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Biomedical subjects

H Yano

Publications and source records attributed to H Yano.

At least 145 records · Page 8Linked to original sources
PubMed1999

Interferon alfa receptor expression and growth inhibition by interferon alfa in human liver cancer cell lines.

Type I interferon (IFN) receptor consists of two chains (Hu-IFN-alphaR1 and Hu-IFN-alphaR2), and Hu-IFN-alphaR2 takes a soluble (Hu-IFN-alphaR2a), short (Hu-IFN-alphaR2b), or long (Hu-IFN-alphaR2c) form. We examined the expression of type I IFN receptor, the growth-suppression effect of IFN-alpha, and their relationship in 13 liver cancer cell lines. With reverse-transcription polymerase chain reaction (RT-PCR) analysis, the expressions of Hu-IFN-alphaR1, Hu-IFN-alphaR2a, and Hu-IFN-alphaR2c were confirmed in all cell lines, and that of Hu-IFN-alphaR2b in 12 cell lines. All cell lines expressed mRNAs of a transcriptional activator, interferon regulatory factor (IRF)-1, and its antagonistic repressor (IRF-2). Flow cytometry revealed weak expression of Hu-IFN-alphaR2 on the cell surface in 12 cell lines. The soluble-form protein of Hu-IFN-alphaR2 was detected at varying levels in culture supernatants of all cell lines with enzyme-linked immunosorbent assay (ELISA). Cell proliferation was suppressed in proportion to the dose of human natural IFN-alpha at 96 hours of culture, but it was not clearly related to the expression of Hu-IFN-alphaR2 protein on the cell surface. Investigations on the morphology, DNA, and cell cycle presented four growth suppression patterns as a result of IFN-alpha: 1) induction of apoptosis and blockage of cell cycle at the S phase (9 cell lines); 2) blockage at the S phase (2 cell lines); 3) induction of apoptosis and blockage at the G2/M phase (1 cell line); and 4) blockage at the G1 phase (1 cell line). There was no evidence showing that changes in the expressions of Bcl-2, Bcl-xL, Bak, and Bax lead directly to IFN-alpha-mediated apoptosis. Our findings demonstrated that IFN-alpha would express growth-suppression effects at varying degrees by inducing inhibition of cell-cycle progression with or without apoptosis, regardless of the expression level of Hu-IFN-alphaR2 protein on the cell surface.

Apoptosis↗
PubMed1999

Molecular cloning and pharmacological characterization of a somatostatin receptor subtype in the gymnotiform fish Apteronotus albifrons.

The actions of the various forms of somatostatin (SRIF), including those of the tetradecapeptide SRIF(14), are mediated by specific receptors. In mammals, five subtypes of SRIF receptors, termed sst(1-5), have been cloned. Using a combination of reverse transcriptase-polymerase chain reaction and genomic library screening in the gymnotiform fish Apteronotus albifrons, a gene encoding the first-known nonmammalian SRIF receptor has been isolated. The deduced amino acid sequence displays 59% identity with the human sst(3) receptor protein; hence, the gene is termed "Apteronotus sst(3)." The predicted protein consists of 494 amino acid residues exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. A signal corresponding to the Apteronotus sst(3) receptor was detected in brain after amplification of poly(A)(+)-RNA by reverse transcriptase-polymerase chain reaction, but not by Northern blot analysis or in situ hybridization, suggesting a low level of expression. Membranes prepared from CCL39 cells stably expressing the Apteronotus sst(3) receptor gene bound [(125)I][Leu(8),d-Trp(22), (125) I-Tyr(25)]SRIF(28) with high affinity and in a saturable manner (B(max) = 4470 fmol/mg protein; pK(D) = 10.5). SRIF(14) and various synthetic SRIF receptor agonists produced a dose-dependent inhibition of radioligand binding, with the following rank order of potency: SRIF(14) approximately SRIF(28) > BIM 23052 > octreotide > BIM 23056. Under low stringency conditions, an Apteronotus sst(3) probe hybridized to multiple DNA fragments in HindIII or EcoRI digests of A. albifrons DNA, indicating that the Apteronotus sst(3) receptor is a member of a larger family of Apteronotus SRIF receptors.

