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Y Jinno

Publications and source records attributed to Y Jinno.

At least 55 records · Page 3Linked to original sources
PubMed1996

Monoallelic expression of the insulin-like growth factor-2 gene in ovarian cancer.

Genomic imprinting is defined as a gamete-specific modification causing differential expression of the two alleles of a gene in somatic cells and is becoming increasingly recognized as playing an important role in a number of human diseases including cancer. We have reported that the loss of the insulin-like growth factor-2 (IGF2) gene imprinting results in the deregulation of both IGF2 alleles, which may contribute to the onset of Wilms tumor. It is important to see whether such abnormal genomic imprinting is implicated in the etiology of common adulthood cancers. In the present study we have examined the expression level and imprinting status of the IGF2 gene in human ovaries and ovarian cancers. We confirm that IGF2 is significantly expressed in ovaries and ovarian cancers. In normal ovaries, both surface epithelium and the ovary proper demonstrate monoallelic IGF2 expression. Among 27 tumors, all 11 heterozygous for the IGF2 locus show monoallelic IGF2 expression (2 of them are proven to be from the paternal allele). The data suggest that the increased IGF2 gene expression in ovarian cancer may be achieved by a mechanism other than loss of imprinting.

Alleles↗
PubMed1995

Genetic association between chromosome 8 microsatellite (MS8-134) and Werner syndrome (WRN): chromosome microdissection and homozygosity mapping.

Werner syndrome (WRN) is an autosomal recessive disorder characterized by premature aging that has been mapped to the short arm of chromosome 8, 8p11.2-p12. To refine the genetic map around the WRN region, we have isolated eight microsatellites for this region from a microdissection library. We typed members of Japanese families with WRN on the basis of homozygosity mapping analysis. There was no obligate recombination between the WRN locus and microsatellite clone, MS8-134 (D8S1055). The maximum lod score was 20.28 at theta = 0.00. Alleles for MS8-134 showed association with WRN in a case-control study (OR = 3.55, 95% CI 1.56-8.07, P < 0.01). Such microsatellites from a microdissection library of the definite chromosome region may be useful for positional cloning of the WRN gene.

Base Sequence↗
PubMed1995

Establishment of functional imprinting of the H19 gene in human developing placentae.

We have found that the imprinted H19 gene can be expressed either biallelically or monoallelically in the developing human placentae. H19 biallelic expression is confined to the placenta until 10 weeks of gestation, after which it becomes exclusively maternal, and does not affect allele-specificity or levels of IGF2 expression. The promoter region of H19 is hypomethylated at all stages of placental development, while the 3' portion shows progressive methylation of the paternal allele with gestation. Our observations demonstrate that the establishment of functional H19 imprinting occurs during the early development of the placenta and provide an opportunity to understand the mechanism by which the H19 primary imprint is manifested in somatic cells.

Alleles↗
PubMed1995

Effects of KRN4884, a novel K channel opener, on the cardiovascular system in anesthetized dogs: a comparison with levcromakalim, nilvadipine, and nifedipine.

Pharmacological profiles of KRN4884, 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine+ ++, were evaluated in in vitro and in vivo experiments. In rat isolated aorta, KRN4884 (10(-10)-10(-5) M) produced a concentration-dependent relaxation. Pretreatment with glibenclamide (10(-7)-10(-6) M) produced a rightward shift of the concentration-response curve for KRN4884. In anesthetized dogs, KRN4884 (3 and 10 micrograms/kg intravenously, i.v.), levcromakalim (3 and 10 micrograms/kg i.v.), nilvadipine (1-10 micrograms/kg i.v.), and nifedipine (1-10 micrograms/kg i.v.) produced decreases in mean blood pressure (MBP), total peripheral vascular resistance (TPR), and coronary vascular resistance (CVR), and increases in aortic blood flow (AoF) and coronary blood flow (CBF). The percentage decrease in CVR was greater than that in TPR with KRN4884 and levcromakalim, but nilvadipine and nifedipine showed no significant differences between CVR and TPR in percentage decreases. Heart rate (HR) was slightly increased by KRN4884 but was not affected by levcromakalim, nilvadipine, or nifedipine. Left ventricular dP/dt (LVdP/dt) was reduced only by nifedipine in a dose-dependent manner. The duration of the hypotensive action of KRN4884 was longer than those of levcromakalim and nifedipine and was similar to that of nilvadipine. The duration of the decreases in TPR and CVR induced by KRN4884 was longer than those induced by levcromakalim and nifedipine and shorter than that induced by nilvadipine. These results suggest that the cardiovascular effects of KRN4884 are very similar to those of the K channel opener levcromakalim and Ca channel blockers such as nilvadipine and nifedipine. However, the hypotensive effects of KRN4884 are long-acting in comparison with those of levcromakalim and the selective effect of KRN4884 on coronary vasculature is greater than those of nilvadipine and nifedipine.

