RESUMO
Under magnetic fields, quantum magnets often undergo exotic phase transitions with various kinds of order. The discovery of a sequence of fractional magnetization plateaus in the Shastry-Sutherland compound SrCu2(BO3)2 has played a central role in the high-field research on quantum materials, but so far this system could only be probed up to half the saturation value of the magnetization. Here, we report the first experimental and theoretical investigation of this compound up to the saturation magnetic field of 140 T and beyond. Using ultrasound and magnetostriction techniques combined with extensive tensor-network calculations (iPEPS), several spin-supersolid phases are revealed between the 1/2 plateau and saturation (1/1 plateau). Quite remarkably, the sound velocity of the 1/2 plateau exhibits a drastic decrease of -50%, related to the tetragonal-to-orthorhombic instability of the checkerboard-type magnon crystal. The unveiled nature of this paradigmatic quantum system is a new milestone for exploring exotic quantum states of matter emerging in extreme conditions.
Assuntos
Campos Magnéticos , Imãs , Fenômenos Químicos , Fenômenos Físicos , RegistrosRESUMO
Ultrasound is a powerful means to study numerous phenomena of condensed-matter physics as acoustic waves couple strongly to structural, magnetic, orbital, and charge degrees of freedom. In this paper, we present such a technique combined with single-turn coils (STCs) that generate magnetic fields beyond 100 T with the typical pulse duration of 6 µs. As a benchmark of this technique, the ultrasound results for MnCr2S4, Cu6[Si6O18]·6H2O, and liquid oxygen are shown. The resolution for the relative sound-velocity change in the STC is estimated as Δv/v â¼ 10-3, which is sufficient to study various field-induced phase transitions and critical phenomena.
RESUMO
Previously we reported on L-DOPA's antinociceptive effect on substance P-induced nociceptive behaviors in mice [Shimizu T, Iwata S, Morioka H, Masuyama T, Fukuda T, Nomoto M. Antinociceptive mechanism of L-DOPA. Pain 2004;110;246-9.]. Since significant hyperalgesia was noted following antinociception, our study was designed to investigate the mechanism of this hyperalgesia. Nociceptive behaviors were enhanced 2 h after L-DOPA administration. L-DOPA induced hyperalgesia occurred after conversion to dopamine because co-administration of benserazide, a DOPA decarboxylase inhibitor, completely abolished the L-DOPA-induced hyperalgesia. The D2 receptor agonist, quinpirole, depressed these behaviors entirely, while the D1 antagonist, SCH23390, inhibited the enhancement of these behaviors by L-DOPA. The D2 receptor antagonist, sulpiride, which induced hyperalgesia of the substance P-induced behaviors in naive mice, did not have any effects on L-DOPA-induced hyperalgesia. Spinal cord dopamine content increased rapidly after L-DOPA administration, exhibiting levels 100 times greater than baseline, and then returned to control after 1 h. These results suggested that the dopaminergic inhibitory system for pain sensation was temporarily impaired by excess amounts of exogenous dopamine that were derived from L-DOPA and both D1 and D2 receptors were involved in L-DOPA-induced hyperalgesia.
Assuntos
Hiperalgesia/induzido quimicamente , Levodopa/farmacologia , Animais , Benserazida/farmacologia , Benzazepinas/farmacologia , Masculino , Camundongos , Quimpirol/farmacologia , Receptores de Dopamina D2/fisiologiaRESUMO
For the study of the effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on early mammalian cell differentiation, a complementary DNA (cDNA) library was constructed on the poly(A)+RNAs extracted from undifferentiated F9 cells derived from a 129/Sv mouse teratocarcinoma OTT6050, and screening was done for the cNDA sequences corresponding to the mRNAs, the levels of which decreased significantly in the F9 cells after the TPA treatment. From about 80,000 clones screened, 3 different cDNA clones, pFT27, pFT43, and pFT60, were isolated and characterized. Levels of the RNAs hybridizable to these clones were decreased by fourfold to more than fiftyfold within 1-10 hours in the presence of TPA. Northern blotting experiments identified transcripts corresponding to these clones: pFT27 hybridized to 3.0 kb RNA, pFT43 hybridized to 1.5 kb RNA, and pFT60 hybridized to 1.0 kb RNA. The levels of these 3 transcripts were also decreased after treatment of the undifferentiated F9 cells with retinoic acid (RA) and dibutyryl cyclic AMP (cAMP). The TPA-induced as well as the RA- and cAMP-induced decreases in the RNAs hybridizable to pFT27 were regulated at the transcriptional level, whereas similar decreases in the RNAs hybridizable to pFT43 and pFT60 were regulated at the post-transcriptional level. These findings show that TPA treatment shares common effects with RA and cAMP on the undifferentiated F9 cells.
