Biomedical subjects
R Sehgal
Publications and source records attributed to R Sehgal.
Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis.
Childhood neuroblastoma tumours of the sympathetic nervous system show a remarkable clinical heterogeneity ranging from spontaneous regression to unfavourable outcome despite intensive therapy. Favourable neuroblastomas often express high levels of trkA mRNA, encoding the tyrosine kinase receptor for nerve growth factor. We have investigated mRNA expression for the neurotrophin receptor trkC in 23 primary neuroblastomas using a sensitive RNAase protection assay. TrkC expression was detected in 19 of these tumours at highly variable levels with a 300-fold difference between the highest and lowest values. Significantly higher levels of trkC mRNA were found in tumours from patients with favourable features such as low age (P < 0.012), favourable tumour stage (P < 0.012) and favourable prognosis (P < 0.05). Children with intermediate or high trkC mRNA expression had better prognosis compared with those with low or undetectable levels (83.3% vs 20%, P = 0.005). Further characterisation of trkC mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) showed that mRNA encoding the full-length cytoplasmic tyrosine kinase domain of the receptor was only expressed in a subset of favourable tumours. These data show that favourable neuroblastomas may express the full trkC receptor while advanced tumours, in particular MYCN-amplified neuroblastoma, seem to either express no trkC or truncated trkC receptors of as yet unknown biological function. These data are suggestive of a role for trkC and its preferred ligand neutotrophin-3, NT-3, in neuroblastoma differentiation and/or regression.
Identification of a 148-kDa surface lectin from Giardia lamblia with specificity for alpha-methyl-D-mannoside.
A lectin specific for alpha-methyl-D-mannoside was purified from the membrane extract of Giardia lamblia by a combination of gel filtration chromatography on Sephadex G-75 and Superose 6-HR 10/30. The homogeneity of the lectin was established by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The molecular mass of the native protein was 148 kDa. The lectin agglutinated rabbit erythrocytes in the presence of Ca2+ at 37 degrees C and pH 7.0. The maximum activity of the lectin was obtained after trypsin treatment. The inhibition study clearly suggests that the binding site of the lectin recognizes alpha-methyl-D-mannoside as the immunodominant sugar.
Feasibility of exercise stress echocardiography for the follow-up of children with coronary involvement secondary to Kawasaki disease.
BACKGROUND: The development of coronary aneurysms as sequelae of Kawasaki disease can result in myocardial ischemia, infarction, and sudden death. Traditionally, these patients have undergone coronary angiography and nuclear stress imaging for risk stratification and follow-up. However, angiography is invasive, and both modalities expose the patient to repeated radiation, which is an important issue in children. The purpose of this study was to determine the feasibility of performing exercise stress echocardiography in children diagnosed with coronary abnormalities secondary to Kawasaki disease. METHODS AND RESULTS: Treadmill exercise stress echocardiographic studies were performed in 28 children ages 6 to 16 years. All had acute Kawasaki disease 1 to 10 years before study, and coronary artery abnormalities were identified during previous echocardiographic imaging. Patients were exercised using a standard Bruce protocol. Transthoracic echocardiographic images, obtained in the parasternal long, short, apical two- and four-chamber views immediately before and after exercise, were digitized for review and analysis. In baseline studies before exercise, wall motion abnormalities were identified in 2 patients; these segments became normal with exercise. Two patients developed new exercise-induced wall motion abnormalities that corresponded to angiographically defined critical stenosis of the left anterior descending coronary artery. No patients had resting or exercise-induced ECG evidence of ischemia. There were no adverse reactions, and 26 of 28 patients had normal exercise tolerance. CONCLUSIONS: Among patients with coronary artery involvement resulting from Kawasaki disease, exercise stress echocardiography is a safe, noninvasive procedure and may identify children with myocardial ischemia that was not detected with ECG stress test alone.
Looking for drugs in ancient texts.
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Serogroups of rotavirus in north India.
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Parasitic infections in day care centres.
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Evaluation of Salmonella porins as a broad spectrum vaccine candidate.
Porins were prepared from smooth strain of Salmonella typhi 0-901 and chemotype of rough mutant of S. typhimurium Ra-30. Mice were immunized with both the porin preparations in different groups and challenged with S. typhimurium LT2-71 and S. enteritidis SH-1269. Porin immunized mice showed significant protection (P < 0.01) against challenge with homologous as well as heterologous strains. Hence, the use of porins may be attempted in future to protect against salmonellosis.
Stimulation of macrophage oxygen free radical production and lymphocyte blastogenic response by immunization with porins.
