Biomedical subjects
Publications and source records attributed to K Tsuchida.
Isolated dissecting aneurysms of the peripheral arteries which are not accompanied by a dissecting aneurysm of the aorta are rarely observed. We report herein the unusual case of a 54-year-old man in whom an isolated common iliac aneurysm was found to be caused by isolated dissecting aneurysms of the left common iliac artery.
The behavioral sensitization has not been observed in rats under three weeks of age when administration of repeated psychostimulants is started. The aim of our study was to determine the effect of methamphetamine (MAP)-induced behavioral sensitization ontogeny on MAP challenge-induced changes of striatal extracellular concentrations of dopamine (DA) and its metabolites, using in vivo microdialysis. Experimental rats aged 7, 14, 21, 28, and 56 postnatal days (PNDs) were injected IP twice daily with 2 mg/kg MAP for three days, followed by 4 mg/kg for three days. Matched control rats were given equivalent volumes of saline according to the same schedule. Dialysis experiments were carried out 21 days after the last MAP or saline injection. All the rats were injected (IP) with a challenge dose of MAP (4 mg/kg). We reconfirmed that MAP-induced stereotyped behavior was enhanced significantly only when MAP pretreatment was started on PNDs 21, 28, and 56, but not PNDs 7 and 14. Correspondingly, the MAP challenge induced significantly greater increases in striatal extracellular DA concentrations in the MAP-pretreated rats compared with control rats only when MAP pretreatment was initiated on PNDs 21, 28, and 56, but not in younger rats.
1. We investigated the effects of CD-349, a dihydropyridine derivative with nitrate ester, on contractile responses induced by high K+, norepinephrine (NE) and Ca2+ in isolated rabbit aorta. 2. CD-349 (10(-9)-10(-5) M) and nifedipine (10(-9)-10(-5) M) equally inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-dependent manner. 8-Br-cyclic GMP (10(-3) M) did not inhibit the KCl-induced contraction of the aortic strips. 3. CD-349 (10(-8)-10(-5) M) and 8-Br-cyclic GMP (10(-6)-10(-3) M) inhibited the 10(-6) M NE-induced contraction of the aortic strips in a concentration-dependent manner. However, nifedipine had no effect on the NE-induced contraction in rabbit aorta. 4. The inhibitory effects of CD-349 on NE-induced contraction were antagonized by treatment with methylene blue and oxyhemoglobin, while they were augmented by treatment with zaprinast. 5. CD-349 (10(-8)-10(-5) M) and 8-Br-cyclic GMP (10(-5)-10(-4) M) inhibited the NE-induced phasic contraction and Ca(2+)-induced contraction of the aortic strips preincubated with NE in Ca(2+)-free medium. However, nifedipine (10(-5) M) had little or no effect on both NE-induced phasic contraction and Ca(2+)-induced contraction of the aortic strips preincubated with NE in Ca(2+)-free medium. 6. CD-349 (10(-7)-10(-5) M) increased the levels of cyclic GMP in rabbit aorta. 7. These results indicate that CD-349 has a hybrid property deriving from Ca(2+)-antagonist and cyclic GMP increasing agents.
1. The purpose of the present investigation is to evaluate muscle contraction in two directions (longitudinal and circumferential to urethra) physiologically and morphologically for alpha-adrenoceptor agonists. 2. Norepinephrine (10(-7)-10(-4) M), phenylephrine (10(-7)-10(-4) M) and clonidine (10(-7)-10(-4) M) induced contractions in a dose-dependent manner on human prostate from patients with benign prostatic hypertrophy (BPH). 3. No significant differences were observed between longitudinal and circumferential directions of human prostate in 50% of the maximal muscle contraction (EC50 values) and the maximal muscle contractions caused by any agents used. 4. Morphometric analysis for muscle in prostates was performed using formalin-fixed, paraffin-embedded sections stained by the Mallory-Azan method. 5. There was no significant difference in the density of the muscle area between longitudinal and circumferential directions of prostatic strips. 6. These results suggest that there are no significant differences in responsiveness of alpha-adrenoceptor agonists and the smooth muscle contents in longitudinal and circumferential directions to urethra, for human hypertrophied prostate.
