Search PubMed⌕ Search

Biomedical subjects

K Ichida

Publications and source records attributed to K Ichida.

At least 19 recordsLinked to original sources
PubMed2001

Mutation of human molybdenum cofactor sulfurase gene is responsible for classical xanthinuria type II.

Drosophila ma-l gene was suggested to encode an enzyme for sulfuration of the desulfo molybdenum cofactor for xanthine dehydrogenase (XDH) and aldehyde oxidase (AO). The human molybdenum cofactor sulfurase (HMCS) gene, the human ma-l homologue, is therefore a candidate gene responsible for classical xanthinuria type II, which involves both XDH and AO deficiencies. However, HMCS has not been identified as yet. In this study, we cloned the HMCS gene from a cDNA library prepared from liver. In two independent patients with classical xanthinuria type II, we identified a C to T base substitution at nucleotide 1255 in the HMCS gene that should cause a CGA (Arg) to TGA (Ter) nonsense substitution at codon 419. A classical xanthinuria type I patient and healthy volunteers lacked this mutation. These results indicate that a functional defect of the HMCS gene is responsible for classical xanthinuria type II, and that HMCS protein functions to provide a sulfur atom for the molybdenum cofactor of XDH and AO.

Aged↗
PubMed2001

Serum uric acid and renal prognosis in patients with IgA nephropathy.

BACKGROUND/AIMS: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nephropathy. METHODS: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.

Adult↗
PubMed2000

XDH gene mutation is the underlying cause of classical xanthinuria: a second report.

BACKGROUND: Classical xanthinuria is a rare autosomal recessive disorder characterized by excessive excretion of xanthine in urine. Type I disease results from the isolated deficiency of xanthine dehydrogenase (XDH), and type II results from dual deficiency of XDH and aldehyde oxidase. The XDH gene has been cloned and localized to chromosome 2p22-23. The aim of this study was to characterize the molecular basis of classical xanthinuria in an Iranian-Jewish family. METHODS: The apparently unrelated parents originated from a community in which consanguineous marriages are common. Subtyping xanthinuria was attempted by homozygosity mapping using microsatellite markers D2S352, D2S367, and D2S2374 in the vicinity of the XDH gene. Mutation detection was accomplished by PCR-SSCP screening of all 36 exons and exon-intron junctions of the XDH gene, followed by direct sequencing and confirmation of sequence alteration by restriction analysis. RESULTS: The index case was homozygous for all three microsatellite markers analyzed. The expected frequency of this genotype in a control population was 0. 0002. These results suggested that xanthinuria in the patient is linked to the XDH gene. Consequently, a 1658insC mutation in exon 16 of the XDH gene was identified. The 1658insC mutation was not detected in 65 control DNA samples. CONCLUSION: A molecular approach to the diagnosis of classical xanthinuria type I in a female patient with profound hypouricemia is described. Linkage of xanthinuria to the XDH locus was demonstrated by homozygosity mapping, and a 1658insC mutation, predicting a truncated inactive XDH protein, was identified. These results reinforce the notion that mutations in the XDH gene are the underlying cause of classical xanthinuria type I.

Amino Acid Sequence↗
PubMed1999

Characterization of a palytoxin-induced non-selective cation channel in mouse megakaryocytes.

We used the whole-cell clamp and fura-2 techniques to study the membrane current and intracellular Ca2+ concentration ([Ca2+]i) changes of mouse megakaryocytes in response to palytoxin (PTX), a highly potent marine toxin. At a holding potential of -60 mV, PTX induced a sustained inward current in a dose-dependent manner. The reversal potentials measured in the presence of various extracellular major cations indicated that the PTX-induced channel had a non-selective permeability to alkali metal ions. Although elimination of intracellular Ca2+ had no effect on the PTX-induced current, removal of external Ca2+ inhibited the current activation. During the sustained phase of the PTX-induced current, treatment with ADP activated an additional current. Pretreatment with ouabain, an inhibitor of Na+-K+-ATPase, suppressed the PTX-induced current. During the stable phase of the PTX-induced current, challenge with NiCl2 (5 mM) or 2,4-dichlorobenzamil (DCB, 25 microM), a non-selective cation channel blocker, partially reversed the current. Simultaneous measurement of the membrane current and [Ca2+]i showed that PTX induced the current response without increasing the [Ca2+]i. Taken together, these results indicate that PTX induces a non-selective cation channel in mouse megakaryocytes. This channel is distinct from the ADP-operated channel and is sensitive to ouabain, NiCl2 and DCB.

