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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 289 records · Page 16Linked to original sources
PubMed1998

Cyclophosphamide given after active specific immunization augments antitumor immunity by modulation of Th1 commitment of CD4+ T cells.

BACKGROUND AND OBJECTIVES: In order to evaluate the regulatory effect of cyclophosphamide (CPA) on active specific immunization (ASI)-induced antitumor immunity, we examined the timing of CPA (100 mg/kg) with ASI, and focused on whether CPA given after ASI augments antitumor immunity by modulation of Th1 commitment of CD4+ T cells. METHODS: We examined the effect of CPA combined with ASI using sonicated tumor supernatant (SS) and recombinant interleukin-1 beta (rIL-1 beta). RESULTS: Survival of i.p. tumor inoculated mice after ASI (days -12, -9, and -6) followed by 100 mg/kg CPA (day -3) (ASI-CPA) was significantly prolonged compared with that of mice treated with ASI alone, whereas CPA (day -15) treatment before ASI (CPA-ASI) completely abrogated the survival prolongation by ASI alone. In early stage (day 0) after ASI-CPA treatment, the CD4+ T cells were determined to play an important role in the protective immunity for the following reasons: 1) the CD4+/CD8+ ratio of spleen cells from immunized mice was higher than that of the control or CPA alone treated group; and 2) the tumor neutralizing activity of fresh spleen cells was abrogated by CD4+ T-cell depletion in vitro. CD4+ T cells of mice treated with ASI-CPA produced more interferon (IFN)-gamma and IL-2 and less IL-4 than those of the ASI alone group. CONCLUSIONS: These results suggest that the protective immunity induced by ASI was augmented through the modification of the Th1 and Th2 balance by CPA injection after ASI.

Animals↗
PubMed1998

Portal branch ligation with a continuous hepatocyte growth factor supply makes extensive hepatectomy possible in cirrhotic rats.

In a cirrhotic liver, the regenerative ability and specific functions are so impaired that excessive resection easily complicates postoperative liver dysfunction, which frequently leads to life-threatening multiple-organ failure. Hepatocyte growth factor (HGF), first identified as the most potent stimulator of DNA synthesis in primary hepatocytes, not only stimulates liver regeneration, but also accelerates hepatic function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the efficacy of preoperative portal branch ligation (PBL) (which can induce compensatory hypertrophy of the unaffected lobes) combined with a continuous HGF supply in the performance of extensive hepatectomy in cirrhotic rats. Cirrhosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN) three times per week for 3 weeks. Five days after the last injection, when 70% hepatectomy is lethal, the rats underwent portal ligation of the left lateral and median branches (corresponding to approximately 70% of the total volume of the liver). Simultaneously, they were continuously treated with either recombinant human HGF (rhHGF) or vehicle from an intraperitoneally implanted osmotic pump. Four days after the portal ligation, the occluded lobes were resected. The HGF treatment rapidly increased both the wet weight of the unoccluded lobes and the hepatocellular DNA synthesis. The blood chemical analysis indicated that HGF significantly suppressed the posthepatectomy liver dysfunction. Most importantly, the HGF treatment markedly improved the survival rate of the rats at 48 hours after the major hepatectomy. In conclusion, PBL combined with a continuous HGF supply makes extensive hepatectomy possible in cirrhotic rats, mainly by promoting the hypertrophy of the unaffected lobes.

Animals↗
PubMed1998

Expression of human macrophage metalloelastase gene in hepatocellular carcinoma: correlation with angiostatin generation and its clinical significance.

Macrophage metalloelastase, a member of the human matrix metalloproteinase family, is believed to play an important role in angiostatin generation, which, in experimental studies, has an antiangiogenic function and is a key molecule in tumor dormancy. However, no clinical studies have been reported regarding the correlation between human macrophage metalloelastase (HME) gene expression and angiostatin production. Therefore, the present study was designed to evaluate the HME messenger RNA (mRNA) expression and angiostatin generation in hepatocellular carcinoma (HCC). Tumorous and contiguous nontumorous tissues were obtained from 40 HCC patients who underwent curative partial hepatectomy. By using Northern blot hybridization, HME mRNA was detected in 25 of the 40 HCC samples and, in all of these cases, the expression in tumorous tissues was stronger than in the nontumorous tissues. In situ hybridization identified the HCC cells as mainly responsible for the signals shown in Northern blot. Angiostatin was detected by Western blot mainly in tumors and showed significant association with HME mRNA expression in tumorous tissues (P = .0008). The patients whose tumors did not express HME mRNA and, thus, did not produce angiostatin, demonstrated poorer survival than those whose tumors showed high expression of HME mRNA and angiostatin generation (P = . 002). The univariate and multivariate analyses revealed that HME mRNA expression is a new and independent variable affecting overall survival (P = .001 and P = .03, respectively). These findings show that the HME gene is expressed in HCC being significantly associated with angiostatin generation by such tumors and that HME mRNA expression may serve as a new molecular prognostic marker in HCC patients after partial hepatectomy.

