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Biomedical subjects

G Kumar

Publications and source records attributed to G Kumar.

At least 55 records · Page 3Linked to original sources

Malignant transformation of mesenchymal hamartoma of the liver: case report and review of the literature.

Here the first case in the literature of both mesenchymal hamartoma and malignant mesenchymoma occurring in a 6-year-old male child, at different times and at different sites in the liver, and also the possible malignant transformation of a mesenchymal hamartoma is reported. The tumor developed from a lesion in the right lobe that was overlooked initially during a left lateral segmentectomy at 18 months of age for a mesenchymal hamartoma. Malignant mesenchymoma is a rare and aggressive tumor. The origin of this tumor is not well understood. There has been no direct support to the hypothesis that malignant mesenchymoma may be the malignant counterpart of mesenchymal hamartoma. The authors provide clinical and histopathologic evidence in our case that suggests the possibility of malignant mesenchymoma arising from a mesenchymal hamartoma. This case emphasizes the need for complete removal of mesenchymal hamartoma and the need for long-term follow-up to detect multifocal lesion or malignant transformation.

Antineoplastic Agents↗

The Internal Medicine Center--an integrated solution for information on internal medicine on the World Wide Web.

The World Wide Web (WWW) has grown from being a resource center for a select group of scientists to a large database of information that is available to both professionals and public. The amount of medical information on the Web has been increasing exponentially and thus, it has become increasingly difficult for anyone to be able to search for a specific quantum of information among this mass. Even in mid 1996, it was noted that the amount of information on internal medicine was growing rapidly. Hence, on 21 March 1997, the Internal Medicine Center (IMC) was created and launched. The IMC is an unique concept and it represents the first time that medical data on the web has been organized into a form that intimately parallels clinical medicine. The rationale behind the creation of the IMC can be summarized in three words: information, speed and convenience. The interface used by this center reflects these goals because overuse of large image files are avoided, hence decreasing the access time and yet keeping the information in an easily comprehensible manner. In conclusion, the IMC serves as a useful tool for the layman as well as the expert because the comprehensive information that it offers can be accessed rapidly and conveniently.

Information Services↗

Asymmetric distribution of muscarinic acetylcholine receptors in Madin-Darby canine kidney cells.

We have characterized the muscarinic ACh receptors (mAChRs) expressed in Madin- Darby canine kidney (MDCK) strain II epithelial cells. Binding studies with the membrane-impermeable antagonist N-[(3)H]methylscopolamine demonstrated that mAChRs are approximately 2.5 times more abundant on the basolateral than on the apical surface. Apical, but not basolateral, mAChRs inhibited forskolin-stimulated adenylyl cyclase activity in response to the agonist carbachol. Neither apical nor basolateral mAChRs exhibited detectable carbachol-stimulated phospholipase C activity. Carbachol application to the apical or the basolateral membrane resulted in a threefold increase in intracellular Ca(2+) concentration, which was completely inhibited by pertussis toxin on the apical side and partially inhibited on the basolateral side. RT-PCR analysis showed that MDCK cells express the M(4) and M(5) receptor mRNAs. These data suggest that M(4) receptors reside on the apical and basolateral membranes of polarized MDCK strain II cells and that the M(5) receptor may reside in the basolateral membrane of a subset of cells.

Adenosine Triphosphate↗

Clinical case definition of malaria at a secondary level hospital in northern India.

Malaria has re-emerged as a major public health problem in India. At present, under the National guidelines; all fevers are presumed to be due to malaria and chloroquine is given as presumptive treatment. This results in overtreatment. We did a pilot study to see whether some clinical predictors of malaria could be identified in the Indian setting. This case control study was done in a secondary level hospital. All those with fever who were smear positive for malaria were enrolled as cases and other patients fever who were smear negative for malaria served as the controls. All the factors under study were ascertained by a history or detailed clinical examination. A total of 41 cases and 95 controls were enrolled. Of the 41 cases, 35 were positive for P. vivax and six were positive for P. falciparum. After multivariate analysis, only splenomegaly (OR = 2.11; 95% CI = 1.27-3.50) and pallor (OR = 2.01; 95% CI = 1.16-3.48) were significantly associated with malaria. It appears that history of fever along with one or both of these two signs can be a useful predictor of malaria in a secondary level hospital in India. The utility and feasibility of a similar approach in a field setting needs to be studied further.

