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Biomedical subjects

H Koide

Publications and source records attributed to H Koide.

At least 37 records · Page 2Linked to original sources
PubMed2000

Urinary podocytes for the assessment of disease activity in lupus nephritis.

BACKGROUND: Detection of podocytes in the urine indicates that severe injury of podocytes occurred in the glomerulus in children. METHODS: The pathological significance of podocytes in the urine was determined in patients with lupus nephritis. Podocytes were detected by immunofluorescence using a monoclonal antibody against podocalyxin present on the surface of podocytes. Subjects who participated in the present study were of the following types: patients with systemic lupus erythematosus with stable renal function (group A, n = 8; WHO classes IlIa, b, IVb, and IVc at the time of biopsy); patients with clinically active lupus nephritis (group B, n = 8; WHO classes IVb and IVc); and healthy control subjects (group C, n = 10). RESULTS: Podocytes were absent in the urine of subjects in groups A and C. However, podocytes were present in the urine of group B subjects. Patients in group B were examined monthly for urinary podocytes and were treated with methylprednisolone followed by prednisolone. Urinary podocytes were absent in all patients in group B after treatment. CONCLUSIONS: These data indicate that urinary podocytes may be markers of the severity of lupus nephritis and that steroid therapy may be effective for podocyte injury in lupus nephritis.

Adult↗
PubMed2000

Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts.

In skeletal myoblasts, Ras has been considered to be a strong inhibitor of myogenesis. Here, we demonstrate that Ras is involved also in the chemotactic response of skeletal myoblasts. Expression of a dominant-negative mutant of Ras inhibited chemotaxis of C2C12 myoblasts in response to basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and insulin-like growth factor 1 (IGF-1), key regulators of limb muscle development and skeletal muscle regeneration. A dominant-negative Ral also decreased chemotactic migration by these growth factors, while inhibitors for phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase (MEK) showed no effect. Activation of the Ras-Ral pathway by expression of an activated mutant of either Ras, the guanine-nucleotide dissociation stimulator for Ral, or Ral resulted in increased motility of myoblasts. The ability of Ral to stimulate motility was reduced by introduction of a mutation which prevents binding to Ral-binding protein 1 or phospholipase D. These results suggest that the Ras-Ral pathway is essential for the migration of myoblasts. Furthermore, we found that Ras and Ral are activated in C2C12 cells by bFGF, HGF and IGF-1 and that the Ral activation is regulated by the Ras- and the intracellular Ca(2+)-mediated pathways. Taken together, our data indicate that Ras and Ral regulate the chemotactic migration of skeletal muscle progenitors.

Animals↗
PubMed2000

Effect of plasma exchange on serum tissue inhibitor of metalloproteinase 1 and cytokine concentrations in patients with fulminant hepatitis.

AIMS: The present study assessed whether the serum concentrations of tissue inhibitor of metalloproteinase 1 (TIMP-1) and cytokines are altered in patients with fulminant hepatitis and whether plasma exchange affects these concentrations. METHODS: Fifteen patients with fulminant hepatitis, 14 patients with severe acute hepatitis, and 20 healthy controls were included in this study. The serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), transforming growth factor beta (TGF-beta), and TIMP-1 were determined in all patients upon hospital admission and before and after a single course of plasma exchange in the patients with fulminant hepatitis. RESULTS: Ten out of the 15 patients with fulminant hepatitis and all patients with severe acute hepatitis survived. Serum TNF-alpha, IL-6, TGF-beta, and TIMP-1 levels in patients with fulminant hepatitis were significantly higher than the levels in patients with severe acute hepatitis (p < 0.01). IL-1beta was not detectable in either group. Plasma exchange reduced the increased serum concentrations of TNF-alpha, IL-6, TGF-beta, and TIMP-1 in patients with fulminant hepatitis (p < 0.01). CONCLUSIONS: These data suggest that increased serum levels of TIMP-1 and cytokines may reflect severe hepatic inflammation and that plasma exchange is an effective therapy to reduce these levels.

Acute Disease↗
PubMed2000

Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy.

OBJECTIVE: To determine whether the antiplatelet drug dilazep dihydrochloride affects the number of urinary podocytes in diabetic patients with microalbuminuria. RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and microalbuminuria (30 men and 20 women, mean age 48.6 years) and 30 age-matched control subjects (18 men and 12 women, mean age 49.2 years) were included in the study. No patients showed serum creatinine levels in excess of 2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy with monoclonal antibodies against podocalyxin. RESULTS: Urinary podocytes were detected in 18 of the 50 microalbuminuric diabetic patients (mean, 1.3 cells/ml). Urinary podocytes were not detected in the remaining 32 patients or in the 30 healthy control subjects. Diabetic patients positive for urinary podocytes were divided into 2 treatment groups: a dilazep dihydrochloride treatment group (300 mg/day; n = 9, group A) and a placebo group (n = 9, group B). Treatments were continued for 6 months. In group A, microalbuminuria decreased significantly from 146 +/- 42 to 86 +/- 28 microg/min (P < 0.01) and urinary podocytes also decreased from 1.3 +/- 0.8 to 0.4 +/- 0.2 cells/ml (P < 0.01). However, in group B, microalbuminuria and urinary podocytes changed little over the study period. CONCLUSIONS: Podocyte injury may occur in patients with early diabetic nephropathy, and dilazep dihydrochloride may be useful for preventing glomerular injury.

