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Biomedical subjects

G Kumar

Publications and source records attributed to G Kumar.

At least 73 records · Page 4Linked to original sources
PubMed1996

The cerebellum-enriched form of nuclear factor I is functionally different from ubiquitous nuclear factor I in glial-specific promoter regulation.

Nuclear factor I (NFI) binding sites are present in a wide range of brain-specific gene enhancer and promoter sequences and appear to play a role in establishing cell type-specific expression within the CNS. The precise mechanisms used by various members of the NFI family of proteins to confer brain-specific expression are unclear. We have addressed this issue by comparing the transactivating capabilities of two forms of NFI in directing gliotropic expression from two different JC virus (JCV) promoter configurations. The JCV is an opportunistic pathogen of humans that causes lytic destruction of the oligodendrocytes and thus demyelination in immunocompromised patients. Our results show that the cerebellum-enriched form of NFI (NFI-A1) transactivates two gliotropic JCV early promoters to a greater extent than the ubiquitous form of NFI (NFI-C1). Activation by NFI-A1 was dramatically greater in glial than in nonglial cells. These results suggest that NFI proteins direct brain-specific expression through combinatorial interactions with cell specific coactivators and/or transcription factors that recognize adjacent sites within brain specific promoters.

Animals↗
PubMed1996

Use of mid-arm and chest circumferences to predict birth weight in rural north India.

STUDY OBJECTIVE: To determine the most appropriate surrogate indicator and its cut off point for identifying low birthweight babies in northern India. STUDY SETTING: A secondary level hospital at Ballabgarh. The patients were from nearby rural and urban areas and mostly belonged to lower and middle socioeconomic strata. PARTICIPANTS: These comprised 733 singleton newborns delivered in the hospital between April and December 1991. DESIGN: Birth weight, arm circumference, and chest circumference were measured in all the newborns. Different cut off points for each index were identified and their validity was tested. Based on the regression equations, a simple chart was drawn up and was used to predict weights for different arm and chest circumferences in the hospital and community settings. MAIN RESULTS: Cut off points for arm and chest circumferences of 8.5 cm and 29.5 cm respectively gave a sensitivity and specificity of around 80%. When the chart based on the regression equations was tested in both the hospital and the community, chest circumference was found to be the better of the two indicators. CONCLUSION: Chest circumference seems to be the most appropriate surrogate measure for birth weight. Cut off points of 29.5 cm and 27.5 cm seem to be satisfactory for predicting birth weight below 2500 g and 1800 g respectively. The birthweight prediction card using chest circumference was effective in predicting birth weight.

Birth Weight↗
PubMed1996

Frontoethmoid mucocele: one-year follow-up after endoscopic frontoethmoidectomy.

Endoscopic sinus surgery for frontal sinus mucocele is gaining popularity. A case study, and the CT scan of a large frontal mucocele with 1-year follow up is presented showing the lining of the sinus cavity well healed and the frontal sinus ostium as patent. Endoscopic sinus surgery, therefore, is a potentially useful method for treating large frontal mucoceles.

Endoscopy↗
PubMed1996

Hepatic mesenchymal hamartoma: a case report and radiological findings.

Primary tumours of the liver are uncommon in childhood. Of these, more than two-thirds are malignant. As such, benign hepatic tumours are often not considered in the differential diagnosis of a hepatic mass in childhood. We report a case of hepatic mesenchymal hamartoma, a rare benign tumour, in a 10-month-old infant. This tumour is characterised by an admixture of ductal structures within a copious loose connective tissue stroma. Only approximately 160 cases had been reported in the literature. Awareness of the ultrasound (U/S) and computed tomography (CT) features, although not diagnostic, is helpful in distinguishing it from the more common malignant tumours. A correct preoperative diagnosis is important as surgical excision is often curative.

Diagnosis, Differential↗
PubMed1995

The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line.

Ligation of membrane immunoglobulin M (mIgM) receptor in the Ramos B-cell line induced tyrosine phosphorylation of several intracellular substrates, including the adaptor protein. Shc. Phosphorylated Shc could be seen to associate with Grb2 in a complex which included hSOS. Inasmuch as hSOS is involved in p21ras activation, we also demonstrated that mIgM ligation activated a Ras-dependent kinase cascade in which sequential activation of Raf-1 and MEK-1 culminates in the activation of p42 mitogen-activated protein (MAP) kinase (ERK-2). The tumour promoter and protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA), also activated Raf-1, MEK-1, and MAP kinase in Ramos cells, but did not induce tyrosine phosphorylation of Shc or Shc/Grb2 association. Okadaic acid, another tumour promoter and serine/threonine phosphatase inhibitor, activated p42 MAP kinase without activating Raf-1 or MEK-1, suggesting the existence of a serine/threonine phosphatase which directly regulates MAP kinase activity.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Evidence for LFA-1/ICAM-1 dependent stimulation of protein tyrosine phosphorylation in human B lymphoid cell lines during homotypic adhesion.

