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Biomedical subjects

F Endo

Publications and source records attributed to F Endo.

At least 19 recordsLinked to original sources
PubMed2000

Statistical and mutational analysis of chronic granulomatous disease in Japan with special reference to gp91-phox and p22-phox deficiency.

Chronic granulomatous disease (CGD) is a group of inherited disorders of host defense caused by a mutation in any of the four components of phagocyte NADPH oxidase, namely gp91-, p22-, p47-, and p67-phox. We have made a precise statistical analysis of 229 registered patients from 195 families in Japan and mutation analysis of 28 and 5 independent patients, respectively, with gp91- and p22-phox deficiency. The gp91- and p22-phox proteins form the membrane cytochrome b558, which plays important roles in the assembly of the active oxidase and electron-transfer reaction, and the lesions in either subunit account for more than 80% of cases. The ratio of male to female patients was 6.6/1, the incidence was calculated to be about 1 out of 220,000 birth, and the life expectancy of the patients born in the 1970s was estimated to be 25-30 years old. For the X-linked gp91-phox deficiency, we found five missense and nine nonsense mutations, seven deletions, three insertions, and four splice site mutations, which included the following novel mutations: four missense, five nonsense, six deletions, one insertion, and two splice site abnormalities. With regard to p22-phox deficiency, two homozygous nonsense mutations and one homozygous deletion, a missense mutation together with a splice site mutation, and two different missense mutations were found. These mutations have not been reported before. Based on the present and reported data from Japan, we discuss the molecular defects of the disease and the difference in statistics between western countries and Japan.

Base Sequence↗
PubMed2000

Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport caused by mutations in the SLC7A7 gene. We report the genomic structure of the gene and the results of the mutational analysis in Italian, Tunisian, and Japanese patients. The SLC7A7 gene consists of 10 exons; sequences of all of the exon-intron boundaries are reported here. All of the mutant alleles were characterized and eight novel mutations were detected, including two missense mutations, 242A-->C (M1L) and 1399C-->A (S386R); a nonsense mutation 967G-->A (W242X); two splice mutations IVS3 +1G-->A and IVS6 +1G-->T; a single-base insertion, 786insT; and two 4-bp deletions, 455delCTCT and 1425delTTCT. In addition, a previously reported mutation, 1625insATCA, was found in one patient. It is noteworthy that 242A-->C causes the change of Met1 to Leu, a rare mutational event previously found in a few inherited conditions. We failed to establish a genotype/phenotype correlation. In fact, both intrafamilial and interfamilial phenotypic variability were observed in homozygotes for the same mutation. The DNA-based tests are now easily accessible for molecular diagnosis, genetic counseling, and prenatal diagnosis of LPI.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

Membranoproliferative glomerulonephritis in congenital portosystemic shunt without liver cirrhosis.

We report two cases with congenital portosystemic shunt who developed renal lesions without liver cirrhosis. Clinically, both cases showed proteinuria and mild hematuria at 9 and 6 years of age, respectively. In one case, the renal lesion was associated with normal renal function, but nephrotic syndrome followed by chronic renal failure were noted in the other. Renal biopsies showed characteristic histological features of membranoproliferative glomerulonephritis (MPGN) with IgA deposits along the glomerular capillary wall. Our cases strongly suggest the association between congenital portosystemic shunt and renal region. The shunt ratio may be an important predisposing factor for this type of nephropathy since a high shunt ratio (> 90%) was noted in both cases.

Child↗
PubMed1999

Immunohistochemical determination of the Wilson Copper-transporting P-type ATPase in the brain tissues of the rat.

Immunohistochemical localization of Copper-transporting P-type ATPase (ATP7B), a gene product responsible for Wilson disease, was visualized in the brain tissues of the Long-Evans agouti rat in detail using tissue-blotting technique and confocal laser microscopy. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brainstem in which high amounts of copper and cuproenzymes, dopamine beta hydroxylase and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) were detected. The present results suggest that ATP7B plays key roles in neurotransmissions of catecholamine pathway and preventing brain tissues from injury by superoxide radicals to regulate the cellular Cu concentration and/or activities of cuproenzymes related to neurotransmissions and a free radical metabolism. Furthermore, it is reasonable to assume that neurotoxicity due to abnormal copper accumulation or irregular regulation of cuproenzymes in the critical brain regions by mutation of the ATP7B gene leads to neurological failures of Wilson disease.

Adenosine Triphosphatases↗
PubMed1999

Surgical indications for patients with hyperammonemia.

