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H Kawachi

Publications and source records attributed to H Kawachi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Strain variation in susceptibility to the development of monoclonal antibody 5-1-6-induced proteinuria in rats.

Susceptibility to the development of MoAb 5-1-6-induced proteinuria was investigated in four different rat strains, i.e. Brown-Norway (BN), Lewis (LEW), Sprague-Dawley (SD) and Wistar. An intravenous injection of 5 mg of MoAb 5-1-6 to female 7-week-old rats of a given strain induced massive proteinuria in BN, LEW and Wistar rats. However, SD rats developed almost no proteinuria. A similar tendency was observed in the second experiment, in which the injected dose of MoAb was adjusted according to the body weight of each rat (3 mg/100 g body weight). Immunofluorescence (IF) and immunoelectron microscopy (IEM) revealed no differences between the binding patterns of the MoAbs to normal rat kidneys derived from each strain. Quantitative study using 125I-labelled MoAb showed that there was no significant difference in the amount of antibody bound to the kidney 1 h and 5 days after injection between two rat strains, LEW and SD. Localization of 5-1-6 in vivo and its kinetics were investigated. In IF a linear-like pattern along capillary walls was observed 2 h after injection in both LEW and SD strains. This linear-like pattern was shifted to a granular pattern in proteinuric LEW rats 6 days after injection, whereas it remained linear-like in non-proteinuric SD rats. IEM confirmed this difference in the localization of injected MoAb 6 days after injection to LEW and SD rats also at the ultrastructural level. We conclude that there is a clear-cut strain difference in the development of proteinuria induced by MoAb 5-1-6. SD rats were less susceptible to MoAb-induced glomerular injury than BN, LEW and Wistar rats. Although the exact reason for strain variation in susceptibility to MoAb-induced proteinuria remains to be clarified, the movement of bound MoAb, presumably together with corresponding antigenic molecule along the glomerular epithelial cell surface followed by endocytosis into the epithelial cell, seems to be closely related to the induction of proteinuria.

Animals↗
PubMed1995

Fish oil ameliorates renal injury and hyperlipidemia in the Milan normotensive rat model of focal glomerulosclerosis.

Rats of the Milan normotensive rat strain (MNS) spontaneously develop severe proteinuria and excessive glomerular thromboxane (Tx)A2 production at a young age. These abnormalities are accompanied by podocyte alterations, progressive focal glomerulosclerosis (FGS), and interstitial fibrosis, resembling human FGS. Since it has been shown that pharmacologic Tx-synthase inhibition protects MNS rats from these changes, it was hypothesized that a fish oil (FO) enriched diet, by enhancing TxA3 production instead of TxA2, might afford similar protection, compared with diets enriched in safflower oil (SO) or lard (LD). Rats were pair-fed 11% fat diets from age of 1 to 11 months. Glomerular TxA2 at 11 months was significantly lower in PO-fed rats than in SO- and LD-fed rats (11 +/- 3.0, 69 +/- 3.0, 59 +/- 19.0 nanograms per min/mg, respectively; P < 0.001). At 3 months, urinary albumin excretion was similar among the groups. Over the course of the study, rats fed FO developed significantly less albuminuria than the SO and LD groups (P < 0.001 by analysis of variance for repeated measures), such that the values at 11 months were 25 +/- 5.8, 49 +/- 8.7, and 68 +/- 13.0 mg/24h, respectively. Serum cholesterol and triglycerides were also significantly lower in FO-fed rats than in SO- and LD-fed rats. The extent of FGS was similar in the three groups, but FO-fed rats had less interstitial injury than the other groups. It was observed that a fish-oil diet substantially alleviated albuminuria, normalized nephrotic hyperlipidemia, and reduced interstitial injury, but did not prevent the development of FGS in the MNS model.

Albuminuria↗
PubMed1995

Visceral epithelial cells in rat glomerular cell culture.

