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Biomedical subjects

T Onodera

Publications and source records attributed to T Onodera.

At least 181 records · Page 10Linked to original sources
PubMed1988

Subacute toxicity of muroctasin in mice and dogs.

The subacute toxicity of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys (L18), muroctasin), a synthetic muramyl dipeptide, was investigated in mice and dogs. Both species exhibited leukocytosis, immunologically activated appearances of the axillary lymphnode and splenic white pulp, and irritatic lesions at the injection site, when treated with MDP-Lys(L18) for 4 weeks. Anemia, and synovitis were also found in dogs. These findings reflected main pharmacological action of MDP-Lys(L18), though there was some species difference.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Chronic toxicity of muroctasin in mice.

The chronic toxicity of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L-18), muroctasin), a synthetic muramyl dipeptide, was investigated in mice. Leukocytosis and immunologically activated appearances of splenic white pulp and lung were seen in mice, when treated with MDP-Lys(L18) for 26 weeks. Furthermore, inflammation around the injection site and synovial epithelium hyperplasia of the tarsal joint occurred in higher incidence in the high dose group. These changes were similar to those seen in the subacute toxicity study with mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Detection of early myocardial infarction in formalin-fixed, paraffin-embedded tissue.

Whether the early infarct area in formalin-fixed, paraffin-embedded tissue could be delineated by the immunohistochemical method using myoglobin-antibody was studied in 23 pig hearts without collateral circulation. Five hearts were examined at 20 minutes, 2 hours, 4 hours, and 6 hours after occlusion of the distal one third of the left anterior descending coronary artery, respectively. Three pigs were killed 24 hours after occlusion. Heart rate and aortic pressure before and after occlusion did not change in any groups. The subepicardial and subendocardial regional blood flows were reduced to almost zero in all hearts after occlusion (0.88 +/- 0.10 to 0.02 +/- 0.02 mL/g/min). Slight myoglobin defects in the ischemic tissue were noted in the five pigs examined 2 hours after occlusion and definite myoglobin defects were detected in all pigs examined at 4, 6, and 24 hours after occlusion. Nitrotetrazorium blue stain of myocardial tissue before formalin fixation showed slight demarcation of the ischemic area at 4 hours after occlusion and definite demarcation at 6 and 24 hours after occlusion. Slight demarcation was noted at 2 hours after occlusion in Masson trichrome stain and 4 hours after occlusion in the hematoxylin-eosin stain. However, definite demarcation of the ischemic area was seen in Masson trichrome stain only at 24 hours after occlusion and was not noted in hematoxylin-eosin stain even at 24 hours after occlusion. Our previous electron microscopic study revealed that, in the pig heart, irreversible cellular damage was transmurally seen at two hours after occlusion of the coronary artery. Therefore, a definite myoglobin defect reflects irreversible cellular damage such as infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Watery diarrhea, hypokalemia, achlorhydria syndrome due to recurrent malignant pheochromocytoma].

A case of malignant pheochromocytoma, with a recurrence 15 years after adrenalectomy and with an associated watery diarrhea, hypokalemia, achlorhydria syndrome, is reported. Histological evaluation of the tumors revealed composite malignant pheochromocytoma-ganglioneuroblastoma (well differentiated type). Vasoactive intestinal polypeptide and catecholamine levels were high both in the plasma and in the tumors. Somatostatin was also rich in the metastatic tumor of the liver, but not in the plasma. Immunohistochemical studies have demonstrated that immunoreactive vasoactive intestinal polypeptide is present in the ganglioneuroblastoma component, and that immunoreactive somatostatin is present in the pheochromocytoma component. Literature on the watery diarrhea, hypokalemia, achlorhydria syndrome associated with pheochromocytoma was reviewed.

Achlorhydria↗
PubMed1987

Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart.

