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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 541 records · Page 30Linked to original sources
PubMed1992

Analysis of responses to endothelins in isolated porcine blood vessels by using a novel endothelin antagonist, BQ-153.

We examined the effects of a novel ETA-selective endothelin (ET) antagonist, BQ-153, on vascular responses to ET-1 and ET-3 in isolated porcine coronary and pulmonary blood vessels, to clarify the roles of ET receptor subtypes in the regulation of vascular smooth muscle tension. With endothelium-denuded vascular tissues, the concentration-contraction curve (CCC) for ET-1 appeared as a single sigmoidal shape for all types of tissue. The CCC for ET-1 was antagonized by BQ-153 (2 and 10 microM) in all tissues, but part of the contraction was resistant. The CCC for ET-3 usually consisted of two different phases with higher (first phase) and lower (second phase) sensitivities to the peptide. Only the second phase of CCC for ET-3 was completely inhibited by BQ-153 (2 microM) in all tissues, while the first phase was resistant. The BQ-153-resistant contractile phases of ET-1 and ET-3-induced vasoconstriction appeared to have similar sensitivity in all tissues, and the contractile activity varied with each type of tissue. With endothelium-intact materials, the potencies of ET-1 and ET-3 for endothelium-dependent vasorelaxation in pulmonary artery were almost equivalent. BQ-153 (10 microM) did not inhibit ET-induced vasorelaxation. These results indicate that ET-induced vasoconstriction is mediated not only through ETA but also through ETnonA (probably ETB), and that the relative proportions of the ET-receptor subtypes mediating contractions vary in different vascular areas. In addition, results showed that ET-induced endothelium-dependent vasorelaxation is mediated through ETB.

Animals↗
PubMed1992

A novel radioligand [125I]BQ-3020 selective for endothelin (ETB) receptors.

A linear endothelin (ET) analog, N-acetyl-LeuMetAspLysGluAlaValTyrPheAlaHisLeu-AspIleIleTrp (BQ-3020), is highly selective for ETB receptors. BQ-3020 displaces [125I]ET-1 binding to ETB receptors (nonselective to ET isopeptides) in porcine cerebellar membranes (IC50: 0.2nM) at a concentration 4,700 times lower than that to ETA receptors (selective to ET-1) on aortic vascular smooth muscle cells (VSMC) (IC50: 940nM). BQ-3020 as well as ET-1 and ET-3 elicits vasoconstriction in the rabbit pulmonary artery. The ETA antagonist BQ-123 failed to inhibit this BQ-3020-induced vasoconstriction. Furthermore, BQ-3020 elicits endothelium-dependent vasodilation. These data indicate that BQ-3020 has ETB agonistic activity. The radioligand [125I]BQ-3020 binds to cerebellar membranes at single high affinity sites (Kd = 34.4pM), whereas it scarcely binds to VSMC. [125I]BQ-3020 binding to the cerebellum was displaced by BQ-3020, ET-1 and ET-3 in a nonselective manner (IC50: 0.07-0.17nM). However, the binding of [125I]BQ-3020 was insensitive to the ETA antagonist BQ-123 and other bioactive peptides. Both [125I]ET-1 and [125I]BQ-3020 show slow onset and offset binding kinetics to ETB receptors. These data indicate that the radioligand [125I]BQ-3020 selectively labels ETB receptors and that the slow binding kinetics of ET-1 are dependent on the peptide sequence from Leu6 to Trp21, but not on the structure formed by its two disulfide bridges.

Amino Acid Sequence↗
PubMed1992

Control of feeding rhythm in the terrestrial slug Incilaria bilineata.

A modulatory neuron of feeding rhythm was newly identified in the buccal ganglia of the isolated central nervous system (CNS) of the terrestrial slug Incilaria bilineata. This neuron was termed the "feeding rhythm modulator" (FRM). Its morphological and electrical properties were compared with those of the MGC (metacerebral giant cell, a cerebral modulatory neuron of feeding rhythm). There was no direct connection between FRM and MGC. In order to investigate the control mechanism of the buccal central pattern generator, feeding rhythm was observed by varying the activities of MGC and FRM simultaneously. At a lower level of activity of MGC, feeding rhythm was not only sensitive to the activity of MGC but also to that of FRM. As the level of activity of MGC increased, feeding rhythm was exclusively controlled by the activity of MGC, and became unaffected by the activity of FRM. This indicates that cerebral neurons such as MGC primarily control feeding rhythm and modulate the contribution of FRM in a hierarchical manner.

