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Biomedical subjects

K Kamiya

Publications and source records attributed to K Kamiya.

At least 325 records · Page 18Linked to original sources

The arsonomethyl group as an analogue of phosphate. An X-ray investigation.

The X-ray structure analysis of three compounds of interest as enzyme substrates is reported. They are the hydrated forms of (I) DL-2-amino-4-arsonobutanoic acid [HO-AsO2--CH2-CH2-CH(NH3+)-CO2H], (II) DL-2-amino-4-phosphonobutanoic acid [HO-PO2--CH2-CH2-CH(NH3+)-CO2H] and the hydrated barium salt of (III) D-3-phosphoglycerate [HO-PO2--O-CH2-CH(OH)-CO2-]. The structures were fully refined to R factors of 0.033, 0.053 and 0.046. For the compounds (I) and (II) the charge distribution was directly determined by locating all H atoms. The co-ordination around As and P is approximately tetrahedral, with the valency angle between the two charged O atoms enlarged to 112 degrees in compound (I), 166 degrees in compound (II) and 122 degrees in compound (III). The As-X bond distances are increased relative to P-X to accommodate the increased atomic radius. The analysis establishes that the compounds are structural analogues. Tables of co-ordinates for H atoms, anisotropic thermal parameters, bond lengths and bond angles for the three compounds have been deposited as Supplementary Publication SUP 50122 (5 pages) with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained directly [see Biochem J. (1983) 209, 5].

Aminobutyrates↗

X-ray structure analysis of thin filaments of a molluscan smooth muscle in the living relaxed state.

In the small-angle x-ray diffraction pattern of the living relaxed anterior byssus retractor muscle of Mytilus edulis, the thin filaments showed the following features. The 59.8-A reflection was much stronger and a little farther from the meridian than the 51.9-A reflection, although they are both contributions of the first-order Bessel function and are comparable with each other in the height from the equator. The 381-A reflection, given by the second-order Bessel function, was weaker than the 59.8-A reflection by more than the difference between the peak values of the first- and second-order Bessel functions, and was not so distant radially from the latter as estimated from the amount of peak shift brought about by the alteration of the Bessel order. A model of the thin filament was made on the basis of inverse Fourier transformation of the scattering amplitude, and the above features were explained by the characteristic shape of actin shown in this model. The actin subunits are elongated along the genetic left-hand helix with a pitch of 59.8 A, and are bonded together along the genetic helix in the inner part of the filament.

Animals↗

Reflex control of ventricular refractoriness in the nonischemic myocardium during coronary occlusion.

The purpose of the study was to determine whether activation of cardiac receptors and arterial baroreceptors by myocardial ischemia could elicit reflex alteration of the effective refractory period (ERP) of nonischemic ventricular myocardium in cats. Changes in ERP of nonischemic area of the right ventricle and mean arterial pressure (MAP) were measured during transient left anterior descending (LAD) coronary artery occlusion in anesthetized cats. LAD coronary occlusion for 90 sec caused a small but significant shortening of ERP (maximal change = 2.5 +/- 2.3 msec) associated with a decrease in MAP. Vagotomy significantly augmented the shortening of ERP to -3.4 +/- 1.6 msec and attenuated the decrease in MAP. After selective cardiac sympathectomy, the reflex response in refractoriness was virtually abolished. In cats with sinoaortic denervation with intact sympathetic nerves, marked attenuation was observed in the reflex change in refractoriness, although the decrease in MAP was significantly greater. These results indicate that: (1) autonomic reflexes activated during acute myocardial ischemia shorten the refractory period of nonischemic ventricular myocardium; (2) the reflex response is predominantly mediated by enhancement of cardiac sympathetic nerve activity resulting from the reduced baroreceptor activity due to concurrent hypotension.

Animals↗

An experimental study of the acute stage of subarachnoid hemorrhage.

A baboon model of subarachnoid hemorrhage (SAH) has been developed to study the changes in cerebral blood flow (CBF), intracranial pressure (ICP), and cerebral edema associated with the acute stage of SAH. In this model, hemorrhage was caused by avulsion of the posterior communicating artery via a periorbital approach, with the orbit sealed and ICP restored to normal before SAH was produced. Local CBF was measured in six sites in the two hemispheres, and ICP monitored by an implanted extradural transducer. Following sacrifice of the animal, the effect of the induced SAH on ICP, CBF, autoregulation, and CO2 reactivity in the two hemispheres was assessed. Brain water measurements were also made in areas of gray and white matter corresponding to areas of blood flow measurements, and also in the deep nuclei. Two principal patterns of ICP change were found following SAH; one group of animals showed a return to baseline ICP quite quickly and the other maintained high ICP for over an hour. The CBF was reduced after SAH to nearly 20% of control values in all areas, and all areas showed impaired autoregulation. Variable changes in CO2 reactivity were evident, but on the side of the hemorrhage CO2 reactivity was predominantly reduced. Differential increase in pressure lasting for over 7 minutes was evident soon after SAH on the side of the ruptured vessel. There was a significant increase of water in all areas, and in cortex and deep nuclei as compared to control animals.

