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M Nagase

Publications and source records attributed to M Nagase.

At least 55 records · Page 3Linked to original sources
PubMed1998

Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats.

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques. METHODS: Chemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg-1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR. RESULTS: Chemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second-order rate constant of 2.9 x 10(10) and 1.6 x 10(10) (mol L(-1) s(-1) respectively, similar to that of dimethylthiourea. CONCLUSION: DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.

Animals↗
PubMed1998

Altered anionic GBM components in monoclonal antibody against slit diaphragm-injected proteinuric rats.

BACKGROUND: We previously reported that monoclonal antibody (mAb) 5-1-6 bound to renal filtration slits induces massive proteinuria without causing ultrastructural changes in the glomerulus. This study evaluated the underlying mechanisms of the increase in glomerular permeability. METHODS: The distribution of endogenous albumin and IgG in the glomerular basement membrane (GBM) was studied in in situ drip-fixed glomeruli of Munich-Wistar rats by use of immunogold immunocytochemistry in the presence and absence of mAb 5-1-6. The density of foot process glycocalyx components was estimated by labeling with Limax fluvus lectin- or Helix pomatia lectin-gold complexes. Anionic sites in the GBM were examined by labeling with cationic gold at pH 2.0 or 7.4. Carboxyl groups, which also furnish an anionic charge to the GBM, were examined by specific biotinylation and colloidal gold probe methods. In addition, the infusion-staining of anionic sites was performed by use of ruthenium red in both Munich-Wistar and Wistar rats. RESULTS: The urinary excretion of albumin and IgG was increased markedly in the treated rats, indicating a non-selective barrier defect. In the control rats, albumin and IgG molecules were mainly located along the inner half of the GBM, and to a lesser degree in the lamina rara externa. In the treated rats, the albumin and IgG moieties were more equally distributed throughout the width of the GBM. Newly appearing, small dense peaks at the outer side of the GBM were evident, indicating a barrier function of outer zone of the GBM and/or epithelial cell layer. No intergroup differences in the density of lectin binding sites on foot processes were seen. The reduction in the number of ruthenium red-positive anionic sites and cationic gold (pH 2. 0)-labeled anionic sites in the lamina rara externa was significant in the treated rats at day 3, indicating a possible alteration of charged proteoglycan in the lamina rara externa. No such changes were seen with cationic gold (pH 7.4)-labeled anionic sites in the GBM. The density of labeled carboxyl groups was significantly reduced in the treated rats relative to the controls. CONCLUSIONS: These results show that the injection of mAb 5-1-6 induced a perturbation of the charge- and probably the size-selective glomerular filtration barrier. The observed reduction in the levels of various negatively charged substances resulted in massive proteinuria, implying that alteration of target antigens can affect the integrity of the GBM constituents maintaining the normal barrier function.

Albuminuria↗
PubMed1998

MPO-ANCA-positive crescentic necrotizing glomerulonephritis and tubulointerstitial nephritis with renal eosinophilic infiltration and peripheral blood eosinophilia.

We present the case of a 67-year-old woman with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive pauci-immune crescentic necrotizing glomerulonephritis and tubulointerstitial nephritis with renal eosinophilic infiltration and peripheral blood eosinophilia. Staining for eosinophil cationic protein indicated that activated eosinophils were involved in the tubulitis, as well as in the glomerular injury. Marked peripheral blood eosinophilia is uncommon in ANCA-positive crescentic necrotizing glomerulonephritis associated with tubulointerstitial nephritis, except in Churg-Strauss syndrome. However, our patient had no clinical history or signs of asthma, no other signs suggestive of allergic diseases, and no histologic findings of granulomas in the kidney, thus failing to fulfill the criteria for Churg-Strauss syndrome.

Aged↗
PubMed1998

Mutations in fibroblast growth factor receptor 2 gene and craniosynostotic syndromes in Japanese children.

