PubMed Health⌕ Search

Biomedical subjects

K Kanatsu

Publications and source records attributed to K Kanatsu.

At least 19 recordsLinked to original sources
PubMed2002

Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats.

Ellagic acid (EA), a naturally occurring plant phenol, has the antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in microspheres on the ulcerative colitis induced experimentally in rats by dextran sulfate sodium (DSS). Experimental colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS solution in drinking water for 7 days. EA of microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substances (TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and TBARS as well as the decreases of body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced colitis in a dose-dependent manner, and a significant effect was observed at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using microspheres) was also effective in reducing the severity of DSS-induced colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced colitis was also obtained by intra-rectal administration of superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.

Animals↗
PubMed2002

Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs.

BACKGROUND: It is well known that neutrophil-derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing. AIM: To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine. METHODS AND RESULTS: Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague-Dawley rat stomachs. Taurine (10-100 mg/kg) given p.o. 30 min prior to NH2Cl dose-dependently prevented these lesions in response to NH2Cl. This action was mimicked by methionine (3-30 mg/kg) but not by glycine (10-100 mg/kg). Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia. Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine. Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro. CONCLUSIONS: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response; (2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and (3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.

Administration, Oral↗
PubMed2001

Protective effect of rebamipide on indomethacin-induced intestinal damage in rats.

BACKGROUND AND AIM: We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. METHODS: The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30-300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. RESULTS: Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 microg/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. CONCLUSION: These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action.

Alanine↗
PubMed1999

A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a patient with LPG, and we characterized the mutant apo E. METHODS: The propositus was a 32-year-old male patient on maintenance hemodialysis because of LPG. The mutation was detected by sequencing of genomic DNA from the patient and was confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI. Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1 cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants were determined in an in vitro competition assay. RESULTS: The propositus had the apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of amplified DNA showed a C to T transition, changing the codon for residue 25 from arginine to cysteine. The proband was a heterozygous carrier for apo E2 (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The pathophysiological effect of this mutation was investigated in vitro by binding studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The ability of recombinant apo E2 Kyoto to displace LDL was reduced to 10% compared with recombinant apo E3. CONCLUSIONS: Apo E2 (Arg25Cys) Kyoto is a novel mutation of apo E that is etiologically related to LPG. However, our case indicates that the development of LPG may involve other genetic or environmental factors. Furthermore, our data suggest that arginine-25 of apo E plays an important functional role by influencing the receptor-binding ability of apo E.

Adult↗
PubMed1999

An adult-onset case of argininosuccinate synthetase deficiency presenting with atypical citrullinemia.

A 52-year-old heavy drinker presented with repeated episodes of disturbance of consciousness and an increase in serum ammonia level, triggered by excessive alcohol intake. He was diagnosed as having adult-onset citrullinemia with deficiency of hepatic argininosuccinate synthetase (ASS) activity. Cranial magnetic resonance imaging (MRI) showed high-intensity lesions in the central pons and the bilateral middle cerebellar peduncles on T2-weighted images. Although almost all cases of adult-onset citrullinemia have been reported to be enzymologically classified as type II, the serum amino acid pattern and serum level of human pancreatic secretory trypsin inhibitor (hPSTI) were atypical for type II in the present case.

Adult↗
PubMed1999

Renal expression of insulin-like growth factor-l in acute renal failure: a preliminary report.

Renal expression of insulin-like growth factor-I (IGF-I) was examined in the specimens obtained at renal biopsy from five patients with acute renal failure (ARF) at the recovering phase. IGF-I peptide and mRNA were demonstrated in the cytoplasm of the epithelial cells of focal proximal tubules in four patients in whom renal function had been ameliorating. The stainings of IGF-I peptide and mRNA were intense in patients with favorable prognosis. Either IGF-I immunoreactivity or mRNA was not detected in the renal tissues in five cases with chronic renal insufficiency and four patients with renal carcinoma. Our preliminary findings suggest that IGF-I is locally produced in the kidney during the recovery period of ARF and might play roles in the repair processes, and extend the experimental observations in animal models into human pathophysiology.

