Beta 2-microglobulin as an indicator of interstitial cell infiltration in IgA nephropathy.
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Biomedical subjects
Publications and source records attributed to K Nitta.
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In previous studies we investigated the metabolism of tin compounds in rats and hamsters following single oral treatments with triphenyltin. The objective of this study was to provide information on the metabolism of triphenyltin in hamsters subchronically treated with dietary triphenyltin for 180 d. Groups were fed diets containing 3 different triphenyltin concentrations: 1.28, 28.82 or 54.77 ppm. The 28.82 and 54.77 ppm groups gained less body weight than the control and 1.28 ppm groups. However, none of the animals showed characteristic symptoms. We detected triphenyltin and its metabolites in the tissues of dosed hamsters. Highest tin concentrations were in livers and kidneys, as diphenyltin and inorganic tin respectively; no significant amounts of triphenyltin were found. Triphenyltin was metabolized relatively rapidly in the hamsters. There was more tin relative to the administered triphenyltin in the livers of the low dietary group compared to the high dietary triphenyltin group. This suggests that low concentrations of triphenyltin are easily absorbed from the gastrointestinal tract. While we previously demonstrated that acutely dosed triphenyltin produced marked hyperglycemia in hamsters, this was not found in the hamsters repeatedly dosed with dietary triphenyltin in the present study.
We reported our experience with a case of AFP producing gastric cancer with liver metastasis successfully treated with FEP therapy by continuous daily venous infusion of 5-FU and low-dose CDDP. A 59-year-old male was diagnosed with liver metastasis 2 months after partial gastrectomy of gastric cancer and then admitted. The patient received five courses of 24-hour continuous infusion of CDDP (5 mg/day, on day 1, 2, 3, 4, 5) and 5-FU (250 mg/day, on day 1, 3, 5) and bolus infusion of Epirubicin (10 mg/day, on day 3). No remarkable side effect was encountered. Complete response at the liver metastasis was observed by CT scan. Serum AFP level was down from 614 ng/ml to the normal range of 0.5 ng/ml after the therapy. The patient has been well for 10 months with complete remission.
The present study was designed to investigate the role of intercellular adhesion molecule (ICAM)-1 in the interaction between glomerular endothelial cells (GEN) and granulocytes. Expression of ICAM-1 was promoted after stimulation with tumor necrosis factor (TNF)-alpha. This effect was dose- and time-dependent. Granulocytes attached to GEN in accordance with the increased expression of ICAM-1 on the cells stimulated with TNF-alpha. In addition, the adhesion of granulocytes to activated GEN with TNF-alpha stimulated specific [51Cr] release from the monolayers. Furthermore, monoclonal antibodies to TNF-alpha dose-dependently inhibited the adhesion of granulocytes to activated GEN. In summary, ICAM-1 is related to the glomerular endothelial cell injury induced by granulocytes activated with TNF-alpha, suggesting that ICAM-1 may play a role in the initiation of certain types of glomerulonephritis with granulocyte infiltration.
The severe hyperacute rejection in pig-to-dog renal xenotransplantation is mainly caused by xenoreactive natural antibodies (NAb). Organ absorption (ex vivo perfusion of spleen and kidney of donor species) was performed to remove xenoreactive NAb. A pig-to-dog renal transplantation model was used for discordant combination xenografting. The experimental animals were divided into 4 groups: group 1, control; group 2, recipients splenectomized prior to renal xenografting; group 3, splenectomy along with ex vivo spleen xenoreactive NAb absorption; and group 4, splenectomy along with ex vivo spleen and kidney xenoreactive NAb absorption. After the pretransplant treatment of the recipients, the serum titer of anti-pig lymphocytotoxic antibodies, hemagglutination antibodies, IgG and IgM were determined. Postoperative assessment was made of urine output and the rejected kidneys examined histopathologically. The serum titer of all measured antibodies markedly decreased after sequential pig spleen/kidney absorption. Total urine output was significantly larger in group 4 than in group 1. The histopathological findings revealed that the severity of hyperacute rejection was markedly decreased in groups 3 and 4 compared to groups 1 and 2. These results indicate that ex vivo absorption using donor spleen and kidney is useful in preoperative removal of xenoreactive NAb and prolongs renal xenograft survival.
These experiments were performed in an attempt to determine whether chronic stimulation of glomerular endothelial cells with recombinant human erythropoietin would alter mesangial cell proliferation. Glomerular endothelial cells in culture incubated with various concentrations of erythropoietin for up to 4 days exhibited dose-dependent endothelin-1 production. Moreover, the conditioned medium from erythropoietin-stimulated glomerular endothelial cells enhanced [3H]thymidine incorporation into mesangial cells. This enhancement was significantly attenuated in the presence of a endothelin A receptor antagonist, BQ-123. These results suggest that endothelin-1 mediates erythropoietin-stimulated glomerular endothelial cell-dependent mesangial cell proliferation, resulting in the progression of glomerulonephritis.
