Double photoionization of helium using many-body perturbation theory.
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Journal Article↗
Biomedical subjects
F Shimizu
Publications and source records attributed to F Shimizu.
Quadratic collisional loss rate of a 7Li trap.
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Journal Article↗
Nephrotoxic serum nephritis in nude rats: the roles of host immune reactions in the accelerated type.
By immunization with rabbit immunoglobulins and the injection of a subnephritogenic dose of rabbit nephrotoxic serum (NTS), accelerated-type nephrotoxic serum nephritis (NTN) was induced in heterozygous (rnu/+) rats but not in athymic nude (rnu/rnu) rats. By transferring rat antibody against rabbit immunoglobulins, marked proteinuria was induced also in nude rats (202.0 +/- 98.4 mg/day on day 3) as in rnu/+ rats (122.6 +/- 35.3 mg/day on day 3). No marked differences in histological findings could be found between both groups. The most marked increase in the number of intraglomerular infiltrating cells was observed in heterozygous rats indicating that the presence of thymus-derived cells leads to the accumulation of more cells in glomeruli. We conclude that humoral immunity alone is enough to accelerate the pathogenic mechanism which induces glomerular injury with heavy proteinuria in this model.
Animals↗
Effect of chlorpromazine on kinetics of injected monoclonal antibody in MoAb-induced glomerular injury.
The effect of chlorpromazine, one of several calmodulin antagonists that inhibit cytoskeletal movement, on the local kinetics of injected proteinuria-inducing MoAb 5-1-6 was examined to test the hypothesis that proteinuria is inhibited if the antigen recognized by MoAb 5-1-6 or injected MoAb remains on the surface of epithelial foot processes. MoAb 5-1-6 was injected into both chlorpromazine-treated (5 mg/100 g body weight) and untreated rats. As a positive control for the chlorpromazine treatment, anti-Fx1A serum was also injected into other chlorpromazine-treated and untreated rats. Chlorpromazine inhibited neither the change in localization of injected MoAb 5-1-6 nor proteinuria, although it showed an inhibitory effect on redistribution of immune complex and the fixation of complement in passive Heymann glomerulonephritis induced by injection of anti-Fx1A serum. We conclude that the kinetics of bound MoAb 5-1-6 are regulated by a system different from that operating in passive Heymann glomerulonephritis.
Animals↗
Quantitative study of mesangial injury with proteinuria induced by monoclonal antibody 1-22-3.
Murine MoAb 1-22-3 has already been reported to bind to the mesangial cell surface and to cause transient proteinuria and mesangial morphological changes characterized by mesangiolysis, subsequent mesangial cell proliferation and mesangial matrix increase by a single i.v. injection. In this study, MoAb-induced glomerulopathy was quantitatively analysed. No correlation between the severity of mesangial morphological changes and the degree of proteinuria was detected (r = 0.190). The minimum dose injected to induce abnormal proteinuria was 25 micrograms. This dose corresponded to 1.79 micrograms/2 kidneys 30 min after MoAb injection. The highest average level of proteinuria was observed in rats injected with 500 micrograms of MoAb, and less proteinuria was observed in rats injected with 10.0, 5.0 and 2.0 mg. Although the amounts of kidney-fixing MoAb and the subsequent deposition of rat C3 in the high-dose-injected group were larger than in the 500 micrograms injected group, the numbers of infiltrating inflammatory cells were the same in both groups. No correlations between the degrees of such mediators and proteinuria were observed.
Animals↗
Divalency of the monoclonal antibody 5-1-6 is required for induction of proteinuria in rats.
A single i.v. injection of 3 mg of the F(ab')2 fragment of MoAb 5-1-6 into rats induced immediate proteinuria (128.1 +/- 80.7 mg/24 h on day 1) which lasted 1-2 days. In contrast, rats administered 10 mg of the corresponding Fab fragment did not develop abnormal proteinuria even though an equivalent dose of the intact MoAb 5-1-6 far exceeded the nephritogenic dose. The total kidney binding of 125I-Fab fragment was 209.5 +/- 34.3 micrograms/2 kidneys. This exceeded that obtained by injection of 3 mg MoAb 5-1-6 IgG1 (58.9 +/- 12.5 micrograms/2 kidneys at 1 h) and was similar to that obtained following injection of 3 mg F(ab')2 fragment (235.3 +/- 16.9 micrograms/2 kidneys). Immunofluorescence (IF) showed a linear pattern along the glomerular capillary wall at 1 h after the administration of MoAb 5-1-6 IgG1, F(ab')2 or Fab fragment. On day 5, fine to coarse granules were observed scattered in F(ab')2-injected rat glomeruli, whereas granules were densely localized in Fab-injected rat glomeruli. Complement-depleted rats injected with 3 mg of MoAb 5-1-6 IgG1 developed proteinuria with the same time course as non-depleted rats. This observation, together with the ability of F(ab')2 to induce proteinuria, indicates that proteinuria induced by MoAb 5-1-6 is complement-independent. This study suggests that MoAb 5-1-6-induced proteinuria is initiated by cross-linking of the epitopes by divalent MoAb 5-1-6 and is independent of complement activity.
