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Biomedical subjects

K Naruse

Publications and source records attributed to K Naruse.

At least 217 records · Page 12Linked to original sources

Is big endothelin converted to endothelin-1 in circulating blood?

Although evidence has been accumulating to support an intracellular processing of big endothelin-1 (big ET-1) to ET-1, molecular conversion in the circulating blood remains to be elucidated. The present study was undertaken to investigate whether big ET-1 was converted to ET-1 in human blood. In the first experiment, normal serum with synthetic big ET-1 exogenously added or serum from patients with chronic renal failure was incubated in vitro at 37 degrees C for 1 h. In the second experiment, synthetic big ET-1 was incubated in the whole blood at 37 degrees C for 1 h. In the third experiment, synthetic big ET-1 was administered intravenously in anesthetized rat and a plasma sample was obtained before and after 15 min and 1 h. After respective incubation, molecular forms of ET were determined by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassay. There was no significant conversion of big ET-1 to ET-1 in the serum obtained from normal and CRF patients. However, there was a slight but significant increase of ET-1 after incubation of big ET-1 in the whole blood or after administration of big ET-1 in anesthetized rat. The conversion in the whole blood was inhibited by 5 mM EDTA. These results suggest that circulating blood may not be a major site of molecular conversion from big ET-1 to ET-1, although conversion does occur in the circulation by blood cell-mediated process.

Animals↗

Molecular form of immunoreactive endothelin in plasma and urine of normal subjects and patients with various disease states.

To elucidate the pathophysiologic significance of the family of endothelin (ET) peptides, we have investigated plasma and urinary immunoreactive (ir-) ET levels and its molecular forms in normal and pathological conditions. Plasma and urine ET were extracted with an Amprep C2 column. The molecular form of ET was determined by a combination of radioimmunoassay and reverse-phase high-performance liquid chromatography. Although plasma ir-ET was composed mainly of big ET and endothelin-1 (ET-1) in normal subjects, that in acute myocardial infarction, chronic renal failure (CRF), essential hypertension, and vasospastic angina pectoris was characterized by an increase of high molecular ir-ET in addition to increases in big ET and ET-1. Urinary ir-ET in both normal subjects and patients with CRF was composed mainly of a high molecular form in addition to big ET and ET-1. These results suggest that the biosynthetic and/or degradation process of ET under pathological conditions appears to be different from that under normal conditions.

Angina Pectoris↗

Relationship between fetal hypoxia and endothelin-1 in fetal circulation.

The role of endothelin-1 (ET-1), a potent vasoconstrictor peptide secreted by endothelial cells, in fetal circulation was investigated in relation to fetal hypoxia. Umbilical venous blood was obtained from 23 subjects who delivered between 36 and 41 weeks of gestation. In all cases, pH of umbilical venous blood was measured immediately after the delivery of placenta. ET-1 was extracted from the umbilical venous plasma by an Amprep C2 column and determined by a specific radioimmunoassay. Immunoreactive ET levels in the umbilical cord plasma (pg/ml, mean +/- SEM) from subjects with umbilical venous blood pH levels below 7.30 (n = 9) were 12.53 +/- 2.03, significantly higher than those with pH levels above 7.30 (6.44 +/- 1.11, n = 14). These results indicate that ET-1 in the fetal circulation may be involved in the regulation of the circulation in response to changes in acid-base balance related to fetal hypoxia.

Adult↗

Antiserum against homologous atrial natriuretic peptide diminishes the natriuretic response during mineralocorticoid escape in rats.

To elucidate the physiological role of atrial natriuretic peptide (ANP) in plasma during mineralocorticoid escape, we investigated the effects of passive immunization with ANP-specific antiserum on deoxycorticosterone (DOCA)-treated rats. Sodium was retained in excess of intake during the first day after treatment with DOCA, and sodium balance returned to control values by the second day, whereas the excretion of potassium exceeded the intake during all days after DOCA treatment. These changes in electrolyte balance were associated with a significant increase in plasma levels of ANP. Administration of ANP-specific antiserum significantly impaired the return to normal sodium balance as well as the augmented kaliuresis that were observed on the second day after injection of DOCA. No significant effect was observed on either sodium or potassium balance after the injection of normal rabbit serum. These results suggest that plasma ANP plays an important role in mineralocorticoid escape.