Animals↗
PubMed1992

High-yield production of recombinant endothelin-1.

A fusion protein (pETB-42P), which encodes the 42-amino acid leader peptide and the 38-amino acid peptide of human big endothelin (ET)-1, was synthesized in Escherichia coli, isolated as inclusion bodies, and purified by DEAE-chromatography. Trypsin digestion of the purified pETB-42P gave big ET-1(1-37) in a yield of 70%; then pepsin digestion of the purified big ET-1(1-37) gave ET-1(1-21) in a yield of 74% (overall yield: 52%). Sequential trypsin and pepsin digestions of the purified fusion protein in the same reaction vessel also allowed recovery of ET-1 in a yield of 60%. One milligram of ET-1 or 2.0 mg of big ET-1(1-37) was obtained from 1.8 liters of culture broth. Recombinant ET-1 thus obtained was identical to authentic ET-1 in terms of amino acid sequence and vasoconstrictor potency, and recombinant big ET-1(1-37) had almost the same in vitro and in vivo biological activities as big ET-1(1-38).

Amino Acid Sequence↗
PubMed1992

In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor.

The novel endothelin (ET) receptor antagonists BE-18257A and BE-18257B were isolated from the fermentation products of Streptomyces misakiensis. The above-mentioned compounds inhibited [125I]ET-1 binding to ETA receptors (selective for ET-1) on porcine aortic vascular smooth muscle cells (VSMCs) with IC50 values of 1.4 and 0.47 microM, respectively. [125I]ET-1 binding to ETB receptors (nonselective to ET isopeptides) in cerebellar membranes was not inhibited by either of these compounds even at 100 microM. The synthesized analogue BQ-123 induced extremely potent inhibition of [125I]ET-1 binding to ETA receptors (IC50 of 7.3 nM), but it barely inhibited [125I]ET-1 binding to ETB receptors (IC50 of 18 microM) and binding of various other peptides to their receptors. BQ-123 shifted the concentration-response curve for ET-1 toward the right in porcine isolated coronary arteries, indicative of competitive antagonism for the ETA receptor. However, there was a small amount of BQ-123-insensitive vasoconstriction that paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the vascular smooth muscle layer. These data suggest that the artery contracts via both ETA and ETB receptors and that BQ-123 selectively inhibits ETA-mediated contraction. Furthermore, BQ-123 revealed large tissue and species differences in the distribution of ETA receptors. Thus, the potent ETA antagonist BQ-123 should be useful in clarifying the (patho)physiological roles of ETA receptors.

Amino Acid Sequence↗
PubMed1992

Human big-endothelin-1 and endothelin-1 release prostacyclin via the activation of ET1 receptors in the rat perfused lung.

Although ET1 and ET2 binding sites were found in rat lung membranes, a selective ET1 receptor antagonist, BQ-123 (10 microM), did not displace [125I]-endothelin-1 ([125I]ET-1) from ET2 sites, illustrating the selectivity of the angatonist for ET1 receptors. In rat perfused lungs, BQ-123 (1 microM) markedly reduced the prostacyclin (PGI2) releasing properties of endothelin-1 (ET-1: 5 nM) and human big-ET-1 (100 nM) suggesting that both peptides induce the release of PGI2 via the selective activation of ET1 receptors.

Animals↗
PubMed1992

BQ-153, a novel endothelin (ET)A antagonist, attenuates the renal vascular effects of endothelin-1.

