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K Yoshimoto

Publications and source records attributed to K Yoshimoto.

At least 91 records · Page 5Linked to original sources
PubMed1998

Absence of germ-line mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in familial pituitary adenoma in contrast to MEN1 in Japanese.

Germ-line mutations of the MEN1 gene were analyzed in five cases of familial and four cases of sporadic multiple endocrine neoplasia type 1 (MEN-1), six cases in three independent pedigrees of familial pituitary adenoma without MEN-1, and three cases of familial isolated primary hyperparathyroidism (FIHP) in Japanese. Eight different types of germ-line mutations in all nine cases of MEN-1 were distributed in exons 2, 3, 7, and 10 and intron 7 of the MEN1 gene. Loss of heterozygosity (LOH) on 11q13 was detected in all nine tumors of these cases with microsatellite analysis. No germ-line mutation of the MEN1 gene was detected in three pedigrees of familial pituitary adenoma and three cases of FIHP. LOH on 11q13 was detected in two cases in one pedigree of familial pituitary adenoma, and one of them showed a heterozygous somatic mutation of the MEN1 gene. No LOH on 11q13 was detected in three cases of FIHP. Based on these, we conclude that the loss of function of menin is etiological for familial or sporadic MEN-1, but not for FIHP or most familial pituitary adenoma without MEN-1.

Adenoma↗
PubMed1998

Analysis of loss of heterozygosity on chromosome 11 and infrequent inactivation of the MEN1 gene in sporadic pituitary adenomas.

To investigate the role of tumor suppressor genes in sporadic pituitary adenomas, we first analyzed loss of heterozygosity on 11q13 with microsatellite analysis in 31 tumors. Loss of heterozygosity on 11q13 was detected in 1 mixed GH/PRL adenoma, and the somatic 22-bp deletion of the multiple endocrine neoplasia type 1 (MEN1) gene encoding menin was detected in this tumor. Trisomy 11 suggested by the decreased mean allelic ratios of 66% or 65% for 16 or 13 microsatellite markers, respectively, in 2 of 31 pituitary adenomas was confirmed by interphase fluorescence in situ hybridization. Screening for mutations of the MEN1 gene did not find mutations with PCR-single strand conformation polymorphism analysis in other pituitary adenomas retaining heterozygosity on 11q13. Based on these, it is concluded that inactivation of the MEN1 gene comprises a rare etiology for tumorigenesis of the pituitary gland, and that trisomy 11 or another gene(s) may contribute to the pathogenesis of sporadic pituitary adenomas.

Adenoma↗
PubMed1998

Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.

We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in patients developing infective peritonitis. To avoid unnecessary antibiotic therapy the possibility of this adverse reaction should be ruled out whenever a CAPD patient receiving a dihydropyridine type calcium channel blocker develops turbid dialysate.

Calcium Channel Blockers↗
PubMed1997

Leaf-specifically expressed genes for polypeptides destined for chloroplasts with domains of sigma70 factors of bacterial RNA polymerases in Arabidopsis thaliana.

Genes for sigma-like factors of bacterial-type RNA polymerase have not been characterized from any multicellular eukaryotes, although they probably play a crucial role in the expression of plastid photosynthesis genes. We have cloned three distinct cDNAs, designated SIG1, SIG2, and SIG3, for polypeptides possessing amino acid sequences for domains conserved in sigma70 factors of bacterial RNA polymerases from the higher plant Arabidopsis thaliana. Each gene is present as one copy per haploid genome without any additional sequences hybridized in the genome. Transient expression assays using green fluorescent protein demonstrated that N-terminal regions of the SIG2 and SIG3 ORFs could function as transit peptides for import into chloroplasts. Transcripts for all three SIG genes were detected in leaves but not in roots, and were induced in leaves of dark-adapted plants in rapid response to light illumination. Together with results of our previous analysis of tissue-specific regulation of transcription of plastid photosynthesis genes, these results indicate that expressed levels of the genes may influence transcription by regulating RNA polymerase activity in a green tissue-specific manner.

