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Biomedical subjects

A Tahara

Publications and source records attributed to A Tahara.

At least 37 records · Page 2Linked to original sources
PubMed1997

Pharmacological profile of YM087, a novel nonpeptide dual vasopressin V1A and V2 receptor antagonist, in dogs.

The pharmacological profile of YM087 (4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin -6-yl) carbonyl]-2-phenylbenzanilide monohydrochloride) was investigated in dogs. YM087 showed high affinity for vasopressin V1A and V2 receptors in radioligand receptor binding studies with dog platelets (V1A) and kidney (V2). Intravenously injected YM087 (3-100 micrograms/kg) dose dependently inhibited the pressor response to exogenous vasopressin in anesthetized dogs. Intravenous (10-100 micrograms/kg) and oral (30-300 micrograms/kg) administration of YM087 dose dependently increased urine flow with little effect on urinary sodium and potassium excretion in normally hydrated conscious dogs. Concomitantly, the urine osmolality dropped below the plasma osmolality (300 mOsm/kg H2O). In contrast, intravenously injected furosemide (300 micrograms/kg) increased urine flow with marked increases in urinary sodium and potassium excretion. These results indicate that YM087 is the first orally effective dual vasopressin V1A and V2 receptor antagonist and that it will be a new tool in the investigation of the physiological and pathophysiological role of vasopressin in the cardiovascular system and kidney. YM087 may be useful for the treatment of patients with congestive heart failure, renal diseases and water-retaining diseases.

Animals↗
PubMed1997

Effect of YM087, a potent nonpeptide vasopressin antagonist, on vasopressin-induced hyperplasia and hypertrophy of cultured vascular smooth-muscle cells.

We investigated the effects of YM087, a potent nonpeptide V1A and V2 vasopressin (AVP)-receptor antagonist, in binding and functional studies on rat vascular smooth-muscle cells (VSMCs). V1A AVP receptors on VSMCs were characterized by using the radioligand [3H]AVP. Specific binding of [3H]AVP was time dependent, reversible, and saturable. A single class of high-affinity binding sites with the expected V1A profile was identified. YM087 showed high affinity for V1A receptors with an inhibitory dissociation constant (Ki) value of 0.24 nM. In addition, YM087 potently and concentration-dependently inhibited AVP-induced increase in intracellular free calcium concentration and activation of mitogen-activated protein kinase. When added to growth-arrested VSMCs, AVP concentration-dependently induced hyperplasia and hypertrophy. YM087 prevented AVP-induced hyperplasia and hypertrophy of these cells in a concentration-dependent manner. YM087 had no agonistic activity in any biological assays used. These results suggest that YM087 displays high affinity for V1A receptors on VSMCs and high potency in inhibiting the AVP-induced physiological response. YM087 is a potent pharmacologic probe for investigating the physiologic and pathophysiologic roles of AVP in several diseases.

Animals↗
PubMed1997

Pharmacological profile of YM087, a novel potent nonpeptide vasopressin V1A and V2 receptor antagonist, in vitro and in vivo.

The biochemical and pharmacological profile of YM087, 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin- 6-yl)-carbonyl]-2-phenylbenzanilide monohydrochloride, a newly synthesized nonpeptide vasopressin (AVP) antagonist, was investigated in several in vitro and in vivo studies. YM087 showed high affinity for V1A receptors from rat liver and V2 receptors from rat kidney with Ki values of 0.48 and 3.04 nM, respectively. YM087 also inhibited [3H]oxytocin (OT) binding to rat uterus (OT receptors) plasma membranes with a Ki value of 44.4 nM, and at 100 microM did not affect the binding of [3H]AVP to anterior pituitary (V1B receptors) plasma membranes, which indicated that it had less affinity for these OT and V1B receptors. YM087 had no effect on cytosolic free calcium concentration ([Ca++]i) itself, but suppressed AVP-induced increase in [Ca++]i of cultured vascular smooth muscle cells at the same concentrations as the binding affinities. Furthermore, YM087 potently blocked AVP-induced cAMP production of cultured renal epithelium cells concentration dependently and had no agonistic activities. In in vivo studies, intravenous administration of YM087 inhibited the pressor response to exogenous AVP in pithed rats and produced an aquaretic effect in dehydrated conscious rats in a dose-dependent manner. These results demonstrate that YM087 is a potent and nonpeptide dual AVP V1A and V2 receptors antagonist and can be used in future studies to help clarify the physiological and pathophysiological roles of AVP.

