PubMed Health⌕ Search

Biomedical subjects

M Doshi

Publications and source records attributed to M Doshi.

At least 19 recordsLinked to original sources
PubMed2004

Fulminant liver failure: an indicator of silent myocardial rupture.

A 56 year old man presented with an atypical chest infection. Remote inferoposterior myocardial infarction was noted on electrocardiography and transthoracic echocardiography. Hepatic failure developed with sudden gross elevation of liver aminotransferases and coagulopathy. No primary hepatic cause could be identified. Subsequent right heart failure led to transoesophageal echocardiography that revealed a large inoperable ventricular septal defect. Histopathological data showed ischaemic hepatitis and reinfarction of the inferoposterior myocardial wall. Acute cardiac events may be silent and precipitate misleading severe hepatic dysfunction.

Blood Coagulation Disorders↗
PubMed2003

n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice.

2-arachidonoylglycerol (2-AG) is a putative endogenous ligand for cannabinoid receptors and was suggested to play an important role in both physiological and pathological events in the central nervous system (CNS) as well as in peripheral organs. The sequential hydrolysis of arachidonic acid (20:4n-6, AA)-containing phospholipids has been proposed as a major biosynthetic route of 2-AG. On the other hand, the manipulation of the dietary n-3 polyunsaturated fatty acid (PUFA) status changes the AA level in tissue phospholipids. We, therefore, conducted two separate experiments to confirm whether the dietary n-3 PUFA status influences the 2-AG level in the mouse brain. In the first experiment, we fed mice with n-3 PUFA-deficient diet, which resulted in a marked decrease in the docosahexaenoic acid (22:6n-3, DHA) levels without a change in the AA level in brain phospholipids as compared with the mice fed with an n-3 PUFA-sufficient diet. The brain 2-AG level in the n-3 PUFA-deficient group was significantly higher than in the n-3 PUFA sufficient group. In the second experiment, we found that short-term supplementation of DHA-rich fish oil reduced brain 2-AG level as compared with the supplementation with low n-3 PUFA. The decrease in the AA level and the increase in the DHA level in the major phospholipids occurred in the brains of the mice fed the fish oil diet compared with those fed the low n-3 PUFA diet. Our results indicate that the n-3 PUFA deficiency elevates and n-3 PUFA enrichment reduces the brain 2-AG level in mice, suggesting that physiological and pathological events mediated by 2-AG through cannabinoid receptor in the CNS could be modified by the manipulation of the dietary n-3 PUFA status.

Animals↗
PubMed2003

Multiple clinical manifestation of HTLV1 infection in a single patient.

HTLV-1 infection is endemic in the Caribbean and several publications have reported the clinical disease entities seen in this population of patients. This case report is an account of a patient admitted to Kingstown General Hospital, St Vincent and the Grenadines, who had severe infective dermatitis, tropical spastic paraparesis (TSP) and Non-Hodgkin's Lymphoma (NHL). As far as we are aware, all three diseases have not been described in a single patient.

Adult↗
PubMed2001

Suppression of platelet-activating factor generation and modulation of arachidonate metabolism by dietary enrichment with (n-9) eicosatrienoic acid or docosahexaenoic acid in mouse peritoneal cells.

Several studies have shown that dietary n-3 polyunsaturated fatty acids (PUFAs) suppress platelet-activating factor (PAF) generation in leukocytes of humans and rodents, which is associated with the antagonism of arachidonic acid metabolism. Dietary eicosatrienoic acid (20:3n-9, ETrA) is also suggested to antagonize arachidonic acid (AA) metabolism, but its effect on PAF generation in leukocytes has not been defined. In the present study, we investigated the effects of an ETrA-rich diet on PAF generation and AA metabolism in mouse peritoneal cells, which were compared with those of a docosahexaenoic acid (DHA)-rich diet. Mice were fed a diet supplemented with a lipid preparation rich in ETrA, a DHA-rich fish oil (FO) or palm oil (PO) for 3 weeks, and peritoneal cells containing more than 80% of monocytes/macrophages were obtained. The peritoneal cells in the DHA and ETrA diet groups generated upon zymosan stimulation a smaller amount of PAF than cells in the PO diet group. In the peritoneal cells of the DHA diet group, AA contents in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were significantly lower than those in cells of the PO diet group, but those in phosphatidylinositol (PI) were not significantly different between the two dietary groups. A considerable amount of ETrA was incorporated into the peritoneal cells of the ETrA diet group, and AA was reduced as compared with the PO diet group. These changes occurred preferentially in PI but to a less extent in PC and PE. The amount of free AA released by the peritoneal cells upon zymosan stimulation was significantly reduced in the DHA diet group as compared with that in the PO diet group, whereas AA release was similar between the PO and ETrA diet groups. In conclusion, the effects of dietary ETrA on AA content in the phospholipid subclasses and AA release were quite different from those of dietary DHA, although both diets suppressed PAF generation in mouse peritoneal cells to a similar extent.

