Localization of glomerular fibronectin in human and experimental glomerulonephritis.
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Animals↗
Biomedical subjects
F Shimizu
Publications and source records attributed to F Shimizu.
Solubilization of immune complex deposits by native 7S IgG molecules in lupus glomerulonephritis--a possible antigen excess effect on rheumatoid factor-IgG complexes.
IgM and IgG class rheumatoid factor (RF) containing glomerular immune complex (IC) deposits were detected in renal biopsy material from 10 out of 123 patients with various forms of glomerulonephritis (GN) by an immunofluorescent assay using FITC conjugated aggregated human IgG(FAHIgG). In lupus GN, six out of 28 cases (23.5%), showed such activity. Solubilization of glomerular IC deposits in frozen sections of lupus GN was observed after a 5 h incubation with native 7S IgG. The binding of FAHIgG to glomerular IC deposits and solubilization of deposits by excess HIgG were also confirmed in sections of two types of rat experimental GN in which HIgG acted as exogenous antigen; in situ IC formation type GN in cationized HIgG planted kidneys and chronic serum sickness type GN. These results suggest a possible antigen excess mechanism contributing to the solubilization of glomerular IC deposits via RF and IgG interactions in lupus GN.
Animals↗
[Antitumor effect of FU-O-G, new antitumor agent, following long term administration].
FU-O-G, the O-glucuronide methylester of 5-fluorouracil (5-FU), is a compound with a unique chemical structure. It is an antitumor agent of the prodrug type which exerts its activity by enzymatically liberating 5-FU in tumor tissues. It has been reported that the antitumor activity of this compound is superior to those of 5-FU and Tegafur (FT-207) in the treatment of various transplantable tumors. In this study, long-term administration of FU-O-G to mice bearing relatively slow-growing tumors such as Lewis lung carcinoma, mammary tumor FM3 A and hepatoma MH-134 was carried out. Consequently, FU-O-G was shown to be remarkably effective against those tumors, whereas 5-FU and FT-207 were hardly effective. Long-term daily administration was shown to be more effective than intermittent dosage in the treatment of Lewis lung carcinoma. In combination therapies of FU-O-G with other antitumor drugs, FU-O-G exhibited a synergistic effect against Lewis lung carcinoma when combined with Carboquone (CQ) or Nimustine hydrochloride (ACNU).
Animals↗
[Studies on the results of operations for carcinoma of the sigmoid colon].
Of 734 patients with colorectal cancer operated on during the past 21 years, 142 had carcinoma of the sigmoid colon. Curative resections were performed in 103 patients and non-curative resections in 22, the resection rate being 88.0%. Among 103 patients with curative resection, resection of the sigmoid colon was performed in 79, and their 5-year survival rate was 84.6%. Eight patients died within 5 years due to recurrence. Many of them had the constricting type macroscopically and Dukes C with positive lymph node metastasis. Therefore, in such cases, resection of the sigmoid colon with extended lymph node dissection or left hemicolectomy should be performed.
Adenocarcinoma↗
The binding of insulin to mouse leucocytes during viral infections.
The effect of viral infections on insulin binding in vivo was evaluated by measuring the binding of 125I-insulin to several different tissues. We found that splenic leucocytes from mice infected with either the diabetogenic (D) or non-diabetogenic (B) variants of encephalomyocarditis virus, herpes simplex virus, or lactic dehydrogenase virus showed up to a 130% increase in insulin binding. As much as a 300% increase in the binding of 125I-insulin to splenic leucocytes was observed in mice given bacterial lipopolysaccharide. In neither virus-infected nor lipopolysaccharide-treated mice was there any substantial change in insulin receptors on thymocytes, liver membranes, or peripheral erythrocytes. Thus, the increased binding of insulin appears to be limited to leucocytes and does not appear to represent a generalized metabolic alteration. These experiments suggest that during infection, the binding of insulin to leucocytes, which is widely used to measure insulin receptors, may not always accurately reflect the insulin receptor status of other tissues.
Animals↗
Effects of single exposure to cadmium on the primary humoral antibody response.
