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Biomedical subjects

M V Kulkarni

Publications and source records attributed to M V Kulkarni.

At least 19 recordsLinked to original sources
PubMed2006

Simultaneous downregulation of CDK inhibitors p18(Ink4c) and p27(Kip1) is required for MEN2A-RET-mediated mitogenesis.

Multiple endocrine neoplasia type 2A (MEN2A) is predisposed by mutations in the RET proto-oncogene. Low expression of the cyclin-dependent kinase inhibitor (CDKI) p27(Kip1) is present in thyroid tumors, and recent evidence demonstrates p27 downregulation by the active RET mutant, RET/PTC1, found in papillary thyroid carcinoma. This implicates decreased p27 activity as an important event during thyroid tumorigenesis. However, p27(-/-) mice develop MEN-like tumors only in combination with loss of another CDKI, p18(Ink4c). This suggests that p18 and p27 functionally collaborate in suppression of tumorigenesis, that loss of both is critical in the development of MEN tumors and that both p18 and p27 are regulated by RET. We report that induction of the constitutively active MEN2A-specific RET mutant, RET2A(C634R), correlates with reduced p18/p27, and elevated cyclin D protein levels, leading to increased CDK activity, increased pRb phosphorylation and proliferation under growth arrest conditions. Mechanistically, RET2A represses p18/p27 mRNA levels while elevating cyclin D1 mRNA levels. RET2A expression also correlates with decreased p27 protein stability. RET2A-mediated regulation of p18 and p27, but not of cyclins D1 and D2, requires functional mitogen-activated protein kinase signaling. Additionally, RET2A-dependent p18 repression is required and sufficient to increase cell proliferation. Perhaps most significantly, MEN2A adrenal tumors also display these changes in cell cycle expression profile, demonstrating the biological relevance of our cell culture studies. Our results demonstrate for the first time that RET2A regulates p18, and suggest that loss of not only p27 but also of p18 expression is a key step in MEN tumorigenesis.

Adrenal Gland Neoplasms↗
PubMed2006

Fourier transform-infrared and Raman spectra, ab initio calculations and assignments for 6-methyl-4-bromomethylcoumarin.

Fourier transform-infrared (4000-400 cm-1) and Raman (3500-50 cm-1) spectral measurements have been made for 6-methyl-4-bromomethylcoumarin. Equilibrium structures, harmonic vibrational frequencies, infrared intensities, and depolarization ratios have been computed at RHF/6-31G* and B3LYP/6-31G* levels of theory. Twisting CH2Br moiety in the geometry optimization leads to the most stable conformer lacking symmetry (C1). This is reflected in the richness of bands in the experimental spectra. A complete assignments of the bands, aided by the ab initio calculations, has been proposed for the 6-methyl-4-bromomethylcoumarin. Due to lack of symmetry, several normal vibrations have been found to be mixed ones.

Coumarins↗
PubMed2005

Synthesis and in vivo analgesic and anti-inflammatory activity of some bi heterocyclic coumarin derivatives.

Sets of coumarinyl ethers having chromone, benzofuranyl and 4-hydroxy coumarins (4, 5, 6) were prepared and tested for analgesic and antiinflammatory activity. The 4-(4'-acetyl-3'-hydroxy-phenoxymethyl)-coumarin 3 were synthesised by the reaction of 4-bromo methyl coumarin with 2, 4-dihydroxy acetophenones, were found to less active. Further compound 3 having the ortho hydroxy moiety was cyclised to chromones 4 and benzofurans 5 were found to enhance the analgesic and anti-inflammatory activity. The cyclisation to 4-hydroxy coumarin 6 was found to be reducing the anti-inflammatory and analgesic activity in this series. These newly synthesized compounds were found to produce less toxicity and less ulcerogenic effects.

Analgesics↗
PubMed2005

Diagnostic role of stool culture & toxin detection in antibiotic associated diarrhoea due to Clostridium difficile in children.

BACKGROUND & OBJECTIVE: Mere diagnosis of Clostridium difficile by culture does not help in the diagnosis of antibiotic associated diarrhoeae (AAD) due to C. difficile. Detection of toxins A and B form the mainstay in the diagnosis of AAD due to C. difficile. This study was undertaken to find out the role of stool culture and toxin detection in the diagnosis of AAD due to C. difficile. As there are very few documented reports from India about AAD due to C. difficile in children in the age group of 5-12 yr, this age group was selected. METHODS: Faecal samples were collected from 250 hospitalized children in the age group of 5-12 yr who developed diarrhoea on receiving antibiotics for different medical problems for more than five days duration. Also faecal samples of 250 age and sex matched controls were collected. Culture for C. difficile was done on cycloserine cefoxitin fructose egg yolk agar (CCFA) and colonies were identified by standard laboratory techniques. ELISA for toxins A and B detection and tissue culture on HeLa cells for toxin B detection were also done. RESULTS: Overall positivity was 18 per cent in this study group compared to the controls (P<0.001). Maximum positive cases were in 5-8 yr age group (84.4%). Severe diarrhoea, liquid stool with mucus and blood, faecal leucocytes >5/high power field, altered flora and presence of Gram-positive bacilli with oval subterminal spores on Gram stain were sensitive predictors for diagnosis of AAD due to C. difficile. Amongst positive cases, 68.9 per cent responded to discontinuation of antibiotics and 31.1 per cent to metronidazole therapy. INTERPRETATION & CONCLUSION: C. difficile was an important pathogen responsible for antibiotic associated diarrhoea (AAD) in children of 5-12 yr age group. Conservative use of antibiotics would be beneficial to decrease the incidence of AAD.