Acrylamides↗
PubMed1998

Two siblings with classical xanthinuria type 1: significance of allopurinol loading test.

Two brothers with classical xanthinuria who lacked xanthine dehydrogenase activity were encountered. Their hypouricemia was caused by underproduction of uric acid. In their duodenal mucosa, no xanthine dehydrogenase (oxidase) activity was detected. The patients had no symptoms except for duodenal ulcer in one case. The conversion of allopurinol to oxipurinol during an allopurinol loading test for determining the type of classical xanthinuria revealed that the patients had classical type 1 xanthinuria, because aldehyde oxidase activity was present. Furthermore, the allopurinol loading test was conducted to determine the optimal examination times and specimens required for this test.

Adult↗
PubMed1998

Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase manifesting as acute renal damage.

A 32-year-old man who had had frequent gouty arthritis over the past 17 years, was admitted for acute renal failure. Acute renal failure was improved rapidly after medication was resumed and the patient was sufficiently hydrated. The hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in the patient had been reduced to about 30% of the normal control. Therefore we considered that this patient suffered from a partial deficiency of HPRT. A point mutation of HPRT gene 68G (guanine) to T (thymine) was detected. This is a mutation that has not been previously reported. Familial analysis indicated that his mother and sister were heterozygotes.

Acute Kidney Injury↗
PubMed1997

Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria.

Hereditary xanthinuria is classified into three categories. Classical xanthinuria type I lacks only xanthine dehydrogenase activity, while type II and molybdenum cofactor deficiency also lack one or two additional enzyme activities. In the present study, we examined four individuals with classical xanthinuria to discover the cause of the enzyme deficiency at the molecular level. One subject had a C to T base substitution at nucleotide 682 that should cause a CGA (Arg) to TGA (Ter) nonsense substitution at codon 228. The duodenal mucosa from the subject had no xanthine dehydrogenase protein while the mRNA level was not reduced. The two subjects who were siblings with type I xanthinuria were homozygous concerning this mutation, while another subject was found to contain the same mutation in a heterozygous state. The last subject who was also with type I xanthinuria had a deletion of C at nucleotide 2567 in cDNA that should generate a termination codon from nucleotide 2783. This subject was homozygous for the mutation and the level of mRNA in the duodenal mucosa from the subject was not reduced. Thus, in three subjects with type I xanthinuria, the primary genetic defects were confirmed to be in the xanthine dehydrogenase gene.

Adult↗
PubMed1996

A rare case of idiopathic hypoparathyroidism with varied neurological manifestations.

A 47-year-old man was admitted for evaluation of unsteady gait, postural instability, and dysarthria. On admission, neurological examinations revealed cerebellar ataxia, extrapyramidal signs including parkinsonism and positive Trousseau's sign. Laboratory findings revealed severe hypocalcemia and hyperphosphatemia, and serum intact parathyroid hormone was not detectable. Brain computed tomography revealed severe calcification of basal ganglia and dentate nuclei. He was diagnosed as idiopathic hypoparathyroidism; treatment with 1 alpha (OH) vitamin D3 brought marked improvement of neurological manifestations. We report a rare case of idiopathic hypoparathyroidism presenting with extrapyramidal and cerebellar dysfunction with a review of literature.

Basal Ganglia↗
PubMed1996

[Hyperuricemia and the kidney].

