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Biomedical subjects

H Yano

Publications and source records attributed to H Yano.

At least 19 recordsLinked to original sources
PubMed1996

Tissue norepinephrine depletion as a mechanism for calcium chloride inhibition of gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The effects of oral calcium chloride (CaCl2) on sodium chloride (NaCl)-enhanced induction of gastric carcinogenesis by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, and the norepinephrine (NE) concentration in the gastric wall, were investigated in Wistar rats. Animals were given the carcinogen for 25 weeks and then chow pellets containing 10% NaCl with or without 8% or 4% CaCl2. In week 52, the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of antral epithelial cells were significantly greater in rats fed NaCl alone than in untreated control rats. Concomitant oral treatment with CaCl2 at 8%, but not 4%, significantly reduced the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of the antral epithelial cells in week 52 compared with those in rats fed NaCl alone. Because NE concentration reflects sympathetic nervous system activity, our findings suggest that the sympathetic nervous system could play a role in NaCl-enhanced gastric carcinogenesis. Our findings also suggest that NE depletion by CaCl2 may be related to its inhibition of NaCl-enhanced carcinogenesis.

Animals↗
PubMed1996

Rat inwardly rectifying potassium channel Kir6.2: cloning electrophysiological characterization, and decreased expression in pancreatic islets of male Zucker diabetic fatty rats.

The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. We have isolated cDNA clones encoding rat Kir6.2. Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel. A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. Thus, decreased expression of Kir6.2 could contribute to the beta-cell dysfunction which characterizes diabetes mellitus in this animal model.

Adenosine Triphosphate↗
PubMed1996

Inhibition of phosphatidylinositol 3-kinase blocks T cell antigen receptor/CD3-induced activation of the mitogen-activated kinase Erk2.

The production of 3-phosphorylated inositol phospholipids is implicated in regulation of cell growth and transformation. To explore the role of these lipids in T cell antigen receptor (TCR)/CD3-induced signaling, we have examined the effects of a specific phosphatidylinositol 3-kinase (PtdIns3K) inhibitor, wortmannin, and overexpression of two PtdIns3K constructs on the activation of down-stream effectors in anti-CD3 treated T cells. We report that treatment of cells with wortmannin blocked anti-CD3-induced activation of the mitogen-activation kinase Erk2 while not affecting phorbol-ester-induced Erk2 activation. An inactive analog of wortmannin, WM12, did not affect TCR/CD3-induced Erk2 activation, and wortmannin had no effect on the activity of Erk2 when added directly to the in vitro assays. Expression of a disruptive PtdIns3K construct also reduced Erk2 activation, while a construct that stimulates PtdIns3K enhanced the activation of Erk2. Receptor-induced activation of other Ser/Thr kinases, such as c-Raf, B-Raf, Mek1, Mek2, Mekk, was not affected by wortmannin. Our results suggest that the production of 3-phosphorylated inositol phospholipids is involved in the activation of Erk2, but does not regulate the enzymes that are thought to be upstream of Erk2.

Amino Acid Sequence↗
PubMed1996

Antisense inhibition of parathyroid hormone-related peptide gene expression reduces malignant pituitary tumor progression and metastases in the rat.

A newly established metastatic rat pituitary tumor (mGH3) possesses a malignant phenotype that is invasive and hypervascular compared with the original GH3 tumors. mGH3 cells exhibit anchorage independence and expression of elevated levels of parathyroid hormone-related peptide (PTHrP) in vitro. To clarify the role of PTHrP in the development of the malignant phenotype, tumor cells were treated with phosphorothioate antisense PTHrP oligonucleotide. Treatment with antisense PTHrP resulted in a scattering phenomenon in the colony formation assay but did not inhibit cell growth in vitro. Inoculation of mGH3 cells in the cerebral ventricle resulted in a rapid growth of tumor cells within 3 weeks and dissemination throughout the entire ventricular system. Although treatment with sense or mismatched PTHrP oligonucleotide did not influence the subsequent tumor growth, the in vivo coinjection and injection of antisense PTHrP 1 week after tumor cell implantation into the right lateral ventricle markedly reduced tumor size and suppressed metastasis formation. The survival rate of mGH3 tumor-injected rats was prolonged by antisense PTHrP therapy. Our results demonstrated the biological involvement of PTHrP in malignant phenotype in rat pituitary tumors, suggesting that antisense PTHrP may provide a novel antimetastatic therapy for malignant somatotroph tumors.

