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T Shimamura

Publications and source records attributed to T Shimamura.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Clinicopathological study on early recurrent hepatoma and its treatment].

Early Recurrence of Hepatoma: PCNA Labeling Index and DNA Ploidy Pattern Sixty-four cases of recurrent hepatocellular carcinoma (HCC) after hepatectomy were divided into two groups; E-group with recurrence within one year, and L-group with recurrence after 1 year. Clinicopathological features and surgical curability were the same in both groups. E-group had significantly higher positive rates of portal invasion, intrahepatic metastasis and rate of patients with more than 40% on PCNA labeling index. While the similar recurrence mode and the same treatment modalities were done, cumulative survival rates after recurrence in E-group had a poorer prognosis than L-group. These results suggest the possibility of lower response for the treatment on the recurrent lesion would be manifest in the E-group. New modalities for prevention of early recurrence of HCC after resection should be developed.

Aged↗
PubMed1997

Attenuation of ischemic liver injury by monoclonal anti-endothelin antibody, AwETN40.

BACKGROUND: Enhanced production of endothelin-1 (ET-1), vasoconstrictive 21 amino acids produced by endothelial cells during ischemia and after reperfusion of the liver, is known to cause sinusoidal constriction and microcirculatory disturbances, which lead to severe tissue damage. Using a 2-hour hepatic vascular exclusion model in dogs, we tested our hypothesis that neutralization of ET-1 by monoclonal anti-ET-1 and anti-ET-2 antibody (AwETN40) abates vascular dysfunction and ameliorates ischemia/reperfusion injury of the liver. STUDY DESIGN: After skeletonization, the liver was made totally ischemic by cross-clamping the portal vein, the hepatic artery, and the vena cava (above and below the liver). Veno-venous bypass was used to decompress splanchnic and inferior systemic congestion. AwETN40, 5 mg/kg, was administered intravenously 10 minutes before ischemia (treatment group, n = 5). Nontreated animals were used as controls (control group, n = 10). Animal survival, hepatic tissue blood flow, liver function tests, total bile acid, high-energy phosphate, ET-1 levels, and liver histopathology were studied. RESULTS: Treatment with AwETN40 improved 2-week animal survival from 30% to 100%. Hepatic tissue blood flow after reperfusion was significantly higher in the treatment group. The treatment significantly attenuated liver enzyme release, total bile acid, and changes in adenine nucleotides. Immunoreactive ET-1 levels in the hepatic venous blood of the control group showed a significant increase and remained high for up to 24 hours after reperfusion. Histopathologic alterations were significantly lessened in the treatment group. CONCLUSIONS: These results indicate that ET-1 is involved in ischemia/reperfusion injury of the liver, which can be ameliorated by the monoclonal anti-ET-1 and anti-ET-2 antibody AwETN40.

Animals↗
PubMed1997

Anti-inflammatory cytokine levels in patients with septic shock.

We measured the plasma levels of anti-inflammatory cytokines, including interleukin 1 receptor antagonist (IL-1ra), IL-4 and IL-10; inflammatory cytokines, including IL-2, IL-6, IL-8 and tumor necrosis factor receptor I and II (TNFR I and TNFR II); and endotoxin in 11 patients with septic shock associated with gram-negative bacteria and 12 patients with sepsis not associated with shock. The plasma levels of IL-1ra and IL-10 were elevated in the septic shock group compared with the sepsis group. TNFR I and TNFR II levels tend to be higher in the septic shock group. The plasma level of TRNF-alpha was significantly correlated with levels of IL-1ra, IL-4, IL-10, TNFR I, and TNFR II. The elevated levels of the anti-inflammatory cytokines, TNFR I, and TNFR II, appeared to reflect an attempt to suppress the shock syndrome.

Adult↗
PubMed1996

ICAM-1 expression on cardiac myocytes and aortic endothelial cells via their specific endothelin receptor subtype.

