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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 271 records · Page 15Linked to original sources
PubMed1994

Platelet activation in diabetic patients with asymptomatic atherosclerosis.

We studied 27 non-insulin-dependent diabetics without apparent atherosclerosis (AS) to investigate whether abnormal platelet function is related to asymptomatic atherosclerosis in diabetes mellitus. The degree of AS was quantitatively evaluated by determining the intimal plus medial thickness (IMT) of the carotid artery wall with ultrasound high-resolution B-mode imaging. Based on our previous finding that the upper threshold of the IMT was 1.1 mm in healthy subjects, the patients were divided into the AS-positive group with the IMT > 1.1 mm, (n = 17) and the AS-negative group with the IMT < 1.1 mm (n = 10). Among five variables measured as the factors concerned with thrombogenesis, only plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were significantly higher in the AS-positive group than in the AS-negative group. Chronic administration of pentoxifylline (300 mg/day) significantly reduced the abnormally high plasma levels of beta-TG and PF4 in 7 patients of the AS-positive group to normal levels, without lowering the normal plasma beta-TG and PF4 levels in the remaining 10 patients. Pentoxifylline treatment did not affect the plasma levels of the 3 other variables, von Willebrand factor, 6-keto prostaglandin F1 alpha and thromboxane B2. This study suggests that the progress of atherosclerosis in diabetes mellitus is associated with in vivo platelet activation and platelet activation does not occur in diabetics without carotid atherosclerosis. Pentoxifylline may impede the vicious cycle in which atherosclerosis is accelerated by platelet activation.

Aged↗
PubMed1994

Effect of strict metabolic control on glucose handling by the liver and peripheral tissues in non-insulin-dependent diabetes mellitus.

To examine the effect of strict glycemic control on the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM), we applied euglycemic hyperinsulinemic clamp combined with an oral glucose load (OGL) to nine non-obese subjects with NIDDM and quantitated insulin-mediated glucose uptake by the liver (HGU) and peripheral tissues (PGU) simultaneously before and after 3 to 4 weeks of intimate glycemic control by preprandial regular insulin injections 3 times a day. The glucose infusion rate (GIR) required to maintain euglycemia during the clamp before OGL was considered as PGU. After OGL, the fraction of ingested glucose that is not extracted by the liver enters the systemic circulation and reduces the GIR required for the clamp. HGU was calculated from the difference between the amount of OGL and the cumulative decrements in GIR after OGL and was expressed as the ratio to the amount of OGL (%). Three to 4 weeks after initiation of strict metabolic control, FPG and HbA1c levels significantly improved (9.1 +/- 0.5 vs. 6.4 +/- 0.4 mmol/l, and 11.2 +/- 0.8 vs. 8.3 +/- 0.3%, P < 0.05). HGU significantly increased to 33.1 +/- 9.5 from 14.5 +/- 4.8%, while PGU did not change (38.2 +/- 5.2 vs. 37.4 +/- 3.9 mumol/kg.min). These data suggest that short-term strict metabolic control ameliorates insulin resistance in NIDDM mainly at the hepatic level.

Adult↗
PubMed1994

Point mutations at glycine-121 of Escherichia coli dihydrofolate reductase: important roles of a flexible loop in the stability and function.

To elucidate the role of a flexible loop in the stability and function of Escherichia coli dihydrofolate reductase, glycine-121 in a flexible loop (residues 117-131), separated by 19 A from active site Asp27, was substituted by site-directed mutagenesis with eight amino acids (Ala, Val, Leu, Asp, Ser, Cys, Tyr, and His). The free energy change of unfolding decreased in the order of G121A > G121D > G121C > G121S, wild-type > G121H > G121Y > G121L > G121V. The thermal denaturation temperature decreased with all mutations, accompanied by a decrease in the calorimetric enthalpy of denaturation. The steady-state kinetic parameter for the enzyme reaction, Km, was only slightly influenced, but kcat was significantly decreased by the mutations, there being 3- (G121C) to 42-fold (G121L) decreases in kcat/Km compared to that of the wild-type enzyme. The effects of mutations on the stability and enzyme activity were statistically examined as a function of the hydrophobicity and volume of amino acids introduced. The diminished stability and activity with increases in the hydrophobicity and volume of amino acids suggest that the main effect of the mutations would be modification of the flexibility of the loop due to overcrowding of the bulky side chains, overcoming the enhancement of the hydrophobic interaction.

Base Sequence↗
PubMed1994

Anti-alpha beta T cell receptor antibody prevents the progression of experimental autoimmune myocarditis.

