4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents.
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Action Potentials↗
Biomedical subjects
K Sawada
Publications and source records attributed to K Sawada.
Intramedullary neutrophil phagocytosis by histiocytes in autoimmune neutropenia of infancy.
We describe a case of autoimmune neutropenia of infancy in which active phagocytosis of mature myeloid cells by bone marrow histiocytes was observed. This finding in the routine hematological investigation has not been reported so far and might be helpful in suggesting the diagnosis of autoimmune neutropenia of infancy, and also in understanding the pathogenesis of peripheral neutropenia in this disease.
Autoimmune Diseases↗
Available removal systems: state of the art.
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Blood Component Removal↗
Effects of 1 alpha-hydroxyvitamin D3 on N-methyl-N-nitrosourea-induced colonic tumorigenesis, and on fecal bile acid profiles with respect to soluble and precipitated phases in rats.
Vitamin D3 inhibited the promotion by exogenous promoters in experimental colonic tumorigenesis. To give more insight into this phenomenon, the effect of 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis was studied in rats without exogenous promoters. Fecal bile acids were analyzed to examine as to whether 1 alpha(OH)D3 increased the concentration of soluble bile acids. Eighty-seven female F344 rats received 2 mg of MNU intrarectally 5 times in 2 weeks, and were divided into 3 groups. One group (n = 29) was left without any treatment. Two groups (each, n = 29) were given 0.2 ml of medium chain triglyceride (MCT) or MCT containing 0.04 microgram of 1 alpha(OH)D3 through an intragastric route thrice weekly for 38 weeks. At autopsy, numbers of rats with colonic tumor were 9 (31%), 10 (34%) and 10 (34%) in the group receiving MNU alone, MNU + MCT and MNU + 1 alpha(OH)D3, respectively (chi 2 = 0.103, P less than 0.95). Fecal bile acid profiles showed no appreciable difference among these groups, nor was observed any increase of soluble bile acids in the MNU + 1 alpha(OH)D3 group. These results indicated that the administration of 1 alpha(OH)D3 did not affect colonic tumorigenesis under the condition where exogenous promoters were not applied, and that 1 alpha(OH)D3 did not seem to interfere the formation of bile acid calcium salts in animals on a regular diet.
Animals↗
Growth of highly purified human CFU-E in serum-free medium.
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Cell Separation↗
[Comparison of cardiac output between in DDD and in VVI by pulsed Doppler echocardiographic method (correction with Swan-Ganz catheter method)].
Difference of cardiac output and stroke volume between that in DDD and that in VVI was studied by pulsed Doppler echocardiography at different pacing rates. Moreover, to evaluate the usefulness of the method by pulsed Doppler echocardiography, cardiac output by the Swan-Ganz catheter method was measured and compared. Fourteen patients age 37-83 years (mean 65 years) with sick sinus syndrome and implanted multiprogrammable dual chamber pacemakers were studied. Cardiac output was measured as the product of the echocardiographically determined cross sectional area of the aortic anulus and the Doppler-determined mean velocity of left ventricular outflow over systole. Cardiac output was greater in DDD with atrial kick than in VVI at each pacing rate, and increased with elevation of the rate, but it was smaller at 120 PPM than at 110 PPM in DDD. Stroke volume was greater in DDD than in VVI at each pacing rate, and maximum volume was at 60 PPM in both modes. The data by pulsed Doppler echocardiography and by Swan-Ganz catheter method have high correlation. Besides being related with pulse rate, these results may be related with such things as myocardial contractility, preload and afterload. For example, the tension of autonomic nervous system, the changing of venous return volume, the disease of arteriosclerosis and old myocardial infarction, temperature, blood viscosity and so on. We will continue the study considering these factors.
Adult↗
[The antibody titer to streptococcal and staphylococcal L-form in Behçet's disease].
The antibody titer to streptococcal and staphylococcal L-form was determined in the serum of Behçet's disease by enzyme-linked immunosorbent assay. These L-form bacteria were induced by the penicillin disk method. In 12 patients with Behçet's disease, the antibody titer to streptococcal L-form was significantly lower than that in the 14 normal controls by Student's t-test (p less than 0.025). The antibody titer to staphylococcal L-form, however, showed no statistical difference between the patients and the controls. In Behçet's disease, antibody formation to streptococcus pyogenes, as well as its L-form, may be specifically disturbed.
