries by 15.86%. The characteristics of the kick points and their practicality have been discussed. The kick point method may provide the most accurate measurement of vessel width possible from these profiles.

Fluorescein Angiography↗

Retinal blood flow changes during pregnancy in women with diabetes.

PURPOSE: To study retinal blood flow (RBF) during pregnancy in subjects with and without diabetes and to relate the changes to progression in diabetic retinopathy. METHODS: RBF in a major temporal retinal vein was measured, where possible, during all three trimesters (T1 to T3) and the postpartum period (PP) using laser Doppler velocimetry (measuring velocity [V]) and monochromatic fundus photographs (measuring diameter [D]). RESULTS: In the subjects without diabetes (n = 19), no significant change in RBF was demonstrated. V was significantly greater in T3 than in PP (P = 0.01). D was significantly smaller in T1 to T3 than in PP (P < or = 0.01). RBF in the subjects with diabetes was significantly higher in T2 and T3 than in PP (P < 0.05). V increased from T1 to T2 (P = 0.04) and decreased from T2 to PP (P = 0.001) and from T3 to PP (P = 0.002). The only significant change in D was a smaller value in T1 than in PP (P = 0.003). However, it was only those subjects whose DR progressed (n = 11) who had a significant increase in RBF during pregnancy (P = 0.0001). CONCLUSIONS: These data suggest that the hyperdynamic circulation present in pregnancy led to compensatory retinal vessel constriction (autoregulation) in the group without diabetes; this was largely absent in the patients with diabetes, with resultant increase in retinal blood flow associated with worsening retinopathy. This finding lends further support to the hypothesis that increased retinal blood flow is a pathogenic mechanism for diabetic retinopathy.

Adult↗

Harakiri: a clinical study of deliberate self-stabbing.

BACKGROUND: Stabbing is an uncommon method of self-harm that has not been previously described in the psychiatric literature. The aim of this study was to describe the clinical features and management of patients presenting with self-inflicted stab injuries. METHOD: Case notes of all patients presenting with deliberate self-inflicted injuries during a 2-year period to a teaching general hospital were screened to identify the sample of interest. Clinical data were then collected by means of a detailed case-note study. RESULTS: Ten patients who deliberately stabbed themselves were identified. The patients fell into two distinct clinical groups: the first consisted mostly of young men with antisocial personalities who were intoxicated at the time of the self-stabbing and who reported ambivalent suicidal intent; the second consisted of psychotic patients, most of whom were actively ill at the time of the self-stabbing, and who reported clear suicidal intent. Patients in the first group were noncompliant with treatment and difficult to engage; those in the second group needed psychiatric hospitalization and often responded to antipsychotic medication. CONCLUSION: Persons who stab themselves tend to fall into two clinical groups that have different diagnoses and management. Distinctions between violent suicidal behavior and self-mutilation are blurred because suicidal intent can be difficult to assess.

Adolescent↗

Evidence for a common binding site for omeprazole and N-ethylmaleimide in subunit A of chromaffin granule vacuolar-type H(+)-ATPase.

Vacuolar-type H(+)-ATPase from adrenal chromaffin granules was found to be sensitive to omeprazole, a known gastric H+/K(+)-ATPase inhibitor, the concentration required for 50% inhibition being 80 microM freshly-prepared and 12 microM acid-treated reagent. ATP and ADP protected the enzyme from inhibition by omeprazole. The activity of the inhibited enzyme was restored by the addition of reduced glutathione. Omeprazole protected the enzyme from inhibition by N-ethylmaleimide and its binding to the subunit A. As subunit A has a nucleotide binding site(s) and as a cysteine residue is involved in the inhibition by N-ethylmaleimide, these results suggested that the two sulfhydryl reagents bind to the same cysteine residue near the nucleotide binding domain in the subunit A, resulting in inactivation of vacuolar-type H(+)-ATPase.

Adenosine Diphosphate↗

Phospholipase D activation regulates endothelin-1 stimulation of phosphoinositide-specific phospholipase C in SK-N-MC cells.