Analysis of Variance↗

Human serum attenuates the activity of protease inhibitors toward wild-type and mutant human immunodeficiency virus.

The potency of therapeutic regimens containing human immunodeficiency virus (HIV) protease inhibitors is related to the ability to maintain concentrations of drug in the plasma of patients that are sufficient for blocking viral replication. The estimation of concentrations required for in vivo activity using in vitro assays is complicated by the fact that extensive binding of many protease inhibitors to serum proteins attenuates their antiviral potency. To provide insight into the relative in vivo potency of current protease inhibitors, we assayed their in vitro activity against wild-type and mutant HIV in the presence of human serum (HS). Using this assay, ABT-378, a new protease inhibitor with trough levels in humans far in excess of the EC50 in the presence of 50% HS, was identified. The antiviral activity of ABT-378 was only modestly attenuated by HS, in contrast to ritonavir, saquinavir, and nelfinavir. Examination of the effect of individual serum components suggested that the activity of ABT-378 is affected predominantly by binding to alpha1-acid glycoprotein (AGP) while the activity of ritonavir is modulated by both AGP and albumin. The method described here may provide insight into the in vivo potency of protease inhibitors and be useful for the preclinical evaluation and selection of new protease inhibitors for clinical studies.

Blood Proteins↗

The combination of photocatalysis and ozonolysis as a new approach for cleaning 2,4-dichlorophenoxyaceticacid polluted water.

Treatment of 2,4-D polluted waters with photocatalysis leads to the buildup of high concentrations of the long living intermediate 2,4-DCP. A new approach using a combination of ozonolysis and photocatalysis gave better degradation results with lower intermediate concentrations. The advantages of photocatalysis giving a constant decline in TOC and of ozonolysis giving no buildup of high intermediate concentrations were combined. Degradation data of 2,4-D for photocatalysis, ozonolysis and the combination of both for different pH ranges are given. Data on the main intermediate 2,4-DCP are given for the three different approaches.

2,4-Dichlorophenoxyacetic Acid↗

Failed magnetic resonance imaging examinations due to claustrophobia.

A recognized cause of incomplete or cancelled MRI examinations is anxiety and claustrophobic symptoms in patients undergoing MR scanning. This appears to be a problem in many MRI centres in Western Europe and North America, where it is said to be costly in terms of loss of valuable scan time, and has led to researchers suggesting several anxiety-reducing approaches for MRI. To determine the incidence of failed MRI examination among our patients and if there are any associations with a patient's sex, age and education level, we studied claustrophobia that led to premature termination of the MRI examination in the University Malaya Medical Centre (UMMC) in 3324 patients over 28 months. The incidence of failed MRI examinations due to claustrophobia in the UMMC was found to be only 0.54%. There are associations between claustrophobia in MRI with the patients' sex, age and level of education. The majority of those affected were male patients and young patients in the 25-45-years age group. The patients' education level appears to be the strongest association with failed MRI examinations due to claustrophobia, where the majority of the affected were highly educated individuals. Claustrophobia in MRI is more of a problem among the educated individuals or patients from a higher socio-economic group, which may explain the higher incidence in Western European and North American patients.

Adult↗

Plant cell biodegradation of a xenobiotic nitrate ester, nitroglycerin.