Amino Acid Sequence↗
PubMed1997

p53 gene mutation in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder tumors and N-methyl-N-nitrosourea-induced colon tumors of rats.

We analyzed p53 mutations in 17 N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder transitional cell carcinomas (TCCs) with or without areas of squamous cell carcinoma (SCC) of Long-Evans Cinnamon (LEC) and F344 rats, and in 7 N-methyl-N-nitrosourea-induced colon adenocarcinomas of LEC rats by polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Of these bladder tumors, one TCC with moderately differentiated SCC had a T to G transversion mutation at codon 141, leading to a Val to Gly amino acid change. No p53 mutation was found in colon adenocarcinomas. Thus a p53 gene mutation seems infrequent in these rat bladder and colon carcinogenesis models even in the late stage.

Animals↗
PubMed1997

Amidophosphoribosyltransferase limits the rate of cell growth-linked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis.

Factors controlling relative flux rates of the de novo and salvage pathways of purine nucleotide biosynthesis during animal cell growth are not fully understood. To examine the relative role of each pathway for cell growth, three cell lines including CHO K1 (a wild-type Chinese hamster ovary fibroblast cell line), CHO ade -A (an auxotrophic cell line deficient of amidophosphoribosyltransferase (ATase), a presumed rate-limiting enzyme of the de novo pathway), and CHO ade -A transfected with human ATase cDNA (-A+hATase) resulting in 30-350% of the ATase activity of CHO K1, were cultured in purine-rich or purine-free media. Based on the enzyme activities of ATase and hypoxanthine phosphoribosyltransferase, the metabolic rate of the de novo and salvage pathways, the rate of cell growth (growth rate) in three cell lines under various culture conditions, and the effect of hypoxanthine infusion on the metabolic rate of the de novo pathway in rat liver, we concluded the following. 1) In -A+hATase transfectants, ATase activity limits the rate of the de novo pathway, which is closely linked with the growth rate. 2) Purine nucleotides are synthesized preferentially by the salvage pathway as long as hypoxanthine, the most essential source of purine salvage, can be utilized, which was confirmed in rat liver in vivo by hypoxanthine infusion. The preferential usage of the salvage pathway results in sparing the energy expenditure required for de novo synthesis. 3) The regulatory capacity of the de novo pathway (about 200%) was larger than that of the salvage pathway (about 20%) with constant hypoxanthine phosphoribosyltransferase activity.

Amidophosphoribosyltransferase↗
PubMed1997

Effects of ion channel blockers on rapid postmortem changes in extracellular dopamine and serotonin levels in the rat nucleus accumbens.

In the present study, we used in vivo brain microdialysis to examine the effects of ion channel blockers tetrodotoxin (TTX), EGTA-free Ca2+ and verapamil on rapid postmortem changes in extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in the ACC of freely moving rats. Extracellular ACC DA levels decreased following the perfusion of the three ion channel blockers in freely moving rats, and then, at death by cervical dislocation, maximum respective 220-, 60- and 90-fold increases were observed in the extracellular output of DA in animals treated with EGTA, verapamil and TTX, respectively. Also, ACC 5-HT decreased following perfusion with the three blockers in the freely moving rats, and then maximum increases of 80-, 30- and 45-fold in the extracellular output of 5-HT were observed at death in animals treated with EGTA, verapamil and TTX, respectively, compared to the baseline. Cervical dislocation-induced rapid postmortem changes were inhibited markedly by perfusion with CSF containing the CA2+ entry blocker verapamil. These observations suggested that rapid postmortem changes in ACC DA and 5-HT release were associated with the action of calcium ion channels and/or voltage gated channels in the CNS.

Animals↗
PubMed1997

p53 gene mutation analysis in porokeratosis and porokeratosis-associated squamous cell carcinoma.