Anesthesia↗
PubMed1995

Fifty novel sequence-tagged sites (STSs) on human chromosome 11q13.4-->q25 identified from microclones generated by microdissection.

Fifty sequence-tagged sites (STSs) from human chromosome region, 11q13.4-->q25 were identified in microdissection-generated microclones. From a total of 124 single-copy microclones obtained from regions 11q14-->q22 and 11q23-->q25, 59 were sequenced, and a PCR primer pair was designed for each of them. Fifty of the 59 clones were mapped to regions ranging from 11q13.4 to 11q25 by means of PCR on a somatic hybrid cell panel with various deletions of the long arm of human chromosome 11. These STSs will contribute to the construction of physical cosmid/YAC maps representing the chromosome regions. They are also useful for analysis of chromosome aberrations, such as translocations, inversions or marker chromosomes.

Base Sequence↗
PubMed1995

Pharmacokinetics and pharmacodynamics of nisoldipine in hypertensive patients with normal and mild to moderate impaired renal function.

The pharmacokinetics and pharmacodynamics of nisoldipine (CAS 63675-72-9, isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, Bay k 5552), a calcium antagonist, were investigated after administration of a single oral 10 mg dose and after 7 same doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with mild to moderate renal dysfunction (impaired renal function, IRF). A significant decrease in blood pressure was observed after consecutive dosing of nisoldipine compared to baseline values over 24 h in both groups. There were no significant differences in plasma profiles of nisoldipine in both groups after either single or consecutive dosing. The plasma concentration-time profiles of the active metabolite, Bay r 9425, were similar to those of nisoldipine in both groups. The pharmacokinetic parameters of nisoldipine and its active metabolite in the NRF and IRF groups did not differ after the single and the consecutive dosing. In addition, there were neither prolongation of apparent elimination half-life (t1/2), nor increases in peak plasma levels (Cmax), or the area under the plasma concentration-time curve (AUC0-infinity) after consecutive dosing in both groups. Cumulative urinary excretion rates of the major metabolites, Bay s 4755 and Bay s 1869, did not differ significantly between the NRF and IRF groups in both single and consecutive studies. In the present study, mild flushing was observed in one patient with IRF. There was no deterioration in renal function during the study. These results suggest that nisoldipine may have a long-lasting antihypertensive effect during consecutive dosing and that it can be used in hypertensive patients regardless of presence of renal dysfunction.

Blood Pressure↗
PubMed1994

Molecular and clinical study of 61 Angelman syndrome patients.

We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion, which commonly extended from D15S9 to D15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci, D15S10 and GABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (q11q13), showed no molecular deletion. Most clinical manifestations, including neurological signs and facial characteristics, were not distinct in each group except for hypopigmentation of skin or hair. Familial cases with submicroscopic deletion were not associated with hypopigmentation. These findings suggested that a gene for hypopigmentation is located outside the critical region of AS and is not imprinted.

Adolescent↗
PubMed1994

A comparison of GC content and the proportion of Alu/KpnI-repetitive sequences in a single dark- and light-band region from a human chromosome.

