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F Endo

Publications and source records attributed to F Endo.

At least 19 recordsLinked to original sources
PubMed1999

Chloride channel CLCN5 mutations in Japanese children with familial idiopathic low molecular weight proteinuria.

BACKGROUND: Familial idiopathic low molecular weight proteinuria (FILMWP) is a renal proximal tubulopathy characterized by mild proteinuria consisting of low molecular weight proteinuria and relatively conserved renal function in young patients, but without rickets. Mutations in the renal chloride channel CLCN5 gene have been reported in three disorders of hypercalciuric nephrolithiasis and in FILMWP. METHODS: To assess the relationship between molecular defects and phenotypic variations, we analyzed the CLCN5 gene from three additional Japanese families with FILMWP using single-strand conformation polymorphism and sequencing. RESULTS: We identified three mutations: a single base insertion at codon 514; a single base deletion at codon 116; and a nonsense mutation, R704X. The R704X mutation is identical to that found in X-linked recessive nephrolithiasis, but there was no renal failure in our patient. The first two mutations caused a shift in the reading frame, and all introduced a premature stop codon, resulting in synthesis of truncated CLC-5 proteins that lacked 220 (29%), 610 (82%), and 43 (6%) amino acids, respectively. These mutations were demonstrated to cosegregate with the disease in each of the three families. CONCLUSIONS: We conclude that the CLCN5 gene is responsible for the renal proximal tubulopathy in many Japanese families and suggest that molecular defects, environmental factors, or other modifying genes may account for the different phenotypes.

Amino Acid Sequence↗
PubMed1998

Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors.

Tyrosinemia type 1, caused by mutations in the fumarylacetoacetate hydrolase gene (Fah), is characterized by severe liver injury. We earlier developed a tyrosinemic mouse model with two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd) deficiencies. Apoptosis of hepatocytes was induced and an acute onset of liver failure occurred after administration of homogentisic acid (HGA), the intermediate metabolite between the enzymes HPD and FAH. Cytochrome c was released from mitochondria prior to liver failure in the Fah-/- Hpd-/- double-mutant mice after the administration of HGA. In a cell-free system, the addition of fumarylacetoacetate induced the release of cytochrome c from the mitochondria. We also found that caspase inhibitors were highly effective in preventing the liver failure induced by HGA in the double-mutant mice. Therefore, fumarylacetoacetate apparently induces the release of cytochrome c, which in turn triggers activation of the caspase cascade in hepatocytes of subjects with hereditary tyrosinemia type 1.

Acetoacetates↗
PubMed1998

Intracellular distribution of the Wilson's disease gene product (ATPase7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson's disease.

In patients with Wilson's disease, both copper incorporation into ceruloplasmin and excretion of this metal into bile are impaired. These conditions are caused by a genetic defect in the Wilson's disease gene (ATP7B). To investigate the Wilson's disease gene protein (ATPase7B) in hepatocytes, we constructed an expression plasmid carrying full-length complementary DNA for human Wilson's disease gene and attempted to express the gene in hepatocytes of LEC rats, an animal model of Wilson's disease. Transfection of hepatocytes, either in vitro or in vivo, was done using a newly developed cationic liposome containing 1,4-bis(3-(N-hexadecyl) aminopropyl) piperazine. Immunological analyses of human ATPase7B with specific monoclonal antibodies showed human ATPase7B to be a membrane protein with a molecular mass of 155 kd. Analysis of human ATPase7B expressed in hepatocytes from LEC rats suggested that this protein is present in the trans-Golgi network and at the plasma membrane, a distribution pattern similar to that of Menkes' disease protein (ATPase7A). These findings suggest that these two putative copper-transporting P-type ATPases function similarly at the cellular level. Cotransfection and coexpression of the human Wilson's disease gene and ceruloplasmin gene in cultured hepatocytes indicate that the distribution of ceruloplasmin is always accompanied by ATPase7B at the perinuclear region, but that part of ATPase7B localizes irrespective of the distribution of ceruloplasmin. Based on these investigations, we propose that ATPase7B exists in the trans-Golgi network and transports copper into this compartment. This seems to ensure an appropriate delivery of copper to the apoceruloplasmin. On the other hand, part of ATPase7B that is not accompanied by ceruloplasmin in the perinuclear region and at the plasma membrane seems to contribute to efflux of this metal from the hepatocytes. Thus the distribution patterns of ATPase7B in hepatocytes may explain the dual roles of this P-type ATPase in hepatocytes.

Adenosine Triphosphatases↗
PubMed1998

Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan.