In this and previous studies, we have shown p53 overexpression immunohistochemically in 14 of 17 porokeratotic specimens obtained from 14 lesions of nine cases, and in all six specimens of squamous cell carcinoma (SCC) arising on porokeratotic lesions of two cases. We screened mutations in exons 5 to 10 of the p53 gene in all these specimens by polymerase chain reaction-single strand conformation polymorphism analysis. Mutations of the p53 gene were detected in two of the six SCCs but not in any of the 17 porokeratotic specimens. These two mutations were C to T transitions at codons 146 and 175 in exon 5, which were a nonsense mutation at a dipyrimidine site and a missense mutation at a CG site, respectively. To our knowledge, neither of these mutations has been identified in skin cancers before. Our observations indicate that mutations of the p53 gene are not the major molecular etiology for porokeratosis, but are related to its skin carcinogenesis, and that p53 overexpression in porokeratosis is not due to p53 gene mutations.

Adult↗
PubMed1997

Cystic glucagonoma with loss of heterozygosity on chromosome 11 in multiple endocrine neoplasia type 1.

A 52-year-old man with a past history of a pituitary adenoma and hyperparathyroidism due to a parathyroid adenoma was admitted because of a solitary tumour of the pancreas revealed by ultrasonography. His family history was unremarkable. Plasma glucagon levels were slightly elevated (280 ng/l, normal range, 40-180 ng/l) with decreased plasma amino acid levels. Plasma glucagon levels disclosed an exaggerated response during an arginine infusion test and paradoxical elevation during a 75 g oral glucose tolerance test. Endoscopic ultrasonography revealed a monolocular cystic mass of about 3 cm in diameter in the body of the pancreas. A pancreatic tumour was diagnosed before surgery as a cystic glucagonoma. Intra-operative ultrasonography showed one cystic mass in the body of pancreas and two other solid tumours, about 1 cm and 0.5 cm in diameter, in the tail of the pancreas. Histologically, all three tumours showed neoplastic epithelial cells with round nuclei forming cords and/or a ribbon-like arrangement. They showed positive staining for Grimelius' silver stain and immunopositive cells for glucagon. Genetic analysis of the main cystic tumour revealed loss of heterozygosity (LOH) on chromosome 11. After the operation, the responses of plasma glucagon to arginine infusion and oral glucose became normal. Here we describe the usefulness of these provocation tests for early diagnosis and post-operative follow-up in a rare cystic glucagonoma associated with multiple endocrine neoplasia type 1 (MEN 1) which had LOH on chromosome 11.

Arginine↗
PubMed1997

Multiple endocrine neoplasia type 1 presented with manic-depressive disorder: a case report with an identified MEN1 gene mutation.

We report a case of multiple endocrine neoplasia type 1 who had repeated hypoglycemic episodes and had previously been diagnosed with bipolar manic-depressive disorder. The patient had a positive family history of multiple endocrine neoplasia type 1 and had multiple pancreatic endocrine tumors, hyperparathyroidism and possibly a pituitary tumor. The pancreatic tumors were resected by subtotal pancreatectomy and examined by histochemical staining and gene analysis. The tumor cells were positive for immunoreactive insulin and glucagon. A microsatellite polymorphism analysis revealed loss of heterozygosity on 11q13 in the tumors. By polymerase chain reaction-based nucleotide sequencing, we identified a germline mutation 483del2 of the MEN1 gene in the normal pancreatic tissue of the patient. This mutation causes a shift of the reading frame of menin mRNA at codon 125. It seems that the wild type allele of the MEN1 gene had been lost in the tumor cells whereas the mutant allele remained intact. This is the first identified MEN1 gene mutation in Japanese families and is different from all MEN1 gene mutations reported previously.

Adult↗
PubMed1997

[A case of cat scratch disease identified by an elevated Bartonella henselae antibody level using enzyme immunoassay].

