APO-1(CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines

Certain B and T cell lines respond to activation signals, e.g.through the antigen receptor, by undergoing apoptotlc cell death.In T cells it has been recently shown that TCR-mediated apoptosisinvolves APO-1/Fas (CD95) receptor-ligand interaction. To investigatewhether the TCR-CD3 complex can trigger alternative apoptosispathways we generated subclones of the T cell line Jurkat whichwere completely resistant towards APO-1-mediated apoptosis.These Jurkat^R cells differed phenotypically from sensitive parentalJurkat^S cells only by the lack of APO-1 protein expression.Although Jurkat^R cells responded normally to anti-CD3 stimulationby expression of APO-1 ligand they failed to undergo anti-CD3-inducedapoptosis. Thus, in Jurkat cells APO-1 -mediated apoptosis wasthe main, and might be the only, mechanism for anti-CD3-inducedcell death. However, BL-60 B cells, highly sensitive to anti-IgM-inducedapoptosis, did not use the APO-1 receptor-ligand system becausethey failed to express APO-1 ligand mRNA. Taken together, ourresults suggest that malignant T and B cell lines may use APO-1receptor-ligand-dependent and -independent antigen receptor-inducedapoptosis pathways respectively. Similarly, differential pathwaysmay be used by T and B cell subsets.     

Myocardial infarction in a large colony of nonhuman primates with coronary artery atherosclerosis.

Relatively few cases of myocardial infarction associated with coronary artery atherosclerosis have been described previously in macaques. In this study the authors report the prevalence and characteristics of coronary artery atherosclerosis and myocardial infarction in 10 rhesus (Macaca mulatta) and two cynomolgus (Macaca fascicularis) macaques that were fed atherogenic diets for 16 months or longer. Our findings show clearly that myocardial infarction occurs in macaques with diet-induced atherosclerosis. The frequency seems to be related to the species, composition of the atherogenic diet, and length of time fed the atherogenic diet. The myocardial lesions are remarkably similar to those described in human beings in terms of location and gross and microscopic characteristics. The characteristics of coronary artery atherosclerosis, including the occurrence of thrombosis, severe stenosis, mineralization, atheronecrosis, and sterol clefts, especially in animals fed the atherogenic diets for longer periods of time, also closely resemble those of the arterial lesions found in human beings. The greatest prevalence of myocardial infarcts was found in rhesus monkeys fed a cholesterol-containing diet with 40% of calories supplied by peanut oil and in cynomolgus macaques from Malaya that were fed the same amount of cholesterol with 40% of calories from lard. Electrocardiographic abnormalities as well as the occurrence of unexpected and relatively sudden death in several of these nonhuman primates are also consistent with signs frequently observed in human beings.     

Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations

We examined 26 individuals with clinical and electron microscopic signs of late infantile neuronal ceroid lipofuscinosis (LINCL). In 22 cases, we found both pathogenic alleles. Sixteen patients exclusively carried either one or a combination of the two common mutations R208X and IVS5-1G > C. In the remaining cases, four missense mutations could be detected, of which R127Q, N286S, and T353P represent novel, previously not described alleles. A clinical performance score was developed by rating motor, visual, and verbal functions and the incidence of cerebral seizures in 3-month intervals during the course of the disease. A Total Disability Score was derived by summing up the single scores for motor, visual, and verbal functions. The 16 individuals with the two common mutations were grouped together (referred to as standard patients), and the 5th, 50th, and 95th centiles were calculated and graphically depicted over time. The scores for motor function and language ability dropped earliest and progressed very similarly in the standard patients. The performance curves of two children with the N286S mutation slightly diverged from the 95th centile. However, the performance curves of one patient with atypical LINCL carrying the R127Q mutation fell far beyond the 95th centile. The presented performance rating clearly and quantitatively delineates the disease course of the LINCL patients and hence offers a useful tool for clinical evaluation of future therapeutic interventions. In addition, the described performance score system can be applied to other types of neuronal ceroid lipofuscinoses and could be adapted to various other neurodegenerative diseases of childhood.     