The purpose of this study was to identify and characterize visceral epithelial cells (VECs) of renal glomeruli in culture. Such cells have been described variably as regular, polygonal cells showing a high rate of replication and a cobblestone-like appearance at confluence and also as irregular, arborized and often multinucleated cells showing a very limited proliferative capacity. We examined early outgrowths from the glomeruli by immunofluorescence microscopy using antibodies specific for VECs (anti-podocalyxin(1A), anti-pp44 and 5-1-6), for endothelial cells (anti-von Willebrand factor (vWF) and RECA-1) and for mesangial cells (anti-Thy-1). 1A and anti-pp44 reacted with several types of irregular, arborized cells, but never with regular, polygonal cells. 5-1-6 did not react with any of the cells. Neither the 1A- nor anti-pp44-positive cells (1A/pp44(+) cells) stained with anti-vWF, RECA-1 or anti-Thy-1. However, all the 1A/pp44(+) cells expressed desmin and vimentin but not cytokeratin. These results show that the 1A/pp44(+) cells are derived from VECs, supporting the idea that most polygonal cells in glomerular cultures are of parietal epithelial origin.

Animals↗
PubMed1995

Developmental expression of the nephritogenic antigen of monoclonal antibody 5-1-6.

The biogenesis of p51, the target of nephritogenic monoclonal antibody 5-1-6, was studied in the developing glomerulus by immunolocalization and metabolic labeling. The localization of p51 was compared with that of ZO-1, a component of the cytoplasmic face of the epithelial slit diaphragm, and with that of podocalyxin, and apical marker of the podocyte. p51 first became faintly, but clearly, detectable on the basal and lateral sides of the developing podocytes at the S-shaped body stage. Staining intensity increased with further maturation and was restricted to the visceral epithelial cells. On immunoelectron microscopy, the antigen was seen along the basal and lateral surfaces below occluding junction at the early capillary loop stage and later, with the interdigitation of foot processes, became concentrated in the slit pores. At no stage was p51 seen on the apical surface. p51 and ZO-1 were closely localized in the mature glomerulus but arrived at their final positions from opposite directions. p51 was on basal and podocalyxin was on apical sides of the glomerular epithelium from the S-shaped body stage onwards. Metabolic labeling studies showed that p51 is actively synthesized during initial glomerular development and that the rate of synthesis declines substantially with maturation. We conclude that p51 is primarily synthesized during the initial glomerular development, becomes concentrated in the slit pores of mature podocytes, and serves as a basal differentiation marker for podocytes.

Aging↗
PubMed1995

[A case report of chronic traumatic thoracic aneurysm (thrombotic closure type) which appeared as a mediastinal tumor in preoperative findings].

Chronic traumatic thoracic aneurysm is considered to be an uncommon disease. A case of 59-year-old man who had a history of blunt chest trauma with a traffic accident thirty years ago is reported. He has no symptoms and no signs since the accident. The roentogenogram of his chest showed widening of upper mediastinum, but aortography did not reveal the aneurysmal dilatation of the aortic arch. CT and MRI study showed an inhomogenous mediastinal tumor simulating neoplasm neighboring the aortic arch. At surgery, it was found to be a thoracic semispherical pseudo-aneurysm (thrombotic closure type) measuring 3 cm diameter with slightly hard fibrous tissue contained aseptic brownish fluids. Following partial clamping of the aorta, the thoracic pseudo-aneurysm was opened and the direct closure of the aortic tear with teflon felt was performed. It is important to check the presence of the thoracic pseudo-aneurysm for following-up the patient after the thoracic trauma.

Aortic Aneurysm, Thoracic↗
PubMed1994

Effect of traditional Chinese medicine (sairei-to) on monoclonal antibody-induced proteinuria in rats.

The effects of traditional Chinese medicine (Sairei-to) on monoclonal antibody (mAb) inducing proteinuria were examined. Four hundred, 200 and 100 mg/kg body weight (BW) of Sairei-to and phosphate-buffered saline (PBS) as a control were injected intraperitoneally into four groups of female Wistar rats every day from 5 days before intravenous injection of mAb to the end of the experimental period. The amount of urinary protein excretion was significantly suppressed in roughly a dose-dependent manner. For example, 116.6 +/- 89.7 mg/day of proteinuria was observed in control groups compared to 4.2 +/- 15.2 mg/day in the 400 mg/kg BW of Sairei-to treated group 2 days after mAb injection (P < 0.01). Statistically significant (P < 0.01) differences were again observed in a repeat experiment (122.1 +/- 53.7 vs 10.2 +/- 10.1 mg/day on the 2nd day) without affecting the glomerular filtration rate. No significant difference was recognized between the total amount of mAb bound to glomeruli 1 h after mAb injection in Sairei-to-treated and non-treated rats, indicating that Sairei-to pretreatment has no effects on the number or quality of antigenic molecules. The effect of Sairei-to on a non-immunological model of proteinuria was also examined. No significant reduction of proteinuria by similar Sairei-to treatment was observed in aminonucleoside of puromycin nephropathy. The authors conclude that mAb-induced proteinuria in rats is significantly suppressed by the traditional Chinese medicine, Sairei-to.