Endothelin-1 (ET-1) and Endothelin-3 (ET-3) increased the expression of intercellular adhesion molecule-1 (ICAM-1) on rat neonatal cultured cardiac myocytes and rat aortic endothelial cells. ET-1-induced ICAM-1 expression on cardiac myocytes was inhibited by a selective ETA receptor antagonist, S-0139, but not by a selective ETB receptor antagonist, BQ788. ET-3-induced ICAM-1 expression on endothelial cells was inhibited by BQ788 but not by S-0139. Protein kinase C (PKC) inhibitor staurosporine inhibited ETs-induced ICAM-1 expression on both cell types. Treatment of the cells with ETs increased neutrophil adhesion, which was inhibited by S-0139 and staurosporine on cardiac myocytes and by BQ788 and staurosporine on endothelial cells. These results suggest that ETs induce neutrophil adhesion to cardiac myocytes and aortic endothelial cells by increasing ICAM-1 expression, which mediate via ETA receptor on cardiac myocytes and via ETB receptor on aortic endothelial cells. ICAM-1 expression induced by activation of ETA and ETB receptors appears to be mediated through the PKC pathway.

Animals↗
PubMed1996

Down-regulation by IL-4 and up-regulation by IFN-gamma of mast cell induction from mouse spleen cells.

While investigating an involvement of other factors aside from endogenous IL-3 and prostaglandin E (PGE) in mast cell induction from mouse splenocytes, we found that the mast cell induction was inversely proportional to IL-4 levels and tended to directly proportionate IFN-gamma levels in the supernatants recovered on days 2 and 4. Thereafter, we examined the effects of rIFN-gamma, rIL-4, and rIL-10 on mast cell induction. IFN-gamma and IL-10 dose-dependently induced mast cells. Time course study showed an importance of adding rIFN-gamma into the cultures at the early phase (on days 0 and 2 of a 12-day culture). When endogenous IFN-gamma at the early phase was neutralized by anti-IFN-gamma Ab, all stimulants, including rIFN-gamma, rIL-10, and PGE1, failed to induce mast cells. On the contrary, rIL-4 dose-dependently suppressed the mast cell induction by rIFN-gamma, rIL-10, LPS, PGE, and dibutyryl cAMP. The inhibitory effect of IL-4 was observed when IL-4 was added into the cultures at the early phase, but not after day 4. The suppressive action of IL-4 was diminished completely by the addition of neutralizing anti-IL-4 Ab. IL-12, a key regulator of IFN-gamma and IL-4 production, also induced mast cells. These results revealed, for the first time, that IFN-gamma is crucial for the survival and/or differentiation of splenic mast cell precursors and that IL-4 is a key inhibitor for the precursors, although IFN-gamma is not a mast cell growth factor and IL-4 is a growth factor for immature and mature mast cells.

Animals↗
PubMed1996

Sensitive enzyme-linked immunosorbent assay for adult T-cell leukemia-derived factor and normal value measurement.

Four different monoclonal antibodies against recombinant adult T-cell leukemia-derived factor (ADF), identical to thioredoxin, were established and used for the determination of ADF concentration in serum. Using two of the monoclonal antibodies, we developed a two-step enzyme-linked immunosorbent assay (ELISA) for ADF. This ELISA showed a highly specific reactivity on ADF with no cross-reactivity to several proteins with homologue sequence on the active center. The detection limit of the assay was 2.0 ng/ml (mean +/- 2 SD). The intra- and interassay coefficients of variation (CV) were 0.81-3.74% (n = 8) and 4.78-6.97% (n = 7), respectively. The normal value of ADF mean concentration from 145 healthy donors was 40.8 ng/ml.

Adult↗
PubMed1996

Evaluation of surgical resection for small hepatocellular carcinomas.

