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Biomedical subjects

H Nawata

Publications and source records attributed to H Nawata.

At least 199 records · Page 11Linked to original sources
PubMed1997

Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated with 5-azacytidine.

The sarcomatoid cells found in cholangiocarcinoma (CC) or hepatocellular carcinoma (HCC) are not well characterized. In this study, a human sarcomatoid CC cell line, ETK-1, was established from a patient, and then morphological and phenotypical characteristics of the ETK-1 cells were evaluated before and after treatment with differentiation-inducing 5-azacytidine (5-azaCR). Phenotypically, the ETK-1 cells appeared immature. Exposure to 5-azaCR induced morphological transformation; a converted cell line, MEK, was successfully established. The MEK cells expressed such hepatocyte-specific proteins as alpha-fetoprotein, albumin, integrin alpha1, and thrombopoietin, but lost such bile duct-specific proteins as integrin alpha3 and integrin beta4. The histopathology of MEK xenografts resembled that of HCC. The ETK-1 cells appeared to be converted into hepatocytes by exposure to 5-azaCR. On the other hand, ETK-1 xenografts were diagnosed as tubular adenocarcinoma, and the tumor cells had a ductal phenotype. This suggests the possibility that ETK-1 cells can differentiate along a biliary epithelial cell lineage. ETK-1 and MEK will be useful in studying hepatocytic differentiation and the transformation from a biliary epithelial cell to a hepatocytic lineage.

Animals↗
PubMed1997

Acinar-islet cell carcinoma presenting as insulinoma.

A case of acinar-islet cell carcinoma presenting as insulinoma is reported. The patient was a 28-year-old man who presented with two convulsive episodes. Fajans' index [immunoreactive insulin (IRI; microU/ml/ glucose mg/dl)] and Turner's [IRI (microU/ml) x 100/glucose (mg/dl) - 30] index were high (2.8 and 308, respectively), as were serum proinsulin levels (550 pg/ml). Abdominal computed tomography and angiography revealed a highly vascular tumor in the pancreatic tail and several similar tumors in the liver. Histologic features of a biopsy specimen from a hepatic tumor were those of a malignant pancreatic endocrine tumor. Insulin secretion by the liver metastases was confirmed by venous sampling after arterial stimulation with calcium. These findings led us to diagnose malignant insulinoma with liver metastases. Serum levels of alpha-fetoprotein and trypsin were markedly elevated, to 2234 ng/ml (normal < 10) and 22,000 ng/ml (normal < 460) respectively, and these levels continued to rise with further growth of the liver metastases. Immunohistochemically, the metastatic liver tumor specimen was positive for alpha-fetoprotein, alpha 1-antichymotrypsin, chromogranin A, and neuron-specific enolase. These findings of amphicrine features in the tumor were indicative of acinar-islet cell carcinoma that produced alpha-fetoprotein and trypsin in addition to insulin.

Adenoma, Islet Cell↗
PubMed1997

Direct contractile effect of cholecystokinin octapeptide on caecal circular smooth muscle cells of guinea pig via both CCK-A and CCK-B/gastrin receptors.

This study was designed to investigate the participation of cholecystokinin(CCK)-A and/or CCK-B/gastrin receptors in CCK-8-induced contraction of guinea pig caecal circular smooth muscle cells, using a novel selective CCK-A receptor antagonist, (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo-pyrrolo-[3,2,1-jk] [1,4]benzodiazepine-3-yl]-1H-indole-2-carboxamide (FK480), and a novel selective CCK-B/gastrin receptor antagonist, (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl]-3-(3-methylphenyl)urea (YM022). Concentration-response curves for the contractile effect of CCK-8 alone and in the presence of 0.1nM FK480, 0.1 nM YM022, or a combination of 0.1 nM FK480 and 0.1 nM YM022 on isolated smooth muscle cells were determined. In addition, the inhibitory effects of various concentrations of FK480 or YM022 on 1 nM CCK-8-induced contraction were examined. At a concentration of 0.1 nM, both FK480 and YM022 shifted the concentration-response curve for CCK-8 to the right (about 100 times) with the same potency. In addition, a concentration-response curve for a combination of 0.1 nM FK480 and 0.1 nM YM022 was shifted to the right (about 100 times) of the curves for 0.1 nM FK480 alone or 0.1 nM YM022 alone. Both antagonists inhibited 1 nM CCK-8-induced contraction of caecal circular smooth muscle cells in a concentration-dependent manner, with the similar inhibitory potency. A significant inhibition was obtained at a concentration as low as 0.1 nM FK480 and 0.1 nM YM022. This study strongly suggested the presence of both CCK-A and CCK-B/gastrin receptors in caecal circular smooth muscle cells of guinea pig, and that the contractile effect of CCK-8 on these cells was mediated via both of these receptors.

