Activation of the CPP32 protease in apoptosis induced by 1-beta-D- arabinofuranosylcytosine and other DNA-damaging agents

The response of human myeloid leukemia cells to treatment with 1-beta- arabinofuranosylcytosine (ara-C) includes the induction of apoptosis. Ara-C induced apoptosis is associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and protein kinase C (PKC) delta. However, the signals involved in this response are unknown. The present studies show that ara-C treatment of U-937 cells is associated with induction of a protease activity that cleaves the tetrapeptides Ac-DEVD- pNA and Ac-DMOD-pNA found at the cleavage sites of PARP and PKC delta, respectively. The ara-C-induced protease activity was sensitive to overexpression of the anti-apoptotic protein Bcl-xL and the baculovirus protein p35. By contrast, overexpression of the cowpox virus protein CrmA blocked apoptosis induced by engagement of the Fas receptor but not that induced by ara-C. CrmA overexpression also had no detectable effect on ara-C-induced cleavage of PKC delta. The results further show that ara-C induces activation of the CPP32 protease by a CrmA- insensitive and p35-sensitive mechanism. Similar results were obtained with cisplatinum, etoposide, and camptothecin. These findings indicate that ara-C and other DNA-damaging agents activate a CrmA-insensitive apoptotic pathway involving CPP32 and that these signals differ from those associated with apoptosis induced by the Fas receptor.     

Blood donor Borrelia burgdorferi sensu lato seroprevalence and history of tick bites at a northern limit of the vector distribution

In order to study the antibody seroprevalence of the causal agent of Lyme borreliosis, Borrelia burgdorferi sensu lato (s.l.), and the history of tick bites at a geographical distribution limit of Ixodes ricinus, we compared healthy blood donors in geographically extreme regions: the borreliosis‐endemic Vestfold County (59°N) and the region of northern Norway. Blood samples were screened using IgG/VlsE ELISA, and positive/borderline samples were confirmed using C6 ELISA and immunoblot assays. Also, donors completed a questionnaire consisting of several items including the places they have lived, and whether they owned any pets. The seroprevalence was 0.48% (5/1048) in northern Norway and 9.25% (48/519) in Vestfold County. Seven donors (of 1048) had experienced a single tick bite in the southern part of Nordland County (65°N) in northern Norway. This first study on B. burgdorferi s.l. antibody seroprevalence and tick bites on humans and pets in northern Norway showed that the seroprevalence of B. burgdorferi s.l. infection and the risk of tick bite in northern Norway are insignificant; the fact that only five positive IgG samples were detected underscores the very low background seroprevalence. These results suggest that so far I. ricinus has not expanded north of the previously established geographical distribution limit.     

Palliation of rectosigmoid neoplasms with Nd:YAG laser treatment

PURPOSE: The aim of this study was to evaluate the effect of Nd:YAG laser treatment as palliation for rectosigmoid neoplasms. METHODS: Indications for laser therapy, the degree and duration of symptom relief, complication rate, and survival time were recorded in consecutive patients. RESULTS: Seventy-four patients entered the study. Poor general health in older patients, and disseminated or complicating disease were the most frequent indications for therapy. Fifty-five (74 percent) patients experienced good symptomatic effect from the treatment. Six complications occurred: five cases of perforation and one case of moderate bleeding. There was no mortality. The median survival was seven months (range, 14 days–39 months). CONCLUSION: Laser treatment is a good palliative method in patients with colorectal cancer, especially in patients with local recurrence or symptoms from nonresected tumors.     

An effective Australian-Chinese peer education program on HIV/AIDS/STDs for university students in China

<正> IntroductionCurrently,there are at least 850,000 peo-ple living with human immuno-deficiency virus(HIV) and acquired immuno-deficiency syn-drome (AIDS) in China.Among them 16-29years old account for about 65%.Accordingto the Chinese health authorities,if the pre-ventive measures are not effective,the figurecould reach as many as 10 million by the year2010.Since there are currently no cure or     

Emergence of beta-lactam multiresistant variants of gram-negative bacilli in the presence of cefotaxime

88 clinical isolates of gram-negative bacilli (23 Enterobacter, 23 Klebsiella, 21 E. coli, and 21 Pseudomonas) all showed susceptibility to one or more cephalosporins and were nitrocefin test negative. When cultured overnight in the presence of 1, 10, or 100 mg/l of cefotaxime, 19 Enterobacter strains grew beta-lactamase-producing variants, 15 of them at concentrations less than or equal to 10 mg/l of cefotaxime. All enzyme-producing variants showed resistance to a number of cephalosporins including non-hydrolyzable cephalosporins and other beta-lactam antibiotics, except mecillinam and thienamycin. With the other gram-negative bacilli resistant mutants did not emerge in the presence of cefotaxime. These findings are discussed in relation to use of third generation cephalosporins as first hand monotherapy in patients.     

An ecotoxicoproteomic approach (SELDI-TOF mass spectrometry) to biomarker discovery in crab exposed to pollutants under laboratory conditions

Ciphergen ProteinChip Technology is a proteomic tool, used for the discovery of new and sensitive biomarkers. This approach was used to evaluate the protein profile of crabs exposed to various pollutants. Two different exposure experiments were performed: spider crabs (Hyas araneus) were exposed for 3 weeks to diallyl phatalate (DAP), bisphenol A (BisA) and polybrominated diphenyl ether (PBDE-47), while shore crabs (Carcinus maeanas) were exposed to crude oil, crude oil spiked with alkylphenols (APs) and 4-nonylphenol (NP). Gender and species-related protein pattern alterations were observed and compared to controls. Results showed different responses to pollutants by the two species. Major disruption in protein peak expression was observed in samples exposed to mixtures of pollutants, i.e. oil spiked with APs. Compared to shore crab, spider crab species showed a lower degree of response in terms of number of altered protein peaks following exposure. In general, female individuals of both species showed a larger number of significantly altered proteins compared to males. Data analysis by non-metric multi-dimensional scaling (MDS) was performed. Bi-dimesional-MDS plots revealed a good separation of groups for both spider and shore crabs. In some cases, a good discrimination can also be observed between the two genders within each treatment. Results highlight the potential of crabs as sentinel organisms for the aquatic environment. The results indicate that SELDI-ToF technology is a powerful tool to discover protein expression signatures for different pollutants and sex dependent responses.