Amino Acid Sequence↗
PubMed1999

Biliary tract duplication accompanied by choledocholithiasis: report of a case.

Duplication of the biliary tract is extremely rare. In fact, to the best of our knowledge, only four previous reports of pediatric patients with this disease have been documented in the Japanese literature. This anomaly was diagnosed by perioperative endoscopic retrograde cholangiopancreatography (ERCP) in three of these patients, and incidentally during surgery for congenital biliary dilatation in the other one. We report herein a case of biliary tract duplication which was diagnosed by T-tube cholangiography, only in the oblique view, after cholecystectomy and choledochotomy with T-tube drainage. The patient was a 13-year-old girl who was initially diagnosed as having choledocholithiasis based on the results of preoperative and intraoperative cholangiography; however, a postoperative T-tube cholangiography revealed residual stones. At this point, duplication of the biliary tract was diagnosed only in the first oblique view. Reoperation was carried out 26 days after the first operation. The biliary tract was dissected completely from the pancreaticobiliary junction to the left and right hepatic ducts in the porta hepatis and found to be duplicated from the level of porta hepatis to the suprapancreatic area. We report our experience of this case, followed by a discussion on the relevant literature.

Adolescent↗
PubMed1999

Laparoscopic surgery for blind pouch syndrome following Roux-en Y gastrojejunostomy: report of a case.

We report herein the case of a 59-year-old man in whom blind pouch syndrome was successfully treated by laparoscopic surgery. The patient had undergone distal gastrectomy and Roux-en Y gastrojejunostomy for a peptic ulcer 35 years previously, and had been suffering from watery diarrhea, anemia, weight loss, and pain in the left upper quadrant of his abdomen for several years. Long-term insufficient oral intake and the malabsorption of nutrients had resulted in severe emaciation. Gastrointestinal contrast study revealed a large blind pouch, 30 x 23cm in diameter, draining into the gastrojejunostomy. Laparoscopic resection of the blind pouch was performed. Despite the presence of dense intraabdominal adhesions, we identified the blind pouch with the help of tattoo marks that had been made at the neck of the pouch preoperatively. After thoroughly dissecting the adhesions around the pouch, we resected the pouch at the neck. The patient had an uneventful postoperative course. This case report demonstrates that large blind pouches such as this may be effectively treated using laparoscopic surgery.

Anastomosis, Roux-en-Y↗
PubMed1999

A long-term survival case of thymic squamous cell carcinoma, performed complete extirpation with vascular reconstruction of the superior vena cava.

A 59-year-old woman who complained of anterior chest pain exhibited an abnormal shadow on chest X ray and was admitted to our hospital. The chest X ray showed a demarcated tumor at the anterosuperior mediastinum and she was diagnosed as having a mediastinal tumor. After the midsternotomy was performed, the mediastinal tumor derived from the thymic tissues was discovered to have invaded the right upper lung, pericardium and superior vena cava. After excising the tumor, anastomosis between the right brachiocephalic vein and superior vena cava, followed by that between the left brachiocephalic vein and right cardiac auricle was performed using expanded polytetrafluoroethylene-ringed vascular grafts (phi 10 mm) for reconstruction. The tumor was diagnosed as a thymic carcinoma (squamous cell carcinoma) pathologically. After surgery, she was treated by cobalt irradiation. One month and again 3 months after the operation, venography showed patency. The patient has not demonstrated recurrence for 9 years and 6 months.

Blood Vessel Prosthesis Implantation↗
PubMed1999

Revascularization and new bone formation in heat-treated bone grafts.