Animals↗
Modulation of human mesangial cell behaviour by extracellular matrix components--the possible role of interstitial type III collagen.
We have investigated the effects of various extracellular matrix (ECM) components on the behaviour of human mesangial cells (HMC) in a gel culture system using a modified MTT assay method. When cultured on a reconstituted basement membrane, Matrigel (M gel), HMC aggregated and formed isolated colonies initially, then extended an array of cell processes to form a dendritic network structure and proliferated very slowly as the culture period progressed. On type I collagen gel (CI gel), however, HMC developed elongated bipolar shapes, migrated into the gel, and showed rapid cell growth. Next, separate ECM components, such as type III and IV collagens, laminin, heparin and heparan sulphate, were incorporated into CI gel and HMC proliferation was assessed. Although attachment of HMC to each gel did not differ significantly, HMC proliferation was inhibited markedly on gels containing type III collagen, heparin and heparan sulphate; type IV collagen suppressed HMC proliferation slightly; and laminin had no significant effect. These data suggest that interstitial type I and III collagens, which are often observed in diseased glomeruli, as well as the basement membrane components, may play important roles in the regulation of HMC proliferation under pathophysiological conditions in vivo. We conclude that HMC behaviour is affected by the surrounding ECM constituents, which appear to function as a refined modulator.
Basement Membrane↗
Double-slit interference with ultracold metastable neon atoms.
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Journal Article↗
A monoclonal antibody (1G10) recognizes a novel human mesangial antigen.
We have identified a unique mesangial matrix protein of the human glomerulus by using a monoclonal antibody, 1G10, generated against culture human glomerular cells. By immunofluorescence, the antigen recognized by 1G10 (1G10 antigen) is present in mesangium and smooth muscle tissue and cannot be detected in any other tissue examined. Immunoelectron microscopy of glomeruli indicated that 1G10 antigen is present exclusively in the mesangial matrix at the endothelial-mesangial interface. The 1G10 antigen is also expressed by cultured mesangial cells, but not by cultured glomerular epithelial cells, umbilical endothelial cells or fibroblasts. 1G10 did not react with the mesangial matrix proteins [fibronectin (FN), laminin (LAM), collagen types I, III, IV, V, and VI (Col I, III, IV, V, VI), heparin sulfate proteoglycan (HSPG), or thrombospondin (TS)] present under normal and diseased states or smooth muscle antigens (myosin, actin), but did react with a 4 M urea extract of renal cortex and a 0.3% deoxycholate extract of isolated glomeruli. Two dimensional immunoblot analysis using the urea extract demonstrated the binding of 1G10 to an approximately 200 KDa polypeptide with pI 6.0. On one dimensional immunoblot this band did not show cross react with polyclonal antisera to FN, LAM, Col IV, V, VI, HSPG or TS. This mesangial matrix component is trypsin and periodate sensitive, suggesting that it has the character of glycoprotein. In renal biopsy specimens from patients with mesangial proliferative glomerulonephritis (GN) and membranoproliferative GN, the expression of the 1G10 antigen increased along with mesangial hypercellularity or increased accumulation of mesangial matrix, but decreased in completely sclerosed glomeruli. No significant changes in 1G10 antigen expression was observed in membranous GN or minimal change nephrosis compared to normal glomeruli. This study suggests that the 1G10 antigen may not only be a useful marker for the clinical assessment of GN, but may also serve as a potential tool for the study of the pathogenesis of glomerular diseases characterized by cellular proliferation and mesangial matrix expansion.
Animals↗
Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.
Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
Biochemical Phenomena↗
Quantitative studies of monoclonal antibody 5-1-6-induced proteinuric state in rats.
