Effects of long term oral administration of ketanserin and trichlormethiazide on blood pressure in stroke-prone spontaneously hypertensive rats.
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Administration, Oral↗
Biomedical subjects
M Minami
Publications and source records attributed to M Minami.
Inhibitory effect of ketanserin on sympathetic nerve activity in rats.
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Animals↗
Down-regulation of suppressor cell induction.
A unidirectional cascade of cell interactions has been described previously that involves at least three distinct populations of suppressor T cells (Ts) that interact in appropriate succession to mediate suppression of delayed hypersensitivity responses to the 4-hydroxy-3-nitrophenylacetyl hapten (NP). The present work focuses on the potential bidirectional effects of one suppressor factor and how it can regulate the homeostatic mechanisms that maintain this suppressor cell cascade. Specifically, the effects of prior administration of mice with a transducer suppressor factor (TsF2) on the generation of NP-specific TS1 suppressor cells were evaluated. It was observed that the TSF2 given 2-14 days prior to administration of the tolerogen (NP-coupled splenic-adherent cells) interfered with the development of inducer TS1 suppressor cells. This down-regulation of suppressor cell induction is mediated by a population of cells that have the following characteristics: NP-binding, Lyt-1+2-, L3T4+, I-J+, and Vicia villosa (VV)-adherent T cells (for convenience these cells are termed anti-suppressor cells). Furthermore, there are genetic restrictions (both H-2 and IgH) between TSF2 and host which control the generation of anti-suppressor cells. The results suggest that TSF2 may have a role in homeostatic mechanisms that regulate the NP-specific suppressor cell cascade. The relationship of anti-suppressor and contra-suppressor cells is discussed.
Animals↗
[Cholangiocarcinoma associated with Caroli's disease].
We report on an autopsy case of cholangiocarcinoma associated with Caroli's disease. A 38-year-old woman was admitted to our hospital suffering from epigastralgia. A diagnosis of Caroli's disease was made after CT, US, and ERCP testing. Because of diffuse intrahepatic bile duct dilatation, the patient was treated with antibioticus. In August 1985, her CA 19-9 level was 3,800 U/ml. This data suggested the development of a carcinoma secondary to Caroli's disease, but no tumor in the liver had been detected in the US and CT examinations. The patient died on February 1, 1986, of hepatorenal failure, approximately seven years after her first admission. An autopsy revealed diffuse dilatation of the intrahepatic bile duct (Caroli's disease) with a cholangiocarcinoma.
Adenoma, Bile Duct↗
[A case report of primary liver cancer with cerebral metastasis after hepatic resection].
A 67-year-old male, who had a left hepatectomy for hepatocellular carcinoma, was readmitted to our hospital because of a left hemiparesis. A brain computed tomography scan and an r-carotid angiogram revealed a large mass involving the right parietal area, and thus a brain tumor removal was performed. A histological diagnosis of the removed brain tumor found it to be a metastatic, hepatocellular carcinoma. The patient died of pulmonary congestion due to lung metastasis, approximately 2 years and seven months after hepatectomy, and 1 year and three months after the removal of this metastatic brain tumor. In selected cases, the removal of a metastatic brain tumor seems to bring about improvements in the quality and duration of life.
Aged↗
Effects of SGB-1534, a new synthesized phenylpiperazine derivative, on blood pressure and heart rate in stroke-prone spontaneously hypertensive rats.
The present study was undertaken to elucidate the effects of a new synthesized phenylpiperazine derivative SGB-1534 on mean arterial blood pressure and heart rate in stroke-prone spontaneously hypertensive rats(SHRSP). SGB-1534 (0.05 and 0.5 mg/kg, i.v.) produced a significantly greater decrease in mean arterial blood pressure in SHRSP than in normotensive Wistar Kyoto rats(WKY). Heart rate also tended to decrease in parallel with the decrease in mean arterial blood pressure in SHRSP. In this study, it was revealed that SGB-1534 has an antihypertensive effect in SHRSP. An attempt was made to elucidate the hypotensive mechanism of SGB-1534 using WKY. SGB-1534 (0.5 mg/kg, i.v.) significantly inhibited pressor responses to norepinephrine (5 micrograms/kg, i.v.) and methoxamine (50 micrograms/kg, i.v.). SGB-1534 (0.5 mg/kg, i.v.) did not affect the preganglionic sympathetic adrenal nerve activity. The present findings suggest that the action site of SGB-1534 is not in the central nervous system, but in the peripheral alpha 1-adrenoceptors in rats.