Animals↗
PubMed1996

A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that shows the features of hepatocellular carcinoma or cholangiocarcinoma under different growth conditions.

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma is a rare tumor of the liver, and its histogenesis remains unclear. The authors addressed this issue in the current article. METHODS: A specimen aseptically obtained from the surgically resected combined hepatocellular and cholangiocarcinoma was processed for primary culture. The morphologic features of the established cell line cultured on a plastic dish and in type I collagen gel matrix, and transplanted in nude mice were examined. RESULTS: The authors established a new human combined hepatocellular and cholangiocarcinoma cell line, designated KMCH-2, from a 40-year-old Japanese man. KMCH-2 cells on a plastic dish proliferated in a monolayered sheet with a population doubling time of 32 to 44 h. KMCH-2 expressed functional characteristics of hepatocellular carcinoma, such as albumin synthesis at protein and mRNA levels, but were poorly differentiated in morphology, showing an overlap of features with cholangiocarcinoma. KMCH-2 cells cultured within type I collagen gel matrix proliferated, forming compact to vaguely trabecular and pseudoglandular arrangements, and differentiated to show morphological characteristics of hepatocellular carcinoma unlike the cells on a plastic dish. Mucin production was not detected in KMCH-2 cells in vitro. Subcutaneous tumors which developed in nude mice injected with KMCH-2 cells represented features of adenocarcinoma with mucin production. CONCLUSIONS: The present results revealed the presence of an albumin-producing human hepatic neoplastic cell, such as KMCH-2, that can differentiate to show not only the features of hepatocellular carcinoma but also those of cholangiocarcinoma under certain growth conditions.

Adult↗
PubMed1996

Insulin enhancement of in vitro wound healing in fetal rat parietal bones.

PURPOSE: This study evaluated the effect of insulin on fracture in fetal rat intramembranous bone using an organ culture system in which bone mineralizes in vitro. MATERIALS AND METHODS: Twenty-day-old fetal rat parietal bones were fractured parallel to the frontal plane and cultured in a serum-free medium with or without insulin for 4 to 12 days. They were then processed for light microscopy. RESULTS: In the specimens not treated with insulin, bony bridges were observed in less than 10% on day 4 and 8, and only 45% on day 12. In bones treated with insulin at 10(-6) mol/L, bony bridges were observed in 73% on day 4 and 100% on day 8 and 12. No callus or cartilage formation was observed during the wound repair process, indicating that intramembranous ossification occurred. CONCLUSION: These findings suggest that insulin has a direct effect on bone cells, which enhances the healing of fractures in intramembranous bone.

Animals↗
PubMed1996

Expressions of basic fibroblast growth factor and its receptors and their relationship to proliferation of human hepatocellular carcinoma cell lines.

On six human hepatocellular carcinoma (HCC) cell lines (KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, and HAK- 1B), we examined expressions and functions of the proteins and messenger RNAs (mRNAs) of basic fibroblast growth factor (bFGF) and its receptor, i.e., fibroblast growth factor receptor-1 (FGFR-1), as well as mRNA expressions of FGFR-2 approximately 4. All six cell lines expressed the proteins and mRNAs of bFGF and FGFR-1, and at least one of FGFR-2 approximately 4 mRNAs. Two of the six cell lines (KYN-1 and KYN-3) presented significant release of bFGF in culture supernatant, while the release in the remaining four cell lines was quite small. Addition of anti-bFGF neutralizing antibody (1, 10, or 20 microg/mL) to culture medium resulted in marked suppression of cell proliferation in all cell lines except HAK-1A. On the other hand, addition of exogenous bFGF (0.1, 1, or 5 ng/mL) to culture medium stimulated cell proliferation except in KIM-1 and KYN-2. When KIM-1 was transplanted to nude mice and anti-bFGF antibody was injected subcutaneously to a space surrounding the developed tumor, tumor proliferation was significantly suppressed in nude mice that received anti-bFGF antibody than in control mice, but there were no histological differences between the groups, including blood space formation in the stroma. In conclusion, hepatocellular carcinoma (HCC) cells may possess a proliferation mechanism regulated by an autocrine mechanism, a paracrine mechanism, or both, which are mediated by bFGF/FGFR.

