T cell immunodeficiency in dyskeratosis congenita.

Dyskeratosis congenita has been found to be associated with abnormal immune function. In this study we report a patient with this association. He developed Pneumocystis carinii interstitial pneumonia, and impaired cell mediated immunity was confirmed by the presence of depressed lymphoproliferative responses to in vitro stimulation with mitogen. Enumeration of T cell subsets showed a severely depressed CD4:CD8 ratio (0.38), which is the likely cause for impaired cell mediated immunity. The T cell activation pathway appeared intact, as his T lymphocytes were able to express activation markers (CD25 and HLA-DR) after mitogen stimulation.     

Influence of finishing time on marginal sealing ability of new generation composite bonding systems

Although variation in finishing techniques has been shown to affect microleakage, little research has been published on the influence of finishing time on the marginal sealing ability of new generation composite bonding systems. The objective of the present study was to evaluate the influence of finishing time on the enamel and dentine marginal sealing ability of four new generation composite systems. Two class V preparations, which were solely in enamel or dentine, were made on the buccal surfaces of 96 freshly extracted molar teeth. The teeth were randomly divided into four groups of 24 and restored with composite resin (Silux Plus^®) utilizing the following bonding systems: Scotchbond Multi-purpose^®, Fuji Bond LC^®, Prime & Bond 2·0^® and Bisco One-step^®. Half of the restorations in each group were finished immediately after light polymerization and stored for 1 week. For the remaining restorations, finishing was delayed for 1 week. The storage medium was isotonic saline at 37°C throughout the experiment. All restorations were then thermocycled, subjected to dye penetration testing, sectioned and scored. The results suggest that the finishing of composite restorations, bonded with the bonding systems evaluated, should be carried out immediately after light polymerization. Delayed finishing does not improve but instead can be detrimental to the marginal seal of the restorations. The effects of delayed finishing are, however, both bonding system and tissue specific.     

Effects of nisoldipine on coronary collateral perfusion and hemodynamics in chronically instrumented dogs

The effect of a new dihydropyridine slow-channel calcium blocking agent, nisoldipine, on hemodynamics and myocardial blood flow in normal and collateral-dependent areas distal to a chronic coronary artery occlusion were studied in chronically instrumented, conscious dogs. Nisoldipine produced significant and dose-related decreases in arterial blood pressure, an elevation of heart rate and large increases in coronary blood flow velocity. In dogs with an Ameroid constrictor previously implanted to enhance coronary collateral development, this agent produced large increases in perfusion distal to a chronic coronary artery occlusion. In addition, despite a reduction in arterial pressure, nisoldipine preserved renal cortical, intestinal and skeletal muscle blood flow while increasing tissue flow within liver and cerebral cortex. Thus, nisoldipine increases oxygen supply to collateral-dependent myocardium in the presence of reduced driving pressure for collateral perfusion.     

"Weber's law" for position: unconfounding the role of separation and eccentricity

Bisection thresholds are approximately proportional to the separation/eccentricity of the targets. This "Weber's law" for position has been invoked over the past century. It is the separation of the reference targets, or their eccentricity which determines the threshold? In previous studies separation and eccentricity are confounded. In the present report we have pitted separation against eccentricity. Bisection thresholds were measured for stimuli presented on an isoeccentric arc, so that separation could be varied while holding the eccentricity of the test lines constant. We used a 5-fold range of separations from 2-10 deg. In this regime, the present results provide strong evidence against Weber's law. When separation is varied but eccentricity held constant, there is no Weber's law. Rather the thresholds are approximately constant. Our results suggest that the judgement of the separation of widely separated objects is similar to a distance measurement using a ruler on the cortex, in that the error of measurement is independent of the separation between objects. The results imply that when we attempt to gauge the distance between widely separated objects it is unlikely that we do so on the basis of the outputs of large spatial filters; rather it appears that we make such judgements by estimating the cortical distance which separates the targets of interest.     

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO₂). The patterns of ischemia without congestion (IHB, ISO₂) during superior mesenteric artery occlusion, and ischemia with congestion (IHB, ISO₂) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO₂, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.Supported by the American Society for Gastrointestinal Endoscopy Career Development Award (H850208, H870212), Veterans Administration Medical Research Funds; and in part by research grants (0162-01, 0162-02; 0291-01) from the Smokeless Tobacco Research Council, Inc.; and by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California.     

