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Biomedical subjects

A Kato

Publications and source records attributed to A Kato.

At least 595 records · Page 33Linked to original sources

Hemodynamic effect of bunitrolol on patients with ischemic heart disease. Comparison with propranolol.

Acute hemodynamic changes induced by two beta-blocking agents, bunitrolol and propranolol, in patients with ischemic heart disease were studied. Besides possessing negative chronotropic and inotropic effects which were demonstrated by decreased heart rate (HR), cardiac index (CI) and double product (DP) of the heart, propranolol significantly increased systemic vascular resistance (SVR, 12%, p less than 0.05) and the time constant of left ventricular (LV) isovolumic pressure fall (T, 10%, p less than 0.01). With bunitrolol, no significant changes were observed in indexes reflecting chronotropic and inotropic states of the heart, and CI and DP were essentially unchanged. Only LV systolic pressure (-5%, p less than 0.01), LV end-diastolic pressure (EDP, -17%, p less than 0.01) and T (-10%, p less than 0.05) decreased significantly. Systemic vascular resistance (SVR) decreased, though insignificantly. Myocardial oxygen supply-demand balance in the resting state was not improved by propranolol as evidenced by the fact that CI decreased in proportion to the decline in DP. In contrast, ischemia at rest was apparently improved by bunitrolol because LV wall stress decreased due to the reduction in LV volume which was suggested by the decline in LV systolic pressure and LVEDP while CI remained constant. Improvement of the time constant T might be strong evidence of relief from ischemia. Bunitrolol might be effective even in patients with overt heart failure, especially that due to ischemic heart disease because of its lack of negative inotropic action and its ameliorating effect on ischemia at rest.

Cardiac Catheterization↗

Proofreading function associated with the RNA-dependent RNA polymerase from influenza virus.

The influenza virus-associated RNA polymerase cleaves capped RNA in an endonucleolytic manner and the transcription is initiated by the addition of GMP, the first substrate to be polymerized under the direction of viral RNA template, onto 3'-termini of resulting capped RNA fragments. In the presence of high concentrations of GTP as a sole substrate, multiple GMP residues were polymerized onto the primers. By the addition of the second substrate CTP, excess GMP residues, other than the 1st residue, were removed prior to elongation. The result may suggest that the RNA-dependent RNA polymerase carries a proofreading function.

Cytidine Monophosphate↗

The complete nucleotide sequence of the tobacco chloroplast genome: its gene organization and expression.

The complete nucleotide sequence (155 844 bp) of tobacco (Nicotiana tabacum var. Bright Yellow 4) chloroplast DNA has been determined. It contains two copies of an identical 25 339 bp inverted repeat, which are separated by a 86 684 bp and a 18 482 bp single-copy region. The genes for 4 different rRNAs, 30 different tRNAs, 39 different proteins and 11 other predicted protein coding genes have been located. Among them, 15 genes contain introns. Blot hybridization revealed that all rRNA and tRNA genes and 27 protein genes so far analysed are transcribed in the chloroplast and that primary transcripts of the split genes hitherto examined are spliced. Five sequences coding for proteins homologous to components of the respiratory-chain NADH dehydrogenase from human mitochondria have been found. The 30 tRNAs predicted from their genes are sufficient to read all codons if the ;two out of three' and ;U:N wobble' mechanisms operate in the chloroplast. Two sequences which autonomously replicate in yeast have also been mapped. The sequence and expression analyses indicate both prokaryotic and eukaryotic features of the chloroplast genes.

Journal Article↗

Fiberoptic observation of thrombosis and thrombolysis in isolated human coronary arteries.

Coronary arteries isolated from cadavers autopsied within 7 hours after death were perfused with canine arterial blood, and the processes of thrombus formation at the segments stenosed with atheroma and the thrombolytic effects of urokinase were investigated by angioscopy. Ten minutes of blood perfusion caused thin mural thrombi localized at the stenotic or nonstenotic segments. During 30 minutes of blood perfusion, the thin mural thrombi of the outlet or inlet of the segment grew into a doughnut-shaped thrombus. Also, the thin mural thrombi in the stenotic segment grew into a streamer-like thrombus and drifted downstream. These thrombi grew in size with increasing perfusion time and finally obstructed the stenotic segment. Globular thrombi close to the outlet also were formed in a few preparations. Unlike the thrombi at the stenotic segment, the mural thrombi in the nonstenotic segments did not grow into massive thrombi. The thrombi were reduced in size within 10 minutes of perfusion with 320 U/ml or more of urokinase. During thrombolysis, sandstorm-like dispersion of the blood cells occurred, small fragments detached from the mother thrombus and flew downstream, or the fibrin core of the thrombus was exposed. The results indicate the usefulness of angioscopy for the dynamic and serial investigation of thrombosis and thrombolysis.

