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Deficiency of X-linked inhibitor of apoptosis (XIAP) caused by XIAP/BIRC4 gene mutations is an inherited immune defect recognized as X-linked lymphoproliferative syndrome type 2. This disease is mainly observed in patients with hemophagocytic lymphohistiocytosis (HLH) often associated with Epstein-Barr virus infection. We described nine Japanese patients from six unrelated families with XIAP deficiency and studied XIAP protein expression, XIAP gene analysis, invariant natural killer T (iNKT) cell counts, and the cytotoxic activity of CD8 alloantigen-specific cytotoxic T lymphocytes. Of the nine patients, eight patients presented with symptoms in infancy or early childhood. Five patients presented with recurrent HLH, one of whom had severe HLH and died after cord blood transplantation. One patient presented with colitis, as did another patient's maternal uncle, who died of colitis at 4 years of age prior to diagnosis with XIAP deficiency. Interestingly, a 17-year-old patient was asymptomatic, while his younger brother suffered from recurrent HLH and EBV infection. Seven out of eight patients showed decreased XIAP protein expression. iNKT cells from patients with XIAP deficiency were significantly decreased as compared with age-matched healthy controls. These results in our Japanese cohort are compatible with previous studies, confirming the clinical characteristics of XIAP deficiency. [ABSTRACT FROM AUTHOR]

Background. We have attempted to predict the development of fulminant hepatic failure at the stage of severe acute hepatitis before the onset of coma. This prediction is valuable because it may be used to block the development of fulminant hepatic failure with appropriate medical treatment. Methods. To establish a discrimination formula, we retrospectively compared 13 clinical and laboratory variables in 36 patients with acute viral hepatitis and prothrombin levels of 40% or less of the control value who later developed fulminant hepatic failure with these variables in 12 patients who recovered spontaneously. A prospective study of 58 patients who developed fulminant hepatic failure and 18 who spontaneously recovered confirmed the validity of this formula. Results. In the retrospective study, we established the following discrimination equation: Z = -0.89 + 1.74 × (causal viruses, 1 point for type A or type B in acute hepatitis B virus [HBV] infection, 2 points for others) + 0.056 × (total bilirubin, mg/dl) -0.014 × (cholinesterase, U/ml). A positive Z value indicates that fulminant hepatic failure will develop. In the prospective study, the specificity, sensitivity, predictive accuracy, and positive and negative predictive values were 0.833, 0.983, 0.947, 0.950, and 0.938, respectively. Conclusions. The present study indicated that fulminant hepatic failure can be predicted, by a simple discrimination equation, at the stage of severe acute hepatitis. [ABSTRACT FROM AUTHOR]

Background. Cryptosporidium parvum infection has been recognized as one of the pathogens causing severe and persistent diarrhea in immunodeficient patients, such as those with AIDS, worldwide. However, in Japan, the frequency of this infection has been rare, except for environmental contamination through the water supply. In this communication, we describe a Japanese patient with AIDS presenting with intestinal Cryptosporidiosis as an initial manifestation. Methods. The oocysts of Cryptosporidium parvum in his stool were detected by the Ziehl-Neelsen method and electron microscopy. The antigen-specificity was proved by immunostaining, using a fluorescein isothiocyanate (FITC)-labeled monoclonal antibody and enzymelinked immunosorbent assay (ELISA), using Cryptosporidium-specific antibody. Results. A 28-yearold Japanese homosexual man was admitted to our hospital because of severe watery diarrhea of 1-week duration. Numerous oocysts of Cryptosporidium parvum were observed in his stool. Cryptosporidium parvum antigen was detected in stool samples. Serological examinations revealed that anti-HIV-1 antibody was positive, and HIV RNA was positive at a high level. He was diagnosed as having AIDS associated with intestinal Cryptosporidiosis. The circulating CD4+ T-cell count was 152/µl. His diarrhea was not alleviated by administration of loperamide and an ordinary antibiotic agent, but ultimately resolved by the administration of the macrolide antibiotic agent, clarithromycin. Conclusions. We emphasize that the presence of Cryptosporidium parvum infection should be kept in mind in searching for pathogens causative of severe diarrhea in AIDS patients. [ABSTRACT FROM AUTHOR]