Murine monoclonal antibody (MoAb) 5-1-6 was already reported to bind to epithelial cell foot processes and to cause proteinuria in rats. In vivo kinetics of the injected MoAb 5-1-6, relationship between the quantity of kidney-binding antibody and proteinuria, and changes in the amount of antigenic molecule recognized by this MoAb in the proteinuric state were studied. The amount of total kidney-binding antibody (TKAb) as determined 1 h after a 2 mg administration was 50.8 +/- 10.4 micrograms/2 kidneys, and TKAb declined to 1.9 +/- 0.4 at day 15. The minimum dose of MoAb required to induce proteinuria was 125 micrograms as the injected dose. This dose corresponded to 12.8 micrograms of TKAb at 1 h and 0.34 micrograms of TKAb at day 5. The amount of MoAb 5-1-6 binding to isolated normal glomeruli was also shown to exceed 147.7 micrograms/76,000 glomeruli, indicating proteinuria to be induced provided more than 8.7% (= 12.8/147.7) of the critical epitopes is specifically occupied by MoAb. The total amount of MoAb 5-1-6 bound to glomeruli in vivo and in vitro was assayed with [125I]-labelled anti-mouse IgG. The amount of [125I] anti-mouse IgG bound to glomeruli was 6.93 +/- 0.45 micrograms/10,000 glomeruli from rat 5 days after this MoAb injection and 26.58 +/- 0.66 micrograms/10,000 control glomeruli, indicating the decrease in the number of MoAb 5-1-6-recognized antigen molecules in glomeruli isolated from the rat in proteinuric state induced by this MoAb. Thus, the MoAb 5-1-6-recognized molecule itself may principally function to regulate the permeability of the glomerular capillary wall and the decrease of the molecule may lead to proteinuria.
Animals↗
Mesangial sclerotic change with persistent proteinuria in rats after two consecutive injections of monoclonal antibody 1-22-3.
Irreversible mesangial changes with persistent proteinuria were induced in rats given two consecutive injections 2 weeks apart of a MoAb 1-22-3 to rat mesangial cell. The characteristics of the resulting lesions were investigated and compared with those of the reversible change induced by a single injection. At 24 h after the second injection, mesangiolytic changes similar to those after a single injection were evident. The accumulation of macrophage-like cells in glomeruli observed at 1 week after the first injection was not evident during the experimental period after the second injection. Hypercellularity with the characteristics of intrinsic mesangial cell and increased mesangial matrix were already present 1 week after the second injection. And mesangial sclerotic change progressed up to 6 months. Deposition of collagen type I and type III and accumulation of collagen fibril at the ultrastructural level were evident in rats 6 months after the second injection. Proteinuria started immediately and continued for more than 6 months after the second injection. The mesangial sclerotic change with persistent proteinuria described here is considered to be a better model for investigating the mechanism of chronic progression of human mesangial proliferative glomerulonephritis.
Animals↗
Epitope-specific induction of mesangial lesions with proteinuria by a MoAb against mesangial cell surface antigen.
A MoAb 1-22-3 (IgG3) was produced in mice immunized with rat glomeruli. A blotting study indicated the antigen molecule recognized by this MoAb has a molecular weight of about 25 kD, which is the same as that of the Thy 1.1 molecule. This MoAb is capable of inducing the morphological changes similar to those induced by anti-thymocyte serum or the anti-Thy 1.1 MoAb, ER4 and massive proteinuria in rats by a single i.v. injection. Proteinuria started immediately after MoAb 1-22-3 injection and peaked on day 5. Reaction products were detected by immunoelectron microscopy in vitro on the limited mesangial cell surface facing endothelial cells and in vivo in partially lysed mesangial cells 30 min after injection. Unlike the proteinuria-inducing MoAb ER4, reactivity of MoAb 1-22-3 was detected neither on endothelial cells, epithelial cells, nor along the glomerular basement membrane in vivo and in vitro. There is a difference in reactivity toward guinea-pig and rabbit materials between MoAb 1-22-3 and the commercial anti-Thy 1.1 MoAb (OX7). The antigenic determinant of MoAb 1-22-3 is concluded to be a new epitope and only the binding of MoAb 1-22-3 to this epitope proved to lead to an abnormal increase of glomerular capillary wall permeability.
Animals↗
Suppressive effect of superoxide dismutase on adriamycin nephropathy.
A single intravenous injection of adriamycin (ADR) results in marked proteinuria and glomerular morphological changes that are similar to minimal-change disease in humans. We examined the effect of superoxide dismutase (SOD) on ADR-induced proteinuria. ADR in a dose of 7.5 mg/kg body weight significantly increased urinary protein by day 14; proteinuria rapidly increased thereafter. Concurrent administration of SOD (50 mg/kg) over 30 min prior to and 30 min following ADR injection markedly reduced proteinuria. Twenty-one days after the treatment with SOD, the amount of urinary protein was 108.6 +/- 43.1 mg/24 h in the experimental animals, while it was 221.6 +/- 102.9 mg/24 h in the ADR control group (p less than 0.05). There were also less severe glomerular morphologic changes in the SOD group versus ADR controls. The protective effects of SOD provide indirect evidence that oxygen free radicals are important mediators of ADR-induced proteinuria.
Animals↗
Altered localization of antigen recognized by proteinuria-inducing monoclonal antibody in experimental nephrosis.
