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Biomedical subjects

T Shiga

Publications and source records attributed to T Shiga.

At least 163 records · Page 9Linked to original sources

Diurnal variation in the diuretic effects of nitrendipine in saline loaded rats.

We have previously reported that the responsiveness of blood pressure to nitrendipine, a dihydropyridine calcium antagonist, varies with its time of administration. The present study was undertaken to examine whether the diuretic effects of the agent also show diurnal variation. Nitrendipine was given orally at 12 a.m. or 12 p.m. to rats, and urine was collected for 8 hours after administration. The urine volume and urinary sodium excretion were greater at 12 p.m. than at 12 a.m. These data indicate that the cardiovascular as well as renal effects of nitrendipine vary with its time of administration.

Animals↗

Chronopharmacology of trichlormethiazide in rats: (III). Influence on serum triglyceride and glucose.

Trichlormethiazide was given orally to rats at 10 a.m. or 10 p.m. for 14 days. The diuretic effects of the agent at 10 a.m. were greater than those at 10 p.m. on day 14. Serum concentrations of triglyceride and glucose increased in both trials. The increments in these parameters were enhanced following trichlormethiazide at 10 a.m. These data indicate that the diuretic effects of trichlormethiazide and its untoward influences on serum metabolic parameters might vary with the administration time during a repeated therapy.

Animals↗

Optical measurement of perfused rat hindlimb muscle with relation of the oxygen metabolism.

Optical measurements of myoglobin (Mb) and cytochromes (Cyts) in the isolated rat hindlimb muscle perfused with cell-free medium were performed at 35 and 15 degrees C under various oxygen supply, in the relation to the oxygen metabolism. Molar ratio of Cyt a + a3, Cyt b, Cyt c + c1, and Mb, oxygen affinity of Mb (P50), and the thermodynamic parameter (delta H degree) of Mb oxygenation in cyanide-perfused muscle were similar to those reported. The "apparent P50" of Mb in cyanide-free muscle was almost two orders larger in magnitude than P50 in the presence of cyanide. O2 uptake by the perfused hindlimb muscle was constant above O2 supply of 0.73 mumol/(min.g muscle) (under a flow rate of 1.0 ml/(min.g muscle) at 35 degrees C). Below the value of O2 supply, the O2 uptake decreased and lactate/pyruvate ratio increased. The critical mean oxygen tension in tissue (estimated by Mb oxygenation) for O2 uptake at 35 degrees C was ca. 10 mmHg. It was found that oxidation level (%) of Cyt a + a3 was equivalent to oxygenation level (%) of Mb at 35 degrees C, while the oxidation level of Cyt a + a3 was higher than the oxygenation level of Mb at 15 degrees C. Based on the results, the uneven distribution of O2 in the muscle tissue and the intracellular O2 gradient were discussed.

Animals↗

[Clinical experience of endotracheal intubation after administration of NC45-10 (vecuronium bromide 10 mg preparation)].

We studied the usefulness of the 10 mg presentation of vecuronium bromide (NC45-10) for endotracheal intubation. Subjects were ASA type I-II patients between 20-65 years of age scheduled for various kinds of surgery who consented to participate in this study. After the entrance of patients into the operating room, we set up monitors and intravenously injected a priming dosage of NC45-10, 0.015 mg.kg-1. Next, we administered thiopental 5 mg.kg-1 and injected initial dosage of either 0.065 mg.kg-1 or 0.1 mg.kg-1 of NC45-10 intravenously 5 minutes after the administration of priming dose. One minute later, we attempted endotracheal intubation. We evaluated the muscle relaxation by the reaction to endotracheal intubation and graded it by the score of 0-3. Satisfactory muscle relaxation on endotracheal intubation was obtained in 80% of the patients with no significant difference between the 2 groups of initial dosage. No side effect or cardiovascular action was observed. It is concluded that this preparation is clinically safe and useful.

Adult↗

Influence of 2,3-diphosphoglycerate on the deformability of human erythrocytes.

Effect of 2,3-diphosphoglycerate (2,3-DPG) on the deformability of human erythrocytes was examined with a rheoscope under shear stress of 8-82 dyn/cm2. With increasing 2,3-DPG in erythrocytes (from 5 to 15 mM/l cells) by incubating with inosine and pyruvate in isotonic 50 mM phosphate-buffered saline, erythrocyte deformability under uniform shear stress was remarkably impaired. But reduction of 2,3-DPG (from 5 to 2.2 mM/l cells) did not affect the deformability. In 2,3-DPG-enriched erythrocytes, increased intracellular hemoglobin concentration (MCHC), decreased intracellular pH, and increased contents of ATP and IMP (and ITP) were observed. (1) When the MCHC (i.e., the internal viscosity) was normalized by suspending in hypotonic medium, the deformability of 2,3-DPG-enriched erythrocytes was greatly improved, but still decreased. (2) The change of intracellular pH between 6.5 and 7.5 (as compared adjusting to same MCHC) did not alter the deformability. (3) The changes of purine nucleotides, ATP (0.6-2.1 mM/l cells), IMP (0-0.9 mM/l cells) and ITP (0-0.5 mM/l cells) did not alter the erythrocyte deformability. In conclusion, decreased deformability of erythrocytes induced by augmentation of 2,3-DPG is due mainly to the increased internal viscosity and due partly to the increased membrane viscoelasticity.