Adult↗
PubMed1998

Hepatocyte growth factor prevents lipopolysaccharide-induced hepatic sinusoidal endothelial cell injury and intrasinusoidal fibrin deposition in rats.

BACKGROUND: Acute endotoxemia is known to cause activation of Kupffer cells as well as serious injury in parenchymal and nonparenchymal cells in the liver. We have recently shown that a continuous recombinant hepatocyte growth factor (rHGF) supply prevents lipopolysaccharide (LPS)-induced liver injury in rats. As an attempt to elucidate the mechanism, here we investigate the cytoprotective effect of rHGF on sinusoidal endothelial cells (SECs) in LPS-induced liver injury in rats. MATERIALS AND METHODS: In order to supply rHGF continuously to the liver, syngenic rat fibroblasts genetically modified to secret rat rHGF were implanted in the spleen. Fourteen days after cell implantation, we injected LPS intravenously and evaluated SEC damage histologically and blood chemically. RESULTS: Phosphotungstic acid-hematoxylin staining revealed that rHGF treatment greatly attenuated intrasinusoidal LPS-induced fibrin deposition. The ultrastructural changes in SECs caused by LPS administration in control rats were barely detectable in rHGF-treated rats. Blood chemical analyses showed that rHGF potently suppressed the LPS-induced increase in serum hyaluronic acid and transaminase levels. CONCLUSIONS: Our results indicate an important role for HGF in SEC protection in vivo and would suggest a novel therapeutic strategy for liver diseases with SEC injury.

Alanine Transaminase↗
PubMed1998

Dual radionuclide single-photon emission computed tomography in the prediction of further ischemic risk after acute myocardial infarction.

To evaluate whether the findings of dual single-photon emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m PPi) and thallium-201 were predictive of further cardiac events in their hospital course, we studied 130 patients recovering from acute myocardial infarction (AMI). Fifty-four patients showed overlapping of Tc-99m PPi and thallium-201 in the same location (overlap positive group), and 76 patients had no overlap (overlap negative group). Of the 130 patients, 36 (28%) had a cardiac event. In patients in the overlap positive group, the incidence of subsequent events was significantly higher than in patients in the overlap negative group (44% versus 16%; p < 0.001). In the overlap positive group, the Tc-99m PPi uptake score and the number of overlap segments in patients with further events was significantly higher than those in patients without further events (10.2 +/- 5.1 versus 6.4 +/- 4.1, p < 0.005 and 5.2 +/- 2.0 versus 3.3 +/- 1.3, p < 0.001, respectively). These results suggest that patients who have a Tc-99m PPi and thallium-201 overlap negative scan can be candidates for early hospital discharge. In contrast, patients who have a greater number of overlap segments may require early catheterization and revascularization, so that simultaneous SPECT imaging Tc-99m PPi and thallium-201 might be useful for identifying patients with further ischemic risk after AMI in their hospital course.

Aged↗
PubMed1998

Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence.

No consensus has been reached on the indications for and effectiveness of surgery for secondary intrahepatic hepatocellular carcinoma (HCC) and extrahepatic metastasis after macroscopically complete removal of primary HCC. Secondary intrahepatic HCCs, usually regarded as recurrence are classified into those arising as a result of multicentric carcinogenesis or intrahepatic metastases derived from the primary HCC. The present study was designed to evaluate the utility of surgical treatment in relation to the pathogenesis of the secondary HCC: classified as multicentric carcinogenesis (MC), intrahepatic metastasis (IM), and extrahepatic metastasis. Thirty patients underwent extirpation of secondary HCC: 22 patients had secondary HCCs in the remnant liver (MC group; n = 8; IM group, n = 14), 6 patients had extrahepatic metastases, and 2 patients had both intrahepatic and extrahepatic metastases. Survival rates after the re-resection in the 22 patients with the secondary intrahepatic HCCs were 94.7% at 1 year, and 50.2% at 3 years postoperatively, and the 8 patients with extrahepatic metastasis had survival rates of 62.5% at 1 year, 37.5% at 3 years, and at 5 years. The survival rates after re-resection in the MC group were 100% at 1 year and 80.0% at 3 years, whereas those in the IM group were 91.7% at 1 year, and 38.1% at 3 years. Surgery can be indicated not only in patients with localized intrahepatic secondary HCCs but also in those with extrahepatic metastasis. In particular, patients with secondary HCCs arising as a result of multicentric carcinogenesis are expected to have a good prognosis.

Adult↗
PubMed1998

Expression of membrane-type matrix metalloproteinase-1 in human pancreatic adenocarcinomas.

