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Biomedical subjects

H Abe

Publications and source records attributed to H Abe.

At least 1,405 records · Page 78Linked to original sources

Conformational change of a globular protein elucidated at atomic resolution. Theoretical and nuclear magnetic resonance study.

A powerful method of conformational energy minimization which uses both first and second derivatives of the energy function is applied both to a small globular protein, bovine pancreatic trypsin inhibitor (BPTI), consisting of 58 amino acid residues and to its chemical derivative obtained by carboxamidomethylation of cysteinyl residues of the 14-38 disulphide bond. Conformational fluctuations are also calculated from the second derivative matrix obtained at the respective minimum energy conformations. Appreciable conformational changes upon chemical modification are observed only in the vicinity of the site of the modification. The nuclear magnetic resonance data on both BPTI and the modified BPTI are analyzed to compare with the calculated conformational changes upon chemical modification. Good correlations are found between the theoretically predicted and experimentally deduced conformational changes. The theoretical method employed here has a general application for the calculation of small conformational changes of globular proteins upon their chemical modification or an amino acid substitution.

Aprotinin↗

Decreased Na+-gradient-dependent D-glucose transport in brush-border membrane vesicles from rabbits with experimental Fanconi syndrome.

The effect of anhydro-4-epitetracycline on sodium gradient-dependent D-glucose transport of rabbit renal brush-border membrane vesicles was studied. The purity of isolated brush-border membrane vesicles as judged by enzyme activities was not different between normal control and anhydro-4-epitetracycline-administered rabbits. There was no difference in estimate of intravesicular volume, either. When NaCl was used for sodium gradient, the overshoot of D-glucose uptake into brush-border membrane vesicles isolated from anhydro-4-epitetracycline-treated rabbits was significantly smaller than that of normal control rabbits. In the cases of NaSCN or Na2SO4, the former was also smaller than the latter, but not significantly so. To avoid the possible effect of membrane potential on D-glucose uptake, the voltage-clamp method was applied. Even in the voltage-clamped condition, the overshoot of D-glucose uptake into vesicles from anhydro-4-epitetracycline-treated rabbits was decreased compared to that of normal rabbits. In vitro incubation of brush-border membrane vesicles with 20 mM anhydro-4-epitetracycline caused no alteration in sodium gradient-dependent D-glucose uptake. Our results demonstrate that there exists a disorder in sodium gradient-dependent D-glucose uptake of renal brush-border membrane in anhydro-4-epitetracycline-treated rabbits, and suggest that this disorder is one of the underlying mechanisms of experimental Fanconi syndrome.

Animals↗

Association of dysgerminoma and gaucher's disease.

A 22-year-old woman presented with splenomegaly and pancytopenia of over two years' duration. A splenectomy was performed because of a suspicion of Gaucher's disease. At the time of operation a left ovarian tumor was found and was removed. A diagnosis of Gaucher's disease was made on the basis of massive infiltration of histiocytes with typical cytoplasmic striations in the spleen, liver, and bone marrow. The ovarian tumor was characterized by a monotonous, diffuse proliferation of large, rounded cells and was diagnosed as dysgerminoma. The association of Gaucher's disease and malignant tumors is rare, only several cases have been reported in the English literature. An additional feature of this case was the appearance of histiocytes showing the characteristic cytoplasmic striations of Gaucher's cells in the stroma of the tumor.

Adult↗

Role of prostacyclin in the response of cerebral blood flow to CO2.

The prostacyclin (PGI2) formation in cerebral vessels, as reflected by the difference in concentration of internal carotid arterial and internal jugular venous radioimmunoassayed 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), was determined under normocapnic and hypercapnic conditions in 5 patients with mild cerebral thrombotic infarction. There was no evidence that endogenous PGI formation in cerebral vessels was stimulated at mild hypercapnia, while an increase of cerebral blood flow (CBF) induced by hypercapnia was observed. These results suggest that endogenous PGI2 may not be a mediator for the response of CBF to CO2.

6-Ketoprostaglandin F1 alpha↗

Relationship between granule-containing cells and blood vessels in the rat autonomic ganglia.

Granule-containing (GC) cells and related blood vessels in the superior cervical ganglion and the pelvic plexus of the rat were examined by light and electron microscopy of serial thin sections. In the superior cervical ganglion, GC cells formed many clusters of more than 20 cells. These clusters were supplied with dense networks of fenestrated capillaries, while the ordinary ganglion cells had continuous capillaries distributed more sparsely. Several continuous capillaries diverged from the networks in the GC cell clusters to join with capillaries around the ganglion cells. In the pelvic plexus, continuous capillaries with well-developed pericytes were distributed similarly around the GC cells and the ganglion cells. Dense networks of fenestrated capillaries in the clusters were never seen. Based on these observations, the physiological significance of the GC cells was discussed.