Assuntos
DNA/isolamento & purificação , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Teratoma/genética , Acetato de Tetradecanoilforbol/farmacologia , Animais , Linhagem Celular , Clonagem Molecular , AMP Cíclico/farmacologia , Células-Tronco de Carcinoma Embrionário , Cinética , Camundongos , Hibridização de Ácido Nucleico , RNA Neoplásico/análise , Transcrição GênicaRESUMO
Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies.
Assuntos
Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Fatores de Transcrição/genética , Adulto , Idoso , Animais , Crise Blástica/genética , Feminino , Genes Supressores de Tumor , Humanos , Fator de Transcrição Ikaros , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Fatores de Transcrição/biossínteseRESUMO
Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.
Assuntos
Linfoma de Burkitt/genética , Proteínas de Ligação a DNA , Genes Dominantes/genética , Fatores de Transcrição/genética , Dedos de Zinco/genética , Adolescente , Adulto , Processamento Alternativo , Células da Medula Óssea/metabolismo , Linfoma de Burkitt/metabolismo , Feminino , Expressão Gênica , Humanos , Fator de Transcrição Ikaros , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/biossínteseRESUMO
BACKGROUND: Acoustic radiation force impulse (ARFI) elastography is a non-invasive method for measuring liver stiffness. However, there are no reports evaluating the value of ARFI elastography for liver fibrosis in chronic hepatitis C patients with a sustained virological response (SVR). AIM: To investigate the diagnostic performance of ARFI elastography for the assessment of liver fibrosis in hepatitis C virus (HCV) infected patients with an SVR. METHODS: In this prospective study, we enrolled 336 patients: 121 HCV patients with an SVR (44.6% women) and 215 patients with HCV (47.9% women). ARFI elastography measurements of all patients were performed on the same day of liver biopsy. RESULTS: The diagnostic accuracies, expressed as areas under the receiver operating characteristic curves for ARFI elastography, in HCV patients with an SVR and those in patients with HCV were 0.818 and 0.875 for the diagnosis of significant fibrosis (≥F2), 0.909 and 0.888 for the diagnosis of severe fibrosis (≥F3), and 0.981 and 0.890 for the diagnosis of liver cirrhosis (F4), respectively. The optimum cut-off values for ARFI elastography were 1.26 m/s for ≥F2, 1.31 m/s for ≥F3 and 1.49 m/s for F4 in HCV patients with an SVR. The liver stiffness values were lower in patients with SVR compared with those in patients with HCV at the same stage of fibrosis. The liver stiffness values were affected by the necroinflammatory activity and the time after SVR. CONCLUSION: Acoustic radiation force impulse elastography is an acceptable method for predicting the severity of fibrosis in patients with hepatitis C virus and a sustained viral response.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite C Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Acústica , Idoso , Biópsia , Feminino , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Resposta Viral SustentadaRESUMO
OBJECTIVES: We assessed the effects of the adenosine triphosphate (ATP)-sensitive potassium channel opener, nicorandil, on ATP- and verapamil-responsive ventricular tachycardias (VTs). BACKGROUND: Adenosine- or ATP-sensitive VTs are thought to be due to a nonreentrant mechanism, presumably delayed afterdepolarization. We suggest that this potassium channel opener may suppress ATP- and verapamil-sensitive VTs. METHOD: The subjects included 13 patients with idiopathic VTs, 7 of whom had sustained VT and 6 of whom had nonsustained VT. We evaluated the effects of ATP, nicorandil and verapamil on VTs. RESULTS: Sustained VT: Verapamil had preventive effects on seven VTs. Four VTs were terminated by ATP, and of these, nicorandil terminated two and prevented exercise-induced VT in the two others. Three ATP-insensitive VTs, which were determined to be due to a reentry by an electrophysiologic study, were not terminated by nicorandil. Nonsustained VT: All six VTs were inhibited by ATP, and five of these were suppressed by nicorandil. Verapamil inhibited four of the five VTs. QT intervals and the corrected QT intervals were significantly shortened by nicorandil. CONCLUSIONS: Nicorandil suppresses ATP- and verapamil-responsive VTs. One of the mechanisms of suppression by nicorandil might be related to a reduction of calcium in the myocardium, because it reduces the action potential duration.
