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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 505 records · Page 28Linked to original sources

Hemangiopericytomatous meningioma metastasized to the liver: report of a case and review of the literature.

A 54-year-old male was admitted to our hospital for treatment of a liver tumor which was pointed out by screening ultrasonography. Computed tomography revealed a tumor in the right lobe of the liver measuring 7 cm in diameter. Angiography revealed a hypervascular tumor. A hepatocellular carcinoma or hypervascular metastatic tumor was suspected. A right hepatic lobectomy was performed. The patient had previously undergone operations for a hemangiopericytomatous meningioma in the occipital fossa in 1972 and 1977. The histological findings of the liver tumor were identical to those for hemangiopericytomatous meningioma, so the etiology was considered to be liver metastasis from the previous meningioma. Nineteen cases of extracranial metastasis of hemangiopericytomatous meningioma have been reported in the literature, but hepatic resections of this metastasizing tumor have been very rare.

Brain Neoplasms↗

The clinical significance of reactivity to individual epitopes of the hepatitis C viral genome.

In order to analyze the clinical significance of the various HCV epitopes, we compared the results of different HCV specific assays with HCV-RNA, determined in serum by RT-PCR method using primers to the 5' untranslated region of HCV-RNA. Among 73 patients with chronic NANB liver disease, 93% were positive for C22-3, 96% for C33C, 81% for C100-3 and 91% for RT-PCR. Positivity rates for 537 healthy subjects were 1.7% for C100-3 and 2.9% for second generation anti-HCV. A total of 6 persons were positive for C22-3 but not C100-3; all were negative for HCV-RNA. In 11 of 30 patients treated with interferon and HCV-RNA became negative and remained so for more than 24 months. In these 11 sustained responders, C100-3 and C33C antibody declined progressively, but C22-3 antibody showed a little change after treatment by quantitative analysis. The discrepancy of changes to NS region and core region after interferon treatment is consistent with a different clinical significance of reactivities to these HCV epitopes. Thus negative reactivity to NS region but positive for core region among healthy subjects may indicate past infection with HCV. Presence of antibodies to NS epitopes is implicated in HCV replication, while core epitopes indicate both present and past HCV infection.

Antigens, Viral↗

Comparison of seroepidemiology of hepatitis C in blood donors between Bangladesh and Japan.

To compare the seroepidemiology of hepatitis C and hepatitis B between Bangladesh and Japan, we tested the second generation antibody to hepatitis C virus (anti-HCV-2) and hepatitis B surface antigen (HBsAg) in serum samples from 163 professional blood donors (161 males and 2 females, mean age 28.6 yr.) and 83 voluntary blood donors from Bangladesh, and 7479 Japanese voluntary blood donors (5036 males and 2443 females; mean age 37.1 yr.). In Bangladesh, anti-HCV-2 is detected in 2.4% of professional blood donors and 0% of voluntary blood donors, furthermore, HBsAg is detected in 29% and in 2.4% of professional and voluntary blood donors, respectively. In Japan, anti-HCV-2 is detected in 0.6% in voluntary blood donors, and HBsAg also in 0.6%. These results indicate that professional blood donors in Bangladesh are highly contaminated by hepatitis B virus and moderately by hepatitis C virus, while voluntary blood donors in both countries are not so highly contaminated by either hepatitis viruses.

Adult↗

Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model.

A newly synthesized ET(A)-selective antagonist, BQ-123, was examined with respect to its anti-endothelin(ET) action in vitro and in vivo and its effect on blood pressure in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). In isolated porcine coronary arteries, BQ-123 (0.07 microM to 6.0 microM) shifted the concentration-response curve for ET-1 to the right without affecting the maximal response of ET-1, its pA2 value being 7.35. Intravenous infusion of BQ-123 at a rate of 1.2 and 30 mg/kg/hr produced a significant decrease in blood pressure in 20- to 29-week-old SHRSP, but did not alter blood pressure in 13- to 16-week-old WKY or in 18- to 19-week-old and 40-week-old SHR. The hypotensive effect of BQ-123 depended on the pretreatment blood pressure level. These results suggest that ET-1 is involved in part in the maintenance of high blood pressure in malignant hypertension, as exemplified by SHRSP.

Amino Acid Sequence↗

MEN type 1 associated with mediastinal carcinoid producing parathyroid hormone, calcitonin and chorionic gonadotropin.

A 34-year-old Japanese woman was admitted to our hospital with a mediastinal tumor. Laboratory data showed high levels of calcitonin (CT), human chorionic gonadotropin (hCG) and parathyroid hormone (PTH) in the serum. Surgery was performed, but the tumor could not be completely resected. The patient died in the 10th postoperative month due to systemic metastasis and cachexia. At autopsy, diffuse parathyroid hyperplasia and multiple islet cell tumors of the pancreas were found. A pathological diagnosis of multiple endocrine neoplasia (MEN) type 1 associated with mediastinal atypical carcinoid tumor was made. Immunohistochemical study indicated the tumor cells of the mediastinum to be positively stained for hCG beta but not for PTH or CT. The tumor tissue contained significantly high levels of CT, PTH and whole hCG. This is the first case report on MEN type 1 associated with mediastinal carcinoid tumor producing PTH, CT and hCG beta.

