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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 181 records · Page 10Linked to original sources
PubMed1997

Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes.

We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin binding to the rat liver and kidney alpha-1 adrenoceptors, with the rank order of potency tamsulosin approximately M4 > M1 > M2 approximately M3 > > AM1 with the latter having a negligible affinity. All compounds differentiated cloned alpha-1 adrenoceptor subtypes with the rank order of potency of alpha-1A > or = alpha-1D > alpha-1B, except for M4 which had the highest affinity for the alpha-1D adrenoceptor. The compounds also concentration-dependently antagonized phenylephrine-induced contractions in the rabbit aorta and prostate. The resulting apparent pA2 values were very similar to those at the cloned rat alpha-1A adrenoceptor. We conclude that most tamsulosin metabolites are high potency antagonists at the alpha-1 adrenoceptors and retain the alpha-1A over the alpha-1B adrenoceptor selectivity of tamsulosin.

Adrenergic alpha-Antagonists↗
PubMed1997

[Low-dose cisplatin added to continuous infusion of 5-fluorouracil or oral administration of UFT for inoperable advanced or recurrent colorectal cancer].

Combined chemotherapy with 5-FU or UFT and CDDP was performed in 22 cases with inoperable advanced or recurrent colorectal cancer. When in hospital, 5-FU 375 mg/m2/day c.i.v.. (days 1-7) and CDDP 3.75 or 7.5 mg/m2/day i.v.. (days 1-5) were administered for as many weeks as possible, while for outpatients UFT 450 mg/m2/day po (days 1-7) and CDDP 3.75 or 7.5 mg/m2/day div. (days 2 and 5 were given for as many weeks as possible. The performance status (PS) of the cases at the beginning of the chemotherapy was lower than 3 in 15 patients and over 3 in 7 patients. The response rate in cases with no history of systemic 5-FU chemotherapy was 30%, and the mean NC period in all cases of NC was 170 days. Half of the symptoms were improved in cases with some symptoms before chemotherapy, and half of the patients whose PS was over 3 could leave the hospital after chemotherapy. Toxicity was seen in 80% of the cases, but those over grade 3 were seen in only 2 cases. The mean administration period of the chemotherapy was 180 days, which shows a high compliance of the method.

Administration, Oral↗
PubMed1997

Characterization of FR173657, a novel nonpeptide B2 antagonist: in vitro and in vivo studies.

Bradykinin (BK) is involved in different pathophysiological conditions, including allergic and (or) inflammatory reactions. Thus, BK antagonists are considered as a potential drug in allergic and (or) inflammatory diseases. Orally active BK antagonist would be desirable for this purpose. Here, we describe the pharmacological characterization of FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8- quinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acr ylamide) obtained from our screening for nonpeptide, orally active B2 antagonists. (i) FR173657 antagonized [3H]BK binding with IC50 values of 4.6 x 10(-10) and 8.6 x 10(-9) M in membrane preparations of guinea pig ileum and lung, respectively. FR173657 inhibited [3H]BK binding to A431, W138, and IMR90 cell lines of human origin with IC50 values of 2.0 x 10(-9), 2.3 x 10(-9), and 1.7 x 10(-9) M, respectively. FR173657 did not affect [3H]des-Arg10-kallidin (B1 ligand) binding onto IMR90 cells. (ii) FR173657 inhibited guinea pig ileum contractions by BK (6 x 10(-8) M) with an IC50 value of 6.1 x 10(-9) M. Acetylcholine- and histamine-induced contraction of guinea pig ileum was unaffected by FR173657. (iii) Oral administration of FR173657 dose-dependently inhibited BK (5 micrograms/kg) and dextran sulfate (activator of kinin-kallikrein cascade) induced bronchoconstriction with ED50 values of 0.075 and 0.057 mg/kg, respectively. In conclusion, FR173657 is a selective potent, orally active B2 receptor antagonist that can be used to investigate the role of BK in allergic and inflammatory diseases.

Administration, Oral↗
PubMed1996

c-Jun stimulates origin-dependent DNA unwinding by polyomavirus large Tantigen.

