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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 397 records · Page 22Linked to original sources
PubMed1996

Teratology study of erythritol in rabbits.

The effect of maternal ingestion of the reduced energy sweetener erythritol was investigated in KBL:JW strain pregnant rabbits. Animals received 1.0, 2.24, or 5.0 g/kg intravenously once daily from Days 6 to 18 of gestation. Maternal effects (auricular edema, and bradypragia) were observed in the high-dose group. No deaths or significant abnormalities occurred in animals given 1.0 or 2.24 g/kg. No effect was observed in the reproductive performance of the dams or in fetal development from ingestion at any of the treatment levels.

Abnormalities, Drug-Induced↗
PubMed1996

The preventive effects of OK432 on endotoxin-induced liver injury: liver protection by the modulation of hepatic macrophage function.

The present study was conducted to clarify whether endotoxin-induced liver injury could be improved by modulating the function of hepatic macrophages using OK432, an immunostimulant derived from Streptococcus. OK432 elevated the capacity of hepatic macrophages to produce superoxide and tumor necrosis factor (TNF), and enhanced the mRNA expression of interleukin-1-alpha, -beta, and TNF-alpha in liver nonparenchymal cells (NPC). However, intravenous (iv) preadministration of OK432 reduced the mRNA expression of TNF-alpha in liver NPC enhanced by the endotoxin injection, decreased the serum level of GOT and lactic dehydrogenase (LDH), and improved the survival rate of endotoxin-injected rats. Histological examination revealed a significant reduction in cell vacuolization and focal necrosis in the livers of the endotoxin-injected rats pretreated with OK432. These results indicate that hepatic macrophages play a crucial role in endotoxin-induced liver injury, and that TNF-alpha is one of the factors most likely to be implicated in the development of endotoxin-induced liver injury. Thus, it is suggested that the administration of OK432 provides liver protection by modulating the responsiveness of hepatic macrophages against endotoxin.

Animals↗
PubMed1996

Immunohistochemical study of metallothionein in pancreatic carcinomas.

Metallothioneins are a family of intracellular metalloproteins that have been thought to be involved in anticancer drug resistance. However, the role of metallothioneins in pancreatic cancer has not been investigated in detail. The immunohistochemical localization of metallothionein was examined in normal human adult pancreas tissue and in 75 pancreatic duct cell carcinomas, using monoclonal anti-metallothionein antibody. Furthermore, in vitro studies on the sensitivity of pancreatic cancer to cisplatin were performed in 10 cases of pancreatic carcinoma. Metallothionein staining was weakly positive in the acinar and islet cells and intralobular ducts but was negative in the large pancreatic ducts. In pancreatic carcinomas, metallothionein staining was diffusely positive in 6 (8%), focally positive in 25 (33%) and negative in 44 (59%) of the 75 pancreatic carcinomas. The expression of metallothioneins in pancreatic tumors was related to metastasis, poor prognosis and poor histological grading (poorer glandular differentiation and nuclear anaplasia). The in vitro study of tumor sensitivity to cisplatin showed no significant correlation between metallothionein expression and resistance to cisplatin. Metallothionein-positive pancreatic carcinoma will be potentially highly malignant or acquire an enhanced ability to produce metallothioneins as the malignant potential increases. The expression of metallothionein could be a prognostic indicator in pancreatic carcinomas.

Adult↗
PubMed1996

Effects of cholecystokinin and carbachol on membrane fluidity in pancreatic acini.

The effects of pancreatic secretagogues on the membrane fluidity of pancreatic acini were investigated using 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene iodide as a probe. Two kinds of pancreatic secretagogues, one category of which induces acute pancreatitis (cholecystokinin and carbachol) and another which does not induce acute pancreatitis (bombesin, CCK-JMV-180, and secretin), as well as lecithin were used to investigate the effect of changes in membrane fluidity of acini. Our study revealed that the membrane fluidity of the pancreatic acini was unaffected by a physiological dose (10(-11) M) of cholecystokinin. However, stimulation with a supramaximal dose of cholecystokinin (10(-8) M) increased membrane fluidity markedly within 20 min. Membrane fluidity increased dose-dependently with increasing CCK stimulation. A supramaximal dose of cholecystokinin also induced bleb formation and increased LDH release. These phenomena were blocked by simultaneous incubation with CR1505 (Loxiglumide), a potent antagonist of peripheral cholecystokinin receptors. A supramaximal dose of carbachol (10(-3) M) also induced increases in the membrane fluidity. Pancreatic secretagogues that do not induce acute pancreatitis did not induce alterations in membrane fluidity. Lecithin increased both membrane fluidity and LDH release. These observations suggest that this increase in membrane fluidity of the pancreatic acini may be related to membrane alteration and to functional damage of the acini. These observations [correction of observation] can serve as a window to detect the development of acute pancreatitis at an early stage.

Animals↗
PubMed1996

Electrogastroenterographic examination of 22 patients before and after cholecystectomy.

