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Although the role of reactive oxygen species (ROS) in chronic renal failure (CRF) is not definitely demonstrated, a consistent number of observations has provided evidence for the presence of oxidative stress in uremic patients undergoing maintenance dialysis. In order to investigate this hypothesis further and to understand the role of antioxidant supplementation, peripheral blood lymphocytes were taken from 36 dialysis patients before and after Vitamin E supplementation in a dosage of 600 mg per day (2x300 mg) for 14 weeks and examined in the alkaline Comet assay for DNA strand breakage. The results were also compared with those of 36 controls with comparable age, sex, and smoking habits, and with no history of renal disease. The DNA breakage observed in the lymphocytes of patients before Vitamin E supplementation was significantly higher than in the controls (P<0.001) but a clear protective effect of Vitamin E supplementation were observed after 14 weeks of therapy.

Primary malignant lymphoma of bladder is one of the rarest extranodal site for lymphomas. Less than 100 cases have been reported so far. A history of chronic cystitis has been shown to be a preceding feature in many cases (40%) of primary bladder lymphoma. Most of the cases reported in the literature have a low-grade lymphoma including the subtypes of mucosa-associated lymphoid tissue. The diffuse large cell lymphoma is the most frequent type among the subtypes of high-grade bladder lymphomas. In this report, a case with high-grade primary malignant lymphoma of bladder is reported and the clinical, pathological aspects of diseases are reviewed.

Background: Crush syndrome has been described as extensive muscle damage, leading to acute renal failure. The aim of this study was to evaluate the possible role of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in crush syndrome., Patients and Methods: A total of 17 patients suffering from crush syndrome, 7 patients without crush syndrome and 10 healthy controls were enrolled in the study. Plasma nitrate, TNF-alpha, IL-1 beta levels and biochemical parameters were measured., Results: All patients with crush syndrome demonstrated acute renal failure. Plasma nitrate levels were elevated significantly in the crush syndrome patients compared with patients without crush syndrome (33.5 +/- 20.1 vs. 15.3 +/- 5 micromol/l, p=0.014). There was no significant difference in TNF-alpha and IL-1 beta levels between control and patient groups., Conclusion: Increased plasma nitrate levels in the crush syndrome may be related either to the elevated production of NO or the diminished excretion of nitrate or both., (Copyright 2002 Elsevier Science B.V.)

We describe one patient with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic amyloidosis and nephrotic syndrome. A true nephrotic syndrome has rarely been reported in patients with CD. In the literature, it has been suggested that clinical and laboratory manifestations generally improved after surgical resection of the tumor. However, in our case, clinical and laboratory findings did not regress after operation followed by colchicine therapy.

The aim of this study was the investigation of hepatitis C virus (HCV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), in hemodialysis patients in order to detect HCV infection, and the determination of virus genotypes in HCV positive patients. A total of 94 patients, 44 female and 50 male (mean age: 49 +/- 17 years old), who were included in hemodialysis program between 1987-1999 (0-13 years) in the Hemodialysis Units of Gazi University, School of Medicine and Ankara Etlik Hospital of Social Insurance Society, were enrolled in the study. Anti-HCV was found positive in 41 patients (43.6%), while HCV-RNA was positive in 36 patients (38.3%). Thirty three of the patients were positive for both anti-HCV and HCV-RNA, 8 were anti-HCV positive HCV-RNA negative, and 3 were anti-HCV negative HCV-RNA positive. HCV was genotyped by Restriction Fragment Length Polymorphism (RFLP) method in 36 HCV-RNA positive patients, and 28 yielded genotype 1b, and 8 showed genotype 1a pattern. PCR products from 5'UTR of HCV-RNA isolated from two patients were also sequenced to confirm the results of RFLP study. The rate of anti-HCV and HCV-RNA positivity was detected statistically higher in patients who exposed hemodialysis longer than 24 months, and in hemodialysis patients who had blood transfusion than the other groups. As a result, our findings supported that the periodic follow-up of HCV-RNA, in addition to anti-HCV would be useful for hemodialysis patients, and genotyping of HCV for the epidemiologic data.