Anti-Bacterial Agents↗
PubMed2003

Multiple giant congenital melanocytic nevi with central nervous system melanosis.

A case of multiple giant congenital melanocytic naevi in whom central nervous system melanosis was detected at 6 weeks of age is described. The infant was asymptomatic, but presence of risk factors such as multiple naevi, giant naevi and naevi on scalp and posterior axial location prompted a magnetic resonance imaging study of the brain. To our knowledge, neurocutaneous melanosis at such a young age has not been reported in Indian literature.

Humans↗
PubMed1998

Atherogenic diet alters folate enzymes in mice: implications of folate deficient homocysteinemia.

The two key enzymes, methylenetetrahydrofolate reductase and methionine synthase involved in methionine synthesis from homocysteine were studied in atherogenic diet fed mice. Methylenetetrahydrofolate reductase activity was elevated while methionine synthase was impaired in atherogenic diet fed group. Impaired methionine synthase activity would adversely affect the methionine synthesis from homocysteine, resulting in a rise in the homocysteine levels, which are atherogenic. This is reflected by the increased levels of very low density and low density lipoprotein cholesterol values and a higher ratio for total cholesterol to high density lipoprotein cholesterol.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

Immunogenicity study of Haemophilus influenzae type B conjugate vaccine in Indian infants.

OBJECTIVE: To assess the immunogenicity in Indian infants to Haemophilus influenzae b oligosaccharide conjugate vaccine (HbOC). DESIGN: Prospective multicenter study. SETTING: Pediatric Out Patient Department of general hospitals in Pune and Mumbai. SUBJECTS: 124 full term healthy infants brought for routine DPT/OPV immunization. METHODS: Infants were administered 3 doses of 0.5 ml of HbOC, on the same day as their DPT/OPV immunization, injected intramuscularly on the limb opposite to that where DPT vaccine was administered. Data on local reactions and general symptoms was collected for three days after every dose. The children had their blood collected for assay of anti PRP (polyribosil ribitol phosphate) antibody titers, along with the first injection and one month after the third injection. One hundred and three infants completed the study protocol with two blood collections. RESULTS: The initial geometric mean titers (GMT) of 0.124 mcg/ml rose by 37 times to 4.552 mcg/ml. Ninety eight children (95.1%) had a final titer of > or = 0.15 mcg/ml, the minimum level associated with protection, and 77 children (74.8%) had a final level of > or = 1.0 mcg/ml, a level associated with long term protection. CONCLUSION: HbOC is immunogenic in Indian infants when used as per the locally recommended DPT/OPV immunization schedule.

Antibodies, Bacterial↗
PubMed1990

Acute spinal cord injury. A study using physical examination and magnetic resonance imaging.

Magnetic resonance imaging (MRI) was performed on 37 patients with acute spinal injury using T1- and T2-weighted images. Three different types of MRI signal patterns were detected in association with these spinal cord injuries. A classification was developed using these three patterns. Type I, seen in ten (27.0%) of the patients, demonstrated a decreased signal intensity consistent with acute intraspinal hemorrhage. Type II, seen in 16 (43.2%) of the patients, demonstrated a bright signal intensity consistent with acute cord edema. Type III, seen in three (8.1%) of the patients, demonstrated a mixed signal of hypointensity centrally and hyperintensity peripherally consistent with contusion. The remaining eight patients had normal cords by MRI. All 37 patients had an admitting neurologic assessment and classification of their spinal injury according to the Frankel classification and the Trauma Motor Index (TMI). At an average of 12.1 months postinjury, their neurologic function was reassessed. Patients with Type I patterns showed no improvement in their Frankel classification and minimal improvement in their TMI, 32.1 to 42.4. In comparison, all of the Type II and III patterns improved at least one Frankel classification. The Type II TMI increased from 70.8 to 91.9 and Type III from 37.3 to 75.7. This preliminary report indicates a distinct correlation between the pattern of spinal cord injury as identified by MRI and neurologic recovery. It appears that the ability of MRI to aid in examination of the condition of the spinal cord will offer a means of predicting neurologic recovery following acute spinal cord injury.

