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Biomedical subjects

H Yano

Publications and source records attributed to H Yano.

At least 235 records · Page 13Linked to original sources

Inhibition by the calmodulin antagonist trifluoperazine of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of the calmodulin antagonist trifluoperazine on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and on the ornithine decarboxylase (ODC) activity and labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and from the beginning of the experiment, received s.c. injections of 15 or 30 mg/kg body weight of trifluoperazine in depot form every other day until the end of the experiment. Preneoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P) were examined histochemically. In week 16, quantitative histological analysis showed that prolonged administration of 30 mg but not 15 mg/kg body weight of trifluoperazine resulted in significant reductions in the number and percentage area of GST-P-positive hepatic lesions. Trifluoperazine also caused significant decreases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and their adjacent hepatocytes. These findings indicate that trifluoperazine inhibits carcinogenesis and suggest that this effect may be closely related to its effect in inhibiting ODC activity and cell proliferation in the enzyme-altered lesions and their adjacent liver.

Animals↗

Inhibition by amiloride of experimental carcinogenesis induced by azaserine in rat pancreas.

The effects of prolonged administration of the diuretic amiloride on pancreatic carcinogenesis induced by azaserine and on the labeling index of carcinogen-induced pancreatic lesions were investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight azaserine and also 5 mg/kg body weight amiloride every other day until the end of the experiment at week 62. Carcinogen-induced pancreatic lesions were examined by histochemical techniques and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histologic analysis showed that prolonged administration of amiloride significantly reduced the number and size (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the subsequent development of pancreatic cancer. Amiloride also significantly decreased the labeling index of carcinogen-induced pancreatic lesions, but not of the surrounding acinar cells. In contrast, amiloride has no significant influence on the number and size of ATPase-negative pancreatic lesions. These findings indicate that amiloride inhibits pancreatic carcinogenesis, and that this effect may be related to the reduction of ATPase-positive lesions and to amiloride's inhibition of cell proliferation in neoplastic lesions of the pancreas.

Adenosine Triphosphatases↗

Sequence of human hexokinase III cDNA and assignment of the human hexokinase III gene (HK3) to chromosome band 5q35.2 by fluorescence in situ hybridization.

Complementary DNA clones encoding human hexokinase III were isolated from a liver cDNA library. There was 84.7% identity between the amino acid sequences of human and rat hexokinase III. RNA blotting showed the presence of hexokinase III mRNA in liver and lung. Fluorescence in situ hybridization localized the human hexokinase III gene (HK3) to chromosome 5, band q35.2.

Amino Acid Sequence↗

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↗

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↗

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↗

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↗

Versatility of the thin groin flap.

The groin flap is one of the most usable flaps. It provides a large amount of skin coverage with an easily concealed donor site. However, when the flap is used to reconstruct areas of the neck, hand, or foot, a secondary procedure for defatting is usually necessary. Thinner flaps are thought to be more useful in these areas. We present an anatomical study of the thin groin flap, including its dissection and defatting, and 12 clinical cases using the thin groin flap for neck (n = 7), foot (n = 4), and scalp (n = 1) reconstruction. The largest successful flap measured 13 x 30 cm. Eight flaps survived completely, two had partial necrosis, and two had total necrosis. Complications were thought to be caused by dissection around the pedicle. Meticulous dissection and thinning are required to create the thin groin flap. Excellent aesthetic results requiring no secondary defatting procedures are possible with this new thin groin flap.

Adolescent↗

Differentiation of species in the Bacillus brevis group and the Bacillus aneurinolyticus group based on the electrophoretic whole-cell protein pattern.

Ninety strains of eleven Bacillus species in the Bacillus brevis group and the Bacillus aneurinolyticus group were compared with the electrophoretic whole-cell protein pattern. The strains were separated into two clusters at the similarity of 55%. One cluster (cluster 1) was consisted of strains from the B. brevis group, and another cluster (cluster 2) was composed of strains from the B. aneurinolyticus group. The cluster 1 was separated into eight subclusters. Out of eight subclusters, seven subclusters contain strains from B. brevis, B. laterosporus, B. agri, B. reuszeri, B. choshinensis, B. formosus, and B. borstelensis. Another subcluster was further separated into two related clusters, which corresponded to B. centrosporus and B. parabrevis, and they were fused at the similarity of 76%. Cluster 2 was separated into two subclusters, which corresponded to B. aneurinolyticus and B. migulanus. The above eleven species showed characteristic patterns distinct from one another, and this correlated well with the published DNA relatedness data. The comparison of the electrophoretic whole-cell protein pattern proved to be useful for evaluation of taxonomic relationships among these taxa.