The ubiquitous ClC-2 Cl(-) channel is thought to contribute to epithelial Cl(-) secretion, but the distribution of the ClC-2 protein in human epithelia has not been investigated. We have studied the distribution of ClC-2 in adult human and rat intestine and airways by immunoblotting and confocal microscopy. In the rat, ClC-2 was present in the lateral membranes of villus enterocytes and was predominant at the basolateral membranes of luminal colon enterocytes. The expression pattern of ClC-2 in the human intestine differed significantly, because ClC-2 was mainly detected in a supranuclear compartment of colon cells. We found significant expression of ClC-2 at the apex of ciliated cells in both rat and human airways. These results show that the distribution of ClC-2 in airways is consistent with participation of ClC-2 channels in Cl(-) secretion and indicate that extrapolation of results from studies of ClC-2 function in rat intestine to human intestine is not straightforward.

This paper reports the isolation and characterization of a complementary deoxyribonucleic acid clone showing sequence homology with genes coding for the eukaryotic elongation factor 1 gamma (EF-1 gamma). The clone encodes an open reading frame of 404 amino acids corresponding to a deduced molecular mass of 46.2 kDa. Database searches revealed 30-64% sequence identity between the Leishmania infantum EF-1 gamma and several eukaryotic homologues. Southern blot analysis indicated that 2 genes tandemly organized were present in the L. infantum genome. The 3' untranslated regions of these 2 genes differed in size. Southern hybridization and pulsed field gel electrophoresis showed that EF-1 gamma genes are highly conserved among members of the Leishmania genus and must be clustered in a single chromosomal locus.

Objective: A lack of productive HIV-1 infection of Kit225 compared to Jurkat T cells, despite similar levels of CD4 and HIV-1 chemokine co-receptors, was found to correlate with the expression of vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide receptor-1 (VPAC1). We therefore examined a role for this seven-transmembrane G protein-coupled neuroendocrine receptor in modulating HIV-1 infection., Methods: Reverse transcription-PCR was used to show the level of VPAC1 expression in different T-cell lines. A signal-blocking antibody to VPAC1 was used to examine its inhibiting effect on HIV-1 infection. Transfection of VPAC1 cDNA in both sense and anti-sense orientation was used to assess the role of VPAC1 in HIV-1 infection. HIV-1 infection was monitored by gag p24 ELISA using HIV-1IIIB or by luciferase activity using pseudo envelope-typed HXB2-NL4-3-luciferase. Analysis of HIV-1 gag DNA and 2-LTR circles was utilized to examine a possible mechanism for the effect of VPAC1., Results: Using VPAC1 signal blocking antibody, we showed that up to 80% of productive infection with HIV-1IIIB was inhibited. We also demonstrated that HIV-1 gp120 has sequence similarity to the natural ligand for VPAC1 and postulate that it can activate this receptor directly. Transfection of VPAC1 cDNA in the anti-sense orientation resulted in a significant loss, up to 50% of productive infection. In contrast, transfection of cells with VPAC1 in the sense orientation increased the productive infection by more than 15-fold and caused a profound increase in syncytium formation. Furthermore, stimulation of VPAC1 on primary cells facilitated in vitro infection with HIV-1 HXB2-NL4-3. Analysis of HIV-1 gag DNA indicated that VPAC1 does not affect viral entry; however, cells that show negligible expression of VPAC1 may not be productively infected as indicated by a lack of 2-LTR circle formation., Conclusion: We have discovered a cellular receptor, VPAC1, that is a novel and potent facilitator of HIV-1 infection and thus, is a potentially important new target for therapeutic intervention.

