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Biomedical subjects

Y Jinno

Publications and source records attributed to Y Jinno.

At least 73 records · Page 4Linked to original sources
PubMed1994

Assignment of the human moesin gene (MSN) to chromosome region Xq11.2-->q12.

The human moesin gene (MSN) was mapped to the long arm of the X chromosome. PCR products for the moesin gene cDNA were used as probes to isolate their corresponding cosmid clones. Fluorescence in situ hybridization (FISH) with two of the isolated cosmid probes showed signals at Xq11.2-->q12, whereas four other cosmids showed FISH signals on chromosome 5. Southern blot hybridization, using a PCR product corresponding to the 3' region of the moesin gene cDNA as a probe (probe-3), on one of the two cosmids that produced signals on the X chromosome gave 5.7- and 3.5-kb HindIII fragments. Further Southern hybridization of the DNA from XY, XX, and XXXXX individuals using probe-3 revealed a gene-dose effect of the X chromosome on the size of a 3.5-kb and a 3.0-kb HindIII fragment; in contrast, an invariant 9.8-kb band was present in the DNA of all individuals tested. Sequencing of an exon-intron border revealed that the two cosmids had predicted sequences. These results indicated that the two cosmids contained MSN, and it was consequently assigned to human chromosome region Xq11.2-->q12. These results strongly suggest that MSN may be removed from candidacy for Wiskott-Aldrich syndrome, which has been putatively mapped to Xp11.3-->p11.22.

Chromosome Mapping↗
PubMed1993

Vasorelaxant action of Ki1769, a new pyridinecarboximidamide, in isolated porcine coronary artery.

The characteristics of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethansulfonate) and its phenethyl and 2-hydroxyethyl derivatives (Ki1769 and Ki3315) were studied in isolated porcine coronary arteries. KRN2391, Ki1769 and Ki3315 produced concentration-dependent relaxation of coronary arteries contracted by 25 mM KCl and the order of relaxant potency was KRN2391 > Ki1769 > Ki3315. At the maximum effect, KRN2391 produced nearly complete relaxation but Ki1769 produced about 66% relaxation. The maximum effect of Ki3315 could not be obtained because of its solubility. The relaxation induced by KRN2391 was antagonized by glibenclamide and methylene blue but relaxations caused by Ki1769 and Ki3315 were antagonized by glibenclamide alone. The antagonistic effect of glibenclamide on Ki1769- and Ki3315-induced relaxations was more potent than that on KRN2391-induced relaxation. KRN2391 induced relaxation of coronary arteries contracted by 40 mM KCl in a concentration-dependent manner but the effect of KRN2391 was smaller against 40 mM KCl-induced contractions than against 25 mM KCl-induced contractions. Ki1769 had almost no effect on coronary arteries contracted by 40 mM KCl. These results suggest that pyridinecarboximidamide derivatives which do not possess a nitroxyl group have vasodilating ability based on a K+ channel opening action.

Animals↗
PubMed1993

Effects of K+ channel openers on ischemic dysfunction and metabolic disturbance in isolated perfused rat heart.

The effects of two structurally different K+ channel openers, KRN2391 and cromakalim, on cardiac mechanisms during ischemia and reperfusion were studied in isolated perfused rat hearts. Isolated buffer-perfused rat hearts pretreated with KRN2391, cromakalim and vehicle were subjected to 25 min of ischemia followed by 30 min of reperfusion. Before ischemia, KRN2391 (1-10 microM) and cromakalim (1-10 microM) increased coronary flow, but did not modify cardiac function or biochemical parameters (adenine nucleotides, energy charge potential: ECP, lactate). During ischemia, KRN2391 (3, 10 microM) and cromakalim (10 microM) significantly accelerated the reduction in cardiac function and attenuated the decreased levels of ATP and ECP, but did not change the lactate content. After 30 min of reperfusion, pretreatment with KRN2391 and cromakalim resulted in a significant improvement in cardiac function, ischemic contracture and biochemical parameters. Thus, both KRN2391 and cromakalim have beneficial effects on biochemical parameters during ischemia and reperfusion, effects which may be related to cardiodepression during ischemia.

Animals↗
PubMed1993

Microdissection and microcloning of genomic DNA markers from human chromosomal region 11q23.