In the Drosophila CNS, both neurons and glial are derived from neuroblasts. We have identified a gene, glial cells missing (gcm), that encodes a novel nuclear protein expressed transiently in early glial cells. Its mutation causes presumptive glial cells to differentiate into neurons, whereas its ectopic expression forces virtually all CNS cells to become glial cells. Thus, gcm functions as a binary switch that turns on glial fate while inhibiting default neuronal fate of the neuroblasts and their progeny. Similar results are also obtained in the PNS. Analyses of the mutant revealed that "pioneer neurons" can find correct pathways without glial cells and that neurons and glia have a common molecular basis for individual identity.
Fulminant hepatic failure is usually fatal without liver transplantation; however, orthotopic liver transportation is often difficult to perform due to the high risk of coagulopathy and the development of multiple organ failure. Auxiliary heterotopic partial liver transplantation (APLT), However, has the potential to provide an effective hepatic support system considering that the host liver is left in situ and the surgical procedure is less invasive. In this report, we describe the beneficial effects of performing 60% APLT on the hepatic function and survival of pigs with acute hepatic failure induced by hepatic artery ligation. The pigs were divided into a control group of nine animals (group 1) that had portal vein and hepatic artery ligation with a side-to-side portacaval shunt, and an APLT group of seven animals (group 2) that had portal vein and hepatic artery ligation with APLT. The two left lateral lobes of the donor liver were resected, reducing the liver weight to about 60%, and the graft was placed in the right subhepatic space. No deaths occurred intraoperatively. In group 1, eight pigs died of massive liver necrosis within 48 h and one died between 48 and 72 h (median survival 23 h). In group 2, two pigs died within 72 h due to preservation or anesthetic problems, but five survived for more than 3 days (median survival 13.4 days), with a significant difference between the two groups (P < 0.05). One animal was killed 30 days after APLT and excellent graft function was demonstrated by the synthesis of clotting factors, ammonia detoxification, and glucohomeostasis. Moreover, evidence of hepatic regeneration was found in the transplanted livers.(ABSTRACT TRUNCATED AT 250 WORDS)
We conducted these experiments to determine whether glomerular endothelial cells (GEN) may play a role in the regulation of glomerular mesangial cells (GMC) growth. When GMC were separately co-cultured with GEN for 24 h, [3H]thymidine incorporation into GMC increased by 22%. In addition, when GMC were co-cultured with GEN for 4 days, the GMC count increased statistically. Conditioned medium (CM) was obtained from confluent GEN monolayers and tested for its effect on GMC growth. When CM was mixed with RPMI 1640 medium containing fetal calf serum (final concentration: 10%), GMC growth was potentiated in a dose-dependent manner. This stimulatory effect of CM from GEN cultures was inhibited by the addition of anti-human platelet-derived growth factor (PDGF) antibody. However, antibodies against interleukin 1-beta, tumor necrosis factor-alpha and endothelin-1 did not affect the stimulatory effect of CM. Moreover, the modulator contained in CM was stable at 100 degrees C, and pH 2.5 at 22 degrees C for 30 min. When treated with 2 mM mercaptoethanol, this activity was almost completely lost. These findings suggest that GEN promote GMC growth in co-culture systems, without direct contact, by means of a PDGF-like substance.
We evaluated acute effects of prostaglandin E1 encapsulated in lipid microspheres (lipo-PGE1), in 14 type 2 diabetic patients with neuropathy. Nerve conduction velocity (NCV), vibratory threshold (VT), skin temperature and subjective symptoms were evaluated for 24 hours after a single drip infusion of lipo-PGE1. In 6 of the 14 patients, the decrease in VT (P < 0.05) more than 50% measured by an SMV-5 vibrometer was observed at 6 hours after the infusion (responders). Subjective symptoms were improved (P < 0.05) in 5 of the 6 responders, whereas it improved in only 1 of the 8 patients who had no change in VT (nonresponders). NCV did not change (P > 0.05) either in the responders or in the nonresponders by the infusion. The responders had less impairment in VT and milder retinopathy and nephropathy than the nonresponders (P < 0.05). Our results demonstrate that vibratory sensation and subjective symptoms can be improved by a single infusion of lipo-PGE1 in type 2 diabetic patients with mild neuropathy.
Recognizing the importance and fertility of the extra vehicular activity technologies in future space development and utilization, some related research activities have been conducted in Japan, though it has not committed itself to developing its own manned space flight capability. The purpose of this paper is to introduce and evaluate these EVA-related activities and to indicate the next step for Japan to get into the era of manned space activities including EVA in reality.