Animals↗
PubMed2000

Secretory autoantibodies in primary biliary cirrhosis (PBC).

It is unclear how breakdown in immune tolerance to the ubiquitous self-antigen pyruvate dehydrogenase complex (PDC), seen in the autoimmune liver disease PBC, gives rise to tissue damage with such a limited distribution (restricted to the liver and salivary and lachrymal glands). One property shared by these tissues is the ability to export secretory IgA by the process of transcytosis. The aim of this study was to address whether active transcytosis of anti-PDC IgA occurs across epithelial surfaces in PBC, a finding that might implicate mucosal specific immune mechanisms in the pathogenesis of this disease. Parotid saliva was collected from PBC patients (n = 44), normal controls (n = 28) and PBC patients post-liver transplantation (n = 11). IgA and secretory component-positive antibodies specific for human PDC were quantified by ELISA and immunoblotting. PBC patients (but not control subjects) had anti-PDC IgA in their saliva. The strong correlation seen between titres detected using anti-IgA and anti-secretory component antibodies suggests that this is predominantly secretory IgA reaching the saliva by the active process of epithelial transcytosis. Titres of anti-PDC IgA remain high in PBC patients saliva post-liver transplant. Findings from studies of IgA in viral infection models raise the possibility that anti-PDC IgA could, whilst undergoing transcytosis, bind to newly translated PDC components in the cytoplasm of the epithelial cells transporting them out of the cell and inducing metabolic damage. This model would, if correct, help to explain the mechanism and tropism of tissue damage in PBC and the aberrant pattern of expression of PDC on the apical surface of biliary and salivary epithelial cells reported in this disease.

Adult↗
PubMed1998

Expression of Panulirus shaker potassium channel splice variants.

In Drosophila shaker voltage-dependent potassium channels, alternative splicing at the amino and carboxy termini produces currents with different electrophysiological characteristics. We have cloned alternatively spliced forms of shaker from the spiny lobster Panulirus interruptus. Alternative exons were found at three sites of the gene; eight different 5' exons, two alternative exons encoding the pore-forming P region, and an alternative 3' exon. Two of the different amino terminal splice forms were expressed with two alternatively spliced pore forms to produce channels with markedly different characteristics. One of the amino termini produced a channel with transient characteristics while the other produced a delayed rectifier-type channel. The effects of alternative exons at the amino terminus and in the P region appear to be additive. Our results provide new information on the structural requirements for rapid N-type inactivation.

Alternative Splicing↗
PubMed1997

Alternative splicing in the pore-forming region of shaker potassium channels.

We have cloned cDNAs for the shaker potassium channel gene from the spiny lobster Panulirus interruptus. As previously found in Drosophila, there is alternative splicing at the 5' and 3' ends of the coding region. However, in Panulirus shaker, alternative splicing also occurs within the pore-forming region of the protein. Three different splice variants were found within the P region, two of which bestow unique electrophysiological characteristics to channel function. Pore I and pore II variants differ in voltage dependence for activation, kinetics of inactivation, current rectification, and drug resistance. The pore 0 variant lacks a P region exon and does not produce a functional channel. This is the first example of alternative splicing within the pore-forming region of a voltage-dependent ion channel. We used a recently identified potassium channel blocker, kappa-conotoxin PVIIA, to study the physiological role of the two pore forms. The toxin selectively blocked one pore form, whereas the other form, heteromers between the two pore forms, and Panulirus shal were not blocked. When it was tested in the Panulirus stomatogastric ganglion, the toxin produced no effects on transient K+ currents or synaptic transmission between neurons.

