Transurethral double-lumen catheter with coiled tip for urodynamic examination.
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Biomedical subjects
Publications and source records attributed to T Fukuda.
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Oral administration of isofloxythepin (0.5-8.0 mg/kg) inhibited decapitation convulsions in a dose-dependent manner as shown by decreasing the incidence and shortening the convulsion's duration, the effects continuing until 24 hr after administration. Zotepine (8, 16 mg/kg, SC) also decreased the duration but not the incidence of the convulsion. However, the other neuroleptics such as haloperidol, spiperone, perphenazine, trifluoperazine, pimozide and sulpiride failed to affect decapitation convulsions. Reserpine (8 mg/kg, SC) inhibited decapitation convulsions, accompanied by decreasing levels of norepinephrine, dopamine and serotonin in the spinal cord. Isofloxythepin at doses of 4 and 8 mg/kg, PO which completely abolished decapitation convulsions, failed to change norepinephrine and dopamine levels but increased serotonin levels in the spinal cord. Isofloxythepin (0.5-8.0 mg/kg) increased serum prolactin levels in a dose-dependent manner and zotepine (16 mg/kg), haloperidol (1 mg/kg) and reserpine (8 mg/kg) also elevated the levels. The results imply that both isofloxythepin and zotepine, but not the other neuroleptics, inhibit convulsions without decreasing spinal levels of norepinephrine which appears to be the amine most directly involved in the occurrence of decapitation convulsions, although these neuroleptics enhance prolactin secretion by blocking dopamine receptors in the pituitary.
The effects of L-histidine (HIS) on the hypermotility and the changes in brain monoamine dynamics induced by methamphetamine (MAMP) were examined in mice. HIS (1000 mg/kg) completely inhibited the hypermotility induced by MAMP (1 mg/kg). MAMP (1 mg/kg) significantly increased the dopamine level and decreased the 3,4-dihydroxyphenylacetic acid level. MAMP (5 and 10 mg/kg) also produced changes in the levels of noradrenaline, serotonin and their metabolites. HIS administered alone caused no significant changes in the levels of these amines and metabolites, nor did it affect MAMP-induced alterations in monoamine dynamics. These results suggest that catecholaminergic mechanisms are not involved in the behavioral anti-MAMP action of HIS.
A series of 2-(4-substituted-1-(homo)piperazinyl)benzimidazoles was prepared and tested for H1-antihistaminic activity in vitro and in vivo. Most of the compounds showed antihistaminic activity and some of the 1-[2-(substituted-oxy)ethyl] derivatives exhibited potent activity. In a structure-activity comparison it was found that the oxygen atom in the 2-(substituted-oxy)ethyl group at the 1-position of the benzimidazole nucleus played an important role for potent antihistaminic activity, especially in vivo. One of the most potent compounds, 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole (69), was 39 times more potent than chlorpheniramine maleate in H1-antihistaminic activity in vivo and was selected for clinical evaluation. The structure of compound 69 is of interest because it provides only a single aromatic unit linked through a chain to a basic nitrogen, while most H1-antihistaminic agents have structures that comprise a double-aromatic unit linked through a chain to a basic tertiary amino group.
A case of extraskeletal myxoid chondrosarcoma is presented. The tumor occurred in the retroperitoneum and systemic metastases were found at autopsy. The primary and metastatic tumors were soft and strikingly myxoid on gross appearance. Microscopic observation revealed undifferentiated malignant tumor having large amounts of myxoid substance and a small amount of well-differentiated chondrosarcoma element in the primary lesions. The authors obtained an immunohistochemical result that the tumor cells showed positivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Regarding S-100 protein, the well-differentiated chondrosarcoma element revealed intense positivity, whereas the poorly differentiated myxoid areas were not positive except for a few tumor cells. This is the first case, to our knowledge, of extraskeletal myxoid chondrosarcoma arising from the retroperitoneum, and immunohistologic findings suggest that alpha-1-antitrypsin and alpha-1-antichymotrypsin may be available markers in poorly differentiated chondrosarcomas showing a negative reaction for S-100 protein.