2,3-Diphosphoglycerate↗

Neuron-glia cell adhesion molecule (Ng-CAM) expression in the chick embryo spinal cord: observations on the earliest developing intersegmental interneurons.

The pattern of expression of the neuron-glia cell adhesion molecule (Ng-CAM) among the presumptive intersegmental interneurons in the early chick embryo spinal cord (stage 14-19) was examined using whole-mount and cryostat preparations double-stained with anti-Ng-CAM antibody and a neuron-specific anti-beta-tubulin antibody. In brachial segments, primitive longitudinal cells (PL-cells), located in the ventrolateral region of the spinal cord, express Ng-CAM both on their cell bodies and longitudinally growing axons, beginning at Hamburger-Hamilton stage 15 (embryonic day (E) 2.5). Shortly thereafter, at stage 16, circumferential cells (C-cells), composed of associational and commissural interneurons in the dorsolateral and lateral region of the spinal cord begin to express Ng-CAM both on their cell bodies and their axons which project ventrally along the lateral surface of the spinal cord. In the following stages. PL-cells express Ng-CAM strongly and begin to fasciculate to form a longitudinal fascicle in the ventrolateral marginal region of the spinal cord. C-Cells either extend their Ng-CAM-positive axons ventrally without fasciculation to join the Ng-CAM positive ipsilateral longitudinal fascicle at stage 17 (which has already been formed by PL-cell axons), or they cross the midline to join the Ng-CAM positive contralateral longitudinal fascicle after growing through the floor plate at stage 19. By stage 19, cell bodies and proximal segments of the C-cell axons exhibit decreased Ng-CAM expression, whereas the distal segment of these axons, including growth cones, strongly express Ng-CAM. Many contacts were observed between Ng-CAM-positive growth cones and axons in the ventral region of the spinal cord, both within the longitudinal fascicle and the floor plate region, suggesting the involvement of Ng-CAM in neurite-neurite interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Contribution of glycoproteins to fibrinogen-induced aggregation of erythrocytes.

The contribution of membrane glycoproteins to the velocity of fibrinogen-induced erythrocyte aggregation was examined using a rheoscope combined with a video camera, an image analyzer and a computer. The structure of glycoproteins was modified with proteolytic enzymes, trypsin or alpha-chymotrypsin. (1) Mild enzymatic treatment of erythrocytes decreased the velocity of erythrocyte aggregation, but more intense treatment increased the velocity remarkably. (2) The erythrocyte aggregation was affected not only by the density of surface negative charge of erythrocytes, but also by the structural changes of glycoproteins. (3) Erythrocyte deformability and the morphological characteristics were not altered by these enzymatic treatments. The physiological significance of glycoproteins of erythrocyte surface for the survival of erythrocytes and for the suspension stability of blood was discussed.

Adult↗

Facilitated transport of oxygen through hemoglobin solutions.

A method for quantitative analysis of hemoglobin color to estimate the oxygen saturation was developed. The method uses an image-input and -processing system composed of a 3-tube video camera and a digital image analyzer. When the system is connected to a microscope, the facilitated diffusion of oxygen in hemoglobin solutions can be observed and analyzed in a position-sensitive manner. The results led to a new transport model expressed as: J = k'CY/d, where J is the oxygen flux, C is the hemoglobin concentration, Y is the oxygen saturation of hemoglobin, d is the distance between the entrance of oxygen and the diffusion front, and k' is a constant.

Algorithms↗

Temperature effect on oxygenation and metabolism of perfused rat hindlimb muscle.

