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Biomedical subjects

M Ohhira

Publications and source records attributed to M Ohhira.

At least 55 records · Page 3Linked to original sources

Inconsistent expression of glycolipid sulfotransferase activity between hepatoma and serum.

Glycolipid sulfotransferase activity in human and rat hepatocellular carcinoma tissues was studied, since an elevated level of the enzyme activity in serum had been demonstrated in cancer patients. The level of the enzyme activity in carcinoma tissues, however, could not be distinguished from that of normal controls. Similar observations were made for rat hepatoma. A higher level of enzyme activity was observed in the female than in the male. Inconsistent expression between hepatoma tissue and serum suggests that humoral factor(s) derived from hepatoma tissue stimulates production of the sulfotransferase, which is released into the blood-stream in the host.

Animals↗

Physiological activities of S-(1,2-dicarboxyethyl)glutathione as an intrinsic tripeptide present in liver, heart and lens.

S-(1,2-Dicarboxyethyl)glutathione (DCE-GS, CAS 1115-52-2) found in rat liver, heart and lens in considerable amounts, showed an anti-inflammatory effect, which was evaluated by testing the inhibition of the experimental conjunctival edema of rats. An intravenous injection (3 mg/kg) prior to the carrageenan injection prevented the conjunctive edema formation by up to 30%. This peptide also inhibited the histamine release from rat mast cells induced by the compound 48/80. The peptide was added to the mast cells before addition of the compound 48/80 and an inhibition of the histamine release up to 96% at a 1 mmol/l concentration occurred. Furthermore, it displayed an antianaphylactic effect in rats using antibody against chicken egg albumin. An injection of the peptide (30 mg/kg) prior to the antigen administration inhibited color deposition up to 43%. Analogues or derivatives of DCE-GS were synthesized and tested for those inhibitory activities. However, there was no other peptide having stronger effects than DCE-GS and little structure-activity relationship among them.

Animals↗

Elevated carbohydrate phosphotransferase activity in human hepatoma and phosphorylation of cathepsin D.

To determine the cause of the increased content of carbohydrate-bound phosphate in tumour lysosomal hydrolases, the activity and kinetics in human hepatocellular carcinoma of two enzymes involved in the formation of mannose-6-phosphate in lysosomal hydrolases UDP-GlcNAc: lysosomal enzyme GlcNAc alpha l-phosphotransferase (GlcNAc-phosphotransferase) and phosphodiester glycosidase were studied. The activity level of the phosphotransferase with artificial and natural substrates was elevated (P less than 0.025 and P less than 0.001, respectively) in hepatoma compared to that in uninvolved tissue, while the phosphodiester glycosidase of hepatoma was at a level similar to that of the uninvolved tissue. To verify a previous observation that cathepsin D of human hepatoma contained increased GlcNAc-phosphomannose, the protease was examined for carbohydrate phosphorylation by the GlcNAc-phosphotransferase. The protease from normal human liver was much more phosphorylated than hepatoma protease, confirming the previous observation. The predominant phosphorylation of the protease occurred in one of two major heavy subunits, with some phosphorylation in one of two minor light subunits.

Adenocarcinoma↗

Detection of PIVKA II produced by human hepatoma cells in nude mice.

A novel experimental nude mouse model, which is useful for investigation of the mechanisms of PIVKA II synthesis, was established by inoculation with PIVKA II-producing human hepatoma cells (huH-1). We have found markedly elevated levels of PIVKA II in the plasma of nude mice transplanted with huH-1 cells and increased PIVKA II content in huH-1 tumor tissues. Whereas we have not found detectable level of PIVKA II neither in the plasma nor in tumor tissues of nude mice transplanted different human hepatoma cells (HLF) which is not producing PIVKA II. Histology of the tumor tissues produced by huH-1 cells revealed a thick trabecular pattern with blood spaces.

Animals↗

Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis.

Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-SOD level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity, alanine aminotransferase activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-SOD was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-SOD may play some role in a protection against the superoxide anion.

Adult↗

[A successful report of emergency CABG for severe calcified thoracic aorta--the porcelain aorta].

The best management for patients requiring CABG with severe calcification of the thoracic aorta has not be established. To clamp ascending aorta in such cases produce cerebral embolization, aortic dissection or mural laceration. We reported a 60-year-old male for unstable angina with LMT lesion. Emergency CABG using IABP was performed with femoral cannulation, moderate hypothermia and induced ventricular fibrillation. His postoperative course was uneventful and coronary arteriography revealed a satisfactory patent graft of the RITA to the LAD system.