Effects of a single intraperitoneal (i.p.) injection of cadmium (Cd) on the primary humoral antibody responses against sheep red blood cells (SRBC) in mice were studied by assaying splenic plaque forming cells (PFC). PFC responses in mice were suppressed when exposed to Cd 2 days after immunization, and inconsistently stimulated when exposed before immunization. Dose-response relationships were observed in the suppressive effect of Cd exposure 2 days after immunization, but not consistently in the stimulative effect of Cd exposure before immunization. Thymus weights and cell numbers decreased markedly 4 days after Cd exposure with or without the antigenic stimulus. Splenic weights increased 2 days after Cd exposure, while the number of spleen cells was dramatically decreased 1 days after Cd exposure and still remained below normal 2 days after exposure.
Animals↗
A study on cadmium-induced nephropathy in rats pretreated with puromycin aminonucleoside.
Nephrotoxicity of cadmium (Cd) was investigated using puromycin aminonucleoside (AN)-pretreated rats. AN pretreatment was performed by iv injection of 100 mg AN/kg body wt 11 days before the initial Cd injection. Since massive proteinuria and focal glomerular deposits were recognized, glomerular permeability is considered to be increased in AN-pretreated rats. AN-pretreated and intact rats were injected sc with 3 mg Cd/kg body wt, 4 times a week. In non-pretreated rats, slight tubular vacuolation was seen after 1-week Cd exposure and severe vacuolation and coagulative necrosis of the tubules was observed after 2-week Cd exposure. On the other hand, AN pretreatment delayed the onset of vacuolation and necrosis for 1 week and made the lesion milder. After 1-week Cd exposure, a larger amount of Cd was excreted into the urine of AN-pretreated rats than of non-pretreated ones, whereas Cd accumulation in the kidney and liver was lower in AN-pretreated rats than in non-pretreated ones. Thereafter, no difference in Cd concentration was recognized between two groups. From these findings, it is suggested that in early stage of Cd administration, Cd was filtered through the glomerular basement membrane modified by AN pretreatment and that this filterable Cd did not have nephrotoxic effects in AN-pretreated rats.
Animals↗
Inhibition of delayed hypersensitivity reaction in mice by cadmium.
The effect of a single exposure to Cd on DH was studied through exposure to Cd at different time intervals in relation to antigen administration. Exposure to Cd significantly suppressed the DH reaction, with a dose-response relationship, when administered 2 or 3 days after immunization of BALB/c and DBA/2 mice with sheep red blood cells. A strain difference in sensitivity to Cd was also demonstrated. These results suggest that a single exposure to Cd impairs the cellular immune response in mice.
Animals↗
Methodological aspects of immunofluorescence applied to nephrology.
The influences of different conditions of specimens and conjugates, especially of pretreatments on the fluorescent patterns of kidneys with positive staining for immunoglobulins were examined. The nature of immunoglobulins might be differentiated by the proper combination of pretreatments. It was also found that fluorescent patterns of kidneys were remarkably changed by different methodological conditions.
Animals↗
Enhancement of IgE antibody production by ovalbumin aerosol in mice.
The effect of aerosolized ovalbumin (OA) on the induction of IgE antibody production was investigated in BALB/c mice. Enhancement of anti-OA IgE antibody production was obtained after the administration of 10 micrograms OA in mice preexposed to 1% aerosolized OA for 6 or 30 min, and after the administration of 1 microgram OA in mice preexposed to aerosolized OA for 30 min. IgE antibody production could also be induced by preexposure to aerosolized OA at a concentration as low as 0.1%. A carrier effect was observed by preexposure to aerosolized OA using a hapten-carrier system. In the latter system, whole body irradiation (200 R) could not enhance IgE response, suggesting that irradiation-sensitive suppressor T cells might be generated in insufficient amount or not at all by aerosolized OA. Preexposure to aerosolized dinitrophenol-OA could not enhance anti-dinitrophenol IgE response. These results suggest that the exposure to aerosolized antigen primed preferentially T helper cells.
Aerosols↗
[Reticuloendothelial blockers--effects of carrageenan and dextran sulfate on the function of the mouse mesangium in processing foreign bodies].
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Animals↗
An active model of immune complex glomerulonephritis in the rat employing cationized antigen.