A human genomic DNA library was constructed by using a microdissection-microcloning procedure with polymerase chain reaction (PCR) techniques on DNA from the chromosome 11q23 region. A total of 450 recombinant pUC clones were isolated from the library. Their insert sizes ranged from 150 to 850 bp with a mean of 320 bp. Fifty pUC clones were randomly selected and analyzed in detail. Southern blot analyses showed that 21 (42%) clones were unique DNA sequences, 20 (40%) clones were repetitive sequences, and 9 (18%) clones had no detectable hybridization. The unique sequences were used further in a secondary screening of a partially digested human genomic DNA library constructed in phage vector, and 4 clones were isolated. The chromosomal locations of these phage clones were confirmed to be in the q23 region of chromosome 11 by fluorescence in situ suppression hybridization. These pUC microclones isolated from the chromosomal region-specific genomic DNA library will be useful in the construction of physical contig maps with yeast artificial chromosome and/or cosmid clones and in the positional cloning of disease-associated genes localized to the q23 region of chromosome 11.

Chromosome Mapping↗
PubMed1993

Isolation of region-specific cosmids by hybridization with microdissection clones from human chromosome 10q11.1-q21.1.

A region-specific plasmid library composed of 20,000 recombinants was constructed by microdissection of human chromosome 10 (10q11.2-q21.1) and subsequent amplification with the primer-linker method of polymerase chain reaction (PCR). Hybridization with total human DNA showed that 32 of 217 microclones studied contained highly repetitive sequences. Further analysis of the remaining 185 microclones proved that 43 microclones, each having an insert longer than 200 bp, contained unique sequences of human chromosome 10 origin. Twenty-five microclones randomly selected from the 43 were used directly as probes to isolate corresponding cosmid clones, resulting in 32 cosmids corresponding to 14 microclones. Of the 25 cosmids that could be mapped by fluorescence in situ hybridization, 24 proved to originate from the microdissected or adjacent region (10p11.2-q22.3) and 1 from a rather distal region (10q24.3-q25.1). In addition, 15 of the 32 cosmids revealed restriction fragment length polymorphisms, including 1 with a variable number of tandem repeats marker. The microdissection library and the obtained cosmids are valuable resources for constructing high-resolution physical and linkage maps of the pericentromeric region of chromosome 10, where the gene predisposing to multiple endocrine neoplasia type 2A (MEN2A) has been mapped.

Base Sequence↗
PubMed1993

The origin of cytologically unidentifiable chromosome abnormalities: six cases ascertained by targeted chromosome-band painting.

De novo chromosome structural abnormalities cannot always be diagnosed by the use of standard cytogenetic techniques. We applied a previously developed chromosome-band-specific painting method to the diagnosis of such rearrangements. The diagnostic procedures consisted of microdissection of an aberrant chromosomal region of a given patient, polymerase chain reaction (PCR) amplification of the dissected chromosomal DNA, and subsequent competitive fluorescence in situ hybridization (FISH) using the PCR products as a probe pool on metaphase chromosomes from the patient and/or a karyotypically normal person. With this strategy, we studied 6 de novo rearrangements (6p+, 6q+, 9p+, 17p+, +mar, and +mar) in 6 patients. These rearrangements had been seen by conventional banding but their origin could not be identified. In all 6 patients, we successfully ascertained the origin. Using an aberrant region-specific probe pool, FISH signals appeared on both the aberrant region and a region of another specific chromosome pair. A reverse probe pool that was generated through the microdissection of normal chromosomes at a candidate region for the origin of the aberration hybridized with both the aberrant and the candidate regions. We thus diagnosed one patient with 17p+ as having trisomy for 14q32-qter, one with 9p+ as having trisomy for 12pter-p12, one with 6q+ as having a tandem duplication (trisomy) of a 6q23-q25 segment, one with 6p+ as having a tandem duplication (trisomy) of a 6p23-q21.3 segment, one with a supernumerary metacentric marker chromosome as having tetrasomy for 18pter-cen, and the last with an additional small marker chromosome as having trisomy for 18p11.1 (or p11.2)-q11.2. The present targeted chromosome-band-painting method provides the simple and rapid preparation of a probe pool for region-specific FISH, and is useful for the diagnosis of chromosome abnormalities of unknown origin.

Base Sequence↗
PubMed1993

Cosmid clones from microdissected human chromosomal region 15q11-q13.

