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Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 343 records · Page 19Linked to original sources
PubMed1994

A potential immunosuppressive effect of anti-lymphocyte function-associated antigen-1 monoclonal antibody on islet transplantation.

The immunosuppressive potentials of mAbs to lymphocyte function-associated antigen-1 (LFA-1) and CD2 molecules were examined in murine islet transplantation. Crude digested islets from BALB/c (H-2d) mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (H-2b) mice. The rat mAbs of KBA (anti-LFA-1) and RM2-1 (anti-CD2) were given intraperitoneally immediately after transplantation and on the first day after grafting at a dose of 0.1 mg/mouse/day. In nontreated animals, the islet allografts were acutely rejected with a mean survival time (MST) of 19.6 +/- 8.3 days. Control isotype-matched anti-CD18 treatment did not prolong the MST of 12.8 +/- 1.6 days. Anti-LFA-1 treatment alone produced indefinite survival in 5 of 10 recipients with MST of 72.2 +/- 33.4 days. Anti-CD2 treatment failed to do so, although MST was marginally prolonged to 32.8 +/- 20.5 days. When both mAbs were given together, additional benefit with anti-CD2 treatment was not observed (MST: 77.4 +/- 31.1 days). In spite of the unresponsiveness to islet allografts, the animals did not suffer from any severe infectious disease. Mice bearing long-term functioning islets rejected third-party skin grafts as well as islet donor strain skin grafts. The long-term surviving islet allografts were also rejected coincidentally. These results indicate that a perioperative short course of anti-LFA-1 mAb treatment can induce unresponsiveness to islet allografts, although it is not systemic, and that costimulatory signals through these adhesion molecules play a central role in inducing an immune response leading to rejection of the allografted islets.

Animals↗
PubMed1994

Cytoprotective effect of prostaglandin I2 analogues on superoxide-induced hepatocyte injury.

BACKGROUND: Prostaglandin I2 (PGI2) analogues have been suggested to protect the liver from ischemia-reperfusion injury, but the exact mechanism remains to be proved. METHODS: Primary cultured rat hepatocytes were exposed to superoxide generated by mixing hypoxanthine and xanthine oxidase, and changes in cell viability, cytosolic free calcium concentration ([Ca2+]i), and adenosine 3',5'-cyclic monophosphate (cAMP) concentration were assessed. The PGI2 analogue (OP2507 or OP41483) at 1 to 100 ng/ml was given as treatment. RESULTS: PGI2 analogues suppressed hepatocyte death in a dose-dependent manner (p < 0.01; OP2507 at 10 and 100 ng/ml, OP41483 at 100 ng/ml). At the end of 1-hour preincubation with OP2507, a significant rise in cAMP concentration was observed. Moreover, addition of dibutyryl cAMP suppressed hepatocyte death. A rise in [Ca2+]i, which preceded cell death, was prevented by PGI2 analogues or dibutyryl cAMP. CONCLUSIONS: The increase in cellular cAMP followed by suppression of [Ca2+]i elevation might be the major cause of the cytoprotective effect of PGI2 analogues in superoxide-induced hepatocyte injury.

Animals↗
PubMed1994

[Immunological and histological analyses of transarterial immuno-embolization therapy (TIE) in operable patients with hepatocellular carcinoma].

Immunological and histological analyses were performed on 14 patients with hepatocellular carcinoma treated by transcatheter immunoembolization (TIE) and subsequently by hepatic resection. They were compared with the cases treated by transcatheter arterial embolization (TAE). Exceptionally high plasma levels of inflammatory cytokines, such as IL-6 and IL-8, were noted 3 hours after TIE insults in the majority of the cases. On the contrary, exceptionally high levels of TNF-alpha were also observed in some cases of TIE treatment. In addition, light microscopically, the lytic necrosis of the tumor and massive infiltration of mononuclear cells were the histological characteristics of this treatment. Interestingly, the population of the infiltrates has altered after TIE treatment. It thus consisted mainly of neutrophils in early phase, subsequently of the mixture of lymphocytes, eosinophils, and plasma cells, and finally of lymphocytes. These results may suggest that certain inflammatory responses caused by TIE may play important roles in this new therapeutic modality.

Carcinoma, Hepatocellular↗
PubMed1994

Hilar lobar vascular occlusion for hepatic resection.