Assuntos
Antiarrítmicos/uso terapêutico , Nicorandil/uso terapêutico , Canais de Potássio/efeitos dos fármacos , Taquicardia Ventricular/tratamento farmacológico , Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/uso terapêutico , Adolescente , Adulto , Antiarrítmicos/administração & dosagem , Antiarrítmicos/farmacocinética , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cromatografia Líquida de Alta Pressão , Eletrocardiografia , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nicorandil/administração & dosagem , Nicorandil/farmacocinética , Taquicardia Ventricular/sangue , Taquicardia Ventricular/fisiopatologia , Resultado do Tratamento , Verapamil/administração & dosagem , Verapamil/uso terapêuticoRESUMO
In order to elucidate mutual interrelationship between neurological and systemic dysfunctions in patients with subarachnoid hemorrhage (SAH) at acute stage, neurological condition, systemic complications and plasma catecholamine (CA) level were studied in 1431 consecutive cases admitted within 72 hours after the onset. Five hundred and twenty-four cases with Glasgow Coma Scale (GCS) score 8 or less were assigned to the group of severely ill cases (G-ill), 907 cases with GCS score 9 or more to that of the less ill group (G-well). Plasma CA level was extremely high at super-acute stage within an hour after bleeding and lowered fairly quickly within 24 hours to the normal range. Assuming the value obtained from a formula of [blood sugar level (mg/dl)/serum potassium concentration (mEq/L)] as stress index (SI), SI correlates well (r = 0.4-0.6) with serum catecholamine level at acute stage. Thus, sympathetic hyperactivity after SAH can be grossly estimated with SI. SI over 40 means that patients might have considerable neurological insults as well as systemic ones. For patients in G-well, SI over 50 means that there may be risks for systemic complications even in cases with good neurological condition.
Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Medição de Risco/métodos , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Doença Aguda , Doenças Cardiovasculares/terapia , Estudos de Coortes , Comorbidade , Feminino , Humanos , Japão/epidemiologia , Masculino , Doenças do Sistema Nervoso/terapia , Prevalência , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Hemorragia Subaracnóidea/terapiaRESUMO
A novel bioactive peptide was recently isolated from ovine hypothalamus and was named PACAP (pituitary adenylate cyclase-activating polypeptide). PACAP was present in two bioactive, amidated forms, PACAP27 and PACAP38 (27 and 38 amino acids, respectively), and showed a 68% sequence homology with vasoactive intestinal peptide (VIP) in the N-terminal 28 residues. PACAP38 was at least 1000 times more potent than VIP in stimulating adenylate cyclase in pituitary cells, but both peptides exhibited comparable vasodepressor activity. Thus, we sought to determine whether PACAP acts on specific binding sites in the anterior pituitary or other tissues and whether these binding sites are different from those of VIP. Binding of [125I] PACAP27 to freshly prepared rat anterior pituitary membranes in the presence and absence of 212 nM unlabeled PACAP27 was specific, saturable, and more rapid at 22 C than at 4 C. Scatchard analysis of this binding site using increasing doses of unlabeled PACAP27 revealed a single high affinity site with a Kd of 446 +/- 141 pM and a maximum number of sites of 1312 +/- 182 fmol/mg protein. These results do not exclude the possibility of a second pituitary binding site with significantly lower affinity. Unlabeled PACAP38 and PACAP38OH exhibited significantly higher affinity binding (3- to 5-fold) than PACAP27 with a similar number of pituitary sites. A variable distribution of binding sites was observed between PACAP27 and VIP when binding to different tissue membranes was measured with 125I-labeled peptides. Very high specific binding of both PACAP27 and VIP was observed in lung membranes. An almost identical relative magnitude of binding was observed between PACAP27 and VIP in lung, liver, duodenum, ovary, and thymus. However, whereas PACAP27 binding to hypothalamic and pituitary membranes was great, VIP binding to these tissues was almost absent. To determine if VIP and PACAP might share a binding site in peripheral tissues, displacement curves were generated using [125I]PACAP27 binding to lung membranes and VIP, PACAP27, and PACAP38 as unlabeled ligands. VIP was highly potent in displacing [125I] PACAP27 binding in lung membrane, and the IC50 values for all three of these peptides were between 1-10 nM. These results suggest that 1) a saturable, high affinity binding site for PACAP is present on anterior pituitary membranes; 2) PACAP27 and PACAP38, but not VIP, share this binding site in the anterior pituitary and possibly the hypothalamus; and 3) PACAP27, PACAP38, and VIP share a similar or identical binding site on lung membranes and possibly other peripheral tissues.
Assuntos
Hipotálamo/metabolismo , Neuropeptídeos/metabolismo , Adeno-Hipófise/metabolismo , Animais , Sítios de Ligação , Ligação Competitiva , Membrana Celular/metabolismo , Feminino , Cinética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Temperatura , Distribuição Tecidual , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Although the posterior pituitary is known to contain the PRL releasing activity or factor (PRF), its chemical identification has been a matter of dispute. In the present study, we purified PRF in porcine posterior pituitary extracts to chemically determine the primary structure. PRF activity was assessed during purification by the release of immunoreactive PRL from superfused rat pituitary cells. Two hundred seventy porcine posterior pituitaries were boiled, homogenized, and extracted with 2 M acetic acid. The acid extract was precipitated with 67% acetone, and the supernatant was absorbed onto a C18 column. The column was eluted step-wise with 10, 20, 30, 40, 50, and 60% acetonitrile (CH3CN) in 0.1% trifluoroacetic acid (TFA). The greatest PRF activity was recovered in the 30% CH3CN/0.1% TFA fraction and was further purified by ion-exchange chromatography on SP-Sephadex, followed by gel-filtration on Sephadex G-50. The Sephadex G-50 fractions with major PRF activity were finally purified by two cycles of reverse phase HPLC, yielding a single peak of PRF. Amino acid, as well as sequence analyses, indicated that the highly purified PRF was oxytocin. Authentic oxytocin showed the same chromatographic behavior and biological activity as those of the isolated peptide. In another experiment, desalted crude extracts of rat and porcine posterior pituitary tissues were directly chromatographed by reverse phase HPLC, and each fraction was assayed for PRF activity. Only two areas showed PRF activity; the largest activity coeluted with oxytocin and the smaller one co-eluted with vasopressin. The fractions which coeluted with oxytocin also showed oxytocin immunoreactivity, as examined by RIA. The results clearly indicated that the major PRF in these posterior pituitary extracts was oxytocin.