Racial, ethnic, and cultural factors of childhood sexual abuse: a selected review of the literature

Considerable research on childhood sexual abuse exists; however, few studies have examined the role of race, ethnicity, and culture in such abuse. Past investigations have focused almost exclusively on several ethnic groups and races, namely whites, blacks, and Hispanics, without much delineation of cultural subgroup differences. Additionally, much of the existing research is conflicting and lacks consistency in the use of ethnic and racial terms and identification of cultural variations among the major groups. This paper will summarize and analyze the literature on childhood sexual abuse in relation to racial, ethnic, cultural, and other factors relevant to African American, Hispanic, and Asian populations. A critique of the current weaknesses in the literature, including contradictions and recommendations for future research are also presented.     

Blood transfusion alters the course and outcome of Plasmodium chabaudi AS infection in mice.

The importance of severe anemia in the mortality of susceptible A/J mice during blood-stage Plasmodium chabaudi AS infection was assessed. Blood transfusion during and 2 to 3 days after peak parasitemia rescued 90% of susceptible mice from severe anemia and death and allowed these mice to clear the infection and acquire immunity to reinfection. However, blood transfusion prolonged the patency of the infection for up to 5 days after peak parasitemia. Blood transfusions in resistant C57BL/6 mice produced an identical effect, that is, prolongation of the patency of parasitemia. In addition, blood transfusion increased the numbers of gametocytes in both mouse strains. In both strains of mice, the rapid reduction in parasitemia, which occurs during crisis, was associated with the development of moderate levels of anemia. The possible mechanisms for the modulation of parasitemia by blood transfusion and the implications of the present observations for our understanding of the events which occur during crisis are discussed. It is proposed that parasitologic crisis is induced and/or maintained by physiological alterations associated with anemia.     

Intimin-dependent binding of enteropathogenic Escherichia coli to host cells triggers novel signaling events, including tyrosine phosphorylation of phospholipase C-gamma1.

Enteropathogenic Escherichia coli (EPEC) interactions with HeLa epithelial cells induced the tyrosine phosphorylation of a host protein of approximately 150 kDa, Hp150. Phosphorylation of this protein band was dependent on the interaction of the EPEC protein intimin with epithelial cell surfaces and was correlated with pedestal formation. Hp150 phosphorylation was specifically inhibited by the addition of cytochalasin D, an inhibitor of actin polymerization, although this appeared to be an indirect effect preventing interaction of intimin with its receptor, tyrosine-phosphorylated Hp90, and thus triggering Hp150 phosphorylation. This suggests the involvement of an actin-based movement of membrane-bound tyrosine-phosphorylated Hp90 to allow its interaction with intimin. Analysis of the tyrosine-phosphorylated Hp150 protein demonstrated that it is heterogeneous in composition, with phospholipase C-gamma1 (PLC-gamma1) being a minor component. Activation of PLC-gamma1 by tyrosine phosphorylation leads to inositol triphosphate and Ca2+ fluxes, events detected following EPEC infection. EPEC also induced tyrosine dephosphorylation of host proteins, including a 240-kDa host protein (Hp240), following EPEC infection. Protein dephosphorylation appears to be a signaling event which occurs independently of intimin. Inhibition of host tyrosine dephosphorylation events by the addition of the tyrosine phosphatase inhibitor sodium vanadate did not prevent actin accumulation beneath the adherent bacteria. We conclude that EPEC induces two sets of signaling events following infection. One set is dependent on EPEC proteins secreted by the type III secretion pathway (EspA and EspB) which induces Hp90 tyrosine phosphorylation and dephosphorylation of host phosphotyrosine proteins. The second set, which is also dependent on the first signaling events, requires intimin interaction with its receptor, tyrosine-phosphorylated Hp90, to trigger Hp150 and PLC-gamma1 tyrosine phosphorylation as well as pedestal formation. Inhibition of pedestal formation by tyrosine kinase inhibitors indicates an important role for tyrosine phosphorylation events during EPEC subversion of host processes.     

The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.