Animals↗

Validity of contrast hyperemia for clinical assessment of coronary flow reserve: the optimal dose of contrast medium and reproducibility of the technique.

The dose-response relation of contrast medium-induced hyperemic response in coronary blood flow (contrast hyperemia) was investigated to determine the optimal dose of contrast medium (CM, Urografin-76) for the assessment of coronary flow reserve in man. The great cardiac venous flow (GCVF) was determined with the continuous thermodilution method during the contrast hyperemia induced by the intracoronary injection of CM of three different doses, ie, 2, 4, and 6 ml/60 kg of body weight, into left coronary artery. Submaximal coronary vasodilation could be obtained by intracoronary injection of 4 ml of CM with minimal changes in systemic hemodynamics. The contrast hyperemia with this dose of CM was reproducible and also closely correlated with that obtained during pacing-induced angina. Thus, we conclude that the contrast hyperemic technique with intracoronary injection of 4 ml of Urografin-76 could be a reliable method to assess the coronary flow reserve.

Blood Circulation↗

Noninvasive assessment of microcirculation of living organs and tissues using laser.

For studying microcirculation of intact tissues or organs, a new noninvasive, heat-transient method using laser photoexcitation is described. As a heating source an argon ion laser or R6G dye laser was used via a quartz fiber optic guide. Infrared radiation from heated tissue was detected by a thermography apparatus. After switching the laser irradiation on and off, a thermal transient curve of a model tissue, the skin, was biphasic: a component with a fast time constant and the other with a slow time constant. The temperature increases of both phases following laser irradiation were linear to the applied power from the laser onto the tissue. The temperature rises as a function of the wavelength of irradiated light have shown that the absorption of the light by tissue hemoglobin is a main heat-generation source. Furthermore, the temperature rises as a function of tissue blood volume and flow have shown that the component with a slow time constant is more related to the tissue hemoglobin concentration and tissue blood flow and heat conductivity. Thus, the analysis of heat-transient curves following laser irradiation gives information as to regional tissue blood volume, blood flow, and tissue heat conductivity.

Animals↗

DNA synthetic activity of right and left ventricular biopsy specimens in patients with cardiomyopathy.

This investigation was designed to evaluate the difference in DNA activity between biopsy specimens obtained from right and left ventricles. Nucleic DNA in the myocardial cells of hypertrophied and congestive forms of cardiomyopathy was analyzed to investigate the relationship between cell function and clinical manifestations. Endomyocardial biopsy specimens were obtained simultaneously from right ventricular septal wall and left ventricular inferolateral wall by a transcatheter biotome. Measurement of DNA was based on the Feulgen reaction and dual wavelength cytophotometry. In this series, 12 patients with hypertrophic cardiomyopathy and four patients with congestive cardiomyopathy were studied. In the normal heart, the DNA value (arbitrary units) of the right ventricle was 138.6, whereas that of the left ventricle was 144.4. In the hypertrophic group, the mean DNA value in the right ventricle was 279.9, whereas that of the left ventricle was 317.5. In the congestive group, the DNA mean value in the right ventricle was 108.8, whereas that of left ventricle was 144.8. The linear relationship (r = 0.67) between right and left ventricular DNA values suggests that cellular function of one ventricle is affected by that of the other side. Higher DNA values of the left ventricle may indicate the difference in work load between the ventricles. The relationships among DNA values, LV wall thickness, LV mass, and parameters of contractility were statistically high.

Adolescent↗

Myocardial energy metabolism of congestive and hypertrophic cardiomyopathy in man.

A key enzyme of glycolysis (pyruvate kinase) and main enzymes of the electron transport system (NADH cytochrome c reductase, succinic cytochrome c reductase, and cytochrome c oxidase) were measured in left ventricular biopsy specimens from six hypertrophic (HCM) and six congestive (CCM) cardiomyopathy. Pyruvate kinase was 104.0 and 45.0 mU/mg protein in HCM and CCM, respectively. NADH cytochrome c reductase, succinic cytochrome c reductase, and cytochrome c oxidase were 146.0, 9.9, and 775.0 mU/mg protein in HCM and 87.4, 5.2, and 502.0 mU/mg protein in CCM, respectively. From these data, it is evident that glycolysis and enzyme activities of the electron transport system are increased in HCM and decreased in CCM. Cardiac function reflects the state of these energy metabolism pathways in the myocardium. The changing energy metabolism in the right ventricle of the emphysema hamster seems to support this concept.