The AP1 protein c-Jun has previously been shown to stimulate polyomavirus (Py) DNA replication in vivo. In order to define the mechanism, we added purified c-Jun protein to the origin-dependent and large T antigen (LT)-dependent in vitro DNA unwinding assay. c-Jun protein was found to stimulate by approximately 5-fold the unwinding of a 290 bp linear DNA fragment containing both the Py origin and the AP1 recognition sequence to which c-Jun binds. Efficient levels of stimulation were specifically observed at limiting concentrations of LT for unwinding. Under similar conditions, Py DNA replication was stimulated to a comparable extent by AP1 in a purified in vitro replication assay. Mobility shift and DNase I footprinting assays showed that c-Jun stimulates the ATP-dependent binding of LT to the origin core by approximately 7-fold. Furthermore, c-Jun was found to interact directly with LT, but not with replication protein A. The activities of c-Jun to stimulate unwinding and origin binding of LT were found to be harbored within the N-terminal region of c-Jun, which is distinct from the DNA binding domain. We speculate that certain transcription factors may possess specific DNA replication domains that function to stimulate the loading of replication factors at the origin during the initiation of DNA synthesis.

Adaptor Protein Complex 1↗
PubMed1996

Cloning of the RhoB gene from the mouse genome and characterization of its promoter region.

Rho proteins have been implicated in a variety of cytoskeletal functions, but it is unclear how Rho proteins regulate these cellular functions and how Rho proteins are regulated. In this study, we cloned the rhoB gene from the mouse genome and characterized its promoter region. The predicted amino acid sequence was identical to that encoded by the human rhoB gene. A site for initiation of transcription was found at position -376 relative to the site for initiation of translation. Deletion analysis of the 5'-flanking region of the rhoB gene revealed that the minimum region of the promoter was located between positions -507 and -376. Northern blotting analysis showed that the expression of the mouse rhoB gene was induced by serum, suggesting that expression of the rhoB gene might be controlled by some signal-responsive element(s).

3T3 Cells↗
PubMed1996

Possible mechanism of the potent vasoconstrictor responses to ryanodine in dog cerebral arteries.

Isolated cerebral (basilar, posterior communicating and middle cerebral) arteries exist in a partially contracted state. To determine the Ca(2+)-buffering function of sarcoplasmic reticulum in the resting state of cerebral arteries, the effects of ryanodine that eliminates the function of sarcoplasmic reticulum, on tension and cellular Ca2+ level were compared in endothelium-denuded strips of the cerebral, coronary and mesenteric arteries of the dog. The addition of ryanodine to strips with basal tone caused a concentration-dependent contraction, which was significantly greater in the cerebral arteries than in the mesenteric or coronary artery. In the presence of 10(-5) M ryanodine, the caffeine (20 mM)-induced contraction was greatly attenuated in these arteries. After washout, the basal tone was greatly elevated in the cerebral arteries. The elevated tone was abolished by 10(-7) M nifedipine. The ryanodine-induced contractions were also abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the basal tone in the cerebral arteries, suggesting the maintenance of myogenic tone. The basal Ca2+ influx in arteries measured after a 5-min incubation with 45Ca was significantly higher in the basilar artery than in the mesenteric artery. The basal Ca2+ influx was not increased by 10(-5) M ryanodine in either artery. The basal Ca2+ influx was decreased by 10(-7) M nifedipine in the basilar artery, but was unchanged in the mesenteric artery. These results suggest that: (1) the basal Ca2+ influx via L-type voltage-dependent Ca2+ channels was higher in the resting state of the cerebral arteries; (2) the greater part of the higher Ca2+ influx was buffered by Ca2+ uptake into the sarcoplasmic reticulum; and (3) therefore the functional elimination of sarcoplasmic reticulum by ryanodine caused a potent contraction in these arteries. Furthermore, the maintenance of myogenic tone in the cerebral arteries suggests that more Ca2+ enters the smooth muscle cell than the buffering ability of sarcoplasmic reticulum can handle.

Animals↗
PubMed1996

Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.