Primary prevention of natural rubber latex allergy in the German health care system through education and intervention

BACKGROUND: The development of occupational asthma and allergic skin reactions caused by natural rubber latex (NRL) allergy are risks for health care workers. There are few published studies to suggest that intervention programs to reduce exposure will lead to primary prevention of sensitization. OBJECTIVE: This study assesses the effects of intervention to reduce the incidence of NRL allergy in personnel working in health care facilities insured by the German statutory accident insurance company for health care workers, Berufsgenossenschaft für Gesundheitsdienst und Wohlfahrtspflege, with approximately 3 million insured employees, by switching to powder-free NRL gloves. METHODS: The timing of introduction of intervention strategies, such as education of both physicians and administrators, together with regulations demanding that health care facilities only purchase low-protein, powder-free NRL gloves are reported. We reviewed the annual numbers of reported suspected cases of NRL-caused occupational allergies and the amount and type of gloves used in German acute-care hospitals since 1986. RESULTS: The purchase of powder-free NRL examination gloves exceeded that of powdered gloves for the first time in 1998. This only became true for powder-free NRL sterile gloves 2 years later in 2000. The incidence of suspected occupational NRL allergy cases rose until 1998 and has declined steadily since. There was a 2-year lag between the beginning of the decline in the purchase of powdered NRL examination gloves and the beginning of a decline in suspected NRL-caused occupational asthma cases. CONCLUSIONS: Despite the effect of increased recognition of NRL allergies, education about NRL allergies in health care facilities combined with the introduction of powder-free gloves with reduced protein levels has been associated with a decline in the number of suspected cases of occupational allergies caused by NRL in Germany on a nationwide scale. These results clearly indicate that primary prevention of occupational NRL allergies can be achieved if these straightforward and practical interventions are properly carried out and maintained.     

The selective processing of briefly presented affective pictures: an ERP analysis

Recent event-related potential (ERP) studies revealed the selective processing of affective pictures. The present study explored whether the same phenomenon can be observed when pictures are presented only briefly. Toward this end, pleasant, neutral, and unpleasant pictures from the International Affective Pictures Series were presented for 120 ms while event related potentials were measured by dense sensor arrays. As observed for longer picture presentations, brief affective pictures were selectively processed. Specifically, pleasant and unpleasant pictures were associated with an early endogenous negative shift over temporo-occipital sensors compared to neutral images. In addition, affective pictures elicited enlarged late positive potentials over centro-parietal sensor sites relative to neutral images. These data suggest that a quick glimpse of emotionally relevant stimuli appears sufficient to tune the brain for selective perceptual processing.     

Evaluation of Mannitol Salt Agar for Detection of Oxacillin Resistance in Staphylococcus aureus by Disk Diffusion and Agar Screening

Mannitol salt agar was evaluated for detection of oxacillin resistance in 136 Staphylococcus aureus isolates. All mecA-positive isolates (n = 54) were correctly categorized as oxacillin resistant by the disk diffusion test (1-μg disk; zone diameter, <16 mm); the specificity was 97.6%. Agar screening (2 μg of oxacillin per ml) revealed a sensitivity of 98.1% and a specificity of 95.1%.     

Drosophila Cyclin B3 is required for female fertility and is dispensable for mitosis like Cyclin B

Cyclin B3 has been conserved during higher eukaryote evolution as evidenced by its identification in chicken, nematodes, and insects. We demonstrate that Cyclin B3 is present in addition to Cyclins A and B in mitotically proliferating cells and not detectable in endoreduplicating tissues of Drosophila embryos. Cyclin B3 is coimmunoprecipitated with Cdk1(Cdc2) but not with Cdk2(Cdc2c). It is degraded abruptly during mitosis like Cyclins A and B. In contrast to these latter cyclins, which accumulate predominantly in the cytoplasm during interphase, Cyclin B3 is a nuclear protein. Genetic analyses indicate functional redundancies. Double and triple mutant analyses demonstrate that Cyclins A, B, and B3 cooperate to regulate mitosis, but surprisingly single mutants reveal that neither Cyclin B3 nor Cyclin B is required for mitosis. However, both are required for female fertility and Cyclin B also for male fertility.     

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