Endothelin (ET)-1, leukotriene D4 and the thromboxane analogue, U-44069, were all shown to produce dose-dependent reductions in renal blood flow after direct injection into the renal artery of anaesthetized pigs. The effects of ET-1 differed from the other two mediators in that ET-1 caused a transient vasodilator followed by a prolonged vasoconstrictor response. The pressor response was not mediated by the secondary release of either leukotriene D4 or thromboxane A2 as evidenced by the lack of effect of appropriate receptor antagonist MK571 (3-[-2(7-chloro-2 quinolinyl) ethenyl]phenyl[3-(dimethylamino-3-oxopropyl)thio]methyl thio propionic acid) and L-670,596 respectively. This response, however, could be inhibited in a dose-dependent fashion by the selective ETA antagonist, BQ-153 (cyclo-D-sulphalanine-L-Pro-D-Val-L-Leu-D-Trp-). Following blockade by BQ-153 the vasodilator response was unaffected and a residual pressor response remained, suggesting that either or both of these effects were mediated either through an ETB or a novel, as yet undefined, endothelin receptor.

Amino Acid Sequence↗
PubMed1992

Role of the liver-enriched transcription factor DBP in expression of the cytochrome P450 CYP2C6 gene.

The CYP2C6 gene becomes maximally transcriptionally activated in livers of postpubertal rats. We examined the role of upstream DNA and liver-specific transcription factors in regulation of this promoter by use of transient transfection of heterologous chloramphenicol acetyltransferase gene constructs and vectors containing cDNAs encoding the liver-enriched transcription factors HNF-1 alpha, C/EBP, and DBP. Only DBP was able to activate the CYP2C6 promoter in HepG2 cells. Transactivation was not observed in one mouse and two human nonhepatic origin cell lines tested. Analysis of various constructs in which CYP2C6 upstream DNA was deleted revealed that DNA between -38 to -103 was involved in DBP-mediated activation. A partially purified preparation of DBP produced a footprint between -43 and -64 bp upstream of the transcription start site. A 32P-labeled double-stranded oligonucleotide, containing sequence information corresponding to -40 to -65, bound to both partially pure DBP and extracts from livers of rats as young as 1 week and as old as 25 weeks of age, as assessed by gel mobility shift analysis. This binding was eliminated by coincubation with excess unlabeled -40/-65 double-stranded oligonucleotide and by an oligonucleotide corresponding to the D site of the rat albumin gene. A gel mobility shift-Western immunoblot analysis revealed that the -40/-65 sequence bound to DBP only in liver nuclear extracts from rats older than 3 weeks; maximal binding was observed by 7 weeks of age, and no binding was detected from 1-week-old rat liver extracts. Interestingly, the DBP-binding regions of both CYP2C6 and albumin bind to C/EBP, but this factor is capable of transactivating only the latter gene. Although the DBP-binding regions in these two genes share no obvious sequence similarities, the CYP2C6 region contains consensus palindromic half sites for DBP-related binding proteins and affinity for recombinant DBP of 17-fold greater than that of the D site of albumin. This difference in affinity is probably responsible for the markedly lower amounts of DBP required for half-maximal activation of the CYP2C6 promoter, as compared with the albumin promoter, in transactivation transfection assays. These data indicate that the CYP2C6 gene may be regulated, at least in part, by DBP, a liver transcription factor produced when rats reach puberty that may also be involved in maintenance of albumin gene transcription.

Age Factors↗
PubMed1992

Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening.

Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H109-H116, 1992.--To study the differing behaviors of the inner (IH) and outer halves (OH) of the left ventricular (LV) free wall during an increasing afterload and changing inotropic states, we determined the LV pressure (LVP) and transmural (TM) and OH wall thickness (WTTM and WTOH) by sonomicrometry in 11 anesthetized dogs. The percent systolic wall thickening (% delta WT) and the fractional contribution (FC) were calculated. At rest, % delta WT of TM, IH, and OH were 22 +/- 1 (mean +/- SE), 33 +/- 3, and 13 +/- 2 (P less than 0.01 vs. IH), respectively. The FC of IH and OH were 74 +/- 5 and 29 +/- 4% (P less than 0.01 vs. IH), respectively. During increasing afterload by aortic constriction (AC) without drugs, % delta WT in IH was reduced to 22 +/- 2%, associated with unchanged % delta WT in OH (12 +/- 3%), whereas the FC of IH and OH were not altered from resting values. During AC with dobutamine infusion (3 micrograms.kg-1.min-1), the % delta WT and FC in each layer were not reduced from resting values. On the other hand, during AC with propranolol (2 mg bolus iv), the reduction of % delta WT in IH was greater (from 29 +/- 4 to 15 +/- 6%, P less than 0.01) than that in OH (from 11 +/- 2 to 10 +/- 3%; P less than 0.01 vs. IH). The FC in the IH was decreased (56 +/- 16%) by AC with propranolol, so that the difference in FC between IH and OH became insignificant (FCOH 40 +/- 13%, P greater than 0.1 vs. FCIH).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Entrainment to external Ca2+ oscillation in ionophore-treated Physarum plasmodium.