Animals↗
PubMed1994

Water and protein permeability is regulated by the glomerular epithelial slit diaphragm.

The glomerular barriers to water and macromolecular movement were examined 2 and 24 h after the administration of a monoclonal antibody (mAb) specific to an antigen located on the epithelial slit diaphragm and the external aspect of the glomerular basement membrane. By micropuncture techniques 2 h after mAb administration, single-nephron GFR (SNGFR) and plasma flow were unchanged but the glomerular capillary hydrostatic pressure gradient and glomerular capillary hydrostatic pressure were increased and the glomerular ultrafiltration coefficient (LpA) decreased to values that were 50% of the normal control. There was no increase in urinary protein excretion at 2 h. However, at 24 h after mAb, nephron plasma flow (SNPF) and SNGFR increased and the glomerular ultrafiltration coefficient returned to values indistinguishable from the normal control. At 24 h, there was a marked increase in protein excretion. The administration of meclofenamate decreased values for SNGFR and SNPF to normal. Immunoglobulin G was exclusively bound to glomerular capillary walls in a linear or continuous fashion at 2 h, but in a discontinuous, granular pattern at 24 h. These studies suggest that after mAb, important limiting glomerular barriers for hydraulic conductivity and protein excretion reside on the epithelial aspect of the glomerular capillary basement membrane, specifically at the level of the slit diaphragm. Studies also suggest that alterations in glomerular capillary hydraulic conductivity can be effectively separated from increases in macromolecular permeability.

Animals↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

[Temporary pacemaker for cardiac operation].

For temporary pacing during open heart surgery, we made a device with a permanent VVI pacemaker by simply fixing a lead to the connecting plug. It is easy to make this device, which allows for beginning pacing quickly, and it dose not interfere with the operation.

Cardiac Surgical Procedures↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[Metabolism of Ca2+ in myocytes and peroxidation products in ischemia-reperfusion injury under extracorporeal circulation].

The metabolism of calcium ion (Ca2+) in myocytes in ischemia-reperfusion injury under extracorporeal circulation (ECC) was studied by cytochemistry and electron microscopy. Ten mongrel dogs were under ECC with aortic cross-clamping for 120 minutes. A cold GIK crystalloid cardioplegic solution was infused via the aortic root intermittently during ischemia, and the myocardial temperature was maintained at 5-10 degrees C with ice slush. The morphological changes of Ca(2+)-ATPase activity in myocytes were estimated using the "lead citrate method". The activities of mitochondria, which had been temporarily decreased just before reperfusion, increased immediately after reperfusion and decreased again 60 minutes later. Electromicroscopy revealed swelling of mitochondria and laceration of myofibrils as well as intracellular edema 60 minutes after reperfusion. Immediately after reperfusion and 60 minutes later, creatine phosphokinase iso-enzyme (CK-MB) release in coronary sinus blood was significantly (p < 0.01) greater than that before the start of ECC. Anaerobic metabolism immediately after reperfusion was more active than that before aortic cross-clamping, as demonstrated by changes in excess lactate (delta XL) and redox potential (delta Eh) of lactate and pyruvate (delta XL, p < 0.05; delta Eh, p < 0.01). Thus, in ischemia-reperfusion injury, alterations of Ca(2+)-ATPase activity of mitochondria reflect the functional and morphological viability of the myocardium. Immediately and 60 minutes after reperfusion, the level of thiobarbituric acid was significantly (p < 0.01) higher and the level of alpha-tocopherol was significantly (p < 0.01) less than respective levels before the start of ECC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