Animals↗
PubMed1997

[Intraocular neovascularization].

To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future.

Adult↗
PubMed1996

Presence of macrophage migration inhibitory factor (MIF) in ependyma, astrocytes and neurons in the bovine brain.

We investigated the immunohistochemical localization of a cytokine macrophage migration inhibitory factor (MIF) in the bovine brain. MIF was present in the ependymal cell linings of the cerebral ventricles throughout. Double immunostaining of the section with anti-glial fibrillary acidic protein (GFAP) antibody and with anti-MIF antibody showed that the astrocytes present in subependymal layer were immunoreactive for MIF. In the hippocampus, the pyramidal cells in the CA3 and CA4 subfields and the granule cells of the dentate gyrus were immunoreactive. The bundles of mossy fibers were stained along their projections to CA3 and CA4 regions. The nuclei of the subpopulation of these MIF-immunoreactive cells were also immunostained. These results indicated the widespread distribution of a cytokine, MIF, in the bovine brain and suggested the possibility that MIF might play additional roles than a proinflammatory mediator role in the brain.

Animals↗
PubMed1996

Affinity purification of macrophage migration inhibitory factor/glycosylation inhibiting factor (MIF/GIF) from bovine brain by using a peptide ligand derived from a novel serpin.

We purified macrophage migration inhibitory factor/glycosylation inhibiting factor (MIF/GIF) from bovine brain by using an affinity column with the C-terminal region peptide of a novel serpin as a ligand. The affinity purified preparation showing a single band on SDS-PAGE contained four peptides on RP-HPLC, which were converged into two peptides time-dependently. Sequence analysis and Western blotting revealed that one was identical to bovine MIF/GIF and the other was an N-terminally modified form of MIF/GIF. These results indicated that there exist at least two forms of MIF/GIF in the bovine brain and that they have an affinity for the C-terminal portion of the serpin.

Amino Acid Sequence↗
PubMed1995

Molecular cloning and characterization of rat V1b vasopressin receptor: evidence for its expression in extra-pituitary tissues.

Arginine vasopressin (AVP) modulates the secretion of ACTH through vasopressin receptor subtype V1b in the pituitary. We recently cloned human V1b, but several inconsistencies were found between the characteristics of this cloned receptor and those of rat pituitary membrane shown by previous workers. To clarify this issue, we report here the molecular cloning and functional expression of the cDNA encoding V1b in rat pituitary. This receptor encodes 425 amino acid protein having the highest identity with the human V1b (81%). Expression of this receptor in COS-1 cells showed pharmacological characteristics of V1b consistent with those of rat pituitary membrane. Northern blot and RT-PCR analyses revealed that mRNA of this receptor was expressed not only in anterior pituitary, but also in other tissues. This finding raises the possibility that V1b may play a role in regulating cell functions of these tissues.

Amino Acid Sequence↗
PubMed1992

Brain natriuretic peptide as a cardiac hormone in essential hypertension.