Vulnerability to relapse is a central issue in the biology of schizophrenia. The common neural mechanisms underlying such vulnerability can be studied using the experimental model of behavioral sensitization induced by repeated administration of low doses of methamphetamine (MAP) to rodents. This review summarizes a series of behavioral and neurochemical studies on MAP-induced behavioral sensitization from the viewpoint that the mechanisms involved in initiation (or development) of psychotic symptoms and their expression differ. The initiation of behavioral sensitization to MAP in rats requires stimulation of dopaminergic neurons, and can be blocked by SCH 23390 (a dopamine D1-receptor antagonist) and BMY 14802 (a sigma-receptor antagonist). The expression of behavioral sensitization induced by subchronic MAP pretreatment takes several forms. First, dopamine release from the cerebral dopaminergic neuron terminal containing areas in response to either to rechallenge with MAP or cocaine, or evoked by intrastriatal ouabain infusion is enhanced. Second, the behavioral responses to dopamine D2- and sigma-receptor agonists are augmented. A third form involves changes indicative of transsynaptic neural circuits, such as increased numbers of D1 receptors in the substantia nigra pars reticulata, enhanced electrophysiological responses to D1 receptor activation, the putative role of excitatory amino acid receptors and interchangeability of MAP and stress. Although MAP-induced behavioral sensitization in rodents serves as a useful animal model, the elucidation of the mechanisms involved in the vulnerability of patients with schizophrenia to relapse of psychotic episodes requires further study.
The magnitude and kinetics of the L-type calcium current were compared in single left ventricular myocytes isolated from 8-mo-old (8M) and 19-mo-old (19M) genetically diabetic rats (WBN/Kob rats) and age-matched control rats. A diabetic state occurred at 19M but not at 8M. The left ventricular contractility was reduced in 19M WBN/Kob rats compared with age-matched control rats. The duration of the action potential was longer in 19M WBN/Kob rats than in the age-matched control rats. Peak inward current density was similar between diabetic rats and age-matched control rats. In addition, aging did not affect the current density at 8M or 19M. The various kinetic parameters of the L-type calcium current were not different between 19M diabetic and control cell types. The percent increase in the amplitude of the calcium current induced by isoproterenol was less in diabetic cells at the age of 19M, but not at the age of 8M, compared with age-matched control cells. Forskolin (10(-5) M), intracellularly applied adenosine 3',5'-cyclic monophosphate (5 x 10(-5) M), and guanosine 5'-[gamma-thio]triphosphate (10(-4) M) were equally effective in increasing the current in 19M diabetic and age-matched control cell types. The present study demonstrates that the basal calcium current density and kinetic parameters of the current were not altered. However, a decrease in response to beta-stimulation occurred in genetically diabetic rats compared with control rats.
We found that a homogenous CD4-/CD8- T cell bearing an invariant TCR encoded by V alpha 14J alpha 281 with a one-base N-region is highly dominant in the periphery (2-3% in spleen). Surprisingly, the high expression of this invariant V alpha 14 TCR is a general phenomenon in all laboratory strains irrespective of MHC haplotype and in some wild mouse subspecies. The majority of V alpha 14+ TCR is associated with J alpha other than J alpha 281 during the neonatal stage, after which the frequency of invariant V alpha 14J alpha 281 TCR expression increases with time reaching a maximum at around 5-8 weeks after birth. The dominant expression of V alpha 14J alpha 281 TCR is found in both euthymic and athymic mice. These results indicate that homogenous V alpha 14J alpha 281 T cells are positively selected in the periphery without thymic influence and that their VJ junction is important for positive selection. We also demonstrate that V alpha 14+ TCR gene rearrangements take place at extrathymic sites, such as bone marrow, liver, and intestine, since frequent nonproductive V alpha 14 TCR products and V alpha 14-J alpha 281 gene mediated signal sequences in circular DNA are detected as a result of TCR rearrangements in extrathymic tissues rather than in the thymus. This indicates the extrathymic development of V alpha 14J alpha 281 T cells. Furthermore, the biological roles of homogenous T cells bearing V alpha 14J alpha 281 TCR and the human counterpart of this invariant TCR are also discussed.
The present study examined ontogeny of behavioral effect of acute cocaine administration and behavioral sensitization to a challenge dose of cocaine in rats previously treated with chronic cocaine. Acute stimulating effects of cocaine in behaviors were observed in as early as 7-postnatal-day (PND) rat. However, they needed higher dose of cocaine than adult rats. Adult pattern of response to acute doses of cocaine was seen in stereotypy and locomotion at 21 PND, and in rearing at 28 PND. Rats at ages of 7, 14, 21 or 28 PNDs received repeated injections of either saline or cocaine 15 mg/kg twice a day for five consecutive days. After an abstinent period of three weeks, sensitization to a challenge dose of cocaine (15 mg/kg) was assessed. Cocaine-induced stereotyped behaviors were significantly enhanced only when cocaine-pretreatment was initiated at PND 21 and 28, but not at the earlier ages of PND 7 or 14. These results suggest that cocaine-induced behavioral sensitization occurs only when subchronic cocaine administration was commenced after PND 21.
