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.     

Plaque-forming cell capability in the senescent

The number of plaque-forming cells (PFC) developed in pokeweed mitogen (PWM)-activated unfractionated or T/B separated, 4:1 reconstituted cultures of peripheral blood lymphocytes (PBL) with well-characterized subpopulations obtained from healthy, aged subjects was compared to that of young blood donors. The absolute number of PBL in the aged was reduced by 36%, and the percentage of sheep erythrocyte-rosette-forming cells (E-RFC) by 27%, compared to the percentage obtained in young donors. The IgM-, IgG- and IgA-immunoglobulin (Ig) secretion was monitored with a protein A PFC assay. The number of PFC in PBL cultures of the aged was 58% of the number found in cultures of the young controls. The number of PFC generated in cultures of autologous irradiated T and untreated B cells showed a 104% increase in the aged whereas a 63% increase was obtained using cells from young individuals. Co-cultures of young B cells with untreated or irradiated young or aged T cells showed a significant rise in the PFC response in cultures with irradiated aged T cells, while an equal number of PFC was generated in cultures of young B cells with young or aged untreated T cells. Our results demonstrate a decreased number of PBL, especially T cells, an impaired B cell function and a pronounced enhancement of the PFC response in cultures of irradiated aged T cells and young or aged B cells, whereas the T helper function of untreated cells was found to be normal. The influence of monocytes on the PFC response did not differ in the two groups.     

Quantitative assessment of psychologic state of patients with anorexia nervosa or bulimia: response to caloric stimulus

Hospitalized patients with anorexia nervosa (N = 17) or bulimia (N = 11) were given a standard liquid meal containing 400 calories. Using analogue scales, bulimic patients were found to have greater anxiety, lower mood, lower sexual arousal, and more fear of fatness than either control or anorectic patients. This finding of increased general "dysphoria" in bulimic patients persisted after the meal without any significant premeal to postmeal changes. Anorectic patients also differed from controls, but less than the bulimic patients. Some measures of anxiety correlated significantly with body mass index before the meal in bulimic patients, whereas in anorectic patients the correlation was significant only after the meal.     

Doctors'' characteristics do not predict long-term glycaemic control in type 2 diabetic patients.

Glycaemic control in type 2 diabetic patients varies widely between general practitioners (GPs). To increase our understanding of this variation, linear random effects models were used to examine the predictive value of GP characteristics on the course of annual HbA1c measurements, in 688 newly diagnosed type 2 diabetic patients between one and five years after diabetes diagnosis. We found that characteristics of centrally supported GPs, such as interest in diabetes, experience, practice type, list size, and weekly working hours, did not predict their patients' glycaemic control.     

Effect of sodium ions on penicillin-induced epileptiform activity in vitro

Summary Intra- and extracellular recordings were obtained from the CA1 region of guinea pig hippocampal slices maintained in vitro. We studied the effect of reducing the extracellular sodium concentration on penicillin-induced epileptiform responses.In control experiments, Tris and choline were assayed as sodium substitutes. Choline was found unsuitable, since it induced repetitive firing in the absence of any convulsant agent. Replacement of 50% of the extracellular sodium ([Na⁺]_o) with Tris reduced the amplitude of the presynaptic fiber volley, the field EPSP, and the population spike. Intracellular studies showed that when [Na⁺]_o was lowered, action-potential amplitudes were reversibly depressed by an amount close to that predicted by the Nernst relation.Orthodromically elicited epileptiform discharges, induced by penicillin, were reduced in a low-sodium medium when constant stimulus currents were employed. If orthodromic stimulus strengths in normal and low-sodium states were equated on the basis of the field-EPSP amplitude, no significant diminution of the depolarizing-wave component of the epileptiform response was observed. These results suggest that a synaptic component underlies penicillin-induced epileptiform discharges.Supported by grants from the Norwegian Research Council for Science and the Humanities and by NIH grants NS 11535 and NS 15772