We investigated the effects of anti-alpha beta T cell receptor antibody in rat experimental autoimmune myocarditis (EAM), using a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.

Animals↗
PubMed1994

Rat dilated cardiomyopathy after autoimmune giant cell myocarditis.

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36 +/- 0.49 versus 2.69 +/- 0.06 g/kg, respectively; P < .005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A simple method for predicting the cyclosporin A erythrocyte-to-plasma distribution ratio in blood, and its clinical assessment.

To adapt the monitoring of cyclosporin A (CyA) to clinical practice, we have developed a model to predict the CyA erythrocyte-to-plasma distribution ratio (CyA-EP), and evaluated its utility in clinical practice. We monitored CyA trough concentrations in whole blood and performed a series of biochemical tests during disease states in patients undergoing immunosuppressive therapy with CyA after transplantation. An estimate of CyA-EP (EPpr) was thus given by the following equation: EPpr = 6.0831 - 0.2944 x (TG+CHO) - 0.0037 x (CyAblood) - 0.0553 x (HCT) + 0.0463 x (BW) + 0.4447 x (CRE) - 0.0366 x (AGE). In this predictive model, EPpr is given as a function of the plasma lipid levels (TG+CHO, mM), the CyA concentration in whole blood (CyAblood, ng/ml), and the hematocrit (HCT, %), as well as the patient's body weight (BW, kg), serum creatinine (CRE, mg/dl) and age (AGE, years). The parameters TG+CHO, CyAblood, HCT, and AGE were negatively correlated with the CyA-EP, whereas BW and CRE exhibited a positive correlation. The predictive performance of this model was satisfactory for clinical use and changes in CyA-EP in transplant patients were obtained from monitoring CyA in whole blood and routine biochemical tests, without directly measuring CyA-EP. Since CyA-EP is an useful indicator for predicting a shift of CyA into tissues and its systemic clearance in plasma, our model to predict the CyA-EP will help the physician select a CyA regimen during immunosuppressive therapy in a variety of disease states after transplantation.

Adult↗
PubMed1994

New chlorine-containing prenylated C6-C3 compounds increasing choline acetyltransferase (ChAT) activity in culture of postnatal rat septal neurons from Illicium tashiroi.

The structures of two new chlorine-containing C6-C3 compounds isolated from the woods of Illicium tashiroi have been established as 2(R)-12-chloro-2,3-dihydroillicinone E (1) and 12-chloroillicinone E (2) by X-ray crystallographic analysis and spectroscopic data, respectively. Compound 1 has been found to significantly increase ChAT activity in culture of P10 rat septal neurons.

Animals↗
PubMed1994

Surface marker analysis of the vascular and epithelia lesions in cattle with sheep-associated malignant catarrhal fever.

Surface marker analysis of the vascular and epithelial lesions in cattle with sheep associated malignant catarrhal fever (MCF) were done by immunohistochemistry using 7 monoclonal antibodies. MHC class I and II antigens were expressed in the degenerated portion of the vascular walls in addition to infiltrated leukocytes. The major population of mononuclear cells in these lesions were phenotypically macrophages. The other cells had BoCD4 or BoCD8, but rarely gamma delta T cell markers. These results suggest involvement of MHC restriction and macrophages, in addition to autoaggressive cytotoxic T lymphocytes, in the development of MCF vascular lesion.

Animals↗
PubMed1994

Effect of digoxin on exercise performance in mildly symptomatic patients with idiopathic dilated cardiomyopathy and sinus rhythm.

The purpose of this investigation was to evaluate the effect of digoxin on aerobic performance in mildly symptomatic patients with congestive heart failure and sinus rhythm. Ten patients (8 men and 2 women) with idiopathic dilated cardiomyopathy (ejection fraction 17 to 33%, mean 27 +/- 4%) who were stable and mildly symptomatic with maintenance digoxin and diuretic therapy were studied. All patients underwent maximal symptom-limited ergometer exercise with analysis of respiratory gases during maintenance digoxin therapy, 4 weeks after digoxin withdrawal, and 4 weeks after digoxin readministration. Exercise capacity was assessed by peak oxygen uptake and anaerobic threshold. Serum digoxin concentration was 1.0 to 1.8 (mean 1.3 +/- 0.2) ng/ml during digoxin therapy, and less than the detectable level after digoxin withdrawal. No patients showed clinical deterioration after digoxin withdrawal. Peak oxygen uptake after digoxin withdrawal (23.7 +/- 3.0 ml/kg/min) did not differ significantly from that during maintenance digoxin therapy (23.8 +/- 2.5 ml/kg/min) or after digoxin readministration (24.1 +/- 2.9 ml/kg/min). The anaerobic threshold after digoxin withdrawal (14.9 +/- 2.5 ml/kg/min) did not differ significantly from that during maintenance digoxin therapy (15.0 +/- 2.1 ml/kg/min) or after digoxin readministration (14.9 +/- 2.2 ml/kg/min). No differences in heart rate and diastolic blood pressure were observed during exercise, but systolic blood pressure during exercise was significantly higher with digoxin therapy (p < 0.05). These results suggest that digoxin has no effect on aerobic performance in mildly symptomatic patients with idiopathic dilated cardiomyopathy and sinus rhythm.