Adult T cell leukemia associated antibody (ATLA-Ab) positive persons were screened by indirect immunofluorescence (IF) testing. Their lymphocytes were collected from concentrated red blood cells (CRC), and cultured in vitro with and without phytohemagglutinin (PHA) for 10 days. The expression of ATL virus (ATLV) positive lymphocytes during the in vitro culture was then analyzed by IF assay using mouse monoclonal antibody ATL-19 reactive to p19 core protein of ATLV. 97% of ATLA-Ab positive CRC (36 cases) demonstrated ATLV positive lymphocytes after being cultured for more than 10 days with PHA, whereas, none of ATLA-Ab negative CRC (22 cases) demonstrated ATLV positive lymphocytes. All of the 10 ATLA-Ab positive CRC that were stored for 2, 4, and 7 days contained lymphocytes which expressed ATLV after in vitro culture, while 7 of 10 CRC stored for 14 days and only 1 of 10 CRCs stored for 20 days, expressed ATLV positive lymphocytes. This data indicates that almost all of the ATLA-Ab positive blood contained ATLV positive lymphocytes, and that the in vitro appearance of these ATLV positive lymphocytes was reduced by storing the CRC for more than 14 days.
Electron microscopically the role of acid phosphatase (acid P) positive lysosomes in the pathogenesis of intramyocardial coronary artery lesions of hypertensive rats with bilaterally constricted renal arteries was studied. At 3 postoperative weeks, acid P positive lysosomes were increased in endothelial cells of the coronary arteries, but at 5 weeks and thereafter, they were decreased in number. In the intima, intimal smooth muscle cells with acid P positive lysosomes appeared at 3 postoperative weeks, but their number remained small as late as 9 postoperative weeks. The internal elastic lamina was fragmented into amorphous masses from 3 postoperative weeks, at 5 weeks and thereafter the fragmentation and disruption became severer, and at 9 weeks the lamina disappeared because of marked disruption. At 3 postoperative weeks, acid P positive extracellular lysosomes were observed in the gaps of the fragmented internal elastic lamina. At 5 weeks and thereafter, extracellular lysosomes and attenuated processes of medial smooth muscle cells with lysosomes were seen extending through the gaps of the fragmented internal elastic lamina. Necrosis of these extending cell processes and lysosomes remaining after the necrosis were observed. The findings suggested that the fragmentation and lytic change of the internal elastic lamina observed in hypertensive rat intramyocardial coronary arteries might be induced by extracellular lysosomes discharged not only from endothelial cells and intimal smooth muscle cells but also from the extending processes of medial smooth muscle cells into the gaps of the internal elastic lamina.
New information on the life cycle and fine structure of Pilosporella chapmani, a microsporidium of the mosquito Aedes triseriatus, is presented. Pilosporella chapmani is shown to have two sporulation sequences, one of them being involved in transovarial transmission. One sequence, involving meiosis and production of a moniliform sporogonial plasmodium, occurs in the larval fat body, resulting in eight uninucleate, spherical, and fully developed spores. The other occurs in oenocytes of adult mosquitoes and results in isolated, binucleate, elongate, and thin-walled spores. Also, for the first time, metabolic products are shown to be expelled into the surrounding host tissues through the wall of the sporocyst.
We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.
Eosinophilic cystitis developed in an asthmatic patient after therapy with the antiasthmatic agent, Tranilast. The progress of this patient and the histopathologic findings of bladder biopsy specimens are reported. A review of recent publications on the possible causative correlations is presented. It appears judicious to perform bladder biopsy if common chemotherapy fails to improve bladder irritability in patients receiving Tranilast therapy. If a diagnosis of eosinophilic cystitis induced by Tranilast is established, immediate withdrawal of the drug with or without steroid therapy is recommended.