Human imnmunodeficiency virus (HIV) infection is one of the possible serious complications associated with bone allografts. In order to prevent infection, grafted bone is sterilized by various treatments. Heat treatment has attracted attention as a simple and practical method. We carried out a histological study of the influence of heat treatment on autogenic bone grafts. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Three types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min, at 80 degrees C for 10 min, and at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the rabbits' ilium. One, 2, 4 and 8 weeks after grafting, we performed microangiography and prepared two types of samples: transparent and haematoxylin-eosin (H&E) stained. Then, using an image analyzer, we quantitatively measured revascularization and new bone formation in the grafted bone. The grafts heat-treated at 60 degrees C showed early and good revascularization and new bone formation, from 1 to 8 weeks. The grafts heat-treated at 80 degrees C showed relatively good revascularization and new bone formation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory revascularization and bone formation, less than 40% of control 8 weeks after grafting. Therefore, heat treatment at 60-80 degrees C does not seriously affect revascularization and new bone formation.

Animals↗
PubMed1999

Integrin alpha6beta1 plays a significant role in the attachment of hepatoma cells to laminin.

BACKGROUND/AIMS: Tumor invasion and metastasis consist of a series of complex events. During this process, the ability of tumor cells to adhere to laminin, a major component of basement membranes, is required at various steps. The expression of laminin-binding integrins and the extent of tumor metastasis and progression appear to be related. In hepatocellular carcinoma, increased expression of laminin-binding integrins is observed. However, little is known concerning the possible functional interactions between laminin-binding integrins and laminin. Therefore, we investigated the participation of laminin-binding integrins in the attachment of hepatoma cells to laminin. METHODS: Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investigated the expression of integrin alpha1, alpha2, alpha3, alpha6, beta1, and beta4 subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attachment of hepatoma cells to laminin was evaluated by an inhibition of cell adhesion assay. RESULTS: Integrin alpha1, alpha2, alpha3, alpha6 and beta1 subunits were expressed at the marginal areas of hepatoma cells, while the integrin beta4 subunit was scarcely detected. Laminin promoted the attachment of hepatoma cells in a dose-dependent manner. Although anti-integrin alpha1, alpha2, beta3 and beta4 subunit antibodies did not inhibit cell attachment to laminin, anti-integrin alpha6 and beta1 subunit antibodies inhibited the attachment by 50% or more. CONCLUSIONS: These findings indicate that integrin alpha6beta1 is very important in the attachment of hepatoma cells to laminin, suggesting the participation of this integrin in metastasis and invasion of hepatoma cells.

Carcinoma, Hepatocellular↗
PubMed1999

Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) alpha in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-alpha immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

Adenocarcinoma↗
PubMed1999

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522.

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer.

Animals↗
PubMed1999

Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori.

OBJECTIVE: Recent reports have shown that patients infected with Helicobacter pylori (H. pylori) have a higher risk of gastric cancer. However, the mechanism of this increased risk is still unclear. In the gastric mucosa, the size of a continuously renewed population of cells is determined by the rates of cell production and of cell loss. Ornithine decarboxylase (ODC) activity is elevated in various gastrointestinal cancers and serves as a marker of mucosal proliferative activity. Apoptosis occurs throughout the gut and is associated with cell loss. Both cell proliferation and cell loss have important roles in H. pylori-associated gastric carcinogenesis. Therefore, we investigated the effect of H. pylori eradication on ODC activity and apoptosis in the gastric mucosa of patients with atrophic gastritis and gastric ulcers. METHODS: Biopsy specimens of the gastric antrum were obtained at endoscopy from 17 H. pylori-positive gastric ulcers patients and 15 H. pylori-positive gastritis patients before and 4 wk after eradication therapy with amoxicillin, omeprazole, and a new anti-ulcer agent, ecabet sodium, and from 10 gastric ulcer patients in whom ulcer healed but H. pylori was left untreated. ODC activity and induction of apoptosis were determined immunohistochemically. RESULTS: H. pylori was successfully eradicated with the triple therapy in 12 (80%) of 15 gastritis patients and 13 (76%) of 17 gastric ulcer patients. ODC activity was present in the gastric mucosa in 21 (84%) patients before eradication but in only four (16%) patients after successful eradication (p = 0.0005). The apoptotic index increased significantly (p = 0.0006) from 4.2% +/- 0.4% before treatment to 7.4% +/- 0.5% after successful eradication. CONCLUSIONS: Successful eradication of H. pylori decreases mucosal ODC activity and increases apoptosis in the gastric mucosa. These findings indicate that by decreasing mucosal cell proliferation and increasing epithelial cell loss, H. pylori eradication may help decrease the subsequent risk of gastric cancer.

