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Biomedical subjects

Y Kawada

Publications and source records attributed to Y Kawada.

At least 19 recordsLinked to original sources
PubMed2001

Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma.

MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9 -positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at -74 bp. These findings suggest that hypomethylation of the CpG at -74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC.

Carcinoma, Renal Cell↗
PubMed2001

High prevalence of eosinophilia in growth hormone-deficient children.

BACKGROUND: To determine the clinical significance of eosinophilia in growth-hormone (GH)-deficient children, a clinical study consisting of 72 children and adolescents (mean age 9 years and 6 months at diagnosis) with GH deficiency (GHD) was undertaken. Patients were treated with GH, along with supplementation for the combined deficiency in patients with multiple hormone deficiency. METHODS: A complete blood count and hemogram with microscopic examination of a peripheral blood smear was performed. RESULTS: Before treatment, differential eosinophil counts exceeded 5% in 30 subjects (41.7%) and absolute eosinophil counts were >350 /microL in 27 subjects (37.5%). Growth hormone therapy did not significantly affect eosinophil counts. There was an inverse relationship between absolute eosinophil count and peak GH value in response to the L-dopa stimulation test (n=65; Rs=-0.252; P=0.044). CONCLUSIONS: For the diagnosis of GHD, one should take into account that GH response to L-dopa stimulation can be selectively blunted in patients with eosinophilia.

Adolescent↗
PubMed2001

Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas.

The INK4a / ARF locus on chromosome 9p21, which encodes two distinct genes, p14(ARF) and p16(INK4a), is frequently altered in human neoplasms. To investigate the potential roles of p14(ARF) and p16(INK4a) genes in human renal cell carcinomas (RCCs), we analyzed 6 human RCC cell lines and 91 primary RCCs for homozygous deletion, promoter hypermethylation and expression of the p14(ARF) and p16(INK4a) gene products using differential PCR, methylation-specific PCR, and immunohistochemistry, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16(INK4a) gene only. Eight of 91 RCCs showed aberrations of p14(ARF) or p16(INK4a) status and six of these featured gross extension into the renal vein. The results suggest that p14(ARF) and p16(INK4a) aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression.

Carcinoma, Renal Cell↗
PubMed2000

Development of a rapid assay for screening point mutations associated with quinolone resistance in the Pseudomonas aeruginosa parC gene.

To detect quinolone resistance-associated mutations within the Ser-80 and Glu-84 codons of the Pseudomonas aeruginosa parC gene, we developed a rapid and simple assay based on polymerase chain reaction (PCR) amplification of the region of the parC gene containing the mutation sites and digestion of the PCR products with a restriction enzyme. The mutations generating alterations at Ser-80 and Glu-84 were detected as restriction fragment length polymorphisms of the PCR products digested with HinfI. Among 22 clinical isolates tested by this assay, mutations at the Ser-80 and Glu-84 codons were detected in all 10 isolates in which the presence of the mutations had been confirmed previously by DNA sequencing. This rapid and simple assay could be a useful screening device for genetic alterations associated with resistance to quinolones in the P. aeruginosa parC gene.

4-Quinolones↗
PubMed2000

In vitro selection of fluoroquinolone-resistant Neisseria gonorrhoeae harboring alterations in DNA gyrase and topoisomerase IV.

PURPOSE: We attempted to select increasingly fluoroquinolone-resistant strains of Neisseria gonorrhoeae in vitro and to assess whether selected mutants harbored alterations in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV, which were analogous to those in fluoroquinolone-resistant clinical isolates. MATERIALS AND METHODS: A fluoroquinolone-susceptible strain was exposed to norfloxacin in vitro. Selected mutants were sequentially exposed to norfloxacin, and this procedure was repeated. For 11 mutants, minimum inhibitory concentrations (MICs) of antimicrobial agents were determined, and mutations in the region corresponding to the quinolone resistance-determining region (QRDR) of the Escherichia coli gyrA gene and the analogous region of the parC gene were analyzed. RESULTS: Mutants obtained in one step exhibited significantly increased MICs of norfloxacin, ofloxacin and ciprofloxacin and had a single amino acid change in GyrA. Two-step mutants exhibited significantly higher norfloxacin MICs. Three of four two-step selected strains had single amino acid changes in both GyrA and ParC. Three-step mutants exhibited further increases in fluoroquinolone MICs and were assigned to the ciprofloxacin-resistant category. Two had a double amino acid change in GyrA, and one had a double GyrA change and a single amino acid change in ParC. CONCLUSION: We selected fluoroquinolone-resistant strains that carried GyrA and ParC alterations analogous to those in clinical isolates. The serial accumulation of changes in the QRDR of GyrA and the analogous region of ParC was associated with a stepwise increase in fluoroquinolone resistance, although the development of additional alterations in other regions of GyrA and ParC or other mechanisms of fluoroquinolone resistance also might contribute to the enhancement in fluoroquinolone resistance. The clinical emergence of fluoroquinolone-resistant strains may be due to in-vivo stepwise selection of strains with genetic alterations in GyrA and ParC, as observed here in the in-vitro selection of fluoroquinolone-resistant mutants.