Bacillus↗

More effective endoscopic resection with a two-channel colonoscope for carcinoid tumors of the rectum.

PURPOSE: Complete resection of small carcinoid tumors of the rectum is difficult with conventional polypectomy, because these tumors are most often located in the submucosal layer of the rectal wall. To completely remove these tumors, we used a two-channel videocolonoscope with which both a grasping forceps and a polypectomy snare could be used simultaneously. We evaluated its clinical usefulness in comparison with one-channel colonoscopic polypectomy. METHODS: At Osaka Medical Center for Cancer and Cardiovascular Diseases, seven carcinoid tumors in seven patients were removed with a one-channel videocolonoscope from 1985 to 1992. In 1993 and 1994, ten tumors in nine patients were removed with a two-channel colonoscope. RESULTS: The rate of complete removal of carcinoid tumors with a two-channel videocolonoscope (9 of 10 tumors, 90 percent) was significantly higher (P < 0.05) than with a one-channel videocolonoscope (2 of 7 tumors, 29 percent). No complications occurred during or after endoscopic resection with a two-channel colonoscope. CONCLUSIONS: Endoscopic resection with a two-channel colonoscope is a useful and safe method for resection of small carcinoid tumors of the rectum.

Carcinoid Tumor↗

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

Adolescent↗

Differential scanning calorimetric studies on bovine serum albumin. IV. Effect of anionic surfactants with various lengths of hydrocarbon chain.

Using defatted and SH-blocked bovine serum albumin (BSA), measurements of differential scanning calorimetry (DSC) have been made at pH 7 on the complexes of BSA and a series of sodium alkyl sulfates used were sodium decyl sulfate (SDeS), sodium octyl sulfate (SOS), sodium hexyl sulfate (SHS) and sodium ethyl sulfate (SES). Results obtained were compared with those on the system BSA-sodium dodecyl sulfate (SDS) studied previously. Two peaks P1 and P2 existed in the DSC curve of BSA. These peaks originate in the heat-induced transition of BSA. The pattern of DSC curve changed with the amount of the ligand added, i.e. with the molar mixing ratio ligand/BSA (1). The change for systems BSA-SDeS, BSA-SOS and BSA-SHS was qualitatively the same as that for the system BSA-SDS (2). Interestingly, SES, which is not a surfactant, interacts with BSA. The change for the system BSA-SES was qualitatively the same as that for the system BSA-Na2SO4. All alkyl sulfates suppressed the heat-induced transition at lower concentrations. A linear relationship was obtained for the plots of log(D/A)1 versus log CMC, where (D/A)1 is the molar mixing ratio of anionic surfactant (D) to BSA (A) at which the most heat-stable complex is formed. This suggests that the hydrophobic force has a serious effect on the formation of heat-stable complexes.

Anions↗

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↗

Expression of Fas and anti-Fas-mediated apoptosis in human hepatocellular carcinoma cell lines.

BACKGROUND/AIMS: Fas transduces apoptotic signals upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. Because little is known about Fas expression and function in hepatocellular carcinoma, these issues are addressed in the current article. METHODS: We examined Fas expressions at protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, on six hepatocellular carcinoma cell lines. RESULTS: Two cell lines constitutively expressed high levels of Fas both on their cell surface and in their cytoplasm, whereas the other four cell lines expressed Fas mainly in their cytoplasm. Fas mRNA of normal size was detected in all cell lines in reverse transcriptase-polymerase chain reaction analyses. Although a Fas mRNA variant, suggesting a soluble Fas molecule, was detected in the two cell lines expressing high levels of Fas, its amount was very small compared to that of normal-sized Fas transcript. Anti-Fas dose-dependently induced apoptosis exclusively in the two cell lines which constitutively express high levels of cell surface Fas. However, after preincubation with interferon-gamma, one cell line with low surface Fas expression became anti-Fas sensitive equivalent to the two cell lines expressing surface Fas at high levels. Studies of two clonally related cell lines showed that dedifferentiated clones had lower Fas expression and resistance to anti-Fas, suggesting deterioration of Fas system after clonal cell dedifferentiation. CONCLUSIONS: These findings suggest sensitivity to anti-Fas is virtually relevant to cell surface Fas, but not to cytoplasmic Fas expression. However, its expression level does not correlate to sensitivity to anti-Fas.

Antineoplastic Agents↗

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↗

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↗

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↗