Adult↗
PubMed1994

Morphological analysis of multinucleated giant cells occurred in experimental autoimmune myocarditis.

Our previous study reported the rich existence of multinucleated giant cells in an autoimmune myocarditis experimentally induced in rats. The present study investigated the histochemical and ultrastructural characteristics of these giant cells. Histochemistry for an acid phosphatase clearly demonstrated multinucleated giant cells dispersed at the inflammatory foci. Ultrastructurally, the giant cells were shown to be single cells, but not clustered cells. Their ultrastructural characteristics were very similar to the basic features of macrophages, except that the giant cells were poor in lysosomes and phagosomes. It was noticeable that some macrophages possessed three or more nuclei, displaying an intermediate form between mononuclear macrophages and multinucleated giant cells. These findings suggest that the giant cell in the experimental autoimmune myocarditis is a single multinucleated cell, and possibly derived from macrophages by cell-to-cell fusion.

Acid Phosphatase↗
PubMed1994

Atherosclerosis in carotid artery of young IDDM patients monitored by ultrasound high-resolution B-mode imaging.

Ultrasound high-resolution B-mode imaging was used to assess the carotid arteries in 105 patients with insulin-dependent diabetes mellitus (IDDM), 4-25 years of age, with duration of diabetes ranging from 0.5-17 years, 529 patients with non-insulin-dependent diabetes (NIDDM), 31-86 years of age, with duration of diabetes ranging from 0.5-49 years, and 104 nondiabetic healthy subjects, 7-76 years of age, to determine the intimal plus medial thickness (IMT) of the arterial wall. The IMT values for IDDM patients 10-19 years of age (0.525 +/- 0.123 mm, n = 68) or 20-25 years of age (0.696 +/- 0.124 mm, n = 14) were significantly greater than those in age-matched nondiabetic subjects (0.444 +/- 0.057 mm, n = 12, P = 0.01169; 0.538 +/- 0.098 mm, n = 34, P < 0.00006). NIDDM patients showed IMT values equivalent to those in normal adults > or = 20 years of age. Multiple regression analysis showed that IMT in IDDM patients was positively related to the duration of diabetes (P = 0.00061) as well as to age (P = 0.00046). No other possible risk factors, such as serum total cholesterol level, serum high-density lipoprotein (HDL)-cholesterol level, serum low-density lipoprotein-cholesterol level, serum triglycerides, serum lipoprotein(a) level, or systolic or diastolic blood pressure, have shown significant correlations with IMT in IDDM patients. However, non-HDL-cholesterol, smoking, and systolic hypertension were independently responsible for increases in IMT values of NIDDM patients as well as age and duration of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Expression of HLA-class II antigen in gastric carcinomas. Its relationship to histopathological grade, lymphocyte infiltration and five-year survival rate.

To investigate whether the expression of HLA-DR antigen in gastric carcinomas is associated with the survival rate, we studied 70 cases of gastric carcinoma using a monoclonal antibody. Forty-seven cases (67%) stained positively, including 31 differentiated carcinomas, and 16 undifferentiated carcinomas. A close correlation was found between expression of HLA-DR antigen and differentiation of the tumor cells. Marked lymphocyte infiltration was seen in the HLA-DR antigen positive cancers. In advanced gastric cancers, the 5-year survival rate of patients with HLA-DR antigen positive cancers was significantly higher (67.5%) than that of patients with HLA-DR antigen negative cancers (40%). The data suggest that the expression of HLA-DR antigen in gastric carcinomas may reflect the degree of tumor cell differentiation, and influence the host immune response and prognosis.

Carcinoma↗
PubMed1994

Bimodal pattern of killing of Chinese hamster V79 variant cells by hydrogen peroxide.