Animals↗

Glycaemic control in pancreatectomized dogs with a wearable artificial endocrine pancreas.

A needle-type glucose sensor has been developed using a platinum electrode covered with immobilized glucose oxidase. Experiments with albumin-saline solution in vitro showed that at 5.5 mmol/l glucose concentration the output current generated was 1.2 +/- 0.4 nA (mean +/- SD). The current increased as a linear function of glucose concentration over the range (0-27.7 mmol/l). The response time to reach 90% of the final plateau value was 16.2 +/- 6.2s. The signal-to-noise ratio of the sensor was 15.8 +/- 2.6 decibels. The temperature coefficient in output was 2.3 +/- 1.0%/degrees C. The current output was not affected significantly by changes in oxygen tension of the solution in the range 25-150 mmHg. In vivo, the output current of sensors inserted into the subcutaneous tissues of dogs was directly related to blood glucose concentrations after oral glucose or meals. Daily checking of the sensors maintained in subcutaneous tissues in five dogs showed that the sensitivity decreased gradually to 87.2 +/- 7.6% at 72 h, and dropped significantly to 57.4 +/- 7.0% of the initial output by 96 h. A wearable artificial endocrine pancreas (18.0 x 17.7 x 7.9 cm, 700 g) was developed, consisting of a needle-type glucose sensor, a microcomputer system and a pump driving mechanism. Three pancreatectomized dogs were fitted with the system by inserting the sensor into subcutaneous tissue. By renewing the sensor every fourth day, the device could maintain the daily glucose variations in diabetic dogs within the range 5-9.5 mmol/l for 7 days.

Animals↗

Effects of phospholamban phosphorylation catalyzed by adenosine 3':5'-monophosphate- and calmodulin-dependent protein kinases on calcium transport ATPase of cardiac sarcoplasmic reticulum.

To elucidate the role of 22000-dalton protein phospholamban, a putative regulator of Ca2+-dependent ATPase of cardiac sarcoplasmic reticulum, we examined the relationship between cyclic AMP- and calmodulin-dependent phosphorylation of phospholamban and their effects on ATPase activity and calcium transport of cardiac sarcoplasmic reticulum. Cardiac microsomes were incubated with [gamma-32P]ATP or unlabeled ATP, catalytic subunit of cyclic AMP-dependent protein kinase and/or exogenous calmodulin, and subsequently assayed for ATPase activity and calcium uptake by cardiac sarcoplasmic reticulum. Cyclic AMP-dependent phosphorylation of phospholamban was independent of Ca2+, whereas calmodulin-dependent phosphorylation of phospholamban was dependent on Ca2+ within a range between 0.2 and 50 microM. Cyclic AMP- and calmodulin-dependent phosphorylation of phospholamban occurred independently; when both kinases were operative, the amounts of phosphorylation were additive. Under these conditions, the phosphoproteins formed by cyclic AMP- and calmodulin-dependent protein kinases electrophoretically migrated as 11000-dalton components when sodium dodecyl sulfate-solubilized phosphoproteins were boiled prior to polyacrylamide gel electrophoresis. The ATPase activity was stimulated by either cyclic AMP- or calmodulin-dependent phosphorylation of phospholamban at Ca2+ concentrations up to 2 microM. The extents of stimulation of ATPase activity were additive when both types of phosphorylation were functional. Calcium uptake was similarly augmented by cyclic AMP- and/or calmodulin-dependent phosphorylation of phospholamban. These results indicate that Ca2+-dependent ATPase and calcium transport of cardiac sarcoplasmic reticulum are regulated by phospholamban phosphorylation catalyzed by cyclic AMP- and calmodulin-dependent protein kinases, thus suggesting a dual role of phospholamban in active calcium transport.

Biological Transport, Active↗

Low Km ALDH isozyme and alcoholic liver injury.