Adenoma, Islet Cell↗

Magnetic resonance imaging findings of craniofacial fibrous dysplasia.

There have been few reports in the literature concerning the magnetic resonance imaging (MRI) appearances of fibrous dysplasia. We reviewed MRIs of 4 patients with craniofacial lesions. Using a 1.5-T Signa Unit (General Electric, Milwaukee, WI), both T1- and T2-weighted MRI scans were performed. In our 4 patients, the fibrous dysplastic lesions were characterized by a decreased signal on both T1- and T2-weighted images. And all lesions had sharply demarcated borders. The fine image of fibrous dysplasia by MRI is extremely useful, not only as a diagnostic aid, but also as an invaluable guide to surgery.

Adolescent↗

BQ123, an ETA receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation.

Endothelin-1 (ET-1) is a potent endogenous vasoactive peptide whose role in regulation of vascular tone is unclear. BQ123 is a recently described ETA receptor antagonist which may be useful in further investigation of the physiologic and pathophysiologic significance of ET-1. To test its efficacy in the pulmonary circulation, the vascular response to exogenous ET-1 with and without BQ123 was assessed in rat pulmonary artery (PA) rings and salt-perfused lungs. In both main and distal (250-350 microns ID) PA rings, BQ123 significantly attenuated ET-1-induced contractility, but was more effective in the larger vessels. Likewise, BQ123 significantly blunted ET-1-induced vasoconstriction in perfused lungs by > 80%. In addition, it had no effect on ET-3-mediated or U46619-mediated vasoconstriction, nor did it influence ET-1-induced vasodilation. Development of ET-1-associated hydrostatic edema was also unaffected by BQ123. We conclude that BQ123 effectively attenuates ET-1-induced vasoconstriction in both PA rings and in isolated perfused lungs. The absence of effect of BQ123 on ET-3 vasoconstriction, ET-1 vasodilation, or ET-1- and ET-3-induced hydrostatic edema formation suggests that these processes may be transduced through a non-ETA receptor.

Amino Acid Sequence↗

The ligand-receptor interactions of the endothelin systems are mediated by distinct "message" and "address" domains.

Pharmacologic responses to endothelins (ETs) are mediated by two subtypes of G-protein-coupled receptors, termed ETA and ETB. A chimeric receptor that has the transmembrane domains (TMDs) IV-VI with the adjacent loop regions from ETB embedded in the remaining regions from ETA exhibits specific binding to the N-terminally truncated ETB agonists 125I-BQ3020 and 125I-IRL1620, to the same level as that of wild-type ETB receptor. Furthermore, the ETA-selective antagonist BQ123 competed for the binding of these ETB-selective radioligands to this chimeric receptor, with Ki values similar to those determined by using wild-type ETA receptor and 125I-ET-1. These findings indicated that the endothelin systems consist of two distinct parts, both on the ligand and receptor sides. The N-terminal loop structure of the agonists and the TMDs IV-VI with adjoining loops of the receptors determine the isopeptide/subtype selectivity. On the other hand, the C-terminal linear portion of the isopeptides and the TMDs I-III and VII plus adjacent loops of the receptors are probably involved in ligand-receptor binding itself. This scheme can be explained by the classic "message-address" concept proposed for a number of peptidergic ligand families.

Binding, Competitive↗

Two receptor subtypes are involved in the contractile component of the guinea pig ileum responses to endothelins.

Endothelin-1 (ET-1) and endothelin-3 (ET-3) induced a biphasic response (relaxation and contraction) in the guinea pig ileum. Short-term activation of protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) inhibited the contractile but not the relaxing component of the responses, as did H-7. Long-term pretreatment with PDBu reversed the short-term inhibition but did not affect the tachyphylaxis induced by ET-1. These results suggest that PKC contributes to ET-1 contraction but not to tachyphylaxis. The ETA antagonist BQ-123, at 34 nM, competitively inhibited ET-1 contraction, but at 340 nM the inhibition was noncompetitive. Dose-response curves for ET-1 relaxation were shifted to the left. For ET-3, BQ-123 (340 nM) only decreased the maximal contractile response of the dose-response curve without affecting the relaxation. We suggest that in this tissue there is one receptor for ET-1-induced contraction, which is competitively antagonized by BQ-123, and another one for ET-3-induced contraction, which is noncompetitively antagonized by BQ-123.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

ETA-dependent pressor effects and release of prostacyclin induced by endothelins in pulmonary and renal vasculature.