A human chromosomal region, 15q11-q13, was microdissected, its DNA was amplified with the primer-linker PCR method, and the PCR products were cloned into a plasmid vector to construct a microclone library. Of 193 microclones analyzed with Southern blot hybridization on hybrid cell panels, 26 (13.5%) were either single-copy (unique) or low-repetitive fragments. By screening of a cosmid library of human genomic DNA using the 26 microclones as probes, 47 positive cosmids were obtained and underwent regional mapping with chromosome fluorescence in situ hybridization (FISH). Sixteen cosmids gave FISH signals at 15p-cen, 5 at 15q11-q13, 6 at 15q22-q26, 3 at other chromosomes, and 17 no signal. These 27 cosmids mapped to chromosome 15 are useful additions to the inventory of DNA markers of this chromosome including the much interested Prader-Willi/Angelman syndrome region.

Base Sequence↗
PubMed1993

Isolation and mapping of microsatellites from a library microdissected from the Werner syndrome region, 8p11.2-p22.

We have constructed a new genetic linkage map of the Werner syndrome (WRN) region, using microsatellites from a library which was developed by a chromosome microdissection and enzymatic amplification method. These microsatellites were used to genotype members of CEPH families using a simplified detection system of polymerase chain reaction (PCR) products. Two-point analysis was used to assign 4 microsatellite markers relative to each marker and other markers reported in the CEPH public data base. We confirmed that these 4 markers are located to the WRN region, 8p11.2-p22. Such microsatellites microdissected from the definite chromosome region may be useful for positional cloning.

Base Sequence↗
PubMed1993

Dystrophin isoforms expressed in the mouse retina.

The dystrophin gene is expressed in various tissues of the mouse. Previous immunohistochemical studies suggested the existence of dystrophin protein in the outer plexiform layer of the retina. We analyzed mRNAs from the retina and other tissues of mice and detected the dystrophin transcripts (DT) with the use of the reverse transcription and polymerase chain reaction (RT-PCR) method. The 5' sequences, corresponding to the first exon, of DT in the retina was mainly the brain type, whereas in the 3' region of DT that corresponds to the C-terminal domain of dystrophin, some additional RT-PCR products were detected. Base sequences in three of them showed homology to those for previously reported human dystrophin isoforms. The DT variations in mice were identical between the retina and the brain. It was thus concluded that dystrophin really expresses in the mouse retina and most of the retinal dystrophin proteins belong to the brain type isoform.

Animals↗
PubMed1993

Functional complementation in mouse-human radiation hybrids assigns the putative murine scid gene to the pericentric region of human chromosome 8.

Fragments of human chromosome 8 were introduced into cells derived from murine scid mice via X-irradiation and somatic cell fusion. The resulting hybrid clones contained human DNA fragment(s) which complemented the hyper-radiosensitivity of the scid cells. Alu-PCR products from these hybrids were used for chromosome painting using the technique of chromosome in situ suppression hybridization, allowing assignment of the human HYRC (hyper-radiosensitivity of murine scid mutation, complementing) gene, a candidate for a V(D)J recombinase gene, to human chromosome 8q11.

Animals↗
PubMed1993

Hemodynamic profile of KRN2391, a novel vasodilator, in anesthetized dogs.

In the present study, we compared the effects of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate), a novel vasodilator, with those of nicorandil and nifedipine on hemodynamic profiles. KRN2391 (1-30 micrograms), nicorandil (10-300 micrograms), and nifedipine (0.1-3 micrograms) increased coronary, mesenteric, renal and femoral blood flows in a dose-dependent manner when intraarterially administered. KRN2391 was approximately 18 times more potent than nicorandil and about five times less potent than nifedipine in increasing coronary blood flow. Intravenous (i.v.) administration of KRN2391, nicorandil, and nifedipine produced increases in coronary and mesenteric blood flows and decreases in these vascular resistances. Although nicorandil i.v. had no significant effect on renal blood flow (RBF), nifedipine i.v. decreased RBF whereas KRN2391 i.v. increased it. Femoral BF (FBF) decreased only at the highest i.v. dose of KRN2391 and decreased after an initial increase with nicorandil. Nifedipine i.v. had no significant effect on FBF. The effects of these three agents in increasing BF and in decreasing vascular resistance were most prominent in coronary vasculature. The duration of the effect of KRN2391 in increasing coronary BF (CBF) was longer than that of nicorandil but was similar to that of nifedipine. The hypotensive effect of KRN2391 was also weaker than its effect in increasing CBF in comparison with nicorandil and nifedipine. Thus, KRN2391 was demonstrated to possess a preferential activity on coronary vasculature.

Anesthesia↗
PubMed1993

Effect of KRN2391 on venous return: comparison with other vasodilators.