In Japan, urea cycle disorders (UCDs) are one of the most frequent inborn errors of metabolism, estimated to have a prevalence of 1 per 50,000 live births. In an attempt to develop more effective treatment and enhance the quality of life, we investigated the clinical manifestations and prognosis of 216 patients with UCDs diagnosed and treated between 1978 and 1995. These included 92 cases of neonatal-onset UCD and 116 of late-onset UCD. Two cases of ornithine transcarbamylase (OTC) deficiency in males and 2 cases of argininosuccinase (AL) deficiency were diagnosed prospectively. By far the most common disorder was OTC deficiency, accounting for 2/3 of all cases. At the end of 1995, the 5-year survival rate was 22% for the neonatal-onset type and 41% for the late-onset type. Among the 20 long-term survivors with neonatal-onset UCD, 18 (90%) had moderate to severe neurodevelopmental deficits; this contrasts with 13 of 47 (28%) survivors with the late-onset type. In analysing 108 UCD cases, peak blood ammonia level during the first hyperammonaemic attack was correlated with neurodevelopmental outcome. When the concentration of blood ammonia was less than 180 mumol/L (5 times normal), there was no severe neurological damage. When the concentration of blood ammonia exceeded 350 mumol/L (10 times normal) at the first hyperammonaemic attack, the patients died or had severe neurological deficits. Our data point to the importance of early diagnosis and aggressive treatment.

Age of Onset↗
PubMed1998

X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X-linked and hemizygous new-born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X-inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X-inactivation patterns and the residual OTC activities. The X-inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X-inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X-inactivation varied considerably, even within the same liver.

Child↗
PubMed1998

Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes.

BACKGROUND: Nedd4 is a ubiquitin-protein ligase containing a calcium/lipid-binding domain, multiple WW domains and a C-terminal Hect domain, which is required for both the ubiquitin transfer and the association with E2 ubiquitin-conjugating enzymes. Nedd4 has been reported to be involved in the selective ubiquitination of some regulatory proteins in transcription and membrane transport. RESULTS: Three mRNA species for human Nedd4 were found to be 6.4-, 7.8- and 9.5-kb in size, and their expression patterns varied among normal tissues and cancer cell lines, indicating the tissue- and cell-specificities of Nedd4 expression. The Nedd4 protein, approximately 120 kDa in weight, was found in the cytoplasm, mainly in the perinuclear region and cytoplasmic periphery, of human cultured cells. Neural differentiation induced not only the down-regulation of Nedd4 but also the localization of the protein to both the cytoplasm and neurites. To identify the ubiquitination pathway that is linked to Nedd4, we demonstrated that specific E2 enzymes, including human Ubc4, UbcH5B, UbcH5C, UbcH6 and UbcH7, could transfer ubiquitin molecules to Nedd4 at the active cysteine residue, whereas E6AP accepted ubiquitins from Ubc4, UbcH5B, UbcH5C and UbcH7. Furthermore, nuclear localization of N-terminal deletion mutant Nedd4 enabled us to investigate the interaction between Nedd4 and E2 enzyme (Ubc4 or UbcH7) in the cell. The simultaneous expression of the full-length Nedd4 and E2 enzyme revealed the both proteins mostly colocalized in the cytoplasmic periphery, while the N-terminal deleted Nedd4 induced the nuclear and perinuclear colocalization with E2 enzyme. CONCLUSION: Our findings suggested that Nedd4 plays an important role in the cell regulation, including neural differentiation through cooperation with specific E2 ubiquitination pathways.

Cell Differentiation↗
PubMed1998

Anticarcinogenic effects of shikaron, a preparation of eight Chinese herbs in mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine.

We studied the effects of Shikaron, which is composed of 8 Chinese herb extracts, on carcinogenesis and the cytotoxic activity and cytokine production of lymphocytes in mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine (BBN). We found a significantly lower incidence of urinary bladder carcinoma in mice treated with BBN plus Shikaron 200 mg/kg/day (5 of 20 mice, 25%), than in mice treated with BBN alone (16 of 20 mice, 80%). Shikaron protected the cytotoxic activity of lymphocytes against YAC-1 cells from suppression by BBN. Cytotoxic activity against P-815 cells significantly increased in mice treated with BBN plus Shikaron, as compared with normal mice and BBN-treated mice. Shikaron also protected production of interleukin-2 and interferon-gamma by lymphocytes from suppression by BBN. These findings strongly suggest that Shikaron exerted an anticarcinogenic effect in carcinogen-treated mice through activation of NK and LAK cells and cytokine production by T lymphocytes.

Animals↗
PubMed1998

[Inflammatory pseudotumor of the ureter: a case report].

A 57-year-old male was admitted because of the right flank pain. The image examinations, retrogradeurography, abdominal CT and MRI, showed a mass located at the upper right ureter. Although the tumor was not typical as ureteral cancer, we could not make a diagnosis of a benign tumor by image examinations. Therefore nephroureterectomy that was surgical method for ureteral cancer was performed. The tumor was diagnosed as inflammatory pseudotumor of the ureter by histological findings. Inflammatory pseudotumor is extremely rare for ulogeital organs. And this lesion is difficult to distinguish from malignancy only by image examinations. Therefore, the surgical resection and pathological studies are necessary.

Diagnosis, Differential↗
PubMed1998

[Hawkinsinuria].

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Amino Acid Metabolism, Inborn Errors↗