Activation of carcinogens by human liver cytochromes P-450.
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Animals↗
Biomedical subjects
T Shimada
Publications and source records attributed to T Shimada.
Trimebutine maleate has inhibitory effects on the voltage-dependent Ca2+ inward current and other membrane currents in intestinal smooth muscle cells.
We examined effects of trimebutine maleate on the membrane currents of the intestinal smooth muscle cells by using the tight-seal whole cell clamp technique. Trimebutine suppressed the Ba2+ inward current through voltage-dependent Ca2+ channels in a dose-dependent manner. The inhibitory effect of trimebutine on the Ba2+ inward current was not use-dependent. It shifted the steady-state inactivation curve to the left along the voltage axis. Trimebutine also had inhibitory effects on the other membrane currents of the cells, such as the voltage-dependent K+ current, the Ca2(+)-activated oscillating K+ current and the acetylcholine-induced inward current. These relatively non-specific inhibitory effects of trimebutine on the membrane currents may explain, at least in part, the dual actions of the drug on the intestinal smooth muscle contractility, i.e. inhibitory as well as excitatory.
Animals↗
Densitometric analysis of beta 1- and beta 2-adrenoceptors in guinea-pig atrioventricular conducting system.
Quantitative autoradiography was used to determine the densities of beta 1- and beta 2-adrenoceptors in the atrioventricular conducting system in guinea-pig. (-)[125I]Cyanopindolol (CYP) was used to label beta 1- and beta 2-adrenoceptors in the absence or presence of the beta 1-adrenoceptor selective antagonist CGP 20712A (100 nM) or the beta 2-adrenoceptor selective antagonist ICI 118,551 (70 nM) or the non-selective beta-adrenoceptor antagonist (-)-propranolol (1 microM). Protein in discrete anatomical regions was determined using a densitometric method based on the dye Coomassie brilliant blue G. In the atrioventricular conducting system the proportion of beta 2-adrenoceptors determined by inhibition of total (-)[125I]-CYP binding by CGP 20712A (100 nM) ranged from 32.5% (atrioventricular node) to 48.7% (left bundle branch). In the atrioventricular node (16.8 fmol/mg protein), bundle of His (12.1 fmol/mg protein), right (17.4 fmol/mg protein) and left (21.1 fmol/mg protein) bundle branches and Purkinje cells there was a higher density of beta 2-adrenoceptors than in the interventricular septum (8.4 fmol/mg protein) and right atria (8.3 fmol/mg protein). The medial smooth muscle of the aorta, aortic valve, adventitia of the aorta, nerve tissue, tricuspid and mitral valves contained only beta 2-adrenoceptors. It is speculated that the use of beta-adrenoceptor antagonists to control cardiac arrhythmias involving a defect in conduction in the atrioventricular node should take into consideration both beta 1- and beta 2-adrenoceptors.
Adrenergic beta-Antagonists↗
Metabolic deactivation of furylfuramide by cytochrome P450 in human and rat liver microsomes.
Metabolic deactivation of furylfuramide by human and rat liver microsomal cytochrome P450 enzymes has been investigated in a system measuring induction of umu gene expression response in Salmonella typhimurium TA1535/pSK1002. Both human and rat liver microsomes catalyzed the metabolism of furylfuramide to inactive form(s) that are incapable of inducing umu gene expression in the tester strain. The reaction required an NADPH-generating system and molecular oxygen and was inhibited by carbon monoxide, suggesting that a cytochrome P450-linked mono-oxygenase system is prerequisite for the deactivation reaction. With liver microsomes from variously pretreated rats, 3-methylcholanthrene was found to be a powerful inducer for the furylfuramide-metabolizing activity, and antibodies raised against rat P450IA1(BNF-B, c) and P450IA2(ISF-G, d) inhibited the microsomal activity. Human liver microsomal furylfuramide-metabolizing activity was also inhibited significantly by anti-P450IA2 IgG but weakly by anti-P450IA1 IgG. In liver microsomes prepared from seven different human samples, the activities of deactivation of furylfuramide were found to correlate with the amounts of immunoreactive protein related to rat P450IA2 and with the monooxygenase activities of metabolic activation of 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (MeIQ) and of ethoxyresorufin O-deethylation. These results suggest that P450IA1 and P450IA2 in rats, and P450PA (IA2, the phenacetin O-deethylase and ortholog of rat P450IA2) in humans are the major enzymes involved in the deactivation of furylfuramide in liver microsomes. The metabolic studies involving HPLC analysis of products followed by spectrophotometric examination have also suggested that furylfuramide can be degraded very rapidly through the aerobic metabolism by liver microsomes.
Animals↗
A new method for repairing skin defects of the lower leg under unsatisfactory conditions: utilization of peroneal island flap from the opposite sound leg.
