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Biomedical subjects

M Masuda

Publications and source records attributed to M Masuda.

At least 505 records · Page 28Linked to original sources

Factor XIa-alpha 1 antitrypsin complex--elevation in the patients with DIC.

We developed an assay for the factor XIa-alpha 1 antitrypsin complex (F.XIa-alpha 1AT complex) in plasma. The purified factor XI (F.XI) activated with beta-XIIa and treated with alpha 1 antitrypsin (alpha 1 AT) served as the standard complex. The assay is an enzyme-linked differential antibody immunosorbent assay. The complex level of tested plasma was measured with peroxidase-labeled anti-alpha 1AT Fab' after the addition of 10-fold diluted test plasma (200 microliter) to the anti-F.XI monoclonal antibody beads. To eliminate the effects of plasma, the standard F.XIa-alpha 1AT complex was diluted with F.XI-deficient plasma (10-fold diluted) which did not contain the complex. Purified F.XI (0.08 micrograms/assay, i.e. 100%) was added to the standard F.XIa-alpha 1AT complex, because the absorbance of the standard complex containing F.XI (0.016-0.12 micrograms/assay, i.e. 20-150%) was a little lower than that of the complex alone. The recovery of the F.XIa-alpha 1AT complex added was over 90%. Neither F.XI nor alpha 1AT alone had the color development. The complex level of 25 normal individuals was below the detectable limit (less than 0.18 ng/assay), whereas the 30 patients with disseminated intravascular coagulation (DIC) had a high level complex (0.18-4.2 ng/assay). This assay may be helpful for the diagnosis of DIC.

Disseminated Intravascular Coagulation↗

Mode of transmission of human T-cell leukemia virus type I (HTLV I) in a human promyelocytic leukemia HL60 cell.

HTLV-I propagated in IMR90 human diploid fibroblasts was transmitted to human myeloid leukemia HL60 cells at a low efficiency. After co-cultivation for 3 months, the viral genome was detected in 14/48 HL60 cell clones. Among the 14 HTLV-I-infected clones, 8 contained subgenomic fragments alone or in addition to the complete HTLV-I genome. The frequency of deleted proviruses (9/24 total proviruses) was unexpectedly high. Hirt's supernatant of some of the clones harboring complete HTLV-I genome(s) in the chromosome contained both linear and circular HTLV-I proviral DNAs. The circular DNAs were composed of one LTR and 2 LTR closed circular proviruses. These clones produced infectious HTLV-I constitutively, which was proved by transmission of the viral genome into fresh IMR90 cells by co-cultivation. However, in these clones, re-integration of extrachromosomal provirus into their own chromosomes was not observed.

Cell Line↗

Murine monoclonal antibodies to human factor XI.

Murine monoclonal antibodies to human factor XI (F.XI) are described. The monoclonal antibodies (2-1, 4-1, 7-1 and 10-1) consisted of IgG1. 4-1 inhibited the activation of F.XI completely in the presence of high molecular weight kininogen and kaolin and the others did so partially, whereas these antibodies had no effect on the activation of F.XI with activated factor XII (beta-XIIa). Four antibodies had no effect directly on the amidolytic activity of activated F.XI (F.XIa). 10-1 inhibited the activation of factor IX in coagulant assay for F.XIa by Mannhalter. And 4-1 and 7-1 did so partially, whereas 2-1 did not. In immunoblotting analysis, all antibodies bound to F.XI, its reduced form and F.XIa. All were directed against the heavy chain of F.XI. All antibodies recognized F.XIa-alpha 1 antitrypsin complex.

Antibodies, Monoclonal↗

Ataxia telangiectasia with generalized skin pigmentation and early death.