Acute Disease↗

[Effect of diltiazem on experimental cerebral vasospasm incomparison with effects of cinnarizine, verapamil and nifedipine].

The contractile activity of arterial muscle cells is controlled by the intercellular free Ca2+ concentration. The membrane systems of both the cell surface and internal organs, seem to be responsible for controlling the myoplasmic Ca2+ level. The mechanism of action of Ca2+ antagonists, typified by verapamil and nifedipine, has been postulated to be a blockade of transmembrane calcium influx. In this study, the vasodilating effect of diltiazem on experimental cerebral vasospasm in vivo was examined using dogs and was compared with those of cinnarizine, verapamil and nifedipine which have already been reported by us. Cerebral vasospasms were induced in adult dogs by injecting 5 ml of fresh arterial blood into the cisterna magna. 10(-6)M diltiazem was injected by one shot into the vertebral artery with cerebral vasospasm. Dilatation of the cerebral arteries were monitored by angiography after administration of diltiazem. Blood pressure, intracranial pressure and pulse rate were measured during intravenous application of the drug in normal animals. Administration of diltiazem released the vasospasm for 30 minutes comparable to the times of the other Ca2+ antagonists. Diltiazem had cerebral vasodilator actions similar to cinnarizine at doses that did not decrease systemic blood pressure, while the other drugs decreased intracranial pressure slightly and nifedipine decreased pulse rate slightly. Therefore, we consider diltiazem to be satisfactory for the treatment of experimental cerebral vasospasm.

Animals↗

Therapeutic effect of ticlopidine, a new inhibitor of platelet aggregation, on chronic arterial occlusive diseases, a double-blind study versus placebo.

The clinical efficacy of ticlopidine, a platelet aggregation inhibitor, was evaluated in a double-blind placebo-controlled study on 193 patients with ischemic ulcers due to chronic arterial occlusion. In the group treated with ticlopidine, significantly better efficacy was noted over the placebo group in terms of judgment on overall improvement by doctors in charge as well as by the committee assessing with color slide films. The drug was particularly effective for the treatment of patients with occlusion in the arteries on the distal side and for the ischemic ulcer with relatively small size. In the group with ticlopidine, granulation was significantly improved compared to the placebo group. Those patients who had pain due to arterial occlusion on the distal side were significantly improved by this agent. The mean diameters of ulcers were clearly reduced. Therefore, this agent could possibly be claimed as an effective remedy against the main symptoms of chronic arterial occlusion. The frequencies of side effects and abnormalities in laboratory tests were comparable in the group treated with ticlopidine to those of the group with placebo. It was, therefore, concluded that this agent has an outstanding clinical value as a conservative treatment in chronic arterial occlusion.

Arterial Occlusive Diseases↗

Establishment and immunologic characterization of 3-methylcholanthrene-induced sarcoma cell lines metastasizing widely in mice and exhibiting distinct and selective propensities for the mode of metastasis.

Successive transplantations of metastatic secondary tumors of a 3-methylcholanthrene-induced sarcoma in (C57BL/Ka X C3H/He)F1 male and female syngeneic mice resulted in the establishment of two unique tumor cell lines with enhanced metastatic potential. Moreover, each line showed distinct and selective propensities for the mode of metastasis. The 1101Pn tumor line, obtained by successive transplantations of metastatic pulmonary nodules, metastasized to many visceral organs via the bloodstream. Another tumor line, 1101Ln, selected by repeated transplantations of lymph node metastases, metastasized to almost all lymph nodes and to the lungs. When the metastatic pulmonary tumor of mice bearing 1101Ln was subcutaneously implanted on the backs of syngeneic mice, the tumor grew locally and eventually metastasized via the lymphatics, with systemic involvement of the lymph nodes. This finding is an indication that the intrinsic properties of tumor cells that form pulmonary metastases in 1101Ln tumor-bearing mice are distinct from those in 1101Pn tumor-bearing mice in terms of metastatic mode. The 1101Pn and 1101Ln tumor lines were nonimmunogenic or less immunogenic than the 505 tumor (the parental, nonselected tumor line). The growth and metastatic action of 505 tumors were enhanced by 400 R whole-body X-radiation, but no such effect was seen with 1101Pn tumors. Pretreatment of mice with OK-432, an immunopotentiator, retarded the growth and metastasis of 505 tumors but exerted little or no effect on 1101Pn tumors. The experimental results suggest that a tumor is composed of a heterogeneous cell population with respect to metastatic potential, metastatic mode, and tumor immunogenicity and that some intrinsic properties of the tumor cell have a primary role in the determination of the mode of cancer metastasis.

Animals↗