To assess the importance of contraction band necrosis (CBN) in reperfusion, CBN, coagulation necrosis (CN), and infarct size, expressed as CBN + CN, were quantitatively analyzed in 25 porcine hearts without collateral circulation. The left anterior descending coronary artery was ligated for 20, 30, 60, and 120 min and then reperfused for 8 hr (groups 1 to 4, respectively). Five hearts were not reperfused (group 5). The areas of CBN and CN were traced at a magnification of X 100 under an inverted microscope and quantified with use of an image analyzer. There was no change in hemodynamics with either occlusion or reperfusion. Regional myocardial blood flow, measured by the generated hydrogen gas clearance method, decreased to almost zero after occlusion but recovered during reperfusion. Percent of risk area infarcted in groups 1 to 4 was 0 +/- 0%, 11 +/- 7%, 80 +/- 9%, and 96 +/- 2%, respectively, and the percent of risk area infarcted in group 4 was the same as that in hearts subjected to permanent occlusion (95 +/- 3%). The percent area of CBN was 100 +/- 0% in group 2, 68 +/- 11% in group 3, 2 +/- 1% in group 4, and 2 +/- 2% in group 5. In group 3, the inner third of the ischemic left ventricular wall showed CN and the middle and outer third CBN. These findings show that in pig hearts without collateral circulation, the transmural infarct, two-thirds of which is occupied by CBN, is evident even when reperfusion is achieved after 1 hr occlusion. Therefore, protection against CBN might reduce infarct size after reperfusion.

Animals↗
PubMed1987

Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy.

To clarify the pathophysiologic role of intramyocardial small artery (IMSA) diseases in hypertrophied hearts, narrowings of the IMSA were quantitatively evaluated in 39 autopsied hearts, 10 from patients with typical hypertrophic cardiomyopathy (HCM), four from patients with HCM showing features mimicking dilated cardiomyopathy (DCM-like HCM), 10 from patients with hypertension, and 15 from normal adults. The relations of narrowings of the IMSA to myocytic hypertrophy, myocardial fiber disarray, and fibrosis were also examined. The external caliber and the ratio of the luminal area to the total vascular area (percent luminal area, % lumen) were calculated by an image analyzer in 85 to 203 IMSAs from each patient. The external calibers of the IMSAs were similar among groups of hearts with HCM, hypertensive hearts, and normal hearts but were greater in those with DCM-like HCM. The mean % lumen of the IMSAs was similarly reduced in the hearts with HCM (29 +/- 5% in the ventricular septum and 31 +/- 5% in the left ventricular free wall) and in hypertensive hearts (30 +/- 8% and 31 +/- 7%) compared with that in normal hearts (40 +/- 5% and 38 +/- 5%) and was the lowest in the ventricular septum of hearts with DCM-like HCM (17 +/- 3%). The mean % lumen of the IMSA was inversely correlated with heart weight (r = -.59), the mean size of myocytes (r = -.66 in the ventricular septum, r = -.63 in the free wall), and percent fibrotic area in the septum (r = -.68). The mean % lumen values of the IMSAs in the tissues with and without disarray in the hearts with HCM were similar. Thus IMSA disease is of pathophysiologic importance in patients with HCM, DCM-like HCM in particular, or with hypertension.

Adult↗
PubMed1987

Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis.

To assess the importance of contraction band necrosis (CBN) in patients with acute myocardial infarction (AMI) treated with selective intracoronary thrombolysis, CBN, coagulation necrosis, and infarct size (expressed as CBN + coagulation necrosis) were analyzed quantitatively in 16 autopsied hearts. Intracoronary thrombolysis was performed from 2 to 6 hr after the onset of AMI, and the time from the onset of AMI to death was 7 to 168 hr. Cineangiography revealed no evidence of good collateral circulation in any of the patients. The 16 patients were classified into three groups: six patients with successful thrombolysis (100% to 99% stenosis, group I), five patients with unsuccessful thrombolysis (100% to 100%, group II), and five patients with 99% stenosis before thrombolysis (group III). Among the three groups, there were no significant differences in the time from the onset of AMI to thrombolysis, the time from the onset of AMI to death, the cause of death, or the degree of collateral circulation. The percentage of the risk area involved by the infarct in group I (82 +/- 6%) was similar to that in group II (80 +/- 11%). Infarct size was not reduced in group I because collateral circulation was not good and because the degree of recanalization after thrombolysis was 1%. However, the percentage of the infarct area with CBN was significantly higher in group I (20 +/- 9%) then in group II (3 +/- 3%). This finding shows that diffuse CBN occurred after reperfusion in patients with AMI treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Early changes of osteochondrosis in medial femoral condyles from rats.