We examined the gene mutations of fibroblast growth factor receptor 2 (FGFR2) in Japanese syndromic craniosynostotic patients. Subjects included 1 patient with Apert's syndrome, 1 patient with Crouzon's syndrome, and 3 patients with Pfeiffer's syndrome, as well as two control patients. The genomic deoxyribonucleic acid of each patient was extracted, and the mutation sites of the FGFR2 gene were amplified and sequenced. One patient with Apert's syndrome showed a FGFR2 mutation of S252W (TCG-->TGG), 1 patient with Crouzon's syndrome had a mutation of C342W (TGC-->TGG), and the 3 patients with Pfeiffer's syndrome had mutations of T341P (ACG-->CCG), C342S (TGC-->TCC), and D321A (GAC-->GCC). The role of FGF families and the effect of FGFR2 mutations on craniofacial morphogenesis are discussed.

Acrocephalosyndactylia↗
PubMed1998

Japanese sisters with Pfeiffer syndrome and achondroplasia: a mutation analysis.

The authors report the rare existence of a family that includes an older sister with Pfeiffer syndrome and a younger sister with achondroplasia. Gene analysis of these patients showed a T341P mutation in the FGFR2 gene in the patient with Pfeiffer syndrome, and a G380R mutation in the FGFR3 gene in the patient with achondroplasia. Both mutations have been reported previously. Their parents had no mutation in either locus. This result suggests the possibility that there may be predisposing factors for different FGFR mutations.

Achondroplasia↗
PubMed1998

Structure-function relationship of T-2 toxin and its metabolites in inducing thymic apoptosis in vivo in mice.

Recently we found that a single administration of T-2 toxin (T-2), a trichothecene mycotoxin, into mice induced DNA fragmentation, a biochemical hallmark of apoptosis, in the thymus. In this study, we investigated the effective chemical structure(s) of T-2-derived metabolites capable of inducing thymic apoptosis in vivo in mice. Metabolic conversion of T-2 to 3'-hydroxy-T-2 toxin (3'-OH-T-2) did not diminish the apoptosis-inducing activity, since essentially the same level of fragmented DNA was detected in the thymus taken from mice injected with either T-2 or 3'-OH-T-2. In contrast, hydrolysis of T-2 and 3'-OH-T-2 at the carbon-4 (C-4) position to HT-2 toxin (HT-2) and 3'-hydroxy-HT-2 toxin (3'-OH-HT-2), respectively, greatly decreased the level of DNA fragmentation. Similarly, hydrolysis of T-2 at the carbon-8 (C-8) position to neosolaniol strongly diminished its ability to induce DNA fragmentation. T-2 tetraol, having no ester groups, was unable to induce apoptosis. Based on the data presented in this study, we concluded that both the acetyl group at the C-4 position and the isovaleryl or 3'-hydroxyisovaleryl group at the C-8 position of the T-2 molecule are important for inducing cell death through apoptosis in the thymus.

Animals↗
PubMed1998

Expression of types I, II, and III TGF-beta receptors in human glomerulonephritis.

Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.

Activin Receptors, Type I↗
PubMed1998

Source of reactive oxygen species in anti-Thy1 nephritis.

In proliferative glomerulonephritis, both macrophages and mesangial cells generate reactive oxygen species (ROS), contributing to the development of glomerular injury. We have attempted to determine which cell produces ROS during anti-Thy1 nephritis (ATN) in rats. The generation of ROS was studied using luminol amplified chemiluminescence (GCL) on isolated glomeruli. Immunohistochemical studies used avidin-biotin complex (ABC) to label macrophages and mesangial cells. Immediately after ATN induction, mesangiolysis and infiltration with ED-1 positive cells (referred to as macrophage) was noted with a peak at day 1. After day 4, mesangial proliferation appeared with a decrease of the ED-1 positive cells and a prominent increase of PCNA positive cells (regarded as mesangial cells). In the early phase of ATN, GCL, reflecting ROS generation, increased along with the appearance of ED-1 positive cells. GCL subsequently decreased as mesangial cells increased. This suggested that macrophage were the principal participants in ROS generation in the early phase of ATN although mesangial cells cannot be completely disregarded in the generation of ROS and development of glomerular injury.

Animals↗
PubMed1998

Analysis of muscle bioenergetic metabolism in rabbit leg lengthening.