To elucidate the mechanism of mutual interaction between intracellular chemical rhythms in the Physarum plasmodium, external Ca2+ oscillation was applied to the ionophore-treated plasmodial strand and its response was measured as tension oscillation. (i) Tension oscillation is entrained and phase locked to the externally applied Ca2+ oscillation. (ii) Two kinds of stable phase relationship, in-phasic and anti-phasic ones, are observed between them. (iii) Transition between the two stable phase relationships is also observed. These results suggest that intracellular rhythms with control tension generation are mutually entrained by means of cytosolic Ca2+ oscillation in the organism and that their interactions have two kinds of stable phase relationships.

Animals↗
PubMed1992

Effect of the combination of anticoagulant and thromboxane synthetase inhibitor (Y-20811) or receptor blockade (S-1452) on preventing thrombotic cyclic coronary flow reduction in dogs with coronary stenosis.

We examined the hypothesis that combined actions of anticoagulant (heparin) and Y-20811, thromboxane A2 synthetase inhibitor (TXSI), or S-1452, receptor blockade (TXRB), can provide better antithrombotic protection than TXSI or TXRB alone. In 20 of 33 dogs instrumented, placement of a critical stenosis at a focus of coronary vascular injury initiated a reproducible cyclic coronary flow reduction (CCFR). TXSI (1 mg/kg, IV) perfectly inhibited CCFR in 6 of 10 dogs (60%), and was associated with a significant decrease in 11-dehydro-TXB2 (85 +/- 8% of control; p < 0.05) and an increase in 6-keto-PGF1 alpha (155 +/- 38%; p < 0.05) in coronary sinus blood samples. In the remaining 4 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. On the other hand, TXRB (1 mg/kg, IV) perfectly inhibited CCFR in 7 of 10 dogs (70%), and was accompanied by a significant increase in 6-keto-PGF1 alpha (214 +/- 65%; p < 0.05) and unchanged TXB2 level. In the remaining 3 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. Thus, the combination of anticoagulant and TXSI or TXRB were more effective than TXSI or TXRB alone in abolishing thrombotic CCFR, suggesting that the combination might be effective for treating patients with impending myocardial infarction.

Animals↗
PubMed1992

Relation between fetal blood gas levels and the outcome of babies in severe preeclampsia.

The purpose of this study is to ascertain that fetal blood gas values obtained by cordocentesis could be a clinical standard to decide whether or not we should terminate pregnancy and switch to exutero salvage for avoiding hypoxic damage. Fetal blood sampling was performed 38 times in 36 cases of severe preeclampsia. The relation between fetal blood gas values and the prognosis of the baby was statistically examined. Six of 36 fetuses of severe preeclampsia died prenatally or postnatally. There were significant differences in delta-values (difference from the normal mean value in each gestational week) of pO2, pCO2, and pH between survivors and non-survivors. delta pO2 value is most reliable to predict fetal prognosis. Since conventional fetal evaluation methods such as fetal heart rate monitoring are unreliable in the early gestational period, fetal gas evaluation is preferable to decide further intervention.

Blood Gas Analysis↗
PubMed1992

[Diagnosis of hepatitis C and its future].