A 68-year-old male was admitted to our hospital because of fever and a 2-week history of inguinal adenomegaly. Since he owned a cat, cat scratch disease was suspected. But it was necessary to distinguish cat scratch disease from lymphoma type adult T-cell leukemia because he showed a high level of antibody against HTLV-1. An excisional biopsy of the inguinal node was performed. Histopathologic examination revealed abscess-forming granulomatous lymphadenitis compatible with cat scratch disease. A Warthin-Starry silver stain showed pleomorphic bacilli in the lymph node. So we confirmed a serological response to Bartonella henselae, the causative agent of cat scratch disease, using enzyme immunoassay (EIA). The IgG antibody level to B. henselae was positive at 42 EIA Unit before treatment. After treatment with intravenous cefepime and oral tosufloxacin, his physical symptoms improved and the antibody level decreased to less than 12 EIA Unit. EIA was very useful for diagnosis of this case. Serology to B. henselae may replace traditional diagnostic criteria for cat scratch disease.

Aged↗
PubMed1997

The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on ethanol-induced sleep time and ethanol elimination in inbred strains of mice with different alcohol preference.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases. Male C57BL/6J and DBA/2J mice were given 6R-BH4 (0, 12.5, 25.0 and 50.0 mg/kg of body weight, i.v.) or saline, and then 4 h later, all animals were injected with ethanol (EtOH) (4.0 g/kg, i.p.), which causes them to lose the righting reflex, to investigate the differences in EtOH-induced sleeping time. 6R-BH4 pretreatment reduced EtOH-induced sleep time in DBA/2J mice with lower alcohol preference (p < 0.05), which showed no changes in the pharmacokinetics of blood EtOH. No changes in EtOH-induced sleep time were observed in C57BL/6J mice with higher alcohol preference. These results indicate that the sensitivity to EtOH in mice with lower alcohol preference was associated with 6R-BH4 activity in the CNS.

Alcohol Drinking↗
PubMed1997

Inactivation of the tumor suppressor gene on 11q13 in brothers with familial acrogigantism without multiple endocrine neoplasia type 1.

Two of three brothers (the second and third brothers) and their uncle (their mother's brother) presented acrogigantism without multiple endocrine neoplasia type 1 (MEN 1). An invasive macroadenoma was found in the second brother, and it was histologically confirmed as a sparsely granulated GH cell adenoma. Two distinct microadenomas were found in the third brother, and these were histologically diagnosed as a mixed GH cell and PRL cell adenoma and a sparsely granulated GH cell adenoma, respectively. The loss of heterozygosity (LOH) was analyzed in two adenomas (GH cell adenoma from the second brother and a mixed GH cell and PRL cell adenoma from the third brother) by determining microsatellite polymorphisms of DNAs from tumors and patients' leukocytes. The LOH was found on the chromosome 11q13, whereas LOH was not detected on 1p31-36, 2p, 3p, 4, 5, 6p, 7, 8, 9p21-22, 12p, and 19q13 in both pituitary adenomas examined. The haplotype analysis showed that the same haplotype on 11q13 was found in their mother and the unaffected first brother as well as in the affected uncle and two brothers. The deleted alleles on chromosome 11q13 in the tumors of two affected brothers were, however, restricted to those transmitted from their unaffected father. These data suggest that inactivation of the MEN 1 gene or other tumor suppressor genes on chromosome 11q13 plays an important role for the development of our familial acrogigantism without MEN 1.

Adenoma↗
PubMed1997

Infrequent mutations of p27Kip1 gene and trisomy 12 in a subset of human pituitary adenomas.

To study the etiologic roles of genes on chromosome 12 for the pituitary tumorigenesis of adenomas, mutations of the p27Kip1 gene and allelic ratios of 18 microsatellite markers on the entire chromosome 12 were studied in 33 pituitary adenomas. The p27Kip1 gene on chromosome 12p12-p13 encoding an inhibitor of complexes between cyclins and cyclin-dependent kinases is supposed to function as the tumor suppressor gene. Among 31 sporadic and 2 familial pituitary adenomas, PCR-single strand conformation polymorphism analysis detected three polymorphic changes but no tumor-specific mutations of the p27Kip1 gene. Genotyping of 18 microsatellite markers on the entire chromosome 12 detected the uniformly decreased allelic ratios ranging from 54-66% in 8 of 33 pituitary adenomas (24%), although no loss of heterozygosity was detected. Fluorescence in situ hybridization confirmed trisomy 12 in all 5 available samples out of these 8 samples. Based on these, we conclude that not mutations of the p27Kip1 gene, but trisomy 12 may be etiologically important in a subgroup of pituitary adenomas.