The risk for renal insufficiency by uric acid precipitation in medulla of kidney correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. The patients with gout or hyperuricemia have sometimes acidic urine and increased uric acid excretion. Accordingly, these patients frequently accompany by renal insufficiency. Improvement of hyperuricosuria, increasing of urine volume, and alkalinization of urine to pH6 6.5, are effective for the prevention from renal insufficiency. Acute renal failure related to hyperuricemia, can also occured secondary to cell lysis. Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hypocalcemia, and acute renal failure after starting chemotherapy to cancers, especially lymphoproliferative malignancies. Administration of allopurinol 500-600 mg and adequate hydration and alkalinization of urine are advocated to prevent acute renal failure. Intensive care with hemodialysis is often required to treat renal failure, because renal failure is reversible in most cases.

Acute Kidney Injury↗
PubMed1996

[Metabolic disorder of purine nucleotide in patients with renal disease].

The serum levels of uric acid, hypoxanthine and xanthine tended to increase with the decrease of renal function. This mechanism was thought to be the decreased excretion of these materials from the kidney. More than ninety percent of the patients with renal insufficiency (Ccr < or = 30 ml/min) showed hyperuricemia. In general, the gouty arthritis was reported to be uncommon in the patients with secondary hyperuricemia due to renal insufficiency. However, the frequency of gouty arthritis was reported to be high in the patients with polycystic disease and lead nephropathy. The therapeutic standard for secondary hyperuricemia with renal insufficiency was not established. Allopurinol is the drug of choice for controlling hyperuricemia due to renal insufficiency in many cases. In renal insufficiency, the drug must be used cautiously and in reduced dosage because increased serum concentration of oxipurinol, active metabolite of allopurinol, may induce severe side effect.

Allopurinol↗
PubMed1995

Newly discovered familial juvenile gouty nephropathy in a Japanese family.

Our attention was initially called to 2 young Japanese sisters with gout and renal insufficiency, which led to an investigation of members of their family with similar conditions. One sister, a 26-year-old woman who had suffered from polyuria since infancy, suffered from gout and renal insufficiency. Her younger sister also had a history of polyuria, hyperuricemia, and moderately reduced renal function. Their urinary uric acid levels were reduced but purine enzyme activities in the erythrocytes were normal. A renal biopsy specimen from the younger sister showed severe interstitial fibrosis with tubular atrophy. An investigation of the family revealed an autosomal dominant transmission pattern. We believe these are new familial cases of juvenile gouty nephropathy found in a Japanese family.

Adult↗
PubMed1995

[An epidemiologic study on pathogenesis of uric acid urolithiasis].

We reviewed 5477 patients with urinary calculi who presented during the years from 1975 to 1993. During this time the percentage of calcium stones has remained at approximately 86%. However over the same period the rate of urinary calculi composed of uric acid has increased and is now about 7.2%. The number of uric acid stones has increased 3.5 times compared to 1975. 355 of 394 (90.1%) with uric acid stones are male. We believe that the increase in the numbers of patients seen with gout, hyperurisemia of a high alcohol intake.

Alcohol Drinking↗
PubMed1993

Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene.

The primary structure of human xanthine dehydrogenase (hXDH) was determined by cloning and sequence analysis of the cDNAs encoding the enzyme. The nucleotide (nt) sequence has an open reading frame of 3999 nt encoding a protein of 1333 amino acids (aa) with a calculated M(r) of 146,604. The deduced aa sequence of hXDH is homologous to the previously reported rat XDH (rXDH) and Drosophila melanogaster XDH sequences with identities of 90.2 and 52.0%, respectively. The aa residues involved in both the reversible and the irreversible conversion from the dehydrogenase type to the oxidase type of rXDH are completely conserved between the rat and the human enzymes. This implies that the molecular mechanisms of the conversion of hXDH from dehydrogenase to oxidase are common to those of the well-characterized rXDH. Five sequence variations were detected in the isolated cDNA clones. Spot blot hybridization using flow-sorted human chromosome revealed that the hXDH-encoding gene (hXDH) was located on chromosome 2.

Amino Acid Sequence↗