Aorta, Thoracic↗

[Successful report of total aortic root replacement by a new technique].

We employed a new procedure of the total aortic replacement in 2 cases which is made of composite graft and reimplantation of the coronary arteries by direct suture technique. These patients took good clinical course and were discharged after operation. We believe that this procedure is a very useful for annuloaortic ectasia or dissecting aortic aneurysm involved coronary artery with aortic regurgitation.

Aged↗

[A case of type B chronic hepatitis showing rapid progression to liver cirrhosis with prolonged positive IgM anti-HBc].

We reported a case of type B chronic hepatitis with high titer of IgM anti-HBc continuously, which progressed to liver cirrhosis rapidly. The patient was a 37-years-old man, and was diagnosed as chronic type B hepatitis with severe activity by laparoscopy and liver biopsy. The titer of IgM anti-HBc persisted high level for more than 2 years. Then the second liver biopsy showed the progression to liver cirrhosis within only about 2 years. It is a very rare case to prolong positive IgM anti-HBc for such a long time. Anti-HBc production of PBMC was enhanced remarkably in this case. We considered that HBc antigens released into serum from hepatocytes with severe exacerbations had enhanced the anti-HBc producing activity of B lymphocytes. And the rapid progression in this case would be due to the episodes of severe exacerbations.

Adult↗

A new anticancer drug delivery system for the management of carcinomatous peritonitis.

To develop a new drug delivery system for the treatment of carcinomatous peritonitis, we constructed 5-fluorouracil poly L-microcapsules (5Fu-mc) by the organic phase separation technique and examined their drug-releasing capacities and anticancer effects. The microcapsules consisted of in vitro dissolvable polymolecular poly L-lactic acid and 5-fluorouracil (5Fu). The 5Fu-mc was about 200 microns in diameter and had a 5Fu content of about 40% (weight/weight). 5Fu-release time from the microcapsules was about 50 hours in vitro and about 48 hours in vivo. After the release of the 5Fu, the poly L-lactic acid was metabolized very slowly in the peritoneal cavity. The 5Fu-mc caused fewer side effects than the equivalent dose of a 5Fu solution. In addition, macroscopic and microscopic examinations of various abdominal organs revealed no toxic effects from the microcapsules. After administration of 5Fu-mc into the abdominal cavity of rats with AH-130 carcinomatous peritonitis, the 5Fu concentration remained at a high level for an extended period in the ascites but fell rapidly to low levels in the plasma. In conclusion, the present studies indicated that the 5Fu-mc were much more effective in prolonging the life of tumor-bearing hosts while producing less systemic side effects than a 5Fu solution.

Alanine Transaminase↗

Measurement of immunoreactive prothrombin precursor and vitamin-K-dependent gamma-carboxylation in human hepatocellular carcinoma tissues: decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxyprothrombin synthesis.

Des-gamma-carboxyprothrombin is an abnormal prothrombin which is drastically increased in the plasma of patients with hepatocellular carcinoma. To investigate the process of the abnormal prothrombin synthesis, the amount of prothrombin precursor was measured with an enzyme-linked immunosorbent assay using a specific antibody directed to human prothrombin; the vitamin-K-dependent gamma-carboxylation of prothrombin precursor was determined in human liver tissues. The tissue content of prothrombin precursor was increased in hepatoma tissues compared with noncancerous liver tissues, while the vitamin-K-dependent carboxylation of prothrombin precursor was markedly decreased in hepatoma tissues of the patients with increased plasma des-gamma-carboxyprothrombin. The present study indicates that in hepatocellular carcinoma an increase in prothrombin precursor concentration does not induce vitamin-K-dependent carboxylase activity, which is ordinarily observed in normal liver; probably an overproduction of prothrombin precursor with reduced gamma-carboxylation causes an increase in plasma des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma.

Adult↗

Measurement of immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma.

Des-gamma-carboxy prothrombin is an abnormal prothrombin which increases in the plasma of patients with hepatocellular carcinoma. To clarify the process of des-gamma-carboxy prothrombin synthesis, immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K (phylloquinone and menaquinone) concentrations were determined in human liver tissue, including hepatocellular carcinoma. In the patients with elevated plasma des-gamma-carboxy prothrombin levels, both immunoreactive prothrombin and des-gamma-carboxy prothrombin significantly increased in hepatoma tissues compared with non-cancerous liver tissue. On the other hand, no significant difference was observed in the endogenous vitamin K (K1, MK-4, MK7) concentrations between hepatoma and noncancerous portions, in either the cases with or without increase of plasma des-gamma-carboxy prothrombin. These data strongly suggested that in the patients with an increase of plasma des-gamma-carboxy prothrombin, overproduction of prothrombin in hepatoma plays in important role in the synthesis of des-gamma-carboxy prothrombin.