Adult↗
Effects of oral administration of sulfolithocholic acid disodium salt and lithocholic acid sodium salt on N-methyl-N-nitrosourea-induced colonic tumorigenesis in conventional rats.
Effects of p.o. administration of sulfolithocholic acid disodium salt (SLCNa) and lithocholic acid sodium salt (LCNa) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis were studied in conventional rats. Female F344 rats received either 0.5 ml of distilled water (DW) alone or DW containing 2.5 mg of MNU twice in 1 wk intrarectally. Then rats were fed freely on a basal diet (PCE-2) or PCE-2 containing LCNa or SLCNa (both at 0.5 mmol/100 g of PCE-2) for 40 wk. Thus, 6 groups were completed: MNU + PCE-2 (n = 30); MNU + LCNa (n = 29); MNU + SLCNa (n = 22); DW + PCE-2 (n = 17); DW + LCNa (n = 20); and DW + SLCNa (n = 19). Numbers of rats bearing colonic tumor were 3 (10%) in MNU + PCE-2, 2 (7%) in MNU + LCNa, and 8 (36%) in MNU + SLCNa group (uncorrected x2 = 9.35 among the 3 groups), but none in those groups without MNU. Total fecal bile acids in the rats given bile salts showed about 2-fold increase compared with those without bile salts. Fecal bile acid profiles between the LCNa and SLCNa groups were indistinguishable except for a slight increase of sulfolithocholic acid in the SLCNa groups. These results indicated that p.o. administration of SLCNa but not LCNa promoted MNU-induced colonic tumorigenesis in conventional rats. Fecal bile acid profiles did not support the higher tumor incidence in the MNU + SLCNa group compared with the MNU + LCNa group, which suggested that an unrecognized mechanism probably relating to desulfation of SLCNa was involved in this phenomenon.
Administration, Oral↗
Excitatory effect of histamine on EEGs of the cortex and thalamus in rats.
When low frequency electrical stimulations were repeatedly applied to the rat midbrain reticular formation, the EEG spectral power recorded at the cortex and thalamus increased markedly, especially in the low frequency bands (0-6 Hz). The intraventricular administration of histamine (Hi) inhibited this increase. Hi-induced inhibition was antagonized by simultaneous injection of an equimolar dose of either pyrilamine or diphenhydramine, but not by that of cimetidine. In accordance with this, 2-methylHi decreased the power in the slow wave region, while 4-methylHi was not effective. It was assumed that the EEG arousal effect of Hi is exerted via H1 receptors but not related to H2 receptors. Adverse effects of H1 blockers on the brain, such as drowsiness, may be produced as a consequence of this inhibitory action.
Animals↗
Effects of 5 beta-chol-3-en-24-oic acid, and lithocholic acid and its sulfates on prostaglandin E2 output in perfusion of the rat colon.
The effects of bile salts on the output of prostaglandin E2(PGE2) were studied in rats by colonic perfusion. Bile salts and their concentrations in infusates were as follows; chenodeoxycholic acid sodium salt (CDCNa), sulfolithocholic acid disodium salt (SLCNa) and sulfotaurolithocholic acid disodium salt (STLCNa) were at 1 mmol/l, lithocholic acid sodium salt (LCNa) was at 0.6 mmol/l, 5 beta-chol-3-en-24-oic acid sodium salt (delta 3Na) was at 0.006 mmol/l, and sulfoglycolithocholic acid disodium salt (SGLCNa) was at 0.8 mmol/l. Median values of PGE2 outputs were 40.9, 52.4, 65.5, trace, 7.6, 9.8 and 9.8 pg/10 min/cm in the CDCNa, LCNa, delta 3Na, SLCNa, STLCNa, SGLCNa and control groups, respectively (control vs CDCNa, LCNa, delta 3Na, SLCNa group, p less than 0.01 by median test). There was such a dissociation in PGE2 output and electrolyte concentration in the perfusates that high concentration of Na+ and Cl- ions was observed only in the SGLCNa group (p less than 0.01 by t-test compared with the control group), whereas in the remainder of the groups substantial net movement of electrolytes and water was not observed. Light microscopy showed no evidence of morphological damage in any group. These results indicated that CDCNa, LCNa and delta 3Na increased PGE2 outputs in the colon at low concentration without functional or morphological changes.
Animals↗
Expression of EBNA-3 family in fresh B lymphocytes infected with Epstein-Barr virus.