Activin type II receptors are transmembrane protein-serine/threonine kinases. By using a reverse-transcription PCR assay to screen for protein kinase sequences, we isolated a cDNA clone, activin X1 receptor, from rat brain that encodes a 55-kDa transmembrane protein-serine kinase which is structurally related to other receptors in this kinase subfamily. The predicted protein consists of 509 amino acids, and the kinase domain shows 40% and 37% identity to the activin and transforming growth factor beta type II receptors, respectively. No activin-binding was observed when activin X1 receptor was expressed alone in COS-M6 cells; however, coexpression with type II activin receptors gave rise to a 68-kDa affinity-labeled complex in addition to the 85-kDa type II receptor complex. The size of this cross-linked band is consistent with the size of the type I activin receptor; furthermore, activin X1 receptor associated with type II receptors, as judged by coimmunoprecipitation with type II receptor antibodies. These data suggest that activin X1 receptor can serve as an activin type I receptor and that the diverse biological effects of activins may be mediated by a complex formed by the interaction of two transmembrane protein-serine kinases.
We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoylamino)ethyl 3-nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a new dihydropyridine derivative with nitrate ester, on contraction and relaxation responses induced by various vasoactive agents in rabbit aorta. CD-832 potently inhibited the specific binding of [3H](+)-PN200-110 to rat brain membranes. The IC50 values for [3](+)-PN200-110 binding were 2.8 nM and 4.9 nM in CD-832 and nifedipine, respectively. CD-832 (10(-8) to 10(-5) M), diltiazem (10(-8) to 10(-5) M) and benidipine (10(-8) to 10(-5) M) inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-dependent manner. Neither nitroglycerin (10(-8) to 10(-5) M) nor nicorandil (10(-8) to 10(-5) M) affected the 64 mM KCl-induced contraction in rabbit aorta. CD-832 (10(-8) to 10(-5) M), nitroglycerin (10(-8) to 10(-5) M) and nicorandil (10(-5) M) had no effect on norepinephrine-induced contraction in rabbit aorta. Nitroglycerin (10(-5) M), atrial natriuretic peptide (10(-8) M), nicorandil (10(-5) M) and CD-832 (10(-7) to 10(-5) M) augmented the isoproterenol-induced relaxation responses of rabbit aorta precontracted with endothelin-1 (1 x 10(-7) to 2 x 10(-7) M). The effects of nitroglycerin (10(-5) M), nicorandil (10(-5) M) and CD-832 (10(-5) M) on isoproterenol-induced relaxation responses were antagonized by treatment with methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Metabotropic glutamate receptors consist of at least six different subtypes termed mGluR1-mGluR6. They belong to the family of G protein-coupled receptors and commonly possess an unusually large extracellular domain preceding the seven transmembrane segments. mGluR1 and mGluR2 show similar affinities for L-glutamate but distinct patterns in their responsiveness to quisqualate and trans-1-amino-1,3-cyclopentane-dicarboxylate (tACPD). To assign structural determinants for the different agonist selectivities, we constructed a series of chimeric receptors at the extracellular domains of mGluR1 and mGluR2 and determined their agonist selectivities by measuring their electrophysiological responses to L-glutamate, quisqualate, and tACPD in Xenopus oocytes. Replacement of the extracellular domain up to about one-half of the amino-terminal extracellular domain of mGluR1 with the corresponding portion of mGluR2 generated a pattern of the agonist selectivity characteristic of mGluR2. The acquirement of this property in agonist selectivity was further indicated by the selective responses of these chimeric receptors to an mGluR2-specific agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine. This investigation demonstrates that the extracellular domain of mGluR is critical in determining agonist selectivity and that the mode of determination of agonist selectivity of mGluR is different from that of other G protein-coupled receptors for small molecule transmitters.
A cDNA encoding the rat transforming growth factor-beta (TGF-beta) type II receptor was isolated by hybridization from a rat pituitary gland cDNA library. The rat TGF-beta type II receptor comprises 567 amino acid residues with a cysteine-rich extracellular domain, a single transmembrane domain and an intracellular protein kinase domain with predicted serine/threonine specificity. The comparison of the amino acid sequences of the rat and human TGF-beta type II receptors indicated that they are highly conserved particularly in the intracellular kinase domain. RNA blot hybridization and reverse-transcription polymerase chain reaction (RT-PCR) analyses showed that rat TGF-beta type II receptor is widely distributed in various tissues and is expressed abundantly in the ovary and lung.