Amino Acid Sequence↗
PubMed1997

The utility of dobutamine echocardiography in preoperative evaluation for elective aortic surgery.

BACKGROUND: Preoperative cardiac evaluations have been advocated prior to major vascular procedures to reduce the incidence of postoperative cardiac complications. This study was undertaken to evaluate the efficacy and predictive value of routine dobutamine echocardiography (DE) in the screening of patients undergoing elective aortic surgery. METHODS: Dobutamine echocardiography was performed preoperatively on all patients having elective aortic procedures by our university surgical group from June 1995 to August 1996. The cardiac morbidity and mortality from this group were compared with that of a similar group undergoing elective aortic procedures from June 1993 to May 1995 with no dobutamine echocardiography (NDE). RESULTS: Although there was no statistically significant difference in either overall mortality (4.4% in NDE vs. 2.3% in DE) or cardiac mortality (2.9% in NDE vs. 0% in DE) between the two groups, cardiac events occurred only in those patients with previous coronary artery disease. In addition, dobutamine echocardiography had a negative predictive value of 97% CONCLUSIONS: Although routine screening is not necessary, selective screening of patients using dobutamine stress echocardiography is justified because of its high negative predictive value.

Adrenergic beta-Agonists↗
PubMed1995

Algorithm for managing a baby with dusky soles.

We have been using dusky colour of the sole in newborns as proxy to cyanosis. An algorithm for management of dusky soles was developed presupposing that a baby can have dusky soles due commonly to hypothermia, hypoxaemia, or hypotension in isolation or in combination. Fifty-one consecutive babies were managed according to a predetermined algorithm based largely on clinical signs. Forty babies were covered by these three broad groups and 37 of them could be managed successfully. Of the remaining babies two were found to have congenital malformations on autopsy and one died of hyperthermia. Algorithmic approach has simplified the management with low failure rate and can be useful when hi-tech neonatal care is unaffordable.

Algorithms↗
PubMed1994

Irritable bowel syndrome in patients discharged from surgical wards with non-specific abdominal pain.

A questionnaire was used to discover the prevalence of seven recognized symptoms of irritable bowel syndrome (IBS) in 96 patients who had been discharged from hospital 1-2 years previously with the diagnosis of non-specific abdominal pain. Compared with 1897 controls from a population survey in the same city, the patients were more likely to have these symptoms; the differences were statistically significant in most cases. The frequency of recurrent abdominal pain with features suggesting an intestinal origin was increased fivefold in male and fourfold in female patients (P < 0.001). Criteria for the diagnosis of IBS were present in 37 per cent of women and 19 per cent of men, versus 5 and 2 per cent respectively in controls (P < 0.001). Approximately half the patients remembered having symptoms of IBS at the time of admission and 70 per cent had had other attacks of abdominal pain. At the time of admission, the hospital notes mentioned the possibility of IBS in only 6 per cent of cases. Most patients would have welcomed an explanation for the pain at the time of their hospital admission.

Abdominal Pain↗
PubMed1991

Cytotoxic effect of IFN-gamma plus TNF-alpha on human islet cells.

We have previously reported that the combination of IFN-gamma plus TNF-alpha is able to induce the de novo expression of HLA class II on human beta cells. In the present study, we have investigated the effect of these cytokines, alone or in combination, on the function and viability of human islet cells in vitro. Three hour insulin release was markedly reduced in human islet monolayer cultures after 4 days' exposure to 1000 U/ml of the combination TNF-alpha plus IFN-gamma (36.7 +/- 7.7, % of the control +/- SEM) or to TNF-alpha alone (49.5 +/- 7% of the control) while IFN-gamma had little effect. On direct inspection cell damage was clearly detected only in the cultures treated with TNF-alpha plus IFN-gamma in which staining by indirect immunofluorescence (IFL) for insulin revealed that the number of beta cells was also significantly reduced, thus suggesting a real cytotoxic effect of this cytokine combination. This effect was not beta cell specific since glucagon release and the number of alpha cells were also reduced in the cultures exposed to IFN-gamma plus TNF-alpha. 51Cr release experiments supported the cytoxicity of these cytokines to normal islet cells. There was a time course relationship between class II induction (2 days) and the cytotoxic effect of IFN-gamma plus TNF-alpha (4 days) on the same islet cells. In conclusion, these results indicate that the combination of IFN-gamma and TNF-alpha exerts a cytotoxic effect on human islet cells in vitro.