The ability of plants to metabolize the xenobiotic nitrate ester, glycerol trinitrate (GTN, nitroglycerin), was examined using cultured plant cells and plant cell extracts. Intact cells rapidly degrade GTN with the initial formation of glycerol dinitrate (GDN) and the later formation of glycerol mononitrate (GMN). A material balance analysis of these intermediates indicates little, if any, formation of reduced, conjugated or cell-bound carbonaceous metabolites. Cell extracts were shown to be capable of degrading GTN with the simultaneous formation of GDN in stoichiometric amounts. The intermediates observed, and the timing of their appearance, are consistent with a sequential denitration pathway that has been reported for the microbial degradation of nitrate esters. The degradative activities of plant cells are only tenfold less than those reported for bacterial GTN degradation. These results suggests that plants may serve a direct degradative function for the phytoremediation of sites contaminated by organic nitrate esters.

Biodegradation, Environmental↗

Human peripheral mononuclear cell responses to UV damage are affected by radiation-induced changes in plasma.

To evaluate the effects of environmental or therapeutic stress adequately, it is important to study cells or tissues under conditions that simulate as closely as possible the in vivo environment. To determine whether the responses of irradiated cells are significantly affected by radiation-induced changes in plasma, human mononuclear cells were isolated from peripheral blood and cultured in their autologous plasma. Freshly isolated cells were irradiated in phosphate-buffered saline. The plasma was irradiated separately. Irradiation of the plasma suppressed mitogen-induced DNA synthesis in unirradiated cells. For cells that were UV-damaged and subsequently stimulated with mitogen, DNA synthesis was enhanced by irradiation of the plasma. Medium in which irradiated cells had previously been incubated enhanced DNA, synthesis in unirradiated cells that had been mitogen stimulated but did not affect the UV-induced shutoff of DNA synthesis in replicating cells or unscheduled DNA synthesis in irradiated cells.

Cell Division↗

Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir.

Coadministration with the human immunodeficiency virus (HIV) protease inhibitor ritonavir was investigated as a method for enhancing the levels of other peptidomimetic HIV protease inhibitors in plasma. In rat and human liver microsomes, ritonavir potently inhibited the cytochrome P450 (CYP)-mediated metabolism of saquinavir, indinavir, nelfinavir, and VX-478. The structural features of ritonavir responsible for CYP binding and inhibition were examined. Coadministration of other protease inhibitors with ritonavir in rats and dogs produced elevated and sustained plasma drug levels 8 to 12 h after a single dose. Drug exposure in rats was elevated by 8- to 46-fold. A > 50-fold enhancement of the concentrations of saquinavir in plasma was observed in humans following a single codose of ritonavir (600 mg) and saquinavir (200 mg). These results indicate that ritonavir can favorably alter the pharmacokinetic profiles of other protease inhibitors. Combination regimens of ritonavir and other protease inhibitors may thus play a role in the treatment of HIV infection. Because of potentially substantial drug level increases, however, such combinations require further investigation to establish safe regimens for clinical use.

Animals↗

Porcine S-antigen: cDNA sequence and expression in retina, ciliary epithelium and iris.

cDNA clones encoding S-antigen (arrestin) were isolated from the expression library constructed from porcine retina and sequenced. The 1490 base pair fragment contained a 1215 base pair open reading frame. From the nucleotide sequence, an amino acid sequence consisting of 405 residues was deduced and a molecular mass of 45,102 daltons was calculated. In order to determine whether the S-antigen mRNA transcript was expressed in anterior eye tissues, mRNA from ciliary non-pigmented epithelial cells and pigmented epithelial cells and iris was analysed by the reverse transcription polymerase chain reaction (PCR) using primers taken from sequences flanking the coding and non-coding regions of retinal S-antigen. Sequence analysis of the expected 611 base pairs in the 5' region and 672 base pairs in the 3' region of DNA fragments indicated that an identical mRNA for S-antigen was expressed in the anterior tissues examined. To investigate the in situ expression of S-antigen mRNA, 35S-labeled sense and antisense RNA probes were synthesized from the cDNA to label frozen sections of retina, ciliary body and iris and the treated sections were examined by autoradiography. The antisense probe labeled the layer between retinal pigmented epithelium and the outer nuclear layer of the retina, ciliary epithelium, and iris epithelium. From the results of sequencing PCR products and in situ hybridization, we concluded that, in porcine eye, the mRNA for S-antigen is expressed not only in the retina but also in the anterior tissues such as the ciliary epithelium and iris epithelium.