Adult↗

Effect of vascular activity in the determination of rate constants for the uptake of 18F-labeled 2-fluoro-2-deoxy-D-glucose: error analysis and normal values in older subjects.

Regional cerebral blood volume (CBV) can be calculated using data obtained during the kinetic analysis of 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) uptake measured by positron emission tomography (PET). As a result the influence of vascular activity upon the determination of FDG rate constants can be minimized. The method is investigated by simulation experiments and by analysis of PET studies on seven older, healthy human volunteers aged 52-70 years. The accuracy of measured FDG rate constants k1, k2, and k3, obtained either by omitting the early portion of the uptake curve or by explicit inclusion of CBV as a fit parameter, is compared. The root mean square error in measured rate constant for the latter method is equivalent to that obtained by omitting the first 2.5-3 min of tissue data and neglecting the CBV term. Hence, added information about the physiological state of the tissue is obtained without compromising the accuracy of the (FDG) rate constant measurement. In hyperemic tissue the explicit determination of the vascular fraction results in more accurate estimates of the FDG rate constants. The ratio of CBV determined by this method to CBV obtained using C15O in six subjects with CBV in the normal range was 0.92 +/- 0.32. A comparison of the CBV image obtained by this method with that obtained using C15O in an arteriovenous malformation case demonstrates the accuracy of the approach over a wide range of CBV values. The mean value for CBV fraction in gray matter obtained by this method in the older control group was 0.040 +/- 0.014. Average gray matter rate constants obtained were k1 = 0.084 +/- 0.012, k2 = 0.150 +/- 0.071, and k3 = 0.099 +/- 0.045 min-1.

Aging↗

Regional cerebral ischemia in the gerbil: measurement of regional cerebral blood flow by quantitative autoradiography.

Alterations in the regional CBF after occlusion of the posterior communicating, middle cerebral, or common carotid artery were investigated in the gerbil with a quantitative autoradiographic technique using [14C]iodoantipyrine. Occlusion of the posterior communicating artery produced severe ischemia in the ipsilateral hippocampus, thalamus, and dorsal mesencephalon. Occlusion of the middle cerebral artery produced severe ischemia in the ipsilateral rostral and central cerebral cortex and lateral caudate-putamen. Occlusion of the common carotid artery produced ipsilateral hemispheric ischemia of variable degrees. The distribution and degree of cerebral ischemia produced by occlusion of one of these arteries correlated closely to the arterial territory and the extent of collateral blood supply. Since the areas affected after occlusion of the posterior communicating or middle cerebral artery differ, those models will be useful for the comparative investigation of the ischemia-related cerebral pathophysiology associated with different sites of primary lesion.

Animals↗

Corneal permeability of aldose reductase inhibitor, M79175. I. In vitro study using corneal permeability apparatus.

Transcorneal permeability of M79175, aldose reductase inhibitor (Eisai), and various factors influencing it were examined using excised rabbit cornea mounted on the methacrylate apparatus. High permeability was exhibited and this was independent of the concentration of M79175. Cornea hydrated by exposure to the eye drop solution of high concentration of benzalkonium chloride, which had an enhancing effect on the permeability of M79175. Corneal hydration was also caused by the solution of low pH. These findings will show the basic conditions for this eye drop solution to be an artificial tear fluid.

Aldehyde Reductase↗

Corneal permeability of aldose reductase inhibitor, M79175. II. In vivo study on pharmacokinetic aspect.

Transcorneal permeability of M79175 was estimated in vivo and the effects of pH and thickening agent on it were examined. The aqueous humor concentration of M79175 versus time profile showed the peak concentration of 850 ng/ml at 20 min after instillation of pH 7.0 eye drop solution. The permeability constant of M79175 was estimated by applying a physiologically based pharmacokinetic model to this profile. As was expected from the results in vitro, high permeability constant was observed in vivo. Lowering the pH of the solution demonstrated the tendency to decrease the concentration at 20 min. Thickening agent, Hydroyethylcellulose, did not change the aqueous humor concentration versus time profile. Ocular tissue distribution was examined using 14C-M79175. As was expected from the results of corneal permeability, high levels of M79175 accumulated to the lens.

