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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 253 records · Page 14Linked to original sources
PubMed1994

Clinical significance of serum 2,5-oligoadenylate synthetase and soluble interleukin-2 receptor in hemophiliacs positive and negative for human immunodeficiency virus type 1.

We measured serum 2,5-oligoadenylate synthetase (2,5-AS) levels and soluble interleukin-2 receptor (sIL-2R) levels in human immune deficiency virus type 1 (HIV-1)-positive and HIV-1-negative hemophiliacs in order to clarify the clinical significance of these parameters in hemophiliacs. Serum 2,5-AS levels were measured by a radioimmunosorbent assay, and sIL-2R levels were measured by an enzyme-linked immunosorbent assay. The mean serum 2,5-AS levels were higher in AIDS-related-complex and AIDS patients, asymptomatic carriers, and HIV-1-negative hemophiliacs than in hepatitis C virus-positive patients and healthy controls. Serial determinations showed that the 2,5-AS levels tended to increase in HIV-1-positive patients, especially those with AIDS-related complex or AIDS, although it showed a substantial decrease in the terminal stage. The serum sIL-2R levels were higher in HIV-1-positive patients, HIV-1-negative patients, and hepatitis C virus-positive patients than in controls. Serial studies showed little change in the HIV-1-positive and HIV-1-negative groups, although sIL-2R levels showed a tendency to decrease with zidovudine treatment. On the basis of the present results, we may well conclude that 2,5-AS and sIL-2R are not specific markers for hemophiliacs with HIV-1 infection. However, serial measurement of these markers can still be useful for assessing the progression of AIDS and the prognosis for patients with AIDS, as well as for monitoring the response to zidovudine.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Reappraisal of effective refractory period testing.

To test the hypothesis that effective refractory period (ERP) testing is an accurate and reproducible measure of the cardiac refractory period, 4 pigs and 12 dogs were studied. We define the conventional ERP as the longest S1-S2 interval associated with noncapture and the triplicate ERP as the average of three ERP values determined by the up-down algorithm. We also determined the probability curve for noncapture after testing multiple S1-S2 intervals. The results showed that the difference between the coupling intervals associated with a 0 and a 100% probability of noncapture was 13 +/- 1 (range 12-16) ms for pigs and 9 +/- 2 (range 4-12) ms for dogs. The conventional and the triplicate ERP were associated with a 71 +/- 20% (range 26-100%) and a 60 +/- 21% (range 12-100%) probability of noncapture, respectively. We conclude that the ERP is a probability function. Therefore a single ERP determination cannot be used as an accurate and reproducible measure of cardiac refractory period unless it is used to detect potential differences in ERP that exceed 16 ms in pigs or 12 ms in dogs. A probability function curve determination will be needed if smaller differences in the ERP are to be detected.

Algorithms↗
PubMed1994

Biosynthesis of guanidine in isolated rat hepatocytes, perfused rat liver and intact animals.

Plasma levels of guanidine (G) are reported to be increased in uremic patients and are synthesized from various guanidino compounds via a chemical reaction involving the hydroxyl radical in vitro. To identify both the metabolic precursor and the synthesizing organ of G, we investigated the concentrations of G in various organs of rats administered several guanidino compounds and we attempted to synthesize G biologically using isolated rat hepatocytes or perfused rat liver. In addition, we investigated the effect of the peroxidative state on the G synthesis in isolated hepatocytes using various reagents which alter this condition. Results show that the concentration of G increased in the kidney, liver and muscle following the administration of L-canavanine. In addition, G increased in the kidney at 90 min after the administration of guanidinoacetic acid (GAA). Moreover, G is synthesized from L-canavanine in isolated rat hepatocytes and perfused rat liver, and G synthesis in hepatocytes is partially inhibited by the addition of superoxide dismutase, catalase, glutathione or ethylenediaminetetraacetic acid. These results suggest that L-canavanine is possibly a biological precursor and GAA is an endogenous precursor of G. Furthermore, it is suggested that these reactions are closely related to the peroxidative state.

Animals↗
PubMed1994

Detection of beta-2-glycoprotein-I-dependent antiphospholipid antibodies and anti-beta-2-glycoprotein-I antibody in patients with systemic lupus erythematosus and in patients with syphilis.

We investigated whether or not antiphospholipid antibodies (aPLs; antiphosphadidylserine antibody, aPS; antiphosphatididylinositol antibody, aPI; antiphosphatidic acid antibody, aPA, and antiphosphadidylethanolamine antibody, aPE) were beta 2-glycoprotein-I (GPI)-dependent antibodies like anticardiolipin antibody (aCL) in patients with systemic lupus erythematosus (SLE). None of the patients with syphilis or healthy controls was positive for any GPI-dependent aPL. By contrast, GPI-dependent aCL (40%), aPS (20%), aPI (18%), aPA (12%) and aPE (8%) were detected in patients with SLE. Among these, 4 patients were negative for aCL, but positive for aPS. Those who were positive for more than 2 types of aPL, along with lupus anticoagulant, had a high incidence of arteriovenous thrombosis, fetal loss, thrombocytopenia and biological false-positive reaction to syphilis. From these findings we conclude that GPI-dependent aPLs, other than aCL, are present in patients with SLE, and we should examine more than 2 types of aPL, such as a combination of aCL and aPS, to avoid overlooking aPL. Furthermore, we confirmed that GPI-independent aPL was not rare in SLE patients, but the clinical significance of this type of aPL in this clinical setting is unclear.

Adult↗
PubMed1994

Superoxide scavenging activity in the extracellular space of the brain in forming edema.

We carried out a time course study of cerebral superoxide scavenging activity using a modified microdialysis technique. Twelve cats were divided into two groups; six were the reperfusion injury models, and six were cold injury models. In the reperfusion injury model, dialysates were collected during 60 minutes of middle cerebral artery occlusion and at 300 minutes during reperfusion. In the cold injury model, dialysates were collected 240 minutes after the injury. Regional cerebral blood flow on the injured side decreased during occlusion in the reperfusion injury model and 60 minutes after injury in the cold injury model. In the reperfusion model, superoxide scavenging activity, as determined with electron spin resonance, increased in the first 30 minutes and decreased 300 and 330 minutes after occlusion. In the dialysate, albumin increased 180 minutes after cold injury, which may show the progress of vasogenic edema. An increase in water content was observed on the injured side of both models, and a correlation between water content and superoxide scavenging activity was found in the reperfusion injury model. By this technique, a method of detecting the alteration of superoxide scavenging activity in the extracellular space of the brain was established.

Animals↗
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↗