Animals↗
PubMed1996

Effect of selective and non-selective muscarinic blockade on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of baclofen, a gamma-amino-n-butyric acid receptor B agonist, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and how its effects are influenced by selective (M1) and non-selective (M1 and M2) pharmacological blockade of muscarinic receptors were investigated in inbred Wistar rats. Rats were given s.c. injections of 8 mg/kg body wt baclofen with and without 0.5 mg/kg body wt atropine (non-selective M1 and M2 muscarinic receptor antagonist) or 1.0 mg/kg body wt pirenzepine (selective M1 muscarinic receptor antagonist) every other day after a 25 week carcinogen treatment. At week 52 baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with atropine significantly attenuated the inhibition by baclofen of gastric carcinogenesis, but combined use with pirenzepine had no significant effect on the inhibition by baclofen of gastric carcinogenesis. Baclofen also significantly decreased the labeling index of the antral mucosa. Baclofen plus atropine attenuated the decrease in the labeling index of the antral mucosa due to baclofen, but baclofen plus pirenzepine had no significant effect on the labeling index. These results suggest that the inhibition of gastric carcinogenesis by baclofen is mediated through muscarinic receptors and M2 receptors, but not M1 receptors, are involved in this response.

Adenocarcinoma↗
PubMed1996

Developmental stage-specific and nitrate-independent regulation of nitrate reductase gene expression in rapeseed.

cDNA clones for two isogenes of nitrate reductase (NR) have been isolated from rapeseed (Brassica napus L.) androgenetic haploid embryos induced by microspore culture. NR mRNA accumulation can be detected by northern hybridization at 14 d after culture initiation when embryos develop to the heart/torpedo-shaped stage. Whole-mount in situ hybridization experiments demonstrate that the mRNA accumulation is developmental stage specific. In addition, even when cultured in media containing no nitrate, embryos accumulated NR mRNA to almost the same level as the control. This indicates the unique regulation of NR in embryogenesis in which NR mRNA transcription is activated in a developmental stage-specific manner that is independent of nitrate induction. In zygotic embryogenesis, a stage-specific accumulation of NR mRNA was also observed. By contrast, the obvious effect of nitrate on NR expression that has been reported in many plant species was also confirmed in rapeseed leaf. Quantitative combined reverse transcription-polymerase chain reaction analysis suggests that the flexible and variable regulation of NR expression, which is organ specific, nitrogen metabolite specific, and developmental stage specific, is caused principally by regulation of one major structural gene.

Base Sequence↗
PubMed1996

Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis. Increased gene expression in the intima of injured carotid arteries and human restenotic coronary lesions.

