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Biomedical subjects

V Patel

Publications and source records attributed to V Patel.

At least 127 records · Page 7Linked to original sources
PubMed1996

Dysregulation of autocrine TGF-beta isoform production and ligand responses in human tumour-derived and Ha-ras-transfected keratinocytes and fibroblasts.

This study examined the autocrine production of TGF-beta 1, -beta 2 and -beta 3 in culture supernatants from tumour-derived (H series, n = 7; BICR series, n = 5), Ha-ras-transfected (n = 4) and normal (n = 2) human keratinocytes using a sandwich enzyme-linked immunosorbent assay (ELISA). Detection limits were 39.0 pg ml-1 for TGF-beta 1, 78.0 pg ml-1 for TGF-beta 2 and 1.9 ng ml-1 for TGF-beta 3. Tumour-derived oral keratinocytes predominantly produced less TGF-beta 1 than normal oral epithelial cells; the expression of endogenous TGF-beta 2 was variable. In keratinocytes containing mutant Ha-ras, TGF-beta 1 production was enhanced and TGF-beta 2 was undetectable. TGF-beta 3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) but the protein was not detected in conditioned media, most probably because of the low detection limits of the ELISA for this isoform. Neutralisation experiments indicated that the latent TGF-beta peptide was secreted in keratinocyte conditioned medium. Seven tumour-derived keratinocyte cell lines (H series) and fibroblasts separated from normal (n = 1) and tumour-derived (n = 2) keratinocyte cultures were examined for their response to exogenous TGF-beta 1, -beta 2 and -beta 3. Six of seven tumour-derived keratinocyte cell lines were inhibited by TGF-beta 1 and TGF-beta 2 (-beta 1 > -beta 2); one cell line was refractory to both TGF-beta 1 and TGF-beta 2. Keratinocytes were inhibited (4 of 7), stimulated (1 of 7) or failed to respond (2 of 7) to TGF-beta 3, TGF-beta 1, -beta 2 and -beta 3 stimulated both normal and tumour-associated fibroblasts, but the tumour-associated fibroblasts showed less response to the ligands than their normal counterparts following prolonged treatment with each isoform. The results demonstrate variable autocrine production of TGF-beta isoforms by malignant keratinocytes, with loss of TGF-beta 1 generally associated with the tumour-derived phenotype and modification of endogenous isoform production dependent on the genetic background of the tumour cells. Further, the variable response of the tumour-derived keratinocytes and contiguous fibroblasts to the TGF-beta isoforms suggests that dysregulation of TGF-beta autocrine and paracrine networks are common characteristics of squamous epithelial malignancy.

Cell Line↗
PubMed1996

Regional retinal blood flow and vascular autoregulation.

The temporal retina is larger than the nasal retina and contains the metabolically active fovea. The variation in the distribution of blood between the temporal and nasal retinal circulations was investigated in 15 healthy volunteers, and the autoregulatory capacity of the temporal and nasal circulations was quantitated using 60% oxygen in the inspired air. Retinal blood flow was determined from red cell velocity using laser Doppler velocimetry and retinal vessel diameter from retinal photographs using a digital image analysis system. Volume flow was lower in the nasal than the temporal circulation by 52.49% (p < 0.001). This is a consequence of both significantly smaller vessels (20.4%, p < 0.001) and slower blood velocity in the nasal circulation (24.64%, p = 0.003) compared with the temporal vessels. After breathing 60% oxygen for 10 minutes, there was significant vasoconstriction (temporal, 10.42 +/- 1.24%, p < 0.001; nasal, 7.66 +/- 1.48%, p < 0.001), slower red cell velocity (temporal, 27.10 +/- 3.92%, p < 0.001; nasal, 27.36 +/- 5.51%, p < 0.001) and a significant reduction in the volumetric flow rate (temporal, 41.16 +/- 3.64%, p < 0.001; nasal, 37.99 +/- 5.07%, p < 0.001). The reduction in the haemodynamic parameters was comparable in the temporal and nasal circulations, indicating similar autoregulatory capacity. Retinal vascular conductance was calculated from volume flow and retinal perfusion pressure. It was 53% larger in the temporal than the nasal circulations. This provides an index of the metabolic needs of the different regions of the retina.

Adult↗
PubMed1996

Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin cells are differentially regulated by PKC isoforms.

Adrenal Glands↗
PubMed1996

Protective effects of calcium from nonfat dried milk against colon carcinogenesis in rats.