Animals↗
PubMed1997

Presence of functional receptors for corticotropin releasing hormone in caecal circular smooth muscle cells of guinea pig.

The presence of specific binding sites for corticotropin releasing hormone (CRH) in caecal circular smooth muscle cells of guinea pig was investigated by binding and pharmacological studies. The specific binding of 125I-CRH to these muscle cells reached an equilibrium after 90 minutes. Several peptides structurally unrelated to CRH did not affect the specific binding of 125I-CRH to these muscle cells. Unlabeled CRH completely inhibited the specific binding of 125I-CRH in a concentration-dependent manner, with an IC50 value of 13.5 nM. A CRH receptor antagonist, alpha-helical CRH (9-41), inhibited the specific binding of 125I-CRH in a concentration-dependent manner with a lower affinity than CRH. In pharmacological study, CRH inhibited the contractile response of these muscle cells to 1 nM cholecystokinin-octapeptide in a concentration-dependent manner, with an IC50 value of 14.1 nM. A CRH receptor antagonist, alpha-helical CRH (9-41), significantly antagonized this inhibitory effect produced by CRH. These results strongly suggest the presence of functional receptors for CRH that mediate relaxation of caecal circular smooth muscle cells of guinea pig.

Animals↗
PubMed1997

Direct inhibitory effect of adrenomedullin and guanylin on isolated caecal circular smooth muscle cells of guinea pig.

Smooth muscle cells isolated from the caecal circular smooth muscle layers of the guinea pig were used to determine whether adrenomedullin and guanylin can inhibit the contractile response produced by 10(-9) M cholecystokinin octapeptide (CCK-8). In addition, to elucidate each intracellular mechanisms, we examined the effects of an inhibitor of cAMP-dependent protein kinase, an inhibitor of particulate guanylate cyclase, and an inhibitor of soluble guanylate cyclase on the adrenomedullin- or guanylin-induced relaxation of the caecal circular smooth muscle cells. Both adrenomedullin and guanylin inhibited the contractile response produced by CCK-8 in a dose-dependent manner, with IC50 values of 0.12 nM and 2.4 pM, respectively. An inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by adrenomedullin. In contrast, an inhibitor of particulate guanylate cyclase and an inhibitor of soluble guanylate cyclase did not have any significant effect on the relaxation produced by adrenomedullin. On the other hand, an inhibitor of particulate guanylate cyclase significantly inhibited the guanylin-induced relaxation, although an inhibitor of cAMP-dependent protein kinase and an inhibitor of soluble guanylate cyclase did not have any significant effect on the guanylin-induced relaxation. In this study, we first demonstrated the direct inhibitory effects of adrenomedullin via cAMP system and guanylin via particulate guanylate cyclase system on the isolated caecal circular smooth muscle cells.

Adrenomedullin↗
PubMed1997

Effect of acarbose on glucose intolerance in patients with non-insulin-dependent diabetes mellitus.