Proliferation of vascular smooth muscle cells (VSMCs) is considered to be one key event underlying the pathophysiology of restenosis after angioplasty. The parathyroid hormone-related peptide (PTHrP) and its receptor, a local autocrine and paracrine regulator of cellular growth in a variety of normal cell types, have been reported in the vicinity of VSMCs. To investigate how PTHrP might be involved in the process of neointimal formation after balloon angioplasty, we examined PTHrP expression in balloon-denuded rat carotid arteries and human coronary arteries that had been retrieved by directional atherectomy. In rat carotid arteries, the RNase protection assay and in situ hybridization demonstrated that PTHrP mRNA expression increased fourfold to sixfold 1 to 7 days after denudation and continued for 28 days, coincident with downregulation of PTH/PTHrP receptor mRNA expression. In situ hybridization and immunohistochemistry revealed that PTHrP expression in balloon-denuded carotid arteries was mainly localized to the neointima. To confirm the involvement of the PTHrP in human coronary artery restenotic lesions, immunohistochemical analysis of human coronary atherectomy specimens (23 primary and 10 restenotic lesions) was then performed. The number of intimal cells that expressed PTHrP protein was significantly higher in restenotic (407 +/- 53 cells/mm2; range, 143 to 739) than in stable angina (50 +/- 12 cells/mm2; range, 18 to 132; P<.05) or unstable angina (129 +/- 16 cells/mm2; range, 21 to 232; P<.05) specimens. These data demonstrate that PTHrP gene expression in VSMCs markedly increases during neointimal formation, supporting the hypothesis that PTHrP may play an important role in vascular stenosis as a regulator of VSMC proliferation.

Adult↗
PubMed1996

[Spontaneous renal rupture due to xanthogranulomatous pyelonephritis; a case report].

A 47-year-old female was admitted with colicky pain in the left flank. Ultrasonography and abdominal CT revealed left perirenal hematoma. Abdominal CT revealed a multilocular cystic lesion in the upper pole of the left kidney. Renal angiography revealed left renal cell carcinoma. Left nephrectomy was performed under a tentative diagnosis of left renal cell carcinoma. However, pathological diagnosis was xanthogranulomatous pyelonephritis. Xanthogranulomatous pyelonephritis is an atypical form of chronic renal parenchymal infection that can be classified as diffuse type or focal type. Preoperative diagnosis of focal xanthogranulomatous pyelonephritis is difficult because of clinical and radiological similarities to renal cell carcinoma. Our case is presented with a brief review of the literature.

Carcinoma, Renal Cell↗
PubMed1996

Fas antigen expression and its relationship with apoptosis in human hepatocellular carcinoma and noncancerous tissues.

Apoptosis, a programmed cell death, can be observed in the tissues of viral or autoimmune hepatitis and of hepatocellular carcinoma. Fas antigen (Fas) was proposed as a protein that triggers apoptosis. To elucidate the relationship between Fas expression and its location in hepatocellular carcinoma cells, we histochemically examined Fas expression by using 25 hepatocellular carcinoma tissues and their corresponding noncancerous tissues, which were surgically obtained from the same patients. In addition, the relationship between Fas expression and apoptotic cell numbers was examined in the hematoxylin-and-eosin-stained specimens obtained from 23 of the 25 patients. Hepatocellular carcinoma tissues expressed Fas less frequently and more weakly than noncancerous tissues. The majority of noncancerous specimens expressed Fas both on the surface and in the cytoplasm, whereas the majority of hepatocellular carcinoma expressed Fas only in the cytoplasm. Apoptotic cell counts were significantly higher in Fas-expressing tissues than in Fas-negative tissues. Among Fas-expressing tissues, the counts were higher in surface Fas-expressing tissues than in tissues that expressed only cytoplasmic Fas (P < 0.01 to 0.05). Our findings indicate that the development of apoptosis in hepatocellular carcinoma tissues relates to not only Fas expression but also its location.

Adult↗
PubMed1995

Suppression by amiloride of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane.

The effects of concomitant administration of bombesin and of the diuretic drug amiloride on the development of large and small intestinal tumors induced by azoxymethane (AOM), the incidence of their metastasis to the peritoneum and the labeling index of intestinal adenocarcinomas were investigated in inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of AOM for 10 weeks and s.c. injections of bombesin and/or a higher or lower dose of amiloride hydrochloride (amiloride) every other day until the end of the experiment in week 45. Administration of bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal adenocarcinomas. Although administration of both doses of amiloride with bombesin had little or no influence on the enhancement of intestinal tumorigenesis by bombesin, the location, histological type, depth of involvement or labeling index of intestinal adenocarcinomas, a higher dose of amiloride significantly reduced the incidence of cancer metastasis to the peritoneum. Our findings indicate that amiloride possesses an anti-metastatic activity.