BACKGROUND: The surgical results for small hepatocellular carcinomas (HCCs) are not necessarily satisfactory. The resectional therapy for small HCC was evaluated to elucidate its benefits and limitations. PATIENTS AND METHODS: Data were analyzed concerning 52 patients having small HCC of <3 cm in diameter and <3 nodules, who underwent hepatic resections from 1978 to 1989. RESULTS: Cumulative and disease-free survival at 5 years after resection were 57% and 37%, respectively. Histologic features, such as differentiation of HCCs, pseudocapsular invasion, and ploidy pattern of nuclear DNA, appeared to be good prognostic indicators. The survival rate of the large-resection group (number of resected segments greater than number of tumor-occupying segments) was significantly better than that in the small-resection group (84% versus 48% at 5 years, P<0.05). CONCLUSIONS: Surgical resection of small HCCs is a safe and effective therapy. A large resection appears to provide better patient survival and tumor-free survival compared to a small resection.

Adult↗
PubMed1996

Interleukin (IL)-12 deficiency in susceptible mice infected with Mycobacterium avium and amelioration of established infection by IL-12 replacement therapy.

Mycobacterium avium is an intracellular microorganism that infects and multiplies within macrophages. Cell-mediated immunity plays an important role in host defense, and interleukin (IL)-12, which is produced mainly by macrophages, is critical for its development. In a mouse model of disseminated M. avium infection, genetically susceptible BALB/c mice had increased mycobacterial growth and decreased IL-12 expression and developed large and numerous granulomas. In contrast, resistant DBA/2 mice exhibited reduced mycobacterial burden with increased IL-12 expression and developed fewer and smaller granulomas. In susceptible mice with established M. avium infection, IL-12 replacement therapy resulted in persistent reduction of mycobacterial burdens. IL-12 itself, however, could not inhibit mycobacterial growth in vitro. By enhancing host defenses, IL-12 exerts a potent mycobactericidal activity in vivo with low toxicity. This suggests that IL-12 replacement therapy is rational for M. avium infection in susceptible hosts.

Animals↗
PubMed1996

A pharmacological pilot study: application of an intermittent schedule of oral uracil and ftorafur (UFT) for hepatocellular carcinoma patients.

Patients with hepatocellular carcinoma (HCC) are highly compromised by failing liver function. To retain good compliance in the administration of uracil and ftorafur (UFT) in such patients, an intermittent schedule for oral administration of UFT was expected to have the same effect as daily continuous use without affecting liver function. A pharmacological pilot study was carried out to confirm the efficacy of this schedule. Sixteen patients with HCC who underwent hepatectomy were given UFT 200 mg b.i.d. for five consecutive days. Blood samples were drawn before the last administration of UFT and at the operation (2 days after the last administration of UFT), and the tumor and adjacent liver tissue were collected. The concentration of ftorafur (FT), 5-fluorouracil (FUra) and uracil (Ura) in serum and liver tissue were measured. Oral administration of UFT 200 mg b.i.d. resulted in a trough level of FT, FUra and Ura in serum of 9.4 micrograms/ml, 13.3 ng/ml and 64.2 ng/ml, respectively. At the operation, FT and FUra in serum had decreased significantly. However, FUra in tissue was still higher than that in serum, in contrast to the results for FT and Ura. There was no difference in the concentration of FUra between the tumors and adjacent liver tissues. No side effect was noted in any of the patients. These results indicated that an intermittent schedule for the administration of oral UFT is not only tolerable but also effective because a sufficient concentration of FUra in the liver tissue is reached and maintained.

Adult↗
PubMed1996

Pharmacological studies on a new antihypertensive agent, S-2150, a benzothiazepine derivative: 2. Hypotensive effects in normotensive and hypertensive rats.

