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Biomedical subjects

H Igarashi

Publications and source records attributed to H Igarashi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Intratumor heterogeneity of centromere numerical abnormality in multiple primary gastric cancers: application of fluorescence in situ hybridization with intermittent microwave irradiation on paraffin-embedded tissue.

Our recent success in retrieving distinct fluorescence signals in response to centromere specific probing of paraffin-embedded tissues after intermittent microwave (MW) treatment provided the opportunity to analyze chromosome numbers or centromere abnormality in situ in human tumors in various clinicopathological settings. In this study, centromere numerical abnormality (CNA) was investigated by fluorescence in situ hybridization (FISH) in a case of multiple gastric cancer having intratumor histological heterogeneity. The different profiles as determined using a total of 20 specific probes on 4 multifocal lesions in the stomach confirmed the multi-clonality of these tumors. FISH with probes specific for chromosomes 10, 11, 16 and 18 revealed intratumor heterogeneity of the CNA, which corresponded to the histological heterogeneity. Our report clearly demonstrates, for the first time, intratumor heterogeneity of CNA and its association with the histological picture, and substantiates the applicability of the MW-assisted FISH protocol to paraffin-embedded pathological specimens.

Centromere↗
PubMed2000

Characterization of Staphylococcus aureus coagulase type VII isolates from staphylococcal food poisoning outbreaks (1980-1995) in Tokyo, Japan, by pulsed-field gel electrophoresis.

Staphylococcus aureus coagulase type VII strains have been the strains most frequently isolated from staphylococcal food poisoning outbreaks in Tokyo, Japan. We applied pulsed-field gel electrophoresis (PFGE) of chromosomal DNA digested with SmaI to characterize 129 coagulase type VII strains. These were isolated from 129 cases occurring in outbreaks in 35 districts during a 16-year period (1980-1995). The 129 outbreak strains were classified into three types, designated A (n = 115), B (n = 10), and C (n = 4). Types A and C were further divided into 33 (A1 to A33) and 4 (C1 to C4) subtypes, respectively. Strains of the same subtypes were isolated from food poisoning cases in the same districts at time intervals of 1 or 2 to 5 years. PFGE typing appears to be a useful method for subdividing strains of S. aureus coagulase type VII. A combination of coagulase typing and PFGE typing would provide more detailed information than the former method alone in epidemiologic investigations of staphylococcal food poisoning.

Bacterial Typing Techniques↗
PubMed2000

Genetic studies with the fission yeast Schizosaccharomyces pombe suggest involvement of wee1, ppa2, and rad24 in induction of cell cycle arrest by human immunodeficiency virus type 1 Vpr.

Accessory protein Vpr of human immunodeficiency virus type 1 (HIV-1) arrests cell cycling at G(2)/M phase in human and simian cells. Recently, it has been shown that Vpr also causes cell cycle arrest in the fission yeast Schizosaccharomyces pombe, which shares the cell cycle regulatory mechanisms with higher eukaryotes including humans. In this study, in order to identify host cellular factors involved in Vpr-induced cell cycle arrest, the ability of Vpr to cause elongated cellular morphology (cdc phenotype) typical of G(2)/M cell cycle arrest in wild-type and various mutant strains of S. pombe was examined. Our results indicated that Vpr caused the cdc phenotype in wild-type S. pombe as well as in strains carrying mutations, such as the cdc2-3w, Deltacdc25, rad1-1, Deltachk1, Deltamik1, and Deltappa1 strains. However, other mutants, such as the cdc2-1w, Deltawee1, Deltappa2, and Deltarad24 strains, failed to show a distinct cdc phenotype in response to Vpr expression. Results of these genetic studies suggested that Wee1, Ppa2, and Rad24 might be required for induction of cell cycle arrest by HIV-1 Vpr. Cell proliferation was inhibited by Vpr expression in all of the strains examined including the ones that did not show the cdc phenotype. The results supported the previously suggested possibility that Vpr affects the cell cycle and cell proliferation through different pathways.

Cell Cycle↗
PubMed2000

Rat and guinea pig pancreatic acini possess both VIP(1) and VIP(2) receptors, which mediate enzyme secretion.