The almost ubiquitously expressed ClC-2 chloride channel is activated by hyperpolarization and osmotic cell swelling. Osmotic swelling also activates a different class of outwardly rectifying chloride channels, and several reports point to a link between protein tyrosine phosphorylation and activation of these channels. This study examines the possibility that transforming growth factor-alpha (TGF-alpha) modulates ClC-2 activity in human colonic epithelial (T84) cells. TGF-alpha (0.17 nM) irreversibly inhibited ClC-2 current in nystatin-perforated whole cell patch-clamp experiments, whereas a superimposed reversible activation of the current was observed at 8.3 nM TGF-alpha. Both effects required activation of the intrinsic epidermal growth factor receptor (EGFR) tyrosine kinase activity, of phosphoinositide 3-kinase, and of protein kinase C. With microspectrofluorimetry of the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, TGF-alpha was shown to reversibly alkalinize T84 cells at 8.3 nM but not at 0.17 nM, suggesting that 8.3 nM TGF-alpha-induced alkalinization activates ClC-2 current. This study indicates that ClC-2 channels are targets for EGFR signaling in epithelial cells.

The number of complex cystic fibrosis transmembrane conductance regulator (CFTR) genotypes identified as having double-mutant alleles with two mutations inherited in cis has been growing. We investigated the structure-function relationships of a severe cystic fibrosis (CF)-associated double mutant (R347H-D979A) to evaluate the contribution of each mild mutation to the phenotype. CFTR mutants expressed in HeLa cells were analyzed for protein biosynthesis and Cl(-) channel activity. Our data show that R347H is associated with mild defective Cl(-) channel activity and that the D979A defect leads to misprocessing. The mutant R347H-D979A combines both defects for a dramatic decrease in Cl(-) current. To decipher the molecular mechanism of this phenotype, single and double mutants with different charge combinations at residues 347 and 979 were constructed as charged residues were involved in this complex genotype. These studies revealed that residue 979, located in the third cytoplasmic loop, is critical for CFTR processing and Cl(-) channel activity highlighting the role of charged residues. These results have also important implications for CF, as they show that two mutations in cis can act in concert to alter dramatically CFTR function contributing to the wide phenotypic variability of CF disease.

A case of adenomatoid tumor of the uterus in a 34-year-old patient, who had received a renal transplant and was undergoing immunosuppresive therapy is presented. At surgery, there were a total of eight nodular intramural and subserous masses thought to be leiomyoma nodules, and tumor excision was unusually, hardly performed because the nodules were strictly adherent to the myometrium. All the specimens yielded the same pathological diagnosis - adenomatoid tumor. This case is unusual because of the multiple nodular pattern and its association with the immunocompromised status of the patient. Although adenomatoid tumors have not been shown to recur, we are in doubt in our case, because the uterus is still intact and the immunocompromised status of the patient might have a role in the extensive growth and also in the possibility of recurrence.

Transfusion-associated graft-versus-host disease (TA-GVHD) is usually a fatal outcome of blood transfusion therapy, caused by viable leucocytes contained in the donor blood. Most cases of TA-GVHD occur when less than 4-d-old blood is transfused. We therefore examined the molecular changes that occur during storage that may account for the paucity of TA-GVHD following infusion of older blood. Leucocyte number and viability were essentially unchanged from freshly obtained blood, but the expression of cell-surface lymphocyte activation antigens (CD3, CD4, CD28, CD2, CD45) decreased rapidly within the first 24 h and continued to fall to less than 20% of original levels by d 9 of storage at 4 degrees C. The decrease in CD antigen expression directly correlated with a decreasing ability to induce activation of the T-lymphocyte cellular signal transduction pathway. As a result, cells became less responsive in a mixed lymphocyte culture (MLC) by d 3, with abrogation of the MLC responsiveness by d 5. Donor leucocytes stored for 4 d or less at 4 degrees C were able to partially re-express CD antigens and reconstitute their signalling pathway when placed at 37 degrees C. whereas those stored for more than 4 d were not. These irreversible changes result from a permanent downregulation of donor cell protein synthesis. These findings provide a mechanism to explain the paucity of TA-GVHD following transfusion of blood that is more than 4 d-old. Further study may show that aged blood provides additional assurances for the prevention of TA-GVHD; however, use of aged blood should not replace current protocols using irradiation.