S-2150 is a new 1,5-benzothiazepine derivative possessing both calcium channel-blocking and alpha 1-adrenoceptor-blocking effects. In isolated rat thoracic aorta precontracted with KCl (18 mM), the 50% inhibitory concentration (IC50) value was 190 nM for S-2150, which was similar to that of diltiazem. In aorta precontracted with phenylephrine (0.3 microM), IC50 values of S-2150 and diltiazem were 29 nM and > 10 microM, respectively. The relative contribution of calcium channel-blocking and alpha 1-adrenoceptor-blocking activities to hypotension was determined by using anesthetized rats before and after masking of the alpha 1-receptors with prazosin. The hypotensive effect of S-2150 [0.3 and 1 mg/kg intravenously (i.v.)] was attenuated by 40% after prazosin treatment, whereas that of diltiazem was not. In conscious spontaneously hypertensive rats (SHRs), renal hypertensive rats, and normotensive rats, S-2150 [10, 30, and 60 mg/kg orally (p.o.)] caused dose-dependent hypotensive effects. The effect of S-2150 was 4-7 times more potent than that of diltiazem. There were no changes in the hypotensive effects with consecutive administration of S-2150 during 6-8 weeks in SHRs and stroke-prone SHRs (SHRSPs). In SHRSPs, S-2150 reduced the mortality by stroke and small arterial hyperplasia in abdominal organs and also ameliorated renal excretory function. These results suggest that S-2150 may be a useful antihypertensive agent possessing both calcium-antagonistic and alpha 1-adrenoceptor-blocking effects.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1996

Mechanism of membrane damage by El Tor hemolysin of Vibrio cholerae O1.

El Tor hemolysin (ETH; molecular mass, 65 kDa) derived from Vibrio cholerae O1 spontaneously assembled oligomeric aggregates on the membranes of rabbit erythrocyte ghosts and liposomes. Membrane-associated oligomers were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting into two to nine bands with apparent molecular masses of 170 to 350 kDa. ETH assembled oligomers on a liposomal membrane consisting of phosphatidylcholine and cholesterol, but not on a membrane of phosphatidylcholine alone. Cholesterol could be replaced with diosgenin or ergosterol but not with 5alpha-cholestane-3-one, suggesting that sterol is essential for the oligomerization. The treatment of carboxyfluorescein-encapsulated liposomes with ETH caused a rapid release of carboxyfluorescein into the medium. Because dextrin 20 (molecular mass, 900 Da) osmotically protected ETH-mediated hemolysis, this hemolysis is likely to be caused by pore formation on the membrane. The pore size(s) estimated from osmotic protection assays was in the range of 1.2 to 1.6 nm. The pore formed on a rabbit erythrocyte membrane was confirmed morphologically by electron microscopy. Thus, we provide evidence that ETH damages the target by the assembly of hemolysin oligomers and pore formation on the membrane.

Animals↗
PubMed1996

[Efficacy of intra-arterial chemotherapy with reservoir for patients with unresectable hepatocellular carcinoma].

Long-term results of intra-arterial chemotherapy using a reservoir (IA) for patients with unresectable hepatocellular carcinoma (HCC) were investigated. Ninety-nine patients with unresectable HCC who were treated in our department during the past 7 years were enrolled in this study. Thirty-four out of the 99 patients were treated by IA with a conventional reservoir (SR group), and 21 by IA with a double-lumen reservoir (DR group) by which IA with occlusion of hepatic arterial flow would be possible. The other 44 patients were treated by transcatheter arterial embolization (TAE group). Cumulative 1-and 2-year survival rates were 54.2 and 21.7% in DR group, respectively, and 50.8 and 35.2% in TAE group, respectively. The results of these two groups were statistically equivalent, and were more favorable than those of the SR group. Cumulative patency rate of reservoirs was maintained at 93.7% after one year and at 61.8% after two years. No difference was recognized in this rate according to the type of reservoir. We concluded that IA with a double-lumen reservoir should be taken into consideration as one of the strategies for treatment of unresectable HCC. However, maintenance of catheter-patency would be necessary for satisfactory outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[DNA ploidy pattern in resected human hepatocellular carcinomas from the view point of biological malignant potential].