To assess the relationship between the polymorphism of aldehyde dehydrogenase (ALDH) isozyme and alcoholic liver injury, ALDH isozyme was analyzed by isoelectric focusing electrophoresis in hair roots from normal volunteers and alcoholics with chronic liver disease. Liver biopsy specimens from alcoholics and non-alcoholics with chronic liver disease were also analyzed. It was found that (1) the frequency of low Km ALDH isozyme in hair roots from chronic alcoholics with liver injury was 90%, which was significantly higher than those from normal volunteers (44%) and from non-alcoholics with chronic liver disease (56%); (2) the isozyme pattern of liver specimens analyzed coincided with that of hair roots; (3) the low Km ALDH isozyme-positive subjects including alcoholics showed no facial flushing, and negative subjects showed facial flushing after drinking alcohol. It is concluded that a much higher frequency of low Km ALDH isozyme was found in chronic alcoholics with liver injury. There was no apparent difference in hepatic biochemical and histological findings between chronic alcoholics with and without low Km ALDH isozyme, suggesting that acetaldehyde does not play a primary role in the pathogenesis of alcoholic liver injury.

Acetaldehyde↗

Effect of acute and chronic ethanol consumption on hepatic tissue oxygen tension in rats.

In vivo hepatic tissue oxygenation was investigated in chronically ethanol-treated rats using micro oxygen electrode and reflectance spectrophotometry. Effect of acute ethanol administration was also studied. Hepatic oxygen tension of rats treated with ethanol chronically (daily ethanol intake, 9-12 g/kg for 9 months) was very low as compared with that of normal rats, the decrease being comparable to that of rats treated with carbon tetrachloride. The hepatic oxygen tension in normal controls shortly after ethanol ingestion increased from basal level (median, 23 mmHg) to 40-70 mmHg, while in chronically ethanol-treated rats, the hepatic oxygen tension decreased transiently, followed by a gradual increase, but it still remained low. In CCl4-treated rats, the hepatic oxygen tension decreased further after the ethanol ingestion. It is concluded that chronic ethanol consumption in rats resulted in hepatic hypoxia with decreased liver blood flow and volume. Also acute ethanol administration does not induce hepatic hypoxia in normal rats, while in rats with injured liver it induces hypoxia.

Alcoholism↗

Overall distribution of vasoactive intestinal polypeptide-containing nerves on the wall of cerebral arteries: an immunohistochemical study using whole-mounts.

The overall distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity on the wall of the cerebral arteries, including its 3-dimensional profile, was investigated by means of the indirect immunofluorescence method using flat-mounts. VIP-immunoreactive fibers run spirally on the wall of the cerebral arteries. On the wall of the large arteries, such as the vertebral artery, basilar artery, internal carotid artery, within and/or without the circle of Willis, posterior and anterior communicating arteries, proximal parts of anterior, mid and posterior cerebral arteries, these fibers are richly distributed and show a dense grid-like appearance. The highest density was identified on the wall of the anterior cerebral artery, internal carotid artery and anterior communicating artery, while the lowest density was on the posterior communicating artery. On the other hand, on the walls of the branches of these arteries or along distal parts of the anterior, mid and posterior cerebral arteries, the number of VIP-immunoreactive fibers decreased markedly.

Animals↗

Why are infant gerbils more resistant than adults to cerebral infarction after carotid ligation?

Younger gerbils have been found to be more resistant than adults to cerebral infarction after carotid ligation. In this study, the perfused cerebral area after bilateral common carotid occlusion was evaluated in infant, young, and adult Mongolian gerbils by the carbon black perfusion method to assess the existence and significance of collateral blood vessels between the vertebrobasilar and carotid circulations. Nineteen gerbils were divided into three groups (i.e., infant, young and adult gerbils aged 3-4, 5-7, and 10-17 weeks, respectively). After bilateral common carotid artery occlusion, carbon black was injected directly into the left ventricle by cardiac puncture through the closed thorax. In five of eight infant gerbils, the whole brain was perfused by carbon black, while in the remaining three, only the cerebellum and brainstem were stained well, and marked bilateral cerebral pallor was observed. On the other hand, carbon black did not perfuse the brain region supplied by the carotid arteries, both in young and adult gerbils (11 animals in total). These results suggest that infant gerbils might have a more highly developed network of collateral blood vessels between the vertebrobasilar and carotid circulations, and the existence of such a significant network might be the basis for the fact that infant gerbils are resistant to cerebral infarction following carotid ligation. We propose that gerbils should be used as a stroke model only when they are 5 weeks old or older.

Aging↗

Transient ischemic attacks: racial differences, treatment, and prognosis.

