Enhancement of antigen-presenting ability of B lymphoma cells by partial inhibition of protein synthesis through inducing B7-1 expression.

During the investigation of the role of protein synthesis in antigen-presenting cell (APC) function of A20-HL B lymphoma cells, we found that partial inhibition of protein synthesis enhanced their APC function. The treatment of A20-HL cells with 0.313-2.5 microM emetine, an irreversible inhibitor of protein synthesis, decreased protein synthesis by 60-70%, and enhanced their APC function to stimulate I-Ad/OVA323-339-specific T cells to produce interleukin-2 in response to ovalbumin (OVA). The emetine-treated and paraformaldehyde-fixed A20-HL cells required only 20 nM OVA323-339 peptide to stimulate the T cells, whereas those untreated and fixed required 200 nM peptide. This enhancement of APC function was mostly because of the induction of B7-1 expression on A20-HL cells by the emetine treatment, since B7-1 molecules were detected on the emetine-treated A20-HL cells, but only negligibly, if at all, on the untreated cells, and an anti-B7-1 monoclonal antibody, 1G10, inhibited the enhanced APC function of the emetine-treated A20-HL cells. The emetine-treatment also increased B7-1 mRNA expression in A20-HL cells, suggesting that the induction of B7-1 expression was due to the increase in the accumulation of mRNA and the translation with residual ability to synthesize protein. Thus, partial inhibition of protein synthesis in A20-HL cells increases B7-1 mRNA accumulation and its expression on the cell surface, which results in the enhancement of their APC function.     

Hypothyroidism and hyperprolactinemia as a possible cause of androgenetic alopecia in the female

31 female patients suffering from androgentic alopecia were examined by means of the TRH test with regard to hypothyroidism and hyperprolactinemia. Before, as well as 20 and 40 minutes after, application of thyroxine releasing hormone (TRH), the serum concentrations of the hypohyseal thyroxine stimulating hormone (TSH) and prolactin (PRL) were measured by radioimmunoassay (RIA). In 7 of the patients (23%), we found increased TSH levels after stimulation with TRH--indicative of hypothyroidism. In 9 of the patients (29%), we observed increased PRL levels after TRH stimulation, indicating prolactinemia. TSH and PRL can interact with androgen metabolism at various levels. Thyroxine may influence the unbound, metabolically active testosterone via the sex hormone binding globulin (SHBG). Prolactine, which is stimulated by TRH, promotes the suprarenal cortisol and androgen production. In 48% of the patients, we found either hypothyroidism or hyperprolactinemia. This suggests that both conditions may contribute to the clinical picture of female androgenetic alopecia, as they interfere with the androgen metabolism.     

National Alliance for Oral Health Consensus Conference on Medically Necessary Oral Health Care: Legal issues

This paper examines medical malpractice law as it applies to medically necessary oral health care. The basic legal concepts and reported cases involving medically necessary oral health care are reviewed. It is concluded that dental professionals and consumer advocates must advance their educational and legislative advocacy efforts so that health professional colleagues and the public will become aware of the importance of these services and insurers will routinely include coverage of medically necessary oral health care in their medical and dental policies. While failure to provide medically necessary oral health care can be violative of patient rights and legally actionable, medical malpractice litigation should always be the behavior modifier of last resort.     

A theory of family,economy, and gender

Historically, the requirements of population replacement have interacted with modes of subsistence technology to shape the differential distribution of power and prestige by sex. Two assumptions undergird Huber's argument: in all societies, producers have more power than consumers; those who control the distribution of valued goods beyond the family have the most power. Evidence comes from societies based on foraging, the hoe, the plow, herding, and industrial technologies. Huber concludes that changes in the work people do have altered the stratification and family systems of plow societies. Declines in mortality and fertility and changes in lactation customs have reduced the time that women spend pregnant or nursing. Increases in educational levels and employment rates enable women to provide sizable shares of family income. These trends have increased the centrality of individual goal attainment in the Western ideational system. Now women, along with men, have been swept into the occupational streams of the industrial revolution, though not quite into the mainstream. Still in question is the extent to which women will hold a fair share of top positions. This will hinge on responsibility for housework and childcare early in a woman's career, a time when most single parents or couples lack resources to command full-time quality care for the daily needs of their children. Ambitious women can avoid much conflict by remaining childless, but that is the point; ambitious men need not make that choice. Women cannot become men's social equals until the most talented women can aspire as realistically as their male counterparts to contribute in proportion to their talents. Thus, the overlap of family, economy, and gender, reshaped by continuing technological change, continues to affect women's status. Industrialization 1st turned the cost-benefit ratio of children upside down. Then wives were drawn into the labor force, raising the opportunity cost of their time, and thereby the cost of children. Now, below-replacement fertility in the West has highlighted the problem of population maintenance. Parenthood may have to be made more attractive by limiting the hours of responsibility. Such measures would be expensive but they would raise women's status in the family and in society in ways that were unimaginable a few decades ago.     

Studies of the mechanism of tolerance induced by short-term immunosuppression with cyclosporine in high-risk corneal allograft recipients. I. Analysis of CTL precursor frequencies

Transplantation of unmatched allogeneic corneas into highly vascularized recipient eyes under the cover of short-term immunosuppression with cyclosporine enables permanent engraftment. The aim of this study was to further elucidate the mechanism(s) underlying this tolerant state. In eight "high-risk" cornea recipients the clone sizes of donor-specific and third-party reactive cytotoxic T cell precursors were assessed by limiting dilution analyses before and at three and six months after transplantation. Acquired allograft tolerance in these patients was not accompanied by clonal reduction of donor-specific CTL-p, whereas in the case of an irreversible rejection the donor-specific CTL pool size was significantly enlarged. This donor-specific CTL-p increase could already be seen two months before clinical manifestation. These patterns differed from that of tolerant renal transplant patients, in whom marked and donor-specific reduction of CTL-p was observed. During rejection identical patterns with increasing donor-specific CTL-p frequencies were seen in both groups of patients. We conclude that induction of tolerance by short-term CsA to unmatched cornea grafts is not caused by clonal reduction of the effector precursor cell pool.     

Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains

Hereditary nephrotic syndrome is a heterogeneous disease, characterizedby heavy proteinuria and renal failure. Mutations of NPHS1 orNPHS2, the genes encoding for nephrin and podocin, lead to earlyonset of heavy proteinuria, and rapid progression to end-stagerenal disease, suggesting that both proteins are essential forthe integrity of the glomerular filter. Podocin is a stomatinprotein family member with a predicted hairpin-like structurelocalizing to the insertion site of the slit diaphragm of podocytes,the visceral glomerular epithelial cells of the kidney. Herewe investigate the pathomechanisms of different disease-causingpodocin mutations. We show that wild-type podocin is targetedto the plasma membrane, and forms homo-oligomers involving thecarboxy and amino terminal cytoplasmic domains. The associationof podocin with specialized lipid raft microdomains of the plasmamembrane was a prerequisite for recruitment of nephrin intorafts. In contrast, disease-causing mutations of podocin (R138Qand R138X) failed to recruit nephrin into rafts either becausethese mutants were retained in the endoplasmic reticulum (R138Q),or because they failed to associate with rafts (R138X) despitetheir presence in the plasma membrane. None of the mutants didaugment nephrin signaling, suggesting that lipid raft targetingfacilitates nephrin signaling. Our findings demonstrate thatthe failure of mutant podocin to recruit nephrin into lipidrafts may be essential for the pathogenesis of NPHS2. ^* To whom correspondence should be addressed. Tel: +49 7612703559;Fax: +49 7612706362; Email: benzing{at}med1.ukl.uni-freiburg.de