Pancreatic acini from most species possess vasoactive intestinal peptide (VIP) receptors. Recently, two subtypes of VIP receptors, VIP(1)-R and VIP(2)-R, were cloned. Which subtype exists on pancreatic acini or mediates secretion is unclear. To address this, we examined pancreatic acini from both rat and guinea pig. VIP(1)-R and VIP(2)-R mRNA were identified in dispersed acini from both species by Northern blot analysis and in rat by Southern blot analysis. With the use of the VIP(2)-R-selective ligand Ro-25-1553 in both species, inhibition of binding of (125)I-labeled VIP to acini showed a biphasic pattern with a high-affinity component (10%) and a second representing 90%. The VIP(1)-R-selective ligand, [Lys(15),Arg(16),Leu(27)]VIP-(1-7)-GRF-(8-27), gave a monophasic pattern. Binding of Ro-25-1553 was better fit by a two-site model. In both rat and guinea pig acini, the dose-response curve of Ro-25-1553 for stimulation of enzyme secretion was biphasic, with a high-affinity component of 10-15% of the maximal secretion and a low-affinity component accounting for 85-90%. At low concentrations (10 nM) of Ro-25-1553 and [Lys(15),Arg(16), Leu(27)]VIP-(1-7)-GRF(8-27), which only occupy VIP receptors, a 4-fold and a 56-fold increase in cAMP occurred, respectively. These results show that both VIP(1)-R and VIP(2)-R subtypes exist on pancreatic acini of rat and guinea pig, their activation stimulates enzyme secretion by a cAMP-mediated mechanism, and the effects of VIP are mediated 90% by activation of VIP(1)-R and 10% by VIP(2)-R. Because VIP has a high affinity for both VIP-R subtypes, its effect on pancreatic acini is mediated by two receptor subtypes, which will need to be considered in future studies of the action of VIP in the pancreas.

Animals↗
PubMed2000

[Bone fracture receiving LH-RH agonists for prostatic cancer].

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers. RESULTS: The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

Aged↗
PubMed2000

Different vulnerability among chromosomes to numerical instability in gastric carcinogenesis: stage-dependent analysis by FISH with the use of microwave irradiation.

Numerical chromosomal abnormalities are a well known characteristic of human cancer, but no "chromosome-wide investigation" encompassing almost all of the chromosomes has ever been reported. Furthermore, although the multistep process of carcinogenesis is widely accepted in human cancer, the stepwise numerical aberration of chromosomes has never been addressed. Touch preparations of 24 (male 20, female 4) surgically resected gastric cancer tissue samples in various stages in terms of depth of invasion were analyzed by fluorescence in situ hybridization using centromere-specific probes including 17 chromosomes, 1-4, 6-8, 10-12, 15-18, 20, X, and Y. Microwave irradiation was performed to increase the sensitivity and specificity of the signal. The depth of the tumor invasion in the gastric wall and histological subtypes were recorded by viewing the histology of the adjacent portion. Numerical chromosomal abnormalities of chromosomes 1 and 2 were found most frequently and from the early stage of gastric cancer. The abnormalities observed were limited to chromosomes 1, 2, 4, and 20 in tumors invading to the middle layer of the submucosa of the gastric wall, but these became more extensive, involving almost all of the chromosomes investigated when the tumor had invaded beyond the proper muscle of the gastric wall. Centromeric numbers of chromosomes 3 and 18 were exceptionally stable even after the tumor progressed to advanced stage. These profiles of the sequential process of numerical chromosomal abnormality were similar in both mucocellular and tubular-type gastric cancer, but the prevalence was significantly lower in the mucocellular type (39.0% versus 68.0%). On the basis of fluorescence in situ hybridization analysis of 17 different chromosome centromeres in gastric cancer in various stages, we conclude that the earliest events in gastric carcinogenesis in terms of chromosomal abnormality occur in chromosomes 1 and 2 and that chromosomal numerical aberrations expand in a stepwise manner with cancer progression.

Adult↗
PubMed2000

[Clinical statistics on patients and operations during a 20-year period (1978-1997) at Department of Urology, Jikei University School of Medicine].

A statistical analysis was made of diseases, patients, and operations at our department in the four affiliated hospitals of Jikei University School of Medicine from 1978 through 1997. Our findings were as follows. Newly diagnosed urogenital malignancies, except testicular tumors, have been increasing in the last two decades among both outpatients and inpatients. Urogenital infections, including tuberculosis, have gradually been decreasing in the last two decades. The treatment of urinary stone diseases was markedly altered by the induction of extracorponeal shock wave lithotripsy.

Female Urogenital Diseases↗
PubMed1999

Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene.

It has been proposed that Ig gene rearrangement in the peritoneal cavity (Pc) B-1 cells might be involved in autoantibody generation. To study possible secondary B cell maturation, we prepared mice carrying a target integration of gfp gene into a rag1 locus (rag1/gfp mice). The GFP+ cells express rag1 mRNA and are undergoing Ig gene rearrangement. RAG1 expression was studied in Pc B-1 cells to detect cells during the stage of Ig gene rearrangement. In contrast to previous reports, Pc B-1 cells did not show RAG1 expression in adolescent or elderly mice. RAG1 expression was not induced in Pc B-1 cells in vivo after stimulation by oral or i.p. administration of LPS. Our results suggest that RAG1 expression in Pc B-1 cells is inhibited for a long period under normal condition and that this suppression is an essential state which maintains allelic exclusion of Ig genes.