Adrenergic Fibers↗
Discrepancy between central sympathoinhibitory action and peripheral hemodynamic effects of pindolol in anesthetized rats.
The present study was carried out to elucidate the relationship between changes in central sympathetic nerve activity and the peripheral hemodynamic effects of pindolol in anesthetized rats. Intravenous pindolol (0.1 mg/kg) produced a decrease in cardiac sympathetic nerve activity without a significant change in heart rate. Renal sympathetic nerve activity was also decreased by pindolol (0.1 and 0.5 mg/kg, i.v.) dose-dependently, but changes in mean arterial pressure were not dose-related. In addition, pindolol (0.1 and 0.5 mg/kg, i.v.) produced a dose-dependent reduction of preganglionic splanchnic nerve activity. These findings suggest that pindolol possesses a central sympathoinhibitory action, but there is a discrepancy between this central effect and peripheral cardiovascular effects of pindolol in rats.
Animals↗
Cor triatriatum dexter with anomalous pulmonary venous drainage and sinus venosus atrial septal defect.
The atypical location of a membrane in a case of cor triatriatum dexter prompted successful repair of accompanying anomalies, with in situ use of the membrane. The anatomy is described with a review of the literature.
Child↗
[Effects of chronic oral administration of ketanserin and trichlormethiazide on blood pressure in stroke-prone spontaneously hypertensive rats].
The present study was undertaken to elucidate the effects of ketanserin and trichlormethiazide on blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP). Oral ketanserin and trichlormethiazide were administered to separate groups for 4 weeks. Combined ketanserin and trichlormethiazide was also administered and the effects observed. 1) In both ketanserin and trichlormethiazide administered groups, significant antihypertensive actions were observed as compared with the non-treated SHRSP. 2) In the ketanserin administered group, a significant increase in water drinking activity was observed, accompanied with an increased urinary volume. 3) In the trichlormethiazide administered group, urinary sodium excretion decreased significantly, accompanied with an increased urinary norepinephrine excretion. 4) Combined administration of ketanserin and trichlormethiazide enhanced the decreases in blood pressure which were produced by single administration of either ketanserin or trichlormethiazide. Moreover, both the increasing tendency in the urinary sodium excretion and the decreasing tendency in the urinary norepinephrine excretion occurred after the combined administration in SHRSP. These findings suggest that ketanserin produces an antihypertensive effect and may act prophylactically for thiazide-induced renal impairment in SHRSP.
Administration, Oral↗
[Type I left ventricular rupture after mitral valve replacement. Report of successful repair in 2 cases].
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Adult↗
Effects of thyrotropin releasing hormone and its analogue, DN 1417, on biopterin concentration and tryptophan hydroxylation in rat raphe slices.
The effects of subchronic administration of thyrotropin releasing hormone (TRH) and its analogue, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN 1417), on serotonin biosynthesis in situ were investigated in tissue slices of the midbrain raphe of rats. TRH or DN 1417 (10 mg/kg per day intraperitoneally) were administered to male Wistar rats for ten days. At twenty four hr after the last injection, tissue slices of the midbrain raphe were prepared and the rate of serotonin biosynthesis was estimated by measuring formation of 5-hydroxytryptophan (5-HTP) from tryptophan during inhibition of aromatic L-amino acid decarboxylase using high-performance liquid chromatography with fluorescence detection. Total biopterin content was determined by a specific radioimmunoassay. 5-HTP formation was decreased 22% and 29%, and total biopterin content 69% and 72%, in TRH- and DN 1417-treated rats, respectively. However, tryptophan concentration in raphe slices did not change. In contrast, the Vmax of tryptophan hydroxylase in the homogenate of the raphe nucleus in the presence of a saturating concentration of (6R)-L-erythro-tetrahydrobiopterin, the naturally occurring pterin cofactor, was significantly increased after repeated administration of TRH or DN 1417. These results indicate that reduction of in situ serotonin biosynthesis in tissue slices from the rats treated with TRH or DN 1417 subchronically contray to the increase in in vitro tryptophan hydroxylase may result from the decrease of the biopterin cofactor, and that changes in concentrations of the biopterin cofactor may play a regulatory role in serotonin biosynthesis in vivo under certain conditions.
