Specificity of a protective memory immune response against Mycobacterium tuberculosis.

We have investigated the memory T-cell immune response to Mycobacterium tuberculosis infection. C57BL/6J mice infected with M. tuberculosis were found to generate long-lived memory immunity which provided a heightened state of acquired resistance to a secondary infection. The T-cell response of memory immune mice was directed to all parts of the bacilli, i.e., both secreted and somatic proteins. Major parts of the memory T-cell repertoire were maintained in a highly responsive state by cross-reactive restimulation with antigens present in the normal microbiological environment of the animals. A resting non-cross-reactive part of the memory repertoire was restimulated early during a secondary infection to expand and produce large amounts of gamma interferon. The molecular target of these T cells was identified as a secreted mycobacterial protein with a molecular mass of 3 to 9 kDa.     

Proinflammatory activation of neutrophils and monocytes by Helicobacter pylori is not associated with cagA, vacA or picB genotypes

Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation induced by H. pylori strains with different virulence genotypes. Bacterial sonicates from 12 strains were used to induce phagocyte up-regulation of adherence molecule CD11b, assessed by fluorescence flow cytometry, and oxidative burst responses, assessed by chemiluminescence. A dose-dependent induction of the expression of CD11b was observed with sonicate from all H. pylori strains on both neutrophils and monocytes. Strains negative for cagA and picB genes had the same inducing activity of upregulation of CD11b as strains positive for these genes. A vacA-S2 type strain had the same activity as vacA-S1 type strains. The induction of toxic oxygen radicals by H. pylori-activated neutrophils gave higher median values for the cagA-positive strains than for the cagA-negative strains. For the monocyte chemiluminescence response, cagA-negative strains gave higher median values compared to cagA-positive strains. We conclude that upregulation of the neutrophil and monocyte adherence molecule CD11b induced by H. pylori sonicates is not associated with the presence of cagA, picB or mosaic pattern of vacA, and that cagA, picB-negative strains and vacA-S2 strains retain their inflammatory capacity.     

A comparison between LCM virus-specific secondary cytotoxic T lymphocytes generated by Con A and by the homologous antigen.

An investigation was made of the properties of cytotoxic T cells induced by Con A and exposure to LCM virus-infected cells. As a basis for such studies, the optimal conditions for in vitro Con A stimulation of in vivo LCM virus-primed C3H mouse splenocytes were determined. The most potent cytotoxicity was obtained when responder cells were cultured in the presence of Con A in a concentration of 2 micrograms/ml for 3 days, but strong cytotoxicity was also measured on days 2 and 4. When stimulation was performed by the homologous antigen maximal response was seen on day 4 although marked cytotoxicity was also noted on day 3. Effector cells produced by the two different procedures showed equally high degrees of cytotoxicity against LCM virus-infected target cells, whereas they did not appear cytotoxic against non-infected targets. If LCM virus-immune mice were treated intravenously with 280 micrograms of Con A per animal, moderate cytotoxicity was demonstrable in splenocytes from these mice 1, 2 and 3 days after treatment. The in vitro generation of secondary cytotoxicity by Con A as well as by the homologous antigen was found to be totally dependent on DNA synthesis. The reactivated cells were investigated for in vivo anti-viral effect by measuring their ability to protect intracerebrally LCM virus-infected mice from a fatal outcome of this infection. LCM virus-primed splenocytes stimulated by the homologous antigen caused complete protection, while Con A-reactivated cells did not protect at all. Secondary cytotoxic cells stimulated by Con A and by LCM virus showed fairly similar in vitro characteristics, but fundamentally different in vivo qualities.     

Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility

BACKGROUND: Male fertility largely depends on the quality of sperm production, which may be affected by environmental and genetic factors. In this study, we explored a possible role of the polymerase gamma (POLG) gene polymorphism, recently reported to be associated with male infertility in some populations. METHODS: The polymorphic CAG repeat (usually 10 codons long) in the POLG gene was studied in 1298 male subjects: 429 patients with infertility/subfertility, and 869 controls (495 men from the general population with unknown fertility and 374 recent fathers). In all subjects, the POLG polymorphism was assessed in relation to their semen quality, and--in the fertile controls--with biological fecundity measured as waiting time-to-pregnancy (TTP) for the couples. In the patients lacking the common POLG allele, the outcome of the assisted reproductive techniques (ART) for the couples was evaluated. RESULTS: The absence of one (10/ not equal to 10) or both common POLG alleles (not equal to 10/not equal to 10) was more frequent among the subfertile patients than among fertile controls (P=0.021 and P=0.04 respectively). The estimated predictive value for infertility in a man homozygous for the POLG polymorphism was 15.5% (95% CI: 4.8-51%). There was a positive association with sperm concentration: 14.3% of the normospermic subfertile patients were homozygous for the absence of the common POLG allele (not equal to 10/not equal to 10), in comparison with 2.3% of unselected controls (P=0.001) and 0.9% of the fertile men (P=0.0001). No association with sperm motility, morphology and TTP was found. Spermatozoa of the three not equal to 10/not equal to 10 patients treated with IVF retained the ability to penetrate the egg, but the fertilization rate was low. Nine homozygous not equal to 10/ not equal to 10 patients were treated with ICSI, resulting in pregnancy in seven couples. CONCLUSIONS: The POLG gene polymorphism should be considered as a possible contributing factor in patients with unexplained subfertility and normal spermiograms. The oocyte penetration ability of sperm may be partially impaired in the not equal to 10/not equal to 10 patients but most of them can be successfully treated with ICSI.     

Care of vaginal symptoms among HIV-infected women

OBJECTIVE: Gynecologic disease is common in HIV-infected women. We examine the sociodemographic, clinical, and provider factors associated with the care of women with vaginal symptoms. METHODS: Women enrolled in the HIV Cost and Services Utilization Study (HCSUS), a nationally representative probability sample of HIV-infected adults, were interviewed between January 1996 and April 1997. Women with vaginal symptoms who sought medical attention were asked, "Did your health care provider examine your vaginal area?" Women were also asked if they received medication for their symptoms. RESULTS: Among 154 women with vaginal symptoms, 127 sought care for their symptoms. Of those who sought care, 48% saw a gynecologist and 52% sought care from nongynecologists, most often their usual HIV care provider. Women who saw a gynecologist for their symptoms were more likely to have received a pelvic examination (92% versus 76%; p =.06) and vaginal fluid collection (98% versus 88%; p =.06) than those who saw their regular HIV provider. Fifteen percent of women received medication for their symptoms without having a pelvic examination; gynecologists were less likely to prescribe without an examination (8% versus 21%; p =.12). CONCLUSION: Gynecologists are more likely to provide adequate care of vaginal symptoms among HIV-infected women than nongynecologists who were HIV care providers. This specialty difference is consistent with quality of care studies for other medical conditions, but the potential gynecologic complications of inadequate evaluation and treatment warrants further investigation.     

Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection

Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.     

Severe acute respiratory syndrome--a new coronavirus from the Chinese dragon's lair

The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14-15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common to the members of the coronavirus family, a model for host cell-virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain of coronavirus are discussed.     

Argyrophilic cells in 202 human mucinous breast carcinomas. Relation to histopathologic and clinical factors

Two hundred two human, mucinous breast carcinomas were investigated for the presence of argyrophilic granules, and these granules were found in 25% of the cases. The granules were located in the cytoplasm and were heterogeneously distributed within the tumors. Tumors with granules were otherwise morphologically indistinguishable from those tumors without granules. The recurrence-free survival was independent of the presence of granules, and no relation was found to other clinical or histopathologic factors. Tumors with granules were found to be estrogen-receptor positive, and they appear to have a slightly less aggressive growth pattern than tumors without granules, but the difference is far from being statistically significant. It is concluded that there is no convincing evidence that this group of primary breast carcinomas with argyrophilia originates from APUD cells.