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K Isogai

Publications and source records attributed to K Isogai.

At least 37 records · Page 2Linked to original sources

[Regional difference in the etiology of liver cirrhosis in Iwate].

To assess regional differences in the etiology of liver cirrhosis in Iwate, we analyzed 324 patients with liver cirrhosis treated at various hospitals. The etiology was HCV 44.8%, HBV 11.1%, HBV + HCV 4.6%, alcohol 27.5% (including heavy drinkers 17.9%), PBC 1.5% and non-B non-C 10.5% in Iwate. The incidence of alcoholic cirrhosis was higher than that in other prefectures, while that of HCV was lower. Especially in the northern area of Iwate, the rate of alcoholic cirrhosis was very high (39.1%--including heavy drinkers 21.8%) while viral cirrhosis was relatively low. Although the alcohol consumption volume in Iwate was not very high, marked alcohol consumption, especially shochu, was observed in the northern area of Iwate. The volume and kind of alcohol consumed in each area differed, and the etiology of liver cirrhosis differed regionally in Iwate. Thus, we should consider these districts and levels of alcohol consumption when treating patients with liver cirrhosis.

Female↗

Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.

We report four new mutations in Japanese patients with mucopolysaccharidosis IVA (MPSIVA) who were heterozygous for a common double gene deletion. A nonsense mutation of CAG to TAG at codon 148 in exon 4 was identified, resulting in a change of Q to a stop codon and three missense mutations. V (GTC) to A (GCC) at codon 138 in exon 4, P (CCC) to S (TCC) at codon 151 in exon 5, and P (CCC) to L (CTC) at codon 151 in exon 5. Introduction of these mutations into the normal GALNS cDNA and transient expression in cultured fibroblasts resulted in a significant decrease in the enzyme activity. V138A and Q148X mutations result in changes of restriction site, which were analyzed by restriction-enzyme assay. P151S and P151L mutations that did not alter the restriction site were detected by direct sequencing or allele specific oligohybridization. Detection of the double gene deletion was initially done using Southern blots and was confirmed by PCR. Haplotypes were determined using seven polymorphisms to the GALNS locus in families with the double gene deletion. Haplotype analysis showed that the common double gene deletion occurred on a single haplotype, except for some variation in a VNTR-like polymorphism. This finding is consistent with a common founder for all individuals with this mutation.

Adolescent↗

Mucopolysaccharidosis type II (Hunter disease): identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients.

Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT-PCR method. Transient expression in the enzyme-deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45-56 kD) were not detected by Western blot analysis. Furthermore, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA.

Adolescent↗

Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-Acetylgalactosamine-6-sulfate sulfatase gene.

Mucopolysaccharidosis IVA is an autosomal recessive lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. The recent isolation and characterization of cDNA and genomic sequences encoding GALNS has facilitated identification of the molecular lesions that cause MPS IVA. We identified a common missense mutation among Caucasian MPS IVA patients. The mutation was originally detected by SSCP, and successive sequencing revealed an A-->T transversion at nt 393. This substitution altered the isoleucine at position 113 to phenylalanine (I113F) in the 622 amino acid GALNS protein and was associated with a severe phenotype in a homozygote. Compound heterozygotes with one I113F-allele mutation have a wide range of clinical phenotypes. Transfection experiments in GALNS-deficient fibroblasts revealed that the mutation drastically reduces the enzyme activity of GALNS. Allele-specific oligonucleotide or SSCP analysis indicated that this mutation accounted for 22.5% (9/40) of unrelated MPS IVA chromosomes from 23 Caucasian patients, including 6 consanguineous cases. Of interest, the I1e 113-->Phe substitution occurred in only Caucasian MPS IVA patients and in none of the GALNS alleles of 20 Japanese patients. These findings identify a frequent missense mutation among MPS IVA patients of Caucasian ancestry, that results in severe MPS IVA when homoallelic, and will facilitate molecular diagnosis of most such patients and identification of heterozygous carriers. In addition to this common mutation, 10 different point mutations and 2 small deletions were detected, suggesting allelic heterogeneity in GALNS gene.

Base Sequence↗

Synthetic studies of sesquiterpenes with a cis-fused decalin system, 5. A synthetic approach to the study of structure-activity relationships of the termiticidal norsesquiterpenoids, chamaecynone and related compounds.

Various analogues of chamaecynone [1] were prepared from alpha-santonin, and the termiticidal activity of these compounds was examined. All compounds possessing a 5 beta H-13-noreudesmane skeleton with a ethynyl group at C-7 showed significant termiticidal activity. Changes in the structure of the A-ring of these compounds also influenced the potency of their termiticidal activity.

Animals↗

[A study on predicting factors of the effect of intra-arterial infusion chemotherapy in patients with bladder cancers: the usefulness of in-vitro chemisensitivity test measuring intracellular ATP contents (ATP assay)].