The effects of temperature on oxygenation and metabolism in perfused rat hindlimb was studied at 35 degrees C and 15 degrees C. Oxygenation of myoglobin and oxidation of cytochrome aa3 in the thigh (quadriceps) muscle were estimated from the difference spectra measured with a rapid-scanning spectrophotometer. Simultaneously, oxygen uptake and release of lactate and pyruvate were measured. (1) In hypothermia, glycolysis played a major role in energy metabolism even though Cyt aa3 was maintained in a more oxidized state than in normothermia. (2) P50 of myoglobin in perfused rat hindlimb was 5.0 mmHg at 35 degrees C, 2.3 mmHg at 25 degrees C and 1.1 mmHg at 15 degrees C. The delta H degree was -13.0 kcal/mol. (3) When about 30% of myoglobin was deoxygenated at both 35 degrees C and 15 degrees C, the oxygen uptake started to decrease and lactate release increased. (4) At 35 degrees C, the oxidation level of cytochrome aa3 was same as the oxygenation level of myoglobin. At 15 degrees C, however, the oxidation level of cytochrome aa3 was clearly higher than the oxygenation level of myoglobin. The oxygen uptake at 15 degrees C was about one third that at 35 degrees C. In conclusion, in order to maintain the aerobic condition of cytochrome aa3 in mitochondria of rat skeletal muscle, a tissue oxygen tension higher than 12 mmHg at 35 degrees C, and higher than 3 mmHg at 15 degrees C is required.

Animals↗

Effects of high alpha-linolenate and linoleate diets on erythrocyte deformability and hematological indices in rats.

Rats were fed either a high alpha-linolenate diet or a high linoleate diet from weaning to 4 mon of age. Soybean oil was used as a control. Phospholipid compositions of erythrocytes from the three dietary groups were not significantly different. However, the difference in the alpha-linolenate (18:3n-3)/linoleate (18:2n-6) ratio of the diets was reflected in the n-3/n-6 ratios of the 20 and 22 carbon highly unsaturated fatty acids except for docosahexaenoic acid (22:6n-3) in the phospholipids. Despite the significant differences in the fatty acid compositions of phospholipids, no measurable differences were detectable in erythrocyte deformability, whole blood viscosity and hematological indices of the three dietary groups. These results indicate that the beneficial effects of the high alpha-linolenate diet, as compared with the high linoleate diet, are exerted without significant changes in these parameters.

Animals↗

Erythrocyte rheology.

Two main subjects of erythrocyte rheology, deformation and aggregation, are discussed in detail, on the basis of biochemical structure. The close relationship between the life span (or cell aging) and the rheology of individual erythrocytes is also briefly described. A currently important problem is emphasized, that is, the molecular aspect of the dynamic cytoskeletal structure and the mechanism of its regulation. This concerns not only the rheological function and the survival of circulating erythrocytes, but also the pathophysiology of abnormal erythrocytes.

Blood Viscosity↗

Deformation response of red blood cells in oscillatory shear flow.

The characteristics of red cell deformation were studied, focusing on deformation response of the cells subjected to oscillatory shear stress. Red blood cells were fractionated into subpopulations of different densities, i.e., low-density and high-density cells. The deformation response of the fractionated cells was evaluated with a rheoscope varying their intracellular viscosity and oscillation frequency of the applied shear stress, and determinants of the deformation response were compared with those of whole cell deformation under stationary shear stress. When the fractionated cells were exposed to sinusoidally oscillated shear stress, the cells underwent oscillatory deformation. The degree of deformation of the low-density cells correspond to the magnitude of the applied shear stress up to an oscillation frequency of 2.7 Hz. Meanwhile, such an oscillatory deformation as to correspond to the applied shear stress was observed up to 1.7 Hz for the high-density cells. It was suggested that intracellular viscosity was an important factor to determine the deformation response of red cells to oscillatory shear stress.

Cell Survival↗

Identification of early developing axon projections from spinal interneurons in the chick embryo with a neuron specific beta-tubulin antibody: evidence for a new 'pioneer' pathway in the spinal cord.

The early development of interneurons in the chick embryo spinal cord was studied using a monoclonal antibody against a neuron-specific beta-tubulin isoform. Early developing interneurons were divided into two cell groups on the basis of their location and the pattern of growth of their axons. One group is composed of cells that establish a primitive longitudinal pathway (PL-cells), whereas the other group contains cells constituting a circumferential pathway (C-cells). The onset of axonal development in both cell groups occurs at stage (st.) 15 (embryonic day, (E), 2) in the branchial segments, which is prior to axonogenesis of motoneurons. PL-cells develop in the region between the floor plate and the motoneuron nucleus. Their axons are the first neuronal processes ('pioneer axons') to arrive in the ventrolateral marginal zone and they project both rostrally and caudally to establish a primitive longitudinal association pathway at the ventrolateral surface of the neural tube. This pathway is formed before axons of C-cells arrive in the ventrolateral region. The first C-cells are initially located in the most dorsal portion of the neural tube, whereas later appearing C-cells are also located in both intermediate and ventral regions of the neural tube. The axons of C-cells project ventrally, without fasciculating, along the lateral border of the neural tube. Some of their axons enter the ipsilateral ventrolateral longitudinal pathway at st. 17. We often observed apparent contacts and interactions between preexisting axons of PL-cells and newly arriving axons of C-cells. The axons of commissural C-cells first enter the floor plate at st. 17 and cross the midline at st. 18. Axons of C cells begin to join the contralateral ventrolateral longitudinal pathway at st. 18+ to st. 19. In the floor plate region, contacts between growth cones and axons were often observed. However, axons in the floor plate at these stages were not fasciculated. These observations establish the timing and pattern of growth of axons from two specific populations of early developing interneurons in the chick spinal cord. Additionally, we have identified an early and apparently previously undescribed 'pioneer' pathway that constitutes the first longitudinal pathway in the chick spinal cord.