Assuntos
Ocitocina/isolamento & purificação , Neuro-Hipófise/análise , Prolactina/metabolismo , Sequência de Aminoácidos , Animais , Bioensaio , Cromatografia Líquida de Alta Pressão , Feminino , Dados de Sequência Molecular , Ocitocina/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Adeno-Hipófise/metabolismo , Ratos , SuínosRESUMO
A heterologous RIA method for pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38) and a homologous RIA method for a shorter form of PACAP with 27 residues (PACAP27) were established to determine PACAP content in central and peripheral tissues in rats. The highest concentration of radioimmunoassayable PACAP38 was found in the hypothalamus, but other brain regions also contained considerable amounts of PACAP38. PACAP38 concentration in the posterior pituitary was comparable with that in the extrahypothalamic brain, but its concentration in the anterior pituitary was very low. Unexpectedly, the testis contained a high abundance of PACAP38, and the total amount of PACAP in both testes exceeded its content in the whole brain. Reverse phase HPLC suggested that the major testicular PACAP38 immunoreactivity represents PACAP38. Among peripheral tissues, adrenal gland contained the second highest concentration of PACAP. Smaller amounts of PACAP were widely distributed in the digestive tract and other peripheral tissues. The concentration of PACAP in stomach, duodenum and jejunum appeared to be greater than in other portions of the gut. In all tissues, PACAP27 represented only a minor portion of total PACAP immunoreactivity.
Assuntos
Encéfalo/metabolismo , Neuropeptídeos/metabolismo , Testículo/metabolismo , Animais , Feminino , Masculino , Concentração Osmolar , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Radioimunoensaio , Ratos , Ratos Endogâmicos , Distribuição TecidualRESUMO
To determine the molecular forms of atrial natriuretic peptide (ANP) in patients with cardiovascular disease, we analyzed the ANP content in the right atrium using reverse phase high performance liquid chromatography and RIA. Tissue from 35 patients, ranging in age from 1 month to 64 yr, was studied. The right atrial ANP content was high in patients with congestive heart failure regardless of age. We found three ANP components (alpha-, beta-, and gamma ANP), as previously found in tissue obtained at autopsy. In patients younger than 20 yr old, the major component was gamma ANP. In older patients, the frequency and content of the two low mol wt forms, especially beta ANP, were increased. The differences in the content and molecular forms of ANP in atrial tissue reflect the pathological state in patients with cardiovascular diseases, as well as the patient's age.
Assuntos
Fator Natriurético Atrial/análise , Doenças Cardiovasculares/metabolismo , Adolescente , Adulto , Idoso , Envelhecimento/metabolismo , Fator Natriurético Atrial/metabolismo , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Átrios do Coração/análise , Átrios do Coração/metabolismo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Peso Molecular , RadioimunoensaioRESUMO
Plasma adrenomedullin (AM) levels are reportedly increased in heart failure, but whether the cardiac production and secretion of AM is increased in heart failure remains unknown. To investigate the sites of production and secretion of AM in heart failure, we measured plasma AM levels and peptide and mRNA levels of AM in various tissues in rats with heart failure. We also examined whether the heart actually secretes AM into the circulation in patients with heart failure. We measured plasma and tissue AM levels by specific radioimmunoassay and AM mRNA by Northern blot analysis in rats with heart failure produced by aortocaval fistula. We also measured plasma AM levels in the coronary sinus and aorta in patients with left ventricular dysfunction before and after rapid right ventricular pacing. The increase in plasma AM levels in heart failure rats correlated with ventricular weight. Tissue AM levels were increased in the heart and lungs but not in the kidneys or adrenals of rats with heart failure. Similarly, tissue AM mRNA levels were also increased in the heart and lungs of heart failure rats. Plasma AM levels were higher in the coronary sinus than in the aorta in patients with left ventricular dysfunction. Rapid right ventricular pacing increased plasma atrial natriuretic peptide but not AM. These results suggest that plasma AM levels are increased in heart failure in proportion to the severity of heart failure and that cardiac production and secretion of AM is increased in heart failure rats. The lung may be another site for increased production of AM in heart failure rats. Human failing heart actually secretes AM into the circulation, and the regulation of AM secretion appears to differ from that of atrial natriuretic peptide.