The expression of a new type of matrix metalloproteinase, membrane-type matrix metalloproteinase-1 (MT-MMP-1), was examined in 24 cases of primary pancreatic adenocarcinomas and 9 cases of secondary liver tumors derived from pancreatic adenocarcinomas, using a non-radioactive in situ hybridization and immunohistochemical methods. Out of 24 cases of primary pancreatic adenocarcinomas, 18 showed positive expression of MT-MMP-1 transcripts in cancer cells and 20 of 24 showed positive expression in the tumor stromal cells. The immunoreactivity of the gene products for MT-MMP-1 was demonstrated to be almost the same, as shown by in situ hybridization in these 24 cases. In particular, both the staining intensity for MT-MMP-1 transcripts and the immunoreactivity of the gene products in the tumor stromal cells of mucinous cystadenocarcinomas were significantly weaker than those of common-type ductal adenocarcinomas among the 24 cases. All of the 9 cases of secondary liver tumors derived from pancreatic adenocarcinomas showed positive expression for MT-MMP- transcripts but less immunoreactivity for the gene products. These results suggest that MT-MMP-1 is transcribed and translated in both cancer cells and the tumor stromal cells in human pancreatic adenocarcinomas. Furthermore, considering that common-type ductal adenocarcinoma of the pancreas usually shows a strong desmoplastic reaction, while mucinous cystadenocarcinoma typically does not, MT-MMP-1 expressed in the tumor stromal cells of common-type adenocarcinomas may be involved in processes leading to the desmoplastic reaction.

Adenocarcinoma↗
PubMed1998

Gastrinoma with multiple liver metastases: effectiveness of dacarbazine (DTIC) therapy.

Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range, >220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than 3(1/2) years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases.

Aged↗
PubMed1998

Effect of a specific synthetic inhibitor of neutrophil elastase (ONO-5046) on the course of acute hemorrhagic pancreatitis in dogs.

In acute pancreatitis, particularly in severe cases, polymorphonuclear neutrophil (PMN) elastase induces tissue damage in remote organs such as the lung, as well in the pancreas itself. Therefore, we examined the therapeutic effect of a specific synthetic inhibitor of PMN elastase (ONO-5046: Ono Pharmaceuticals, Osaka, Japan) on the lung, liver, and kidney, as well as pancreas, in severe hemorrhagic pancreatitis in dogs. Acute hemorrhagic pancreatitis was induced by the injection of a mixture of autologous bile and porcine trypsin into the main pancreatic duct. Lipopolysaccharide (LPS) was administered intravenously as a septic challenge. Two animal groups were used. In one group, continuous infusion of ONO-5046 was started prior to the injection of LPS (ONO group). In the other group (control), saline was infused instead. At the end of the experiment (330 min after the injection of bile and trypsin), the pancreas revealed severe hemorrhagic pancreatitis, and a large amount of bloody ascites had accumulated in the peritoneal cavity. The white blood cell count was markedly reduced in response to the induction of pancreatitis, and was decreased further by the septic attack, irrespective of the administration of ONO-5046, although the count increased again in the ONO group. Serum levels of amylase and alpha2-macroglobulin-trypsin complex increased similarly in both groups following administration of bile and trypsin. Serum Ca levels decreased in both groups. At the end of the experiment, the wet weight of the lung was slightly higher in the control group (without ONO-5046). Microscopically, the pancreas showed severe hemorrhage accompanied by extensive interstitial edema in both groups. The lung and liver demonstrated mild infiltration of inflammatory cells in the interstitium in both groups, although the inflammatory change in the liver was slightly milder in the ONO group. These findings indicate that severe hemorrhagic pancreatitis cannot be alleviated by the administration of a specific inhibitor of PMN elastase alone, although this may lessen damage to remote organs such as the liver and lung. The white blood cell count decreased markedly after the induction of acute pancreatitis, and much more after a septic challenge. This seems to be closely related to the accumulation of bloody ascites in the peritoneal cavity.

Amylases↗
PubMed1998

Inhibition of tumor growth and microvascular angiogenesis by the potent angiogenesis inhibitor, TNP-470, in rats.

The antiangiogenic effects of TNP-470 on the neovascularization of tumors were studied by examining ultrastructural alterations in the vasculature and interstitial fluid pressure (IFP) of tumors. Wistar rats were first inoculated subcutaneously (s.c.) with the Walker 256 carcinosarcoma cell line, then either vehicle medium or TNP-470, 30 mg/kg, was injected s.c. on day 1. A tumor growth assay, the necrotic area, and the IFP in the tumor were all measured on day 12. The antiangiogenic effects of TNP-470 were studied by scanning electron microscopic images of tumor vascular casts. TNP-470 was observed to inhibit tumor growth and increase the necrotic area significantly. In the TNP-470-treated group, the IFP in the superficial layer, defined as 2-3 mm from the tumor capsule, and in the deep layer, defined as 8-10 mm from the tumor capsule, were significantly higher than the corresponding values in the control. Moreover, vascular casts showed a significant reduction in the budding of sprouts in the superficial layer, and a decrease in the maximum diameter of the tumor vessels in the deep layer. It is possible that the higher IFP in the TNP-470-treated tumors might have prevented tumor vessel dilation. The findings of this study demonstrated that TNP-470 inhibited the budding of tumor vessel sprouts, and increased the IFP. These processes seem to act synergistically to suppress tumor angiogenesis.