Animals↗

Visible spectroscopic technique for flowing erythrocytes in capillary.

An optical spectroscopic system for determining the rate of oxygen release from flowing erythrocytes in microvessel is developed. The apparatus consists of following units attached to an inverted microscope. 1) A scanning spectrophotometer, equipped with a grating and a photon counter, was connected to an eyepiece of the microscope through a narrow light-guide, as to obtain the absorption spectrum (wave length range: 450-650 nm) of a focused spot (phi = 7 microns). 2) The velocity of erythrocyte flow was measured by dual-spots cross-correlation method, using two photomultipliers (connected to A/D converter and microcomputer) with two light-guides inserted into another eyepiece. 3) The diameter of vessel was estimated from digitized video-images, using a color image-processor. The ability of the apparatus was tested with (a) hemoglobin solution, (b) flowing erythrocyte suspension and (c) capillaries of rat mesentery. The rate of oxygen release through the vessel wall was calculated.

Animals↗

Phase II clinical trial of high-dose recombinant human tumor necrosis factor.

Based on a phase I study in 1986, 22 patients have been entered in a phase II study of high-dose human tumor necrosis factor (rH-TNF) since May 1987. Of these patients, 18 are evaluable at present, 2 are still under investigation, and 2 have dropped out. All had advanced stages of cancer (9 soft-tissue sarcomas, 3 melanomas, 5 hypernephromas) and inclusion in the study was ethically acceptable (informed consent). The daily dose of rH-TNF was 15 x 10(5) units/m2, escalated to 21 x 10(5) units/m2 (683-956 micrograms/m2 every week; range 1-6 cycles). Additional prophylactic ketoprofen administration was carried out. Of the 18 evaluable patients, 4 responded with no change (2/4, clinical improvement) and 14 showed progressive disease. The main toxicities observed were hypotension (decrease in systolic blood pressure, 21-60 Torr), leukocytosis, increases in ALAT/ASAT (WHO grade 0-4), fever (WHO grade 1-2), chills (mild to moderate), neurotoxicity (WHO grade 0-2), and nausea/vomiting (WHO grade 0-3).

Adult↗

Rheological properties of erythrocytes in recombinant human erythropoietin-administered normal rat.

Recombinant human erythropoietin [rhEPO (180 iu/micrograms); 1 or 10 micrograms polypeptide equivalent/kg] was intravenously administered daily to 6-week-old normal rats for 1 week. Rheologically, (1) blood viscosity at shear rate of 40-380 s-1 increased in a manner entirely dependent upon the haematocrit, (2) no change in erythrocyte deformability was detected by high shear rheoscopy, and (3) the velocity of rouleau formation in autologous plasma (at 7.5 s-1) decreased. Haematologically, rhEPO administration induced considerable polycythaemia with reticulocytosis in a dose-dependent manner, accompanying increased cell volume and decreased intracellular haemoglobin concentration, thus the density distribution of erythrocytes shifted towards low specific gravity. Plasma viscosity and plasma protein composition were unaffected by rhEPO-administration. In erythrocyte metabolism, no drastic alteration in the level of 2.3-DPG or ATP was detected.

Animals↗

Near UV-induced free radicals in ocular lens, studied by ESR and spin trapping.

An electron spin resonance (ESR) study on UV-photolysis of human and canine lens nuclei was carried out at room temperature. (1) At least two kinds of free radical signals, a narrow signal and a broad one, were detected at around g = 2.004. The latter is similar to that observed upon irradiation of a model solution containing both tryptophan and cysteine. (2) Two spin adducts were detected upon irradiation of canine lens in the presence of a spin trapping reagent (DMPO, 5,5-dimethyl-1-pyrroline N-oxide), i.e. a spin adduct of sulphur-centered radical (most likely glutathione thiyl radical) and the protonated adduct of solvated electron (presumably due to photo-ionization of tryptophan). (3) A tentative and simplified reaction mechanism of UV-induced damage is discussed on the basis of these observations.

Animals↗