Porins were prepared from smooth strain of Salmonella typhi 0-901 and chemotype rough mutant of S. typhimurium Ra-30. Porins could significantly stimulate the immune systems of mice. Immunization of mice with the porins provoked synthesis of anti-porin antibodies. Macrophages from the immunized mice showed increased capacity to generate oxygen free radicals, and lymphocytes from these mice showed proliferative response to the porins. Thus porins may play a role in providing protection from salmonellosis by stimulating the antibody production and increasing the capacity of macrophages to generate oxygen free radicals along with stimulation of lymphocytes.
Macrophage-mediated enterocyte damage in BALB/c mice infected with different strains of Giardia lamblia.
The mechanism of mucosal injury in Giardia lamblia-infected animals and humans is not well understood, although the role of gut macrophages in killing the trophozoites is well known. It is speculated, however, that macrophage products have a role in tissue injury and inflammatory response during infection, as in other inflammatory diseases. Therefore, in the present study an attempt was made to examine the mechanism involved in enterocyte damage during giardiasis. This was achieved using co-culture of enterocytes and gut macrophages obtained from infected BALB/c mice. The extent of tissue damage was assessed by measuring the marker enzyme of enterocyte damage, lactate dehydrogenase. To investigate the role of the various proteases and free oxygen radicals released by activated macrophages on enterocyte damage, inhibitors of various proteases and free oxygen radicals were used. Superoxide radical and certain proteases were found to have important roles in bringing about enterocyte damage during this infection in mice. Parasite load, lactate dehydrogenase release, and extent of lipid peroxidation were more pronounced in mice infected with symptomatic strains than in asymptomatic ones. The theory of inflammatory cell-mediated enterocyte damage in Giardia lamblia infection is proposed.
A cholera-coli related enterotoxin production by different Shigella species.
A cholera-coli related enterotoxin production was studied in 50 different Shigella isolates from cases of childhood diarrhoea. Four out of 6 Sh. dysenteriae, 18/37 Sh. flexneri and 2/4 Sh. sonnei were found to be enterotoxin producers by RIL test. All strong RIL positive strains were isolated from cases of severe diarrhoea, indicating the association of enterotoxin production and severity of acute diarrhoea. Two major protein bands were observed in SDS-PAGE and W.B. EIA assay in all positive RIL extracts. These immuno-reactive bands were at 31 kDa and 14 kDa positions resembling A-B subunit structure of cholera-coli family of enterotoxins.
An experimental model of ameboma in guinea pig.
Among the wide variety of clinicopathological manifestations of intestinal amebiasis, amebomas occur rarely and their pathogenesis is not well understood. When cholesterol-fed, 2- to 4-week-old guinea pigs were infected intracecally with a virulent, monoaxenic strain of Entamoeba histolytica, gross and histologically characteristic amebomas developed in 85% of the animals by the 3rd day, in 94% by the 9th day, and in 96% by the 12th day postinfection, by which time most of them had died. Amebomas were confirmed by histopathology. Thus, a model of consistent production of amebomas was documented.
Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection.
The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates born to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0, 1, 2 months) of the vaccine alone, while 27 infants were given hepatitis B immunoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels > or = 10 IU/l) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 v. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies born to anti-HBe positive mothers.
Vertical transmission of hepatitis B in north India.
A total of 2337 mother-baby paired sera were screened for the presence of hepatitis B surface antigen. Fifty eight mothers (2.48 per cent) were positive for HBsAg. Six babies (10.3 per cent) were positive for HBsAg at birth. The risk of the babies acquiring the infection during the first year of life varied with the serological status of the mothers. In HBeAg positive mothers the babies were at the greatest risk, with 11/15 (73.3 per cent) babies acquiring the infection by twelve months. If the mothers were only HBsAg positive the risk was lower (17.3 per cent), and if the mother was anti-HBe positive also then the baby had the least chance of becoming infected (9 per cent).
Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers.
The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates, respectively. 58 infants who could not be vaccinated constituted the control group. It was observed that in the unvaccinated group approximately 70% of the infants became infected. In both the vaccinated groups, the seroconversion and seroprotection rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up, but, at 12 months, infants given HBIG and vaccine showed better seroprotection rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine was also better in both the groups if the mothers were anti-HBe positive. Despite immunization, 14.2% and 25% infants in group I and II, respectively, became chronic carriers if their mothers were HBeAG positive.
Occupational risks in sewage work.
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Use of inactivated or oral poliovirus vaccine in India.
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