Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Validity of Electrode Placement at Fpz to Detect Alpha Wave

Abstract: The possibility on placing electrodes at Fpz-A₂ instead of C₃-A₂ was investigated to obtain a more stable configuration avoiding obstruction by the hair. Our original system of alpha wave detection by a microcomputer was used, and a total of 22 all-night hypnograms of five healthy young students waa recorded. Pearson's moment correlation coefficients of alpha wave % between the two positions were 0.780–0.948. Except for one subject, alpha wave % taken at Fpz-A₂ tended to be 3–5% lower than that at C₃-A₂. The above analysis indicates that using EEG electrode position of Fpz-A₂ is valid and useful as a stable electrode configuration for a long-time monitoring.     

EFFECTS OF SARAFOTOXIN S6c ON RENAL HAEMODYNAMICS AND URINE FORMATION IN ANAESTHETIZED DOGS

1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor agonist, on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal blood flow (RBF), with no change in systemic blood pressure and heart rate; RBF then decreased gradually to below the basal value. There were significant and dose-dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, whereas urinary excretion of sodium and glomerular filtration rate (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, N0₂^? and N0₃^? (UNO*V). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and iV^G-nitro-L-arginine (NOARG; 40 (jig/kg per min), a NO synthase inhibitor, the renal vasodilator effect of S6c was abolished and marked reductions in RBF and GFR were observed. The S6c-induced diuretic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNO_xV at the basal level and the administration of S6c did not increase UNOxV. 4. These results suggest that an intrarenal arterial infusion of S6c enhances the production of NO in the kidney and that this enhancement contributes to the peptide-induced renal vasodilation. In contrast, it is unlikely that S6c-induced water diuresis is related to NO production stimulated by this peptide.     

A case of thymoma with thymic cyst]

A 43-year-old man was pointed out an abnormal shadow on chest X-ray film. Chest CT showed a solid mass and a cyst at anterior superior mediastinum. Operation revealed a capsulated thymoma and a multilocular thymic cyst. PTH and CA19-9 level in the cystic fluid was elevated. Histological examination demonstrated the clear separation of the mixed type thymoma and the thymic cyst. There were few reports for cases of thymoma with a thymic cyst.     

Experimental study of spinal cord compression by epidural tumors using electron probe X-ray microanalysis and confocal laser scanning microscopy

Changes in the nerve fibers of the spinal cord were studied in rat experimental epidural tumor models. Light microscopy showed demyelinization in all with rats paraparesis and paraplegia. Cross-sectional views of nerve fibers stained with 3,3dipentyloxacarbo-cyanine iodide, obtained by confocal laser scanning microscopy, showed distorted, shrunken fibers with a low fluorescence intensity. Changes in the electrolyte contents of nerve fibers were studied by electron probe X-ray microanalysis. The K concentration in axons and the myelin sheath was increased in the paraparesis group, but was decreased in the paraplegia group. These findings suggest that, in the paraparesis group, compression of the spinal cord damaged cell membrane channels, which subsequently caused an increase in intracellular K, a decline in the action potential, and low-intensity fluorescence of nerve fibers. On the other hand, in the paraplegia group, destruction of cell membranes caused a decrease in intracellular K until it approached the extracellular level. This reduced both the action potential and the fluorescence intensity. As Ca and Mg concentrations in both axons and the myelin sheath increased in relation to the severity of neurologic damage, it appears that these electrolytes may also play an important role in damage to nerve fibers.     

Screening of H-ras Gene Point Mutations in 50 Cases of Bladder Carcinoma

Background Mutation converts the H-ras gene into an activated oncogene in about 10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for activation. A simple and accurate method to detect point mutations in these codons may be clinically useful for early diagnosis of bladder cancer.
Methods Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine.
Results Definite or possible point mutations were found in 6 (1 2%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample.
Conclusion The prevalence of point mutations at codon 1 2 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer.     

Beta 2-microglobulin synthesis of mononuclear cells in chronic dialysis patients.

Beta 2 microglobulin (B2M) has been identified as a major component of amyloid deposits. This study was designed to determine whether changes occur in the synthesis of B2M in dialysis patients. Mononuclear cells (MNC) were isolated in peripheral blood from healthy volunteers, patients on hemodialysis (HD) and on continuous ambulatory peritoneal dialysis (CAPD). MNC were cultured in a medium of RPMI 1640 with or without interleukins IL-1, IL-2 or interferon INF-r. B2M in the cultured cells and supernatant was measured by enzyme immunoassay. IL-2 or INF-r stimulated B2M synthesis was significantly lower (25%) in patients on HD than in normal controls regardless of the type of dialysis membranes used, with no change in basal B2M synthesis. No differences were detected between healthy volunteers and CAPD patients. Preincubation of MNC with complement--activating or non-complement--activating membrane had no influence on B2M synthesis. The basal B2M synthesis of MNC significantly increased after a 4-hour HD regardless of the membranes used, and IL-2 and IFN-r stimulated synthesis were both essentially the same before and after HD. It was thus concluded that maximum capacity for B2M synthesis of MNC decreases in hemodialysis patients. This low responsiveness of MNC may be partially the cause for the reduction in cell-mediated immune response in HD patients.     

Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis.

BACKGROUND--Anticholinergic bronchodilator drugs improve lung function in chronic bronchitis but less is known of their effects on the volume and physical properties of sputum in conditions associated with excessive airway secretions. This study examines the effects of the regular use of oxitropium bromide in such patients. METHODS--The study was conducted in a parallel, double blind, placebo controlled fashion. Patients were divided into two groups: the first group (n = 17) received oxitropium bromide from a metered dose inhaler (two puffs three times daily; 100 micrograms/puff) for eight weeks, and the second group (n = 16) received placebo. Lung function was measured as forced expiratory volume in one second (FEV1) and vital capacity. In evaluating airway secretion, daily amount of expectorated sputum, percentage solid composition, viscoelastic properties including elastic modulus and dynamic viscosity, and sputum microbiology were determined. RESULTS--Oxitropium bromide increased FEV1 and decreased the mean (SE) sputum production from 61(4) to 42(3) g/day after treatment, whereas placebo had no effect. Bacterial density and sputum flora were unchanged, but solid composition and elastic modulus increased from 2.52(0.43)% to 3.12(0.34)%, and 68(12) dyne/cm2, respectively, in the group taking oxitropium bromide. CONCLUSIONS--Regular treatment with oxitropium bromide not only improves airflow limitation but also reduces sputum production, probably through the inhibition of both mucus secretion and water transport, the latter component being predominant.     

Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver.

Organic anion transporter 2 (Oat2 [SLC22A7]) is a multispecific organic anion transporter. Although several substrates of human Oat2 (hOat2) have been elucidated, a possible involvement of hOat2 in drug interaction is less defined. The purpose of this study was to investigate the interaction of theophylline with erythromycin mediated by hOat2 using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, hOat2 mediated the transport of theophylline and erythromycin. The finding indicates that the two compounds are novel substrates for hOat2. The apparent K(m) values for the uptake of hOat2 that mediated the transport of theophylline and erythromycin were 12.6 muM and 18.5 muM, respectively. The hOat2-mediated uptake of [(14)C]theophylline and [(14)C]erythromycin was cis-inhibited by adding erythromycin and theophylline, respectively. Our present findings suggest that hOat2 may, at least in part, be involved in the theophylline-erythromycin interaction in the human liver.