We studied a relationship between in vitro sensitivity of the tumors to anti-cancerous drugs and histopathological effectiveness of an intra-arterial infusion chemotherapy in 15 patients with bladder cancers. The in vitro sensitivity test was performed by measuring intra-cellular ATP contents (ATP assay). The intra-arterial chemotherapy were performed by injecting methotrexate (MTX), adriamycin (ADM) and eisplatin (CDDP) from the internal iliac artery. When the intra-cellular ATP contents of the tumor cells treated with an anti-cancerous drug decreased to less than 50% of the untreated tumor cells, the tumor was evaluated as sensitive to the drug. The effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. When the histopathological responses of higher than grade 2 were observed in the tumor, the chemotherapy was evaluated as effective. In 8 of 9 tumors sensitive to ADM, chemotherapy were effective histopathologically and in all 6 tumors resistant to ADM, histopathological response of the chemotherapies were poor. The overall coincidence ratio between sensitivity to ADM and the histopathological effectiveness of the chemotherapy was 93%, showing statistically significant correlation. In 7 of 12 tumors sensitive to CDDP, the chemotherapies were effective and in 2 of 3 tumors resistant to CDDP, the chemotherapies were ineffective. Although the overall coincidence ratio between the sensitivities to CDDP and chemotherapeutic effectiveness was 60%, there was no significant correlation between them. In 7 of 8 tumors sensitive to both of ADM and CDDP, the chemotherapies were effective and in 6 of 7 tumors resistant to at least one of them, the chemotherapies were ineffective. (ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

[Clinical investigation of clean intermittent catheterization].

We evaluated 120 patients with neurogenic bladder treated by clean intermittent self catheterization (CIC) in our department. These cases were divided into 2 groups: early treatment cases in which CIC started within 1 year after onset of dysuria, and late treatment cases in which CIC started after more than 1 year. Urinary tract infections (UTI) were recognized in 35% of the early treatment cases and 80% of the late treatment cases in the subsequent period. Pyelonephritis was experienced in 4% of the early treatment cases and 12% of the late treatment cases. Antibiotics therapy was considered unnecessary for asymptomatic UTIs. After CIC treatment, hydronephrosis detected by intravenous pyelography (IVP) and ultrasonography was improved in 18 of the 20 cases, and no cases showed deteriorated renal function. In the cases with neurogenic bladder after radical operations of the uterus or rectum, 45% of the early treatment cases have become free from CIC within 3 months postoperatively, and 84% eventually became free. Most of the late treatment cases have been continuing CIC. We considered that CIC was unnecessary when the residual urine was less than 100ml based on the periodical urinalysis and observation of renal function.

Adolescent↗

Intra-arterial administration of methotrexate, adriamycin, and cisplatin as neoadjuvant chemotherapy for bladder cancer.

As neoadjuvant chemotherapy for advanced bladder cancer, the intra-arterial administration of methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP; IA-MAC) was evaluated. A total of 48 patients with bladder cancer (greater than or equal to T2 or CIS) were selected and received 30.1 mg MTX, 34.5 mg ADM, and 89.1 mg CDDP as an average course. The mean tumor-regression rate after 2 or 3 weeks was 52.3%, and patients with grade 3 transitional-cell carcinoma showed the best results, achieving a 69.6% regression rate. In 30 cases (63%), downstaging was observed. Among the 46 patients who underwent subsequent surgical therapy, the bladder could be preserved in 26 cases by transurethral resection or segmental resection. According to the criteria of the Japanese Association of Cancer Therapy, a histological effect of GIII or better was obtained in 15 cases (29%). The histological effect correlated well with the tumor-regression rate. As compared with intravenous therapy with MTX, vinblastine, ADM, and CDDP (M-VAC), IA-MAC treatment was well tolerated due to its lower degree of bone marrow suppression, and it resulted in a longer disease-free interval and better survival. In addition, the period prior to surgical therapy was shortened in this study. These results suggest that IA-MAC chemotherapy can be useful as an arm of multidisciplinary treatment of advanced bladder tumors.

Aged↗

Studies on the synthesis of sesquiterpene lactones, 14. Syntheses of (-)-arbusclin D and (+)-4-EPI-arbusclin D: the stereochemical assignment of arbusclin D.

Efficient syntheses of (-)-arbusclin D and (+)-4-epi-arbusclin D are reported. By these syntheses the C-4 stereochemistry of arbusclin D and the absolute configuration of (-)-arbusclin D have been determined to be a s shown in structure 1. The biological activities, such as cytotoxic activity toward P-388 lymphocytic leukemia, plant growth regulating activity, and antimicrobial activity of compounds 1, 3, 7, 9, 12, and 14 were also studied.

Animals↗

Monoclonal antibody HNK-1 selectively stains a subpopulation of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex.

Monoclonal antibody HNK-1 is shown to outline selectively a subpopulation of GABAergic neurons containing a specific calcium-binding protein parvalbumin (PV) in the adult rat parietal cortex, using pre- and postembedding immunocytochemistry at light microscopic level. About 98% of HNK-1 stained cells in the rat parietal cortex were PV immunoreactive. About 95% of HNK-1 immunoreactive cells were also shown to be stained with a lectin, Vicia villosa agglutinin (VVA), with a specific affinity for terminal N-acetylgalactosamine, which has been previously shown to stain selectively a subpopulation of PV-containing GABAergic neurons in this region. Furthermore almost all HNK-1 immunoreactive cells were also stained with a monoclonal antibody, 3B3, which is specific for chondroitin sulfate proteoglycan. 3B3 was shown in the present study to stain selectively a subpopulation of PV-immunoreactive neurons in the adult rat parietal cortex. In addition, a direct comparison of two monoclonal antibodies HNK-1 and VC1.1 revealed that these two were identical in their staining properties and that they defined the same subset of PV-containing GABAergic neurons in the rat parietal cortex.

Animals↗