An active model of in situ immune complex glomerulonephritis involving a cationic antigen was established. Three weeks after immunization with human IgG, the left kidneys of Wistar rats were perfused with 100 micrograms of cationized human IgG (pI greater than 9.5) via the left renal artery. At this time the animals exhibited a mean serum concentration of 0.58 +/- 0.33 mg anti-human IgG antibody per milliliter. Renal tissue was examined at regular intervals by immunofluorescence, light, and electron microscopy thereafter. Cationized human IgG and rat IgG were distributed along the glomerular capillary wall in a pattern that became increasingly granular with time; rat C3 was also present. Histologically, a severe proliferative lesion was seen with crescent formation in 10-20% of the glomeruli; adhesions of glomerular tufts to Bowman's capsule were common and with time spike formation in the glomerular basement membrane became very prominent. Extensive subepithelial dense deposits were seen by electron microscopy. Proteinuria was present in 19 of 26 animals within 24 hours, and in 30 of 31 by Day 7. Protein excretion fell from Day 14 onward, but some animals exhibited chronic proteinuria. The model described here represents another situation in which cationic antigens can induce subepithelial immune complexes, namely, the rapid release of small quantities of antigen into a previously sensitized host. This sequence could well mirror the events occurring in nature more closely than the previously described passive in situ model.
Animals↗
Identification of envelope glycoprotein encoded by env gene of human T-cell leukemia virus.
Envelope gene product of human T-cell leukemia virus was identified as a glycoprotein with an apparent molecular weight of 62,000 daltons, by using rabbit antiserum against a synthetic decapeptide whose structure had been predicted from the nucleotide sequence. Sera from patients with adult T-cell leukemia also reacted with this glycoprotein.
Adult↗
Nephropathy induced in rats by repeated intravenous injections of rabbit anti-FX1A antibody.
Repeated intravenous injections of small amounts of rabbit anti-rat FXIA antibodies (RAFA) induced a renal damage with the morphological features of epimembranous glomerulonephritis with significant and persistent proteinuria. These findings indicated that repeatedly injected RAFA accumulated in glomeruli and that there seems to be a threshold in quantity of RAFA localized in glomeruli to induce renal damage with proteinuria.
Animals↗
Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross-reactive antibody response.
Antibody specific for the amino-terminal region of cholecystokinin octapeptide (CCK-8) was generated in a highly reproducible way in New Zealand white rabbits by a novel immunization procedure which involves immunization with CCK-8 peptide conjugate coupled with keyhole limpet hemocyanin (KLH) and inhibiting cross-reacting antibody formation by treatment of the animals with a potent tolerogenic conjugate of beta-alanyl-tetragastrin and a copolymer of D-glutamic acid and D-lysine (D-GL). The antisera thus produced specifically react with an amino-terminal region of CCK-8 but not with the non-sulfate form of CCK-8, nor with the carboxy-terminal region which shares a cross-reactive determinant among gastrin and cholecystokinin-related peptides (caerulein, CCK-4, CCK-8, CCK-33 and CCK-39). The antisera produced by this method allowed us to measure specifically CCK in extracts from tissue such as duodenum containing gastrin and CCK at comparable levels.
Amino Acids↗
Effect of subacute exposure to NO2 on lymphocytes required for antibody responses.
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Animals↗
The role of corticosterone in cadmium-induced thymic atrophy in mice.
Serum corticosterone levels were determined at intervals after i.p. injection of 1.8 mg cadmium (Cd)/kg body weight. Thymus weight decreased significantly 3 days after injection. The effect of Cd injection on serum corticosterone levels was almost indistinguishable from that of saline injection. Further, Cd-induced thymic atrophy was observed in adrenalectomized mice as well as in sham-operated ones. These results suggest that corticosteroid effect is not essential for the induction of thymic atrophy by Cd.
Adrenalectomy↗
Interaction of cationized antigen with rat glomerular basement membrane: in situ immune complex formation.
The influence of charge and size on antigen binding to the rat glomerular basement membrane (GBM) was investigated. Chemically cationized ovalbumin, human serum albumin (HSA), human immunoglobulin G (Hu IgG), horse spleen ferritin and human immunoglobulin M (Hu IgM) were injected into rats intravenously. By immunofluorescence significant glomerular binding occurred when the pI exceeded a threshold value of 8.5 to 9.5. At a given pI antigen binding increased with molecular size. Cationized Hu IgM bound only weakly to the glomerular capillary wall, presumably excluded due to size. Subepithelial immune deposits were formed only when antibody was injected subsequently. Detailed electron microscopic studies on in situ formation of immune complexes were performed using cationized horse spleen ferritin. Early on subendothelial deposits were very marked, giving way to subepithelial deposits with time. Under the conditions employed, it appears that deposits can be formed directly at the subepithelial locus but that complexes are also formed subendothelially, dissociating into free molecules or small complexes and then migrating through the lamina densa and reforming.
Animals↗