Nuclear DNA ploidy analysis was studied in patients with hepatocellular carcinoma (HCC) who underwent hepatic resections. These patients were classified three groups according to the following prescriptions. Group A (n = 100) was a group of patients of which excluded ones treated by absolute non-curative resection, Group B (n = 43) was patients who underwent absolute curative resection or relative curative resection, and Group C (n = 81) was patients whose tumor sizes were more than 2 cm in Group A. Aneuploid pattern was found in 59 cases (59.0%) in Group A, 22 cases (51.2%) in Group B and 54 cases (66.7%) in Group C. The rate of aneuploid pattern was significantly higher in patients with carcinomas more than 2 cm in diameter, fc-inf positive growth, Stage III + IV and PCNA LI > or = 40% in Group A, those with carcinomas more than 2 cm in diameter, fc-inf positive growth, im-positive and Stage III + IV in Group B, and those with PCNA LI > or = 40% in Group C. The postoperative prognoses of patients with aneuploid pattern in Group A and Group C were significantly poorer than those of the diploid one in cumulative survival rates and survival rates after recurrence. Patients with aneuploid pattern in Group B had a poorer prognosis than those with diploid one in cumulative survival rates and disease-free survival rates. These results suggest that nuclear DNA ploidy analysis was a useful marker of biological malignant potential in resected human HCCs.

Carcinoma, Hepatocellular↗
PubMed1996

Nitrite/nitrate (NOX) and type II phospholipase A2, leukotriene B4, and platelet-activating factor levels in patients with septic shock.

We measured serum concentrations of nitrite/nitrate (NOX), type II phospholipase A2 (PLA2), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in patients with sepsis. These findings were compared between patients with and without septic shock. Serum concentrations of NOX, type II PLA2, LTB4, and PAF acetylhydrolase (PAF-AH) were significantly higher in the group with septic shock (P < 0.0001; P = 0.0060; P = 0.0052; P = 0.0052), indicating the severity of the disease. There were significant correlations between the serum NOX level and serum levels of type II PLA2, LTB4, and PAF-AH (r = 0.6890, P < 0.0001; r = 0.3755, P = 0.0409; r = 0.5095, P = 0.0040, respectively). It is speculated that LTB4 and PAF, both produced with type II PLA2, interact with each other and are involved in the deterioration of pathologic features associated with sepsis. Furthermore, nitric oxide (NO) and eicosanoids interact to play an important role in vascular dilatation during septic shock.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

Nitrite/nitrate oxide (NOx) and cytokine levels in patients with septic shock.

To investigate the involvement of nitrite/nitrate oxide (NOx) in septic shock, and to evaluate the relationships between NOx and cytokines in patients with this disorder, we evaluated 11 patients with septic shock and 12 patients with sepsis unassociated with shock. NOx were measured with an automated system based on the Griess reaction. The plasma concentrations of various cytokines were determined by enzyme-linked immunosorbent assay. Endotoxin was determined by a specific assay after the plasma samples were processed by a perchloric acid method. The mean plasma levels of NOx in the group with shock significantly exceeded those in the group without shock. Significant correlations were observed between the plasma levels of NOx and those of endotoxin, tumor necrosis factor-alpha, and interleukin 8 in both groups. NOx appeared to be involved in the development of septic shock in humans. Endotoxin and cytokines appeared to be involved in the production of NOx.

Cytokines↗
PubMed1996

Interleukin 11 levels in patients with disseminated intravascular coagulation.

We assessed the blood interleukin 11 (IL-11) levels in patients with disseminated intravascular coagulation (DIC). The IL-11 level exceeded the detection limit, i.e., IL-11 was positive, in 14 of the 21 patients in the group with DIC complicated by sepsis, with a mean value of 20.4 pg/ml. In the group with DIC uncomplicated by infection, IL-11 levels were above the detection limit in 8 of the 17 patients, and the average level was 10.6 pg/ml. The difference between the IL-11-positive rate in the two groups was not significant. Although IL-11 levels tended to be higher in the group with sepsis as a complication, the difference was not significant. The elevated IL-11 levels observed in patients with DIC, with or without complication by infection, seem quite appropriate as a biological response to increased platelets.

Adult↗