Voltage Gated Calcium Channels Negatively Regulate Protective Immunity to Mycobacterium tuberculosis

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity

In vivo fluorescence imaging of the transport of charged chlorine6 conjugates in a rat orthotopic prostate tumour

Polymeric drug conjugates are used in cancer therapy and, varying their molecular size and charge, will affect their in vivo transport and extravasation in tumours. Partitioning between tumour vasculature and tumour tissue will be of particular significance in the case of photosensitizer conjugates used in photodynamic therapy, where this partitioning can lead to different therapeutic effects. Poly-l-lysine chlorine6 conjugates (derived from polymers of averageMr 5000 and 25 000) were prepared both in a cationic state and by poly-succinylation in an anionic state. A fluorescence scanning laser microscope was used to follow the pharmacokinetics of these conjugates in vivo in an orthotopic rat prostate cancer model obtained with MatLyLu cells. Fluorescence was excited with the 454–528 nm group of lines of an argon laser and a 570 nm long pass filter used to isolate the emission. Results showed that the conjugates initially bound to the walls of the vasculature, before extravasating into the tissue, and eventually increasing in fluorescence. The anionic conjugates produced tissue fluorescence faster than the cationic ones, and surprisingly, the largerMr conjugates produced tissue fluorescence faster than the smaller ones with the same charge. These results are consistent with differences in aggregation state between conjugates. © 1999 Cancer Research Campaig

Dutch guideline on total hip prosthesis

Contains fulltext : 97840.pdf (publisher's version ) (Open Access

Attitudes towards work and family roles and their implications for career growth of women: A report from India

This paper explored attitudes towards work and family roles of professional men and women in India. Ninety-two husband-wife pairs from salaried, upper middle class, dual-career families in India participated in the study. Propositions based on adult development theories of men and women, regarding reward value derived from and commitment made to occupational, parental, marital, and homemaker roles over the life cycle, were tested. Results indicated that there was no change with age, in attitudes towards occupational and homemaker roles. Instead, gender-based differences in attitudes towards these roles were observed. Attitudes towards the marital and parental role varied across the life cycle, although not in keeping with propositions based oil the adult development theories of men and women. There was no reversal in attitudes towards work and family roles of men and women after midlife. Rather, some reversal in attitudes appeared to occur between the marital and parental role, over the life span of both men and women. Results are reviewed within the Indian cultural context and their implications for the career development of women are discussed

Case Report - HLA Chimerism in allogenic haplo-identical peripheral blood stem cell transplant

HLA antigens were used as markers to establish the presence of chimerism (i.e. simultaneous presence of two lymphocyte populations from recipient as well as donor) in a patient with chronic granulomatous disease treated with one haplotype matched stem cell transplant. Neutrophil engraftment occurred on Day 6 post peripheral blood stem cell transplant (PBSCT). Platelet counts were maintained above 20x10[9]/L. Six months after the allogenic PBSCT, lymphocyte population was chimeric and cells of both donor (father) and host HLA type were present. The patient revealed a shift in his HLA antigen profile and there was evidence of donor cell engraftment. The HLA phenotype A26,CwXX,B8,DRB1*03//A32,Cw4,B35,DRB1*16// represented his true phenotype whereas A11,Cw7,B62,DRB1*14 represented donor (father) origin.. HLA system as a genetic marker is a useful additional approach to determine engraftment following an allogenic haplo-identical stem cell transplantation