We compared the cardiohemodynamic effects of KRN2391, a novel coronary vasodilator, with those of nicorandil, nifedipine, cromakalim, and nitroglycerin (NTG) administered intravenously (i.v.) to anesthetized open-chest dogs. KRN2391 (10 and 30 micrograms/kg) decreased mean blood pressure (MBP) and superior vena cava flow (SVCF), and increased inferior vena cava flow (IVCF), total venous return (TVR), pulmonary artery blood flow (PAF), and right atrial pressure (RAP). Administration of KRN2391 (30 micrograms/kg) decreased heart rate (HR). Nicorandil (100 and 300 micrograms/kg) decreased MBP and SVCF, and produced transient increases followed by decreases in IVCF, TVR, PAF, and RAP. HR was decreased by administration of nicorandil (300 micrograms/kg). Nifedipine (1 and 3 micrograms/kg) decreased MBP and increased SVCF, IVCF, TVR, PAF, and RAP. HR was not affected by either dose of nifedipine. Cromakalim (10 micrograms/kg) decreased MBP, SVCF, and increased HR, IVCF, TVR, PAF and RAP. Nitroglycerin (3 micrograms/kg) decreased MBP, SVCF, IVCF, TVR, PAF, and RAP. In dogs that received glibenclamide (5 mg/kg, i.v.), the changes in MBP, SVCF, IVCF, TVR, PAF, and RAP caused by KRN2391 were reduced in comparison with those in dogs that received vehicle for glibenclamide. The decreases in IVCF, TVR, and PAF induced by nicorandil were not affected by glibenclamide, but the decrease in MBP was diminished and the decrease in RAP was augmented. The hemodynamic changes caused by cromakalim were almost inhibited by glibenclamide, whereas those caused by NTG were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Vasorelaxant mechanism of KRN2391 and nicorandil in porcine coronary arteries of different sizes.

1. The relaxant mechanisms of action of KRN2391, a novel vasodilator, and nicorandil on epimyocardial coronary artery (2.5- 3.0 mm outer diameter) and mid-myocardial coronary artery (0.8-1.0 mm outer diameter) were investigated in porcine isolated coronary arteries. In addition, the vasorelaxant responses of KRN2391 and nicorandil were compared with those of nitroglycerin and cromakalim, a K+ channel opener, in epi- and mid-myocardial coronary arteries. 2. Nitroglycerin showed a more potent relaxant effect on epi-myocardial coronary arteries than on mid-myocardial coronary arteries, whereas cromakalim produced greater relaxation responses in mid-myocardial coronary arteries. There was no difference between epi- and mid-myocardial coronary arteries in terms of the relaxant effect of KRN2391 and nicorandil. 3. Relaxation induced by KRN2391 in epi- and mid-myocardial coronary arteries was inhibited by oxyhaemoglobin, a pharmacological antagonist of nitrovasodilators, and glibenclamide, a pharmacological antagonist of K+ channel opening drugs. However, the inhibitory effect of glibenclamide on KRN2391-induced relaxation was greater in mid-myocardial coronary artery than in epi-myocardial coronary artery. 4. Relaxation induced by nicorandil was inhibited by oxyhaemoglobin alone in epi-myocardial coronary arteries and by both oxyhaemoglobin and glibenclamide in mid-myocardial coronary arteries. 5. In epi- and mid-myocardial coronary arteries, relaxation induced by cromakalim was inhibited by glibenclamide but not by oxyhaemoglobin, whereas relaxation induced by nitroglycerin was inhibited by oxyhaemoglobin but not by glibenclamide. 6. These results suggest that KRN2391 and nicorandil exhibit a dual mechanism of action acting partly as a nitrate and partly as a K+ channel opener. The mechanism of action of these drugs depend on the segment of coronary artery studied. Furthermore, the dual mechanism of action of KRN2391 and nicorandil seems to contribute to the equipotent relaxant effect between epi- and mid-myocardial coronary arteries.

Animals↗
PubMed1993

Comparison of the effects of KRN2391 and other coronary dilators on porcine isolated coronary arteries of different sizes.