A number of studies have demonstrated the protective effect of dietary calcium against risk for colon cancer. The objective of this experimental study was to test the efficacy of two sources of dietary calcium, elemental calcium in the form of CaCO3 and dairy calcium as nonfat dried milk (NFDM), in colon tumor inhibition. Male weanling F344 rats were fed six test diets containing low (LF, 5%) and high (HF, 20%) levels of corn oil and low (0.5%) and high (1.0%) levels of calcium supplemented as CaCO3 or NFDM in a 2 x 3 factorial design. Tumors were induced with two weekly injections of azoxymethane at 12 mg/kg body wt. After 27 weeks on the test diets, animals were necropsied for tumor analysis. There was no difference in tumor incidence for fat or calcium source main effects, but a significant interaction was seen between fat and calcium source, with the lowest tumor incidence seen in the HF/NFDM group. Calcium compartmentalization studies demonstrated no effects of calcium on serum calcium levels but increased urinary and fecal water calcium in the higher-calcium diets. Increased dietary calcium also decreased fecal bile acid concentrations, but there was no effect on fecal water bile acids. Intermediate biomarkers of colon carcinogenesis were not affected by the dietary treatments except for fat effects on carcinogen-induced nuclear aberrations. These results indicate that source of calcium is not critical but that total dietary context may affect efficacy of calcium against colon carcinogenesis.

Animals↗
PubMed1996

Radiotherapy for Hodgkin's disease in pregnancy.

Hodgkin's disease diagnosed during pregnancy poses a dilemma as there are risks of abortion and fetal malformation with the use of radiotherapy and chemotherapy. A patient with Hodgkin's disease during pregnancy treated with radiotherapy is presented.

Abnormalities, Radiation-Induced↗
PubMed1996

Protein kinase C isoforms in bovine aortic endothelial cells: role in regulation of P2Y- and P2U-purinoceptor-stimulated prostacyclin release.

1. Enhanced synthesis of prostacyclin (PGI2) and inositol polyphosphates in bovine aortic endothelial cells in response to ATP and ADP is mediated by co-existing P2Y- and P2U-purinoceptors. Here we examine the regulation of these responses by isoforms of protein kinase C (PKC). 2. Immunoblots with antisera specific for 8 different PKC isoforms revealed the presence of alpha, epsilon and zeta, while no immunoreactivity was found for beta, gamma, delta, eta and theta isoforms. PKC-alpha was largely cytosolic in unstimulated cells and almost all translocated to the membrane (Triton X-100 soluble) after a 1 min treatment with the PKC activating phorbol myristate acetate (PMA); PKC-epsilon was always in a Triton X-100 insoluble membrane fraction, while PKC-zeta was found in both soluble and membrane bound (Triton X-100 soluble) forms in the unstimulated cells and was unaffected by PMA. 3. Treatment with PMA for 6 h led to a 90% downregulation of PKC-alpha, while the immunoreactivity to the epsilon and zeta isoforms remained largely unchanged. 4. After either 10 min or 6 h exposure to PMA the PGI2 response to activation of both receptors was enhanced, while the inositol 1,4,5-trisphosphate response to P2Y-purinoceptor activation was substantially attenuated and the P2U-purinoceptor response was unchanged. Thus the PGI2 response to PMA under conditions when 90% of the PKC-alpha was lost resembles that seen on acute stimulation of PKC by PMA, and the PGI2 response does not correlate with phospholipase C response. 5. Inhibition of PKC with the isoform non-selective inhibitors, Ro 31-8220 and Go 6850 abolished the PGI2 response to both P2U- and P2Y-purinoceptor stimulation. However, Go 6976, which preferentially inhibits Ca2+ sensitive isoforms (such as PKC-alpha) and not Ca2+ insensitive isoforms (such as PKC-epsilon), had no effect on the PGI2 response. 6. The results show that there is a requirement for PKC in the stimulation of PGI2 production by endothelial P2Y- and P2U-purinoceptors. Both downregulation and inhibition studies show that PKC-alpha is not responsible for the regulation of the response to P2-purinergic stimulation, and imply that the response is mediated by PKC-epsilon (PKC-zeta is unresponsive to PMA), or an as yet uncharacterized PKC isoform.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Improvement of thrombocytopenia due to hypersplenism after transjugular intrahepatic portosystemic shunt placement in cirrhotic patients.

Thrombocytopenia secondary to hypersplenism is a well-known complication of portal hypertension. The effects of transjugular intrahepatic portosystemic shunt (TIPS) on hypersplenism have not been adequately studied. In this report, we describe 11 patients who had significant improvement in their thrombocytopenia due to hypersplenism after TIPS. There was a statistically significant improvement in the platelet counts after TIPS placement, in virtually every case during the follow-up period, although some patients had platelet counts less than 100,000/mm3 at the end of the follow-up period. Statistically significant hemodynamic improvement in the gradient pressure was observed immediately after TIPS. Furthermore, all patients tolerated the procedure well, and TIPS-related complications were encountered during the follow-up period. Our data suggest that TIPS is an effective, noninvasive alternative to surgical interventions in the management of hypersplenism in cirrhotic patients, who are generally high-risk surgical candidates.

Adult↗
PubMed1996

Cognitive evaluation of the user interface and vocabulary of an outpatient information system.