Limited resection can be a therapeutic approach in patients with cirrhosis with very low remnant hepatic function after resection. In this study, two hilar vascular clamping methods (hilar selective clamping [n = 13] and hilar lobar clamping method [n = 8]), which were used for resection of hepatocellular carcinoma in patients with cirrhosis, were compared based on cardiovascular stability during clamping, intraoperative bleeding, operative time and postoperative course. In the past, the Pringle method had been used (n = 19) and those instances were included for comparison. The mean operation time of the lobar clamping group was 209 +/- 41 minutes, which was significantly less than that of the selective clamping group (259 +/- 44 minutes, p < 0.05). Furthermore, the mean intraoperative blood loss of the lobar clamping group was 920 +/- 400 milliliters, which was significantly less than that of the selective clamping group (1,640 +/- 590 milliliters, p < 0.01). The postoperative total bilirubin and glutamine-oxaloacetic transaminase levels tended to be high in the Pringle group, but there was no significant difference between the groups. Although the blood pressure during clamping significantly decreased in all groups, the decrease was profound in the Pringle group as compared with those in the other two groups. Thus, as a method for controlling afferent blood flow during hepatic resection in patients with cirrhosis, we recommend the lobar clamping method as a simple, safe and effective way to minimize bleeding and maintain cardiovascular stability.

Blood Pressure↗
PubMed1994

Role of intracellular calcium in superoxide-induced hepatocyte injury.

The mechanisms of hepatocyte injury caused by exogenous superoxide were investigated with the use of cultured rat hepatocytes. Cell viability, cytosolic free calcium concentration and cell surface structure were observed. Superoxide was produced by adding hypoxanthine and xanthine oxidase to the buffer. Cytosolic free calcium concentration was calculated by means of ratio imaging of fura 2 fluorescence with multiparameter digitized microscopy. In the buffer containing 1.27 mmol/L of calcium, lactate dehydrogenase release into the buffer began to increase at 1 hr and reached a plateau in 5 hr. Eighteen minutes after the addition of hypoxanthine and xanthine oxidase, small blebs were recognized on the cell surface with a scanning electron microscope; then a gradual rise in cytosolic free calcium concentration was observed. Thirty minutes after exposure to superoxide, large blebs were recognized with a phase-contrast microscope, when cytosolic free calcium concentration had risen to about 700 nmol/L. Depriving the buffer of calcium (< 10 mumol/L) significantly suppressed bleb formation and cell death, and cytosolic free calcium concentration was found to remain around the basal level (200 nmol/L). When ethylene glycol-bis (beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid was added to the buffer, bleb formation and cell death were suppressed more completely, and cytosolic free calcium concentration decreased. Superoxide dismutase combined with catalase or nifedipine allowed the hepatocytes to maintain their viability and suppressed cytosolic free calcium concentration elevation. Calpeptin, a Ca(2+)-dependent neutral protease inhibitor, did not affect the rise in cytosolic free calcium concentration but prevented cell injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Systemic production of interleukin-6 following acute inflammation.

The present study was designed to evaluate whether IL-6 is produced locally or systemically following acute inflammation. Full-thickness scale burns were made on rats. Serum IL-6 levels (SIL-6) showed a constant time-dependent change with a single peak 6 hours after the burn. SIL-6 elevation was correlated with the ratio of burn area to total body surface area. The liver, spleen, lymph node and skin harvested after the burn secreted significantly higher amounts of IL-6 after tissue culture when compared with those taken from sham rats. The venous serum drainage from the burn site induced significantly higher IL-6 production of splenocytes than the arterial and control venous sera. In conclusion, IL-6 production is rapidly and systemically triggered by a humoral factor following acute inflammation in vivo, resulting in constant kinetics for SIL-6.

Animals↗
PubMed1993

Specific expression of the pancreatic-secretory-trypsin-inhibitor (PSTI) gene in hepatocellular carcinoma.

