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Biomedical subjects

H Sawada

Publications and source records attributed to H Sawada.

At least 487 records · Page 27Linked to original sources

[Studies on biological characteristics of enterovirus type 70 (EV 70)].

Enterovirus type 70 (EV 70) is a new type of enterovirus, which is a causative agent of "Acute Hemorrhagic Conjunctivitis" (AHC). It appeared for the first time in Ghana in 1969, and occurred in Japan in 1971. The optimal temperature for growth of EV 70 is 33-35 degrees C, and lower than that of other enteroviruses. Ninety two isolates of EV 70 were investigated to know the biological characteristics. Isolates were obtained in Japan and foreign countries in Africa, Asia and Europe in 1971-1981, and contained eighty seven from eye swabs, three from feces and two from throat swabs. Reproductive capacity of EV 70 at 38 degrees C varied from one isolate to the other. The ratios in log of 33 degrees C yield to 38 degrees C yield ranged from 0.2 to 3.2, and showed no tendency to obtain reproductive capacity at high temperature chronologically after invasion to Japan. In order to find whether EV 70 obtains the reproductive capacity at 38 degrees C, three isolates, which had high pfu ratios (33 degrees C/38 degrees C, log), 2.6-3.2, were subjected to 5 passages by plaquing method. It was found that they obtained the capacities remarkably, and the ratios decreased to -0.5-0.6. As EV 70 exhibits a physicochemical characteristic of enteroviruses, the reproductive capacity in organ cultures of human fetal small intestine was investigated. The results indicated that EV 70 isolates grew distinctly, though the degree of that was less in comparison with coxsackievirus B1 and echovirus 11, and that they increased in the capacities by passages in the intestine. These findings suggested that EV 70 developed the reproductive capacities at high temperature and that in human intestine experimentally. By neutralization tests using two kinds of antisera against EV 70, it was found that serological characteristics of EV 70 changed after invasion to Japan. Intratypic antigenic mutants were first isolated in some parts of Honshu areas in 1972, and took the place of prototype-like isolates throughout Japan in the following one or two years, and after that, no prototype-like isolates obtained anywhere. The same trend was observed in isolates in foreign countries. To investigate differences and changes of these biological characteristics of EV 70 more precisely, further observations seemed to be necessary.

Enterovirus↗

[High dose ACNU and radiation therapy with autologous bone marrow rescue for a patient with cerebellar medulloblastoma: case report].

High dose ACNU and radiation therapy with autologous bone marrow rescue was performed in a 3-year-old boy suffering from cerebellar medulloblastoma, whose main mass had been removed at operation when widespread subarachnoid tumor dissemination was already present. The myelosuppression, which is a major side effect of high dose chemotherapy, was successfully prevented by the autologous bone marrow grafting and the serial CT scans showed complete disappearance of the tumor. However, the patient died on the 53rd day after the administration of ACNU of respiratory complication which was most likely due to pulmonary fibrosis. Although the autologous bone marrow rescue therapy is a technical advance to cope with myelosuppression secondary to chemotherapy, side effects of the other organs, particularly of the respiratory system, remain to be solved. The optimal treatment schedule should be established as soon as possible.

Antineoplastic Agents↗

[Mode of action of fluoropyrimidines, in relation to their clinical application].

From results which we obtained in experiments on 5-fluoropyrimidine analogs, it was demonstrated that the mode of action of these compounds was as follows: In human cancer, in contrast to experimental animal tumors, it was demonstrated that thymidine phosphorylase (Thd Pase) activity was dominant compared to that of uridine phosphorylase (Urd Pase). This observation would indicate that 5-fluorouracil (5-FU) was mainly metabolized to produce 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), via 5-flu fluoro-2'-deoxyuridine(FdUR). FdUMP would inhibit DNA synthesis by blocking thymidilate synthetase activity, resulting in the death of cancer cells. Thd Pase activity by which 5-FU is converted to FdUR would participate greatly in the antitumor effect of the compounds because of the fact that FdUR has 1,000 times greater antitumor activity than 5-FU. Moreover, some of the fluoropyrimidines are activated by this enzyme to produce 5-FU. It should be emphasized that Thd Pase activity is higher in tumor tissue than in normal tissues. This finding would mean that the compounds would exert a selective (antitumor) activity on cancer cells. In addition, a clinical trial of fluoropyrimidines showed them to be effective when administered to patients in order to maintain a lower effective level of 5-FU in tumor tissues for a longer period of time. Such experiences would also lend more weight the possible of the mode of action of the of fluoropyrimidines mentioned above.