JK32.1 and SKW6.4 are Epstein-Barr virus (EBV)-positive human B cell lines that undergo spontaneous, lymphocyte function-associated antigen 1 (LFA-1) dependent homotypic adhesion in culture. This process is associated with induction of tyrosine phosphoproteins of molecular mass 90, 106, and 120 kDa and could be reproduced when these cells were centrifugationally aggregated. Antibodies to the beta 2 (CD18) chain of LFA-1 interfered with induction of p120, p106, and p90 during cellular aggregation. Response induction was abrogated when cells were incubated with protein tyrosine kinase (PTK) inhibitors (erbstatin, genistein, and geldanomycin) or cytochalasin B prior to aggregation. An in vitro kinase assay did not reveal activation of focal adhesion kinase. Although the role of LFA-1-dependent tyrosine phosphorylation in B cells is uncertain, patients with the leukocyte adhesion defect (LAD) exhibit humoral abnormalities. Moreover, aggregation did not induce specific tyrosine phosphoproteins in an EBV-transformed B cell line from a LAD patient. These results suggest that an LFA-1-dependent PTK pathway may play an important role in human B cell function.

Antibodies, Monoclonal↗
PubMed1995

Comparative in vitro cytotoxic effects of taxol and its major human metabolite 6 alpha-hydroxytaxol.

Taxol is metabolized by the liver microsomal cytochrome P450 enzyme system into its principal metabolite 6 alpha-hydroxytaxol (6HT). In the present in vitro studies 6HT was compared to taxol with respect to its effects on tubulin depolymerization, mitotic arrest, clonogenic survival and apoptosis in HL-60 cells. 6HT was generated by incubating taxol with human liver microsomes in a NADPH-generating system. HL-60 cells were incubated for 24 h with either taxol or 6HT, washed and placed in drug-free suspension or cultured for colony growth in agarose. For the suspension and colony culture growth of the cells, the IC50 concentrations of 6HT were 500 +/- 46 and 350 +/- 37 nM, while those of taxol were 3.2 +/- 0.2 and 2.8 +/- 0.5 nM, respectively. Immediately after a 24-h exposure of HL-60 cells to 50 nM taxol, electrophoresis of genomic DNA from HL-60 cells revealed an internucleosomal DNA fragmentation 'ladder'. In addition, 39% of the cells were arrested in mitosis and 16% showed the morphologic features of apoptosis. In contrast, an identical treatment with 6HT resulted in the mitotic arrest of only 2.8% of the cells, with 4.0% displaying apoptosis (P < 0.01); internucleosomal DNA fragmentation was not observed. 6HT was also significantly less effective than taxol in inhibiting the temperature-induced depolymerization of microtubules in a cell-free system. However, at equipotent concentrations, the effect of 6HT on tubulin depolymerization, mitotic arrest or apoptosis was similar to that of taxol. In addition, at concentrations of taxol or 6HT at or below their IC50, there was little tubulin depolymerization, mitotic arrest or apoptosis. The results presented here show that the biotransformation of taxol to 6HT substantially detoxifies taxol.

Apoptosis↗
PubMed1995

Denitration of glycerol trinitrate by resting cells and cell extracts of Bacillus thuringiensis/cereus and Enterobacter agglomerans.

A number of microorganisms were selected from soil and sediment samples which were known to have been previously exposed to nitrate ester contaminants. The two most effective bacteria for transforming glycerol trinitrate (GTN) were identified as Bacillus thuringiensis/cereus and Enterobacter agglomerans. For both isolates, denitration activities were expressed constitutively and GTN was not required for induction. Dialysis of cell extracts from both isolates did not affect denitration, which indicates that dissociable and depletable cofactors are not required for denitration. With thin-layer chromatography and high-performance liquid chromatography, the denitration pathway for both isolates was shown to be a sequential denitration of GTN to glycerol dinitrate isomers, glycerol mononitrate isomers, and ultimately to glycerol. GTN was observed to be completely converted to glycerol during a long-term incubation of cell extracts.

Bacillus cereus↗
PubMed1995

The JC virus minimal core promoter is glial cell specific in vivo.