Twenty hepatocellular carcinomas (HCC) were analyzed by Northern blotting to test the expression of pancreatic secretory trypsin inhibitor (PSTI). This gene was expressed in all HCCs, but not in other tumors, including mammary, thyroid, pulmonary and ovarian cancers. Some gastric and colonic cancers weakly expressed PSTI. Among cell lines examined in a similar manner, PSTI was expressed in all of 4 derived from hepatoma. On the other hand, among 15 cell lines derived from cancers other than hepatoma, only 3, derived from pancreatic, colonic and gastric cancers, weakly expressed PSTI. A CAT assay using a deletion set of the 5' region from the cloned PSTI gene has shown that in hepatoma cell lines, the expression of this gene is dependent on the presence of 2 regulatory regions that include an IL-6 responsive elements and an AP-I-binding site. However, in non-hepatoma cell lines, the 2 regulatory regions are not necessary for expression. The blood level of PSTI in 27 patients with HCC was significantly increased, and it was positively correlated with tumor size, suggesting that specific expression of PSTI in HCC causes this effect and that elevated blood level of PSTI without inflammation indicates the presence of HCC.

Adult↗
PubMed1993

Frequent multiplication of the long arm of chromosome 8 in hepatocellular carcinoma.

Frequent allelic losses at loci on several chromosomes have been detected in human hepatocellular carcinomas, but other types of chromosomal abnormalities have not been characterized well. Using eight polymorphic DNA markers on chromosome 8, we examined 120 primary hepatocellular carcinomas for abnormalities in the copy number of these loci in tumor cells. A 2- to 6-fold increase in intensities of bands representing single alleles was observed in 32 of the 78 tumors that were informative for one or more of the markers, indicating an increase in copy number ("multiplication") of alleles on 8q. The regions that multiplied varied from almost the entire long arm to a distal segment of chromosome 8, but a terminal region distal to 8q24.11 was multiplied in all 32 cases. Similar multiplications on 8q were detected in nine of 56 colorectal carcinomas that were informative for one or more of the markers. Our study demonstrated that polymorphic DNA markers can be used to detect numerical abnormalities of chromosomal material in solid tumors in which cytogenetic analysis is technically difficult.

Alleles↗
PubMed1993

Allelic loss at chromosome band 8p21.3-p22 is associated with progression of hepatocellular carcinoma.

Human hepatocellular carcinomas (HCC) frequently show loss of heterozygosity at loci on the short arm of chromosome 8. To define a region on 8p commonly deleted in HCC, we used 20 restriction fragment length polymorphism markers to carry out detailed deletion mapping in 142 HCC. Of the 124 informative cases, 56 (45%) showed allelic losses in tumors. While more than half of them had lost alleles at every locus on the short arm, others lost them partially or interstitially. Common deletion of an 8-cM region flanked by cMSR-32 and cC18-245, at 8p21.3-p22, suggested the presence of a tumor suppressor gene(s) in this interval. Correlation between allelic losses on 8p and clinicopathological parameters were examined in the 51 cases for which detailed clinical data were available; allelic losses on 8p were observed in none of five tumors at stage T1 (0%), nine of 20 tumors at stage T2 (45%), and 17 of 26 tumors at stage T3/T4 (65%). A higher frequency of allelic losses on 8p was observed in poorly differentiated tumors (10/14, 71%) than in well differentiated tumors (3/13, 23%). The association of allelic losses on 8p with advanced clinical stage and poor differentiation implies that loss or inactivation of a tumor suppressor gene(s) on 8p may play a role in the progression of HCC.

Carcinoma, Hepatocellular↗
PubMed1993

Serum interleukin-6 levels as an indicator of acute rejection after liver transplantation in cynomologous monkeys.

This study was designed to evaluate whether the sequential monitoring of serum interleukin-6 levels (SIL-6) could be helpful for diagnosing the occurrence of hepatic allograft rejection. An SIL-6 post-transplant study was conducted on nine cynomolgus monkeys which had undergone orthotopic hepatic allotransplantation, six of which were treated with FK-506 (a new immunosuppressant agent isolated from Streptomyces tsukubaensis) and three of which were not. All the nontreated animals showed biochemical abnormalities from days 5-6, characterized by a marked elevation of serum alkaline phosphatase levels, and they eventually died on days 8, 12, and 63 (group I). Acute cellular rejection was confirmed by histological study of the hepatic grafts taken at autopsy or biopsy. On the other hand, four of the treated animals (group IIa) survived more than 30 days. Biochemical examination of this group showed no abnormal signs apart from a slight elevation of alkaline phosphatase (< 2000 IU/l). Histological examination carried out around 30 days after transplantation revealed a transient infiltration of polynuclear cells into Glisson's area, with the portal vein and bile duct remaining intact. The remaining two animals (group IIb) died of dehydration and arterial thrombosis on days 5 and 7, respectively. A kinetic study of SIL-6 conducted during the first 2 weeks showed quite different patterns among the three groups. All recipients in group I demonstrated two peaks following grafting on days 1 and 3 or 4, the second peak of above 2.0 U/ml preceding biochemical abnormalities by 2 to 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

Induction of unresponsiveness in rats after either intraportal injection of donor antigen or intravenous injection combined with splenectomy.