Aldehyde Reductase↗

Phasic contractions of canine and human coronary arteries induced by potassium channel blockers.

To gain insight into mechanisms underlying phasic coronary vasospasm in patients with variant angina pectoris, we studied whether phasic contractions could be induced in isolated canine and human coronary arteries by agents which block potassium channels. Phasic contractions of canine coronary arteries were always induced by 3,4-diaminopyridine (10(-2) M) and less frequently by 4-aminopyridine (10(-2) M). These agents also caused phasic contractions in human, swine and monkey coronary arteries and in canine basilar, carotid, renal and femoral arteries. The cycle length of phasic coronary contractions ranged from 30 sec to 1 hour, and the developed tension was 2.5 times greater than for potassium contractions. The contractions continued for more than 11 hours. Morphologically, perinuclear vacuolization, a characteristic change of vasospasm, appeared in the coronary smooth muscles. The phasic contractions were not eliminated by tetrodotoxin, atropine, phentolamine or yohimbine, but they were eliminated by nicorandil which activates potassium channels and nifedipine which blocks slow calcium channels. The results indicate that potassium channel blockers can induce phasic arterial contractions.

4-Aminopyridine↗

Growth experiment of Hantaan virus in A549 cells: an attempt to improve the immunofluorescent antibody technique for hemorrhagic fever with renal syndrome.

An assay method for the infectivity of Hantaan virus, a causative agent of HFRS (hemorrhagic fever with renal syndrome), was developed by the use of IFA (immunofluorescent antibody technique). With the aid of this method, the growth characteristics of Hantaan virus, 76-118 strain, were followed in A549 cells. At a maximal MOI (multiplicity of infection) of 1.6 VAIU (viral antigen-inducing units) per cell, the conventionally available value, plateau level potencies of the viral antigen and virus infectivity were attained at eight and ten days postinfection, respectively, and most of the infective virus produced accumulated in the culture fluids of infected cells. When infections were defined with MOI values in terms of VAIU per cell, development of the viral antigen was highly consistent and followed a given pattern of kinetics. Based on these findings, a protocol for preparation of the viral antigen in IFA was presented, wherein spot culture and FBS treatment were emphasized as effective procedures to minimize non-specific staining.

Animals↗

[Mechanism and overcoming of resistance in ACNU-resistant sublines of rat brain tumors].

One of the most serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of such resistance to ACNU and the means to overcome it, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU were selected in vivo. Uptake and retention of ACNU in these resistant cells were studied with [14C] ACNU. The results indicated that the resistance exhibited by both sublines of C6/ACNU and 9L/ACNU were due to both reduced uptake and retention of the drug. In an attempt to clarify the more detailed biochemical mechanism of resistance in these cells, we surveyed various membrane-modifying agents which potentiate the sensitivity of these resistant cells to ACNU. Among a number of membrane-modifying agents, calcium antagonists, especially nicardipine and verapamil, were found to cause retention of ACNU in the resistant cells and to enhance the effect of ACNU on these resistant cell lines. It might therefore be concluded that ACNU resistance can be overcome by membrane-modifying agents, such as nicardipine and verapamil.

Animals↗

[Studies on the mechanism of ACNU resistance in sublines of rat C6 glioma and 9L gliosarcoma in vitro].

One of the serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of this resistance against chemotherapeutic agents, especially ACNU, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride] were selected previously in vivo from rat C6 glioma and 9L gliosarcoma, respectively. Uptake and retention of ACNU in these resistant cells were studied with [14C]ACNU. The result indicated that the resistance exhibited by both sublines of C6/ACNU and 9L/ACNU cells were due to the reduced uptake and retention of the drug. The study of the effects of oxidative phosphorylation inhibitor, DNP (2, 4-dinitrophenol), on the uptake and retention of ACNU suggested that there is an active outward transport mechanism for ACNU in 9L/ACNU cells. It might be concluded that ACNU-resistant brain tumor cells are resistant to ACNU by virtue of both the reduced uptake of the drug and the increased active efflux.