Age Factors↗
PubMed1996

Potent inhibition of spontaneous rhythmic contraction by a novel beta 2-adrenoceptor agonist, HSR-81, in pregnant rat uterus.

We examined the effect of HSR-81 ((-)-(R)-alpha-[(tert-butylamino)methyl]-2-chloro-4-hydroxybenzyl alcohol L-tartrate), a newly developed, potent and selective beta 2-adrenoceptor agonist, as well as ritodrine and isoproterenol, on the spontaneous rhythmic contraction in uteri isolated from late pregnant, middle pregnant and non-pregnant (dioestrous and oestrous) rats. The three agonists inhibited the spontaneous rhythmic contraction at all the stages in a concentration-dependent manner. The pD2 value for HSR-81 was greater in late pregnancy than in dioestrus and oestrus. In the uterine preparations of late pregnancy and dioestrus, ICI-118,551 (1-(7-methylindan-4-yloxy)-3-isopropyl-aminobutan-2-ol , a selective beta 2-adrenoceptor antagonist) and atenolol (a selective beta 1-adrenoceptor antagonist) produced a parallel rightward shift of the concentration-response curves for HSR-81. The pKB values for ICI-118,551 and atenolol suggest that the inhibitory effect of HSR-81 was mediated through beta 2-adrenoceptors in the two stages. In the membranes prepared from rat uteri in late pregnancy and dioestrus, the equilibrium dissociation constant for [125I]iodocyanopindolol binding was not significantly different between the two stages. The three beta-adrenoceptor agonists and the two antagonists competed for the specific [125I]iodocyanopindolol binding and the pKi values were not significantly different between the two stages. However, the maximum number of binding sites was significantly greater in late pregnancy than in dioestrus. The configuration of the competition curves and the pKi values for the two antagonists confirmed the fact that these membranes contain predominantly beta 2-adrenoceptor subtype. These results indicate that the potent inhibition of the spontaneous rhythmic contraction by HSR-81 in the pregnant uterus may be due to the increased number of beta 2-adrenoceptors.

Adrenergic beta-2 Receptor Agonists↗
PubMed1996

Post-traumatic syringomyelia.

STUDY DESIGN: This study retrospectively analyzed patients who developed post-traumatic syringomyelia secondary to spinal cord injury. OBJECTIVES: To identify an indicator that would predict the outcome of surgical treatment for post-traumatic syringomyelia. SUMMARY OF BACKGROUND DATA: Syrinx-subarachnoid shunting was chosen as a surgical treatment for post-traumatic syringomyelia. No previous study has been published concerning magnetic resonance imaging findings' ability to predict surgical results before surgery. METHODS: Nine patients diagnosed by magnetic resonance imaging with post-traumatic syringomyelia were the subjects of this study. The magnetic resonance imaging findings and surgical results were analyzed. RESULTS: Neurologic deterioration was found in five patients. Ascending dissociated sensory disturbances and motor weakness were noticed to occur characteristically above the level of the spinal cord injury. The other four patients complained of a slight worsening of numbness without displaying neurologic deterioration. The five patients with neurologic deterioration were treated with a syrinx-subarachnoid shunting. Two of the five patients experienced sustained neurologic improvement after a midline myelotomy, which allowed the fluid within the syrinx to spout out and cause the expanded spinal cord to collapse. This was called a "high-pressure syrinx." In these two patients, the preoperative magnetic resonance imaging demonstrated a positive flow-void sign. On the other hand, drainage of the syrinx in the three patients with a negative flow-void sign did not collapse the expanded spinal cord, and the surgical results were considered fair. This was called a "low-pressure syrinx." CONCLUSIONS: Post-traumatic syringomyelia was classified into two types. A preoperative distinction could be made based on the presence or absence of the flow-void sign on a T2-weighted magnetic resonance image.

Adolescent↗
PubMed1996

Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginal discs.

