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H Tochimaru

Publications and source records attributed to H Tochimaru.

At least 19 recordsLinked to original sources
PubMed1999

A Japanese case with Frasier syndrome caused by the splice junction mutation of WT1 gene.

The Wilms' tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and also subsequent normal function of this system. Recently, the splice mutations in intron 9 of WT1 gene have been detected in Frasier syndrome, which is characterized by streak gonads, pseudohermaphroditism, slowly progressive nephropathy and frequent development of gonadoblastoma. Here to elucidate the molecular basis in a Japanese patient of Frasier syndrome, WT1 gene was analyzed by polymerase-chain-reaction (PCR) and direct sequencing. We identified the splice junction mutation in intron 9 of WT1, which is recognized as a mutation hot-spot in intron 9. This finding concludes that 1) the mutation in intron 9 might be the cause of Frasier syndrome, and 2) the mutation hot-spot in Japanese and Caucasian patients is similar.

Adolescent↗
PubMed1998

4q33-qter deletion and absorptive hypercalciuria: report of two unrelated girls.

We report on two unrelated girls with multiple malformations, each of whom had a der(4)t(4;?)(q33;?) chromosome--an unbalanced translocation chromosome with deletion of the 4q33-qter segment and addition of a segment of an unknown chromosome. One of the two girls had asymptomatic kidney stones. Both had excess urinary calcium excretion (0.53 and 0.84 mg/mg creatinine, respectively), exaggerated excretion on oral calcium load, and reduced but excessive excretion on restricted calcium intake. The urinary calcium excretion of their parents was normal. Both girls were thus diagnosed to have sporadic absorptive hypercalciuria. It was deduced that the 4q33-qter segment contains the putative gene for absorptive hypercalciuria.

Abnormalities, Multiple↗
PubMed1996

Identification and immunohistochemical localization of macrophage migration inhibitory factor in human kidney.

Macrophage migration inhibitory factor (MIF) was the first lymphokine identified in activated T-lymphocytes. MIF can induce proinflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alpha. In this study, we identified MIF expression in a tissue specimen of a normal portion of a nephrectomized human kidney by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Furthermore, immunohistochemical study using an anti-human MIF polyclonal antibody demonstrated that MIF was mostly present in the renal tubule epithelial cells and, to a lesser extent, in Bowman's capsular epithelial cells. We also carried out immunohistochemistry on cultured human renal proximal tubule epithelial cells, which showed that MIF was present in the cytoplasm of the epithelial cells. These results suggest the possibility that MIF takes part in the mechanism of inflammation and immunological events in the human kidney.

Blotting, Western↗
PubMed1993

Current topics in childhood lupus nephritis.

Lupus nephritis is a major predictor of the prognosis of systemic lupus erythematosus (SLE). The present paper discusses lupus nephritis from clinical and immunopathological points of view. Although recent advances in diagnosis and treatment improve the prognosis of children with SLE, there remain many unsolved clinical problems. One of the current topics in the treatment for SLE is intermittent intravenous cyclophosphamide therapy which is effective even for the steroid-resistant patients with severe lupus nephritis, at least for short-term observation. Immunopathologically, the following issues are discussed: (i) The C5b-9 terminal complement complex plays an important role in the pathogenesis of lupus nephritis. The possible interaction of vitronectin and SP-40,40 is also mentioned; (ii) A semi-quantitative analysis of the charge barrier of the glomerular basement membrane reveals that the charge barrier dysfunction plays an important role in the pathogenesis of proteinuria in lupus nephritis. This study also demonstrates that the charge of immune deposits is important for the initiation of glomerular injury in lupus nephritis; (iii) It is demonstrated that the histopathological diversity of lupus nephritis is based on biological properties of nephritogenic auto-antibodies in murine lupus models.

Adolescent↗
PubMed1992

Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease.

The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats. The serum concentrations of copper and ceruloplasmin were significantly lower than those of control rats from the 4th wk (10-12% and 5-19%, respectively). Copper contents in kidney of LEC rats did not exhibit an increase over those of control rats until 12 wk, but then increased to nearly 40 times higher during fulminant hepatic failure. Accumulation of copper was not detected in the brain or small intestines of LEC rats until 13 mo. The hepatic copper concentration, its subcellular distribution, and serum copper concentration of F1 rats (LEC x Long-Evans Agouti) exhibited the same levels as those of Long-Evans Agouti rats. In addition to their similarity concerning inheritance of autosomal recessive means and clinical course, we found causality relating copper accumulation to the pathogenesis of the disease. We propose that LEC rats will be the most promising animal model for the study of Wilson's disease.

Age Factors↗
PubMed1991

Urinary excretion of terminal complement complexes in glomerular disease.