Adult↗
PubMed1988

In vivo localized proton spectroscopic studies of human gastrocnemius muscle.

In vivo proton magnetic resonance spectroscopy studies of gastrocnemius muscle were performed in six normal volunteers. Both spatially resolved spectroscopy (SPARS) and stimulated echo acquisition mode (STEAM) sequences were used for volume localization. A number of water suppression sequences have been combined with these localization schemes. Among the various techniques investigated in these studies, STEAM with an inversion pulse (T1-discriminated spectrum) seems to have the best potential for in vivo localized high-resolution proton spectroscopy studies of human muscle.

Adult↗
PubMed1988

Magnetic resonance imaging of acute spinal cord trauma: preliminary report.

Forty-three magnetic resonance studies were performed on 28 patients with suspected spinal cord injury using a 1.5 Tesla magnet and surface coils. Imaging was performed between day 1 and day 16 post injury. In several patients, repeat magnetic resonance studies were performed to evaluate the resolution of the cord lesions. Three types of magnetic resonance signal patterns were seen in association with the cord injuries. Patients with intraspinal hemorrhage did not have significant neurological recovery, whereas patients with cord edema/contusion recovered significant neurological function. Magnetic resonance imaging appears to be useful in the diagnosis of acute cord injury and also appears to demonstrate the potential for predicting neurological recovery.

Adolescent↗
PubMed1988

1.5 tesla magnetic resonance imaging of acute spinal trauma.

Fifty patients with spinal injury above L2 were studied with MRI; forty-two had initial and followup studies permitting correlation of MRI abnormalities with neurologic improvement. Two discrete patterns of MRI abnormality were identified, presumably representing cord hemorrhage and edema respectively. A third pattern appeared to represent a mixed type of injury. The correlation between the MRI patterns of cord injury and neurologic recovery was excellent. The ability of MRI to demonstrate and characterize acute cord injury appears to exceed that of other diagnostic techniques.

Acute Disease↗
PubMed1987

Detection of caval obstruction by magnetic resonance imaging after intraatrial repair of transposition of the great arteries.

Vena caval obstruction may cause significant morbidity after intraatrial repair of transposition of the great arteries (TGA). Two noninvasive methods of diagnosing vena caval obstruction were compared with cardiac catheterization. Echocardiographically gated magnetic resonance imaging (MRI) and echocardiographic evaluation (2-dimensional saline contrast echocardiography and pulsed Doppler flow measurement) were performed on 15 patients 0.7 to 13.5 years after intraatrial repair of TGA (8 Mustard, 7 Senning). At catheterization, complete superior vena cava or partial caval obstruction (gradient greater than 5 mm Hg from cava to systemic venous atrium) was present in 7 of 15 patients. Superior vena cava obstruction was directly visualized by MRI in both patients with catheterization-proved complete superior vena cava occlusion. A dilated azygous/hemiazygous venous complex (greater than or equal to 5 mm cross-sectional diameter) was seen by MRI in 5 of 7 patients with complex or partial vena caval obstruction and in no patient without vena caval obstruction. MRI showed superior vena caval dilatation (ratio of superior vena caval diameter to aortic diameter greater than 1.45) in 3 of 5 patients with partial vena caval obstruction and in 0 of 8 without vena caval obstruction. Direct visualization of narrowing within the atrium was unreliable for any MRI plane because of the 3-dimensional nature of the intraatrial baffle. Two-dimensional saline contrast echocardiography, successfully performed in 12 of 15 patients, detected complete superior vena caval obstruction only in the 2 patients with catheterization-proved complete superior vena cava occlusion. Contrast echocardiography failed to identify any of the 5 patients with partial vena caval obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

In vivo proton spin-lattice relaxation times of normal and dystrophic muscles.

In vivo spin-lattice relaxation times (T1) of water and lipid protons were measured in normal and dystrophic chicken pectoralis muscles at different ages. Values were obtained with a surface coil used as both a receiver and a transmitter. A 2 theta-T1-theta-Acquisition sequence was used for these measurements. Accuracy was verified with an inversion-recovery method using a slotted tube resonator as the transmitter and a surface coil as the receiver. It was observed that the T1 values of water protons in normal muscles decrease with age, the T1 values of water protons do not change with age in dystrophic muscles, and the T1 values of lipid protons increase with age in normal and dystrophic muscles. These results indicate a failure of the normal maturation of dystrophic muscles.

Animals↗
PubMed1987

MRI of mumps encephalitis: comparison with CT evaluation.

The evaluation of a patient with mumps encephalitis by computed tomography (CT) and magnetic resonance (MR) imaging is reported. Correlation of findings on MR and CT in relation to clinical symptoms is presented. MR was found to be more sensitive in the number of lesions detected (11) as compared to CT (3). Thus, it seems that MR imaging may be a sensitive diagnostic adjunct in cases of suspected viral encephalitis.

Child, Preschool↗