Recently, we reported that hepatic allografts are permanently accepted when transplanted after intraportal injection (IP) of donor spleen cells (SPCs). The mechanism of this effect was investigated using various protocols for antigen injection. ACI (RT1a) and Buffalo (RT1b) rats were used as donors and recipients, respectively. Experimental groups were divided into the following groups depending on treatment: IP, intravenous injection (IV), splenectomy (Spx), and intravenous injection after splenectomy (IV+Spx). Accumulation of donor antigen in the various organs was examined by injecting 51Cr-labeled SPCs. Cellular and humoral responses after SPC injection was assessed by delayed-type hypersensitivity response and complement-dependent cytotoxicity (CDC) assay. Heterotopic cardiac transplantation and orthotopic hepatic transplantation were performed 10 days after each treatment. The accumulation ratio in the liver was significantly higher in the IP and IV+Spx groups than in the IV group. Delayed-type hypersensitivity responses were lower in the IP and IV+Spx groups than in the IV or Spx groups. The CDC titer 7 days after inoculation was significantly lower in the IP and IV+Spx groups than in the IV group. In order to examine whether the treatment actively suppressed the immune response, the animals were rechallenged with SPCs given intravenously 10 days after the initial injection. Elevation of CDC titer was suppressed in the IP and IV+Spx groups, but not in the IV and Spx groups. Significant prolongation of cardiac allograft survival was not observed in the IV and Spx groups. Prolongation was observed in the IP and IV+Spx groups. The survival of hepatic allografts in the IV group was decreased. No significant prolongation of graft survival was observed in the Spx group. In contrast, all hepatic allotransplants in the IP and IV+Spx groups survived over 45 days. These findings suggest that the accumulation of donor SPCs in the liver may play an important role in inducing unresponsiveness after intraportal injection of donor SPCs.

Animals↗
PubMed1993

Treatment of hepatocellular carcinoma by chemoembolization: evaluation with 3DFT MR imaging.

OBJECTIVE: We evaluated the usefulness of an MR imaging technique that used dynamic three-dimensional Fourier transformation (3DFT) fast imaging with steady-state precession (FISP) with gadopentetate dimeglumine for detecting viable regions of hepatocellular carcinoma following transcatheter arterial chemoembolization with iodized oil (Lipiodol). Images obtained with the 3DFT FISP technique were directly correlated with hepatectomy specimens. SUBJECTS AND METHODS: Dynamic 3DFT FISP MR imaging was performed after transcatheter arterial chemoembolization and before partial hepatectomy in 10 patients with 10 tumors of hepatocellular carcinoma. Imaging parameters were 20/8/30 degrees (TR/TE/flip angle) with a slab thickness of 21-75 mm and seven or 15 partitions. 3DFT FISP images were obtained at the slice level where a tumor had been detected on T1- and/or T2-weighted spin-echo MR images before, just after (early phase), and 1 and 2 min after (late phase) IV administration of gadopentetate dimeglumine (0.1 mmol/kg). We directly compared the dynamic MR images of the 10 patients with the gross and microscopic findings. RESULTS: On early-phase images, tumors of hepatocellular carcinoma showed no enhancement in three patients and partial intense enhancement in seven. Viable regions of the tumor showed intense enhancement relative to the surrounding liver parenchyma in the early phase, whereas necrotic regions showed no enhancement in either the early or the late phase. Both viable and necrotic regions had lower signal intensities than did the surrounding liver parenchyma in the late phase. By using dynamic 3DFT MR imaging, we were able to accurately assess the effect of transcatheter arterial chemoembolization with iodized oil in nine of the 10 patients. However, in one patient in whom microscopically viable cells were seen in the capsule of the carcinoma, viable regions could not be detected with our technique. CONCLUSION: Dynamic 3DFT MR imaging was useful in differentiating viable regions of hepatocellular carcinoma from necrotic regions following transcatheter arterial chemoembolization with iodized oil.

Aged↗