Subcellular localization and some biochemical properties of the flavivirus Kunjin nonstructural proteins NS2A and NS4A

1. The mean incidence of deaths from ascites in the UK in 1993 was 1.4% (0.7% in 1991 and 0.9% in 1992) and 0.8% from sudden death syndrome (SDS). In total, the economic loss to the UK Broiler Industry in 1993 as a result of these 2 conditions was 24 Pounds M. 2. Clear geographical differences emerged in the occurrence of ascites, with, not only the lowest incidences being observed in Northern Ireland, but also the peak of the mortality from ascites occurring much later in the rearing cycle than in other regions on the mainland. 3. In all regions the incidence of SDS was lower than that of ascites but the reason for this disparity remains to be established. 4. Some of the variables associated with the road transportation of day-old chicks from the hatchery to the farm appeared to influence the incidence of ascites. These included distance or time travelled, stocking density, internal lorry temperature and the length of time the lorry was heated before transport as well as the time the shed was heated before chick arrival. Temperature was also an important factor during growth (brooding and finishing). 5. Negative pressure-powered ventilation was preferred in most organisations but more ascites was seen with positive pressure ventilation. However, the lowest incidence of ascites occurred with natural ventilation. There was more ascites relative to shed orientation when the wind direction was from the west compared to the east. 6. This survey identifies the extent of the problem of broiler ascites in the UK and also highlights the importance of good management control of day-old chicks, not only following placement, but even before their arrival on the farm.     

Prognostic value of plasma fibrinogen concentration in patients with unstable angina and non-Q-wave myocardial infarction (TIMI IIIB Trial)

The records of 60 patients with gallbladder carcinoma (GBC) operatively treated between 1966 and 1993 at Belen Hospital, Trujillo, Perú, were retrospectively reviewed. The ratio of men to women was 1:7.5 and the average of age was 61 years. The accuracy of ultrasonography and oral cholecystograms for the specific diagnosis was 21% and 0% respectively. The surgical procedures employed were simple cholecystectomy (n = 56), right hepatectomy (n = 2). Whipple operation (n = 1) and extended cholecystectomy (n = 1), and our resectability rate for GBC is currently 50%. Simple cholecystectomy was a potentially curative surgical procedure in patients with in situ cancer (stage O) and early GBC (stage 1). In hospital mortality was 11.6% and 5-year survival rate for the total series was 15%. Gallstones were present in 95% of patients and most tumors (58%) had grown by diffuse infiltration or were associated with empyema (38%). Tumor stage, depth of invasion, tumor grade histologic type were all predictive of patient outcome. This report reinforces the difficulty in diagnosis and the poor prognosis for patients with GBC. We hold the view that more radical approaches for invasive cancers will enhance the operative results.     

Dose of hemodialysis and survival: differences by race and sex

CONTEXT: Although blacks receive lower doses of hemodialysis than whites, their survival when receiving dialysis treatment is better than that for whites. Previous studies of the relationship between the dose of dialysis and patient survival have not controlled for differences in patient characteristics. OBJECTIVE: To examine the association of mortality with the dose of hemodialysis for clusters of patients categorized by race and sex. DESIGN: Retrospective analysis of laboratory data and mortality outcomes from 1994, using a national database of hemodialysis patients. PATIENTS: A total of 18144 black and white patients receiving hemodialysis 3 times weekly who either lived the entire year receiving hemodialysis or died. MAIN OUTCOME MEASURES: The fractional reduction of urea in a single dialysis session as the measured hemodialysis dose (urea reduction ratio [URR]) after controlling for race, sex, age, and diabetes mellitus. Mortality was determined by strata of URRs and albumin and creatinine levels. RESULTS: Across all age categories, blacks had lower URRs than whites, and men had lower URRs than women. In an age-adjusted model for evaluating interactions among URRs, race, sex, and diabetes, the association of URR with mortality risk was weak among blacks, particularly black men. After adjustment for age and diabetes, death probability curves were most steep for white women with URR values less than 60%. The death probability curves were least steep for black men. There was no meaningful difference between death probability and albumin or creatinine concentration among the race by sex clusters. CONCLUSION: Using URR, the usual measure of hemodialysis dose, the assumption that the association between dialysis dose and survival is uniform across demographic groups appears incorrect. Comparisons of the quality of dialysis patient care should not rely on URR alone to predict patient survival.     

G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator

The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in PEL and stimulates signalling pathways linked to cell proliferation in a constitutive (agonist-independent) way. Here we show that signalling by this KSHV G-protein-coupled receptor leads to cell transformation and tumorigenicity, and induces a switch to an angiogenic phenotype mediated by vascular endothelial growth factor, an angiogenesis and Kaposi's-spindle-cell growth factor. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines that are angiogenesis activators and mitogens for Kaposi's sarcoma cells and B cells. We conclude that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in KSHV-mediated oncogenesis.     

Clarification of the relationship between free radical spin trapping and carbon tetrachloride metabolism in microsomal systems

It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl radical adduct (PBN/.CCl3) is metabolized to either the C-phenyl-N-tert-butylnitrone/carbon dioxide anion radical adduct (PBN/.CO2-) or the glutathione (GSH) and CCl4-dependent PBN radical adduct (PBN/[GSH-.CCl3]). Inclusion of PBN/.CCl3 in microsomal incubations containing GSH, nicotinamide adenine dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH-.CCl3] or PBN/.CO2- radical adducts. Microsomes alone or with GSH had no effect on the PBN/.CCl3 radical adduct. Addition of NADPH to a microsomal system containing PBN/.CCl3 presumably reduced the radical adduct to its ESR-silent hydroxylamine because no ESR signal was observed. The Folch extract of this system produced an ESR spectrum that was a composite of two radicals, one of which had hyperfine coupling constants identical to those of PBN/.CCl3. We conclude that PBN/.CCl3 is not metabolized into either PBN/[GSH-.CCl3] or PBN/.CO2- in microsomal systems.