The present study was performed to determine whether KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulphonate), a novel vasodilator, shows different effects on porcine isolated coronary arteries of different sizes. The vasodilating effects of KRN2391 on porcine large (2.5-3.0 mm outer diam.) and small (0.8-1.0 mm) coronary arteries were also compared with those of cromakalim, nicorandil, nifedipine, nitroglycerin and adenosine. The relaxant effects of these drugs were examined in coronary arteries contracted by 25 mM KCl. Nitroglycerin caused greater relaxation in large vessels than in small vessels. In contrast, adenosine, nifedipine and cromakalim caused greater relaxation in small vessels. However, there was no difference between large and small vessels in the relaxing effects of KRN2391 and nicorandil. These unique features of KRN2391 and nicorandil appear to be beneficial in ischaemic heart disease.

Adenosine↗
PubMed1993

Mapping of the bone morphogenetic protein 1 gene (BMP1) to 8p21: removal of BMP1 from candidacy for the bone disorder in Langer-Giedion syndrome.

Fifteen cosmids containing sequences from the human bone morphogenetic protein 1 gene (BMP1) were isolated from a cosmid library. The probe was a 483-bp DNA obtained by the reverse transcriptase-PCR method using primers designed according to the reported BMP1 sequence. When the positive cosmids were tested for chromosome fluorescence in situ hybridization, all showed signals at 8p21. The results indicated that BMP1 is not responsible for Langer-Giedion syndrome, whose putative gene has been assigned to 8q24.

Base Sequence↗
PubMed1993

Mechanism of action of KRN2391, a novel vasodilator, in canine mesenteric artery.

The present study was performed to clarify the mechanism of vasodilation of KRN2391 in canine mesenteric artery compared with those of nicorandil and cromakalim. We used the responses of isolated cranial mesenteric artery in vitro and changes in mesenteric blood flow in vivo as indicators reflecting the responses of a conductive artery and resistive arterioles, respectively. In isolated cranial mesenteric artery, KRN2391 (10(-8)-10(-5) M), nicorandil (10(-7)-10(-4) M) and cromakalim (10(-7)-10(-5) M) relaxed contractions caused by 25 mM KCl in a concentration-dependent manner. The concentration-relaxation curve for KRN2391 was shifted to the right by either methylene blue (10(-5) M) or glibenclamide (10(-6) M), but the inhibitory effect of methylene blue was more potent than that of glibenclamide. The concentration-relaxation curve for nicorandil was shifted to the right by methylene blue, but not by glibenclamide. In addition, the curve for cromakalim was shifted to the right by glibenclamide, but not by methylene blue. In in vivo experiments, the injections of KRN2391 (0.3-3 micrograms/kg), nicorandil (10-100 micrograms/kg) or cromakalim (1-10 micrograms/kg) into the mesenteric artery increased mesenteric blood flow in a dose-dependent manner. Glibenclamide (5 mg/kg, i.v.) attenuated the increase in mesenteric blood flow caused by KRN2391, nicorandil and cromakalim, but had no effect on that caused by nifedipine (1 microgram/kg). The ED20 value increased about 4.7-fold for KRN2391, 3.7-fold for nicorandil and 11.5-fold for cromakalim after administration of glibenclamide, as estimated from the % change to the absolute increase in mesenteric blood flow induced by nifedipine (1 microgram/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mechanism of action of KRN2391 in canine coronary vascular bed.

The present studies were performed to clarify the mechanism of action of KRN2391 in various sizes of canine coronary artery. We used the responses of isolated large and small coronary arteries and the changes in coronary blood flow (CBF) as indicators reflecting the responses of conductive arteries and resistive arterioles, respectively. In isolated small coronary artery, the effect of KRN2391 (10(-8)-10(-5) M) was antagonized by either methylene blue or glibenclamide. In isolated large coronary artery, the vasorelaxant effect of KRN2391 (10(-8)-10(-5) M) and nicorandil (10(-7)-10(-4) M) were antagonized by methylene blue (10(-5) M) but not by glibenclamide (10(-6) M). The relaxant effect of cromakalim was antagonized by glibenclamide but not by methylene blue in isolated large coronary artery. Intracoronary arterial injection of KRN2391, nicorandil or cromakalim produced an increase in CBF dose-dependently. Glibenclamide (5 mg/kg, i.v.) attenuated the increase in CBF caused by KRN2391, nicorandil and cromakalim. ED20, the dose that produced an increase in CBF by 20 ml/min, increased about 5-fold for KRN2391 and nicorandil and about 12-fold for cromakalim after administration of glibenclamide. These results suggest that the mechanism of action of KRN2391 and nicorandil depends on the segment of coronary arteries; i.e., they show a nitrate action alone in large coronary artery, and a K-channel opening action in addition to a nitrate action as the size of the coronary artery decreases.

Animals↗