Albuminuria↗
PubMed1999

Treatment with polymyxin B-immobilized fiber reduces platelet activation in septic shock patients: decrease in plasma levels of soluble P-selectin, platelet factor 4 and beta-thromboglobulin.

OBJECTIVE: To clarify whether plasma concentrations of soluble P-selectin, platelet factor-4 (PF-4) and beta-thromboglobulin (betaTG) are altered in patients with septic shock and whether polymyxin B-immobilized fiber (PMX-F) treatment affects these changes. SUBJECTS: Thirty patients with septic shock who were treated with PMX-F (group A), 20 such patients who received conventional therapies (group B) and 20 healthy control subjects(group C). METHODS: ELISA using commercial kits. Endotoxin elimination by direct hemoperfusion using PMX-F. RESULTS: Blood endotoxin levels decreased significantly from 49.4+/-8.8 pg/ml to 13.0+/-4.5 pg/ml after PMX-F treatment. The pretreatment plasma concentrations of soluble P-selectin, PF-4 and betaTG in patients in groups A and B were significantly higher than those in group C (p<0.001). Plasma concentrations of these factors decreased significantly in group A after PMX-F treatment (p<0.01); however, the concentrations in group B were not altered after conventional treatment. The survival rate of group A (60%) was higher than that of group B (30%). CONCLUSIONS: Our findings suggest that soluble P-selectin, PF-4 and betaTG may be associated with septic shock and that PMX-F is effective in reducing these markers in patients with septic shock.

Adult↗
PubMed1999

Gene therapy for renal anemia in mice with polycystic kidney using an adenovirus vector encoding the human erythropoietin gene.

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is primarily used for patients with anemia associated with end-stage renal disease. We evaluated the efficacy of EPO gene therapy using adenovirus vector for chronic renal failure mice expressing severe renal anemia. METHODS: Recombinant HuEPO gene transfer to mesothelial cells was performed in vitro and in vivo. Recombinant replication-deficient adenoviruses containing rHuEPO cDNA (AdCMVEPO), E. coli lacZ gene (AdCMVlacZ), or an nonexogenous gene (AdNull as control vector) driven by the cytomegalovirus promotor/enhancer were constructed. The oligosaccharides associated with the rHuEPO from AdCMVEPO-treated mesothelial cells were analyzed. For in vivo study, the DBA/2FG-pcy mouse, a model for human autosomal recessive polycystic kidney disease resulting in chronic renal failure with progressive anemia, was used. RESULTS: The sialylated oligosaccharides associated with the rHuEPO produced in AdCMVEPO-treated mesothelial cells occupied 78 +/- 0.7% of the total oligosaccharide pool. A single intraperitoneal administration of AdCMVEPO induced rHuEPO synthesis in the peritoneal cells and a marked increase in erythrocyte production. The maximal increase in hematocrit (43 +/- 4%) was observed on day 28, and it remained elevated for 40 days. CONCLUSION: These results indicate that intraperitoneal administration of AdCMVEPO improves renal anemia in mice with chronic renal failure and that the mesothelial cell is an appropriate target cell for gene transfer.

Adenoviridae↗
PubMed1999

Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in the Japanese population, is characterized by congenital muscular dystrophy in combination with cortical dysgenesis (micropolygyria). Recently, we identified, on chromosome 9q31, the gene responsible for FCMD, which encodes a novel 461 amino acid protein which we have termed fukutin. Most FCMD-bearing chromosomes examined to date (87%) have been derived from a single ancestral founder, whose mutation consisted of a 3 kb retrotransposal insertion in the 3' non-coding region of the fukutin gene. FCMD is the first human disease known to be caused primarily by an ancient retrotransposal integration. We under-took a systematic analysis of the FCMD gene in 107 unrelated patients, and identified four novel non-founder mutations in five of them: one missense, one nonsense, one L1 insertion and a 1 bp insertion. The frequency of severe phenotypes, including Walker-Walberg syndrome-like manifestations such as hydrocephalus and microphthalmia, was significantly higher among probands who were compound heterozygotes carrying a point mutation on one allele and the founder mutation on the other, than it was among probands who were homozygous for the 3 kb retrotransposon. Remarkably, we detected no FCMD patients with non-founder (point) mutations on both alleles of the gene, and suggest that such cases might be embryonic-lethal. This could explain why few FCMD cases are reported in non-Japanese populations. Our results provided strong evidence that loss of function of fukutin is the major cause of FCMD, and appeared to shed some light on the mechanism responsible for the broad clinical spectrum seen in this disease.

Base Sequence↗
PubMed1999

Abnormal distribution of mesangium-specific laminin in glomeruli of patients with idiopathic membranous nephropathy.

Using a monoclonal antibody, the distribution of the mesangium-specific laminin that binds only to the mesangium in normal kidney, was studied immunohistochemically in renal tissues obtained from patients with different glomerulonephritides including idiopathic membranous nephropathy. In minimal change nephrotic syndrome and IgA nephropathy, the mesangium-specific laminin staining was restricted to the mesangium, as is observed in the normal kidney. However, in patients with idiopathic membranous nephropathy, the monoclonal antibody against the mesangium-specific laminin reacted with the glomerular peripheral capillary walls including subepithelial protrusions or 'spikes', as well as with the mesangium. These results suggest that the quality of laminin produced in response to the challenge of immune deposits in the peripheral capillary walls may be different from that in the rest of the glomerular basement membrane in idiopathic membranous nephropathy.

Animals↗