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The high-affinity calcium-binding sites of bovine and human alpha-lactalbumin as well as equine lysozyme were analyzed by 113Cd NMR spectroscopy. In the case of equine lysozyme, the addition of isotopically enriched 113Cd2+ results in a signal at delta = -75.9 ppm corresponding to the metal ion bound to the lone Ca(2+)-binding site of the protein. A peak at virtually the identical resonance position (delta = -77.1 ppm) was observed in the analogous experiment with bovine alpha-lactalbumin. In addition, a signal upfield of these (delta = -94.7 ppm) was observed for 113Cd(2+)-substituted human alpha-lactalbumin. The chemical shifts of these proteins are in the vicinity of those reported for other Ca(2+)-binding proteins. The field dependence of the 113Cd signals for all three proteins and bovine calmodulin were compared. At each field, the 113Cd signal linewidths for the alpha-lactalbumins and the lysozyme are somewhat broader than those observed for the EF-hand protein. In addition, the 113Cd linewidths for the lactalbumins and the lysozyme, especially bovine alpha-lactalbumin, increase dramatically with the square of the magnetic field strength, indicative of the presence of nuclear relaxation via chemical shift anisotropy and chemical exchange. The protein-bound 113Cd signals for the alpha-lactalbumins are also markedly affected by changes in the amount of K+ present, since Cd2+ and K+ can compete for occupation of the high-affinity Ca(2+)-site. Their linewidths also to some extent depend on the concentration of the protein itself.(ABSTRACT TRUNCATED AT 250 WORDS)
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To investigate the physiological role of a kidney-specific chloride channel (ClC-K1), we sought to determine its exact localization by immunohistochemistry and its functional regulation using Xenopus oocyte expression system. The antiserum specifically recognized a 70-kD protein in SDS-PAGE of membrane protein from rat inner medulla and an in vitro translated ClC-K1 protein. Immunohistochemistry revealed that ClC-K1 was exclusively localized to the thin limb of Henle's loop in rat inner medulla. In comparison with the immunostaining with anti-aquaporin-CHIP antibody that only stains the descending thin limb of Henle's loop (tDL), ClC-K1 was found to be localized only in the ascending limb (tAL) which has the highest chloride permeability among nephron segments. Immunoelectron microscopy confirmed that the staining of ClC-K1 in tAL was observed in the region of both apical and basolateral plasma membranes. Expressed chloride current in Xenopus oocytes by ClC-K1 cRNA was regulated by extracellular pH and extracellular calcium. Furosemide inhibited the expressed current (Ki = 100 microM), whereas N-ethyl-maleimide stimulated the current. These functional characteristics were consistent with the in vitro perfusion studies of chloride transport in tAL. The localization and the functional characteristics described here indicate that ClC-K1 is responsible for the transepithelial chloride transport in tAL.
Adhesion of lymphocytes to glomerular endothelial cells might be a critical step in the development of acute and chronic glomerulonephritis. The protective effect of anti-CD11a and anti-intercellular adhesion molecule (ICAM-1) antibodies on the cytotoxity elicited by phorbol 12-myristate 13-acetate (PMA)-stimulated lymphocytes was investigated by using cultured bovine glomerular endothelial cells (GEN). Both anti-CD11a and CD18 antibodies inhibited GEN injury induced by the activated lymphocytes in a dose-dependent manner. In addition, both antibodies also inhibited the adhesion of the activated lymphocytes to the GEN monolayers. These results suggest that it is important for activated lymphocytes to bind to GEN via adhesion molecules for cytotoxity to be produced by the activated lymphocytes.
A 48-year-old woman with nephrotic syndrome underwent renal biopsy. Light microscopy showed nodular sclerosis and thickening of the glomerular capillary wall. Immunoglobulins (Ig) G, especially IgG2, IgM, IgA, C3, C1q were detected along the glomerular capillary walls by immunofluorescent microscopy. Electron microscopy revealed that fibrillar materials of about 25 nm were accumulated in the subepithelial area of the glomerular basement membrane. These materials were negative for Congo-red staining. Neither cryoglobulinemia nor paraproteinemia including light chains was found. This case was diagnosed as membranous nephropathy by clinical findings and pathological examinations, and seemed to be a case of fibrillary glomerulonephritis.
We report here two cases of mixed cryoglobulinemia showing renal involvement associated with hepatitis C virus (HCV) infection. The subjects were 62- and 63-year-old males. Both patients presented with purpura on the legs, which was diagnosed as allergic vasculitis by skin biopsy. Case 1 followed a clinical course of progressive nephrotic syndrome with mild hematuria. He also had diabetes mellitus and hypertension. In contrast, case 2 showed only mild hematuria without proteinuria at the time of the renal biopsy. Both cases had immunological disarrangements, such as severe hypocomplimentemia and seropositive rheumatic factor. Recently, it was reported that patients with type II mixed cryoglobulinemia had HCV seropositivity, and revealed membranoproliferative glomerulonephritis. These facts strongly suggested that renal lesions are the result of direct damage mediated by cryoglobulinemia and an activated complement pathway through an immune complex mechanism related to HCV.