Animals↗

[Prognostic significance of the initial clinical findings in patients over 40 years of age with secundum atrial septal defect].

Controversy concerning medical versus surgical management of elderly patients with secundum atrial septal defect (ASD II) remains unsolved. To clarify this problem, we studied relation between initial clinical findings and long-term prognosis of patients with isolated ASD II over 40 years of age. Of 47 patients medically managed, 13 patients died during the follow-up period. Among these, 11 died of congestive heart failure (CHF), and 2 died of non-cardiac disease. Mean age and follow-up period of these 11 were 68.1 +/- 9.0 and 6.7 +/- 5.1 years, respectively, and those of 34 survivors were 61.9 +/- 7.5 and 7.7 +/- 5.8 years, respectively. All 6 patients of functional capacity III-IV (NYHA classification), and 5 of NYHA II, died. Seven patients of NYHA II progressed to NYHA III-IV, and the other 20 of NYHA II and all 7 patients of NYHA I remained unchanged during the follow-up. Overt CHF (p less than 0.001), mitral and/or tricuspid regurgitation (p less than 0.01), combination with arterial hypertension and/or ischemic heart disease (p less than 0.05), atrial fibrillation (p less than 0.01), P-sinistrocardiale (p less than 0.001), and R/S (V6) less than 2.0 (p less than 0.01), cardiothoracic ratio greater than 55% (p less than 0.001), width of right descending branch of the pulmonary artery greater than 25 mm (p less than 0.01), and mitral valve prolapse in the echocardiogram (p less than 0.05) were significantly frequent in the cases clinical deterioration. Of 32 patients, whose functional capacities were NYHA II initially, 12 showed progression and 20 were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Computerized processing of two-dimensional echo-cardiograms: its application for quantitating left ventricular regional contractility and three-dimensional echocardiography].

This study assessed the computerized processing of two-dimensional echocardiograms for quantitating left ventricular regional contractility and for computer reconstruction of the left ventricle; so-called three-dimensional echocardiography. Computer analysis of two-dimensional echocardiograms for quantitative evaluations of the left ventricular regional contractility in myocardial infarction: A new practical method for computer digital image processing of two-dimensional echocardiograms was developed for quantitating left ventricular regional contractility. Short-axis cross-sectional images of the left ventricle at the levels of the mitral valve (MV), papillary muscles (PM) and the apex (AP) were recorded using a phased array sector scanner in thirty patients with healed myocardial infarction and fifteen normal control subjects. The echocardiographic data were recorded on the video tape and transferred to a minicomputer via interface circuits, digitized, and processed automatically. Each digitized image consisted of 256 X 256 pixels with a gray scale of 256 values. The edges of the endocardial and epicardial walls were detected by applying sequential steps including smoothing, dynamic thresholding, region growing, and filling of small holes. The rationale of edge detection depended on assuming that abrupt changes in gray levels occurred at the boundary, and that the points with maximum gradient values were boundaries of the left ventricular wall. Best-fit contours of endocardial and epicardial edges were drawn by fitting a spline. Besides this automatic edge tracing, endocardial and epicardial edges were also manually traced using a digi-pen system, whose results coincided well with automatic tracings. After detection of edges of endocardial and epicardial walls, the short-axis cross sectional left ventricular wall at each level was divided into eight segments. The geometric center of the end-diastolic left ventricular cavity and the axis connecting this with the posterior end of the right side of the septum was used as the reference point and line (fixed reference system). End-diastolic and end-systolic segmental hemiaxes, segmental area, segmental wall thickness and changes during the cardiac cycle were measured and calculated automatically in each segment using a computer. Regional contractility of the left ventricle was evaluated by percent systolic changes of the segmental hemiaxis, area and wall thickness. These values were significantly reduced in the infarcted left ventricular wall as defined by left ventriculography and coronary angiography.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A method for scanning electron microscopy of mitotic apparatus of cells in culture.