Animals↗

[Development of experimental meningeal gliomatosis models using nude mice].

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of human glioma cell lines into nude mice. The tumor growth was steady and fast in MG nude mice if 10(7) cells were implanted. Median survival time (MST) of nude mice inoculated with tumor cells was inversely related to the number of cells inoculated. There was a correlation between in vitro and in vivo (MG models) growth rate, which means that the cell kinetics in vitro are reflected in vivo. The clinicopathological features observed in nude mouse MG models were similar to those seen in diffuse leptomeningeal involvement of gliomas in humans. The models will be useful for investigating the pathophysiology of meningeal gliomatosis and the efficacy of chemotherapeutic agents.

Animals↗

Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography.

Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using 18F-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of 18F. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced (especially in gray matter) and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. These changes in the peri-tumoral region may be secondary to edema. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. On a narrow margin of tumor and brain, corresponding to a zone of increased vascularity, CBF was moderately high. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

Animals↗

Location and nucleotide sequence of the genes for tobacco chloroplast tRNAArg (ACG) and tRNALeu(UAG).

The location and nucleotide sequence of the genes and flanking regions for tRNAArg(ACG) and tRNALeu(UAG) on tobacco chloroplast DNA have been determined. The gene arrangement is 5S rRNA-260 bp-tRNAArg-581 bp-tRNAAsn-5.2 kbp-tRNALeu. The tRNAArg and tRNALeu genes are expressed in the chloroplasts. The opposite strand of the tRNAArg gene contains a tRNAArg-like sequence. The tRNAArg, tRNAAsn and tRNALeu coding regions are contained in open reading frames.

Base Sequence↗

Purification and enzymatic properties of an RNA polymerase-RNA complex from influenza virus.

An RNA polymerase-viral RNA complex was purified from influenza A/PR/8 virions by combination of cesium trifluoroacetate centrifugation and phosphocellulose column chromatography. Surface proteins were removed from the detergent-treated virions by the centrifugation. Starting from the M protein-free ribonucleoprotein (RNP) fraction, an RNA polymerase-RNA complex lacking NP protein was isolated by repeated chromatography on phosphocellulose columns. The isolated RNA polymerase-RNA complex, which is composed of PB1, PB2, PA and vRNA, cleaved capped poly(A) endonucleolytically at 10-12 nucleotides from the 5' end and incorporated GMP into the 3' end of the resulting capped fragments. In the presence of all four ribonucleotide triphosphate substrates, the cleaved fragments were elongated to polynucleotides in the absence of exogenous vRNA. The RNA synthesis was primed not only by capped polynucleotides but also dinucleotide ApG. These results indicate that the purified RNA polymerase-RNA complex is as active in viral mRNAs synthesis as native RNP and that NP protein is not required for the catalytic function.

Centrifugation, Isopycnic↗

Quantification of glucose utilization in an experimental brain tumor model by the deoxyglucose method.

Reevaluation of lumped and rate constants is necessary when Sokoloff's 2-deoxyglucose (DG) method is used to measure glucose utilization in pathological tissue. We describe here a modification of Sokoloff's lumped constant measurement that permits simultaneous estimation of both lumped and rate constants from a single animal experiment. A subcutaneous tumor model (AA ascites tumor) was used for measurement of these constants with a procedure similar to Sokoloff's that kept the plasma tracer concentration constant. Measured constants were as follows: lumped constant, 0.654 +/- 0.081; k1, 0.196 +/- 0.038 min-1; k2, 0.262 +/- 0.067 min-1; k3, 0.117 +/- 0.044 min-1. These constants were used to quantify glucose utilization in the implanted brain tumor. To test the validity of this method, we compared a fraction of the free DG pool calculated using the tumor constants with a fraction measured directly by chromatographic analysis of tissue samples from both subcutaneous tumor and implanted brain tumor. The values derived by chemical analysis agreed well with those predicted by the calculations. The value of k4 varied from 0.0031 +/- 0.0018 min-1 for the tumor tissue to 0.0214 +/- 0.0024 min-1 for tumors with a large necrotic center. This method would be especially useful when applied to xenograft human gliomas in nude mice for quantification of glucose utilization in human gliomas by means of positron emission tomography.

Animals↗