We report a patient who received aortic valve replacement and experienced early postoperative coronary artery spasm, which led to inferolateral myocardial infarction. The spasm was unresponsive to conventional medication. However, after systemic circulatory and respiratory control, a good prognosis was obtained.
We investigated the effects of VA-045, an apovincaminic acid derivative, on isolated blood vessels. VA-045 (10(-7)-10(-5) M) and vinpocetine (10(-7)-10(-5) M) inhibited the 64 mM KCl-induced and 10(-6)M norepinephrine (NE)-induced contraction of rat aortic strips. VA-045 (10(-7)-10(-4) M) and vinpocetine (10(-7)-10(-4) M) inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterase in porcine coronary artery. VA-045 (3 x 10(-9-3 x 10(-6) M) relaxed the 64 mM KCl-induced contraction of the canine basilar artery without affecting the peripheral arteries. These results indicate that VA-045 selectively dilates canine cerebral artery, and that it may be a useful agent for the treatment of cerebrovascular diseases such as stroke.
Effects of CD-349, a novel 1,4-dihydropyridine, and other calcium antagonists on membrane potentials in spontaneously beating and the membrane currents in voltage-clamped rabbit sinoatrial (SA) node cells were examined. CD-349 10(-8) M significantly decreased the maximum rate of depolarization and prolonged action potential duration (APD) and the cycle length (CL) without affecting action potential (AP) amplitude (APA) and maximum diastolic potential (MDP). CD-349 affected only the last part of pacemaker potential (phase 4 depolarization) and then lengthened the cycle. These effects of CD-349 became accentuated as the drug concentration increased. Sinus arrest occurred in two of five preparations at 10(-7) M, and occurred in all preparations at a concentration of 10(-6) M. The concentration inducing arrest of CD-349 was about one-tenth lower as compared with that of nifedipine. In voltage-clamped SA node cells, CD-349 in concentrations of 3 x 10(-8) and 10(-7) M decreased the slow inward current; the steady-state outward current and the hyperpolarization-activated inward current were also reduced, but less markedly. Nifedipine decreased the slow inward current, the potency of which was one third less than that of CD-349. Diltiazem and verapamil were weaker in prolonging cycle length and in inducing arrest as compared with CD-349 and nifedipine. These results suggest that CD-349 is a more potent calcium antagonist for decreasing pacemaker activity of rabbit SA node cells as compared with the other three calcium antagonists tested.
A pentanucleotide repetitive sequence, (TTAGG)n, has been isolated from a silkworm genomic library, using cross-hybridization with a (TTNGGG)5 sequence, which is conserved among most eukaryotic telomeres. Both fluorescent in situ hybridization and Bal 31 exonuclease experiments revealed major clusters of (TTAGG)n at the telomeres of all Bombyx chromosomes. To determine the evolutionary origin of this sequence, two types of telomeric sequence, (TTAGG)5 and a hexanucleotide repetitive sequence, (TTAGGG)4, which is conserved mainly among vertebrate and several invertebrate telomeres so far examined, were hybridized to DNAs from a wide variety of eukaryotic species under highly stringent hybridization conditions. The (TTAGGG)5 oligonucleotide hybridized to genomic DNAs from vertebrates and several nonvertebrate species, as has been reported so far, but not to any DNAs from insects. On the other hand, the Bombyx type of telomere sequence, (TTAGG)n, hybridized to DNAs from 8 of 11 orders of insect species tested but not to vertebrate DNAs, suggesting that this TTAGG repetitive sequence is conserved widely among insects.
We have synthesized new 1,4-dihydropyridine derivatives having nitrooxyalkylester moieties at the 3- and 5-positions in order to develop potent and long-lasting vasodilators. The antihypertensive activities of these compounds were compared with that of nifedipine. One of them, 2-nitrooxypropyl 3-nitrooxypropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5- pyridinedicarboxylate (CD-349) was selected for further development. The structure-activity relationship is discussed.
1,4-Dihydropyridine derivatives having two nitrooxyalkyl moieties as esters at the 3 and 5 positions possess antihypertensive activity. To understand how substituents affect the biological activity, the quantitative structure-activity relationship (QSAR) of 27 compounds was analyzed using the Fuzzy adaptive least-squares (FALS 91) method. The QSAR models suggested that the hydrophobicity and electronic effect at the 4 position of the 1,4-dihydropyridine along with the special structures of the nitrooxyalkylester components are important for antihypertensive activity.