Animals↗
PubMed1998

Membrane-type matrix metalloproteinase-1(MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas.

BACKGROUND/AIMS: The matrix metalloproteinase (MMP) family play important roles in the invasion of cancer cells by degrading the extracellular matrices. The current study was designed to determine the expression pattern of membrane-type matrix metalloproteinase-1 (MT1-MMP) in hepatocellular carcinomas and its participation in invasion potential. METHODS: MT1-MMP mRNA expression was examined in 25 human hepatocellular carcinoma specimens using Northern blot, and the correlation to clinicopathological features was evaluated. In situ hybridization and immunohistochemistry were performed to study the localization and the cells responsible for the production. RESULTS: Northern blot analysis revealed high levels of MT1-MMP mRNA expression in tumorous portions in all cases, whereas in non-tumorous portions moderate or faint expression was evident in 22/25 cases. In 21/25 cases, the expression levels in tumorous portion were higher than those in non-tumorous portion. In particular, hepatocellular carcinoma with capsule infiltration demonstrated significantly higher expression than those without (p<0.05). In situ hybridization and immunohistochemical study revealed MT1-MMP transcripts and proteins in cancer cells and stromal cells, respectively. MT1-MMP positive cells were preferentially observed in the invading border of tumor nests. The MMP-2 transcript showed a similar pattern to that of MT1-MMP by in situ hybridization. CONCLUSION: The present study showed that the MT1-MMP gene is strongly expressed in hepatocellular carcinoma cells and is involved in the invasion potential of hepatocellular carcinoma, and also that MT1-MMP may be one of the key molecules responsible for the invasion potential of hepatocellular carcinoma. Furthermore, the evidence suggests that MT1-MMP and MMP-2 cooperate in the process of cancer invasion.

Adult↗
PubMed1998

Double-outlet right ventricle with complete atrioventricular canal.

A case of double-outlet right ventricle, unbalanced complete atrioventricular canal, hypoplastic aortic arch, coarctation of the aorta, and atrioventricular valve regurgitation was treated with a staged approach. At 4 days of life the patient underwent aortic arch repair, atrial septectomy, common atrioventricular valve regurgitation repair, and pulmonary artery banding. When she was 14 months of age a biventricular repair was accomplished by two-patch complete atrioventricular canal repair and arterial switch procedure.

Atrioventricular Node↗
PubMed1998

Quantitative analysis of alpha-fetoprotein mRNA in circulating peripheral blood of patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas.

In conjunction with strategies introduced in recent years to identify cancer micrometastasis through amplification of cancer-associated mRNA, we developed a highly sensitive system to detect alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients. The aim of the present study was to make our original system quantitative. Peripheral venous blood from patients with hepatocellular carcinoma and alpha-fetoprotein-producing gastric carcinoma was subjected to reverse transcription followed by our original three-step polymerase chain reaction co-amplifying both the original sequence and our synthetic competitor. We succeeded in modifying our system for quantitative analysis, and investigated the perioperative change, the postoperative change and the change after chemotherapy in order to illustrate the possible application of this method. The quantitative analysis of alpha-fetoprotein mRNA present in the peripheral blood represents a useful tool for analyzing the relationship of surgery to recurrence, the effect of chemotherapy, and to predict impending recurrence in patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas.

Carcinoma, Hepatocellular↗
PubMed1998

Enterostatin (Val-Pro-Asp-Pro-Arg)-like immunoreactivity in rat urine: relationship to corticosterone output.

Numerous studies have documented a role for enterostatins in appetitive behavior. However, due to the lack of knowledge about the distribution of enterostatins in tissues and body fluids, it has not been possible to examine the role of endogenous enterostatin in this process. To this end, using a polyclonal antibody raised against enterostatin -- Val-Pro-Asp-Pro-Arg (VPDPR), we examined the nature and distribution of enterostatin-like immunoreactivity in the rat urine by ELISA and chromatography. The results reported here show for the first time the presence of VPDPR-like immunoreactivity (VPDPR-LI) in rat urine. Further characterization of rat urine VPDPR-LI revealed that it is not due to VPDPR but to another peptide similar to VPDPR. Furthermore, as urinary excretion of corticosterone increases, the level of VPDPR-LI in urine decreases.

Amino Acid Sequence↗