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Bovine herpesvirus 1 (BoHV-1)-encoded UL49.5 (a homologue of herpesvirus glycoprotein N) can combine different functions, regulated by complex formation with viral glycoprotein M (gM). We aimed to identify the mechanisms governing the immunomodulatory activity of BoHV-1 UL49.5. In this study, we addressed the impact of gM/UL49.5-specific regions on heterodimer formation, folding and trafficking from the endoplasmic reticulum (ER) to the trans-Golgi network (TGN) - events previously found to be responsible for abrogation of the UL49.5-mediated inhibition of the transporter associated with antigen processing (TAP). We first established, using viral mutants, that no other viral protein could efficiently compensate for the chaperone function of UL49.5 within the complex. The cytoplasmic tail of gM, containing putative trafficking signals, was dispensable either for ER retention of gM or for the release of the complex. We constructed cell lines with stable co-expression of BoHV-1 gM with chimeric UL49.5 variants, composed of the BoHV-1 N-terminal domain fused to the transmembrane region (TM) from UL49.5 of varicella-zoster virus or TM and the cytoplasmic tail of influenza virus haemagglutinin. Those membrane-anchored N-terminal domains of UL49.5 were sufficient to form a complex, yet gM/UL49.5 folding and ER-TGN trafficking could be affected by the UL49.5 TM sequence. Finally, we found that leucine substitutions in putative glycine zipper motifs within TM helices of gM resulted in strong reduction of complex formation and decreased ability of gM to interfere with UL49.5-mediated major histocompatibility class I downregulation. These findings highlight the importance of gM/UL49.5 transmembrane domains for the biology of this conserved herpesvirus protein complex.

RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway that subjects two nonrelated but broadly evolutionarily conserved translational regulators (CPB-3/CPEB and GLD-1/STAR) to proteosomal degradation in Caenorhabditis elegans germ cells at the transition from pachytene to diplotene of meiotic prophase. Both RBPs are recognized by the same ubiquitin ligase complex, containing the molecular scaffold Cullin-1 and the tumor suppressor SEL-10/FBXW7 as its substrate recognition subunit. Destabilization of either RBP through this Skp, Cullin, F-box-containing complex (SCF) ubiquitin ligase appears to loosen its negative control over established target mRNAs, and presumably depends on a prior phosphorylation of CPB-3 and GLD-1 by MAPK (MPK-1), whose activity increases in mid- to late pachytene to promote meiotic progression and oocyte differentiation. Thus, we propose that the orchestrated degradation of RBPs via MAPK-signaling cascades during germ cell development may act to synchronize meiotic with sexual differentiation gene expression changes., Competing Interests: The authors declare no conflict of interest.

Lipid disorders are one of the known metabolic changes associated with chronic renal failure (CRF) [1, 2]. They are present as: hypertriglyceridemia--existed in 60% of CRF patients and hypercholesterolemia observed in 20-30% of people with this syndrome. These disorders, what was shown also in our own studies, are existing in different intensity in patients treated with maintenance haemodialysis [3], peritoneal dialysis [4] and after renal transplantation as well [5]. Mechanism of hypertriglyceridemia, despite over thirty years of studies, is still not finally elucidated. The opinion that it is a result of impaired triglyceride removal (due to decreased activities of both lipoprotein and hepatic lipases) is well documented, however the role of lipogenesis in its development is obscure [6, 7]. The reports concerning this problem contain contradictory data. In our studies performed several years ago we have shown that lipogenesis rate in white adipose tissue of uremic rats is significantly augmented [8, 9, 10] due to activation of free fatty acid synthase. Therefore, recently we paid once again our attention on the activity of this lipogenesis rate limiting enzyme responsible for the long term regulation. We measured its activity, protein abundance and mRNA level in liver and epididymal white adipose tissue of rats with surgically induced renal failure (two-stage subtotal nephrectomy). The results support the thesis that lipogenesis takes a part in a hypertriglyceridemia found in renal failure. There have been observed a significant increase in plasma triglyceride and VLDL concentrations in uremic animals and it was associated with the increase of FAS activity, FAS protein abundance and FAS mRNA. The results were similar in both studied tissues. Moreover, there have been also observed the increased activities of malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. All these enzymes participate in NADPH production, which is a necessary substrate for fatty acid biosynthesis [11, 12, 13]. Concluding, it appears that the rise in plasma triglyceride and VLDL concentrations observed in CRF rats is not only the result of increased liver and white adipose tissue lipogenesis rate. One has to remember, that these date are strictly original and enabling to elucidation further pathogenesis of hyperlipidemia in CRF. In the second set of experiments performed also in rats with experimentally induced CRF we have found that hypercholesterolemia observed in those animals is dependent on the significant activation of cholesterol synthase, induced by increased production of this enzyme (increment of protein abundance and synthase mRNA [14, 15]. Simultaneously, we have performed original studies on the diurnal rhythm of cholesterologenesis, showing that activity of this process is significantly augmented during whole twenty four hours [15]. Summarizing, one have to underline that our observations have important impact to the elucidation of lipid disturbances pathomechanism. Nevertheless further studies are necessary to establish how experimental data are corresponding with human pathology.