Animals↗
PubMed1999

Activity and substrate specificity of the murine STK2 Serine/Threonine kinase that is structurally related to the mitotic regulator protein NIMA of Aspergillus nidulans.

We isolated a murine STK2 (mSTK2) cDNA that is homologous to murine Nek1 serine/threonine kinase, a family member related to the cell cycle regulator kinase NIMA of Aspergillus nidulans. Structural comparison demonstrated that the kinase domain of mSTK2 is highly similar to NIMA/Nek family but the C-terminal region is not similar to any proteins except for human STK2 (hSTK2). Similarly to Nek1, mSTK2 is expressed ubiquitously among various organs and is upregulated in the testis. The expression and localization of mSTK2 are not associated with the cell cycle progression of mitogen-activated lymphocyte and DNA-transfected fibroblast. The substrate specificity of mSTK2 is similar to NIMA, but the phosphorylation is observed exclusively upon threonine residues rather than serine. The mSTK2 is shown to be a new member of the NIMA/Nek family with similar substrate specificity, which might participate in a different role from NIMA kinase involved in the cell cycle regulation.

Amino Acid Sequence↗
PubMed1999

Reduction of telomeric repeats as a possible predictor for development of hepatocellular carcinoma: convenient evaluation by slot-blot analysis.

Hepatocellular carcinoma (HCC) mainly arises from the liver with chronic inflammation. Because telomere reduction reflects replicative history in somatic cells, we analyzed the possibility that liver tissues surrounding HCC consist of the cells carrying substantial reduction of telomere. We studied 20 HCC and surrounding noncancerous liver tissues (SL) obtained by surgical resection, and 10 laparoscopically obtained needle biopsy specimens of the liver with chronic inflammation including no overt HCC (CI). Five liver tissues without chronic liver diseases (ND) were also examined. Extracted genomic DNAs were blotted on a nylon membrane, and probed at first with radio-labeled d(TTAGGG)(3) and reprobed with radio-labeled d(CCT)(7). The intensity caused by d(TTAGGG)(3) was divided by that of d(CCT)(7). The ratio was defined as telomeric repeats content (TC). Dilution experiments reproducibly revealed almost the same TC. The reduction rate of telomere length through aging estimated by regression analysis of TC was 0.62% per year. Concomitant analyses of TC and average telomere length revealed that both values were significantly correlated (r =.45; P =.009). To compare TC in the liver with respect to chronic inflammation, the value was divided by TC in peripheral blood leukocytes (PBL) from the same donor. The ratio was defined as relative TC (RTC). There was a statistically significant decrease of RTC in CI compared with that in ND (P =.03). Furthermore, RTC in SL was significantly lower than that in CI (P =.0001). These observations suggest that RTC value in liver tissues may digitally indicate a replicative history of hepatocytes under chronic inflammation, and a risk of HCC development.

Adult↗
PubMed1999

High serum levels of M-CSF and G-CSF in Kawasaki disease.

To examine any role of macrophage colony-stimulating factor (M-CSF), in the immune responses in Kawasaki disease (KD), we serially assayed M-CSF and several related cytokines using ELISA. In 10 paediatric patients with KD the level of M-CSF was significantly higher in the acute phase than in the convalescent phase (1476.1 +/- 443.6 v 805.0 +/- 184.7 U/ml). Higher levels of serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were also found in the acute phase. These results suggest that M-CSF, G-CSF and interleukin-6, derived from monocytes as monokines or derived from vascular endothelial cells, might play an important role in the acute phase of KD.

Child↗
PubMed1999

Doc2alpha is an activity-dependent modulator of excitatory synaptic transmission.

Doc2alpha is a synaptic vesicle-associated Ca2 + -binding protein. To study the role of Doc2alpha in synaptic transmission and modulation, we generated homozygous null Doc2alpha mutant mice. In the CA1 region of hippocampal slices in the mutant mice, excitatory synaptic responses evoked with prolonged 5 Hz stimulation showed a significantly larger frequency facilitation followed by a steeper depression than those in wild-type mice, whereas there was no difference in synaptic transmission at lower frequencies or in paired-pulse facilitation. These results suggest that Doc2alpha regulates synaptic transmission when high Ca2 + concentrations in the presynaptic terminal are sustained. Furthermore, the mutant mice showed impairment in long-term potentiation and passive avoidance task. Thus, Doc2alpha may regulate transmitter release during repetitive synaptic activation, thereby contributing to memory formation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Regulation of small intestinal transit by central nervous calcitonin receptor.