Analysis of Variance↗

[Carbohydrate phosphotransferase in human hepatoma and phosphorylation of cathepsin D].

Two enzymes (N-acetylglucosamine-1-phosphotransferase and phosphodiester glycosidase) involved in formation of mannose-6-phosphate at lysosomal hydrolases were studied for the activity and kinetics in human hepatocellular carcinoma. The activity level of the phosphotransferase with an artificial substrate was elevated (p less than 0.025) in hepatoma compared to that in normal liver, while the phosphodiester glycosidase of hepatoma was in a similar level with that of control. The elevation was more remarkable with a physiological substrate, cathepsin D. (P less than 0.001). Since cathepsin D from normal liver was previously demonstrated to contain less phosphomannose compared to the hepatoma protease, the protease was investigated for carbohydrate phosphorylation by the phosphotransferase. The liver protease was much more phosphorylated than the hepatoma protease, endorsing the previous observation. The predominant phosphorylation of the protease occurred in heavy subunit.

Carcinoma, Hepatocellular↗

[A successful one stage treatment in angina pectoris and intermittent claudication of both legs].

A successful surgical case of concomitant aorto-coronary bypass grafting and aorto-right iliac, left femoral bypass grafting was presented. A sixty-two years old male admitted to our institution with complaints of angina pectoris and intermittent claudication of both legs who had a history of acute inferior myocardial infarction for which emergency percutaneous coronary balloon dilatation was carried out prior to this admission. In this admission, he was found out to have diabetes mellitus moreover and he hoped to have one staged operation for two different type of the disease. After general anesthesia, at first, aorto-right coronary bypass grafting with saphenous vein graft was carried out under cardio-pulmonary bypass, then aorto-right iliac, left femoral bypass grafting with a dacron bifurcated graft was made only with one time of systemic heparinization. His postoperative course was uneventful and discharged in good condition. We conclude that simultaneous aorto-coronary bypass and revascularization of both legs can be done with minimal risk.

Angina Pectoris↗

[Surgical treatment of the prosthetic valves in reoperation].

Surgical treatment and problems in patients required reoperation for malfunctioning prosthetic valves are reviewed in our institute. The cinefluoroscopy and pulse doppler echocardiography were helpful for diagnosis of artificial valve dysfunction. In recent two decades valve replacement were performed in 382 cases and number of re-implanted valve were 469. Among them the cases of reoperation were 21 and reimplanted valves were 25 (5.6%); 4.7% in aortic, 5.0% in mitral, 6.7% in tricuspid position. Three cases of those patients had three operations. Main causes of reoperation were primary tissue failure in Carpentier-Edwards porcine xenograft (6 cases, 23%) and cloth wear in Starr-Edwards ball valve (9 cases, 38%) and thrombosis in St. Jude Medical bi-leaflet valve (3 cases, 15%). In most cases St. Jude Medical valve were chosen for the alternative prosthetic valve in reoperation. We applied IABP support to seven patients for severe low cardiac output syndrome after the operation and overall mortality was 24% in reoperation. It concluded that St. Jude Medical valve may be most reliable because of low incidence of postoperative complication in our institute.

Adult↗

[Left ventricular performance before and after left ventriculotomy and removal of a left ventricular aneurysm].

The effects of left ventriculotomy on left ventricular performance were studied in seven patients with ventricular tachyarrhythmia (VT) and nine patients with left ventricular aneurysm (LVA). Hemodynamic and left ventriculographic findings were evaluated before and after operations. In VT the non-contracting areas, measured at end-diastole, as mean 10.8 +/- 7.1% of the left ventricular internal surface area. There was no significant fall in left ventricular ejection fractions (EF), cardiac indexes (CI) and left ventricular end-diastolic volume indexes (LVEDVI) after left ventriculotomy. In LVA, the non-contracting areas decreased from 31.0 +/- 7.4% to 13.7 +/- 13.5% (p less than 0.01) in association with a reflex decrease in LVEDVI from 117 +/- 31.8 ml/m2 to 90.4 +/- 24.7 ml/m2 (p less than 0.05). EF increased from 40.8 +/- 7.00% to 54.6 +/- 10.7% (p less than 0.01). There was no significant change in CI and left ventricular stroke volume index after left ventricular aneurysmectomy. The observations indicate that left ventriculotomy of limited size is an acceptable and a safety approach to the ventricular tachyarrhythmias and another cardiac operations.

Adolescent↗