The object of this study was to define the pattern of gastrointestinal myoelectrical activity before and after cholecystectomy. After surgery, on the first postoperative day, the mean and maximal activities of the gastrointestinal tracts decreased significantly, but there was no significant change in the pattern and the duration of the nonreactive period. A dyskinetic effect and/or weakness of electrical activity was observed in all patients before operation, and the same pattern persisted after operation for one month. This suggests the future onset of the so-called postcholecystectomy syndrome, which may result from the fundamental pathological effect of gallstones.

Adult↗
PubMed1996

Exocrine pancreatic function in the early period after pancreatoduodenectomy and effects of preoperative pancreatic duct obstruction.

Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700 +/- 4300 IU/day), and recovered on days 9-15 (48,000 +/- 8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440 +/- 260 IU/day) and BT-PABA test results were low (45 +/- 17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient, rs = 0.715, P < 0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.

4-Aminobenzoic Acid↗
PubMed1996

Transformation of severe aplastic anemia into acute myeloblastic leukemia with monosomy 7.

A cytogenetically normal man with severe aplastic anemia was treated with granulocyte colonystimulating factor (G-CSF), erythropoietin (EPO), cyclosporin A, anti-thymocyte globulin, and interleukin-6 (IL-6), which resulted in a gradual improvement in his neutrophil count and hemoglobin level. After 2 years of the therapy, monosomy 7 was detected during cytogenetic analysis of his bone marrow, which evolved during a period of 5 months into acute myeloblastic leukemia. An in vitro proliferation assay of cytokine responses showed that leukemic blasts were sensitive only to G-CSF, and not to EPO or IL-6. Although allogeneic bone marrow transplantation from an HLA-matched unrelated donor was carried out in the non-remission stage, the patient died of systemic fungal infection on day 25, without any evidence of hematological engraftment. As long-term use of cytokines and immunomo-suppressants in patients with severe aplastic anemia may induce or hasten the onset of a malignant transformation, careful attention must be paid to clonal evolution. Due to the poor prognosis of secondary myelodysplasia and leukemia, allogeneic bone marrow transplantation for such patients must be carried out early in the course of the disease.

Adult↗
PubMed1996

Sex and age differences in soluble guanylate cyclase activity in human platelets.

Soluble guanylate cyclase is a key enzyme of nitric oxide (NO)-related intracellular signal transduction in platelets. In the present study, we investigated the effects of sex and age on the enzyme activity in human platelets. Soluble guanylate cyclase activity was determined by generation of cyclic GMP in platelet cytosol. No significant differences in the basal activity of soluble guanylate cyclase were observed between in men and women, and between in young and old subjects. However, soluble guanylate cyclase activity in response to sodium nitroprusside, an exogenous NO donor, was higher in young men than in young and old women. Furthermore, the enzyme activity was lower in old than in young men, but there were no differences in female platelets between from young and old subjects. The present data suggest that NO-related signal transduction system in the platelet is affected by sex and age, which, to certain extent, contributes to different sensitivity of human platelets.

Adult↗
PubMed1996

HLA-DR antigen and interleukin-2 receptor expression on primary-cultured human hepatic macrophages in relation to liver cirrhosis and hepatitis virus infection.

We analyzed primary-cultured human hepatic macrophages (HHMphi) from 12 patients with non-cirrhotic and cirrhotic livers for cell surface expression of HLA-DR antigen and interleukin-2 receptor (IL-2R). Compared to the relatively abundant HLA-DR antigen, IL-2R expression was generally low. No significant difference was observed between HLA-DR antigen expression nor IL-2 receptor expression. HHMphi from patients with serum hepatitis viral markers, however, expressed significantly more HLA-DR antigen than did HHMphi of patients without viral markers, which suggest a possible role of HHMphi as antigen-presenting cells (APC) in viral hepatitis. This direct, quantitative measurement of cell surface molecule expression on hepatic macrophages of human may provide an important clue to the pathophysiology of human liver disorders.

Aged↗
PubMed1996

A case of coronary artery spasm during spinal anesthesia.

We present a rare case of coronary artery spasm during spinal anesthesia in a patient who had neither complications nor prior history of coronary artery disease. Some factors are involved in the occurrence of perioperative coronary artery spasm. Many cases of coronary artery spasm during general anesthesia, or general plus epidural anesthesia, have been reported. Although spinal anesthesia by itself has not been reported to be a cause of coronary artery spasm, it is likely, in the current case, that the combination of the activated parasympathetic nerve system by the retraction of the peritoneum and spinal anesthesia might have caused the coronary artery spasm. Anesthesiologists need to be aware that coronary artery spasm may occur during spinal anesthesia, especially when the peritoneum is retracted.

Adult↗
PubMed1996

Identification of carcinoembryonic antigen mRNA in circulating peripheral blood of pancreatic carcinoma and gastric carcinoma patients.

