Inhibition of host RNA polymerase II-dependent transcription by vesicular stomatitis virus results from inactivation of TFIID

The present study tested the hypothesis that one or more tyrosine kinase(s) are downstream of protein kinase C (PKC) in the signal transduction pathway responsible for the cardioprotective effect of ischemic preconditioning (PC). Isolated rabbit hearts were subjected to 30 min of regional ischemia followed by 2 h of reperfusion. Infarct size was measured by triphenyltetrazolium staining and expressed as a percentage of the area at risk. Infarction in control hearts was 32.9+/-1.8%. Ischemic PC with 5-min ischemia/10-min reperfusion reduced infarct size to 11.5+/-1.5% (P<0.05). Infusion of the tyrosine kinase inhibitors, genistein (50 microM) or lavendustin A (0.5 microM), alone did not affect the level of infarction. When infused around the 5-min PC ischemia genistein failed to block protection (13.7+/-1.0%). However, when present at the onset of the 30-min ischemia both genistein and lavendustin A completely aborted protection (31.4+/-2.0 and 28.1+/-1.5%, respectively). Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 0.05 nmol) was as protective is ischemic PC (14.9+/-3.0%; P<0. 05). Similar to PC, PMA-induced protection was completely prevented by both genistein and lavendustin A. Conversely, anisomycin (50 ng/ml), an activator of MAP kinase kinases (dual tyrosine and threonine kinases), was very protective (7.5+/-1.6%; P<0.05) and this protection was still present when PKC was inhibited by 5 microM chelerythrine (12.1+/-1.6%; P<0.05). In conclusion, activation of a tyrosine kinase during the long ischemia appears to be required for cardioprotection in the rabbit heart. Furthermore, the ability of tyrosine kinase inhibitors to block PMA-induced protection in conjunction with the failure of PKC inhibition to prevent anisomycin-induced protection suggests that the tyrosine kinase is downstream of PKC and that the tyrosine kinase may be a MAP kinase kinase.     

An automated fluorescent PCR method for detection of shiga toxin-producing Escherichia coli in foods

An automated fluorescence-based PCR system (a model AG-9600 AmpliSensor analyzer) was investigated to determine whether it could detect Shiga toxin-producing Escherichia coli (STEC). The AmpliSensor PCR assay involves amplification-mediated disruption of a fluorogenic DNA signal duplex (AmpliSensor) that is homologous to conserved target sequences in a 323-bp amplified fragment of Shiga toxin genes stx1, stx2, and stxe. Using the Amplisensor assay, we detected 113 strains of STEC belonging to 50 different serotypes, while 18 strains of non-Shiga-toxin-producing E. coli and 68 strains of other bacteria were not detected. The detection limits of the assay were less than 1 to 5 CFU per PCR mixture when pure cultures of five reference strains were used and 3 CFU per 25 g of food when spiked ground beef samples that were preenriched overnight were used. The performance of the assay was also evaluated by using 53 naturally contaminated meat samples and 48 raw milk samples. Thirty-two STEC-positive samples that were confirmed to be positive by the culture assay were found to be positive when the AmpliSensor assay was used. Nine samples that were found to be positive when the PCR assay was used were culture negative. The system described here is an automated PCR-based system that can be used for detection of all serotypes of STEC in food or clinical samples.     

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.     

Identification of atypical Aeromonas salmonicida: inter-laboratory evaluation and harmonization of methods

Estrogen therapy increases plasma HDL levels, which may reduce cardiovascular risk in postmenopausal women. The mechanism of action of estrogen in influencing various steps in hepatic HDL and apolipoprotein (apo) A-I synthesis and secretion are not fully understood. In this study, we have used the human hepatoblastoma cell line (Hep G2) as an in vitro model system to delineate the effect of estradiol on multiple regulatory steps involved in hepatic HDL metabolism. Incubation of Hep G2 cells with estradiol resulted in the following statistically significant findings: (1) increased accumulation of apoA-I in the medium without affecting uptake/removal of radiolabeled HDL-protein; (2) accelerated incorporation of [3H]leucine into apoA-I; (3) selective increase in [3H]leucine incorporation into lipoprotein (LP) A-I but not LP A-I+A-II HDL particles (HDL particles without and with apoA-II, respectively); (4) increased ability of apoA-I-containing particles to efflux cholesterol from fibroblasts; (5) stimulated steady state apoA-I but not apoA-II mRNA expression; and (6) increased newly transcribed apoA-I mRNA message without effect on apoA-I mRNA half-life. The data indicate that estradiol stimulates newly transcribed hepatic apoA-I mRNA, resulting in a selective increase in LP A-I, a subfraction of HDL that is associated with decreased atherosclerotic cardiovascular disease, especially in premenopausal women.     