We evaluated the effect of acarbose, an alpha-glucosidase inhibitor, on glucose intolerance in patients with non-insulin-dependent diabetes mellitus (NIDDM). Acarbose was given orally (300 mg/day) for 24 weeks to 20 NIDDM patients. Data in an oral glucose tolerance test (OGTT) were evaluated before and after 24 weeks of treatment using principal component analysis. Acarbose administration significantly reduced the postprandial plasma glucose level over 24 weeks of treatment. Principal component analysis suggested that the patients were separated into responders and non-responders. There was a significant improvement of fasting and postprandial glucose levels after 12 and 24 weeks in the responders, but not in the non-responders. Plasma glucose level following the OGTT improved significantly after 24 weeks of treatment in the responders (Hotelling T2 value = 47.098, P = 0.022500), but not in the non-responders. The immunoreactive insulin level did not change in either group. Results thus suggest that acarbose improved insulin resistance in some patients with NIDDM (responders as classified by principal component analysis).

Acarbose↗
PubMed1997

Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines.

The tyrosine kinase activity of BCR-ABL fusion proteins plays an important role in the pathogenesis of leukemia that is for the Philadelphia chromosome (Ph1). Because nuclear c-ABL is regulated during the cell cycle through a specific interaction with the retinoblastoma protein (pRB), the possible interaction of BCR-ABL with pRB in Ph1-positive cell lines was investigated. P145 c-ABL as well as P190 and P210 BCR-ABL proteins interacted with pRB. Furthermore, c-ABL and BCR-ABL associated with both phosphorylated and nonphosphorylated forms of pRB. These findings suggest that BCR-ABL interferes with pRB function and thereby regulates cell growth.

Animals↗
PubMed1997

Difference in serum-induced prostacyclin production by cultured aortic and capillary endothelial cells.

Prostacyclin (PGl2) generated by vascular endothelial cells play an important role in the maintenance of vessel wall homeostasis. Human plasma-derived serum (PDS) stimulated PGl2 synthesis by both cultured bovine aortic endothelial cells (BAEC) and adrenal capillary endothelial cells (BCEC), but the PGl2 response of the latter cells was far smaller. When BAEC were cultured with a high concentration of glucose (400 mg/dl), the PGl2 synthesis induced by 20% PDS was significantly lower than in the culture with a physiological concentration of glucose (100 mg/dl) (258 +/- 45 pg/10(4) cells/h vs. 402 +/- 52 pg/10(4) cells/h, n = 4, P < 0.05). On the other hand, there was no significant difference in the PDS-induced PGl2 synthesis between BCEC cultured with high and physiological concentrations of glucose. Additionally, 10% PDS obtained from patients with non-insulin dependent diabetes mellitus (n = 6) stimulated significantly less PGl2 synthesis than that from healthy subjects (n = 4) in the case of both BAEC (133 +/- 27 pg/10(4) cells/h vs. 402 +/- 38 pg/10(4) cells/h, P < 0.05) and BCEC (72 +/- 15 pg/10(4) cells/h vs. 118 +/- 12 pg/10(4) cells/h, P < 0.05), with the difference in PGl2 synthesis being smaller for BCEC. These findings indicate that the PDS-induced PGl2 synthesis differs between cultured vascular endothelial cells from large and small vessels with the decrease in PGl2 by diabetic PDS and high glucose being more marked for BAEC than BCEC.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Expression of the placenta-specific, 100 kDa ras GTPase activating protein in several human cancer cell lines and normal human tissues.

The ras GTPase activating protein (ras GAP), a regulator of Ras activity, has two isoforms; ras GAP 120 and ras GAP 100. The latter, whose molecular size is about 100 kDa, is generated alternative splicing from the ras GAP 120 gene and is considered placenta-specific, while the former is expressed ubiquitously. As point mutations of ras are frequently observed in human tumors, we investigated the expression of ras GAP in several human cancer cell lines and samples of human colon cancer using immunoprecipitation and immunoblot analysis with an anti-GAP monoclonal antibody, B4F8, as well as reverse transcription-polymerase chain reaction (RT-PCR). ras GAP 100 protein was detected in 4 of 9 colonic, 1 of 6 gastric and 1 of 4 lung cancer cell lines as well as ras GAP 120, but not in colon cancer specimens. In contrast, ras GAP 100 mRNA was present in all tested cell lines and colon cancer specimens. Then, we investigated ras GAP 100 expression in normal tissues, ras GAP 100 protein was not detected in human normal tissues except placenta. Contrary, ras GAP 100 message was expressed in normal tissues derived from liver, stomach, colon and lymphocyte although the level of which was smaller than that in placenta. These findings demonstrate that ras GAP 100, reportedly placenta-specific, is distributed in other normal tissues at least at mRNA level and its expression is augmented in some cancer cell lines.

