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Biomedical subjects

M Kaur

Publications and source records attributed to M Kaur.

At least 37 records · Page 2Linked to original sources

I-cell disease (Mucolipidosis II).

I-cell disease (Mucolipidosis II) is one of the lysosomal storage diseases which presents in the neonatal period, and within six months will phenotypically resemble the severe forms of the group of disorders called the "mucopolysaccharidoses" but without mucopolysacchariduria. In Mucolipidosis II, fibrocytes exhibit "abnormal lysosomes". Activities of several lysosomal enzymes are low in fibroblast cultures but high in mucolipidosis II serum. We present a patient with I-cell disease diagnosed on the basis of clinical, radiological and biochemical features. The mother of this child was pregnant and the fetus was also found to be affected.

Child, Preschool↗

Acute lymphoblastic leukaemia with giant intracytoplasmic inclusions--a case report.

Acute Lymphoblastic Leukaemia (ALL) with intracytoplasmic inclusions is a rare and unusual subtype of acute leukaemia. Here we describe a case of ALL with intracytoplasmic inclusions in an adult female. These inclusions stained negative for Myeloperoxidase (MPO), Sudan Black E (SBB) and alpha-naphthyl acetate estarase (ANAE) and positive for Periodic Acid Schiff (PAS). This case is being presented for its unusual occurrence and to recognise the characteristics of this subtype of ALL to avoid a misdiagnosis of AML.

Adult↗

Receptor-Ck regulates the expression of cyclin-dependent kinase inhibitors (p16; p27).

The present study was addressed to understand the interrelationship between Receptor-Ck induction-activation coupling; isoprenoids (derived from mevalonate pathway) and cyclin-dependent kinase inhibitors. The results reported here unambiguously reveal that isoprenoids regulate the expression of genes coding for CDK inhibited p16 and p27. Further, Receptor-Ck dependent signalling, known to control the mevalonate pathway, had a direct effect upon the p27 gene expression. Based upon these studies coupled with our earlier findings we propose that Receptor-Ck has an important role in the regulation of cell cycle machinery.

Cell Cycle↗

Dynamics of contraceptive use in a rural community of Haryana.

A cross-sectional survey was carried out to study the dynamics of contraceptive use in three villages of Raipur Rani block in district Panchkula, Haryana. A female social worker interviewed 600 ever-married women aged 15-44 years using a semi-structured interview schedule. More than 75% of the respondents were aware about modern contraceptives. Fifty-nine percent of the couples had used contraceptives. Among the 351 ever-users, the first contraceptive method used was sterilization in 41.3%, condom in 35.6%, IUD in 17.9%, and oral pills in 5.1%. Subsequently, many of them either discontinued or shifted to other methods. At the time of survey, 236 (39.3%) were using a contraceptive. Most of the current users (225) had opted for tubectomy, and only a few (4) had accepted vasectomy. Supplies of contraceptives were obtained mainly from government hospitals and sub-health centres. Common reasons for discontinuation were perceived untoward effects (37.1%), desire for more children (32.6%), and failure of the contraceptive method (19.0%). Most of the respondents obtained contraceptives from Government health posts. Counselling and follow-up services should should be strengthened so that contraceptives are used regularly and effectively for longer periods.

Adolescent↗

Diagnostic accuracy of rapid enzyme linked immunosorbent assay for the diagnosis of human hydatidosis.

Rapid enzyme linked immunosorbent assay (ELISA) was compared with the standard ELISA and indirect haemagglutination (IHA) techniques for the diagnosis of human hydatidosis. Eighty nine serum samples including 17 from hydatidosis patients (10 surgically confirmed and 7 clinically suspected), 50 from patients with other parasitic diseases and 22 samples from normal healthy individuals were analysed for anti-hydatid IgG antibodies using sheep hydatid cyst fluid antigen. The sensitivity and specificity respectively was found to be 82.3 and 100 per cent by rapid ELISA; 88.23 and 90.27 per cent by standard ELISA and 70.58 and 100 per cent by IHA technique. No cross reactions were observed with rapid ELISA technique using samples from cysticercosis and amoebiasis patients and normal healthy controls. The present study indicates that rapid ELISA can easily be performed in place of the standard ELISA for the serodiagnosis of human hydatidosis with the advantage of minimising reporting time and manpower hours.

Antibodies, Helminth↗

Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine.