Acute Kidney Injury↗
PubMed1998

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Adult↗
PubMed1998

Demonstration of DNA replication factor C in human glomerular lesions.

Glomerulosclerosis is a common pathological finding in many human glomerular diseases that ultimately leads to end-stage kidney disease. The regulatory mechanism that controls mesangial proliferation as well as accumulation of mesangial matrix, however, is not known. Recently, a protein factor (MSW) which binds to the specific sequence of the promoter of the alpha 1 and alpha 2 type IV collagen genes was cloned. MSW was found to be identical to a large subunit (Alp145) of DNA replication factor C. These findings suggest that MSW may have important functions in mesangial cell proliferation and type IV collagen synthesis, both of which are prominent findings in glomerulosclerosis. In the present study, we report that augmented expression of MSW protein in human glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis). Minimal expression of MSW protein was observed in human glomerular diseases that rarely show glomerulosclerosis (membranous nephropathy, and minimal change nephrotic syndrome). There was a significant correlation between the levels of MSW expression and type IV collagen expression. Elevated expressions of both proliferating cell nuclear antigen and MSW were also observed in most patients with proliferative glomerular diseases. These studies suggest that MSW protein plays a regulatory role in the development of mesangial cell proliferation and matrix expansion during progression of glomerular injuries.

Adult↗
PubMed1997

[A case of nephrotic syndrome associated with minimal renal amyloidosis--a four-year follow-up].

A 61-year-old male had nephrotic syndrome in association with minimal renal amyloidosis. The amyloid deposits were inconspicuous and had been initially overlooked, and the biopsy specimen was thought to show minimal glomerular changes. Accordingly he was diagnosed as having minimal change nephrotic syndrome (MCNS). Thereafter, administration of 40 mg/day of prednisolone was started. A few weeks after treatment, proteinuria decreased, but did not disappear. Four years later, he was readmitted for the treatment of the nephrotic syndrome. The second biopsy at 65 years of age revealed typical renal amyloidosis by light microscopy. Congo red staining and electron microscopy confirmed the presence of amyloid deposits. The serum A protein (SAA) level was 328 micrograms/ml. Furthermore, the first biopsy specimen revealed minimal renal amyloidosis by Congo red staining. At the time, 40 mg/day of prednisolone proved ineffective for the proteinuria. However, after methylprednisolone pulse therapy, the proteinuria decreased and the nephrotic syndrome improved. After discharge, administration of 20 mg/day of prednisolone was maintained. One year later, the patient showed no evidence of recurrence of the nephrotic syndrome and the SAA level decreased (from 328 micrograms/ml to 74.4 micrograms/ml). Prednisolone proved to have a beneficial effect on the reduction of proteinuria and SAA levels. We strongly recommend careful examination for amyloid deposits in all kidney biopsy specimens with the appearance of MCNS on older patients whose proteinuria does not respond to the administration of prednisolone.

Amyloidosis↗
PubMed1996

Intraglomerular deposition of intact cross-linked fibrin in IgA nephropathy and Henoch-Schönlein purpura nephritis.