Though it is said that some immunosuppressive agents are implicated in the development of hyperlipidemia in kidney recipients, this subject is still controversial. Main plasma lipid parameters, as well as apolipoproteins A1 and B were measured periodically in 39 kidney first cadaveric, nondiabetic recipients during 24 months of clinic follow-up after transplantation. Standard triple immunosuppressive therapy: prednisone + cyclosporine + azathioprine was administrated from the beginning. After the second year of kidney transplantation, a significant reduction refers to values of TC, LDL, apo A1 and apo B. In the group with antirejection - methylprednisolone therapy, and without it only TG in the 24th month and apo B in the 1st month were statistically lower in the latter group (both p < 0.05). In the multiple regression test, a linear coincidence was observed between apo A1, apo B and prednisone cumulative dosage after the 1st month, TG and cyclosporine in the 6th month and LDL and cyclosporine in the 12th month after transplantation. It appears that steroids had an impact on lipids directly after transplantation, while cyclosporine did so thereafter., (Copyright 2000 S. Karger AG, Basel)

Background: There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane., Methods: 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate)., Findings: At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension)., Interpretation: There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

Unlabelled: Bacterial endocarditis (BE) is one of the most severe complications of hemodialysis (HD). The aim of the study was to analyse frequency and severity of BE in patients treated with HD in our dialysis unit. During the period 1969-1993276 patients were treated with HD in Gdańsk. In 23 cases (9F, 14M) HD treatment was complicated with BE. Patients were divided into two groups on basis of diagnostic criteria: I-13 patients (5F,8M) with BE diagnosed by means of clinical picture and positive blood culture.; II-10 (4F, 10M) with diagnosis additionally confirmed by echocardiography. In patients from group I BE was observed more often during the first 2 years of HD. In group II during 3-5 years of dialysis therapy, gram negative microorganisms were the most frequent etiological factors. The mean period of antibiotic therapy was 35 days. In all patients from group II changes in the bicuspid valve, in 60% of them additionally in aortic valve and in one patient also in the tricuspid valve were observed. In five patients changes in the parietal endocardium were also present. Development of organic valvular changes was observed in nine patients. Seven of 22 patients died during the acute phase of BE and two others from complications connected with BE. The longest survival of patients after BE was over 10 years., Conclusions: 1. The threat of BE in patients treated with HD decreased between 1987 and 1993 in comparison with the initial period of our HD station operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyslipidemia is one of the first metabolic dysfunction observed among patients with end stage renal disease. It can also induce acceleration of renal tissue damage. Kidney transplantation may cause recovery of some dysfunction in lipid metabolism while influencing deterioration of others. The aim of this study was to monitor dynamics of basic lipid parameters in the first year after kidney transplantation. The sample included 25 patients (9W, 16M), aged 18-59, avg. 36. We have measured concentration of the following parameters in blood serum: triglycerides (TG), total cholesterol (CH-C) and apolipoprotein B (Apo B). Simultaneously, functions of transplanted kidney were tested with use of routine methods. The immunosuppressive treatment of patients followed the scheme: cyclosporine + prednisolone + azathioprine. The treatment influence on lipid disorders was measured by relevant correlation coefficients. The obtained results point to the observation that in the first year after kidney transplantation the TG concentration gradually decreases, with simultaneous continuous increase of CH-C concentration, mainly due to LDL concentration increase. No influence of immunosuppressive treatment on lipid parameters was observed. However, lipid dysfunction, especially TG, correlated with kidney function.

Recent observations indicate quite high incidence of tuberculosis (tbc) in haemodialysis population. But there are really only few reports of arthritis the infection. Mycobacterial process in this location may imitate many other pathological states. Our report refers to 45-year-old man with right knee the infection and the peri-arthritic tissue, which developed after 8 years of renal replacement treatment. No evidence of the was noted before. Chronic pain, swelling and instability of the knee led finally to surgical extraction of diagnostic material, which contributed to final diagnosis. We consider this report to be important because of only few reported cases of the arthritis. Additionally unnecessary delay in commencement of treatment may lead to bone destruction.