Adenocarcinoma↗
PubMed1995

Biochemical and pharmacological studies with KT7692 and LY294002 on the role of phosphatidylinositol 3-kinase in Fc epsilon RI-mediated signal transduction.

Wortmannin inhibited phosphatidylinositol 3-kinase (P13-kinase) and Fc epsilon RI-mediated histamine secretion in RBL-2H3 cells to a similar degree, with IC50 values of 3 and 2 nM, respectively. Although P13-kinase is an acknowledged regulator of intracellular trafficking and secretion, wortmannin has proved to be a difficult drug to use in assessing the role of P13-kinase because it inhibits another important enzyme, myosin light-chain kinase (MLCK; IC50 = 200 nM). In the present study we synthesized a unique derivative of wortmannin, O-acetyl-delta 16-wortmannin-17-ol (KT7692), that has an inhibitory potency against PI3-kinase one-hundredth that of wortmannin, but retains a similar potency to wortmannin against MLCK. Histamine secretion was influenced 100-fold more by wortmannin than by KT7692.2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a structurally different PI3-kinase inhibitor from wortmannin, inhibited PI3-kinase with an IC50 of 2 microM but had little effect on MLCK activity in this concentration range. LY294002 also inhibited histamine secretion in RBL-2H3 cells with an IC50 of 5 microM. These results provide further evidence that PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion after stimulation of Fc epsilon RI. Furthermore KT7692 in combination with wortmannin and LY294002 would be a powerful tool for clarifying the involvement of PI3-kinase as distinct from that of MLCK in signal transduction systems of various cellular responses.

Androstadienes↗
PubMed1995

Expression of autocrine motility factor receptor in human esophageal squamous cell carcinoma.

Autocrine motility factor and its receptor (gp78) have been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected gp78 expression in buffered-formalin-fixed, paraffin-embedded sections of esophageal squamous cell carcinomas using an anti-gp78 monoclonal antibody (MAb), 3F3A, and examined the relationship between gp78 expression and clinicopathological and prognostic factors. In 55 of 101 (54%) patients, gp78 was detected in the tumor cells. The frequency of gp78-positive expression was significantly associated with tumor size, infiltrative growth, depth of invasion and lymph node metastasis. The cumulative survival rate of patients with gp78 was significantly lower than that of patients without gp78. Our results suggest that autocrine motility factor receptor (gp78) expression could be a useful biomarker for malignancy grading and prognosis in patients with esophageal squamous cell carcinoma.

Adult↗
PubMed1995

Transcriptional regulation of the chicken caldesmon gene. Activation of gizzard-type caldesmon promoter requires a CArG box-like motif.

Caldesmon, which plays a vital role in the actomyosin system, is distributed in smooth muscle and non-muscle cells, and its isoformal interconversion between a high M(r) form and low M(r) form is a favorable molecular event for studying phenotypic modulation of smooth muscle cells. Genomic analysis reveals two promoters, of which the gizzard-type promoter displays much higher activity than the brain-type promoter. Here, we have characterized transcriptional regulation of the gizzard-type promoter. Transient transfection assays in chick gizzard smooth muscle cells, chick embryo fibroblasts, mouse skeletal muscle cell line (C2C12), and HeLa cells revealed that the promoter activity was high in smooth muscle cells and fibroblasts, but was extremely low in other cells. Cell type-specific promoter activity depended on an element, CArG1, containing a unique CArG box-like motif (CCAAAAAAGG) at -315, while multiple E boxes were not directly involved in this event. Gel shift assays showed the specific interaction between the CArG1 and nuclear protein factors in smooth muscle cells and fibroblasts. These results suggest that the CArG1 is an essential cis-element for cell type-specific expression of caldesmon and that the function of CArG1 might be controlled under phenotypic modulation of smooth muscle cells.

Animals↗