PURPOSE: A natriuretic peptide, brain natriuretic peptide (BNP), has been isolated from porcine hearts. We performed this study to determine if BNP is secreted from the heart and to identify changes, if any, in the plasma BNP concentration in essential hypertension. PATIENTS AND METHODS: We measured the immunoreactive (ir) BNP concentration at intracardiac sites including the coronary sinus of five patients with heart disease during cardiac catheterization. We examined plasma ir-BNP in 48 hypertensive patients, 15 borderline hypertensive patients, and 25 normotensive subjects. RESULTS: Plasma ir-BNP in the coronary sinus was greater than at other cardiac sites. The concentration was significantly higher in hypertensive subjects than in borderline hypertensive or normotensive subjects. Hypertensive patients with left ventricular hypertrophy (LVH) established by echocardiography had higher plasma ir-BNP levels than those without LVH. In the hypertensive group, plasma ir-BNP was closely correlated with the LV mass index. In these patients, BNP levels were correlated with mean arterial pressure and inversely correlated with the LV ejection fraction, although these correlations were weak. Reverse-phase high-pressure liquid chromatography showed that the major component of circulating ir-BNP in the hypertensive and normotensive subjects corresponded to authentic human BNP-32. CONCLUSIONS: Human BNP-32 was secreted through the coronary sinus from the heart and may act as a cardiac hormone. Plasma BNP was increased in many of the hypertensive subjects with LVH. The increase in BNP seemed to be related to LVH or the cardiac overload associated with LVH.

Adult↗
PubMed1992

Clinical significance of reverse redistribution on thallium-201 single-photon emission computed tomography in patients with acute myocardial infarction.

To determine the clinical significance of reverse redistribution (RR), resting thallium-201 myocardial single-photon emission computed tomography was performed once or twice in 80 patients in subacute phase (1 week to 2 months) of myocardial infarction. Thirty eight patients demonstrated RR on at least one study (group RR) and 32 a fixed defect only (group FD). Group RR had significantly smaller defects than group FD. Standardizing the relation of the severity of wall motion abnormality of left ventricle on echocardiogram with that of perfusion defect, in group RR wall motion abnormality in the acute and subacute phase reflected the defect of delayed image, while that in chronic phase, which was thought to reflect the viability of myocardium in the infarct region, reflected the defect of initial image. In serial thallium-201 studies, only the defect of delayed image of group RR improved on the second study, while the defect of initial image of group RR and defect of group FD did not improve. Wall motion of group RR improved with the disappearance of RR, and when RR remained, wall motion did not improve so much. We concluded that RR was thought to be demonstrated in viable myocardium with severe wall motion abnormality.

Adult↗
PubMed1992

Extensive specifically localized myocardial calcium deposition in a hemodialysis patient.

A 51-year-old female who was hospitalized for evaluation of frequent episodes of hypotension, died unexpectedly. At autopsy, there were many fine, white granular deposits in the myocardium, which were more prominent in the subepicardium of the left ventricle than in the subendocardium. Pathologic calcification is sometimes seen in chronic hemodialysis patients and in some organs the sites of calcium deposition are quite specific. There have been few reports concerning the pattern of calcium deposition in the myocardium and, to our knowledge, the reason for this characteristic distribution is unknown. However it may relate to hydrogen ion concentration in the myocardium.

Calcinosis↗
PubMed1991

Plasma levels of platelet-derived growth factor in normal subjects and patients with ischemic heart disease.

Plasma levels of platelet-derived growth factor (PDGF) were measured in 24 normal control subjects, 31 patients with stable angina pectoris, 25 patients with unstable angina pectoris, and 31 patients with acute myocardial infarction (AMI) by a sensitive direct radioimmunoassay. The plasma PDGF level in normal control subjects was 273 +/- 25 pg/ml; there was no significant correlation between the plasma PDGF level and age. Plasma PDGF levels in patients with unstable angina pectoris and acute myocardial infarction were significantly lower than those in normal control subjects and patients with stable angina pectoris (p less than 0.05). In patients with acute myocardial infarction the plasma PDGF level in the chronic phase was significantly higher than that in the acute phase (p less than 0.05). These observations raise the possibility that PDGF is involved in the pathophysiology of ischemic heart disease.

Adult↗
PubMed1991

Circulating immunoreactive endothelin in patients undergoing percutaneous transluminal coronary angioplasty.

Circulating immunoreactive endothelin (ir-ET) in the coronary sinus (CS) and the femoral artery (Ao) was measured in patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Plasma ir-ET level in the CS was significantly increased from 1.6 +/- 0.8 pg/mL to 2.0 +/- 1.0 pg/mL after PTCA (P less than .05). Plasma ir-ET level in the Ao tended to increase after PTCA, but it was not significant. Plasma ir-ET level in the CS was not related to the plasma thromboglobulin level, plasma thrombin-antithrombin complex level, mean blood pressure, or heart rate. These results suggest that the increase of plasma ir-ET level in the CS may be associated with the coronary endothelial injury by PTCA.