To detect adenocarcinoma cells in the circulating peripheral blood, we "analyzed the presence of carcinoembryonic antigen (CEA) mRNA in the peripheral blood obtained from patients with pancreatic carcinoma (PC) or with gastric carcinoma (GC) and also, as controls, from pancreatitis or gastritis patients without carcinomas, a gastric lymphoma patient and four healthy volunteers. Because of the small number of carcinoma cells expected in the peripheral blood, the analysis was performed by the reverse transcription followed by an original two-step polymerase chain reaction. By this sensitive method, 3 of 9 PC patients and 2 of 9 GC patients were positive for CEA mRNA. Except for 1 highly advanced PC patient, 3 of 4 CEA mRNA-positive patients developed recurrence after curative resection or liver metastasis after palliative operation within 9 months after the analysis. None of the control patients was positive for CEA mRNA in the peripheral blood. The results suggest that our sensitive RT-PCR method for detecting CEA mRNA in the peripheral blood is practically useful to find the hematogenous spreading of adenocarcinoma cells.

Aged↗
PubMed1996

Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor.

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms (P<.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells (P<.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.

Aged↗
PubMed1996

Chemical mediators released by primary-cultured human hepatic macrophages in patients with and without cirrhosis: a study in tumor-bearing patients.

To elucidate the possible role of chemical mediators in modulating the host-defense activity of patients with cirrhosis, primary-cultured human hepatic macrophages (HHMphi) were obtained from cirrhotic and noncirrhotic patients who received liver resections because of the presence of malignant liver tumors. The cirrhotic and noncirrhotic groups consisted of patients with similar malignancies: noncirrhotic patients had normal liver function and normal liver histology for nontumorous portions. The cultured HHMphi were analyzed for their ability to release chemical mediators with specific activities in the host defense system. Dose-dependent increases in superoxide release, interleukin-1 (IL-1) release, and, within a relatively narrow range, prostaglandin-E2 (PGE2) release were observed in opsonized zymosan (oz)-stimulated HHMphi derived from both cirrhotic and noncirrhotic patients. The release of O2- and PGE2 from HHMphi derived from cirrhotic patients was significantly less than HHMphi derived from noncirrhotic patients, whereas the release of IL-1 was significantly greater. Although, because of the limited sample availability, only tumor-bearing patients were studied, the mediator-releasing ability of HHMphi derived from cirrhotic patients was significantly different from the ability of HHMphi derived from noncirrhotic patients with similar malignancies. This phenomenon may be related to altered host defenses in patients with cirrhosis.

Adjuvants, Immunologic↗
PubMed1996

Quantitation of alpha-fetoprotein and albumin messenger RNA in human hepatocellular carcinoma.

To analyze gene expression of alpha-fetoprotein (AFP) and albumin in hepatocellular carcinoma (HCC), messenger RNAs (mRNAs) of these proteins in six human hepatoma cell lines and in 30 cases of HCC were quantitatively analyzed by competitive reverse transcription (RT) followed by polymerase chain reaction (PCR). The transcriptional levels of both AFP and albumin genes in HepG2 and Huh 7 cell lines were 10(10) copies/microgram RNA, in contrast to approximately 10(5) copies/microgram RNA in HLE and HLF cell lines. AFP and albumin mRNA levels in three normal livers were 10(5) and 10(10) transcripts/microgram RNA, respectively. In 30 cases with HCC AFP mRNA level in neoplasm was 10 to 10(5)-fold enhanced as compared with that of nonneoplastic portion, and correlated with serum AFP level and tumor size (P < .01). In contrast, albumin mRNA level was not reduced in the neoplasms presenting enhanced AFP mRNA levels, indicating that AFP and albumin gene expression in situ is not necessarily mutually exclusive. Prospective analysis revealed that an increased serum AFP was shown at the time of recurrence among patients with enhanced AFP mRNA levels in neoplasm only, indicating that AFP mRNA levels in neoplasm could be a clinically predictable tool.

Aged↗
PubMed1996

Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential.

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC.

Adult↗
PubMed1996

kan-1 (bile acid CoA:amino acid N-acyltransferase) messenger RNA as a novel predictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy.

We identified kan-1 complementary DNA (cDNA), the sequence of which is identical to bile acid CoA:amino acid N-acyltransferase (BAT), a liver enzyme that catalyzes the conjugation of bile acids with glycine or taurine. Kan-1(BAT) messenger RNA (mRNA) levels of the resected specimens obtained from 37 hepatocellular carcinoma (HCC) patients were studied in an attempt to evaluate prognostic significance in HCC patients after partial hepatectomy. Using Northern blot hybridization, kan-1(BAT) mRNA levels were quantified in tumorous and nontumorous tissues, and the ratio of the former to the latter was defined as the kan-1(BAT) ratio. Twelve patients had a kan-1(BAT) ratio < 0.5 (low kan-1[BAT] ratio), and 25 patients had a ratio >0.5 (high kan-1[BAT] ratio). The patients with a low kan-1(BAT) ratio demonstrated poorer survival than the patients with a high kan-1(BAT) ratio (P = .0013). The overall estimated hazard ratio for death in patients with a low kan-1(BAT) ratio was 68.05 according to a multivariate model (P = .0005). Thus, the kan-1(BAT) ratio may serve as a new molecular prognostic marker in HCC patients, following hepatic resection.

Acyltransferases↗