To investigate the significance of intraglomerular coagulation and fibrinolysis in IgA nephropathy (IgA-N) and Henoch-Schönlein purpura nephritis (HSPN), the distribution of intact cross-linked fibrin (XFb) modulated by plasmin activity was examined in 25 patients with IgA-N and in 12 with HSPN. In addition to the conventional method detecting fibrin-related antigen (FRA) with an antibody against fibrinogen, the enhanced intensity of immunoreactivity of cross-linked FRA (KL-FRA) using the monoclonal antibody DD3B6/22 after plasmin exposure was evaluated to assess intraglomerular deposition of intact XFb. Also, intraglomerular invasion of macrophages was detected using the monoclonal antibody KP1 against CD68. Sixteen of a total of 37 specimens (43%) showed increased intensity of XL-FRA staining after plasmin treatment which is considered to reflect the distribution of intact XFb. Increases in the intensity of XL-FRA staining were observed mainly in mesangium and partially along glomerular capillary loops and also in a few cases in the crescents. The incidence (67%) of increases in XL-FRA staining after plasmin exposure in HSPN specimens was significantly higher than that in IgA-N specimens (32%; p < 0.05). In the group positive for XL-FRA after plasmin exposure, the numbers of macrophages per glomerulus were significantly higher (n = 15; mean +/- SD = 1.6 +/- 0.9) than in the negative group (n = 6; 0.5 +/- 0.6; p < 0.01). In HSPN, the number of macrophages per glomerulus (n = 8; 1.9 +/- 1.0) was higher than that in IgA-N (n = 13; 0.9 +/- 0.9; p < 0.05). Based on these results, we conclude that XFb is often produced and distributed in intact form in the glomeruli both in IgA-N and HSPN, associated with a relatively low intraglomerular plasmin activity, and that intraglomerular coagulation may progress in accordance with macrophage infiltration, especially in HSPN.

Fibrin↗
PubMed1994

Effects of an anti-platelet drug (dilazep) in IgA nephropathy: comparison of clinical effects with renal biopsy findings.

To investigate renal biopsy findings arising in response to treatment with an anti-platelet drug in IgA nephropathy, 46 patients were treated with dilazep dihydrochloride (Dilazep), and a retrospective comparison was performed between the clinical effects and renal biopsy findings. After 6 months of treatment, 18 patients (39%) were judged to be improved if their proteinuria was ameliorated by a 25% or greater decrease with improved or persistent renal function. The group of improved patients exhibited mean decreased levels of urinary proteins in the range from 1.9 to 0.8 g/day after treatment (p < 0.01). By contrast, the unimproved group showed increased urinary proteins in the range from 1.2 to 2.0 g/day (p < 0.05). The improved group showed histological findings with fewer glomeruli exhibiting sclerosis and/or cellular crescents, with a lesser increase in mesangial matrix and with smaller tubulo-interstitial lesions than the unimproved group. By immunofluorescence, the improved group was found to have smaller amounts of glomerular IgA and IgG deposits. These findings suggest that an anti-proteinuric effect of Dilazep administration can be expected in patients with IgA nephropathy with relatively mild glomerulo-sclerotic lesions.

Adult↗
PubMed1993

[Polyneuropathy with IgM-antibody to myelin-associated glycoprotein without detectable M-protein by conventional analysis--report of a case].

A 56-year-old man gradually developed paresthesia and muscular weakness of the left hand and feet for two years. On admission, neurological examination showed predominantly sensory polyneuropathy. Electrophysiological study and sural nerve biopsy demonstrated segmental demyelination, but any underlying congenital, toxic, metabolic or neoplastic cause was failed to reveal. The serum IgM level was 576 mg/dl, while IgG and IgA were normal. An immunoblot analysis and ELISA showed serum IgM antibody that reacted with human MAG. Serum IgM M-protein, however, was detectable not by conventional serum protein electrophoresis and immunoelectrophoresis, but by immunofixation. Anti-MAG antibodies should be evaluated in the patients with slowly progressive demyelinating polyneuropathy of unknown etiology, even if no serum M-protein is detected by conventional methods. Serum M-protein may play a role of pathogenesis of demyelination, and immunofixation method could be beneficial to detect small amount of M-protein.

Autoantibodies↗
PubMed1991

Analysis of IgG immune complexes in sera from patients with membranous nephropathy: role of IgG4 subclass and low-avidity antibodies.

