Altered functional responsiveness of thymocyte subsets from CD3delta- deficient mice to TCR-CD3 engagement

CD3delta-deficient (delta degrees) mice are defective in alphabeta T cell development. Here we explore the capacity of TCR-CD3 signaling complexes expressed on delta degrees thymocytes to mediate the following functional outcomes in response to antibody cross-linking: (i) the transition from the CD4-CD8- to CD4+CD8+ stage, (ii) the transition from the CD4+CD8+ to CD4+CD8- or CD4-CD8+ stages and (iii) the induction of apoptosis. We provide evidence that CD3deltaepsilon complexes are dispensable for mediating the anti-CD3-mediated CD4-CD8- to CD4+CD8+ transition. On the other hand, CD3delta is critical at the CD4+CD8+ stage. We demonstrate that CD4+CD8+ thymocytes from delta degrees mice, unlike delta degrees CD4-CD8- thymocytes and wild-type CD4+CD8+ thymocytes, require prolonged or consecutive stimuli to elicit functional responses. Depending on the nature of the secondary stimulus, delta degrees thymocytes can be induced to undergo apoptosis or preferential maturation to the CD4-CD8+ stage. Taken together these results indicate that the signaling capacity of the TCR-CD3 complex is noticeably altered in the absence of CD3delta. The essential role of CD3delta at the CD4+CD8+ stage of development correlates with the onset of TCRalpha rearrangement, consistent with a critical structural and/or functional relationship between CD3delta and TCRalpha.      

Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells.

Human neutrophils stimulated with phorbol myristate acetate were able to destroy suspensions or monolayers of cultured human endothelial cells. Neutrophil-mediated cytotoxicity was related to phorbol myristate acetate concentration, time of incubation and neutrophil number. Cytolysis was prevented by the addition of catalase, while superoxide dismutase had no effect on cytotoxicity. The addition of the heme-enzyme inhibitors, azide or cyanide, markedly stimulated neutrophil-mediated damage while exogenous myeloperoxidase failed to stimulate cytolysis. Neutrophils isolated from patients with chronic granulomatous disease did not destroy the endothelial cell targets while myeloperoxidase-deficient neutrophils successfully mediated cytotoxicity. Endothelial cell damage mediated by the myeloperoxidase deficient cells was also inhibited by catalase but not superoxide dismutase. The addition of purified myeloperoxidase to the deficient cells did not stimulate cytotoxicity. Glucose-glucose oxidase, an enzyme system capable of generating hydrogen peroxide, could replace the neutrophil as the cytotoxic mediator. The addition of myeloperoxidase at low concentrations of glucose oxidase did not increase cytolysis, but at the higher concentrations of glucose oxidase it stimulated cytotoxicity. The destruction of endothelial cells by the glucose oxidase-myeloperoxidase system was inhibited by the addition of hypochlorous acid scavengers. In contrast, neutrophil-mediated cytolysis was not effectively inhibited by the hypochlorous acid scavengers. Based on these observations, we propose that human neutrophils can destroy cultured human endothelial cells by generating cytotoxic quantities of hydrogen peroxide.     

Tropical pyomyositis

A 22 year old male presented with symptoms of diffuse muscle pain and multiple abnormal laboratory findings that were eventually attributed to tropical myositis. Computed tomography scan was more reliable than ultrasound and served as a guide to needle aspiration and pathologic diagnosis.     

The geometry of triple-balloon dilation

Triple-balloon dilation (TBD) of a variety of luminal structures has been successfully, though infrequently, used. A mathematical model is presented for the selection of balloon sizes, and equations and tables are derived that allow the user to estimate more accurately the size of balloons needed for TBD of structures with large lumina. With TBD, an approximately circular lumen can be formed. Also, TBD allows smaller, higher-pressure balloons to be used instead of single, low-pressure, large balloons. However, multiple puncture sites may be required for TBD.     

The correction of the hepatotoxicity of antitubercular preparations with tocopherol acetate and riboxin]

It has been established in experiments on white rats that prolonged (for 2 weeks) intoxication with antituberculous drugs (isoniazid plus rifampicin plus pyrazinamide) results in cytolytic liver injury. This manifests by hyperaminotransferasemia, initiation of lipid peroxidation, suppression of the antioxidant system and bile production. Daily injections of tocopherol acetate (15 mg/kg) and riboxine (100 mg/kg) together with administration of antituberculous drugs reduce their hepatotoxicity. The combined use of these hepatoprotectors and antioxidants provides a dramatic increase of their efficacy in durable intoxication with antituberculous drugs.     

Computed tomography based scoring system in a prospectively ascertained cohort of patients with chronic pancreatitis

ObjectiveNo standardized system is currently used to report the presence or severity of parenchymal and ductal features of chronic pancreatitis (CP) on CT scan. We report a modification to the previously proposed Cambridge classification to serve this purpose.MethodsContrast-enhanced CT scans of 158 well-phenotyped patients with CP enrolled in the North American Pancreatitis Studies (NAPS2) during 2000–2014 from the University of Pittsburgh were retrospectively reviewed by a subspecialty trained abdominal radiologist. Presence and severity (score scale 0–4) of pancreatic duct (PD) dilation, obstruction and contour irregularity, pancreatic calcifications, atrophy and extent of pancreatic involvement were recorded to grade the morphological severity of CP and stratify patients into distinct morphologic patterns. Findings were also correlated with clinical features.ResultsPancreatic atrophy, calcifications, PD dilation and PD irregularity were observed in 80%, 68%, 65%, 58% cases, respectively. An obstructive stone or PD stricture was present in 63%, and 86% had diffuse pancreatic involvement. Using these features, CP was noted to be moderate or severe in 61%, and classified morphologically as obstructive with/without calcifications, calcific but non-obstructive and non-calcific/non-obstructive in 65%, 20%, 15%, respectively. Functional abnormalities but not the presence of pain generally correlated with imaging findings.ConclusionA structured scoring system can provide qualitative and quantitative assessment of imaging findings in CP and an opportunity for adoption into clinical practice and research for initial evaluation and longitudinal follow-up. Our findings need validation in a prospective cohort before widespread adoption.