The glial cell specificity of the human papovavirus JC (JCV), an etiologic agent for progressive multifocal leukoencephalopathy, is thought to be due to the presence of both positive and negative regulatory elements upstream of the TATA region within the JCV promoter. Here we report that the JCV minimal core promoter, containing only the TATA box and an 8-bp poly(T) region immediately upstream, is sufficient to initiate transcription of an attached gene in glial cells and functions as an autonomously active initiator. We further define the sequences required for this core promoter's glial cell specificity by appropriate substitution and point mutation analysis. Ectopic expression of Tst-1, a POU domain transcription factor that has been implicated in the regulation of oligodendrocyte development, leads to higher activation of the JCV minimal core promoter in Tst-1-deficient glial cells than in non-glial HeLa cells. These results suggest a requirement for a glial cell coactivator(s) for the optimum activation of the JCV minimal core promoter by Tst-1. A discrete affinity of Tst-1 for the JCV core promoter (Kd, 1.4 x 10(-8) M) is also shown to be optimal for its promoter strength. Mutations within the core promoter that maintain this affinity for Tst-1 show maintenance of promoter strength, whereas mutants carrying a change that results in an increased affinity for Tst-1 show reduced transcriptional activity. These results suggest that moderate affinity of Tst-1 for the JCV TATA region may allow the interaction of some glial cell-specific coactivator(s) along with the basal transcription machinery to direct glial cell-specific transcription from the JCV core promoter.

Animals↗
PubMed1995

Use of the Beck Anxiety Inventory with adolescent psychiatric outpatients.

The Beck Anxiety Inventory was administered to 105 outpatients between 13 and 17 years old who were diagnosed with various types of psychiatric disorders. A principal factor analysis was performed, and two factors were found representing subjective and somatic symptoms of anxiety. The item compositions of these factors were comparable to those previously described for adolescent inpatients. The results are discussed as supporting the use of the inventory for evaluating self-reported anxiety in outpatient adolescents.

Adolescent↗
PubMed1995

Psychosocial correlates of suicidal ideation in adolescent psychiatric inpatients.

The Beck Scale for Suicide Ideation (BSI) was administered to 121 inpatients between 12 and 17 years old who were diagnosed with mixed psychiatric disorders. Twelve background and clinical characteristics, previously found to be associated with adolescent suicidal ideation, were entered into a multiple regression to estimate the BSI scores, along with the Beck Anxiety Inventory, the revised Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), and the Youth Self-Report. The BHS and the BDI were the only two variables that contributed unique variance to the explanation of the BSI scores.

Adolescent↗
PubMed1995

Clinical profile of cholera in young children--a hospital based report.

Clinical profile of cholera was studied in children attending Diarrhea Training and Treatment Unit from January-December 1993. Out of a total 8714 cases of acute watery diarrhea, 64 children (0.7%) were suspected to have cholera on the basis of acute onset loose water/rice watery stools, high purge rate with or without excessive vomiting and/or severe dehydration. Stool culture was positive for cholera in 33 cases (51.6%). All the isolates were V. cholerae 01 biotype El Tor serotype Ogawa. Sixty four per cent of stool culture positive cases were below 5 years of age. The results assume importance because out of 28 children < 2 years with clinical suspicion of cholera, 11 cases (39.3%) were culture positive for V. cholerae, youngest child being 3 months old. Comparison of various parameters revealed that presence of vomiting > 4 episodes/ day (p < 0.005), frequency of stools >12/24 hours (p <0.002), rice watery stools (p < 0.01) and presence of severe dehydration (p < 0.01) were significant parameters associated with positive stool culture. Beside examination of stool sample by hanging drop method was an excellent diagnostic tool (p < 0.001) with a sensitivity of 51.5%, specificity 100% and positive predictive value of 100%. The isolates of V. cholerae were susceptible to furazolidone, cephelexin, nalidixic acid, norfloxacin and gentamicin. Our observations indicate that cholera is not uncommon in infants and young children. Like children in the older age group, acute onset diarrhea with watery/rice watery stools and high purge rate with or without excessive vomiting and/or rapid development of severe dehydration should arouse suspicion of cholera in younger children also. They should be investigated for cholera even in non-endemic areas and in the absence of cholera outbreaks.

Age Distribution↗
PubMed1994

Involvement of Janus kinases, p52shc, Raf-1, and MEK-1 in the IL-6-induced mitogen-activated protein kinase cascade of a growth-responsive B cell line.