To elucidate the mechanism of cytotoxicity of H2O2, we selected H2O2-resistant Chinese hamster V79 cells by single-step selection from a pool of spontaneous variants. The resistant cells showed bimodal sensitivity to H2O2 without exhibiting a significantly higher level of the detoxicating enzymes, catalase, glutathione peroxidase and superoxide dismutase. Mode-one and mode-two killing were observed at lower (< 300 microM) and higher (> 2 mM) H2O2 concentrations, respectively. Mode-one but not mode-two killing was prevented by iron chelators. Pretreatment with low concentrations of ascorbic acid preferentially enhanced the killing at higher H2O2 concentrations. These resistant cells were cross-resistant to t-butyl hydroperoxide and cumene hydroperoxide.

Animals↗
PubMed1994

Immunohistochemical localization of acidic and basic fibroblast growth factors in human benign and malignant thyroid lesions.

The localization of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) was investigated immunohistochemically in human benign and malignant thyroid lesions. Immunostaining for aFGF and bFGF displayed diffuse or granular deposits of the reaction products in the cytoplasm of neoplastic cells, especially in the marginal region of follicular adenoma, follicular carcinoma and papillary carcinoma. All lesions except for diffuse hyperplasia, which was completely negative in immunostaining for all antibodies, showed an increased immunostaining for bFGF (Ab-1) over that of aFGF and bFGF (Ab-2). Basement membranes of follicular and papillary structure and the fibroblasts located in the stromal tissues were free from immunostaining for all antibodies. The ratio of positive immunostaining for all antibodies was highest in papillary carcinoma, with an incidence of more than 80.0%, followed, in descending order, by widely invasive follicular carcinoma, minimally invasive follicular carcinoma, follicular adenoma and normal thyroid, in which some follicular cells exhibited weak reaction products. aFGF with a molecular weight of 18 kDa was identified in papillary carcinoma of the thyroid. From these data, we concluded that aFGF is synthesized in the neoplastic follicular cells of the thyroid, and aFGF and bFGF may have important roles in the neoplastic proliferation of follicular cells.

Adenocarcinoma, Follicular↗
PubMed1994

Characterization of new inbred strains of Dahl-Iwai salt-sensitive and salt-resistant rats.

Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were newly established as inbred strains. To characterize the strains, the Dahl-Iwai S and R rats were fed low-salt (0.3% NaCl) and high-salt (8.0% NaCl) diets from 5 weeks after birth, and systolic blood pressure and pathologic findings were examined at intervals. The distributions of alleles at 19 biochemical and immunologic loci also were examined in the aforementioned strains, together with those for the inbred SS/Sea and SR/Sea strains, which were derived from inbred SS/Jr and SR/Jr strains, respectively. The Dahl-Iwai S rats were hypertensive after 3 weeks of consuming the 8.0% NaCl diet and died from 6 to 10 weeks after the diet was initiated. Renal lesions developed after 4 weeks' consumption of the high-salt diet. The Dahl-Iwai S rats were not hypertensive until at least the age of 21 weeks while they consumed the 0.3% NaCl diet, whereas it was reported that the SS/Jr rats became hypertensive at about 20 weeks of age when they consumed the low-salt diet. The Dahl-Iwai R rats were normotensive whether fed the 0.3 or 8.0% NaCl diet. Hydronephrosis was not observed in the Dahl-Iwai R rats, though it develops in SR/Jr rats with high frequency. Different distributions were detected for kidney alkaline phosphatase-1 (Akp-1) and amylase-1 (Amy-1) alleles between the Dahl-Iwai S and SS/Sea strains, and for esterase-14 (Es-14) and seminal vesicle protein-1 (Svp-1) alleles between the Dahl-Iwai R and SR/Sea strains. The phenotypic differences between the substrains of inbred Dahl rats could be ascribed to different genetic backgrounds.

Aging↗
PubMed1994

Recurrent death among early gastric cancer patients: 20-years' experience.

Six hundred and ninety-six patients, from among a total of 1,868 cases, were diagnosed as having gastric cancer, and underwent surgical treatment at this Medical Institution, between 1972 and 1992. Eighteen patients (2.6%) died of recurrent disease, four (0.6%) tumors being mucosal, and fourteen (2.0%) submucosal, in accordance with depth of invasion. The clinico-pathological findings were analysed to clarify the risk factors of recurrence in patients with early gastric cancer, as follows: (a) submucosal invasion, (b) mixed type IIa+IIc in gross appearance, (c) tumor size more than 40 mm in diameter. In mucosal cancers, recurrence occurred in patients with lymph-vessel invasion and lymph-node metastasis. In terms of the site of the recurrent lesion, the patients had predominantly hepatic recurrence. We conclude that there are specific factors related to the increased risk of recurrence, that can be evaluated pre-operatively. By identifying the risk factors of recurrence, we can optimize the therapeutic approach to these patients.

Female↗