A female infant with clinical and laboratory features of ataxia telangiectasia (AT) showed two clinical features exceptional for the disease, i.e. generalized skin pigmentation and an unusually early death at the age of 15 months. Her clinical features supportive of the diagnosis of AT included growth and developmental retardation and muscle weakness. Findings indicating immunodeficiency included recurrent pulmonary infections, failure of PHA stimulation of PB lymphocytes, decreased levels of serum IgM and IgA and on autopsy, an atrophic thymus without Hassall's corpuscles. Her cultured skin fibroblasts showed increased spontaneous chromosome breakages and hypersensitivity to X-ray irradiation, as would be expected for AT fibroblasts. She showed elevated blood HbF levels, macrocytic anaemia, granulocytopenia and thrombocytopenia, findings suggestive of a preleukaemic or leukaemic process. Yet aspirates of her bone marrow revealed no malignant cells. Autopsy revealed bilateral Pneumocystis carinii pneumonia, telangiectatic lesions in all the internal organs studied, sparse and degenerative Purkinje cells in the cerebellar cortex and atrophic ovaries. In view of these findings, it was concluded that the patient had a hitherto undescribed variant of ataxia telangiectasia.

Ataxia Telangiectasia↗

Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate.

Sodium dichloroacetate (DCA) was administered orally at a dose of 50 mg per kg body weight twice or three times per day to a newborn infant with lactic acidosis of unknown cause (patient 1) and to a 15-year-old boy with mitochondrial encephalomyopathy associated with lactic acidosis (patient 2). In patient 1, during treatment with DCA, DCA accumulated in the blood judging from the findings that the urinary excretion of DCA increased cumulatively and the blood lactate level rapidly decreased to the normal range. In patient 2, the blood DCA level gradually increased during treatment to a concentration of 250 micrograms ml-1 and the blood lactate level decreased and was maintained within the normal range. DCA was detected in the brain (25 micrograms g tissue-1) and the liver, kidney and muscle (33.8, 33.8 and 26.3 micrograms g tissue-1, respectively) obtained at autopsy of patient 1, and in the cerebrospinal fluid of patient 2 at a concentration of 125 micrograms ml-1 when the blood concentration was 250 micrograms ml-1. The lactate levels in the cerebrospinal fluid decreased from 7 and 4 mmol l-1 to 2.4 and 2.6 mmol l-1 in patients 1 and 2, respectively. Thus DCA may be useful in clinical treatment of chronic congenital lactic acidosis because it seems to cross the blood-brain barrier. However, it must be given at non-toxic doses, determined by monitoring the concentrations of lactate and DCA in the blood, because orally administered DCA tends to accumulate in tissues.

Acetates↗

Myocardial distribution of retrograde flow through the coronary sinus of the excised normal canine heart.

Myocardial distribution of the retrograde flow through the coronary sinus in the canine heart was evaluated by observing the corrosion casts of the myocardial vessels after coronary sinus injection of a low-viscosity resin, Mercox, a compound that passes through capillaries. The apex and the left ventricular free wall were well perfused at the microvascular level, even in the presence of complete left main coronary artery occlusion, whereas the right ventricular free wall was not perfused effectively at this level in any heart. Although there was considerable variation in the perfusion of the ventricular septum from heart to heart, the entire septum was not perfused in some of the hearts. We considered this poor perfusion of the septum to be due to the presence of well-developed thebesian veins in the septum. Retrograde coronary sinus perfusion of cardioplegic solution may be a valuable alternative to protect the left ventricular free wall, especially in cases of critical coronary artery stenosis or occlusion. However, antegrade perfusion should be used also, whenever possible, for adequate protection of the septum and the right ventricular free wall.

Animals↗

Effect of taurine and homotaurine on bile acid metabolism in dietary hyperlipidemic rats.