Assuntos
Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Peptídeos/metabolismo , Glândulas Suprarrenais/metabolismo , Adrenomedulina , Animais , Feminino , Coração/anatomia & histologia , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/metabolismo , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Peptídeos/sangue , Ratos , Ratos Wistar , Valores de Referência , Análise de Regressão , Disfunção Ventricular Esquerda/metabolismo , Função Ventricular Direita/fisiologiaRESUMO
Although synthetic atrial natriuretic peptide is known to increase urinary volume and sodium excretion and to reduce arterial blood pressure, the physiological role of endogenous atrial natriuretic peptide is still unclear. We investigated the effects of specific rabbit antiserum against alpha-rat atrial natriuretic peptide on hemodynamics, diuresis, and natriuresis in anesthetized rats. A significant rise in mean blood pressure lasted for about 60 minutes after intravenous administration of the antiserum, with the maximal increment being approximately 7%. Similarly, a significant increase in cardiac output was obtained 20 minutes after injection at an increment of approximately 11%. Heart rate, however, remained unchanged. On the other hand, significant reductions in urine output and urinary sodium and potassium excretion lasted for about 20 minutes after administration of the antiserum, with maximal decrements being 63%, 63%, and 60%, respectively. No significant effects on hemodynamics, diuresis, and natriuresis were observed following injection of normal rabbit serum. These results indicate that endogenous atrial natriuretic peptide has an important physiological role in the regulation of hemodynamics and water-electrolyte balance.
Assuntos
Fator Natriurético Atrial/imunologia , Soros Imunes/imunologia , Anestesia , Animais , Diurese , Hemodinâmica , Potássio/urina , Ratos , Ratos Endogâmicos WKY , Sódio/urinaRESUMO
It has been reported that plasma concentrations of adrenomedullin (AM), a novel vasodilator peptide, are higher in patients with essential hypertension than those in normotensive subjects. To clarify the clinical significance of increased levels of AM in patients with essential hypertension, in this study we examined the relationship between plasma concentrations of AM and the structure of the left ventricle or carotid artery. Plasma AM concentrations; renin activity; and norepinephrine, epinephrine, and creatinine concentrations in 50 patients with untreated essential hypertension without renal dysfunction and heart failure were measured. We also measured the mean wall thickness of the left ventricle and left ventricular mass index by M-mode echocardiography and intimal-medial thickness and arterial distensibility of the carotid artery by ultrasonography. Hypertensive patients were divided into two groups: hypertensives with and those without left ventricular hypertrophy. Plasma AM concentrations in hypertensive patients with left ventricular hypertrophy were significantly higher than in hypertensive patients without left ventricular hypertrophy (7.87+/-2.70 vs 5.74+/-1.65 fmol/mL, P<.01). In all hypertensive patients, plasma AM concentrations were not correlated with blood pressure, plasma renin activity, plasma norepinephrine, plasma epinephrine, or plasma creatinine concentration. Plasma AM concentrations were positively correlated with left ventricular mass index or mean wall thickness (r=.37, P=.009; r=.40, P=.004, respectively) and inversely correlated with carotid artery distensibility (r=-.33, P=.02), whereas plasma AM concentrations were not correlated with intimal-medial thickness. These results suggest that the observed elevation of plasma AM in patients with essential hypertension with normal renal function may be partly related to cardiac hypertrophy and decreased carotid artery distensibility.
Assuntos
Artérias Carótidas/patologia , Hipertensão/sangue , Peptídeos/sangue , Adrenomedulina , Adulto , Idoso , Cardiomegalia , Feminino , Humanos , Hipertensão/complicações , Hipertrofia , Masculino , Pessoa de Meia-IdadeRESUMO
The cloned cDNA for rat thromboxane (TX) synthase with a size of 1851 bp contained a 1599-bp open reading frame which encoded a 533-amino acid protein sharing 79.7% identity with human TX synthase. RNA blot analysis was carried out with rat cells and tissues. Rat peritoneal macrophages most abundantly expressed mRNA for TX synthase, and its level was not changed by in vivo stimulation of casein. Bone marrow, spleen, lung and thymus also expressed the TX synthase gene. These findings suggest the possibility that TXA2 plays a role in the immune system.
