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Biomedical subjects

V Kumar

Publications and source records attributed to V Kumar.

At least 325 records · Page 18Linked to original sources
PubMed1996

Culturally appropriate measures for monitoring child development at family and community level: a WHO collaborative study.

Culturally appropriate techniques for monitoring child psychosocial development were prepared and tested in China, India and Thailand on a total of 28,139 children. This is the largest study of its kind ever undertaken. Representative groups aged between birth and 6 years were examined and the results were used to produce national development standards-separately for rural and urban children in China and India, and for all children combined in Thailand-which are considered to be more satisfactory than foreign-based standards. In each country, between 13 and 19 key milestones of psychosocial development were selected for a simplified developmental screening operation and these have been incorporated on a home-based record of a child's growth and development. Between 35 and 67 tests have been devised in each country to test the children at first-referral level.

Child↗
PubMed1996

Pancreatic sarcoidosis.

Sarcoidosis affects every organ in the body; the most frequently involved structures are the lung, lymph nodes, liver, spleen, eyes, joints and heart. Gastrointestinal system affliction is uncommon. The pancreas is rarely affected by sarcoidosis. A review of the literature revealed only 13 patients with biopsy proven granulomas in pancreas or peripancreatic nodes. In a review of all autopsies performed between 1950 and 1993 at Los Angeles County + University of Southern California School of Medicine, Los Angeles, USA, the authors found one patient with pancreatic and 5 with peripancreatic lymph node granuloma. The authors also describe three previously unreported cases of pancreatic sarcoidosis. From the discussion, a clinically useful and pragmatic profile of pancreatic sarcoidosis emerges. Two thirds of the patients with pancreatic sarcoidosis have abdominal pain, and three quarters of them have bilateral hilar adenopathy. The occurrence of abdominal pain in a woman with bilateral hilar adenopathy with or without pulmonary infiltration should lead one to think of pancreatic sarcoidosis. The diagnosis should be established by a tissue biopsy because the laboratory and radiographic techniques do not differentiate pancreatic sarcoidosis from other inflammatory and malignant disorders of the pancreas. The prognosis of pancreatic sarcoidosis is good.

Adult↗
PubMed1996

Median nerve somatosensory evoked potentials in rubber factory workers.

Somatosensory evoked potentials (SEPs) on median nerve stimulation were studied in 38 rubber factory workers to detect possible subclinical impairments in the somatosensory pathway as a result of exposure to rubber factory chemicals. Results showed trend towards the prolongation of latencies of all the major peaks of SEP such as P1, N1, P2, N2, P3, N3 in exposed workers besides changes in peak to peak amplitudes (higher P1-N1 and lower N2-P3). These changes may be attributed to synergistic action of solvents and other rubber factory chemicals on the generators of SEPs located higher up at the thalamo-cortical level.

Adolescent↗
PubMed1996

Brainstem auditory evoked potentials (BAEPs) in tobacco smokers.

Brainstem auditory evoked potentials (BAEPs) were studied in 10 chronic male tobacco smokes (average age 26.55 years) with history of smoking 3 to 14 years to detect early subclinical impairments in auditory pathway. The values of BAEPs were compared with those of 28 age matched normal male non-smokers (control). The results revealed significant prolongation of latencies of wave I and III indicating that conductivity of sensory impulse along acoustic nerve and pons is affected in chronic smokers which may be attributed to adverse effect on myelination by nicotine and toluene present in tobacco smoke.

Adult↗
PubMed1996

Melatonin: a master hormone and a candidate for universal panacea.

The molecule of melatonin seems to have been evolutionarily conserved. Its presence has been demonstrated in almost all groups of organisms, from plants, protozoa to people. During evolution, melatonin is claimed to have mediated dark adaptation. The universal presence of melatonin may be because it is lipophilic in nature which enables it to cross all biological (lipid membrane) barriers and to diffuse into every compartment of the cell, and because it serves as an antioxidant and is used as a free radical scavenger. In vertebrates, the pineal gland is the single largest source of melatonin production although, especially in non-mammalian vertebrates, other organs (e.g. retina, harderian gland etc.) may contribute significantly to the blood melatonin levels. In invertebrates, on the other hand, the pineal gland is absent and, therefore, melatonin secretion is clearly derived from another source(s). Regardless of the site of synthesis and the nature of organisms (diurnal, nocturnal or crepuscular), melatonin is secreted in the night and melatonin biosynthetic pathway remains essentially the same. Tryptophan, an amino acid derived from dietary sources, undergoes a series of enzymatic reactions to produce melatonin. The rhythm in melatonin secretion is generated endogenously by the circadian pacemaker(s) in the suprachiasmatic nuclei (SCN), and regulated by environmental light:dark cycle. Melatonin through its action on the SCN synchronizes disrupted or free-running circadian rhythms, and regulates a variety of daily and seasonal changes in the physiology and behaviour of animals. Emerging scientific evidence for the role of melatonin as therapeutic agent in the treatment of circadian rhythm-associated sleep disorders in persons having normal social working hours and shift workers, in jet lag, in immunological functions etc. have considerably increased interest in this hormone molecule. The role of melatonin in organisms physiology has now been widely recognized, and the wealth of information accumulated in the past two decades indicate it to be the best hormone candidate to be investigated for a universal panacea.