Adenoma↗
PubMed1997

Infrequent mutations of p16INK4A and p15INK4B genes in human pituitary adenomas.

The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15NK4B genes in tumorigenesis of the pituitary gland, 31 sporadic pituitary adenomas and 2 pituitary adenomas in familial acrogigantism were examined for loss of heterozygosity on 9p21-22 and screened for mutations in the p161NK4A and p15INK4B genes. To identify pituitary adenomas which had lost 9p21-22, pituitary adenomas were genotyped with markers flanking the p16INK4A and p15INK4B loci. The frequency of mutations in coding regions of the p16INK4A and the p15INK4B genes in pituitary adenomas was determined with polymerase chain reaction-single strand conformation polymorphism analysis and sequencing of variants. Of the 33 pituitary adenomas, two revealed loss of 9p21-22 sequences, but none of them had tumor-specific mutations. We conclude that mutations of the p16INK4A and p15INK4B genes are not required for tumorigenesis of the pituitary gland.

Adenoma↗
PubMed1997

Effects of ethanol on the levels of brain 6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin in the inbred strains of mice. DBA/2J, C3H/HeJ and C57BL/6J with different alcohol preferences.

6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases, the former two of which are the initial and the rate-limiting enzymes in the biosynthesis of the catecholamines and serotonin, respectively. The present study was designed to determine the changes in concentrations of 6R-BH4 in striatum and midbrain of the inbred strains of mice, DBA/2J, C3H/HeJ and C57BL/6J, with different genetically determined alcohol preferences, following the injection of ethanol (EtOH). The intraperitoneal administration of EtOH (0, 1, 2 and 4 g/kg) significantly and dose-dependently reduced the levels of striatal and midbrain 6R-BH4 in DBA/2J mice with the lowest alcohol preference, and EtOH (4 g/kg, i.p.) reduced the level of striatal 6R-BH4 in C3H/HeJ with medium alcohol preference. Following the administration of EtOH (4 g/kg, i.p.), brain 6R-BH4 levels in C57BL/6J mice with high alcohol preference were lowered compared with the control group, but the difference did not reach statistic significance. EtOH has a tendency to reduce the brain 6R-BH4 levels in mice with lower alcohol preference or higher sensitivity to EtOH. Based on these findings, it was proposed that differences in alcohol drinking behavior in the inbred strains of mice was influenced by brain 6R-BH4.

Alcohol Drinking↗
PubMed1996

Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune diabetes.

Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1 clones transduced with an SRalpha promoter-linked murine IL-10 (mIL-10) cDNA of 2.0-6.0 x 10(6) cells were adoptively transferred to nonobese diabetic (NOD) mice at age 8 d. Cyclophosphamide (CY) was administered at age 37 d (plus CY), and the incidence of diabetes and the histological grade of insulitis were examined at age 47 d. After the adoptive transfer of IL-10-transduced Th1 cells, polymerase chain reaction (PCR) and reverse-transcription (RT)-PCR detected the neo gene and the retrovirus vector-mediated IL-10 mRNA in situ in recipient islets, respectively. RT-PCR detected the decrease of IFN-gamma mRNA relative to IL-10 mRNA in IL-10-transduced Th1 clones in vitro and also in recipient islets. All four wild type Th1 clones plus CY induced the insulitis grade of 2.75 and diabetes in 66% of recipient NOD mice. IL-10-transduced two Th1 clones plus CY induced periinsulitis with the grade of 1.43 and diabetes in 8.0%. The 1:1 mixture of wild type Th1 cells and IL-10-transduced Th1 cells plus CY induced periinsulitis with the grade of 1.85 and diabetes in 20%. The suppression of diabetes through decreasing IFN-gamma mRNA by the tissue-specific delivery of IL-10 to pancreatic islets with IL-10-transduced Th1 cells affords us the starting basis to develop the gene therapy for autoimmune diabetes.

Adoptive Transfer↗