Animals↗
A monoclonal antibody raised to tumor-specific T cell-derived suppressor factors also recognizes T suppressor inducer factors of the 4-hydroxy-3-nitrophenyl acetyl hapten suppressor network.
A monoclonal antibody (mAb), B16G, was raised from BALB/c mice immunized with affinity-purified T suppressor factors (TsF) specific for the murine mastocytoma P815. This mAb was found to bind to polyclonal TsF isolated from the spleens of tumor-bearing animals, and to the TsF released from a P815-specific T cell hybridoma. In this study, B16G was tested for its reactivity with TsF produced in the 4-hydroxy-3-nitrophenyl acetyl hapten system. The factors from three types of suppressor T cell hybridomas, each representing the immortalized analogues of the inducer T suppressor cell (Ts1), transducer suppressor cell (Ts2), and effector suppressor cell (Ts3) network populations, were tested. B16G was found to be reactive with two sources of TsF1 as assayed by enzyme-linked immunosorbent assay and delayed-type hypersensitivity bioassay. By contrast, TsF2 and TsF3 were nonreactive with B16G. These results indicate that B16G recognizes class-specific suppressor factor determinants, and that the transducer/effector factors of the network are apparently serologically distinct. Because the B16G mAb fails to recognize 4-hydroxy-3-nitro-phenyl acetyl-specific TsF3 that share idiotype-related determinants with TsF1 yet binds to TsF1 molecules that have interacted with antigen, the binding is apparently independent of the site of antigen recognition. Additionally, the results show that the tumor-specific TsF1 raised in one suppressor system share serologic determinants with anti-hapten TsF1 raised in another.
Animals↗
Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis.
We have isolated a near full-length cDNA encoding human leukotriene A4 hydrolase, which synthesizes a potent chemotactic and spasmogenic compound, leukotriene B4. A human spleen cDNA library was screened with a 48-mer oligonucleotide probe, synthesized according to the partial amino acid sequence of the human leukocyte enzyme. The nucleotide sequence of the cDNA had an open reading frame of 1,833 base pairs, which contained regions coding for the N-terminal amino acid sequence, the amino acid sequence for the probe design, and several other peptide sequences of the enzyme. The complete primary structure of the enzyme composed of 610 amino acid residues (molecular weight, 69,153) was deduced from the cDNA.
Amino Acid Sequence↗
Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers.
Leukotriene A4 hydrolase from the human lung was purified to apparent homogeneity. The molecular weight (68,000-71,000), the amino acid composition, and the N-terminal amino acid sequence were similar to those of the human neutrophil enzyme but different from those of human erythrocyte enzyme. The lung enzyme was inactivated by its substrate, leukotriene A4. To elucidate the substrate and the inactivator specificity of this enzyme, we synthesized various geometric and positional isomers of leukotriene A4. 14,15-Leukotriene A4, leukotriene A4 methyl ester, and geometric isomers of leukotriene A4 could not serve as substrates, but they inactivated the enzyme. On the other hand, styrene oxide and (5S)-trans-5,6-oxide-8,10,14-cis-12-trans-eicosatetraenoic acid neither served as substrates nor inactivated the enzyme. These results indicate that whereas allylic epoxide structures of arachidonic acids are responsible for inactivation of the enzyme, the free carboxylic acid, 5,6-oxide, and the tetraene structure with the 7,9-trans-11,14-cis configuration are required as a substrate for leukotriene A4 hydrolase.
Arachidonic Acids↗
Antibody inhibition of suppressor cell induction.
The IJ genetic restrictions of suppressor T (Ts) cells are controlled by H-2-related determinants that are expressed on antigen-presenting cells. This has led to the hypothesis that Ts cells carry receptors for a self H-2-related ligand that is expressed on specialized antigen-presenting cells. We refer to this H-2-related ligand as the IJ interacting molecule. This report evaluates the ability of rabbit antibodies directed against idiotypes on monoclonal anti-IJ antibodies (the latter are presumably reactive with the Ts cell receptor) to bind IJ interacting molecule and to inhibit antigen presentation to Ts cells. Such anti-idiotypic reagents were prepared against T cell-reactive monoclonal anti-IJk and anti-IJd antibodies. The F(ab')2 fragments of these anti-idiotypic reagents blocked Ts cell induction. The inhibition was haplotype specific and mapped to the IJ region. The anti-idiotypic antibodies blocked the generation of Ts1, Ts2, and Ts3 cells. The cellular target of the blocking activity mediated by these anti-idiotypic antibodies is a macrophage. This was shown by using a cloned macrophage hybridoma line for both Ts induction and absorption of antibody activity. The combined data support the concept that macrophages express IJ interacting determinants that are responsible for Ts cell induction.