Infrared spectroscopy of human tissue. IV. Detection of dysplastic and neoplastic changes of human cervical tissue via infrared microscopy

It has been widely asserted that low self-esteem causes violence, but laboratory evidence is lacking, and some contrary observations have characterized aggressors as having favorable self-opinions. In 2 studies, both simple self-esteem and narcissism were measured, and then individual participants were given an opportunity to aggress against someone who had insulted them or praised them or against an innocent third person. Self-esteem proved irrelevant to aggression. The combination of narcissism and insult led to exceptionally high levels of aggression toward the source of the insult. Neither form of self-regard affected displaced aggression, which was low in general. These findings contradict the popular view that low self-esteem causes aggression and point instead toward threatened egotism as an important cause.     

Atopic dermatitis

Atopic dermatitis is an important manifestation of the atopic diathesis with increasing incidence. The average lifetime prevalence in Switzerland is about 13%. The skin disease is characterised by severe itching, eczematous skin lesions with often distinctive distribution, dryness of the skin and a personal of family history of atopic diseases. The following article summarises some clinical, epidemiological, therapeutical and pathogenetical aspects of atopic dermatitis. Studies from the allergy unit of Zurich contributed to a better understanding of the disease. Thus, Storck was contributing various studies about neurovegetative and circulatory dysregulations in patients with atopic dermatitis. Furthermore, he already realised in 1955 a relation between exacerbations of eczema and the sensitisation to inhalatory allergens. Schnyder demonstrated that asthma, rhinitis and atopic dermatitis have the same genetic background and Wüthrich contributed important data about the natural history of the disease and the occurrence and relevance of total and specific IgE antibodies.     

Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence for sympathetic vasoconstriction

We examined the gelatinolytic activity in human oral squamous-cell carcinoma tissues in order to evaluate the capability of intravasation and extravasation of cancer cells. By a microdissection-zymography, we demonstrated separately the gelatinolytic activities in cancer cell nests and stroma adjacent to the cancer cells. The gelatinolytic activities, such as pro-matrix metalloproteinase (MMP)9 and active-MMP2 in most of cancer cell nests were much higher than those of normal gingival epithelium. Moreover, the activities of active-MMP2 in cancer cell nests of metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). These results suggest that active-MMP2 in cancer cells can be a predictive marker for metastasis formation in oral squamous-cell carcinoma patients.     

Ageing in reptiles

Like in fishes, the reptiles appear to show three types of senescence. The African skink, Mabuya buettneri, shows rapid senescence similar to death at mating observed in Salmon and marsupial mouse. Most of the lizards and snakes undergo gradual senescence comparable to the pattern exhibited by a majority of vertebrates. On the other hand, turtles, tortoises and crocodiles continue to grow throughout life and are thus credited with slow or negligible senescence. Evidences and mechanisms of rapid or negligible senescence in reptiles are still fragmentary and unclear. Findings in a few species of lizards (Calotes versicolor) and snakes (Natrix natrix) showing gradual senescence support the concept of commonalities in ageing phenomena in vertebrates. An age-related increase in the stability of collagen and accumulation of altered enzyme molecules, a decrease in metabolism and response to stress-enhanced anti-oxidative defence mechanisms and the nature of responses to hormones, restricted diet and lower environmental temperature corroborate the concept. On the other hand neither the increase in mortality rate and accumulation of lipofuscin nor the reproductive senility have been shown conclusively in ageing reptile populations. It is likely that there are multiple mechanisms of senescence in reptiles. Further studies on selected species from among the 6,000 living species are necessary to unravel the phenomena.     

Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.