The mitotic apparatus of HeLa cells which had been covered with surface structures was successfully exposed for scanning electron microscopy. HeLa cells were cultured on carbon coated coverslips. After synchronization they were lysed with non-ionic detergent in a microtubule- stabilizingbuffer and embedded in styrene. Then the surface layer of the cells was sectioned away with a glass knife. Styrene was removed by treating the specimens with isoamylacetate and the cells were processed for scanning-electron microscopy. Various stages of mitotic apparatus were obtained with good preservation. Chromosomes appeared as aggregates of filamentous and granular structures. Microtubules appeared as filaments 40 nm in diameter.

Chromosomes, Human↗

Isolation and characterization of multiforms of aldehyde reductase in chicken kidney.

Three multiforms of NADPH-dependent aldehyde reductase have been purified to homogeneity from chicken kidney. The enzymes were monomeric proteins with similar molecular weights around 39 000 but with different pI values. Two of them exhibited, almost the same heat stability, a broad optimal pH of 6-6.5 and preference for NADPH as a cofactor. They were high-Km aldehyde reductases which reduced various aldehydes, hexonates, alpha-diketones, xylose, glucuronolactone and ethyl acetoacetate, and which were inhibited to similar degrees by heavy metal ions, organic acids, p-chloromercuribenzoate, indomethacin and phenobarbital. The third aldehyde reductase was distinct from the other two enzymes in its heat lability, sharp acidic pH optimum of 6.0, and dual cofactor specificity. The enzyme showed low Km values for the above-mentioned substrates except hexonates and 4-carboxybenzaldehyde, and it specifically reduced lauryl aldehyde, acetoin and ketosteroids. This enzyme was less sensitive to the above-mentioned inhibitors than the high-Km aldehyde reductases, but the enzyme was moderately inhibited by chlorpromazine and was activated about 1.5 times by the addition of sulfate ions. It was demonstrated using antibodies against one of the high-Km forms and the low-Km form of aldehyde reductase that the two high-Km forms were immunologically identical with each other but not with the low-Km form, and that the high-Km and low-Km forms were widely distributed in various tissues of chicken.

Alcohol Oxidoreductases↗

Ascidian sperm chymotrypsin-like enzyme; participation in fertilization.

The action of a chymotrypsin-like enzyme from sperm extract from the ascidian Halocynthia roretzi was studied using several substrates. It was found that the most susceptible substrate had the most powerful inhibitory effect on fertilization in this animal. Among the substrates, the order of susceptibility coincided with the order of inhibitory ability, which indicates that the enzyme is involved in the fertilization process.

Animals↗

Affinity separation of an acid phosphatase from rat tissues and Gaucher spleen with immobilized Cibacron Blue.

An acid phosphatase species which was activated by Fe2+ was determined to be partially soluble but mainly particulate in rat spleen. The particulate enzyme could be extracted into 1 M KCl. This enzyme bound to Cibacron Blue-immobilized Sepharose (Blue-Sepharose) and was desorbed by 2 M KCl with a good yield, while the other acid phosphatases in rat spleen did not adsorb on Blue-Sepharose. The enzymes eluted on Blue-Sepharose chromatography of both the soluble and particulate fractions were electrophoretically identical. The enzyme hydrolyzed aryl monophosphates, phosphoproteins, and nucleoside di- and triphosphates. The activity for the three kinds of substrate was similarly activated by Fe2+, ascorbic acid and cysteine, and inhibited by molybdate, Cu2+ and F-. Cibacron Blue inhibited the enzyme competitively with respect to a substrate, p-nitrophenyl phosphate, but kinetic analysis suggested that more than one dye molecule binds to the enzyme. The Blue-Sepharose technique could be applied not only to quantitative separation of acid phosphatases similar to the spleen enzyme from bone and epidermis of rat, but also to that of a tartrate-resistant acid phosphatase from human spleen with Gaucher's disease.