Class II major histocompatibility complex (MHC) antigens have been demonstrated on the surface of thyroid epithelial cells (thyrocytes) from patients with autoimmune thyroid disease. The present study was designed to investigate how the expression of class II MHC antigens is involved in autoimmune processes in Graves' disease by studying cellular interactions among thyrocytes, lymphocytes within thyroid glands (TG), and peripheral blood (PB) lymphocytes. Thyrocytes were prepared by collagenase digestion, and T or non-T cells were separated by E-rosette formation. Thyrocytes were cocultured in the presence or absence of interferon-gamma, and the expression of HLA-DR antigens on cultured thyrocytes was examined by an indirect immunofluorescence method using monoclonal anti-HLA-DR antibody and monoclonal anti-HLA-DQ antibody. The cellular interactions were assessed as the proliferative response of T cells to autologous stimulators, such as thyrocytes or lymphocytes. Expression of HLA-DR antigens on thyrocytes after culture for 18 h in the absence of interferon-gamma was found in two thirds of the patients with Graves' disease studied (n = 18). Interferon-gamma induced and maintained the expression of HLA-DR antigens on thyrocytes. The percentages of HLA-DR+T cells were significantly higher among TG-T cells than among PB-T cells [32.6 +/- 12.4% (+/- SD) vs. 12.2 +/-5.0%; n = 18; P less than 0.01]. Thyrocytes from Graves' patients induced proliferation of both autologous PB-T cells and TG-T cells, and TG-T cells stimulated proliferation of autologous PB-T cells. In conclusion, interferon-gamma induces HLA-DR antigen expression on thyrocytes from patients with Graves' disease, and these cells induce proliferation of autologous T cells, which may, in turn, act on thyrocytes to perpetuate the process.
Antibodies present in serum of patients with rheumatoid arthritis (RA), autoimmune thyroid diseases, and myasthenia gravis are preferentially cytotoxic to suppressor T lymphocytes from normal subjects induced by Concanavalin A. The aim of this study was to determine whether the lymphocytotoxic antibodies found in patients with these diseases also react with regulatory T cells to facilitate production of the autoantibodies responsible for each disease. Peripheral blood mononuclear cells (PBMC) from normal subjects were treated with serum from patients and complement. After washing, residual viable cells were cultured with pokeweed mitogen for 7 days. Immunoglobulin M rheumatoid factor and antihuman thyroglobulin antibody (anti-hTgAb) in the culture supernatants were measured by RIA. Anti-hTgAb was produced in culture supernatants of PBMC treated with serum samples from patients with autoimmune thyroid diseases, whereas serum samples from patients with RA, myasthemia gravis, or normal subjects did not stimulate production of detectable anti-hTgAb. In contrast, Immunoglobulin M rheumatoid factor was produced by normal PBMC treated only with serum from patients with RA. When normal T cells treated with serum were cultured with autologous untreated non-T cells in the presence of pokeweed mitogen, autoantibodies also were produced. Furthermore, the production of anti-hTgAb was suppressed by adding untreated T cells to the mixture of treated T cells and untreated non-T cells. These results suggest that lymphocytotoxic antibodies found in patients with autoimmune disorders may cause disease-associated suppressor T cell dysfunction.
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Tremor induced by TRH and oxotremorine was recorded by a capacitance transducer, and its intensity and frequency were evaluated using power arrays. In mice treated with TRH (20 mg/kg, i.p.), the latency of tremor was 17.1 +/- 1.7 min (mean +/- S.E.) and the duration was 20.4 +/- 2.2 min, while the frequency was 13.7 +/- 0.3 Hz. In animals with oxotremorine (0.5 mg/kg, i.p.), the latency was 4.3 +/- 0.4 min and the duration was 18 +/- 2.2 min, while the frequency was 12.7 +/- 0.3 Hz. The latter frequency, however, was significantly shifted to a lower frequency as a function of time. In TRH-induced tremor, vertical movements appeared in the same degree as horizontal movements. In oxotremorine-induced tremor, the vertical movements were few, whereas the horizontal movements were observed in a degree similar to those of TRH. The TRH tremor was suppressed by haloperidol and propranolol, but not by atropine. On the contrary, the oxotremorine tremor was inhibited by atropine, but not by haloperidol or propranolol. These results suggest that mechanisms of tremor induced by TRH differ qualitatively from those by oxotremorine; dopaminergic and beta-adrenergic receptor mediated functions may be linked to the developments of tremor caused by TRH, while cholinergic systems have a little effect in mice. The apparatus used in this study and power spectral analysis with power arrays may provide a useful method for simultaneous evaluation of the latency, duration, intensity and frequency of tremors.