BQ-123, a selective endothelin A (ETA) receptor antagonist, was used to study the receptors involved in the ET-1-induced release of prostacyclin (PGI2) in perfused rat lung and rabbit kidney and the pressor effects of ET-1 in rabbit renal vasculature. In perfused rat lung, infusion of ET-1 (5 nM) significantly increased the release of PGI2, which was markedly reduced after a 15-min infusion of BQ-123 (1 microM). In rabbit kidney, the PGI2 release induced by ET-1 (10 nM) was abolished by a 15-min pretreatment with BQ-123 (1 microM). In both preparations the ET-1-induced release of PGI2 was fully restored 60 min after the interruption of BQ-123 infusion. In rabbit kidney a dose-dependent increase of perfusion pressure was also observed after bolus injections of ET-1 (5 and 10 pmol). The pressor responses to ET-1 were abolished by BQ-123 (0.1 microM), and 60 min after interruption of the infusion of the antagonist, the responses to ET-1 were restored to 68% and 99% of control values, respectively. Two selective ETB receptor agonists, IRL 1620 and BQ-3020, were inactive as pressor and prostanoid-releasing agents at doses and concentration 25-50 times higher than for ET-1 in perfused rabbit kidney. A higher concentration of BQ-123 (1 microM) did not modify the pressor responses to angiotensin II (5 nmol). Our results support the hypothesis that ET-1-induced release of vasodilatory prostanoids from perfused rat lung and rabbit kidney and constriction of rabbit renal vasculature are triggered by activation of ETA receptors.

Animals↗

Radioimmunoreactive plasma bradykinin levels and histological changes during the course of cerulein-induced pancreatitis in rats.

The plasma bradykinin (BK) and serum amylase levels and histological changes in rats during the course of acute pancreatitis induced by a large dose of cerulein were examined. Animals were given four intraperitoneal injections of 20 micrograms/kg body wt of cerulein at hourly intervals. The plasma concentration of BK-like immunoreactivity (BK-LI), measured by a highly sensitive and specific radioimmunoassay established in this study, was found to reach a peak 6 h after the first injection of cerulein and then to remain elevated. On the other hand, the serum amylase and the histological alterations (i.e., interstitial edema, vacuolization, and inflammatory infiltration) were maximal 9 h after the first injection and returned to nearly normal after 24 h. These observations suggest that the BK generation is indicative of the participation of the kallikrein-kinin system in the pathophysiological change and that the plasma BK-LI level is a good marker of cellular damage and inflammation within the pancreas during the course of acute pancreatitis.

Acute Disease↗

Enhancement by endothelin-1 of microvascular permeability via the activation of ETA receptors.

1. The objective of the present experiments was to assess the involvement of endothelin-A (ETA) receptors in mediating the effects of endothelin-1 on microvascular permeability in conscious rats. 2. Bolus injection of endothelin-1 (0.1 and 1 nmol kg-1, i.v.) resulted in a dose-dependent prolonged pressor effect preceded by a transient depressor response. These changes were accompanied by a dose-dependent loss of plasma volume. Endothelin-1 (1 nmol kg-1) enhanced the vascular permeability of the upper and lower bronchi, kidney, stomach, duodenum and spleen (up to 270%) as measured by the extravasation of Evans blue dye. 3. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg kg-1, i.v.) significantly blunted the pressor response to endothelin-1 without affecting the depressor response. BQ-123 inhibited by 87% the endothelin-1 (1 nmol kg-1)-induced plasma volume loss. BQ-123 markedly attenuated protein extravasation elicited by endothelin-1 in the upper and lower bronchi and kidney, whereas it completely inhibited the permeability effect of endothelin-1 in the stomach and duodenum. BQ-123 by itself had no significant effect on the parameters studied. 4. The endothelin-1 analogue, [Trp(For)21]-endothelin-1, in which Trp21 is formylated, was as potent a pressor agent as endothelin-1, but had no depressor action. Bolus injection of [Trp(For)21]-endothelin-1 (0.1 and 1 nmol kg-1, i.v.) evoked similar plasma volume losses to those observed following administration of equimolar doses of endothelin-1. Furthermore, 1 nmol kg-1 [Trp(For)21]-endothelin-l evoked increases in protein extravasation similar to endothelin-l, 1 nmol kg-1.5. The present findings suggest that endothelin- 1 enhances microvascular permeability, in part, via the activation of ETA receptors.

Amino Acid Sequence↗

Characterization of receptors for endothelins in the perfused arterial and venous mesenteric vasculatures of the rat.