Blotting, Southern↗
PubMed1997

Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune pancreatitis with effective steroid therapy.

The most common forms of chronic pancreatitis are related to alcohol ingestion, whereas the entity of non-alcohol-associated (idiopathic) pancreatitis is poorly understood. Autoimmunity has been suggested as a possible etiologic factor of idiopathic chronic pancreatitis. A total of 362 Japanese patients underwent endoscopic retrograde pancreatography (ERP) for suspected pancreatic disease, and 161 were diagnosed with chronic pancreatitis. Among them, we found three cases (1.86% incidence) of unique chronic pancreatitis, in which ERP revealed diffuse narrowing of the main pancreatic duct with an irregular wall. We diagnosed these three patients as having pancreatitis associated with an autoimmune mechanism morphologically and biochemically and started them on steroid therapy. The characteristics of the these three patients were as follows: hypergammaglobulinemia, eosinophilia, ultrasonography showing hypoehoic diffuse swelling in the pancreas (sausage-like appearance), ERP showing diffuse narrowing of the main pancreatic duct with irregular like thumbprint-like marks, reversible exocrine insufficiency, and positive anti-carbonic anhydrase II antibody. After one month of the treatment with steroids, pancreatitis dramatically improved morphologically and enzymatically. Here we describe these cases of the suspected autoimmune chronic pancreatitis. We must recognize the concept and the features of autoimmune pancreatitis in order to avoid unnecessary surgery as pancreatic cancer.

Aged↗
PubMed1997

Parvovirus B19-associated haemophagocytic syndrome with lymphadenopathy resembling histiocytic necrotizing lymphadenitis (Kikuchi's disease).

A 15-year-old girl developed a haemophagocytic syndrome caused by human parvovirus B19 (PVB19). The cervical lymph node histology, resembling that of histiocytic necrotizing lymphadenitis (HNL, Kikuchi's disease), included several transformed lymphocytes, numerous histocytes, and massive necrosis. We detected PVB19-positive cells in the lymph node by immunohistochemistry. Possible autoimmune mechanisms in HNL-like diseases triggered by PVB19 are discussed.

Adolescent↗
PubMed1997

Endoscopic ultrasonography: a promising method for assessing the prospects of endoscopic mucosal resection in early gastric cancer.

BACKGROUND AND STUDY AIMS: A recent challenge that is increasingly being faced in endoscopy is the use of endoscopic mucosal resection (EMR) to treat differentiated intramucosal gastric cancers smaller than 2 cm. The usefulness of pretherapeutic endoscopic ultrasonography (EUS) in assessing whether this form of treatment is possible remains controversial. PATIENTS AND METHODS: We retrospectively investigated the value of pretherapeutic EUS evaluation in 58 patients with macroscopically early gastric cancer that was histologically differentiated and less than 2 cm in diameter. The patients were classified as negative for endoscopic mucosal resection if EUS showed modifications of the third layer, and as positive if such modifications were not seen. All patients underwent radical surgery and the preoperative EUS findings were compared with the histological findings. RESULTS: The prevalence of metastatic adenopathy was 3% (two of 58). In the lymph-node staging, endosonography had a sensitivity of 0% (neither of two cases), and a specificity of 93% (52 of 56). In assessing the indication for EMR, EUS had a sensitivity of 93% (27 of 29), and a specificity of 86% (25 of 29). CONCLUSIONS: These results suggest that EUS is a promising method of evaluating the indication for endoscopic mucosal resection in early gastric cancer. EUS may improve pretherapeutic prediction of tumor curability by EMR, and may reduce the need for standard gastrectomy.