Endothelin-1 (ET-1) is known to stimulate phospholipase C (PLC) activity in SK-N-MC human neuroblastoma/epithelioma cells: here we show that phospholipase D (PLD) is also stimulated. The generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) by ET-1-stimulated PLC was attenuated by protein kinase C (PKC) activation and enhanced by PKC inhibition. An enhancement of ET-1-stimulated Ins(1,4,5)P3 accumulation was also seen when the product of PLD activity was either diverted into phosphatidyl butanol in the presence of butanol, or phosphatidate phosphohydrolase (PPH) activity was inhibited by DL-propranolol. We conclude that there is an inhibitory, PKC-mediated, feedback loop in these cells which is dependent, in part, on the activation of PKC by product(s) of the PLD/PPH pathway. This provides a novel role for agonist-stimulated PLD activation.

Butanols↗

Endothelin-1 stimulated phospholipase D in A10 vascular smooth muscle derived cells is dependent on tyrosine kinase. Evidence for involvement in stimulation of mitogenesis.

The mechanism whereby endothelin stimulates mitogenesis of vascular smooth muscle cells is not understood. Here we show that endothelin-1 stimulates phospholipase D by a protein kinase C and tyrosine kinase dependent mechanism, and present evidence that implicate the phosphatidic acid formed by phospholipase D in the mitogenic response.

Animals↗

Consistent chromosomal anomalies in keratinocyte cell lines derived from untreated malignant lesions of the oral cavity.

Cytogenetic analysis has been carried out on 8 early passage cell lines derived from 8 untreated human oral squamous cell carcinomas. Clonal aberrations were detected in the karyotypes of each cell line. A high frequency of breakpoints were noted on chromosomes 1, 7, 8, 9, 11, and X. An isochromosome 8 was present in 6 out of 8 cell lines; isochromosome 9 (3 cell lines) and isochromosome 11 (1 cell line) were also found. In 4 out of 8 cell lines X chromosome harboured breakpoints, a novel finding in oral squamous cell carcinomas. Breakpoints were common on chromosome 1, with 1p12-p13 most frequently involved. Tandem duplication of 11q13-q23, which contains a number of growth regulatory genes, was also noted in 2 cases. We correlate the sites of proto-oncogenes and other growth control genes with chromosomal breakpoints and suggest that several of these may play a role in the pathogenesis of oral cancer.

Adult↗

Antigenic sites on type 2 poliovirus.

Monoclonal escape variants isolated from the Sabin strain of type 2 poliovirus were examined. Mutations were identified in regions known to be antigenic in other serotypes, although the extent to which they were linked by common antibodies varied. One complex site involved regions of VP2 and VP3 which were not linked in early studies, but have recently been shown by others to be linked in type 1.

Antibodies, Monoclonal↗

The effect of acetazolamide on the retinal circulation.

The effect of the carbonic anhydrase inhibitor, acetazolamide, on the retinal circulation was studied in 10 healthy volunteers. Acetazolamide was administered intravenously at a dose of 500 mg. Retinal blood flow was determined from red cell velocity using laser Doppler velocimetry and vessel diameter measurement using computerised digital image analysis of monochromatic fundus photographs. There was a significant increase in retinal blood flow at 30 minutes and 60 minutes after acetazolamide injection (p = 0.002). Retinal vessels showed vasodilatation reaching significant levels 60 minutes after the injection (p < 0.03). An increase in red cell velocity was observed at 30 and 60 minutes (p < 0.002). A significant reduction in intraocular pressure occurred at 30 and 60 minutes after the injection (p < 0.001). The mechanisms responsible for the increase in retinal blood flow acted via significant increases in perfusion pressure (p < 0.05), red cell velocity (p < 0.002) and retinal vessel dilatation (p < 0.03). An increase in tissue PCO2 and a reduction in pH are thought to be responsible for the vascular dilatation. The increase in retinal blood flow with acetazolamide may serve to limit optic disc and retinal ischaemia in acute glaucoma and central retinal artery occlusion respectively.

Acetazolamide↗