As a new procedure for the repair of tissue defects in the lower leg under unsatisfactory conditions, we have devised a surgical procedure for peroneal island flap transfer from the opposite sound leg. This report presents three patients treated by cross-leg island flaps with reversed blood flow. This procedure can be applied for reconstruction of the leg with severe circulatory disturbance caused by arterial damage due to trauma and arterial disease such as Buerger's disease. Furthermore, joint exercise is possible because the pedicle is long and no rigid immobilization is required.
Humans↗
The vasculature of the peroneal tissue transfer.
Peroneal vascularized composite-tissue transfer has many useful applications and advantages. An anatomic study of the peroneal artery and vein and their branches was carried out on 80 adult cadaver legs. The number of cutaneous branches averaged 4.8 +/- 1.4 per leg. The length of the cutaneous branches averaged 5.4 +/- 1.5 cm. The external diameters of cutaneous branches at the skin distribution site were 0.6 +/- 0.2 mm for the artery and 0.8 +/- 0.3 mm for the vein. The communicating branches were branched at anterior or posterior tibial vessels 6.1 +/- 2.4 cm proximal to the lateral malleolus. The range of rotation of the island flap when transposed proximally was 14.3 +/- 3.3 cm proximal from the head of the fibula, and when transposed distally, the range of rotation was 16.9 +/- 5.3 cm distally.
Aged↗
Relaxation of mesenteric artery of stroke prone spontaneously hypertensive rats by calcium removal.
1. The time courses of the relaxation, induced by removal of extracellular Ca2+, of K-depolarized mesenteric artery preparations from stroke prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were compared. 2. The time course of the decline in extracellular Ca2+ was estimated from the time course of the relaxation and the concentration-response curve of K(+)-depolarized preparations to Ca2+. The time course of the decline in the intracellular free Ca2+ concentration was also estimated from the reported relation between Ca2+ concentration and the contraction of skinned vascular smooth muscle. 3. The time course of relaxation was exponential, the curve being made up of three components. The time course was slower in preparations from SHRSP, especially the first component of the relaxation curve. 4. The time courses of the decline in the intracellular and extracellular Ca2+ concentrations were also exponential, being made up of three components and were also slower in the preparation made from SHRSP. 5. The wall and muscle layer of the mesenteric arteries used in the present experiments were significantly thicker in the SHRSP preparations. 6. Calculation of the half relaxation time, based on the diffusion of Ca2+ across the blood vessel wall, suggested that the slower relaxation in preparations from SHRSP is due largely to the thicker muscle layer, although differences in Ca2+ sequestration by the smooth muscle cells may also be involved.
Animals↗
Detection of human T-cell leukemia virus type I (HTLV-I) provirus in an infected cell line and in peripheral mononuclear cells of blood donors by the nested double polymerase chain reaction method: comparison with HTLV-I antibody tests.
Human T-cell leukemia virus type I (HTLV-I) provirus DNA from the cultured cell line HUT 102 and from peripheral mononuclear cells (PBMC) of anti-HTLV-I antibody-positive Japanese blood donors was detected by the nested double polymerase chain reaction (PCR) method. This procedure consists of a first amplification and a second amplification with the products of the first amplification and primers interior to the first primers. Using this method, we demonstrated that it is possible to detect single-template DNA. Polyacrylamide gel electrophoresis of the nested double PCR products, with our primers, revealed three bands with excess amounts of template DNA, two bands with moderate amounts, and a single band with limited amounts. The amount of provirus in PBMC was roughly estimated from the results of the nested double PCR. Particle agglutination (PA) assays and indirect immunofluorescence testing (IF) with mixed MT-2 cells and Molt-4 cells as targets to detect anti-HTLV-I antibody were performed, and the results were compared with those of the nested double PCR of the pX region. None of the 101 PA-negative samples were positive in either the IF or PCR test. Of the 155 samples that were antibody positive by the PA assay, 57 were positive by both PCR and IF. Furthermore, the results of the IF and PCR tests coincided completely. It was therefore concluded that the IF method is most appropriate for confirmation of the PA assay currently used in most diagnostic laboratories and blood centers.
Base Sequence↗
Enhanced ultrastructural preservation of cartilage proteoglycans in the extended state.
We investigated the preservation of proteoglycan (PG) structure in rat epiphyseal cartilage using N-N-dimethylformamide (DMF) dehydration before embedding. After aldehyde fixation, specimens with and without routine osmium post-fixation were dehydrated in graded DMF and embedded in either Spurr's resin or Lowicryl K4M resin. Standard ethanol dehydration with Spurr or Lowicryl embedding techniques resulted in the formation of condensed PGs, called matrix granules. DMF dehydration before embedding greatly improved the preservation of PG structure and resulted in an extended appearance of PGs closely resembling the fine filamentous network of cartilage tissues processed by rapid freezing and freeze-substitution. However, en bloc staining of aldehyde-fixed specimens with cationic reagents before or during DMF dehydration induced the condensation of PGs and resulted in the formation of matrix granules. These observations demonstrate that DMF, a mild dehydration agent, dramatically improves PG preservation without a harmful effect on aldehyde-fixed PG structure and can be utilized regardless of routine post-fixation.
