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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 73 records · Page 4Linked to original sources
PubMed2000

Further observations and characterization of monoclonal antibodies reacting with B cell alloantigens associated with rheumatic fever and rheumatic heart disease.

Elevated levels of B lymphocytes with a unique surface alloantigen have been reported to be characteristic of patients with acute rheumatic fever or rheumatic heart disease. Mouse monoclonal antibodies (mAbs) to this alloantigen have been proposed as being useful in identifying individuals at risk for the development of these sequelae of group A streptococcal infection. However, previous studies have suggested that the discriminating ability of the mAbs was highest when the mAbs were made by using lymphocytes from the same ethnic population. To confirm and extend this observation, additional mouse mAbs were developed and their properties defined. These three mAbs-PG-12A, PG-13A, and PG-20A-reacted with B cells from more than 90% of North Indian patients with acute rheumatic fever or rheumatic heart disease. Each of these three new mAbs identified the highest levels of reactive B cells in patients with active acute rheumatic fever. Lower levels of positive reacting lymphocytes were found in individuals with quiescent chronic rheumatic heart disease, and markedly reduced percentages of reactive cells were observed in normal control subjects. The proportion of reactive lymphocytes in individual patients varied according to which of the three was tested, suggesting the possibility of a spectrum of "rheumatic" epitopes in susceptible individuals. The data further suggested that enhanced discriminatory ability for identifying "at-risk" susceptible patients could be obtained by testing with a combination of mAbs. If reduction in the incidence of acute rheumatic fever can be facilitated by early identification of susceptible individuals, accurate and sensitive detection of a marker antigen would result in more cost-effective public health measures. Additional population studies are required to more precisely define and confirm these detection techniques.

Adult↗
PubMed2000

Differential induction of tobacco MAP kinases by the defense signals nitric oxide, salicylic acid, ethylene, and jasmonic acid.

In tobacco, two mitogen-activated protein (MAP) kinases, designated salicylic acid (SA)-induced protein kinase (SIPK) and wounding-induced protein kinase (WIPK) are activated in a disease resistance-specific manner following pathogen infection or elicitor treatment. To investigate whether nitric oxide (NO), SA, ethylene, or jasmonic acid (JA) are involved in this phenomenon, the ability of these defense signals to activate these kinases was assessed. Both NO and SA activated SIPK; however, they did not activate WIPK. Additional analyses with transgenic NahG tobacco revealed that SA is required for the NO-mediated induction of SIPK. Neither JA nor ethylene activated SIPK or WIPK. Thus, SIPK may function downstream of SA in the NO signaling pathway for defense responses, while the signals responsible for resistance-associated WIPK activation have yet to be determined.

Cyclopentanes↗
PubMed2000

Allergic colitis presenting in the first day of life: report of three cases.

Allergic colitis can occur within hours of birth and should be considered in the differential diagnosis of any newborn in whom hematochezia develops. This diagnosis should be considered after excluding infectious and anatomic disorders common to this age group. The diagnosis is supported by the healthy appearance of affected infants and specific proctosigmoidoscopic and histopathologic findings. Infants with allergic colitis usually respond to withdrawal of the offending antigen, by the use of hydrolyzed cow's milk protein formula or more elemental formulas, or if the infant has been breast fed, by the strict removal of the offending antigen from the breast-feeding mother's diet.

Biopsy↗
PubMed2000

Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?

The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.

Abnormalities, Drug-Induced↗
PubMed2000

Antidotal efficacy of pyridinium oximes and cholineacetyltransferase inhibitors against organophosphorus intoxication in rodents.

In an attempt to develop effective antidote against organophosphorus intoxication, some new imidazole-pyridinium mono-oximes, long chain pyridinium mono-oximes and cholineacetyltransferase inhibitors were synthesised. These compounds were evaluated for their in vivo therapeutic protection and neuromuscular function studies in rodents. The results indicate that SPK-series oximes may be useful against sarin poisoning without any beneficial effect against VX (O-Ethyl S-2-NN-diisopropylaminoethyl methylphosphonofluoridate) intoxication. The cholineacetyltransferase (ChAT) inhibitors may not be of any help against any of the OP compounds studied in this study.