Animals↗

Biological denitration of propylene glycol dinitrate by Bacillus sp. ATCC 51912.

In previous studies, bacterial cultures were isolated that had the ability to degrade the nitrate ester glyceryl trinitrate (i.e., nitroglycerin). The goal of the present study was to examine the ability of resting cells and cell-free extracts of the isolate Bacillus sp. ATCC 51912 to degrade the more recalcitrant nitrate ester propylene glycol dinitrate (PGDN). It was observed that the PGDN-denitrating activity was expressed during growth even when cells were cultured in the absence of nitrate esters. This indicates that nitrate esters are not required for expression of denitration activity. Using cell-free extracts, PGDN was observed to be sequentially denitrated to propylene glycol mononitrate (PGMN) and propylene glycol with the second denitration step proceeding more slowly than the first. Also it was observed that dialysis of the cell-free extracts did not affect denitration activity indicating that regenerable cofactors [e.g., NAD(P)H or ATP] are not required for denitration.

Bacillus↗

Problems in differentiating sexually from nonsexually abused adolescent psychiatric inpatients by self-reported anxiety, depression, internalization, and externalization.

To ascertain whether self-reported psychopathology differentiated sexually and nonsexually abused adolescents, the Beck Depression Inventory, Beck Anxiety Inventory, and the Achenbach Youth Self-Report were administered to 111 psychiatric inpatients between 13 and 17 years of age who were diagnosed with various psychiatric disorders. Data about 14 background and clinical characteristics that were purported to be associated with sexual abuse were also collected. Forty (67%) of the 60 girls reported sexually abusive experiences, whereas six (12%) of the 51 boys reported such experiences. None of the scales were correlated with sexual abuse in either sex, and a history of physical abuse was the only characteristic that was significantly correlated with sexual abuse for both sexes. Furthermore, none of the scales was correlated with identity of sexual abuser, age of first abuse, age of last abuse, number of abuses, days of abuse, penile insertion, and the reporting of the abuse to the authorities in the sexually abused girls.

Adolescent↗

Zinc deficiency affects cell cycle and deoxythymidine kinase gene expression in HUT-78 cells.

Although zinc is known to be involved in cell proliferation and DNA synthesis, the mechanism by which zinc may regulate these processes is not understood. We have studied the role of zinc on cell proliferation and gene expression of a DNA synthesizing enzyme, deoxythymidine kinase (TK), in a T helper human malignant lymphoblastoid cell line (HUT-78). In zinc-deficient and zinc-sufficient media, the cell doubling time (mean +/- SD) of HUT-78 was 59 +/- 8 hours and 32.6 +/- 6 hours, respectively. The effect of zinc was T cell specific, inasmuch as the cell growth of another T malignant lymphoblastoid cell line, MOLT-3 (immature T cells), was not affected by zinc deficiency. Iron, copper, or manganese did not completely correct the cell growth of zinc-deficient HUT-78 cells. TK activity and the relative accumulation of TK-mRNA were significantly decreased in zinc-deficient cells during the G1 phase of cell cycle in comparison with zinc-sufficient cells. Nuclear run-on experiments and actinomycin-D studies showed that the transcription of TK-mRNA was affected adversely by zinc deficiency. Cell cycle studies showed that more zinc-deficient cells remained in S phase and did not undergo mitosis in comparison with zinc-sufficient cells. In conclusion, our data show that zinc is a T cell-specific growth factor and that a decreased gene expression of DNA-synthesizing enzyme TK in zinc-deficient HUT-78 cells in G1 phase affected adversely the DNA synthesis in S phase and delayed cell cycle.

Cell Cycle↗

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↗