Anti-Infective Agents↗
PubMed2000

Improved synthesis of paroxetine hydrochloride propan-2-ol solvate through one of metabolites in humans, and characterization of the solvate crystals.

Paroxetine, a potent and selective inhibitor of 5-hydroxytryptamine (serotonin) uptake, was prepared through a piperidine derivative, which was reported to be one of the paroxetine metabolites in humans. Thus, the piperidine derivative was converted to its N-tert-butoxycarbonyl (N-Boc) derivative, which was then converted to N-Boc paroxetine. Paroxetine hydrochloride propan-2-ol (isopropyl alcohol (IPA)) solvate crystals were directly obtained from the N-Boc paroxetine by adding hydrogen chloride to the N-Boc paroxetine IPA solution. The amount of IPA content in the crystals was reduced by drying with a continuous change of powder X-ray diffraction patterns. Other characterizations of the solvate crystals were also conducted.

Crystallography, X-Ray↗
PubMed1999

Gonadoblastoma, mixed germ cell tumor, and Y chromosomal genotype: molecular analysis in four patients.

This study reports on Y chromosomal genotypes of three patients with gonadoblastoma and one patient with gonadoblastoma and mixed germ cell tumor. Molecular analysis for 35 Y chromosomal loci was performed for DNA samples taken from peripheral leukocytes and lymphoblastoid cell lines, showing that the four patients shared the region between DYS267 at interval 4A and DYF50S1 at interval 6D, with the exception of the region around DYS202 at interval 5K. In the patient with gonadoblastoma and mixed germ cell tumor, Y chromosomal material was preserved in the gonadoblastoma but was lost from the mixed germ cell tumor. The results, in conjunction with previous reports, suggest that GBY (gonadoblastoma locus on the Y chromosome) may be located to a roughly 5-Mb pericentromeric region between DYS267 at interval 4A and DYS270 at interval 5A. The presence of Y chromosomal material in gonadoblastoma is consistent with GBY being involved in the development of gonadoblastoma, and the absence of Y chromosomal material in mixed germ cell tumor would be explained as a consequence of Y chromosomal loss from rapidly proliferating gonadal cancer cells.

Adolescent↗
PubMed1999

Ischio-spinal dysostosis: a previously unrecognised combination of malformations.

BACKGROUND: Ischial hypoplasia is an extremely rare malformation, both as an isolated anomaly and as a syndromic constituent. OBJECTIVE: To elucidate the clinical and radiological characteristics in five patients with the combination of ischial hypoplasia and spinal malformations. MATERIALS AND METHODS: The clinical records and radiographs of two females and three males, ranging in age from 3 months to 38 years, were evaluated. RESULTS: Ossification defects of the ischial rami were symmetrical and total in four patients, whereas the right ischial ramus was partly ossified in the other patient. All patients possessed multiple segmental defects of the spine, with rib anomalies of varying severity. One patient characteristically showed multiple rib gaps, resulting in respiratory distress. Severe anomalies of the cervical spine were evident in two patients. Four patients exhibited lumbosacral hypoplasia, which ultimately led to cauda equina syndrome in three older patients. One patient had mild facial dysmorphism and another had a diversity of anomalies, including ichthyosiform skin changes. Four patients were sporadic cases, whereas the other patient was born to consanguineous parents. CONCLUSIONS: The combination of anomalies in these patients constitutes a recognisable pattern of malformations but may represent a heterogeneous group of disorders.

Abnormalities, Multiple↗
PubMed1999

Müllerian duct cyst extending into the abdomen.

Müllerian duct cysts occupying the pelvic/abdominal region are rare. We describe a müllerian duct cyst extending into the lower abdomen in a 47-year-old man complaining of urinary retention. We removed the cyst through a suprapubic retrovesical approach. No malignancy was found in the surgical specimen.

Abdomen↗
PubMed1999

Adequacy of the new guidelines on clinical evaluation of drug efficacy in acute uncomplicated cystitis.

The adequacy of the newly revised criteria for the evaluation of clinical efficacy of antimicrobial agents in acute uncomplicated cystitis harmonized to the IDSA/FDA guidelines was studied. Low bacterial counts were significantly more frequently found in midstream urine than in catheter urine. Non-uropathogens were isolated with significantly higher frequency from patients with bacteriuria of 10(3) colony forming units (cfu)/ml than from patients with higher bacterial counts. It is important to exclude non-uropathogens when patients with bacteriuria of 10(3) cfu/ml are included in the study. Although the clinical failure rate was very low in patients with eradication of the pathogen, the clinical cure rate was only 67% in patients with microbiological failure. Microbiological and clinical outcomes coincided in 93% of the patients. However, the coincidence rate was lower when the eradication rate was low.