The effect of Y-8894 on the abnormal electrocorticogram (ECoG) of alcuronium-immobilized rats, induced by destruction of the internal capsule with heat, was compared with that produced by imipramine, amantadine and Ca-hopantenate. ECoG power in the delta + theta (1-7 Hz), alpha (7.5-12.5 Hz) and beta (13-30 Hz) bands was used as an index. Delta + theta power increased following destruction of the internal capsule with heat. The increased delta + theta power (abnormal ECoG) lasted for 60 min following the injection of saline at 60 degrees C for 3 min. Y-8894 (0.1-1 mg/kg, i.v.) apparently improved the abnormal ECoG dose-dependently by significantly reducing the increased delta + theta power. Similar results were obtained with amantadine (10 mg/kg, i.v.), but its potency was weaker than that of Y-8894. Imipramine (1 mg/kg, i.v.) and Ca-hopantenate (30 mg/kg, i.v.), however, both failed to modify the abnormal ECoG. All drugs, except Ca-hopantenate, decreased the magnitudes of the alpha and beta bands. The above results suggest that Y-8894 may be effective in ameliorating cerebral dysfunction induced experimentally by the lesion of the internal capsule.
Placental 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity was studied in order to evaluate the mechanism of continuation of pregnancy and initiation of labor. The placentas obtained at various gestational weeks were homogenized and fractionated into "nuclear", "mitochondrial", "microsomal" and "supernatant" fractions. Each fraction was incubated with 14C-progesterone and a hydrogen donor. Enzymatic activity was measured by the conversion of progesterone to 20 alpha-dihydroprogesterone. The highest activity of 20 alpha-HSD for progesterone was found to be localized in "microsomal" fraction. The Km constant of 20 alpha-HSD was 4.5 X 10(-6)M for progesterone in "microsomal" fraction. It was found that placental microsomal 20 alpha-HSD required NADPH as well as NADH. 20 alpha-HSD activity for progesterone increased as gestational weeks advanced. The addition of DHA-sulfate and DHA inhibited 20 alpha-HSD activity for progesterone significantly, suggesting that the steroid produced by the feto-placental unit may be involved in the metabolism of progesterone in human placenta.
This study was designed to determine the in vitro release of tegafur from a suppository and the in vivo bioavailability of tegafur in rats. Two different suppository preparations (product A-1 and product A-2) containing 750 mg of tegafur were tested for in vitro release of tegafur by the Muranishi Method (membrane diffusion method) and the partially modified paddle method (permeability through dialysis tubing). When determined by either method, the amount of tegafur released from product A-2 during the whole experimental period was significantly greater than that released from product A-1. When tested by the Muranishi method, however, the difference in the amount released during the first 10-min period was not significant. A greater bioavailability of tegafur after rectal administration was obtained by product A-2 more than product A-1. A significant correlation was observed between the in vitro release and the in vivo bioavailability. The present results indicate that there are considerable differences in physiochemical characteristics between product A-1 and product A-2.
Methamphetamine (MA) toxicity in aggregated mice was studied by varying the number of mice and the proportion of MA treated mice kept in the same confined space. The lethality was measured 24 h after intraperitoneal injections of MA at doses ranging from 10 to 100 mg/kg. MA lethality, over a wide dose range (15 to 50 mg/kg), was higher in aggregated mice than in those maintained in isolation. The greater the proportion of MA-treated mice in aggregation was, the higher the MA lethality was. In aggregations of 10 mice, MA was lethal at lower doses than in aggregations of 5 mice. These results indicate that the lethality of MA is influenced by confinement and aggregation.