BACKGROUND/PURPOSE: The authors surgically treated seven of eight patients with congenital portosystemic shunt and hyperammonemia. This entity is uncommon in children. METHODS: The patients included five boys and three girls with a mean age of 8 years (range, 7 months to 24 years). Preoperative symptoms included hyperammonemia. Hepatic encephalopathy was evident in five patients. Diagnosis and assessment were made by ultrasound scan, magnetic resonance imaging (MRI), angiography, and 123 I-iodoamphetamine per-rectal portal scintigraphy. Surgical banding was done for five patients and transvenous coil embolization for two. One patient was not a surgical candidate because there were no intrahepatic portal veins. RESULTS: In four of the five patients treated using surgical banding, and in both patients who underwent coil embolizations, hyperammonemia and clinical symptoms improved soon after surgery. However, in the remaining patient, hyperammonemia worsened after surgery, and reoperation was needed because of a severe portal hypertension, possibly caused by malconformation of hepatic veins. CONCLUSIONS: For patients with congenital portosystemic shunt, early diagnosis and surgery are needed to prevent damage to central nerves caused by persistent hyperammonemia. Maldevelopment of the intrahepatic portal veins is a surgical option, if the patient has a normal liver architecture, but malconformation of hepatic veins or severe anomalies such as cardiac defects would rule out surgical intervention.

Adolescent↗
PubMed1999

Successful coil embolization in an infant with congenital intrahepatic portosystemic shunts.

The authors report the case of a 7-month-old Japanese infant with congenital intrahepatic portosystemic shunts. He had hypergalactosaemia and hyperammonemia at age 1 month. The diagnosis was made by ultrasonography and angiography. Coil embolization was performed successfully, and then hyperammonemia and hypergalactosaemia improved soon after surgery.

Embolization, Therapeutic↗
PubMed1999

The long-term prognosis of congenital portosystemic venous shunt.

Congenital portosystemic venous shunt (PSVS), considered to be a rare disease, can lead to hepatic encephalopathy (HE). With improvements in diagnostic imaging techniques, the number of infants and children with documented PSVS has increased. The natural course of the disease and indications for surgical closure of the shunt vessel have not been well defined. We reviewed 51 cases of congenital PSVS in Japan; 34 patients had an intrahepatic PSVS, and 17 had an extrahepatic PSVS. There were 12 patients with HE at the time of diagnosis. The frequency of HE increased in subjects over 60 years of age. Children with HE had a shunt ratio exceeding 60%. When the shunt ratio was less than 30%, HE did not occur. Twenty of 28 patients under the age of 15 years had hypergalactosemia at the time of neonatal screening. Part of the congenital intrahepatic PSVS spontaneously closed. Surgical closure of a PSVS may be an approach expected to prevent HE when the shunt ratio exceeds 60%.

Adolescent↗
PubMed1999

Mass screening for Wilson's disease: results and recommendations.

Wilson's disease is a treatable inherited disorder of copper metabolism. Established treatments include the use of oral chelating agents and the establishment of a minimum copper diet, although prognosis mainly depends on the extent of liver or nervous system damage present before treatment. Once irreversible damage has occurred, the effect of these treatments is diminished and the patient's quality of life compromised. Therefore, the establishment of a mass screening system able to detect Wilson's disease patients presymptomatically has been discussed. Recently, a monoclonal antibody specific to holoceruloplasmin has been developed. This antibody was used in a nationwide screening trial of 126,810 newborn infants, but no Wilson's disease patients were identified. However, three patients out of 24,165 were diagnosed with Wilson's disease using this specific antibody in a screening performed during the period from late infancy to elementary school. The age of 3 years is thought to be the best point for Wilson's disease mass screening. In this paper, a review of mass screening for Wilson's disease in Japan using a specific monoclonal antibody to holoceruloplasmin is presented.

Antibodies, Monoclonal↗
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↗
PubMed1999

Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.

Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by recurrent episodes of unexplained fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. Human TRKA encodes a high-affinity tyrosine kinase receptor for nerve growth factor (NGF), a member of the neurotrophin family that induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. We have recently demonstrated that TRKA is responsible for CIPA by identifying three mutations in a region encoding the intracellular tyrosine kinase domain of TRKA in one Ecuadorian and three Japanese families. We have developed a comprehensive strategy to screen for TRKA mutations, on the basis of the gene's structure and organization. Here we report 11 novel mutations, in seven affected families. These are six missense mutations, two frameshift mutations, one nonsense mutation, and two splice-site mutations. Mendelian inheritance of the mutations is confirmed in six families for which parent samples are available. Two mutations are linked, on the same chromosome, to Arg85Ser and to His598Tyr;Gly607Val, hence, they probably represent double and triple mutations. The mutations are distributed in an extracellular domain, involved in NGF binding, as well as the intracellular signal-transduction domain. These data suggest that TRKA defects cause CIPA in various ethnic groups.

Base 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↗