Cystic fibrosis (CF) is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR), a transmembrane protein that acts as a cAMP-regulated chloride channel The disease is characterized by inflammation but the relationship between inflammation, abnormal transepithelial ion transport, and the clinical manifestations of CF are uncertain. The present study was undertaken to determine whether three nonsteroidal anti-inflammatory drugs (NSAIDs) (aspirin, ibuprofen, and indomethacin) modulate CFTR gene expression in T-84 cells. Treatment with NSAIDs reduced CFTR transcripts, and decreased cAMP-stimulated anion fluxes, an index of CFTR function. However, the two phenomena occurred at different concentrations of both drugs. The results indicate that NSAIDs can regulate both CFTR gene expression and the function of CFTR-related chloride transport, and suggest that NSAIDs act via multiple transduction pathways.

Real-time ultrasonography (US) of the gastric antrum after ingestion of a mixed solid-liquid meal was performed in 60 patients (median age, 8.2 years; range, 3-17) being investigated for symptoms suggesting upper intestinal dysfunction (vomiting, regurgitation, abdominal pain, early satiety, and anorexia) and in 13 controls (median age, 5 years; range, 3-15). The diagnostic work-up allowed identification of 14 patients with esophagitis (group A) and 26 with Helicobacter pylori (HP) gastritis (group B); median age in group A was 9 years (range, 3-15) and in group B was 9.5 years (range, 3-17). Group A patients had significantly more prolonged gastric-emptying times (median, 180 min; range, 110-270) than did controls (median, 150 min; range, 110-180; p < 0.01); however, group A times were not significantly longer than those of group B patients (median, 160 min; range, 90-265). In the remaining 20 patients (group C; median age, 7.1 years; range, 3-15) without a specific diagnosis, markedly delayed gastric emptying was detected (median, 237 min; range, 165-270; p < 0.01 vs. group B patients and vs. controls; p < 0.05 vs. group A patients); in this group, GI manometry revealed findings of deranged motility of the gut. Distension of the antral area (percentage of increase vs. baseline values) 60 and 90 min after feeding was higher in group C (60 min: median, 185%; range, 70-614%; 90 min: median, 175%; range, 60-400%) than in both controls (60 min: median, 80%; range 26-148%; 90 min: median 90%; range 20-253%; p < 0.01) and HP patients (60 min: median, 120%; range, 35-311%; 90 min: median, 98%; range, 23-400%; p < 0.05); there was no significant difference versus esophagitis patients. The latter differed from controls only for the 60-min postfeeding antral distension (p < 0.01), whereas HP patients did not differ from controls. In group C patients, symptomatic dyspeptic score correlated with both 60- and 90-min fed antral distension (r = 0.61 and r = 0.64, respectively; p < 0.05), but no correlation was found with gastric-emptying time. In group A patients, histologic score of esophagitis correlated with 60-min postfeeding antral distension (r = 0.56; p < 0.05), whereas poor correlation was found with 90-min postfeeding antral distension and with gastric-emptying time. However, the latter significantly correlated with 90-min fed antral distension in esophagitis patients (r = 0.70; p < 0.01). We conclude that US imaging of the antral area of the stomach reveals abnormalities of gastric motility in most children referred for dyspeptic symptoms; this technique should be included among the investigative tools in the diagnostic approach to these patients.

1. The effect of erythropoietin and some trace elements on superoxide dismutase (SOD) activity of dialysis patients have been studied. 2. SOD activity of dialysis patients was found to be decreased. 3. The effect of erythropoietin on SOD activity was not found in vitro. 4. Plasma and erythrocyte aluminum increased in dialysis patients, but no significant change in plasma copper was found. 5. Plasma zinc levels of dialysis patients were found to be decreased. 6. These results suggest that inhibition of erythrocyte SOD activity of dialysis patients may contribute to their anemia.