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Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 325 records · Page 18Linked to original sources
PubMed1995

Requirement of CD4+ T cells and antigen-presenting cells for primary in vitro generation of CD8+ cytotoxic T cells against Ld-binding self-peptide p2Ca.

We investigated the cellular requirement for primary in vitro generation of cytotoxic T-lymphocytes (CTL) in BALB/c spleen cells against Ld-binding self-peptide p2Ca. Depletion of CD4+ T-cells in vitro by pretreatment with anti-CD4 monoclonal antibody (mAb) and complement or in vivo by administration of anti-CD4 mAb abrogated generation of CTL. Depletion of adherent cells by passing spleen cells through a nylon wool (NW) column also abrogated generation of CTL. Addition of peritoneal exudate cells (PEC) to spleen cells passed through the NW column restored CTL generation. These findings indicate that both CD4+ T-cells and antigen-presenting cells (APC) were necessary for CTL generation. Treatment of PEC with paraformaldehyde (PFA), but not mitomycin-C (MMC) abrogated their ability to restore CTL generation when mixed with spleen cells from the NW column, suggesting that an endocytic pathway could be involved in presentation of p2Ca on APC.

Amino Acid Sequence↗
PubMed1994

Electron spin resonance signals of non-heme iron as an indicator of ischemia-reperfusion injury of the liver.

Although many different methods have been proposed to assess the viability of preserved or reperfused liver, none of them are definitive. In this study, we investigated the usefulness of electron spin resonance (ESR) spectrometry in the rat liver ischemia model. Ischemia was induced in Wistar rats weighing 250-300 g by clamping the portal triad. At 15, 30, 60, or 90 min after the clamping, the liver was reperfused by removing the clamp. Liver specimens obtained before and after the clamping and also 30 min after reperfusion were frozen with liquid nitrogen and analyzed at 140K by ESR spectrometry. Two significant signals of g-values of 2.0 and 1.96 were observed with the fresh liver. The former was thought to be a mixture of CoQ, flavin, and succinate radicals. The intensity of this signal did not change throughout the experimental period. The latter was regarded as the signal from non-heme irons of mitochondria. The intensity of this signal decreased as the ischemic time became longer (the ratio to the signal intensity of the fresh liver was 0.69 +/- 0.19, 0.22 +/- 0.08, 0.20 +/- 0.05, and 0.18 +/- 0.09 at the end of 15, 30, 60, and 90 min of ischemia, respectively). After reperfusion, each ratio recovered to 0.95 +/- 0.12, 0.77 +/- 0.06, 0.56 +/- 0.15, and 0.37 +/- 0.20, respectively. This suggests that detectable signals with Fe(II)-Fe(III) decreased and became undetectable as the reduced form of non-heme irons under the anoxic state. Then, after reperfusion, the reduced form of non-heme irons decreased and the oxidized form increased. Incomplete recovery was thought to be due to decrease in the viability or function of liver cells. ATP and energy charge had the same tendency as the non-heme iron signal observed with ESR. There was a significant correlation between the non-heme iron signal and energy charge (y = 0.73x + 0.32, r = 0.78, P < 0.001), demonstrating that the signal intensity reflects the viability or function of liver cells. This study suggests that the signal from non-heme irons detected by ESR can be a good parameter of the metabolic state of the liver in ischemia and reperfusion. This method is simple and quick and should be applicable in clinical liver transplantation.

Adenosine Diphosphate↗
PubMed1994

A 3-Mb physical map of the chromosome region 8p21.3-p22, including a 600-kb region commonly deleted in human hepatocellular carcinoma, colorectal cancer, and non-small cell lung cancer.

To isolate a putative tumor suppressor gene(s), we have constructed a physical map and a detailed deletion map of chromosome region 8p21.3-p22, where loss of heterozygosity (LOH) has been frequently seen in human hepatocellular carcinomas (HCC), colorectal cancers (CRC), and non-small cell lung cancers (NSCLC). The smallest commonly deleted region at 8p21.3-p22 in HCC and CRC was between the loci defined by C18-245 and C18-2644; in NSCLC, a region between C18-1051 and C18-2644 was commonly deleted. A contiguous physical map of 12 cosmid markers in the 8p21.3-p22 region was constructed by means of multi-color fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE). On the basis of this physical map, which spans roughly 3.1 Mb, the estimated sizes of the commonly deleted regions were at most 1.2 Mb in HCC and CRC and 0.6 Mb in NSCLC. As four of the 12 physically ordered markers are located within the 0.6 Mb region commonly deleted in all three tumor types, nearly one fourth to one fifth of the target region has already been covered with cosmid inserts.

Animals↗
PubMed1994

New development of transarterial immunoembolization (TIE) for therapy of hepatocellular carcinoma with intrahepatic metastases.

The prognosis of patients with multiple hepatocellular carcinoma (HCC) remains disappointing. In this study, we devised a new therapeutic modality for HCC consisting of transarterial immunoembolization (TIE) using OK-432 and fibrinogen and then analyzed the preliminary results. In the first series, we applied the treatment to 19 patients with advanced HCC who had proved to be insensitive to several previous conventional treatments. In all, 14 patients (74%) with unresected HCC have currently survived for between 2 and 16 months after TIE. The remaining 5 patients died at 17, 14, 8, 7, and 4 months after TIE. The serum levels of tumor markers decreased in all of the patients, and a marked reduction in tumor size was observed in six patients after TIE. A high fever occurred in all cases, and abdominal pain and loss of appetite were also observed after TIE. However, deterioration of liver function was negligible. After confirmation of the safety of this method, we started a second study series in which this TIE treatment was selected as the first choice. Six patients have been treated to date. All patients in this group underwent hepatic resection at 6-48 days following TIE. Histological examination of the resected specimens following TIE showed massive infiltration of mononuclear cells around tumor cell nests and lytic necrosis as well as coagulation necrosis of the main tumor and the intrahepatic metastases. In conclusion, our results indicate that TIE may be a safe and promising therapy for patients with HCC.