1. Endothelin-1 and -3 induced marked arterial and venous constrictions in the perfused mesenteric vasculature of the rat with endothelin-3 being at least 20 times less active than endothelin-1, on both arterial and venous sides of the vasculature. 2. Two ETB selective agonists, BQ-3020 and IRL 1620 (500 pmol), induced weak constrictions of the venous mesenteric vasculature and were inactive in the arterial side at doses up to 1000 pmol. 3. In mesenteric vasculatures precontracted with either methoxamine (arterial side) or the thromboxane A2-mimetic, U46619 (venous side), acetylcholine or bradykinin produced vasodilations of both arterial and venous vessels, whereas endothelin-3 induced vasodilations only on the arterial side. 4. A selective ETA receptor antagonist, BQ-123, blocked, in a concentration-dependent and reversible fashion, the vasoconstrictions induced by endothelin-1 on both sides of the mesenteric circulation (IC50; arterial side: 0.013 microM; venous side: 0.032 microM). 5. In contrast, the vasodilator responses induced by endothelin-3 on the arterial side of the precontracted mesenteric vasculature were not affected by BQ-123. 6. The present study illustrates the presence of ETA receptors which are responsible for vasoconstriction by endothelins in the arterial and venous mesenteric vasculatures. Furthermore, we suggest that the vasodilations induced by endothelin-3 in the arterial vasculature uniquely, are ETB receptor-mediated.

Amino Acid Sequence↗

Epidemiology and long term prognosis of hepatitis C virus infection in Japan.

In Japanese blood donors, positivity for antibodies to hepatitis C virus (HCV) ranges from 0.2% in subjects under 20 to 3.9% in those over 50 years. It is estimated that at least 2.3 million Japanese have contracted HCV infection through contaminated blood. HCV carrier state was confirmed by polymerase chain reaction for HCV-RNA in subjects positive for antibodies to more than one viral protein (70% of cases). Subjects positive for core antibody alone, however, were found to be HCV-RNA negative with normal liver function, and are considered to have only a past history of HCV infection (30% of cases). Acute hepatitis C progresses to chronic infection in about 90% of cases. In comparison with hepatitis B, chronic hepatitis C leads more frequently to cirrhosis and liver cancer, and rarely remits spontaneously. In typical HCV infection, aminotransferase activities fluctuate markedly in the early stages, then become relatively stable for 10 years or more, with chronic persistent hepatitis shown by histological examination. Thereafter, aminotransferase activities may change dramatically, with progression to chronic active hepatitis and rapid development of cirrhosis and hepatocellular carcinoma. On average, it takes about 30 years for chronic hepatitis C to progress from initial infection to cirrhosis and cancer, but the disease progresses much more rapidly in elderly patients.

Adult↗

Effect of platelet on protein degradation in rat skeletal muscle.

The effects of activated platelet (Plt) on muscle degradation were investigated, employing the in vivo disseminated intravascular coagulation (DIC) model induced by thrombin injection and the in vitro tissue culture system of skeletal muscles in rats. Both the release of tyrosine and leucine into the culture medium during 2 h incubation from the muscles harvested 30 min after thrombin injection increased by about 50% compared with control muscles. The addition of thrombin-activated platelet supernatant (TAPS) significantly increased the release of leucine into the incubation medium of the soleus muscles dissected from normally fed rats by 31% in comparison with the respective controls. No significant effect was observed in terms of the release of tyrosine or leucine from the incubated muscles by aspirin treatment before obtaining TAPS, or by the addition of thrombin itself up to the concentration of 0.67 micron/ml which was contained in the incubation medium of TAPS. These data suggest that protein catabolism is accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The supernatant of activated Plt might contain a factor which modulates protein metabolism. That factor is different from prostaglandins or thrombin. Thus, active consumption of Plt may contribute to an increase of muscle breakdown in various catabolic states.

Animals↗

Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension.

Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.

Animals↗

Information propagation by spatio-temporal pattern change of Ca2+ concentration throughout Physarum polycephalum with repulsive stimulation.

The development of a spatio-temporal pattern of Ca2+ concentration (Ca2+ pattern) in the plasmodium of Physarum polycephalum during repulsive response was studied using fura-2. In the migrating cell, the gradient of the Ca2+ concentration (Ca2+ gradient) immediately showed a decrease in local concentration in the area (S-site) stimulated by 50 mM KCl. The concentration rose and then decreased in a site neighboring the S-site. This transient increase of Ca2+ concentration, the duration of which was approx. 10 minutes, was propagated to the site most distant from the S-site. There, the Ca2+ concentration gradually rose and remained at a high level. Twenty-five minutes after stimulation, a new Ca2+ gradient was established throughout the plasmodium. The migratory direction of the cell as a whole then changed. In this process, although the period of Ca2+ oscillation changed at the S-site, this change was only local to the site. During the information processing of the local repulsive stimulus, the transient Ca2+ increase propagated the local information about the stimulus to the non-stimulation sites (NS-sites), leading to the generation of a new pattern and the start of coordinated migration of the plasmodium.

Animals↗