Adult↗
PubMed1999

Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations.

OBJECTIVE: Telomerase activity is reported to be specific and very frequent in human malignancy. K-ras mutations are also very frequently detected in pancreatic cancer, but their specificity for pancreatic cancer is controversial. We examined the telomerase activity and K-ras mutations in pancreatic juice from patients with pancreatic disease. METHODS: Pancreatic juice was obtained endoscopically at endoscopic retrograde pancreatography from 10 patients with pancreatic cancer, three with chronic pancreatitis, and three with a normal pancreas. The telomerase activity in pancreatic juice was assayed by telomeric repeat amplification protocol. K-ras mutations in exon 1 codon 12 were examined by the two-step polymerase chain reaction combined with restriction enzyme digestion, followed by single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Telomerase activity of >5.0 was detected in eight of 10 (80%) subjects with pancreatic cancer, but in none with chronic pancreatitis or normal pancreas. K-ras mutations were detected not only in eight of 10 (80%) subjects with pancreatic cancer but also in two of three with chronic pancreatitis and in one of three with a normal pancreas. CONCLUSIONS: It was shown that the detection of telomerase activity in pancreatic juice is a more useful diagnostic tool for pancreatic cancer than that of K-ras mutations.

Aged↗
PubMed1999

Phytate and phosphorus movements in the digestive tract of horses.

This experiment was conducted to study phytate degradation and the effect of dietary phytate level on phosphorus absorption in the gastrointestinal tract of horses. Six Thoroughbred horses were fed diets containing low-phytate diet or high-phytate diet for 5 days. The diets were supplemented with Cr2O3 as an unabsorbable marker. The horses were killed 3 h after the last feeding and digesta in some segments of the intestine were collected. In both dietary groups, the daily passage of phytate phosphorus was decreased in the upper small intestine and in the lower large intestine. The daily passage of phytate phosphorus in the lower large intestine did not differ between these groups. Although the passage of total phosphorus increased in the upper small intestine and in the upper large intestine of both groups, its passage decreased in the lower large intestine. These results suggest that phytate phosphorus is degraded in the upper small intestine and in the lower large intestine of both groups. Phosphorus is suggested to be mainly absorbed in the lower large intestine. Therefore, phytate phosphorus is considered to be easily absorbed in horses because the major site of phosphorus is the lower large intestine where most of phytate is already degraded.

Animal Feed↗
PubMed1999

Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive K+ channel activity.

The insulin response to the sulfonylurea glibenclamide was markedly impaired in pancreatic beta-cell line MIN6 cells with chronic glibenclamide treatment (MIN6-Glib). The intracellular calcium concentration increased only slightly in response to glibenclamide in MIN6-Glib. While the properties of the voltage-dependent calcium channels were not altered, the conductance of the K(ATP) channels, the primary target of glibenclamide, was significantly reduced in MIN6-Glib. The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. MIN6 cells have both high- and low-affinity binding sites for glibenclamide. The binding affinities at these two sites were unchanged, but the maximum binding capacities at both sites were similarly increased by chronic glibenclamide treatment. Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. In addition, electron microscopic examination revealed a majority of the SUR1 to be present in a cluster near the plasma membrane in control MIN6, while it tends to be distributed in the cytoplasm in MIN6-Glib. These data suggest that chronic glibenclamide treatment causes the defect in acute glibenclamide-induced insulin secretion by reducing the number of functional K(ATP) channels on the plasma membrane of the beta-cells.