Previous experiments suggest that a key event in the commitment of cultured mammalian cells to entering S phase is a rise in activity of the transcription factor E2F. In this report, we study the role of Drosophila E2F in imaginal disc cells in vivo, by examining the distribution of the endogenous protein and studying the consequences of ectopic E2F expression. First, we find that endogenous E217 falls from high to very low levels as cells initiate DNA synthesis during a developmentally regulated G1-S-transition in the eye disc. Second, we find that ectopic E2F expression drives many otherwise quiescent cells to enter S phase. Subsequently, cells throughout the discs express reaper (a regulator of apoptosis) and then die. Third, we find that ectopic E2F expression during S phase in normally cycling cells blocks their re-entry into S phase in the following cell cycle. Although we do not know the fate of these cells, we suspect that ultimately they are killed by ectopic E2F. Taken together, our results show that an elevation in the level of E2F is sufficient to induce imaginal disc cells to enter S phase. Furthermore, they suggest that the downregulation of E2F upon entry into S phase may be essential to prevent the induction of apoptosis.

Animals↗
PubMed1996

T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases.

This paper shows that elimination of a small subpopulation of peripheral T cells can elicit activation/expansion of self-reactive T cells from the remaining T cells and produce a wide spectrum of organ-specific and systemic autoimmune diseases in normal mice; reconstitution of the eliminated T-cell population prevents autoimmune development. This regulatory T-cell population expresses the CD25 molecule, apparently includes 'activated' T cells, and suppresses immune responses to non-self as well as self antigens in an antigen-nonspecific manner. Although the degree of abnormality in the T-cell regulation significantly influences the spectrum, incidence, and severity of autoimmune disease, the T-cell abnormality itself cannot determine the specificities of the elicited autoimmune responses since a comparable degree of abnormality causes different autoimmune diseases depending on the mouse strains used. Host genetic elements thus significantly contribute to determining the specificities. These findings taken together indicate that one aspect of natural self-tolerance is maintained by a T cell-mediated or -dependent control of potentially pathogenic self-reactive T cells in the periphery, and that defective control, caused by environmental insults or genetic abnormalities, suffices to activate self-reactive T cells, eliciting various autoimmune diseases depending on the genetic makeup of the host.

Animals↗
PubMed1996

Surgical treatment for right ventricular perforation caused by transvenous pacing electrodes: a report of three cases.

We experienced three cases of right ventricular perforation that were induced by transvenous pacing electrodes. The patients were a 72-year-old man who underwent percutaneous transluminal coronary recanalization and angioplasty, an 80-year-old woman who had temporary transvenous pacing for a complete atrioventricular block induced by acute valvular heart failure, and a 44-year-old man who had received a permanent pacemaker. All three patients were treated surgically. The first and second patients demonstrated either cardiac tamponade or hemopericardium necessitating pericardial drainage. Spontaneous hemostasis did not occur in cases 1 and 2, due to either anticoagulant therapy or myocardial degeneration. Such patients require surgical closure of the perforation and pericardial drainage as soon as pericardial effusion is confirmed. In contrast, middle-aged individuals without myocardial damage, such as patient 3, need only a simple removal and repositioning of the electrode followed by serial echocardiography.

Adult↗
PubMed1996

Increased production of PDGF by angiotensin and high glucose in human vascular endothelium.

The mechanisms responsible for the abnormalities in the vascular wall associated with long standing diabetes mellitus are incompletely understood. The aim of this investigation was to assess the effects of angiotensin II and high glucose on the production of platelet-derived growth factor (PDGF) in human endothelial cells. For this purpose, a primary culture was obtained from fresh human umbilical cords by collagenase digestion of the vein interior. A high glucose medium increased the production of PDGF and a similar effect was observed by the addition of mannitol. These data are consistent with a stimulatory effect of glucose on PDGF that is mediated by the osmotic effect of this substance. Angiotensin II significantly increased PDGF in human endothelial cells and the effect was accompanied by a transient increase in cytosolic calcium. The angiotensin II-induced intracellular Ca2+ increases, PDGF production were completely abolished by saralasin and neomycin, respectively. We postulate that the increased production of PDGF by the vascular endothelium in response to high glucose and angiotensin II may participate in the development of the diabetic angiopathy.

Angiotensin II↗
PubMed1996

Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry.

The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I- octen-6-ynyl] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner 40 micrograms) and elastase (Elaszym 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

Arteries↗