Animals↗
PubMed2000

Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease.

BACKGROUND: Platelets are an elective site for oxidative stress owing to their high content of polyunsaturated fatty acid. Increased lipid peroxidation and elevated platelet thiobarbituric acid-reacting substances (TBARS) signal oxidative stress. This possibly leads to retinal neovascularization in Eales' disease. METHODS: TBARS levels were estimated in consecutive cases of Eales' disease with neovascularisation (n = 26), Eales' disease without neovascularisation (n = 17) and healthy controls (n = 17). RESULTS: Platelet TBARS levels in the cases of Eales' disease with neovascularisation, Eales' disease without neovascularisation, and healthy controls were 0.66 +/- 0.1, 0.57 +/- 0.11 and 0.42 +/- 0.14 n moles TBARS formed/hour/10(8) platelets respectively. Student's t-test showed a significant increase in platelet TBARS levels in cases with neovascularisation as compared to cases without neovascularization (p < 0.05) and healthy controls (p < 0.01). CONCLUSION: The increase in platelet TBARS levels in proliferative Eales' disease is consistent with an emerging view that lipid peroxides may be associated with retinal neovascularisation.

Adolescent↗
PubMed2000

Management of diabetic retinopathy.

Diabetic retinopathy remains a major cause of blindness despite increased understanding of this disease and identification of successful treatments. The Diabetic Retinopathy Study identified risk factors associated with a high risk of blindness and confirmed the benefits of panretinal photocoagulation. The Early Treatment Diabetic Retinopathy Study defined the retinal characteristics, indications of treatment and results of laser treatment of clinically significant macular oedema. The Diabetic Retinopathy Vitrectomy study established the benefits and timing of vitrectomy for non-clearing vitreous haemorrhage and severe proliferative diabetic retinopathy. The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study have also demonstrated the value of tight control of blood sugar and blood pressure in diabetic retinopathy. These studies developed specific recommendations for the management of diabetic retinopathy. Optimum use of this information can minimize visual loss due to diabetic retinopathy.

Diabetic Retinopathy↗
PubMed2000

Effect of centrally administered nitric oxide modulators in Brewer's yeast-induced nociception in rats.

Possible modulation of Brewer's yeast-induced nociception by centrally (icv) administered nitric oxide (NO) modulators, viz., NO synthase (NOS) inhibitors, NO precursor, donors, scavengers and co-administration of NO donor (SIN-1) with NOS inhibitor (L-NAME) and NO scavenger (Hb) was investigated in rats. Administration of NOS inhibitors and NO scavenger Hb increased the pain threshold capacity significantly, whereas NO donors SIN-1, SNP and NO precursor L-arginine were found to be hyperalgesic. D-arginine, the inactive isomer of L-arginine and methylene blue, inhibitor of soluble guanylate cyclase failed to alter the nociceptive behaviour in rats. Co-administration of SIN-1 with L-NAME and Hb found to increase the nociceptive threshold. The results indicate, that centrally administered NO modulators alter the nociceptive transmission induced by Brewer's yeast in rats.

Animals↗
PubMed1999

Sustained suppression of plasma HIV RNA is associated with an increase in the production of mitogen-induced MIP-1alpha and MIP-1beta.

The chemokine receptor CCR5 has been shown to be a major coreceptor for HIV-1. The chemokines that bind to this receptor (MIP-1alpha, MIP-1beta, and RANTES) are potent inhibitors of HIV replication and may play an important role in the pathophysiology of HIV disease. We investigated the effect of potent antiretroviral therapy (ritonavir and saquinavir) on the production of MIP-1alpha, MIP-1beta, and RANTES in 19 HIV-infected patients who had sustained decreases in plasma HIV RNA levels (<200 copies/ml). Chemokine concentrations were measured in serum, plasma, and PHA-stimulated PBMCs at baseline and 24 and 48 weeks after initiating therapy. MIP-1alpha, MIP-1beta, and RANTES levels in serum and plasma did not significantly change in the 48-week period. In contrast, MIP-1alpha and MIP-1beta secreted by PHA-stimulated PBMCs increased at 24 weeks, with this increase sustained at 48 weeks, whereas no significant change was observed in PHA-induced RANTES production. A significant positive correlation was found between the changes in PHA-induced chemokine production and baseline CD4+ T cell counts. These data demonstrate that sustained suppression of viral replication by potent antiretroviral therapy has a potentially beneficial effect on chemokine production and early initiation of this therapy appears to confer a more favorable chemokine profile.