To enhance the efficacy of DNA malaria vaccines, we evaluated the effect on protection of immunizing with various combinations of DNA, recombinant vaccinia virus, and a synthetic peptide. Immunization of BALB/c mice with a plasmid expressing Plasmodium yoelii (Py) circumsporozoite protein (CSP) induces H-2Kd-restricted CD8+ cytotoxic T lymphocyte (CTL) responses and CD8+ T cell- and interferon (IFN)-gamma-dependent protection of mice against challenge with Py sporozoites. Immunization with a multiple antigenic peptide, including the only reported H-2Kd-restricted CD8+ T cell epitope on the PyCSP (PyCSP CTL multiple antigenic peptide) and immunization with recombinant vaccinia expressing the PyCSP induced CTL but only modest to minimal protection. Mice were immunized with PyCSP DNA, PyCSP CTL multiple antigenic peptide, or recombinant vaccinia expressing PyCSP, were boosted 9 wk later with the same immunogen or one of the others, and were challenged. Only mice immunized with DNA and boosted with vaccinia PyCSP (D-V) (11/16: 69%) or DNA (D-D) (7/16: 44%) had greater protection (P < 0. 0007) than controls. D-V mice had significantly higher individual levels of antibodies and class I-restricted CTL activity than did D-D mice; IFN-gamma production by ELIspot also was higher in D-V than in D-D mice. In a second experiment, three different groups of D-V mice each had higher levels of protection than did D-D mice, and IFN-gamma production was significantly greater in D-V than in D-D mice. The observation that priming with PyCSP DNA and boosting with vaccinia-PyCSP is more immunogenic and protective than immunizing with PyCSP DNA alone supports consideration of a similar sequential immunization approach in humans.

Animals↗

Receptor-Ck controls the expression of Bcl-2 and cyclin d genes.

By making use of receptor-Ck positive lymphocytes (from normal human subjects) as well as receptor-Ck negative lymphocytes (from untreated chronic myeloid leukemic (CML) patients) as cellular models, we were able to show that receptor-Ck-dependent signalling is involved in the regulation of genes coding for Bcl-2 and cyclin D. Further, experiments directed to resolve the mechanism by which this receptor regulates these genes revealed that receptor-Ck, upon activation by cholesterol, initiates the cleavage of a 125 kDa cytoplasmic protein leading to the generation of a 47 kDa factor having specific affinity for genomic sterol regulatory element (SRE)/SRE-like sequence present in the promoter region of genes coding for Bcl-2 and cyclin D. Based upon these observations, we propose that the inability of leukemic cells to express receptor-Ck is responsible for the deregulated over-expression of genes coding for Bcl-2 and cyclin D and this phenomenon may be of importance in understanding leukemic haematopoiesis.

Base Sequence↗

Ethanol effects on lipid peroxidation and glutathione-mediated defense in rat small intestine: role of dietary fats.

The effect of ethanol feeding for 5 weeks on lipid peroxidation status of small intestine was studied in rats maintained on either a rat pellet (RP) or a semisynthetic diet containing coconut oil (CCO), corn oil (CO), or fish oil (FO). Highest rate of iron/ascorbate-induced lipid peroxidation was observed in intestinal mucosa of FO-fed rats, which was further elevated (p < 0.05) upon ethanol administration. Purified brush borders from all the ethanol-treated dietary groups were more susceptible to iron-induced lipid peroxidation. Level of nonprotein thiols was increased by ethanol feeding to rats given CO or FO. FO-fed rats exhibited increased activities of glutathione reductase (GR), glutathione-S-transferase (GST), and catalase (Cat). Glutathione peroxidase (GPx) was the lowest in the CCO group. Ethanol-treated FO group exhibited increased GST and GPx activities compared to controls, whereas in rats fed the RP or CO diet, ethanol feeding significantly decreased GST activity. GR and Cat activities were not affected under these conditions. Thus, ethanol exposes the small intestinal mucosa to oxidative stress. The effects were more pronounced in rats fed n-3 fatty acid-rich (FO) diet. The corresponding rise in GPx and GST levels may reflect the adaptive changes in intestine.

Animals↗

Human platelets contain a novel 47 kDa thiol-oxidase having affinity for genomic sterol-regulatory sequence.

The present study provides evidence to support that human platelets possess a 47 kDa dual functional molecule having thiol-oxidase activity as well as high affinity for the SRE sequence in the human genome. On the basis of these as well as earlier results, we propose that Receptor 'Ck' dependent regulation of this dual functional 47 kDa molecule may provide a mechanism for the maintenance of cellular cholesterol homeostasis. Further, this mechanism may also explain the molecular basis of cholesterol-feedback lesion observed under premalignant conditions.

Blood Platelets↗

Receptor-Ck-dependent regulation of genes involved in the cell cycle.

The present study was addressed to understand the interrelationship between Receptor-Ck activation, mevalonate pathway and primary response genes such as c-fos, c-myc and cyclin 'D' involved in the cell cycle. The results reported here unambiguously revealed that the phosphatidic acid (generated through the activation of Receptor-Ck by cholesterol) regulates mevalonate pathway, DNA synthesis as well as expression of genes coding for c-fos, c-myc and cyclin 'D'. By using the specific blockers of ras farnesylation as well as phospholipase D, it became apparent that phosphatidic acid regulates two processes: (a) activation of Gap-ras pathway leading to the expression of c-fos, c-myc proto-oncogenes probably through the activation of NF1 transcription factor; (b) cleavage of 125 kDa endoplasmic reticulum protein leading to the generation of 47 kDa protein factor which not only regulates mevalonate pathway but also has an ability to heterodimerize with Receptor-Ck protein and this heterodimer may be responsible for the regulation of cyclin 'D' expression probably by binding to the SRE like sequence present in the promoter region of this gene. On the basis of these findings, we propose a pathway through which Receptor-Ck upon endocytosis regulate these primary response genes (c-fos, c-myc, cyclin 'D') involved in the cell cycle.