Animals↗
PubMed1995

Rapid rejection of H2k and H2k/b bone marrow cell grafts by CD8+ T cells and NK cells in irradiated mice.

Acute rejection of transplanted bone marrow cell (BMC) grafts can occur within 48 h in unsensitized, lethally irradiated mice, and NK cells have been implicated as the effector cells. Recently, we observed that both CD8+ TCR-alpha beta+ T and NK cells of irradiated mice could rapidly reject allogeneic lymph node cell grafts. In this study, we evaluated the ability of NK and CD8+ T cells to mediate rejection of H2k or H2k/b BMC grafts by pretreating groups of mice with depleting mAbs. H2k BMC were transplanted into syngeneic, B6 (H2b), BALB/c (H2d), NZB (H2d), and (NZB x B6)F1 (NZB6F1, H2d/b) hosts. Proliferation measured 5 days after cell transfer indicated that syngeneic, B6, and BALB/c hosts accepted H2k BMC grafts. However, CD8+ T cells from NZB and poly I:C-treated BALB/c hosts, and NK cells from poly I:C-treated NZB6F1, hosts, rejected H2k BMC grafts. In NZB6F1 hosts, there was an added effect of anti-TCR-alpha beta and anti-NK1.1 mAbs. It is possible that T and NK cells cooperate in rejecting H2k or H2k/b BMC grafts in certain hosts. Transplantation of H2k/b, but not H2k/d, BMC into similar recipients had the same fate as H2k BMC. Thus, certain CD8+ T cells may share a similar recognition system with NK cells.

Animals↗
PubMed1995

Major histocompatibility complex binding affinity of an antigenic determinant is crucial for the differential secretion of interleukin 4/5 or interferon gamma by T cells.

Differential activation of CD4+ T-cell precursors in vivo leads to the development of effectors with unique patterns of lymphokine secretion. To investigate whether the differential pattern of lymphokine secretion is influenced by factors associated with either the display and/or recognition of the ligand, we have used a set of ligands with various class II binding affinities but unchanged T-cell specificity. The ligand that exhibited approximately 10,000-fold higher binding to I-Au considerably increased the frequency of interferon gamma-producing but not interleukin (IL) 4- or IL-5-secreting cells in vivo. Using an established ligand-specific, CD4+ T-cell clone secreting only IL-4, we also demonstrated that stimulation with the highest affinity ligand resulted in interferon gamma production in vitro. In contrast, ligands that demonstrated relatively lower class II binding induced only IL-4 secretion. These data suggest that the major histocompatibility complex binding affinity of antigenic determinants, leading to differential interactions at the T cell-antigen-presenting cell interface, can be crucial for the differential development of cytokine patterns in T cells.

Amino Acid Sequence↗
PubMed1995

NK cell subsets in the regulation of murine hematopoiesis. I. 5E6+ NK cells promote hematopoietic growth in H-2d strain mice.

NK cells are able to reject bone marrow allografts in lethally irradiated mice. 5E6 is a marker expressed on a subset of NK cells that is responsible for the rejection of H-2d homozygous bone marrow cell (BMC) allografts. This suggests that the 5E6+ NK cell subset somehow recognizes and is deleterious for H-2d BMC. However, unlike Ly-49+ NK cells, 5E6+ cells are not deleted or even down-regulated in H-2d-homozygous mice. We wanted to determine, therefore, the role of the 5E6+ and 5E6- NK cell subsets in the normal physiologic regulation of hematopoiesis in H-2d strains of mice. Surprisingly, both in vivo depletion studies of normal mice and studies in which the subsets were purified and cultured with syngeneic BMC in vitro demonstrated that in H-2d mice, the 5E6+ subset of NK cells did not inhibit, but instead promoted, growth of H-2d BMC. Depletion of the 5E6+ subset also resulted in decreased marrow engraftment after syngeneic bone marrow transplantation in H-2d mice. Analysis of the cell culture supernatants of the purified subsets indicated that the functional effects of the subsets on hematopoiesis correlated with the relative amounts of hematopoietic growth-promoting cytokines produced by the NK cells. These results demonstrate that physiologically relevant subsets of NK cells exist that are involved in the homeostatic regulation of hematopoiesis and that they can be distinguished on the basis of 5E6 expression.

Animals↗
PubMed1995

Novel benzo[b]quinolizinium cations as uncompetitive N-methyl-D-aspartic acid (NMDA) antagonists: the relationship between log D and agonist independent (closed) NMDA channel block.