Anti-HIV Agents↗
PubMed1999

Isolation and characterisation of the cDNA encoding a glycosylated accessory protein of pea chloroplast DNA polymerase.

The cDNA encoding p43, a DNA binding protein from pea chloroplasts (ct) that binds to cognate DNA polymerase and stimulates the polymerase activity, has been cloned and characterised. The characteristic sequence motifs of hydroxyproline-rich glyco-proteins (HRGP) are present in the cDNA corres-ponding to the N-terminal domain of the mature p43. The protein was found to be highly O-arabinosylated. Chemically deglycosylated p43 (i.e. p29) retains its binding to both DNA and pea ct-DNA polymerase but fails to stimulate the DNA polymerase activity. The mature p43 is synthesised as a pre-p43 protein containing a 59 amino acid long transit peptide which undergoes stromal cleavage as evidenced from the post-translational in vitro import of the precursor protein into the isolated intact pea chloroplasts. Surprisingly, p43 is found only in pea chloroplasts. The unique features present in the cloned cDNA indicate that p43 is a novel member of the HRGP family of proteins. Besides p43, no other DNA-polymerase accessory protein with O-glycosylation has been reported yet.

Amino Acid Sequence↗
PubMed1999

Liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice.

Gene therapy transfer of angiostatin and endostatin represents an alternative method of delivering angiogenic polypeptide inhibitors. We examined whether liposomes complexed to plasmids encoding angiostatin or endostatin inhibited angiogenesis and the growth of MDA-MB-435 tumors implanted in the mammary fat pads of nude mice. We determined that plasmids expressing angiostatin (PCI-Angio) or endostatin (PCI-Endo) effectively reduced angiogenesis using an in vivo Matrigel assay. We then investigated the efficacy of these plasmids in reducing the size of tumors implanted in the mammary fat pad of nude mice. Both PCI-Angio and PCI-Endo significantly reduced tumor size when injected intratumorally (P < 0.05). Compared to the untreated control group, the mice treated with PCI-Angio and PCI-Endo exhibited a reduction in tumor size of 36% and 49%, respectively. In addition, we found that i.v. injections of liposomes complexed to PCI-Endo reduced tumor growth in the nude mice by nearly 40% when compared to either empty vector (PCI) or untreated controls (P < 0.05). These findings provide a basis for the further development of nonviral delivery of antiangiogenic genes.

Angiostatins↗
PubMed1999

Apoptosis in isolated adult cardiomyocytes exposed to adriamycin.

Adriamycin (doxorubicin) is a highly potent antineoplastic agent, but its use is limited by the risk of developing cardiomyopathy and congestive heart failure. Available evidence suggests that adriamycin-induced congestive heart failure is mediated by oxidative stress. We examined the possibility of adriamycin-induced apoptosis in isolated adult rat cardiomyocytes and its inhibition by trolox, a water-soluble antioxidant. Cardiomyocytes isolated from rat hearts were exposed to 20 microM adriamycin for 1 h and examined at different post-treatment durations (0-23 h). Adriamycin caused a significant decrease in rod-shaped cells and an increase in round cells. Both Hoechst 33258 staining and TUNEL assay revealed a significantly increased number of apoptotic myocytes and nucleosomal fragmentation upon exposure to adriamycin. In agarose gel electrophoresis, DNA laddering was found to be more intense in adriamycin-exposed myocytes. A bright smear at the leading edge of the gels suggested indiscriminate fragmentation of DNA and myocyte necrosis by adriamycin. Both types of DNA degradations due to adriamycin were significantly reduced by trolox. We suggest that adriamycin-induced cell death involves both apoptosis and necrosis and these may be mediated by oxidative stress.