Four transcripts belonging to the EBNA-3 family were detected during immortalization of human tonsillar lymphocytes with the Epstein-Barr virus. These four transcripts were also detected in immortalized B-lymphoblastoid cells (LCL) and the Burkitt's lymphoma cell line, Namalwa. A 5.0-kb transcript hybridized with the EBNA-3A probe; a 8.5-kb transcript hybridized with the EBNA-3B and -3C probes; and a 5.6- and a 3.6-kb transcript hybridized with the EBNA-3C probe. Sequencing and cDNA analysis showed that the EBNA-3C transcripts contained exons of the most rightward BamHI-E open reading frames, BERF-3 and BERF-4. Moreover, sequencing of cDNA clones revealed exons in the 5' portion homologous to regions in EBV BamHI-C, -W, and -U. Hybridization experiments with EBV BamHI-W and -U probes identified the 8.5- and 5.6-kb transcripts but not the 3.6-kb transcript in LCL. Organization of these transcripts from the EBNA-3 family is discussed.
Antigens, Viral↗
Excitatory effect of histamine on the arousal system and its inhibition by H1 blockers.
To clarify whether the sedative effect of H1 blockers is exerted in relation to H1 receptors in the brain, EEG activity recorded from the cortex and thalamus of rats was studied by power spectral analysis. EEG processing was performed by the FFT method and displayed as compressed spectral arrays. When a train of low frequency electrical stimulation was applied to the midbrain reticular formation of conscious rats, there was an increase in spectral power recorded at the cortex and thalamus, especially in the low frequency bands (0-6 Hz). The intraventricular administration of histamine suppressed the increase in power; this inhibition was antagonized by simultaneous administration of pyrilamine or diphenhydramine, though not in in combination with cimetidine or ranitidine. As in the case of histamine, the administration of 2-methylhistamine decreased power in the slow wave region, while administration of 4-methylhistamine did not. It was assumed that the arousal effect of histamine is exerted via H1 and not related to H2 receptors. Adverse effects of H1 blockers, such as drowsiness, may be caused by their inhibition of histamine's arousal effect.
Animals↗
Supplemental administration of 1 alpha-hydroxyvitamin D3 inhibits promotion by intrarectal instillation of lithocholic acid in N-methyl-N-nitrosourea-induced colonic tumorigenesis in rats.
The effect of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on promotion by intrarectal instillation of lithocholic acid (LC) in N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis was studied in a rodent model. Ninety-two female F344 rats received intrarectal injection of 2.5 mg of MNU twice in one week followed by 1 mg of LC or its vehicle alone three times weekly for 48 weeks. Those which received LC were given a concomitant intragastric administration of 0.04 micrograms of 1 alpha(OH)D3 or its vehicle alone three times weekly. In the group receiving MNU alone (n = 30) five rats bore colonic tumors; in the MNU + LC group (n = 32) 15 and in the MNU + LC + 1 alpha(OH)D3 group (n = 30) six rats bore colonic tumors (MNU + LC versus MNU + LC + 1 alpha(OH)D3 group, P less than 0.05). These results indicated that promotion of MNU-induced colonic tumorigenesis by LC was suppressed by supplemental administration of 1 alpha(OH)D3.
Animals↗
Identification of peanut agglutinin receptors on mouse testicular germ cells.
Peanut agglutinin receptors expressed specifically in mouse testicular germ cells have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and lectin blotting techniques. Two major components were estimated to have molecular weights of 86,000 and isoelectric points of 6.1 +/- 0.3 and 6.2 +/- 0.3. Minor components with molecular weights of 71,000-74,000 and isoelectric points of 6.1 +/- 0.3 were also detected. Specific expression of these receptors on testicular germ cells was confirmed using the testes of mutant mice, Sld/Sld, devoid of germ cells.
Animals↗
Human colony-forming units-erythroid do not require accessory cells, but do require direct interaction with insulin-like growth factor I and/or insulin for erythroid development.
