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β-Site APP-cleaving enzyme (BACE) initiates the processing of the amyloid precursor protein (APP) leading to the generation of β-amyloid, the main component of Alzheimer's disease senile plaques. BACE (Asp2, memapsin 2) is a type I transmembrane aspartyl protease and is responsible for the β-secretase cleavage of APP producing different endoproteolytic fragments referred to as the carboxy-terminal C99, C89 and the soluble ectodomain sAPPβ. Here we describe two transgenic mouse lines expressing human BACE in the brain. Overexpression of BACE augments the amyloidogenic processing of APP as demonstrated by decreased levels of full-length APP and increased levels of C99 and C89 in vivo. In mice expressing huBACE in addition to human APP wild-type or carrying the Swedish mutation, the induction of APP processing characterized by elevated C99, C89 and sAPPβ, results in increased brain levels of β-amyloid peptides Aβ40 and Aβ42 at steady-state. [ABSTRACT FROM AUTHOR]

Presents a study that described hepatotoxicity in HIV-infected patients treated with ritonavir and saquinavir with or without stavudine. Information on liver enzyme elevation (LEE); Risk factors for LEE; Clinical management of the patients and the patients' outcome; Side effect of antiretroviral therapy.

We studied nine freshmen and 14 senior oarsmen undergraduates during seven months of training and compared them with 17 age and sex-matched sedentary control subjects in order to assess the influence of heavy physical exercise on cardiac dimensions and maximal oxygen uptake. Standard M-mode echocardiographic techniques were used. At the start of the season senior oarsmen had a greater left ventricular end-diastolic dimension, and a thicker interventricular septum and posterior left ventricular wall than control subjects and freshmen oarsmen. The two latter groups did not differ from each other. During the training period there was a slight and gradual increase in left ventricular end-diastolic dimension, and interventricular septum and posterior wall thickness in freshmen. In seniors only left ventricular end-diastolic dimension increased significantly. Maximal oxygen uptake showed a distinct increase between the fourth and seventh month during the period of intensive rowing training. There was no relation between echocardiographic variables and maximal oxygen uptake. A combination of heavy dynamic and static exercise can thus lead to significant changes in both left ventricular wall thickness and chamber size within months. Echocardiographic variables measured at rest cannot be used as a suitable index of performance capacity. [ABSTRACT FROM PUBLISHER]

We investigated the in vitro effect of cultured human thymic epithelial monolayer cells on mononuclear cells (MNC) from patients with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related complex (ARC), Patients having undergone bone-marrow transplantation (BMT), who showed a similar deficiency of T-lymphocytes expressing CD4 (Leu-3, T4), and healthy blood donors served as controls. Most epithelial monolayer cells were of thymic medulla origin, as documented using a panel of monoclonal antibodies to thymic epithelial cells. In AIDS/ARC patients the CD4-positive cells (ranging between 4 and 30%, of MNC) increased by a factor of 1.56 (s.e.m. 0.15, n = 12) during a 2 h incubation on the monolayer. Human fetal lung fibroblasts were inactive in this respect. There was no consistent change in cells expressing CD3 (Leu-4, T3). CD5 (Leu-l) or CD8 (Leu-2, T8). In BMT patients and healthy controls, neither thymus epithelium nor fibroblasts had any effect on T cell marker expression. Incorporation of tritiated thymidine by stimulated or unstimulated lymphocytes was increased after incubation for 3 days on either epithelium or fibroblasts. We conclude that CD4 expression is induced on MNC from AIDS/ARC patients during a 2 h incubation on epithelial monolayers. [ABSTRACT FROM AUTHOR]

We performed a cross-sectional study at an outpatient AIDS clinic to assess the prevalence of Campylobacter species in stool specimens from 201 consecutive patients infected with human immunodeficiency virus (HIV). We characterized campylobacters phenotypically and genetically by using primers for the group of common species (i.e., C. jejuni, C. coli, C. lari, and C. upsaliensis) and for most individual uncommon species. We performed cultures with use of a membrane filter technique on nonselective blood agar and found that Campylobacter species were the most frequent enteropathogenic bacteria: the organisms were recovered from 7 (16%) of 43 patients with diarrhea and 5 (3%) of 158 patients without diarrhea (P = .001). We isolated only one campylobacter with use of conventional culture techniques on selective media. Phenotypic characterization of 10 campylobacter strains resulted in the misidentification of four isolates. C. upsaliensis was the most frequently isolated species, followed by C. jejuni and C. coli. Two strains could not be identified with the available primers. Two of 12 Campylobacter strains were resistant to erythromycin, and two were resistant to ciprofloxacin. We conclude that Campylobacter species other than C. jejuni can frequently be detected in the stools of HIV-infected patients and that these organisms could be associated with diarrhea. [ABSTRACT FROM PUBLISHER]

This study examined the factors associated with the development of a first episode of Pneumocystis carinii pneumonia (PCP) in 5,025 patients with AIDS, including 1,976 patients with primary PCP at the time of AIDS diagnosis and 635 with primary PCP occurring subsequently. Compared with untreated patients, patients treated with zidovudine were at similar risk of developing PCP during the first year of therapy but were at greater risk after longer intervals of treatment. The following factors were associated with an increased risk of PCP (either at the time of AIDS diagnosis or thereafter): lack of primary PCP prophylaxis, male homosexualitylbisexuality, diagnosis of AIDS in northern Europe, and CD4 cell count below 200 × 106/L at the time of AIDS diagnosis. Patients with severe weight loss had a 60% higher risk of developing PCP during follow-up than those without such weight loss. Thus, the occurrence of PCP depended on geographic location, mode of acquisition of human immunodeficiency virus and AIDS, degree of immunodeficiency, and use of various treatment regimens. [ABSTRACT FROM PUBLISHER]