Adult↗
PubMed1991

Two-dimensional and Doppler echocardiographic findings in a case of subaortic "fibrous sac".

We described a 37-year-old man with a subaortic "fibrous sac", admitted for congestive heart failure. On 2-dimensional echocardiography a saccular structure was seen to extend from the left coronary cusp of the aortic valve to the outflow tract of the left ventricle. By color Doppler imaging, a grade 3 aortic regurgitation was recognized. Aortic regurgitant flow was recorded from the left coronary cusp to the saccular lesion. When congestive heart failure became exacerbated, the repeat examination showed the regurgitant flow passing through the perforated bottom of this lesion and reaching the left ventricular cavity. On microscopic examination of the excised valve, capillary proliferation and inflammatory changes were recognized near the annular region of the left coronary cusp. The edge of the valve leaflet and the other 2 cusps were intact. It is likely that our patient had a mycotic aneurysm near the aortic ring. We speculate that aortic regurgitation followed inflammation. It dilated the left ventricular cavity and contributed to congestive heart failure. Inflammation also weakened the tissue near the annulus, causing it to protrude into the subaortic region thus forming a small aneurysm. It may have grown to become a large saccular structure under high aortic pressure. That is, it became a "giant" endocardial pocket with inflammatory process. Finally, the rupture of this sac caused a massive aortic regurgitation, exacerbating congestive heart failure.

Adult↗
PubMed1990

Circulating immunoreactive endothelin in ischemic heart disease.

Circulating immunoreactive endothelin (ir-ET) was measured in nine patients with acute myocardial infarction (AMI), 10 patients with stable angina pectoris (SAP), and 25 normal control subjects. In patients with AMI, the plasma ir-ET level was elevated in the acute phase and was highest on the day of onset (AMI: 3.8 +/- 1.7 pg/ml, normal control value: 0.5 +/- 0.2 pg/ml). The plasma ir-ET level showed a positive correlation with the wall motion abnormality index (rs = 0.56, p less than 0.01), thrombin-antithrombin III complex (rs = 0.55, p less than 0.01), and beta thromboglobulin (rs = 0.39, p less than 0.05). An especially high plasma ir-ET level was detected in patients in whom the Killip subset was IV. The plasma ir-ET level was not increased in patients with SAP (0.8 +/- 0.3 pg/ml). The plasma ir-ET level is increased in the acute phase of AMI. A pathophysiologic state characterized by cardiac dysfunction, an activated coagulation system, and platelet hyperactivity may be associated with this increase in plasma ir-ET.

Angina Pectoris↗
PubMed1990

The complement system in ischemic heart disease.

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.

Angina Pectoris↗
PubMed1990

Significance of Q wave disappearance in the chronic phase following transmural acute myocardial infarction.

The mechanism and prognostic implications of Q wave regression following transmural acute myocardial infarction (AMI) were assessed in 54 patients. Of these subjects, 14 lost their Q waves. Exercise myocardial thallium-201 (201Tl) scintigraphy and two-dimensional echocardiography were performed before the patients were discharged from hospital. Two-dimensional echocardiography and electrocardiography were simultaneously repeated about 18 months after AMI. Both the relative 201Tl activity in the infarcted area and the improvement of echocardiographic wall motion index were higher in patients who had lost their Q waves than in those with retained Q waves (70 +/- 14% vs 58 +/- 13%, p less than 0.01; 5.2 +/- 3.0 vs 2.0 +/- 3.4, p less than 0.01, respectively). The prevalence of post-infarction angina pectoris was significantly higher in the former (29% vs 0%, p less than 0.01). We concluded that remnants of viable myocardial muscle might be responsible for Q wave regression following transmural acute myocardial infarction, and the prevalence of post-infarction angina pectoris was high among these patients.

Adult↗