The effect of lengthening on muscle metabolism was measured and correlated to the percent lengthening at early and late time points. Using the rabbit tibial lengthening model, the authors examined the effects of lengthening on the tibialis anterior muscle using phosphorus-31 magnetic resonance spectroscopy. Thirty-six rabbits were divided into five groups, four groups by percent lengthening (0%, 15%, 20%, and 25%), with each group divided into subgroups of early (end distraction) and late (12 weeks after end distraction), and the fifth group using the opposite untreated leg as control. Several parameters measuring metabolism of muscle using phosphorus-31 magnetic resonance spectroscopy analysis were compared. No changes occurred to 15% lengthening, but significant decreases were measured at 20% and 25% lengthening. After a 25% lengthening, the decreased metabolism persisted at 12 weeks after distraction, indicating the possibility of permanent damage. After 20% lengthening, the same parameters improved but never to normal levels. The authors conclude that lengthening to 15% is safe for muscle, but 20% to 25% lengthening may result in permanent metabolic damage. The current study also suggests that phosphorus-31 magnetic resonance spectroscopy may provide a viable clinical method for evaluating muscle damage during lengthening.

Adenosine Triphosphate↗
PubMed1998

[Membranoproliferative glomerulonephritis-like lesion with fibrillary deposition associated with multicentric Castleman's disease].

We report a case of a 65-year-old man presenting with multicentric Castleman's disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion with fibrillary deposits. The lesion was characterized by highly organized ultrastructual deposits that were negative for Congo-red stain and for immunoglobulin, light chain and C3. Thus, this renal lesion was considered histologically to be fibrillary glomerulonephritis presenting by light microscopy as mesangiocapillary glomerulonephritis. To our knowledge, among the limited number of cases of renal lesion associated with MCD ever reported, this is the first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6 (IL-6), known as an indicator of MCD activity and as an autocrine growth factor for mesangial cells, was chronologically measured. Augmentation of urinary IL-6 simultaneously with that of extra renal symptoms of MCD and associated renal disease may indicate an underlying role of this cytokine in the present case. Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is derived from extrarenal lymphonodi, and not to an in situ product of the glomeruli. However, it may have been related to glomerular injury.

Aged↗
PubMed1997

Enhanced expression of endothelial oxidized low-density lipoprotein receptor (LOX-1) in hypertensive rats.

Oxidized low-density lipoprotein (Ox-LDL) has been implicated in the attenuated endothelium-dependent vasodilatation in atherosclerotic arteries and, possibly, in hypertension. The aim of the present study was to investigate gene expression of recently-identified endothelial Ox-LDL receptor (LOX-1) in hypertensive state. SHR-SP, WKY, Dahl salt-sensitive (DS) and salt-resistant rats (DR) were fed salt-loaded or control diet. RNA was extracted from the aorta and vein. LOX-1 expression was examined by Northern blotting. LOX-1 mRNA was low in the aorta and vein of WKY, whereas it was markedly upregulated in those of SHR-SP. LOX-1 expression was low in the aorta of DR on both diets and of DS on a control diet, whereas it was elevated in that of salt-loaded DS. These results indicated that LOX-1 expression in the aorta and vein was upregulated in hypertensive rats, which may be involved in the impaired endothelium-dependent vasodilation in these rats.

Animals↗
PubMed1997

Glomerular handling of immune complex in the acute phase of active in situ immune complex glomerulonephritis employing cationized ferritin in rats. Ultrastructural localization of immune complex, complements and inflammatory cells.