Acute Disease↗
PubMed1999

Loss of tissue immunoreactive androgen receptor in prostate cancer presenting initially as an intracranial tumor.

We report a case of prostate cancer that presented initially as an intracranial tumor. Biopsy specimens of the prostate before endocrine treatment were nearly negative immunohistochemically for prostate-specific antigen and the androgen receptors. All metastases including those in the brain expressed neither androgen receptor nor prostate-specific antigen at the protein and mRNA levels. The tumor, which did not respond to the anti-androgen therapy, had an aggressive course. In this case, the androgen-independent growth and rapid progression might be associated with the initial loss of the antigen and androgen characteristics of the prostate.

Adenocarcinoma↗
PubMed1999

A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. Recently, it was reported that mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH. In the present study, we have analyzed the StAR gene of a Japanese patient with CLAH. PCR amplification and subsequent nucleotide sequencing of the StAR gene and those of her parents revealed that the patient has a compound heterozygous mutation of this gene. In one allele, an undescribed G to C transversion in codon 217, which occurred at the last base of exon 5 and thus altered the splice donor site sequence, apparently resulted in a substitution of Arg to Thr (AGG to ACG: R217T), and in the other allele, a C to T transition in codon 218 caused a substitution of Ala to Val (GCG to GTG: A218V), which has been previously shown to abolish StAR activity. In vitro expression analysis of an allelic minigene that consists of exons 4-6 of the R217T mutant StAR gene showed that the G to C transversion in the splice donor site of exon 5 caused by the R217T mutation disrupts normal splicing, resulting in the complete skipping of exon 5, which alters the translation reading frame of exon 6, introduces a stop codon at amino acid position 174, and thus impairs the activity. A functional expression study of the R217T replacement mutant revealed that the mutant has no steroidogenesis-enhancing activity if the transcript of the R217T mutant allele is ever spliced normally and translated into the protein. From the genetic analysis of 50 healthy subjects, the novel R217T mutation was unlikely to be due to polymorphism. Together, these results indicate that this patient is a compound heterozygote for the mutation in the StAR gene (T217R and A218V) and that these mutations inactivate the StAR function and give rise to clinically manifest CLAH.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Synthetic inhibitors of DNA topoisomerase I and II.

A new type of synthetic inhibitor of DNA topoisomerase I and II was examined and several of these derivatives exhibited strong dual activity against these enzymes. This series of compounds showed high cytotoxic activities against cancer cells, but only a limited number of compounds showed any noticeable activity in an in vivo test against murine P388. Non-specific toxicity was observed in the in vivo tests.

Animals↗
PubMed1999

[Intra-arterial chemotherapy via reservoir system for advanced bladder cancer and prostate cancer].

A clinical study was performed on the efficacy of intra-arterial chemotherapy using a reservoir system for advanced urological malignancies. The reservoir system was indwelted in the femoral subcutaneous layer by Seldinger's method. Fifteen cases of inoperable complicated advanced bladder cancer and 10 cases of postoperative local recurrent bladder cancer were administered intra-arterial chemotherapy using a reservoir system. Then, 23 cases of local relapsed prostate cancer and two cases of endpocrine-resistant prostate cancer were administered the chemotherapy. The administered anti-cancerous agents were methotraxate, cis-platinum and adriamycin, then 5-FU or carboplatin was administered as maintenance therapy. The mean number of courses of chemotherapy was six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. The overall clinical efficacy was a positive response (PR) and no change (NC): for 18 and 7 cases of bladder cancer, and 11 and 14 cases of prostate cancer, respectively. The median duration of stabilization was 23 months for bladder cancer and 12 months for prostate cancer. The adverse effects were fever than those with systemic chemotherapy.

Adult↗
PubMed1999

[Statistics on the operations at the Department of Urology, Toyota Memorial Hospital during an 11-year period (1987-1997)].

A clinical statistic survey was carried out on the operations performed at our Hospital from 1987 through 1997. The total number of operations was 3,383 and the number of operations excluding extracorporeal shock wave lithotripsy (ESWL) was 1,672, consisting of 227 (13.6%) operations of the kidney and ureter, 194 (11.6%) operations of the bladder, 481 (28.8%) operations of the prostate and urethra, and 705 (42.2%) operations of the penis and scrotal contents. Since new endourological technology and ESWL were developed for clinical application, the mode of operation has dramatically changed during the last 11 years, trending toward minimally invasive surgery.

Humans↗