To obtain direct evidence for a molecular basis of differentiation between regular Giemsa dark (G)- and light (R)-band regions of human chromosomes, two regions of chromosome 11, q14-q22 (G-band) and q23-q25 (R-band), were microdissected. The DNA fragments were amplified by the linker-primer polymerase chain reaction and cloned into pUC19. Microclones from each library were then compared by colony hybridization with repetitive DNA sequences, by Southern blot hybridization of each microclone to total human genomic DNA and mouse-human hybrid cell DNA containing only human chromosome 11, and by sequencing of unique and Alu-repetitive clones. Among the G-band-derived microclones analyzed, 43.0% were single-copy (unique) sequences and 23.2% contained highly repetitive sequence elements; in the R-band-derived library, 54.2% were unique clones and 20.3% had highly repetitive elements. The G-band library was significantly richer in clones positive for KpnI sequences (4.1% in the G-band library vs 2.8% in the R-band library). No significant difference was found in the proportion of Alu repetitive clones present in the two libraries, but Class IV Alu sequence derivatives were more frequently observed in the R-library than in the G-library. Sequence analysis revealed no significant difference in GC content or in the ratio of CpG sequence to GpC dinucleotide between 30 microclones derived from G-bands and 29 microclones derived from R-bands.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition↗
PubMed1994

Excess functional copy of allele at chromosomal region 11p15 may cause Wiedemann-Beckwith (EMG) syndrome.

Wiedemann-Beckwith syndrome (WBS) is a genetic disorder with overgrowth and predisposition to Wilms' tumor. The putative locus of the gene responsible for this syndrome is assigned to chromosome region 11p15.5, and genomic imprinting in this region has been proposed: the paternally derived gene(s) at 11p15.5 is selectively expressed, while the maternally transmitted gene(s) is inactive. We examined 18 patients for the parental origin of their 11p15 regions. DNA polymorphism analyses using 6 loci on chromosome 11 showed that 2 patients with duplications of 11p15 regions from their respective fathers and one from the mother, indicating the transmission of an excessive paternal gene at 11p15 to each patient. Our results, together with the previous findings in karyotypically normal or abnormal patients and in overgrowth mouse experiments, are consistent with imprinting hypothesis that overexpression of paternally derived gene(s) at 11p15.5, probably the human insulin-like growth factor II (IGF-II) gene, may cause the phenotype. Total constitutional uniparental paternal disomy (UPD) or segmental UPD for the 6 loci examined of chromosome 11 was not observed in our 12 sporadic patients. In order to explain completely the inheritance of this syndrome in patients with various chromosomal constitutions, we propose an alternative imprinting mechanism involving the other locus that may be paternally imprinted and may suppress the expression of this gene.

Alleles↗
PubMed1994

Effect of KRN2391 on canine ventricular arrhythmia models.

1. KRN2391 (3-30 micrograms/kg, i.v.) produced a decrease in mean blood pressure (MBP) with concomitant increase in heart rate (HR) and change in electrocardiogram (ECG) such as the shortening of PP and PQ intervals and the prolongation of QTc and these changes in HR and ECG were attenuated by pretreatment with propranolol (1 mg/kg) in normal dogs. 2. KRN2391 at 30 micrograms/kg induces neither suppression nor aggravation of ventricular arrhythmias caused by adrenaline and digitalis. 3. In two-stage coronary ligation-induced arrhythmia, KRN2391 inhibited arrhythmia at 48 hr. 4. These results suggest that KRN2391 may be effective on arrhythmia related to ischemia. In addition, it is considered that arrhythmia is not induced even by a high dose of KRN2391 in the normal condition.

Animals↗
PubMed1994

Pharmacological analysis of the inhibitory effects of KRN2391 on endothelin-1-induced contraction in isolated large coronary artery of the pig.