Prognosis of transient ischemic attack (TIA) in 45 patients, diagnosed as TIA out of 75 suspected TIAs, was investigated for an average follow-up of 12.9 months. Twelve (27%) of the 45 patients progressed to complete stroke during the follow-up period. Patients with severe atherosclerotic lesions and with intracranial arterial lesions or with lesions of both intracranial and extracranial sites were predominant among the 29 cases examined angiographically, and the majority progressed to stroke. The prognosis was poorer than in the cases with mild atherosclerotic lesions or cases with only extracranial arterial lesions. From such characteristics of cerebral atherosclerosis of TIA in the Japanese with predominant intracranial severe arterial lesions, a different genesis for the development of cerebral atherosclerosis between Japanese and Americans or other Caucasians may be expected in cases with TIAs. With respect to the relation of recurrence of TIA to prognosis, a single episode of TIA in the past placed the patient at a greater risk of early infarction, where a high incidence (57%) of progression to stroke was found during the follow-up period. Treatment by superficial temporal artery to middle cerebral artery anastomosis or anticoagulant drug medication seemed to improve the prognosis of TIA as compared with antiplatelet aggregation therapy. These results suggest that embolus formation from an embolic source of arterial lesions may play some part in the pathogenesis of TIA and occurrence of subsequent stroke.

Adult↗

Bi-hemispheric CBF and its CO2 reactivity of TIAs and completed strokes in ICA occlusions.

Bi-hemispheric cerebral blood flow (CBF) measurements during rest and hyperventilation, with intra-arterial 133Xe injection method, were investigated in 19 cases, angiographically diagnosed as unilateral internal carotid artery (ICA) occlusion, including 8 cases with TIAs and 11 cases with completed strokes as the onset. Indices of cerebral vascular resistance and CO2 reactivity with decreasing arterial PCO2 were also investigated. A significant decrease (P less than 0.05) of hemispheric mean CBF was noted in the ischemic hemisphere, but normal flow values in the unaffected hemisphere and preserved CO2 responsiveness during hyperventilation were observed in both the affected and unaffected hemispheres in patients with TIAs. Moreover, a direct relationship between CBF and blood pressure, observed in 11 cases with completed strokes, was not recognized in 8 cases with TIAs. A degree of the abnormalities of the affected hemisphere in cerebral circulation was suggested to be somewhat different between TIAs and completed strokes in ICA occlusions, and bi-hemispheric CBF measurements would be an useful method for evaluating the various indices of the CBF in ICA occlusions.

Adult↗

Cerebral blood flow and CO2 reactivity in transient ischemic attacks: comparison between TIAs due to the ICA occlusion and ICA mild stenosis.

Hemispheric mean cerebral blood flow (CBF), together with its CO2 reactivity in response to hyperventilation, was investigated in 18 patients with transient ischemic attacks (TIAs) by intraarterial 133Xe injection method in a subacute-chronic stage of the clinical course. In 8 patients, the lesion responsible for symptoms was regarded as unilateral internal carotid artery (ICA) occlusion, and in 10 patients, it was regarded as unilateral ICA mild stenosis (less than 50% stenosis in diameter). Resting flow values were significantly (P less than 0.05) decreased in the affected hemisphere of TIA due to the ICA occlusion as compared with the unaffected hemisphere of the same patient, regarded as the relative control. It was not decreased in the affected hemisphere of TIA due to the ICA mild stenosis as compared with the control. With respect to the responsiveness of CBF to changes in PaCO2, it was preserved in both TIAs, due to the ICA occlusion and ICA mild stenosis. Vasoparalysis was not observed in either types of TIAs in the subacute-chronic stage. However, in the relationship of blood pressure and CO2 reactivity, expressed as delta CBF(%)/delta PaCO2, pressure-dependent CO2 reactivity as a group was observed with significance (P less than 0.05) in 8 cases of TIA due to the ICA occlusion, while no such relationship was noted in 10 cases of TIA due to the ICA mild stenosis. Moreover, clinical features were different between TIAs due to the ICA occlusion and ICA mild stenosis, i.e., more typical, repeatable TIA (6.3 +/- 3.7 times) with shorter duration (less than 30 minutes) was observed in TIAs due to the ICA mild stenosis, while more prolonged, less repeatable TIA (2.4 +/- 1.4 times) was observed in TIAs due to fixed obstruction of the ICA. From these observations, two different possible mechanisms as to the pathogenesis of TIA might be expected, e.g., TIA of microembolic origin due to the ICA mild stenosis, and TIA of hemodynamic origin due to fixed obstruction of the ICA, for whom the bypass surgery might be beneficial, i.e., all TIAs are not based on the same mechanism.

Arterial Occlusive Diseases↗