Salmon calcitonin (sCT) suppresses small intestinal transit (SIT) or motility, but the mechanism is not well understood. Bolus s. c. administration of a pharmacologic dose of sCT (140 IU/kg) to mice significantly decreased plasma calcium and phosphorus, and suppressed SIT from 1 to 8 h for plasma calcium and phosphorus or 20 h for SIT (respective maximal effects were seen at 5 h, between 2 and 8 h, and between 1 and 5 h). Significant SIT inhibition did not occur at doses smaller than 140 IU/kg. Reverse transcription-polymerase chain reactions and Southern analysis demonstrated high levels of calcitonin receptor mRNA in diencephalon and lung, moderate levels of mRNA in cerebellum, kidney, and muscle, and barely detectable amounts in cerebral cortex and thymus. No message was detectable in duodenum, jejunum, liver, testis, or heart. Specific binding of [125I] sCT was demonstrated in the diencephalon. Intracerebroventricular (i.c.v.) administration of sCT inhibited SIT time- and dose-dependently. Maximal inhibition was obtained at a dose of 4 IU/kg, 20 min after injection. Pretreatment with sCT (140 IU/kg s.c.) completely abolished inhibition of SIT by i.c.v. sCT (4 IU/kg). These results suggest that sCT binds to receptors in the central nervous system and inhibits small bowel transit.

Animals↗
PubMed1999

Long-term vascular effects of Nomega-nitro-L-arginine methyl ester are not soley mediated by inhibition of endothelial nitric oxide synthesis in the rat mesenteric artery.

Nomega-nitro-L-arginine methyl ester (L-NAME), one of the synthetic L-arginine analogues with inhibitory effects of nitric oxide (NO) synthesis, is now widely used to examine the role of NO in various organs. We and others demonstrated that long-term treatment with L-NAME causes hypertension and cardiovascular lesions (perivascular fibrosis and medial thickening), especially at microvascular levels. However, convincing evidence is still lacking that these long-term cardiovascular effects of L-NAME are solely mediated by the inhibition of the synthesis of endothelium-derived NO (EDNO). This study was thus designed to better understand the effects of long-term treatment with L-NAME with special reference to EDNO synthesis. Male Wister-Kyoto rats were orally administered L-NAME for 8 weeks. Blood pressure significantly increased at 3 days and 1 and 8 weeks of the treatment. Endothelium-dependent relaxations to acetylcholine (ACh) of the aorta were reduced 3 days after the treatment, recovered at 1 week, and again reduced at 8 weeks, whereas the relaxations of the small mesenteric artery were unaltered throughout the experimental periods. At 8 weeks, indomethacin-sensitive, endothelium-dependent contractions to ACh were noted. The relative contributions of NO and endothelium-derived hyperpolarizing factor also were unchanged. Citrulline assay demonstrated that substantial levels of constitutive NO synthase activity remained in the aorta during the experiments. The long-term treatment with L-NAME caused perivascular fibrosis and medial thickening, not only in the aorta but also in the mesenteric artery. These results suggest that mechanism(s) other than simple inhibition of EDNO synthesis is involved in the long-term cardiovascular effects of L-NAME in the rat mesenteric artery.

Animals↗
PubMed1999

Important role of endothelium-derived hyperpolarizing factor in shear stress--induced endothelium-dependent relaxations in the rat mesenteric artery.

Shear stress is one of the most important stimulators for the release of endothelium-derived relaxing factors. Although shear stress-induced release of nitric oxide (NO) has been extensively investigated, it remains to be elucidated whether endothelium-derived hyperpolarizing factor (EDHF) contributes to the endothelium-dependent relaxations to shear stress. This study was designed to address this point in the isolated rat mesenteric artery. Large mesenteric arteries (400-500 microm) and resistance mesenteric arteries (150-250 microm) of the rat were precontracted with phenylephrine (at 80 mm Hg of perfusion pressure), and the changes in vessel diameter in response to variable flow (0-300 microl/min) were continuously examined. The relative contributions of vasodilator prostaglandins, NO, and EDHF were analyzed by the inhibitory effects of indomethacin (10(-5) M), N(G)-nitro-L-arginine (L-NNA, 10(-4) M), and KCl (40 mM), respectively. The shear stress-induced relaxations were totally endothelium dependent in both-sized blood vessels, and the contribution of NO was more prominent in large arteries than in resistance arteries, whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large- and intermediate-conductance Ca2+ -activated K channels) and apamin (an inhibitor of small-conductance Ca2+ -activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. These results indicate that EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, where K channels, especially calcium-activated K channels, appear to be involved.

Animals↗