This paper describes an innovative approach to the evaluation of the user interface and vocabulary of a medical information system. The use of video recording for collecting usability data is detailed. The technique employed involves the collection of data consisting of transcripts of physicians as they "think aloud" while interacting with the system, along with a video record of the complete user-computer interaction. Using methods of analysis from cognitive science, the study was able to distinguish the source of physician problems in using the system's interface and in interacting with its controlled medical vocabulary. Analysis of the protocols indicated that all subjects encountered several generic problems, the most common ones indicative of a need for greater consistency in the interface design. Based on this evaluation, parts of the user interface have been re-implemented in an ongoing process of iterative system development.

Ambulatory Care Facilities↗
PubMed1995

Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H(+)-ATPase and F0F1-ATP synthase.

Various lipophilic cations, such as quinacrine mustard and dequalinium, which are known to inhibit mitochondrial F1-ATPase, strongly inhibited vacuolar H(+)-ATPase purified from bovine adrenal chromaffin granules. Quinacrine mustard bound irreversibly to vacuolar H(+)-ATPase subunit A, and the 115 kDa accessory polypeptide and dithiothreitol had no effect. The binding was competitively inhibited by chlorpromazine and quinacrine, and these compounds specifically reduced the amount of labeling of subunit A. Quinacrine mustard also prevented the binding of [alpha-32P]ATP to subunit A but had no effect on the binding of [3H]N-ethylmaleimide to either subunit A or the 115 kDa accessory polypeptide. These results suggest that the binding site of quinacrine mustard in subunit A is not related to the N-ethylmaleimide-binding site(s), which is important for activity.

Amino Acid Sequence↗
PubMed1995

Explanatory models of mental illness in sub-Saharan Africa.

Knowledge of explanatory models of illness can be used to conduct cross-cultural epidemiological studies which, while being culturally sensitive, are also comparable with other studies. This paper reviews studies from sub-Saharan Africa which examine beliefs relating to mental illness. There is a rich diversity of beliefs, but within this diversity are a number of shared concepts. Thus, many African cultures do distinguish between the mind and body. The mind is cited as residing in the head as well as the heart or abdominal region. Spiritual causes are frequent explanations for mental illness. Though there are some similarities with biomedical concepts of mental illness, there are also significant variations. Psychotic illness is often recognized as 'madness' though emphasis is on behavioural symptoms rather than delusions; neurotic presentations are much more varied, often somatically defined and may not be considered to be mental illnesses at all. Emic psychiatric instruments need to be developed if future cross-cultural psychiatric research is to be both comparable and culturally valid.

Africa South of the Sahara↗
PubMed1995

An ignorant belief network to forecast glucose concentration from clinical databases.

Ignorant Belief Networks (IBNs) are a class of Bayesian Belief Networks (BBNs) able to reason on the basis of incomplete probabilistic information and to incrementally refine the precision of the inferred probabilities as more information becomes available. In this paper, we will describe how can be used to develop a system able to forecast blood glucose concentration in patients affected by insulin dependent diabetes mellitus (IDDM). The major difference between our approach and the traditional ones is that probability distributions over the IBN are not provided by some human expert or by the current literature but they are directly extracted from a clinical database of IDDM patients. This choice capitalizes on the large amount of information generated by the daily control of blood glucose and allows the system to improve the accuracy of predictions as more information becomes available. We will show how, even with a very small subset of the information needed to specify a BBN, the IBN is able to carry out predictions about the future blood glucose concentration in a patient by explicitly taking into consideration the level of ignorance embedded in the network.

Artificial Intelligence↗
PubMed1995

Presence of human papillomavirus sequences in tumour-derived human oral keratinocytes expressing mutant p53.

A series of eight oral epithelial cell lines derived from untreated human oral squamous cell carcinomas, which had arisen in patients with different tobacco histories, were examined for the presence of human papillomavirus (HPV) DNA, expression of stable p53 protein and p53 point mutation. Polymerase chain reaction (PCR)-based screening, but not Southern blot analysis, showed HPV-16 early region sequences to be present at low copy number (< 1 copy per cell) in two cell lines at early passage (3-5) in vitro (H400, T45), implying that only subpopulations of cells harboured viral DNA. HPV sequences were undetectable in cells at later passage (12-15), suggesting that viral sequences had been lost during growth in vitro, or that negative selection of HPV-containing cells had occurred. High levels of p53 were detected in the two HPV-positive cell lines and in three others (H103, H314, H357) by Western blotting, suggesting expression of mutant (stable) p53 molecules. A sixth cell line (H157) expressed a truncated p53. Sequence analysis of exons 2-11 of the p53 gene revealed missense mutations in six cell lines, one of which (H413) did not result in high levels of protein, and nonsense mutations in the remaining two cell lines (H157, H376). The results suggest that p53 mutation is a frequent genetic event in oral cancer. In addition, the expression of mutant p53 in oral cancer cells does not preclude a papillomaviral aetiology for these tumours. Analysis of p53 expression alone may result in underestimation of the frequency of p53 mutations in human cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