ATP-Binding Cassette Transporters↗
PubMed1999

Expressions of epidermal growth factor family and its receptor in hepatocellular carcinoma cell lines: relationship to cell proliferation.

In 6 HCC cell lines, clear expressions of EGFR and TGF-alpha were found in flow cytometry, while expressions of EGF, HB-EGF and AR were quite low. TGF-alpha secretion into culture supernatants became measurable when TPA 0.5 microM was added. TPA accelerated the proliferation of KYN-3 cells, and anti-TGF-alpha neutralizing antibody suppressed this proliferation in a dose-dependent manner. Addition of exogenous TGF-alpha, EGF, AR, or HB-EGF with heparin accelerated cell proliferation. In non-stimulated cultures, cell proliferation was suppressed by anti-EGFR neutralizing antibody, but not by the antibodies for EGF, TGF-alpha, AR and HB-EGF. HCC may possess a paracrine system regulated by these 4 ligands, and an autocrine system, under a certain condition, via TGF-alpha and EGFR.

Amphiregulin↗
PubMed1999

Establishment and characterization of a new human hepatocellular carcinoma cell line, HAK-3, and its response to growth factors.

A new human hepatocellular (HCC) cell line, HAK-3, was established from a resected HCC of a Japanese, female patient. HAK-3 retains morphologic features of the original HCC, and proliferates in a monolayered sheet (doubling time: 26 h). HAK-3 is a single aneuploid cell population with a DNA index of 2.42, the karyotype is human, chromosomes are 80-85 (mode: 83), and secretes fibronectin and tissue polypeptide antigen. Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) dose-dependently accelerated the cell proliferation, while deletion-type hepatocyte growth factor (dHGF) tended to suppress the proliferation, and transforming growth factor (TGF)-alpha showed almost no influence. dHGF induced the decrease of cell adhesiveness, changed the cell morphology to spindle-shaped cells, increased cell movement, and showed chemotactic effects with the increase of its concentration gradient in cultures. HAK-3 would be useful in studies on the acceleration mechanisms of cancer cell proliferation by growth factors and of chemotaxis by dHGF.

Carcinoma, Hepatocellular↗
PubMed1999

Modulation of fas-mediated apoptosis in osteosarcoma cell lines.

Fas/APO-1 (or CD95) is a 45-kDa cell surface glycoprotein that transduces cellular death signals for apoptosis upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. We examined the Fas expression at the protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, in 14 osteosarcoma cell lines. Ten of 14 ostesarcoma cell lines constitutively expressed detectable levels of Fas on the cell surface with positive cell rates ranging from 10.2 to 72.4%. Four other cell lines expressed Fas almost exclusively in the cytoplasm. An antibody against Fas was able to induce Fas-mediated cell death only in two cell lines with high levels of surface Fas. In the presence of the protein synthesis inhibitor cyclohexamide, antibody to Fas led to an induction of apoptosis in ten of the osteosarcoma cell lines antibody-concentration dependently. These data suggest that Fas is a potential protein related to apoptosis in osteosarcomas when the sensitizing activity of cyclohexamide on anti-Fas-mediated cytotoxicity was exerted.

Antibodies, Monoclonal↗
PubMed1999

[Treatment with 5-FU modulated by low-dose CDDP for advanced cancers and recurrent cases of metastasis].

Advanced gastric, colon and esophageal cancers (n = 21) were treated with 5-FU (250 mg) modulated by CDDP (5 mg). The reductive ratio of tumor was 6/21 (28.6%). Six cases of partial response (PR) were limited with no surgical treatment and exploratory laparotomy of all cases, and the effectiveness rate was 54.5% (6/11). Few side effects, such as dysfunction of bone marrow and kidney, were noted. Even if side effects occurred, they were mild. We concluded that excellent treatment with 5-FU modulated by CDDP has markedly improved the efficacy.

Adult↗