Assuntos
Macrófagos Peritoneais/metabolismo , Tromboxano-A Sintase/biossíntese , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Humanos , Dados de Sequência Molecular , Fases de Leitura Aberta , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Mapeamento por Restrição , Tromboxano-A Sintase/genéticaRESUMO
The effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the mRNA levels of two enzymes, thromboxane synthase (TXS) and prostaglandin endoperoxide synthase (PES), responsible for the synthesis of thromboxane A2 from arachidonic acid, were studied in human erythroleukemia (HEL) cells by RNA blot analysis. TPA induced both TXS and PES mRNAs in HEL cells in a dose-dependent manner at 36 h. The half-maximal and maximal effects for the induction of both mRNAs were at approximately 3 x 10(-9) M and at 10(-8) M, respectively. TXS and PES mRNA levels increased in a time-dependent fashion by TPA, and reached to 7- and 3.5-fold of the control, respectively after 48 h of TPA treatment. These results suggest that expression of TXS and PES genes in HEL cells were simultaneously stimulated by TPA.
Assuntos
Inibidores de Ciclo-Oxigenase/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Tromboxano-A Sintase/biossíntese , Indução Enzimática/efeitos dos fármacos , Humanos , Cinética , Leucemia Eritroblástica Aguda , RNA Mensageiro/biossíntese , Células Tumorais CultivadasRESUMO
We characterized highly selective receptors for PACAP, the pituitary adenylate cyclase activating peptide, in the tumoral acinar cell line AR 4-2J derived from the rat pancreas. PACAP, a novel hypothalamic peptide related to vasoactive intestinal peptide (VIP), was tested as the full natural 38-residue peptide (PACAP-38) and as an N-terminal amidated 27-residue derivative (PACAP-27). The binding sites showed considerable affinity for [125I]PACAP-27 (Kd = 0.4 nM) and PACAP-38, while their affinity for VIP and the parent peptide helodermin was 1000-fold lower. These receptors were coupled to adenylate cyclase, the potency of PACAP-38 and PACAP-27 (Kact = 0.2 nM) being much higher than that of VIP (Kact = 100 nM) and helodermin (Kact = 30 nM). Chemical cross-linking of [125I]PACAP-27 followed by SDS-PAGE and autoradiography revealed a specifically cross-linked peptide with an Mr of 68,000 (including 3000 for one PACAP-27 molecule).
Assuntos
Adenilil Ciclases/metabolismo , Neuropeptídeos/metabolismo , Pâncreas/análise , Hipófise/enzimologia , Receptores de Superfície Celular/análise , Receptores do Hormônio Hipofisário , Sequência de Aminoácidos , Animais , Ativação Enzimática , Dados de Sequência Molecular , Peso Molecular , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores de Peptídeo Intestinal Vasoativo , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
Human thromboxane (TX) synthase (EC 5.3.99.5) was produced by the baculovirus expression system using cDNA encoding human TX synthase [(1991) Biochem. Biophys. Res. Commun. 78, 1479-1484]. A recombinant baculovirus TXS7 was expressed in Spodoptera frugiperda Sf9 insect cells. The expressed protein was recognized by monoclonal antibody, Kon 7 raised against human TX synthase [(1990) Blood 76, 80-85]. The recombinant TX synthase catalyzed the conversion of prostaglandin (PG) H2 to TXA2 and 12-hydroxy-heptadecatrienoic acid (HHT). Both conversions of PGH2 to TXA2 and HHT by the expressed TX synthase were completely inhibited by a specific TX synthase inhibitor, OKY-046 (5 microM).