1. The relaxant effect of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridine-carboximidamide-mo nomethanesulfonate (with both K+ channel opener and nitrate actions), nifedipine (Ca2+ channel blocker), nitroglycerin (nitrate) and cromakalim (K+ channel opener) were investigated in isolated porcine large coronary arteries contracted by endothelin-1. These drugs inhibited endothelin-1-induced contraction in a concentration-dependent manner. 2. The relaxation induced by KRN2391 was nearly complete at their maximum effects, but nifedipine and cromakalim could not produce complete relaxation. 3. The concentration-relaxation curves for KRN2391 underwent a rightward shift in the presence of methylene blue or glibenclamide. The concentration ratios of KRN2391 calculated based on EC50 values were 2.8 and 3.7 in the presence of methylene blue and glibenclamide, respectively. 4. The concentration-relaxation curves for nitroglycerin and cromakalin underwent a rightward shift in the presence of methylene blue and glibenclamide, respectively, and the concentration ratios of nitroglycerin and cromakalim were 12.0 and 6.3. 5. These relaxant effects of KRN2391 and nitroglycerin on endothelin-1-induced contraction of porcine coronary artery were greater than those of cromakalim and nifedipine. This potent relaxant action of KRN2391 on endothelin-induced contraction is thought to be based on both a nitrate action and a K+ channel opening action.

Animals↗
PubMed1994

Comparative analysis of vasodilating mechanisms of Ki1769, Ki3315 and KRN2391, pyridinecarboximidamide derivatives, in porcine isolated coronary artery.

1. The vasodilating mechanisms of pyridinecarboximidamide derivatives which have a nitroxyl group (KRN2391), a phenyl group (Ki1769) or a hydroxyl group (Ki3315) were studied in porcine isolated coronary artery. 2. KRN2391 (10(-6) M) increased cyclic GMP formation but did not affect intracellular cyclic AMP level. Ki1769 (10(-5) M) and Ki3315 (10(-3) M) had no effect on intracellular cyclic GMP and cyclic AMP levels. 3. Despite producing submaximal relaxation at KRN2391 (10(-6) M) and nitroglycerin (10(-6) M), the increase in cyclic GMP caused by KRN2391 was lower than that caused by nitroglycerin. 4. Methylene blue (10(-5) M) inhibited KRN2391- and nitroglycerin-induced relaxations but did not affect Ki1769- and Ki3315-induced relaxation. 5. Glibenclamide (10(-6) M) inhibited KRN2391-, Ki1769- and Ki3315-induced relaxation but did not affect nitroglycerin-induced relaxation. 6. These results suggest that the nitroxyl group of KRN239 contributes to its nitrate action and the pyridinecarboximidamide moiety plays an important role of developing a K channel opening action.

Animals↗
PubMed1994

Pharmacological analysis of the effect of KRN2391 on coronary vasculature in perfused rat heart.

1. The antagonism by glibenclamide of the effects of KRN2391, cromakalim and nifedipine on coronary flow (CF) were compared in isolated perfused rat hearts. 2. KRN2391, cromakalim and nifedipine increased CF in a concentration-dependent manner. In the presence of glibenclamide, the concentration-effect curves on CF for KRN2391 and cromakalim shifted to the right but that for nifedipine did not change. 3. The EC50 values increased about 6.6-fold for KRN2391 and 19.0-fold for cromakalim in the presence of glibenclamide. 4. These results suggest that the increase in CF induced by KRN2391 is due to both glibenclamide-sensitive and insensitive mechanisms.

Animals↗
PubMed1994

Mosaic and polymorphic imprinting of the WT1 gene in humans.

We have examined the imprinting of the Wilms' tumour suppressor gene (WT1) in human tissues. We confirm that WT1 is biallelically expressed in the kidney, however, in five of nine preterm placentae WT1 was expressed largely or exclusively from the maternal allele. Monoallelic expression of WT1 was also found in two fetal brains. These data demonstrate that WT1 can undergo tissue specific imprinting. Furthermore, because monoallelic expression of WT1 was not found in all placentae examined, WT1 imprinting may be genetically polymorphic within the human population.

Alleles↗
PubMed1994

Assignment of the human PAX4 gene to chromosome band 7q32 by fluorescence in situ hybridization.

Of the nine known members of a human paired box-containing gene family (Pax), only PAX4 has not been precisely localized. We screened a cosmid library of human genomic DNA using polymerase chain reaction products for PAX4 as a probe and isolated three positive cosmid clones. Sequence analysis revealed that at least two of them had exon-like sequences and showed extensive homology to Pax-4 in the mouse. These two cosmid clones were mapped to human chromosome band 7q32 by fluorescence in situ hybridization.

Animals↗