Animals↗
Regulation of external work of concentric hypertrophied left ventricles in unanesthetized hypertensive dogs.
This study aimed to evaluate the change in external work and its control mechanism in the concentric hypertrophied heart induced by systemic hypertension. The calculated stroke work, myocardial contractility, afterload, and preload were examined in the baseline period (Control Stage, CS) and in the eighth week after the induction of perinephritic hypertension (Hypertensive Stage, HS) in unanesthetized dogs. These variables were examined with echocardiograms and high-fidelity left ventricular (LV) and ascending aortic pressures. Mean aortic pressure was significantly (p less than 0.05) elevated from 95 +/- 10 to 134 +/- 27 mmHg in HS. The ratio of end-diastolic wall thickness to radius significantly (p less than 0.05) increased in the HS. The calculated stroke work of the LV chamber was significantly (p less than 0.05) increased from 7022 +/- 1203 to 8860 +/- 1548 X 10(3) erg in HS while the stroke work normalized for wall thickness by calculating the wall stress was not altered (3069 +/- 1086 v.s. 2989 +/- 866 erg; CS v.s. HS) with no significant change in heart rate in HS. In the HS, the end-systolic wall stress (afterload) and the slope of end-systolic wall stress-dimension relationship (myocardial contractility) were unchanged while the end-diastolic wall stress (preload) slightly reduced. These results suggest that, in the concentric hypertrophied left ventricle induced by systemic hypertension, the LV myocardial external work is normal, whereas the LV chamber external work increases.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Field emission scanning electron microscopic study on the noninfarcted myocardium after myocardial infarction.
Intracellular membranous ultrastructural changes in the noninfarcted myocardium of the left ventricle were studied by examining experimental myocardial infarction in rats with a field emission scanning electron microscope. The left coronary artery was ligated at its origin for 7 days. The resulting infarcts comprised approximately 40% of the total area of the left ventricles. In a light microscopic study, the transverse diameter of myocytes had increased to 17.1 +/- 2.9 microns in the noninfarcted myocardium, compared to 14.1 +/- 3.1 microns in the myocardium of sham-operated rats (p less than 0.01). For the scanning electron microscopic study, the specimens were processed according to the Osmium-DMSO-Osmium method. Marked morphological changes of intracellular membranous structures were found in the noninfarcted myocardium, especially in the lacelike network of sarcoplasmic reticulum which occasionally formed large flattened cisternae, and in the marked proliferation of surface caveolae. It is speculated that these early ultrastructural changes in the noninfarcted myocardium reflect an adaptation of microorganellae in the failing hearts of the rats.
Animals↗
Changes of lymphocyte subpopulations and natural killer cells in mice sensitized with Toxoplasma lysate antigen before and after Babesia infection.
When 8-week-old BALB/c mice were sensitized with two intramuscular injections of Toxoplasma lysate antigen (TLA) at 2 week interval, the numbers of sIg(+), Thy-1,2(+), Lyt-1,2(+) Lyt-2,2(+), and Asialo GM1(ASGM1)(+) cells in the spleen, liver and peripheral blood increased by 2 to 4 times over those found in unsensitized mice of the same age. When TLA-sensitized and unsensitized mice were infected with Babesia, 4 of 10 (40%) of the TLA-sensitized mice survived infection, while none of the unsensitized control mice lived longer than 14 days after Babesia infection. By contrast, sensitization of nude mice with TLA had no effect on survival, and mice did not live more than 12 days. The number of thymic Thy-1,2(+) cells decreased in TLA-sensitized and unsensitized BALB/c mice by almost 80% within 10 days after infection (AI). During the same time, the numbers of B cells, T cells, and NK cells increased in the spleen, liver and peripheral blood of both sensitized and unsensitized mice. Especially notable were increases in numbers of Lyt-2,2(+) cells in the spleen and blood and increases in numbers of NK cells in the spleen, liver and blood in both TLA-sensitized and unsensitized mice. When spleen cells from TLA-sensitized and unsensitized mice were cultured in the presence or absence of TLA for 6 days, assays for cytotoxicity using NK-insensitive P-815 target cells and NK-sensitive YAC-1 target cells demonstrated higher rates of cytotoxicity in cultures of TLA-sensitized spleen cells.
Animals↗
Morphological studies of the cardiac lymphatic system.