Animals↗
The effects of phorbol ester on alloantigen presentation.
B cells and Ia+ thyroid cells fail to stimulate alloreactive T cells in a primary mixed leukocyte reaction (MLR) and fail to activate some allo-class II (I-A) reactive T cell hybridomas. We now demonstrate that B cells can specifically stimulate a primary MLR in combination with the phorbol ester, PMA, but not with interleukin 1 (IL 1) or calcium ionophore. The primary MLR induced with B cells plus PMA can be blocked by either monoclonal anti-I-A or anti-L3T4 antibodies. In contrast, thyroid cells that can be induced to express Ia antigens after incubation with interferon-gamma fail to stimulate a primary MLR even in the presence of PMA or IL 1. We confirmed these observations by using the alloreactive T cell hybridoma, HTB-9.3, which does not react to stimulator B cells. In the presence of PMA, however, this I-Ab-specific hybridoma line was able to respond to relevant but not to control stimulator B cells. Furthermore, the response of HTB-9.3 to B cells plus PMA was also blocked by anti-I-A or anti-L3T4 antibody. In contrast to B cells, Ia+ thyroid cells could not activate HTB-9.3 even in the presence of PMA or IL 1. The data indicate that for primary class II restricted allo-responses, B cells provide signals that can be complemented with the phorbol ester PMA, whereas Ia+ thyroid cells do not, suggesting the existence of additional requirements for T cell activation.
Animals↗
Murine thyroid follicular epithelial cells can be induced to express class II (Ia) gene products but fail to present antigen in vitro.
To determine whether thyroid follicular epithelial cells (TFEC) might be involved in the induction of autoimmune thyroiditis, they were tested for their potential to express Ia antigens, and for their ability to present antigen in vitro. Results showed that Ia antigens, absent on normal TFEC, could be readily induced with interferon gamma, as detected by immunofluorescence. Maximal expression of Ia antigens in over 50% of TFEC was observed after 4 days of culture in the presence of IFN-gamma, and was quantitatively comparable to spleen cells by cytofluorometric analysis. Moreover, primary TFEC in culture secreted thyroglobulin (tg) and interleukin 1. However, TFEC consistently failed to stimulate various populations of T cells. These included lymph node cells sensitized to tg, a T-cell clone specific for azo-benzene-arsonate tyrosine (ABA), and a hybridoma specific for beef insulin. Likewise, Ia-positive TFEC did not stimulate T-cell hybridomas restricted to the class II alloantigen I-Ab, while stimulating a hybridoma specific for the class I alloantigen Kb. T-cell unresponsiveness could not be explained by inhibitory activity of TFEC, released either into the culture supernatant or exerted by cell contact. The data indicate that Ia-positive TFEC failed to serve as class II-restricted antigen-presenting cells (APC) in vitro and thus argue against a primary role for these cells in the inductive phase of thyroiditis.
Animals↗
Moderating effect of low doses of ethanol on reoxygenation injury in the anoxic myocardium.
We have investigated the action of ethanol on the reoxygenation injury in isolated rat hearts. Perfusion of the anoxic Krebs-Henseleit medium for 40 minutes followed by 30 minutes of perfusion with aerobic medium produced considerable myocardial cell injury. Incorporation of ethanol (21.7 mMol), in both anoxic and aerobic perfusion media resulted in a marked reduction of cell injury and inhibition of creatine kinase. Contraction band necrosis was reduced to 0.25 as compared to 1.14 per field in the nontreated hearts. The tissue Ca++ was decreased to 8.2 as compared to 12.12 mumol/g/dry weight in the non-treated hearts and tissue ATP was increased by 50% in the treated tissue (9.33 mumol/g/dry wt) as compared to the non-treated anoxic tissue (5.5 mumol). Thus, ethanol appears to lessen myofibrilar contraction bands and preserve plasma membrane integrity during anoxia and reoxygenation. This suggests a scavenging role of free radicals which include hydroxy radicals or closely related species, in the pathogenesis of anoxic cell injury and beneficial effect of ethanol in low doses on the post anoxic reoxygenation injury.
Adenosine Triphosphate↗