Adult↗
PubMed1994

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison between L-TAE with farmorubicin and L-TAE with adriamycin: preliminary results (second cooperative study). Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized controlled clinical trial was conducted to compare the use of farmorubicin (FARM) and adriamycin (ADR) in Lipiodol transcatheter arterial chemoembolization (L-TAE) as a treatment of hepatocellular carcinoma. In all, 192 hospitals participated, and 415 patients were enrolled in the study during the period from October 1989 through December 1990, and their data were collected. The patients were randomly allocated to group A (FARM) or group B (ADR) by a central telephone registration. Several clinical characteristics were slightly worse in group A than in group B, but there was no statistically significant difference. The actual doses of FARM and ADR were 72 mg/body and 48 mg/body, respectively. Additional treatments, including repeated TAE or surgery, were given to 248 patients. The 1- and 2-year survival rates were 69% and 44% for group A and 74% and 57% for group B, respectively. The difference was marginally significant (P value in the log-rank test, 0.038). When each group of patients was classified into two subgroups, i.e., high-risk and low-risk categories, based on the severity index calculated by the Cox regression model from significant prognostic factors, the ADR subgroup was significantly superior to the FARM subgroup in the low-risk category, but there was no significant difference between the subgroups in the high-risk category. The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction did not show any significant difference between the groups. At the above-mentioned doses, ADR seemed to have efficacy almost the same as or slightly superior to that of FARM in L-TAE for the treatment of hepatocellular carcinoma.

Adult↗
PubMed1994

Expression of the pancreatic secretory trypsin inhibitor gene in the liver infected with hepatitis B virus.

Pancreatic secretory trypsin inhibitor, an acute phase reactant protein, is expressed in the liver in response to inflammatory cytokines, especially in hepatocellular carcinoma. Northern blots of 25 dissected liver tissues from non-hepatitis, chronic hepatitis and cirrhosis patients revealed that 10 (40%) expressed pancreatic secretory trypsin inhibitor. The expression seemed to be closely associated with hepatitis B viral infection, since among the 11 hepatitis B virus-infected samples, nine (81%) were pancreatic secretory trypsin inhibitor-positive. In contrast, this augmented expression was absent in non-infected livers (0/5; 0%), and rare in those infected with hepatitis C virus (1/9; 11%). There was no significant correlation between the pancreatic secretory trypsin inhibitor expression in the liver and the serum level of glutamic pyruvic transaminase, the hepaplastin test, the 15-min retention rate of indocyanine green, or the histological findings of the liver tissues such as lymphocyte infiltration and pseudolobular formation. Furthermore, we identified an almost three-fold increase in the transactivation of pancreatic secretory trypsin inhibitor gene expression in HepG2 cells after transient transfection with HBV-DNA or the X gene in an expression vector. These results suggest that the induction of pancreatic secretory trypsin inhibitor gene expression in livers with chronic hepatitis and cirrhosis is directly affected by hepatitis B virus.

Adult↗
PubMed1994

Low temperature collagenase digestion for islet isolation from 48-hour cold-preserved rat pancreas.

We examined the efficacy of relatively low temperature collagenase digestion at 20 degrees C on the yield and viability of islets after long-term cold preservation. Wistar rat pancreases were distended with University of Wisconsin solution via a pancreatic duct at the time of harvesting to which collagenase and 2.5 mM calcium chloride were added. The pancreases were cold-preserved at 4 degrees C for 24 or 48 hr. After storage, they were incubated for collagenase digestion at 37 degrees C or 20 degrees C for various incubation periods to obtain the peak yield. At 20 degrees C, in vitro collagenase activity measured by the FALGPA method was one fourth of that at 37 degrees C, and pancreases were well digested with a prolonged digestion period (60-90 min vs. 15-20 min for the 37 degrees C group). In vitro insulin secretion of islets isolated from freshly removed pancreases was maintained at 20 degrees C for 120 min in University of Wisconsin solution as compared with 30 min at 37 degrees C. Therefore, the preserved pancreases used in this study were incubated either at 37 degrees C or 20 degrees C at various times in order to obtain peak islet yields. The islet yields from 24-hr cold-preserved pancreases at 37 degrees C and 20 degrees C digestion were 573 +/- 59/rat (n = 6) and 497 +/- 84/rat (n = 11), respectively, and those from 48-hr cold-preserved pancreases were 395 +/- 113/rat (n = 6) and 414 +/- 75/rat (n = 6), respectively. The yields from 24- and 48-hr cold-preserved pancreases were significantly low compared with 635 +/- 52/rat for fresh pancreases (n = 15), but there was no significant difference between the 2 methods. The viability of the isolated islets, which was examined by transplantation to streptozotocin-induced diabetic C57BL/6 mice, showed a significant difference in the capacity to ameliorate diabetes. The functional success rate of islet transplantation after 24-hr cold preservation was equally good (8/8 for 37 degrees C group vs. 9/10 for 20 degrees C group), but the rate for those from 48-hr cold-preserved pancreases was significantly better with digestion at 20 degrees C than at 37 degrees C (1/8 for 37 degrees C group vs. 7/8 for 20 degrees C group, P < 0.05). We concluded that viable islets can be isolated from 48-hr cold-preserved pancreases with the low temperature collagenase digestion method, which shows promise as a modality for successful clinical islet transplantation.

Animals↗