Cell-mediated immune response in mice treated with steroidal contraceptives.

The splenomegaly assay (Simonsen, 1962) was standardized using different strains of rats and mice. Male Wistar rat (donor)-female Swiss mouse (host) was found to be the suitable combination that could be employed in subsequent experiments to study the potential of contraceptive steroids to alter CMIR. The index of splenomegaly appeared to increase in case of mice treated with combination oral contraceptives (Ovulen, Ovral or Enovid). The differences observed, however, neared significance only in the case of Ovral (0-05 less than P less than 0-1). Neither chlormadinone acetate nor megestrol acetate significantly altered the index of splenomegaly.     

Growing problem of methicillin resistant staphylococci--Indian scenario

In the present study MRSA prevalence increased from 12% in 1992 to 80.83% in 1999. Indian literature shows that MRSA incidence was as low as 6.9% in 1988 and reached to 24% and 32.6% in Vellore and Lucknow in 1994 and was of the same order in Mumbai, Delhi and Bangalore in 1996 and in Rohtak and Mangalore in 1999. However, in some of the centres it was as high as 87%. All the MRSA isolates in India including in the present study were sensitive to vancomycin and resistance to netilmycin appears to be low among MRSA isolates in India. All the MRSA isolates were also found to be sensitive to teicoplanin in the present study. Like in other Indian studies, resistance to cotrimoxazole, erythromycin, gentamicin, other penicillins and cephalosporins appeared to be a common feature for MRSA isolates in the present study.     

CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice

Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.     

Conceptual and methodologic challenges of assessing the short-term efficacy of Guggulu in obesity: data emergent from a naturalistic clinical trial

An open comparative trial was conducted in 58 adult obese patients (Body Mass Index > or = 25 kg/square metre). Group I (n = 27), non-drug, was advised diet (1200-1600 cals) and a brisk walk for 30 minutes. Group II, in addition, received Guggulu (Medohar) 1.5-3 gms/day for 30 days. Mean difference in weight loss between Guggulu and non-drug group was 0.32 kg (ns) on day 15 and 0.58 kg on day 30 (ns). The mean weight reduction in patients (> 90 kgs) was 1.92 kg (ns) and 2.25 kg (ns) higher in Guggulu group. All patients weighing > 90 kg lost weight in Guggulu group whilst 3 in non-drug group did not lose weight. Guggulu was tolerated well. The data from this pilot study suggest a synergistic diet-Guggulu interaction over 30 days in patients weighing > 90 kgs which needs to be confirmed in a large placebo controlled study.     

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.     

Fatal renal failure as the first manifestation of sarcoidosis diagnosed on necropsy in a young man: a case report

Renal involvement as the first manifestation of sarcoidosis is rare and has never been reported in India. This report describes a 35 year old man who was admitted to the emergency department with a clinical diagnosis of acute on chronic renal failure, secondary to obstructive uropathy. Postmortem examination unexpectedly revealed disseminated sarcoidosis.     

Analysis of immune responses against T- and B-cell epitopes from Plasmodium falciparum liver-stage antigen 1 in rodent malaria models and malaria-exposed human subjects in India

Liver-stage antigen 1 (LSA-1) is a potential vaccine candidate against preerythrocytic stages of malaria. We report here the immunogenicity of linear synthetic constructs delineated as T(H)-cell determinants from the nonrepeat regions of Plasmodium falciparum LSA-1 in murine models and human subjects from areas where malaria is endemic in Rajasthan State, India. Seven peptide constructs (LS1.1 to LS1.7) corresponding to predicted T-cell sites from both the N- and C-terminal regions and peptide LS1R from a repeat region of PfLSA-1 were synthesized to analyze the cellular immune responses. These linear peptides were also tested for humoral responses in order to determine if there were any overlapping B-cell epitopes in the predicted T-cell sites. Most peptides induced cellular responses in peptide-immunized BALB/c and C57BL/6 mice as measured by proliferation and cytokine analysis. Cross-reactive T-cell recognition of P. falciparum-based peptides in Plasmodium berghei-immune animals was evaluated, but only one peptide, LS1.2 (amino acids 1742 to 1760) triggered T-cell proliferation and interleukin-2 and gamma interferon secretion in P. berghei-immune splenocytes of BALB/c and C57BL/6 mice as well as in Thamnomys gazellae (natural host of P. berghei ANKA). In an enzyme-linked immunosorbent assay with the peptides, only one peptide, LS1.1, was recognized by anti-P. berghei liver-stage serum. Three peptides (LS1. 1, LS1.2, and LS1.3) of the eight peptides tested in this study were recognized by a relatively large percentage of P. falciparum-exposed human subjects; the reactivities ranged from approximately 45% for LS1.3 to approximately 60% for LS1.1 and LS1.2. Interestingly, all of the eight putative T-cell determinants were also recognized by the sera collected from malaria patients, although the response was variable in nature. These T(H)- and B-cell epitopes may be of potential value for preerythrocytic antigen-based malaria subunit vaccine formulations.     

Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis

Summary: Recent work from several laboratories has shown that, in contrast to the widely held notion that one autoimmune disease is caused by one or a few related autoantigenic determinants, autoimmunity is fundamentally a continuously evolving process. The autoimmune responses shift, drift and diversify with time not only to other determinants in the original antigen but also to other antigens. We have described a form of determinant spreading - reciprocal T-B determinant spreading–where the induction of first T cells by peptides from an autoantibody molecule could lead to help provided to a variety of B cells displaying a cross-reactive version of the original determinant. The response spreads in this way by reciprocal T-B stimulation until large cohorts of T and B cells have expanded. Such spontaneous expansion must be important in clinical disease, since tolerance induction to a limited set of T-cell determinant peptides derived from an anti-DNA antibody VH region delayed the appearance of IgG anti-dsDNA antibodies and onset of lupus nephritis in the NZB/NZW Fl mouse model of systemic lupus erythematosus. Understanding the diversification patterns in autoimmune responses has enormous implications in developing peptide-targeted therapies.