Adenocarcinoma↗
PubMed1997

Human diploid fibroblast cell culture medium contains a factor that increases cytosolic Ca2+ and stimulates prostaglandin synthesis by cultured bovine aortic endothelial cells.

Previously, we demonstrated that conditioned medium (CM) from cultures of human diploid fibroblast cells contains a factor that stimulates the production of prostacyclin (PGI2) by cultured bovine aortic endothelial cells (BAEC). To study the mechanism by which CM stimulates PGI2 production, we measured the effect of removal of extracellular calcium (Ca2+) on the concentration of cytosolic Ca2+ and on the production of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of PGI2. The CM-induced production of 6-keto-PGF1 alpha was dependent on extracellular Ca2+ and did not require nascent protein synthesis. Application of CM to BAEC induced a transient increase in cytosolic Ca2+ concentration that was dependent on extracellular Ca2+. Bradykinin induced the production of 6-keto-PGF1 alpha by BAEC. However, bradykinin induced an increase in cytosolic Ca2+ concentration in the presence or absence of extracellular Ca2+. Voltage dependent Ca2+ channel blocker (verapamil, diltiazem) did not inhibit either the CM-induced increase in cytosolic Ca2+ or the production of 6-keto-PGF1 alpha by BAEC. These data suggest that CM increases the cytosolic Ca2+ concentration and stimulates PGI2 production by BAEC. The increase in cytosolic Ca2+ concentration occurred via the influx of extracellular Ca2+ independent of L-type Ca2+ channels blocked by verapamil or diltiazem.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Effect of Irsogladine on gap junctions in cerulein-induced acute pancreatitis in rats.

The capacity for intercellular communication (IC) via gap junctions is found in normal pancreatic acinar cells. The major role of IC is considered to be the maintenance of tissue homeostasis and the regulation of signal transmissions. Up to now, the participation of IC via gap junctions in acute pancreatitis has not been reported. We investigated the role of IC in cerulein (Cn)-induced acute pancreatitis in rats using irsogladine, an enhancer of IC via gap junction. Acute edematous pancreatitis was induced in rats by two intraperitoneal injections of 40 micrograms/kg Cn. Rats received various doses (25, 50, or 100 mg/kg body weight) of irsogladine orally, 15 and 2 h before the first Cn injection. The normal control group received only vehicle. The severity of pancreatitis was evaluated enzymatically and histologically 5 h after the first Cn injection. In Cn-induced acute pancreatitis, irsogladine significantly lowered the serum amylase level, the pancreatic wet weight, and the pancreatic amylase and DNA contents, in a dose-dependent manner. Particularly, the amylase content improved to the level of the normal controls. Histologically, the severity of pancreatitis was reduced significantly by treatment with irsogladine and no discernible vacuolization was seen in the group with 100 mg/kg irsogladine treatment. By immunofluorostaining pancreata with anti-connexin 32 (Cx32; a gap junction protein) antibody, we found that pancreatic acini were diffusely positive for Cx32 in the control group, but the number of Cx32-positive grains decreased markedly, to 19%, in the pancreatitis group. With 100 mg/kg irsogladine treatment, the number of Cx32 grains recovered to 70% of the normal control value. These findings indicate that IC via gap junction is disturbed in Cn-induced pancreatitis, which may result in the breakdown of tissue homeostasis and the progression of acute pancreatitis.

Acute Disease↗
PubMed1997

All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats.

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134+/-119 IU/L and 72.7%) compared with the control group (713+/-411 IU/L and 18.2%; P< 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-alpha (TNF-alpha) and superoxide anions produced by activated macrophages. Serum levels of TNF-alpha 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5+/-7.0 ng/mL) as compared with the control group (105.2+/-39.3 ng/mL; P< 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.

Animals↗