The ultrastructural localization of immune complex (IC) and inflammatory mediator systems in the glomerulus was investigated in active in situ IC glomerulonephritis employing cationized ferritin in rats. Glomerulonephritis was induced by unilateral renal perfusion of cationized ferritin as antigen (Ag) in preimmunized rats, and anti-ferritin antibody (Ab), C3 and the rat C5b-9 complex were localized by means of immunogold electron microscopy. Ag-Ab complexes were initially formed subendothelially, associated with C3, and attracted platelets, polymorphonuclear leucocytes (PMN) and monocytes. Then Ag-Ab complexes, without C3, passed across the glomerular basement membrane to re-aggregate subepithelially accompanied by C3 deposition after 1 day. Ag-Ab complexes without C3 accumulated in the inter-podocyte space within 1 day and were seen in the epithelial cells at 6 h. C5b-9 complexes were found in subepithelial immune deposits and in membrane vesicles of the epithelial cells, but only in very small amounts in subendothelial immune deposits. Accumulated platelets, PMN, and monocyte were in direct contact with endothelial cells or subendothelial IC. PMN and monocytes contained Ag, Ab and C3 in intracytoplasmic vacuoles. Ag-Ab complexes were also found in the mesangial matrix adjacent to the subendothelial region after 2 h and increased slightly in number, with expansion of the mesangial area thereafter. Most ICs formed in the subendothelial space rapidly formed lattices of a size that activated C3 and were then translocated to the subepithelial space. The potential ability of C3 to solubilize ICs in the subendothelial region may be important in this process. Endocytosis of subendothelial ICs by PMN and/or monocytes and the movement of ICs to the mesangial matrix may also contribute to the removal of IC from the subendothelial space.

Acute-Phase Reaction↗
PubMed1997

Ultrastructural background of albuminuria in rats with passive Heymann nephritis.

BACKGROUND: Although it is widely known that proteinuria in rats with passive Heymann nephritis (PHN) is prevented by treatment with cobra venom factor (CVF), the precise mechanisms of complement-dependent proteinuria have not been fully elucidated. The aim of this study was to evaluate morphologically whether the size of subepithelial electron-dense deposits (EDDs) contributes to the onset of albuminuria. METHODS: The size of subepithelial EDDs and anionic sites in the lamina rarae externa (LRE) overlaid with subepithelial EDDs were evaluated by ruthenium red and compared between PHN and PHN treated with CVF in rats. RESULTS: Overt albuminuria was present on days 3 and 4 after injection of anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n = 6) (53.6 +/- 38.8 vs 1.02 +/- 0.55 mg/day, P < 0.01, on day 4). Rat C3 was detected along the glomerular capillary walls on day 4 post-injection in rats with PHN, but not in rats with PHN + CVF. Subepithelial EDDs were observed in both groups. Quantitative morphometric analysis revealed that CVF-treatment decreased the size of subepithelial EDDs as well as the extent of retraction of glomerular epithelial cells. In both groups the density of anionic sites in the LRE overlaid with EDDs was decreased compared with the LRE without subepithelial EDDs. However, no difference was noted between the two groups. CONCLUSIONS: Depletion of serum complement decreases subepithelial EDDs as well as the number of sites with decreased anionic charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a pivotal role in the onset of albuminuria.

Albuminuria↗
PubMed1997

Tissue distribution and localization of natriuretic peptide receptor subtypes in stroke-prone spontaneously hypertensive rats.

OBJECTIVE: To investigate tissue distribution and localization of the natriuretic peptide receptor (NPR) subtypes' messenger RNA (mRNA) and to compare their expression between stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto (WKY) rats. METHODS: Total RNA was extracted from organs of SHR-SP and WKY rats aged 13 weeks. The mRNA level was examined by RNase protection assay. The localization of the transcripts was determined by in-situ hybridization. RESULTS: In SHR-SP aged 13 weeks, NPR-A was expressed most abundantly in the adrenal gland, lung and aorta, in that order. NPR-B was expressed highly in the uterus and ovary, and also in the lung, adrenal, and brain. NPR-C was expressed predominantly in the atrium and mesentery, less so in the lung, vein, and kidney. In the adrenal gland, NPR-A was expressed mainly in zona glomerulosa cells. In the atrium, NPR-C was expressed throughout the wall. In the mesentery, NPR-C mRNA was detected mainly in adipocytes. In the kidney, NPR-C was found predominantly in podocytes. Whereas the levels of expression of NPR subtypes in most tissues examined did not differ between SHR-SP and WKY rats, the NPR-C mRNA level was significantly greater in the kidneys of SHR-SP than it was in those of WKY rats. CONCLUSIONS: These results indicated that each NPR subtype had a distinct tissue distribution pattern and that the expression of NPR-C in the kidneys of SHR-SP was greater than that in the kidneys of WKY rats.