Cell Survival↗
PubMed1990

HLA DR, DP, DQ induction in human islet beta cells by the cytokine combination IFN-gamma + TNF-alpha.

Human islet beta cells do not express HLA Class II normally, yet, in the diabetic pancreas, beta cells are selectively positive for Class II and this may facilitate their recognition by T cells. It has been demonstrated that human beta cells can be induced to express Class II when cultured with IFN-gamma + TNF-alpha or IFN-gamma + TNF-beta. To assess whether or not they can be induced to express the products of the Class II subregions, DR, DP and DQ, human islet cultures from 10 pancreas were supplemented with the combination of IFN-gamma + TNF-alpha using MoAbs specific for DR, DP and DQ products, and antibodies to insulin and glucagon. The combination IFN-gamma + TNF-alpha (100-1000 U/ml each) was able to induce the expression of the three subregions in both beta and alpha cells. The induction of subregion expression followed the hierarchy DR greater than DQ greater than or equal to DP. The capability of beta cells to express all three Class II subregions supports the possibility that these cells can present their self antigens to T cells.

Gene Expression Regulation↗
PubMed1986

Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas.

Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes.

Cells, Cultured↗
PubMed1985

Cyclic GMP in the retinas of normal mice and those heterozygous for early-onset photoreceptor dystrophy.

Cyclic GMP metabolism has been investigated in the retinas of mice that are heterozygous for a 'photoreceptor dystrophy' gene and have a lowered concentration of cGMP in their photoreceptor cells. The concentration of rhodopsin, retinal morphology and guanylate cyclase kinetics were normal. Cyclic GMP phosphodiesterase had a lowered affinity for cGMP. In accord with previous observations, chelation of exogenous calcium had no effect on cGMP levels in light-adapted retinas but increased them in dark-adapted tissue. The difference between cGMP concentrations in heterozygous and normal retinas in the dark was then eliminated. It was concluded that a modulator of cGMP phosphodiesterase activity is most likely to be causing the lowered steady-state level of cGMP in heterozygous retinas and that calcium is not involved.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1979

Mycotic aneurysm of the ulnar artery.

A mycotic aneurysm is an uncommon, but serious, complication of infective endocarditis, occurring as a result of an infected embolus being lodged in the vasa vasorum or lumen of an artery. Involvement of the ulnar artery is rare, but its peripheral location renders its diagnosis more simple. A case of mycotic aneurysm of the ulnar artery complicating infective endocarditis is reported, with successful management by ligation and excision.

Adult↗
PubMedDate not supplied

Effect of palliative and corrective surgery on ventricular volumes in complete atrioventricular canal.

The effect of pulmonary artery banding (PAB) and intracardiac repair on ventricular volumes was studied in 35 patients with uncomplicated complete atrioventricular canal (CAVC). Right ventricular (RV) and left ventricular (LV) end-diastolic volumes (EDV), determined from biplane cineangiograms using Simpson's rule, were expressed as a percent of normal mean (% Nl) for body surface area; normal range (mean +/- 1SD) is equivalent to 75%-125% Nl. In preoperative studies (RV 26, LV 33), EDV averaged 149 +/- 51% and 184 +/- 50% Nl, respectively, P vs Nl less than 0.001 for both. In one of 26 patients, RV was very small (45% Nl), and one of 33 had a small LV (70% NI). In 13 patients studied post-PAB, RVEDV and LVEDV were lower than in the preoperative group (P less than 0.001) and averaged 114 +/- 40% and 126 +/- 52% Nl, respectively. In three of 13, RV was small (67% and 71% Nl) or very small (56% Nl). Three others had a small (71% and 67% Nl) or very small (56% Nl) LV. In serial pre- and post-PAB studies (RV 9, LV 11), EDV was increased or normal in all preoperatively. In seven of nine, RVEDV decreased, falling below normal range in three. In eight of 11, LVEDV decreased, falling below normal in three. Following repair, RV and LVEDV averaged 80 +/- 20% Nl and 126 +/- 23% Nl, respectively, in seven patients. Four of the seven had RVEDV below normal range. Two patients with a small ventricle had intracardiac repair and did well.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