Animals↗

Electrophysiological analysis of structural aspects of voltage-dependent SR K+ channel.

This article presents a brief review on the electrophysiological analysis of the structural aspects of the voltage-dependent SR (sarcoplasmic reticulum) K+ channel. In the first half, early attempts to determine the physical dimensions of the ion conducting mechanism such as the mouth, narrow tunnel, or ion selective filter of the channel, are reviewed. The depicted cartoon of the SR K+ channel, as an extremely short, busy district with a big mouth on each side, is quite similar to the recently-obtained reconstructed structural image of the acetylcholine receptor channel. In the latter half, we introduce our recent attempts to draw a physical image of the gating mechanism of the SR K+ channel. We examined, for example, the location of the gate and the voltage sensor, and the relationship between them. It is suggested that the gate and the sensor are connected tightly and that the sensor would be exposed to the surface of the lumen side of SR when the gate opens. Finally, the issue of substates in SR K+ channel is discussed. It is implied that the substrate-conductances reflect a partial occlusion of the pore by an intermediate-open gate.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Immunocytochemical localization of endothelin in cultured bovine endothelial cells.

To investigate the intracellular localization of endothelin in cultured endothelial cells, an immunocytochemical study was carried out by the post-embedding protein A-gold technique with endothelin-specific antiserum. Gold particles were seen on the rough endoplasmic reticulum, the Golgi cisternae, the Golgi vesicles, small vesicles beneath the cell membrane, and the lysosomes. By contrast, no secretory granules were observed. These results suggest that endothelin is secreted by a constitutive pathway and that the lysosome may play an important role in regulating the biological activity of endothelin.

Animals↗

Aminoglycoside blockade of Ca2(+)-activated K+ channel from rat brain synaptosomal membranes incorporated into planar bilayers.

Ca2(+)-activated K+ channels from rat brain synaptosomal membranes were incorporated into planar lipid bilayers, and the effects of aminoglycoside antibiotics on the single channel conductance (258 +/- 13 pS at 100 mM K+) were investigated. Aminoglycosides reduced the single channel conductance from the 'cis' (cytoplasmic) side in a dose- and voltage-dependent manner. Voltage dependence of the blockade indicated an interaction between positively charged amino residues of aminoglycoside antibiotics and a binding site located within the electric field of the ion-conducting pathway. The order of blocking potency was consistent with that of the number of amino residues of aminoglycosides (neomycin (6) greater than dibekacin (5) greater than ribostamycin (4) = kanamycin (4], while the electrical distance (z delta = 0.46-0.49) of the binding site kept almost constant for each drug. These z delta s were almost the same with those (0.46-0.51) of alkyl-diamine blockers with two amino residues (total net charge of +2) and approximately twice of those (0.25-0.26) of alkylmonoamine blockers (total net charge of +1). Assuming that amino residues of aminoglycosides and alkylamines shared the same binding site located at 25% voltage drop from the cytoplasmic surface of the channel, the site would have to be at least large enough to accommodate one diamino sugar residue of the aminoglycoside in order to simultaneously interact with two positively charged amino groups. Dose- and voltage-dependent blockade of the channel by gallamine, an extremely bulky trivalent organic cation, supported the picture that the channel has a wide mouth on the cytoplasmic side and its 'pore' region, where voltage drop occurs, may also be quite wide and nonselective, suddenly tapering to a constriction where most charged cations block the channel by 'occluding' the K(+)-conducting pathway.

Amines↗

Effects of endothelin on renal hemodynamics and excretory functions in anesthetized dogs.

The effects of endothelin on renal hemodynamics and excretory functions were investigated in anesthetized dogs. Infusion of endothelin at a rate of 1 ng/kg.min resulted in a slight but significant decrease in renal blood flow and an increase in renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg.min significantly decreased cardiac output, glomerular filtration rate, urine volume, and urinary sodium and potassium excretion, whereas it increased systemic vascular resistance. Mean arterial pressure and heart rate showed a transient decrease and increase, respectively, at doses higher than 50 ng/kg.min. Plasma renin activity and plasma aldosterone concentrations were increased only at the dose of 100 ng/kg.min. These effects lasted for more than 60 min. These results suggest that endothelin may have an important role in the modulation of renal functions as well as in the modulation of systemic hemodynamics.

Aldosterone↗

Renal and hemodynamic effects of endothelin in anesthetized dogs.