Butanols↗

Simultaneous induction of multiple antigen-specific cytotoxic T lymphocytes in nonhuman primates by immunization with a mixture of four Plasmodium falciparum DNA plasmids.

CD8(+) T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8(+) T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8(+) T-cell responses against multiple P. falciparum proteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding four P. falciparum proteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8(+) T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8(+) T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans.

Amino Acid Sequence↗

LDL-dependent regulation of Bcl-2 and cyclin 'D' gene expression in lymphocytes from normal and CML patients.

Effect of low-density lipoprotein (LDL) on the expression of Bcl-2 as well as cyclin 'D' genes was studied in Receptor 'Ck' (+ve) and Receptor 'Ck'(-ve) human lymphocytes. LDL had no effect upon the elevated levels of Bcl-2 and cyclin 'D' gene products in Receptor 'Ck' (-ve) lymphocytes (from untreated CML patients), whereas in Receptor 'Ck' (+ve) lymphocytes (from normal subjects), the exposure to LDL regulated the level of cyclin 'D' gene product without initiating the expression of bcl-2 gene product. However, blockage of Receptor 'Ck' in normal lymphocytes, through its specific antibody (Ab-RCk) in presence or absence of LDL, resulted in the induction of both cyclin 'D' (at 4 h interval) and bcl-2 (at 12 h interval) gene products. Based upon these results, we propose that Receptor 'Ck' deficiency in cells may inherit defective apoptosis and capacity proliferation leading to leukemic transformation.

Cyclin D↗

Factors influencing psychosocial development of preschool children in a rural area of Haryana, India.

In a cross-sectional survey, 3746 children aged less than 6 years residing in 47 randomly selected villages of district Ambala (India), were studied to find out the environmental risk factors influencing psychosocial development. A culture appropriate test battery comprising 67 test items was administered, and psychosocial development score of each child was computed by scoring each test item passed as 1 and failed as 0. At each age level children having score in lower quartile were categorised as having slow psychosocial development and those in upper quartile were labelled as having accelerated development. Logistic regression revealed that per capita income, education of mother, nutritional status of the child, number of rooms and environmental hygiene in the house, presence of a high school within easy travel distance, availability of a caretaker when mother is busy, child attending a nursery (anganwadi), households having access to newspaper, child having toys or toy substitutes, TV, books, story telling by the mother were found to have a significant association with psychosocial development of preschool children. The risk factors identified in this survey can be used for screening families at risk in rural communities and for selection of interventions for promotion of psychosocial development of children.

Analysis of Variance↗

Development of two monoclonal antibodies against Plasmodium falciparum sporozoite surface protein 2 and mapping of B-cell epitopes.

The Plasmodium yoelii sporozoite surface protein 2 (PySSP2) is the target of protective cellular immunity. Cytotoxic T cells specific for the Plasmodium falciparum analog PfSSP2, also known as thrombospondin-related anonymous protein (TRAP), are induced in human volunteers immunized with irradiated sporozoites. PfSSP2 is an important candidate antigen for a multicomponent malaria vaccine. We generated and characterized three monoclonal antibodies (MAbs) specific for PfSSP2/TRAP. The MAbs PfSSP2.1 (immunoglobulin G1 [IgG1]), PfSSP2.2 (IgG2a), and PfSSP2.3 (IgM) were species specific and identified three distinct B-cell epitopes containing sequences DRYI, CHPSDGKC, and TRPHGR, respectively. PfSSP2.1 partially inhibited P. falciparum liver-stage parasite development in human hepatocyte cultures (42 and 86% in two experiments at 100 microg/ml). Mice immunized with vaccinia virus expressing full-length PfSSP2 protein produced antibodies to (DRYIPYSP)3, and humans living in malaria-endemic areas (Indonesia and Kenya), who have lifelong exposure and partial clinical immunity to malaria, had antibodies to both (DRYIPYSP)3 and (CHPSDGKCN)2. Mice immunized with multiple antigen peptides MAP4 (DRYIPYSP)3P2P30 and MAP4 (CHPSDGKCN)3P2P30 in TiterMax developed antibodies to sporozoites that partially inhibited sporozoite invasion of human hepatoma cells (39 to 71% at a serum dilution of 1:50 in three different experiments). The modest inhibitory activities of the MAbs and the polyclonal antibodies to PfSSP2/TRAP epitopes do not suggest that a single-component vaccine designed to induce antibodies against PfSSP2/TRAP will be protective. Nonetheless, the MAbs directed against PfSSP2, and the peptides recognized by these MAbs, will be essential reagents in the development of PfSSP2/TRAP as a component of a multivalent P. falciparum human malaria vaccine.

Amino Acid Sequence↗