Animals↗
PubMed1999

Regional differences in non-enzymatic antioxidants in the heart under control and oxidative stress conditions.

Antioxidants are known to play an important role in mitigating oxidative stress injury. Regional concentrations of non-enzymatic antioxidants, redox ratio and lipid peroxides were studied in normal, ischemic and ischemic-reperfused rat hearts. Isolated perfused rat hearts were made globally ischemic for 45 min and reperfused for 15 min. Right ventricular wall (RVW), septum (S) and left ventricular wall (LVW) from control, ischemic (I) and reperfused (I-R) hearts were analysed. Tocopherol, retinol and ascorbic acid concentrations in different regions of perfused control hearts were not different. Reduced glutathione (GSH) was significantly lower in the RVW, while S and LVW had about three-fold higher levels. Oxidized glutathione (GSSG) was lower in the RVW and most concentrated in the LVW. The GSH:GSSG ratio was highest in the septum while RVW and LVW had similar values. Lipid hydroperoxide (LPx) concentrations in the three regions of control hearts were not different from each other. In I and I-R hearts, vitamin E declined in all three regions but the loss was significant only in the septum in the I group and in the septum and LVW of the I-R group. Vitamin A showed significant loss in all three regions of the I-R group. Vitamin C declined significantly only in the RVW of the I-R group. GSH increased in the RVW of the I and I-R groups compared to controls. GSSG was increased in the RVW and septum of the I group and in all regions of the I-R group. The redox ratio, GSH:GSSG, decreased in all regions of both I and I-R groups. LPx were increased in the septum of the I group and in all regions of the I-R group. Despite unique regional differences in non-enzymatic antioxidants, a comparable increase in LPx in the I-R group and similar extent of reduction in the redox ratio in different regions of the I and I-R groups, suggest that each myocardial region may use different antioxidant mechanisms to withstand oxidative stress.

Animals↗
PubMed1999

Biochemical and immunological changes on oral glutamate feeding in male albino rats.

High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32 +/- 2 degrees C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

Administration, Oral↗
PubMed1999

Detection of EWS-FLI-1 fusion in Ewing's sarcoma/peripheral primitive neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed paraffin-embedded tissue.

The balanced translocation t(11;22)(q24;q12) is specific for the Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/PNETs) and results in the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription polymerase chain reaction (RT-PCR). Recent studies also have used fluorescence in situ hybridization (FISH) to show the translocation; however, most of these have been performed on cell lines or touch preparations and short-term cultures of tumors. Moreover, the existing probes generally have shown only the break in the specific chromosomes rather than the translocation itself. We describe our findings with a new set of probes that localize to 22q12 (EWS) and 11q24 (FLI-1) and directly show the translocation as juxtaposed red-green signals on der(22) in nuclei extracted from formalin-fixed, paraffm-embedded tissues. After establishing the specificity of the probes (on metaphase spreads and interphase nuclei in two translocation-positive cell lines and normal peripheral blood lymphocytes), we evaluated 11 ES/PNETs and 10 other tumors (four alveolar rhabdomyosarcomas, three neuroblastomas, two lymphomas, one extramedullary myeloid tumor) using a two-color FISH assay. All 11 ES/PNETs showed fusion signals in 20% to 80% of evaluable nuclei. In two lymphoma cases, random overlapping signals were present in 2% and 4% of nuclei, whereas the remaining eight tumors were negative. The presence of t(11;22) was confirmed by RT-PCR in 10 of 11 ES/PNETs. We conclude that FISH analysis with this newly designed probe pair is a specific and sensitive method of detecting t(11;22) on routinely processed tissue and can be useful in the differential diagnosis of ES/PNETs from other small round blue cell tumors when only fixed tissue is available.

Adolescent↗