The presence of heterogeneous erythroid progenitor cells, contaminant cells, or serum may alter erythroid colony development in vitro. To obtain highly purified colony-forming units-erythroid (CFU-E), we cultured partially purified human blood burst-forming units-erythroid (BFU-E) in methylcellulose with recombinant human erythropoietin (rHuEPO) for 7 d and generated cells that consisted of 30-60% CFU-E, but no BFU-E. A serum-free medium was used that allowed development of the same number of erythroid colonies as serum containing medium, but with a greater percentage of larger colonies. This medium consisted of delipidated crystalline bovine serum albumin, iron saturated transferrin, lipid suspension, fibrinogen, thrombin, Iscove's modified Dulbecco's medium/F-12[HAM], and insulin plus rHuEPO. When CFU-E were cultured in a limiting dilution assay and the percentage of nonresponder wells was plotted against cell concentration, both serum-free cultures and serum-containing cultures yielded overlapping straight lines through the origin indicating that CFU-E development did not depend on accessory cells and that insulin acted directly on the CFU-E. Human recombinant interleukin 3 (IL-3) and/or granulocyte-macrophage colony-stimulating factor had no effect on CFU-E growth, while they markedly enhanced BFU-E growth. Physiological concentrations of recombinant human insulin-like growth factor I (IGF-I) enhanced CFU-E growth in the absence of insulin and, together with rHuEPO in serum-free medium, provided a plating efficiency equal to that of serum-containing medium. Limiting dilution analysis in serum-free medium with IGF-I showed a straight line through the origin indicating that IGF-I also acted directly on the CFU-E and not through an effect on accessory cells. These data demonstrate that CFU-E do not require accessory cells, but do require IGF-I and/or insulin which act directly on the CFU-E.
Adult↗
[Gene expression during lens transdifferentiation from pigmented epithelial cells].
Pigmented epithelial cells of chicken and human dedifferentiate in the medium containing phenylthiourea and testicular hyaluronidase, and then trans-differentiate into lens cells in vitro. To understand the molecular mechanisms of transdifferentiation, gene expression during lens transdifferentiation was analyzed. As the first step, pigment cell and lens specific genes were isolated and expression of these gene was analyzed by Northern blotting . These results clearly shown that lens transdifferentiation proceeds via neutral cell state in which both pigment and lens specific genes are repressed. Oncogene expression was also analyzed. An elevated expression of the c-myc gene was observed during dedifferentiation process. It is expected that elevated expression of c-myc gene might prevent the cells from entering the G0 phase and thus lead to dedifferentiated state.
Animals↗
Receptors for erythropoietin in mouse and human erythroid cells and placenta.
High and lower affinity receptors for erythropoietin (EP) were initially identified on a very pure population of EP-responsive erythroblasts obtained from the spleens of mice infected with anemia strain of Friend virus (FVA). The structure of the receptor for EP in these cells was determined to be proteins of 100 and 85 Kd by cross-linking 125I-EP. In this investigation, studies on the receptors for EP were extended to other mouse erythroid cells and human erythroid cells as well as to the placentas of mice and rats. Only lower affinity receptors for EP were detected on erythroblasts purified from the spleens of mice infected with the polycythemia strain of Friend virus and a murine erythroleukemia cell line, both of which are not responsive to EP in culture. Internalization of 125I-EP was observed in both groups of cells. The structure of the receptor determined by cross-linking 125I-EP was two equally labeled proteins of 100 Kd and 85 Kd molecular mass in all these mouse erythroid cells. The structure of the receptor was found to be very similar in human erythroid colony forming cells cultured from normal blood. These cells respond to EP with erythroid maturation and were previously shown to have high and lower affinity receptors. Placentas from mice and rats were found to have only lower affinity receptors for EP, and when placental membranes were cross-linked to 125I-EP, the same 100 Kd and 85 Kd bands were found as seen in mouse and human erythroid cells. The structure of the receptor was similar in cells that have high affinity receptors (FVA-infected and human erythroid colony-forming cells) and nonresponsive erythroid cells and placenta that have lower affinity receptors, but only the cells with the high affinity receptors respond to the addition of EP with erythroid maturation.
Animals↗
[Endoscopic treatment of early gastric cancer in patients undergoing chronic hemodialysis].
Endoscopic treatment of early gastric cancer (type Ila in all patients) was performed in four patients undergoing chronic hemodialysis. Surgical treatment was contraindicated because of various risk factors in these patients. Endoscopic treatment was performed by concomitant use of YAG laser irradiation, local ethanol injection and mucosal resection. After endoscopic treatment, stomach biopsy revealed no cancer in four patients. In one patient who is alive now, no sign of cancer recurrence has been noted for about two years after endoscopic treatment. This patient has undergone hemodialysis on outpatient department. The remaining three patients died from diseases other than gastric cancer. When one of them was autopsied, no gastric cancer demonstrated. Taking the prognosis related to life in to consideration, endoscopic treatment should be used positively when surgical treatment of early gastric cancer cannot be performed in patients undergoing chronic hemodialysis.
Aged↗