Acid Phosphatase↗

Isolation and characterization of a post-proline cleaving enzyme and its inhibitor from sperm of the ascidian, Halocynthia roretzi.

A post-proline cleaving enzyme and its endogenous inhibitor have been demonstrated to be present in sperm of the ascidian, Halocynthia roretzi. The enzyme was extracted with artificial sea water from frozen and thawed sperm and isolated from accompanying acrosin-like and chymotrypsin-like enzymes by DEAE-cellulose chromatography. It was then separated from the endogenous inhibitor by ammonium sulfate fractionation and DEAE-Sephacel chromatography. Three subsequent chromatographic operations using hydroxylapatite, Sephadex G-150 and Z-Gly-Pro-Leu-Gly-aminohexyl-Sepharose yielded the highly purified enzyme. The molecular weight and isoelectric point of the enzyme were estimated to be 66,000 and 5.5, respectively. The pH optimum of the activity was 7.0. The enzyme was inactivated with diisopropylphosphorofluoridate, phenylmethylsulfonyl fluoride, Z-Gly-Pro-chloromethyl ketone and sulfhydryl-directed reagents; these inhibitor susceptibilities were similar to those reported for the enzymes of mammalian origins. The ascidian enzyme hydrolyzed oxytocin, angiotensin II, luteinizing hormone releasing hormone and neurotensin at the carboxyl side of proline residues. The endogenous inhibitor was heat stable. The molecular weight of its main component was estimated to be about 8,000. The presence of salt at high concentrations weakened the enzyme-inhibitor interaction. Z-Gly-Pro-chloromethyl ketone inhibited fertilization of the ascidian, suggesting possible involvement of the post-proline cleaving enzyme in fertilization.

Animals↗

Three dimensional reconstruction of the left ventricle from multiple cross sectional echocardiograms. Value for measuring left ventricular volume.

The accuracy of a system for reconstructing a three dimensional image of the left ventricle from randomly recorded multiple short axis images was tested by comparing the calculated left ventricular volume with the directly measured left ventricular volume in 11 excised porcine hearts. The system comprised a real time phased array sector scanner, a transducer locating system, and a computer system for digitising outlines of the left ventricle, displaying the reconstruction image, and calculating the left ventricular volume. The reconstructed image was similar to the real image and the calculated left ventricular volume showed a high correlation with the directly measured left ventricular volume. This method was accurate in vitro and is expected to be available for clinical measurement of left ventricular volume.

Animals↗

Coronary angiographic findings in various types of unstable angina--study on the pathophysiology of unstable angina.

Coronary angiographic findings were studied in 129 patients with various types of unstable angina in order to clarify the pathophysiology of unstable angina. The subjects were divided into 3 types: effort angina (E), rest angina (R), and effort and rest angina (E+R), and each of these 3 types was subdivided into group I (new onset), II (recurrent) and III (changing pattern). 1) R had less severe coronary lesions than E or E+R. 2) Severity and distribution of coronary atherosclerotic lesions in unstable angina were similar to those in stable angina. 3) Incidence of coronary spasm is higher in unstable R and E+R than in stable R and E+R, respectively. 4) Unstable R and E+R with frequent attacks were associated with a higher frequency of coronary spasm and severe proximal coronary stenosis than those without frequent attacks, respectively. 5) Among unstable E+R-III (changing pattern), the patients who developed E+R from E showed significantly higher incidence of multiple vessel disease than those who developed E+R from R and significantly lower incidence of spontaneous spasm than those with E+R, who remained with the same pattern but in whom the frequency and/or the intensity of the attack increased, without any significant difference in the severity of coronary stenosis from other 2 subgroups. It is concluded that coronary spasm as well as severe coronary atherosclerotic lesions may be responsible for the unstable state of angina. Especially in R and E+R, coronary spasm is the most important factor responsible for the unstabilization of angina.

Adult↗