To evaluate renal terminal complement activation in patients with glomerular diseases, we measured terminal complement complexes (TCCs) in plasma and urine with sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a C9 neoepitope expressed on TCC and a polyclonal antihuman C7 antibody. TCCs were detectable in plasma but not in urine in most of normal controls. In plasma, TCC levels were elevated in 4 of 22 patients with lupus nephritis and in 6 of 12 with membranoproliferative glomerulonephritis. However all patients with IgA nephritis, focal glomerulosclerosis, idiopathic membranous nephritis and idiopathic minimal change nephrotic syndrome (MC) showed normal values. In urine, TCCs were detectable in almost all patients with heavy proteinuria (greater than or equal to 100 mg/ml) except MC. The TCCs present in urine were partially purified by gel filtration using Sepharose 6B and were found to contain C5, C6, C7, C8, C9 and S protein by ELISA. Although the molecular weight of TCC is similar to that of IgM, the fractional excretion rate of TCC was about 100 times higher than that of IgM. These results suggest that TCCs detectable in urine contain SC5b-9 complexes and are mostly of renal origin.

Adolescent↗
PubMed1991

[Electron microscopic study of the glomerular basement membrane charge barrier and the charge of immune deposits in lupus nephritis].

In order to evaluate the pathogenesis of proteinuria and the charge of immune deposits in lupus nephritis, anionic sites of periodate-lysin-paraformaldehyde (PLP) fixed renal tissue (5 patients with renal pelvic tumor as normal control and 17 patients with lupus nephritis), were stained with the critical electrolyte concentration method. Cuprolinic blue (CB) was used as a cationic probe. Ultra-structural study and semi-quantitative analysis were done. In the normal glomerular basement membrane (GBM), the CB stainable anionic sites appeared as filamentous structure with several short lateral branches. On the basis of electron microscopic observation of isolated proteoglycan, it is suggested that the central filaments are the protein core and the branches are the glycosaminoglycans of proteoglycan molecules. These filamentous anionic sites were located mainly in the laminae larae and lie close to each other forming a mesh-like network pattern. The semi-quantitative analysis of the normal GBM revealed that the number of anionic sites in the lamina rara externa (LRE) was 22.9 +/- 1.9-23.7 +/- 1.4/1000 nm GBM and in the lamina rara interna (LRI) 14.0 +/- 1.6-15.1 +/- 1.5/1000 nm GBM. These findings suggest that the anionic sites composed of heparan sulphate proteoglycan occupy large area of the laminae larae and prevent permeation of anionic molecules. In non-proteinuric 5 patients with class II lupus nephritis, the number of anionic sites of the GBM (LRE; 21.3 +/- 2.0-22.3 +/- 1.8/1000 nm GBM, LRI; 13.5 +/- 2.0-14.2 +/- 2.0/1000 nm GBM) showed no significant difference from that of the normal GBM. In contrast, the GBM of proteinuric patients with class IV (6 patients, LRE; 14.8 +/- 2.7-19.3 +/- 1.8/aooo nm GBM, LRI; 5.8 +/- 1.9-11.3 +/- 2.4/1000 nm GBM) and (V) (6 patients, LRE; 13.0 +/- 2.4-17.9 +/- 2.8/1000 nm GBM, LRI; 12.0 +/- 1.9-13.0 +/- 2.5/1000 nm GBM) exhibited loss of the anionic sites in association with the localization of the immune deposits (ID). From these findings, it is concluded that in severe and active lupus nephritis the failure of charge barrier of the GBM is responsible for the proteinuria. The ID observed in the patients with lupus nephritis were not stained with CB. This finding suggests that net charge of the ID could be cationic and that cationic immune complex and/or antibody could involve in the pathogenesis of lupus nephritis.

Adolescent↗
PubMed1990

Renal tubular involvement mimicking Bartter syndrome in a patient with Kearns-Sayre syndrome.

A 10-year-old boy had short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, and sensorineural hearing loss (Kearns-Sayre syndrome). In addition to ragged-red fibers observed on modified Gomori trichrome staining, there were scattered fibers exhibiting no cytochrome c oxidase activity, indicating a focal deficiency. Cytochrome c oxidase and other respiratory chain enzyme activities were normal biochemically. The patient also had renal tubular dysfunction, including isosthenuria, decreased urine-concentrating ability, and excessive excretion of potassium and magnesium. In addition, he had hyperreninemia and hyperaldosteronism but no hypertension. The renal dysfunction was thought to have resulted from a primary defect in the thick ascending limb of the loop of Henle, mimicking Bartter syndrome. In contrast to previously described cases of cytochrome c oxidase deficiency with de Toni-Fanconi Debré syndrome, the patient had less intensive muscle abnormalities. A renal biopsy specimen showed ultrastructural changes in mitochondria that were similar to those seen in biopsy specimens of muscle. A large-scale deletion (8.8 kilobases) in mitochondrial DNA was found in biopsy specimens of muscle and kidney.

Bartter Syndrome↗
PubMed1990

IgA nephritis in Behçet's disease: case report and review of the literature.

We describe a 13-year-old girl with the incomplete type of Behçet's disease who had recurrent oral and genital ulcers, folliculitis, proteinuria and hematuria. Renal biopsy specimens revealed diffuse proliferative glomerulonephritis with strongly positive IgA deposits in the glomerular mesangial area, which is histologically indistinguishable from primary IgA nephritis. Further studies of the IgA subclasses showed that IgA1 deposits were predominant in the glomerular mesangium. Primary IgA nephritis is thought to be associated with polymeric IgA1. So it appears that there may be a common underlying disease or mechanism involved in both primary IgA nephritis and the IgA nephritis in Behçet's disease.

Adolescent↗