The distribution and structure of the mammalian cardiac lymphatic system have been investigated by puncture injection, intra-arterial injection of silver nitrate, hydrogen peroxide immersion, and light and electron microscopy. The cardiac lymphatic system consists of drainage vessels and lymphatic capillaries. The drainage vessels contain many valves and are mainly situated subepicardially following branches of the coronary artery. The lymphatic capillaries are composed of a thin layer of endothelial cells, and form relatively dense networks in a fishnet arrangement. These lymphatic networks are richer in the ventricles than in the atria, being present in the subepicardial myocardial and subendocardial regions. In addition, networks are found in all cusps of the atrioventricular valves, and in the sinuatrial node and atrioventricular system. The lymphatic system maintains cardiac homeostasis by receiving proteins, electrolytes and excess fluid from the interstitial tissue and returning them to the venous system.
Animals↗
Two serogroups of Vibrio cholerae non-O1 possessing somatic antigen factors in common with Hakata serogroup of V. cholerae.
Two serogroups of Vibrio cholerae non-O1 possessing somatic antigen factors in common with Hakata serogroup of V. cholerae are described. One group was included in the Hakata serogroup and has its own antigen other than all O-antigens of the Hakata group. The other group had its own major antigen, but not factor F specific for the Hakata group.
Agglutination Tests↗
A new selective, differential agar medium for isolation of Vibrio cholerae O1: PMT (polymyxin-mannose-tellurite) agar.
A new selective and differential agar medium, polymyxin-mannose-tellurite (PMT) agar was devised to differentiate easily colonies of Vibrio cholerae O1 from those of V. cholerae non-O1. The differentiation between colonies of the two vibrios is based on mannose-fermentation. Colonies of V. cholerae O1 on the agar are agglutinated with O1 antiserum of V. cholerae much more easily than those on thiosulfate-citrate-bile salts-sucrose (TCBS) agar.
Agar↗
Evaluation of a simple staining method for flagella using "flagella staining solution-Shionogi".
A flagella staining method using "Flagella Staining Solution-Shionogi" was tested for its reliability and convenience for a routine procedure in the clinical laboratory. The staining has proved to be accurate and reliable and can be used easily as a simple staining method.
Bacteria↗
[Coronary circulation, myocardial metabolism and cardiac catecholamine flux in patients with syndrome X].
To clarify the pathogenesis of syndrome X (Sx), hemodynamics, coronary circulation, myocardial lactate metabolism and cardiac catecholamine flux were studied before and during bicycle ergometry in 25 patients (pts) and these data were compared with those in 15 with effort angina (EA) and in eight controls. The results were as follows: 1. The cardiac index during exercise decreased in EA pts probably due to their coronary lesions, while those in the controls and Sx were well preserved. 2. An increase of coronary blood flow during exercise, both in Sx and EA pts, was significantly impaired and the myocardial extraction ratio of lactic acid was significantly lower compared with those in the controls. The cardiac norepinephrine release during exercise was markedly higher in Sx, compared with that in controls and in EA. These results suggested that in Sx, excessive sympathoadrenergic stimulation may play an important role in restricting coronary reserve and in accelerating myocardial anaerobic metabolism.
Angina Pectoris↗
[Early diastolic dysfunction of the left ventricle and its relation to histopathological findings in patients with diabetes mellitus].
The relation of left ventricular diastolic function and the histopathological findings of the myocardium in patients with diabetes mellitus were observed using echocardiography and endomyocardial biopsy. The subjects consisted of six diabetic patients (mean age 49.3 years) and eight normal control subjects (mean age 44.8 years). Coronary angiography had no significant stenotic lesions in their coronary arteries. Their diabetic complications were mild to moderate in severity. Echoes from the left ventricular margin of the septum and from the posterior left ventricular wall were traced on a digitizing board; then the isovolumic relaxation period, rapid filling period, slow filling period and atrial contraction period were determined to calculate fractional shortening (FS), isovolumic relaxation time (IRT), and three filling volumes (RFV, SFV and ACV). The quotients of the left ventricular filling volume and stroke volume were also determined. Right ventricular endomyocardial biopsies were performed to determine the diameters of myocytes, the percentage of fibrosis and the eccentricity e, as a parameter of the degree of myocardial dysarrangement. The results were as follows: IRT was significantly longer and RFV/SV was significantly greater in patients with diabetes mellitus than those among the controls. Also the diameters of myocytes and the percentage of fibrosis were significantly greater, while the eccentricity e was less compared to that of the controls. There were no significant correlations, among IRT, RFV/SV, the diameters of myocytes, and eccentricity e, but the percentage of fibrosis significantly correlated with IRT and RFV/SV (r = 0.62, r = -0.63). IRT and RFV/SV were mainly responsible for the percentage of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