Several epitopes of the hepatitis C virus (HCV) have been identified, but the biological and clinical significance of antibodies to each protein is not well understood. Core antigens include C-22, JCC, P 0 and CP-9. Among epitopes in the non structural (NS) regions, C-33C is in the NS3, C100-3 in the NS3/4, 511 in the NS4 and C825 in the NS5 regions. First generation anti-HCV has C100-3 epitope and second generation anti-HCV consists of three epitopes which are C-22, C-33C and C100-3. In order to analyse the clinical significance of the various HCV epitopes, We compared the results of these 9 different HCV specific assays with HCV-RNA, as 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, 94% were positive for C-22, 94% for JCC, 91% for P 0, 89% for CP-9, 97% for C-33C, 84% for C100-3, 65% for 511, 55% for C825, 58% for GOR and 91% for RT-PCR. Positive rates for Core region epitopes were very similar to each other and to the presence of HCV-RNA. Antibodies to NS region epitopes were more variable, with those to NS4 and NS5 region being less sensitive than HCV-RNA. Positivity rates for 537 healthy subjects were 1.1% for C100-3, 2.7% for JCC. 6 persons who were positive for C100-3 were also positive for JCC and 4 of those were positive for HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Epitopes↗
PubMed1992

[A case of idiopathic pulmonary fibrosis with histology of usual interstitial pneumonia that responded to pulse therapy followed by combined immunosuppression with prednisolone and azathioprine].

A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8 mg/kg) and azathioprine (15 mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia. Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %DLco 72%, PaO2 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects.

Aged↗
PubMed1992

[Detection of mediastinal lymph node metastasis from lung cancer with positron emission tomography (PET) using 11C-methionine].

Twenty-five patients with primary non-small cell lung cancer underwent the positron emission tomography (PET) using 11C-methionine to detect the mediastinal lymph node metastasis. We introduced the positron angiography to recognize precisely the anatomical orientation of the mediastinal lymph nodes. The 11C-uptake of the lymph node was expressed with distribution absorption ratio (DAR). A total 107 lymph nodes were examined. The average DAR in metastatic lymph nodes (n = 28) was 3.89 while that of non-metastatic nodes (n = 79) was 2.38 indicating a significant difference (p < 0.001). The most adequate threshold for detection of metastasis was 3.3 with sensitivity of 100%, and specificity of 87.3% and overall accuracy of 89.7%. Metastasis of squamous cell carcinoma was diagnosed more accurately than that of adenocarcinoma. Thus, PET using 11C-methionine may offer a new method to detect the mediastinal lymph node metastasis from lung cancer.

Adult↗
PubMed1992

[Immunological reactions in patients with pulmonary aspergilloma].

A 52-year-old man with pulmonary aspergilloma is reported. In immunoassays, type I, III and IV hypersensitivity reactions of Gell & Coombs were observed. The finding of such immunological reactions, especially type I hypersensitivity, has rarely been observed in this disease. The present study was performed to investigate these reactions, especially to determine whether type I allergy participates in pulmonary aspergilloma. We reviewed 126 cases of pulmonary aspergilloma reported in the Japanese literature between January 1980 and April 1991. The following results were obtained: Elevation of serum IgE was observed in 49% of the subjects examined, positive IgE RAST score in 28%, precipitating antibody against A. fumigatus in 79%, and positive lymphocyte stimulation test using A. fumigatus antigen in 68%. In conclusion, type I, III and IV hypersensitivity of Gell & Coombs appears to participate in pulmonary aspergilloma. The occurrence of type I hypersensitivity is not rare in this disease.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1992

Structure-activity relationship for ETB agonism in truncated endothelin-1 analogs.

The essential part of the ETB-selective agonist N-acetyl-GluAlaValTyrPheAlaHisLeuAspIleIleTrp (N-Ac-4AlaET-1(10-21)) for ETB agonism was studied by single amino acid replacement. Single L-alanine substitutions at positions 14, 17, 20 and 21 and the corresponding D-amino acid substitutions at positions 14 and 16-21 resulted in remarkable decreases in ETB binding activity. Furthermore, these analogs elicited endothelium-dependent vasorelaxation in parallel with ETB binding activity. These data indicate that the amino acid residues of Phe14, Leu17, Ile20 and Trp21 and the backbone structure at Phe14 and His16-Trp21 in ET-1 are important for ETB agonism.

Alanine↗