Osteochondrosis developed from the early growing process of articular cartilage at the caudal-central region of the medial femoral condyle in rats. Articular cartilage was thick at the region. Mineralization of the matrix in the thick deep zone was incomplete and major parts remained unmineralized. Cavity formation in the mineralized matrix resulting in osteochondrotic lesions was present in the deep zone at 6 weeks of age and was followed by an appearance of viable chondrocytes around it. Osteochondrotic lesions were present from the age of 10 weeks for females and 12 weeks for males. Cavities were expanded and increased in number, and eosinophilic necrotic foci were additionally seen. These changes were extended throughout the deep zone, and viable chondrocytes were also increased in number. The thick deep zone was retained and had no detectable invasions of blood vessels from the subchondral bone. At 20 weeks of age, necrotic areas containing large clefts were present in the basal layer of the thick deep zone and fibrotic lesions were seen beneath them. In normal cases, invasions of blood vessels were seen in the basal layer of the deep zone and also in the cavities of the cartilage; the deep zone was markedly thinned at 20 weeks of age.

Aging↗
PubMed1987

Limitation of coronary thrombolysis: experimental study of reperfusion after ischemia.

Contraction band necrosis (CBN), coagulation necrosis (CN) and infarct size, expressed as CBN + CN, were quantitatively analyzed in 15 pig hearts without collateral circulation. The left anterior descending coronary artery was ligated for 60 and 120 minutes and then reperfused for eight hours (group 1 and 2, respectively). Five hearts were not reperfused (group 3). There was no change in hemodynamics with either occlusion or reperfusion. Regional myocardial blood flow, measured by the generated hydrogen gas clearance method, decreased to almost zero after occlusion but recovered during reperfusion. Percent infarct area of the perfused area in group 1, 2 and 3 were 80 +/- 9, 96 +/- 2% and 95 +/- 3%, respectively. The percent area of CBN was 68 +/- 11% in group 1, 2 +/- 1% in group 2 and 2 +/- 2% in group 3. We conclude that in pig hearts without collateral circulation, the transmural infarct, two-thirds of which is occupied by CBN, is evident even in reperfusion following one-hour occlusion. Therefore, in patients with acute myocardial infarction, coronary thrombolysis should be performed within one hour after the onset of the infarction to reduce the infarct size.

Animals↗
PubMed1987

Pathogenetic role of myocardial fiber disarray in the progression of cardiac fibrosis in normal hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy.

To define the pathogenetic role of myocardial fiber disarray in the progression of cardiac fibrosis, the percent area of fibrosis in tissue with disarray was compared with that in tissue without disarray. Thirty autopsied hearts, 10 from patients with hypertrophic cardiomyopathy, 10 from patients with hypertension and 10 from normal adults, were studied. The percent areas of fibrosis in tissues with and without disarray were significantly different (p less than 0.01) among hearts with hypertrophic cardiomyopathy (12.6 +/- 4.0 and 8.2 +/- 3.3%), hypertensive hearts (6.6 +/- 3.6 and 2.5 +/- 1.4%) and normal hearts (2.8 +/- 1.2 and 1.0 +/- 0.4%). The percent area of fibrosis in tissue with disarray was greater than in that without disarray in all 3 groups and the ratios of these percentages were similar in the 3 groups: 2.9 +/- 4.2 in hypertrophic cardiomyopathy 2.5 +/- 1.7 in hypertensive hearts and 2.5 +/- 1.8 in normal hearts. The conclusions are: 1) disarray promotes fibrosis to a similar degree, not only in hypertrophic cardiomyopathy, but also in hypertensive hearts and normal hearts; 2) the increased level of fibrosis in hearts with hypertrophic cardiomyopathy and in hypertensive hearts, together with widespread fibrosis in hearts with hypertrophic cardiomyopathy in particular cannot be explained by disarray alone.