Animals↗
PubMed1997

Long-term effect of manidipine on renal function and structure in uninephrectomized spontaneously hypertensive rats.

1. Long-term effects of manidipine hydrochloride (MAN), a calcium channel blocker, were examined in three groups of spontaneously hypertensive rats (SHR). Group 1 was given uninephrectomy (UNX) and MAN treatment, group 2 was given UNX and was not treated with MAN and group 3 was given neither UNX nor MAN treatment. 2. At week 15 after UNX, inulin clearance in group 1 rats decreased compared with rats in groups 2 and 3, but remained at the same level at week 40, when the level in group 2 rats declined below that in rats in groups 1 and 3. 3. Glomerular and tubulointerstitial lesions did not differ at week 15 after UNX among the three groups, whereas at week 40 both were advanced in the order of groups 2, 1 and 3. 4. Proteinuria did not differ between rats in groups 1 and 2 over the experimental period. 5. At week 15, the kidney weights of group 1 rats were greater than those of group 2 rats, indicating more prominent tubular hypertrophy in the former group. This was confirmed by morphometry of the proximal tubuli. In contrast, the glomerular volumes of rats in groups 1 and 2 were enlarged compared with that of rats in group 3, with no difference between the former two groups. 6. The findings suggest that MAN exerts renoprotective effects in SHR, both with regard to function and morphology. An effect on glomerular haemodynamics was considered to more likely be the mechanism underlying the renoprotective effect of MAN rather than that of a lowering of systemic blood pressure. 7. Augmented tubular hypertrophy after MAN treatment was an unexpected finding of the present study and the biological significance of this finding remains to be explored.

Animals↗
PubMed1997

Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive rats.

The natriuretic peptide system is suggested to be involved in the pathogenesis of salt-sensitive hypertension; a recent report indicated that disruption of the atrial natriuretic peptide precursor gene caused salt-sensitive hypertension. However, natriuretic peptide receptor (NPR)-A knockout mice did not show enhanced salt sensitivity of blood pressure. The aim of the present study was to investigate the role of NPR-C, the other receptor for atrial natriuretic peptide, in increased salt sensitivity of blood pressure. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were placed on a 0.3% or 8% NaCl diet for 4 weeks. Blood pressure was elevated by salt loading only in DS rats. RNase protection assay demonstrated that NPR-C transcript level in the kidney was reduced by chronic salt loading in both DR and DS rats, whereas expression of NPR-A and NPR-B was not altered. The reduction of NPR-C mRNA in response to salt loading was enhanced in DS compared with DR rats. In situ hybridization indicated that the salt-induced NPR-C change was attributed mainly to suppressed expression of NPR-C in the podocytes. NPR-C gene expression was regulated by salt loading in a tissue-specific manner; the marked decrease in NPR-C mRNA by salt loading was seen only in the kidney. These data suggest that the exaggerated salt-induced reduction of NPR-C in the kidney of DS rats may play an important role in the pathogenesis of salt hypertension in this animal, possibly related to impaired renal sodium excretion.

Animals↗
PubMed1997

Inhibitory effects of glucocorticoids on proliferation of canine mast cell tumor.

The inhibitory effect of glucocorticoids (GCs) on proliferation of canine mast cell tumor (MCT) was studied using two types of MCT cells; JuMC cells and LuMC cells derived from spontaneous canine cutaneous and intestinal MCT, respectively. In in vitro study, growth of JuMC cells was significantly inhibited with more than 1 nM GCs and apoptotic-like cell death was seen, while that of LuMC cells was never inhibited even with 10 microM GCs. Growth rate of masses in nude mice developed by inoculation of JuMC cells was reduced in a dose-dependent manner by administration of GC, while growth inhibition of masses developed by inoculation of LuMC cells was minimal with increasing GC doses. Competitive binding studies and Scatchard analysis demonstrated the presence of high-affinity, low capacity GC receptors in both JuMC and LuMC cells. Kd was estimated to be 1.30 nM in JuMC cells and 0.45 nM in LuMC cells, respectively. It is concluded that canine cutaneous MCT cells responded to GCs in vitro and in vivo, whereas intestinal MCT cells did not, though both types of cells had specific GC receptors.

Animals↗