Change in the localization of the antigen recognized by the proteinuria-inducing monoclonal antibody (MA) 5-1-6 in experimental nephrosis was studied by indirect and biotin-avidin immunofluorescence, and immunoperoxidase at light and electron microscopical levels. The proteinuric state was induced by the administration of the aminonucleoside of puromycin (PAN) or adriamycin. The antigen decreased in quantity and/or its distribution changed with an increase in the amount of protein excreted in both experimental models. Recovery from the alterations observed during the development and proteinuria appeared to occur when PAN-induced proteinuria subsided. This antigenic molecule may thus be essential for maintaining the normal permselectivity of glomerular capillary walls.
Animals↗
Establishment of murine macrophage-like mutant and hybrid cell lines: comparative analysis of the differentiation induced by 1 alpha,25-dihydroxyvitamin D3 and recombinant murine interferon-gamma.
The purpose of this study is to establish the monocyte/macrophage-like cell lines which are sensitive to potent systemic and local factors, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2 VD3) and interferon-gamma (IFN-gamma). We established two variant mouse macrophage-like cell lines, whose responses to 1 alpha,25(OH)2 VD3 and IFN-gamma differed from one another. The AH-sensitive mutant cell line (G3) was induced by allowing P388D1 tolerant to 8-azaguanine. G3 mutant cells were then fused with the 1 alpha,25(OH)2 VD3-stimulated bone marrow cells isolated from DBA/2 mice. After AH selection the hybrid cell line (XC) was established. The G3 mutant cell line and the XC hybrid cell line had macrophage-like characteristics, such as surface antigens, Fc receptor, C3 receptor, and lysosomal enzymes. The treatment of G3 mutant cells with 1 alpha,25(OH)2 VD3 inhibited cell proliferation with morphological changes, and increased acid phosphatase activity, phagocytic activity, and F4/80 antigen expression on the cell surface. In contrast, IFN-gamma inhibited cell proliferation without effect on acid phosphatase activity and phagocytic activity but increased F4/80 antigen expression. In XC hybrid cells, on the other hand, IFN-gamma, but not 1 alpha,25(OH)2 VD3, inhibited cell proliferation with morphological changes but increased phagocytic activity and F4/80 antigen expression. In addition, IFN-gamma, but not 1 alpha,25(OH)2 VD3, dose-dependently increased multinucleated cell formation of both cells. These findings suggest that the G3 mutant cell line with macrophage-like characteristics is 1 alpha,25(OH)2 VD3- and IFN-gamma-sensitive, and that the XC hybrid cell line is, despite its macrophage-like characteristics, only IFN-gamma-sensitive. Therefore, these newly established cell lines will provide useful systems in studying the differentiation of monocyte/macrophage lineage.
Acid Phosphatase↗
Production by cultured human monocytes of mesangial cell proliferation factor(s) differing from interleukin-1 and interleukin-6.
Conditioned media from human peripheral blood leucocytes treated with lipopolysaccharide (LPS) induced a marked increase in the 3H-thymidine incorporation of cultured mesangial cells at low serum concentration (four to six times higher than control). Two sizes (100-70 and 8-12 kD) of monocyte-derived mesangial cell proliferating factors (MDF) were separated by column chromatography. Their peaks were distinct from those of thymocyte proliferating activity. The addition of anti-human interleukin-1 (IL-1) or anti-recombinant human interleukin-6 (IL-6) antibody to the fractionated MDF failed to have any effect on the mitogenic activity toward mesangial cells. The addition of anti-human platelet-derived growth factor (PDGF) antibody to the low molecular weight fraction decreased mesangial cell mitogenic activity (40-60% of control), but addition to the higher fraction did not (80-100% of control). From these data it seems that a large portion of the monocyte-derived mesangial cell growth factor was not comprised of IL-1 or IL-6 but of PDGF-like molecules; and that there is an unknown mesangial cell proliferating factor (or factors) besides IL-1, IL-6 and PDGF.
Adult↗
Monocytes secrete factors regulating glycosaminoglycan synthesis in mesangial cells in vitro.
The present study was conducted to determine the manner in which monocytes increase mesangial matrices, particularly glycosaminoglycans (GAGs) which interact with various other matrix components such as collagens, laminin, fibronectin and lipoproteins. A supernatant of human peripheral blood monocyte cultures activated by lipopolysaccharide (LPS) contains stimulating factors for glycosaminoglycan synthesis in rat mesangial cells (MCs). The culture supernatant in this study was concentrated and fractionated by gel chromatography and the GAG-stimulatory factor was found to have a molecular weight of 10-17 kD. This factor was shown to be present in fractions different from that of IL-1. Gel and ion-exchange chromatography studies of GAGs synthesized by MCs indicated the elution patterns of GAGs in the presence and absence of the monocyte culture supernatant to be essentially the same. Local infiltration of monocytes into the glomerulus, often seen in various types of glomerular injury, may be an important factor in the accumulation of the mesangial matrix.
Animals↗