Cardiomegaly↗
PubMed1987

Morphological features of hypertrophic cardiomyopathy with congestive heart failure and a small left ventricular cavity.

To clarify the morphologic basis of marked congestive heart failure in cases of hypertrophic cardiomyopathy with a small left ventricular cavity, the size of myocytes, the extent of myocardial fiber disarray and fibrosis were quantitatively evaluated in two autopsied cases. Compared with the control hypertrophic cardiomyopathy, both cases had larger myocytes and less fibrosis, and one of them had markedly extensive myocardial fiber disarray. Probably, the hypertrophy of the myocytes or myocardial fiber disarray or both rather than myocardial fibrosis are important in the pathogenesis of severe congestive heart failure in these cases.

Adult↗
PubMed1987

Effects of malotilate on rat erythrocytes.

Rats developed anemia during treatment with high doses of malotilate, a hepatotropic agent. A repeated dose of 1,000 mg/kg caused a 20-30% decrease in the number of red blood cells and in hematocrit and hemoglobin values within the first week. In response to the anemia, the reticulocyte count increased, and target cells, acanthocytes and Howell-Jolly bodies appeared in the peripheral blood. In the spleen, hemosiderin deposition was enhanced. The life span of 51Cr-labelled erythrocytes was shortened from 15 to 2 days in the high-dose group, whereas plasma iron disappearance and hemoglobin synthesis were significantly potentiated. Hemorrheological examinations revealed an increase in blood viscosity. Hemolytic resistance to mechanical stimuli was reduced, but that to osmotic stimuli was enhanced. At the same time as the onset of the anemia, serum and red cell membrane cholesterol and phospholipid began to increase on day 4 or 6. Incorporation of cholesterol into red cell membranes in vitro was significantly potentiated when serum obtained from rats after a single administration of 1,000 mg/kg was added to the culture. These results suggest that malotilate causes an increase in the surface area of the erythrocytes by accelerating the incorporation of cholesterol into their membranes, and such erythrocytes might be rheologically impaired and captured more easily by the spleen.

Anemia↗
PubMed1987

Inhibitory effect of L-methionine-deprived amino acid imbalance using total parenteral nutrition on growth of ascites hepatoma in rats.

The antitumor effect of an amino acid imbalance characterized by the absence of L-methionine was investigated in AH-109A ascites hepatoma-bearing rats with the technique of total parenteral nutrition (TPN). A central venous catheter was placed at the superior vena cava of the rat and hypertonic glucose solution plus an amino acid mixture, an ordinary amino acid compound but lacking L-methionine and L-cysteine, was administered as protein source for seven days. Increases in the volume of ascites and the number of tumor cells were significantly inhibited in the rats receiving glucose plus L-methionine-free amino acid mixture compared to the control rats given glucose only, glucose plus ordinary amino acid mixture and laboratory rations. Unfavorable side effects of TPN with amino acid compound lacking L-methionine and L-cysteine were loss of body weight and development of hypoproteinemia. No evidence of hepatic injury and bone marrow suppression due to this treatment were obtained from the results of biochemical and hematological studies. In liver cells and ascites tumor cells, morphologically, prominent enlargement of the nucleoli was observed in the rats treated with the amino acid mixture lacking of L-methionine and L-cysteine.

Amino Acids↗