A series of permanently charged benzo[b]quinolizinium cations having lower lipophilicity than MK-801 or phencyclidine (PCP) were synthesized. Data relating agonist independent block of N-methyl-D-aspartic acid (NMDA) ion channels to log D are described. Closed channel access is predicted to result in a more noncompetitive profile of antagonism compared to selective open channel blockers, which are uncompetitive inhibitors. Reduced closed channel block may underlie the absence of PCP or MK-801-like behavioral side effects observed for benzo[b]-quinolizinium cations.

Animals↗
PubMed1995

Aminoalkylindoles: structure-activity relationships of novel cannabinoid mimetics.

Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands. In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of [3H]Win 55212-2 (5). Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists. The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (H) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position. A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist. Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids. The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors make sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid. Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).

Animals↗
PubMed1995

Cloning and functional characteristics of murine large granular lymphocyte-1: a member of the Ly-49 gene family (Ly-49G2)

Large granular lymphocyte (LGL) 1 is a cell surface glycoprotein expressed on a subset (50%) of C57BL/6 natural killer (NK) cells. Immunoprecipitation experiments reveal that the LGL-1 protein exists as a disulfide-linked 40-kD homodimer. Functional studies of LGL-1+ cells indicate that selected H-2d target cells are not lysed efficiently by these interleukin (IL)-2-cultured NK cells. These findings suggested that LGL-1 may be a member of the Ly-49 gene family. Here we report the molecular cloning of the LGL-1 cDNA from a severe combined immunodeficient-adherent lymphokine-activated killer cell library transfected into Cos-7 cells and find LGL-1 to be homologous to the Ly-49 gene at both the nucleotide (85%) and amino acid levels (73%). Sequencing of our LGL-1 cDNA has revealed it to be nearly identical to the Ly-49G2 cDNA recently isolated by cross-hybridization with an Ly-49 probe. LGL-1 represents a type II transmembrane protein of 267 amino acids with its carboxyl end exposed extracellularly. The LGL-1 protein contains 11 highly conserved cysteine residues and a 25-amino acid transmembrane region. Southern blot analysis demonstrates that there are a number of homologous genes in mouse DNA that hybridize strongly to LGL-1. Northern analyses using poly A+ RNA from LGL-1+ NK cells indicate that LGL-1 is expressed as a 1.4 kb mRNA. Two-color flow cytometry analysis (FCA) of C57BL/6 splenic NK cells demonstrates that LGL-1 and Ly-49 label overlapping subsets of cells. FCA identifies four subsets of NK cells as defined by LGL-1 versus Ly-49 staining. We have sorted these individual subsets, expanded them in IL-2, and performed cytotoxicity experiments to determine their target cell profiles in relation to class I expression. Results of these studies are complex, but indicate that Ly-49 may not be the only molecule that recognizes class I as an inhibitory signal for cytotoxicity. LGL-1+ cells also fail to lyse several H-2d-expressing tumor targets and concanavalin A lymphoblasts from BALB/c but not C57BL/6 mice. This inhibition of lysis by LGL-1+ NK cells is negated by addition of monoclonal antibody (mAb) 4D11 that recognizes the LGL-1 protein. When mAbs to the class I molecules H-2Dd and H-2Ld (alpha 1 alpha 2 domains only) are added to cytotoxicity assays, LGL-1+ cells lyse H-2d targets very effectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Cloning and characterization of 5E6(Ly-49C), a receptor molecule expressed on a subset of murine natural killer cells.

5E6 is a cell surface molecule expressed on a subpopulation of murine natural killer (NK) cells that are involved in the specific rejection of H-2d or H-2f (hemopoietic histocompatibility determinant 2) bone marrow cell grafts. Here, we isolated and cloned the gene encoding 5E6 and determined the nucleotide sequence of the cDNA. 5E6 is nearly identical to Ly-49C; the deduced amino acid sequence reveals a polypeptide of 266 amino acids with a molecular weight of 31,284 that contains multiple cysteine residues to explain its disulfide-linked homodimer structure and five potential N-linked glycosylation sites. 5E6 is a type II integral membrane protein with an extracellular carbohydrate recognition domain characteristic of C-type (Ca(2+)-dependent) animal lectins. Chromosomal mapping indicates that 5E6 is located within the NK gene complex on chromosome 6. The sequence of 5E6 mRNA and the degree of glycosylation of 5E6 protein are under genetic control. Immunoprecipitation before removal of N-linked sugars reveals different size molecules. There are several nucleotide differences among BALB/c, B6, and NZB mRNAs; however, none of them would be expected to affect N-glycosylation. Of particular interest are two findings: (a) BALB/c, B6, and (BALB/c x B6)F1 5E6 reduced molecules are approximately 65, 54, and 54 kD, and (b) the cDNA sequence of (BALB/c x B6)F1 is identical to B6. Thus, there appears to be allelic exclusion of 5E6 expression that may be related to the ability of F1 hybrid mice to reject parental H-2d bone marrow cell grafts.

Amino Acid Sequence↗