The effects of taurine (2-aminoethanesulfonic acid) and its homologue, homotaurine (3-aminopropanesulfonic acid), on biliary and fecal excretion of bile acids were investigated in dietary hyperlipidemic rats. Taurocholic acid was a major component in the bile of rats on laboratory chow and the ratio between glycine and taurine conjugated bile acids (G/T ratio) was 0.14. In feces, more free bile acids were present than in bile and the G/T ratio increased to 1.49. The biliary bile acid level increased approximately 2-fold in rats fed a diet containing 0.5% cholesterol and 1.0% cholic acid for 10 days. The glycine conjugated bile acid level increased approximately 7.5-fold, so that the G/T ratio was reversed to 1.17. the level of fecal bile acids increased approximately 19-fold while the G/T ratio remained at 1.43. Taurine or homotaurine (500 mg/kg/d each) was orally administered for 10 d concurrently with the cholesterol diet. Taurine suppressed elevation in the glycine conjugated bile acid level so the bile acid composition was roughly similar to that of the rats on laboratory chow and the G/T ratio became 0.06. In fecal excretion, the bile acid level increased significantly 1.2-fold over that of the control and the G/T ratio was 0.45. Homotaurine did not significantly alter the biliary bile acid level or the composition. These results indicated that taurine stimulated the excretion of bile acids, resulting in a reduction in serum cholesterol. Homotaurine did not influence bile acid metabolism.

Animals↗

Effects of taurine on neutrophil function in hyperlipidemic rats.

In dietary hyperlipidemic rats, an increase in serum lipid level may cause an increase in membrane lipid level of the neutrophils, and phagocytosis and bactericidal capacity may be thereby lowered. Treatment with taurine (470 mg/kg/day, p.o.) strengthened the bactericidal capacity of neutrophils which was decreased by cholesterol diet feeding, as the capacity was stronger on the 40th day than that in animals fed laboratory chow. The results suggest that taurine may play an important role in the mechanism of host defense through the neutrophil function.

Animals↗

[Reverse redistribution in dipyridamole-loading thallium-201 images using single photon emission computed tomography].

This study demonstrated the clinical significance of reverse redistribution, i.e., a decrease in the relative Tl activity in the redistribution image compared to that of the stress image after administration of dipyridamole. Dipyridamole was infused intravenously at a rate of 0.142 mg/kg per min for four min, and a stress image was obtained 10 min after the injection of two mCi 201Tl. Each patient returned for redistribution scanning in the identical position three hours after the isotope injection. The myocardial image of Tl was analyzed by single photon emission computed tomography and its washout rate was calculated by the segmental ROI method. Myocardial function and the motion of left ventricular wall were analyzed by 99mTc-RBC-gated cardiac pool imaging. The results were as follows: Reverse redistribution was noted in 27 (21.6%) of 125 consecutive Tl dipyridamole and redistribution myocardial imaging studies. The stress image demonstrated normal perfusion (group 1) and reduced perfusion (group 2) of Tl. Group 1 consisted of 17 patients with diabetes mellitus, supraventricular arrhythmias, hypertension, and others. Group 2 consisted of 10 patients with subendocardial infarction, diabetes mellitus, and hypertension, and others. The percentage prevalence of reverse redistribution among patients with supraventricular arrhythmia was 62.5% (five of eight patients), with subendocardial infarction 60.0% (three of five), with hypertension 42.8% (six of 14), and with diabetes mellitus 40.0% (eight of 20), while in those with transmyocardial infarction and angina pectoris no reverse redistribution percentage was found. The washout rate of Tl in normal perfusion areas was 44.0 +/- 12.8%, the reverse redistribution of group 1 was 47.4 +/- 12.8%, and of group 2 was 51.2 +/- 8.2%. The washout rate of the reverse redistribution of group 2 was significantly greater than that of the normal areas. In gated cardiac pool imaging, patients in group 2 had significantly larger areas showing abnormal contraction of the left ventricular wall and significantly lower ejection fraction than did group 1. In the electrocardiogram ST segment depression was noted more frequently in group 2 than group 1. No Q wave was present in the corresponding reverse redistribution area. These results suggest that reverse redistribution might occur in a region with a combination of scarred and normal myocardium, the metabolically affected myocardium, and an area with relatively increased myocardial blood flow. The patients in group 2 seem to have the more pathological myocardium than do those in group 1.

Adult↗