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Biomedical subjects

R Fotedar

Publications and source records attributed to R Fotedar.

44 records · Page 3Linked to original sources

Defective plasma membrane H(+)-ATPase or orthovanadate resistant mutants from Candida albicans, a pathogenic yeast.

Orthovanadate-resistant mutants of diploid yeast Candida albicans were isolated by using two step mutational process. Such mutants had altered plasma membrane H(+)-ATPase activity. Based on the levels of PM-ATPase activity, these mutants could be grouped into two categories; one group included those mutants which did not exhibit reduction in PM-ATPase activity while the other displayed a reduction of upto 40% in enzyme activity. These mutants exhibited a number of distinct phenotypic characteristics and altered abilities with regard to phenotypic divergence. Results demonstrate the importance of PM-ATPase in overall physiology of this pathogenic yeast.

Animals↗

Multistep pathway for replication-dependent nucleosome assembly.

We have used cell-free DNA replication to study the relationship between DNA replication and chromatin assembly. As others have reported, we find that DNA replication facilitates nucleosome assembly. We show here that replication-dependent nucleosome assembly occurs in at least two steps. The first step requires replicating DNA; the second step occurs after replication has been completed and is promoted by a nuclear extract. Consistent with this multistep model, we observe that the replicated simian virus 40 minichromosome is organized into a repeating array of DNA-protein particles that are structurally distinct from mature nucleosomes. These particles may be precursors in a pathway of nucleosome assembly since in the second, replication-independent step the nuclear extract converts this nascent chromatin into nucleosomes.

Burkitt Lymphoma↗

Cockroaches as vectors of pathogenic bacteria.

One hundred and thirty two cockroaches of species Blattella germanica--96 from hospital ward (test group) and 36 from residential areas (control group) were caught during Nov. 1985 to Nov. 1986. A variety of pathogenic and non-pathogenic bacteria were isolated from test and control group of insects. Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis, and Micrococci were isolated only from the test group of cockroaches. A high percentage (98.95 per cent) of test cockroaches were found to be carriers of various microorganisms as compared to the control group (80.55 per cent), the difference being statistically significant (p less than 0.001). Quantitative analysis in this study revealed that higher number of microorganisms are carried by test group of insects in the hospital environment. This, thereby suggests that these insects can play an important role in the etiology of hospital acquired infections.

Animals↗

The role of recombinant IL-2 and IL-1 in murine B cell differentiation.

This study was undertaken to compare and assess the relative contribution by IL-2 and IL-1 to the maturation into antibody-forming cells (AFC) of normal, mitogen-activated, proliferating B cells. Antigen affinity-enriched B cells were cultured under conditions at which T cells and macrophages are limiting. B cells were induced to proliferate upon stimulation with lipopolysaccharide (LPS), but not to mature into AFC. Maturation into AFC of LPS-stimulated B cells required the presence of recombinant interleukin-2 (IL-2). B cells stimulated with IL-2 alone were neither induced to proliferate nor to differentiate into AFC. Recombinant interleukin-1 (IL-1), in the presence of LPS, failed to induce the B cells to differentiate into AFC. However, IL-1 strongly synergized with IL-2 in further enhancing the AFC response. Although it has been known for some time that IL-2 and IL-1 contribute to the B cell response, our results indicate that these lymphokines primarily control the maturation of proliferating B cells into AFC.

Animals↗

Activation of cation transport by lymphokines in B cells without induction of DNA synthesis or immunoglobulin gene transcription.

We report on an experimental model that permitted us to evaluate the biologic relevance of membrane-associated biochemical events with respect to cell proliferation and maturation, each induced by distinct sets of signals. Antigen-affinity-enriched murine B cells cultured in the presence of a proliferative signal induced by LPS showed activation of Na+/K+ ATPase and enhanced the uptake of proline, followed by RNA, protein, and DNA synthesis, without the generation of antibody. Stimulation with both the proliferative signal(s) and the maturation signal(s) derived from lymphokines of an EL-4 thymoma induced B cells to proliferate and synthesize mRNA encoding mu-chain of IgM and to mature into IgM-secreting cells. Most important, the secretory product of EL-4, in the absence of LPS, activated Na+/K+ ATPase but failed to stimulate uptake of proline and synthesis of DNA or mu-specific mRNA. A similar response was observed in splenocytes depleted of T cells and in unfractionated spleen cells. Thus a component secreted by EL-4 can induce some of the early molecular events characteristic of the proliferative response but lacks the ability to initiate blast transformation and DNA synthesis.

Animals↗

How relevant are growth and maturation factors to the B lymphocyte response induced by LPS?

For the purpose of arriving at a unifying concept concerning the mechanisms in control of B lymphocyte responses, LPS or anti-lg receptor antibodies have conveniently served as substitutes for antigen. We report that the proliferative B cell responses in serum protein free medium to each of these polyclonal activators differ in the requirement for B cell growth factors (BCGF). Murine B lymphocytes which were prestimulated with anti-lg (Fab')2 antibody could readily be induced by semipurified BCGF (containing some IL2 activity) to incorporate thymidine. In contrast, B lymphocytes which were prestimulated with LPS failed to respond to BCGF, but could be restimulated by LPS. We have also shown that the dependence on B cell maturation factors of antigen affinity enriched B lymphocytes to develop into antibody forming cells (AFC) in response to LPS, depends on the antigen for which they were selected. B cells that have been affinity enriched with chicken red blood cells (CRBC) and stimulated by LPS to proliferate require maturation factors in order to generate a CRBC specific IgM response. In contrast, B cells that have been affinity enriched for TNP may be induced by LPS alone to generate TNP specific AFC independent of maturation factors. The results question the general validity of theoretical concepts concerning the role of lymphokines in B cell triggering, where such concepts are derived from experiments with LPS-activated B cells.

Animals↗

Cellular response to DNA damage. Link between p53 and DNA-PK.

Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to ionizing radiation and display an inability to repair double strand DNA breaks. DNA-PK is a member of a protein kinase family that includes ATR and ATM which have strong homology in their carboxy-terminal kinase domain with PL-3 kinase. ATM has been proposed to act upstream of p53 in cellular response to ionizing radiation. DNA-PK may similarly interact with p53 in cellular growth control and in mediation of the response to ionizing radiation.

Animals↗

Pancreatic islet transplantation: utility of ductular obstruction and exocrine atrophy model?

Introduction of 'silent' exocrine atrophy (and endocrine 'enrichment') in pancreatic grafts following ductular blockade may have a role in human diabetes by circumventing currently elusive islet isolation/purification protocols. To explore this potential, pancreatic isografts were performed in 12 pairs of inbred Wistar NIN rats. Donor pancreatectomy was performed after distal clamping and canulation of common bile duct and injection of 0.5 ml. polyacrylamide gel (blocked n = 7) or normal saline (un-blocked n = 5) respectively. One to 2 m.m. fragments of the resulting mildly distended pancreases were transplanted in to 2 sites (renal capsule and iliac fossa subcutaneously) of cach recipient. Post-operative biopsies of the transplanted grafts (unilateral nephrectomy and iliac fossa biopsies) revealed macroscopic and microscopic evidence of necrotizing pancreatitis in both the groups at both the sites (histiocytic and giant cell infiltration, fat necrosis and focal calcification with destruction of exocrine and endocrine cells) as early as 1 and 3 weeks. Possible detrimental factors include: volume and pressure of ductal injection, graft sites (confined spaces), post-operative wound infection and bio-compatibility of the material used for ductular blockade.

Acrylic Resins↗