The levels of circulating immune complexes (CIC) were determined using an anti-C3d binding assay in patients with various types of glomerulonephritis (GN). It was found that IgG class CIC were positive in 20% (7/35) of patients with idiopathic membranous nephropathy (MN) and in 80% (8/10) of patients with lupus glomerulonephritis (LN). Of these patients, IgG4 subclass CIC were observed more frequently in 29% of MN and 60% (3/5) of minimum change nephrotic syndrome, and, with less amounts, in 10% (1/10) of membranoproliferative GN (MPGN) and 20% (2/10) of IgA nephropathy. On the other hand, the patients with LN showed a lower positivity (30%) of IgG4-CIC as compared with that of IgG-CIC. In the comparison of mean levels, only MN patients showed significantly higher value than normal individuals (p less than 0.05). In patients with MN, the CIC of the other IgG subclasses (IgG1, IgG2, IgG3) were not significantly elevated and their positivities were low (9-11%). The study on the salt-dependent dissociability of CIC, which is considered to reflect the avidity of antibodies in CIC, showed that the IgG-CIC of 11 of 15 patients with MN were dissociable to various extents even at the physiological concentration. These findings suggested that IgG4 subclass specificity and low avidity may be pathogenic characteristics of IgG-CIC in certain populations of patients with MN.

Antibody Affinity↗
PubMed1991

Relationship of intraglomerular coagulation and platelet aggregation to glomerular sclerosis.

In order to investigate the relationship between intraglomerular coagulation and glomerular sclerosis, the distribution of fibrin-related antigen (FRA) in glomeruli without extracapillary lesions was examined by immunoperoxidase microscopy in 80 patients with IgA nephropathy (IgA-N). A total of 302 glomeruli were examined, including 20 with global sclerosis, 31 with segmental sclerosis (SS glomeruli), and 251 nonsclerosed glomeruli. In the nonsclerotic areas of SS glomeruli, the deposition of FRA was significantly greater than in the nonsclerosed glomeruli. In the nonsclerosed glomeruli FRA was mainly found in the mesangium, while in the nonsclerotic areas of SS glomeruli FRA was not only present in the mesangium but also in the endothelium of the glomerular capillary loops. FRA-positive microclots were also often observed attached to the endothelium of the capillaries of the nonsclerotic areas of SS glomeruli. Cross-linked FRA was also observed in the endothelium of the same capillaries using the monoclonal antibody DD3B6/22. Deposition of von Willebrand factor (vWF) was greater in the endothelium than in the mesangium in the same areas. Aggregated platelets adhering to the glomerular capillary walls in these areas were frequently detected using the monoclonal antibody P2. Such distribution of platelets and vWF showed that the endothelium of the nonsclerotic areas of SS glomeruli was more severely damaged than that of nonsclerosed glomeruli. These findings suggest that endothelial cell damage might activate the intraglomerular coagulation, which might be one of the factors in the development of global glomerular sclerosis.

Antigens, Human Platelet↗
PubMed1989

Immunoelectron microscopic localization of fibrin-related antigen in human glomerular diseases.

The distribution of fibrin-related antigen (FRA) in glomeruli was examined by immunoelectron microscopy in 9 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome, and 10 patients with IgA nephropathy (IgA-N), using antisera against human gamma--chain, alpha-chain, mu-chain, and fibrinogen. Electron-dense reaction products of FRA were observed in the endothelium, subendothelium, and/or in electron-dense deposits (EDD). Among the three glomerular diseases, the amount of electron-dense reaction products of FRA in the endothelium was highest in MN. This suggests that coagulation occurs on the endothelium in MN. Although the mesangial EDD of IgA-N were intensely stained with reaction products of FRA, the staining was weak in the subepithelial EDD of MN. This suggests that FRA hardly penetrates into the subepithelial EDD in MN.

Antigens↗
PubMed1989

Ultrastructural distribution of von Willebrand factor in human glomerular diseases.

The distribution of the von Willebrand factor (vWF) as the factor-VIII-related antigen in glomeruli was examined by immunoelectron microscopy in 10 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome (MCNS), and 11 patients with IgA nephropathy (IgA-N). Electron-dense reaction products of vWF were observed in the endothelium and mesangium in all specimens examined. However, they were not detected in subepithelial electron-dense deposits of MN. The amount of electron-dense reaction products of vWF in the endothelium was significantly higher in MN than that in MCNS or IgA-N. This finding suggests that the glomerular endothelium in MN is the site of the local activation of coagulation and platelet aggregation system in glomerular capillary wall lesions.

Glomerulonephritis, IGA↗