We have previously shown that the IL-6R in a growth-responsive B cell line, AF10, induces activation of mitogen-activated protein (MAP) kinase. Here we demonstrate the activation of Raf-1 and MEK-1, which act as a MAP kinase kinase kinase and a MAP kinase kinase, respectively, in the MAP kinase cascade induced by IL-6 in AF10 cells. IL-6 also induced tyrosine phosphorylation of the signaling transducing subunit of the IL-6R in AF10 cells, along with tyrosine phosphorylation of the gp130-associated tyrosine protein kinase JAK1 and the adaptor molecule p52shc. Although induction of tyrosine phosphorylation and activation of MAP kinase by IL-6 in a differentiation-responsive B cell line, SKW 6.4, were below the limits of detection, the phorbol ester PMA did activate Raf-1, MEK-1, and MAP kinase without inducing the phosphorylation of gp130, JAKs, or p52shc. These results suggest that JAK kinase family members associated with the IL-6R may participate in the activation of MAP kinase in AF10 cells by way of an adaptor protein and Ras-dependent kinase cascade.

Adaptor Proteins, Signal Transducing↗
PubMed1994

A 70- to 80-kDa glial cell protein interacts with the AGGGAAGGGA domain of the JC virus early promoter only in the presence of the neighboring cis DNA elements.

The neurotropic virus JC (JCV) causes the demyelinating disease progressive multifocal leukoencephalopathy. JCV is transcriptionally regulated by both positive and negative cis elements. Previous studies have shown that the AGGGAAGGGA sequence, in isolation, interacts with a 53- to 56-kDa cellular protein and acts as a silencer for the late promoter. We have reexamined the role of the AGGGAAGGGA element in the glial cell-specific transcriptional regulation of JCV by studying it in a longer natural context of elements of the JCV early promoter. Transcriptional analysis in C6 glial cells of selectively mutated AGGGAAGGGA domains within the nt 98-153 region of the JCV early promoter revealed that both GGG regions in the AGGGAAGGGA sequence are required for glial cell-specific transcription. The interactions of cellular proteins with the AGGGAAGGGA domain were also found to be dependent upon the presence or absence of neighboring cis elements. The TATA region was found to facilitate the interaction of specific proteins with the AGGGAAGGGA domain. Domain-specific photocrosslinking studies revealed the binding of a glial cell protein of approximately 70-80 kDa to the AGGGAAAGGGA domain only when it was flanked by its neighboring cis elements, the TATA and NF-1 domains of the JCV promoter.

Affinity Labels↗
PubMed1994

The T-cell antigen receptor utilizes Lck, Raf-1, and MEK-1 for activating mitogen-activated protein kinase. Evidence for the existence of a second protein kinase C-dependent pathway in an Lck-negative Jurkat cell mutant.

T-cell antigen receptor (TCR) ligation of an Lck-deficient Jurkat mutant, J.CaM1, with anti-CD3 or anti-TCR beta monoclonal antibodies failed to induce tyrosine phosphorylation and activation of p42MAPK. The same stimuli activated mitogen-activated protein (MAP) kinase in J.CaM1 cells transfected with Lck, demonstrating that Lck plays a critical role in MAP kinase activation. Utilizing immunocomplex kinase assays, we demonstrated that TCR/CD3 ligation activated a MAP kinase kinase kinase (Raf-1) as well as a MAP kinase kinase (MEK-1) in Jurkat but not in J.CaM1 cells. It was possible, however, to activate Raf-1, MEK-1, and p42MAPK in J.CaM1 cells during treatment with the phorbol ester phorbol 12-myristate 13-acetate, which activates protein kinase C (PKC). This demonstrates the presence of a PKC-dependent pathway which functions independently from Lck in MAP kinase activation. Stimulation of Jurkat cells with either anti-TCR beta or anti-CD3 monoclonal antibody failed to induce substantial tyrosine phosphorylation of Shc proteins or their association with Grb2 which forms a complex with the guanine nucleotide exchange factor hSOS. However, the same stimuli induced tyrosine phosphorylation of another putative guanine nucleotide exchange factor, p95Vav, in Jurkat but not J.CaM1 cells. Moreover, Lck was reversibly co-immunoprecipitated with p95Vav, and the stoichiometry of binding increased in anti-CD3-treated Jurkat cells. Phorbol 12-myristate 13-acetate did not induce tyrosine phosphorylation of p95Vav. These data show that the TCR activates MAP kinase by way of a signaling cascade, which depends upon Lck, and may be mediated by downstream events involving PKC or p95Vav which act on Raf-1 and MEK-1.

Cell Line↗