The effects of endothelin on systemic hemodynamics and renal functions were investigated in anesthetized dogs. Infusion of endothelin at a dose of 1 ng/kg/min decreased renal blood flow and increased renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg/min significantly decreased cardiac output, glomerular filtration rate, renal plasma flow, urine volume, and urinary sodium excretion. Mean arterial pressure showed a transient decrease at doses higher than 50 ng/kg/min. These results showed that endothelin in systemic administration has effects on renal functions as well as on systemic hemodynamics.

Anesthesia↗

Increased levels of beta-human atrial natriuretic peptide-like immunoreactivity in chronically overloaded atrial tissue.

The levels and molecular form of atrial natriuretic peptide-like immunoreactivity (ANP-LI) in human atrial tissue were investigated. The levels of right atrial ANP-LI were significantly higher in mitral disease than in other cardiac or noncardiac diseases. The increased ANP-LI was mainly accounted for by an increase in beta-human ANP-LI (beta-hANP-LI). Both total ANP-LI and beta-hANP-LI levels were associated with the presence of atrial fibrillation and with increased atrial pressure. Plasma beta-hANP-LI levels were also increased in mitral disease. These results suggest that human atrium with hemodynamic overloads is characterized by increased tissue levels of ANP and by a shift to the beta-hANP form.

Adult↗

[Carcinoma of the renal pelvis and ureter. An investigation of 384 registered cases in the Tokai Urological Cancer Registry].

Registration of renal pelvic and ureteral tumor was done from 1980 through 1986, in the Tokai Urological Tumor Registry. Among the 404 cases of the carcinoma, 384 cases (210 renal pelvis, 174 ureter) were subjected to the present study. A total of 319 cases (83.1%) showed a complete cure, while 20 cases (5.2%) were considered as partial cure, and 45 cases (11.7%) were classified to progressive disease group. Chemotherapy was performed on 151 patients including systemic administration to 141 patients (33.9%) and 11 patients received combined intravesical instillation therapy. Irradiation was performed on 49 patients (12.8%). Degree of histological and morphological differentiation of renal pelvis and ureter tumor were studied in 341 cases of transitional cell carcinoma (88.8%); G0, 0.3%, G1, 12.9%, G2, 49.3%, Gx, 5.2%. Stage of the tumor were T1, 33.6%; T2, 12.5%; T3, 14.6%; T4, 13.3%; Tis, 0.3%; Tx, 24.7%. Five-year relative survival for carcinoma of the renal pelvis was 46.6%, and for the ureter it was 53.1%. Five-year survival according to histological differentiation of transitional cell carcinoma and according to the stage of the tumor were as follows; G1, 91.6%; G2, 58.5%; G3, 27.2%; Ta, 84.6%; T1. 74.2%; T2, 48.5%; T3, 24.1%, T4, 7.3%. The rate of survival was correlated with histological differentiation of the tumor cells. The survival was poor in cases who had the components of squamous cell carcinoma and/or adenocarcinoma. Overall survived case were 177, 122 patients died of cancer, 20 patients died of other causes than cancer, and 1 patient died from immediate surgical effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Classification of the intrafusal muscle fibres in the frog muscle spindle: histochemical and immunofluorescent studies.

Intrafusal muscle fibres from bull-frog semitendinosus, iliofibularis and sartorius muscles were classified into three types using the histochemical, immunofluorescent and morphological characteristics, with reference to the extrafusal muscle fibres, which were classified into five types in accordance with Rowlerson & Spurway (1988). Immunofluorescent reactions with antibodies against slow or fast myosins obtained from anterior or posterior latissimus dorsi muscles (ALD or PLD), respectively, of chicken were used as the primary criterion. Histochemical profiles of muscle fibres were classified into nine types of myosin ATPase activity as the secondary criterion. Anti-PLD intrafusal fibres (polar zone) with ATPase profiles of moderate to high acid and alkaline stabilities correspond to large nuclear bag fibres in the classification of Diwan & Ito (1989), whereas anti-ALD fibres (polar zone) with alkaline-labile ATPase profiles correspond to medium nuclear bag fibres. On the basis of diameter, anti-PLD fibres (polar zone) with ATPase profiles of moderate to low acid stability and moderate to high alkaline stability seem to correspond to two types of small nuclear chain fibre. Variations between muscles, between intra- and extrafusal fibres and also between zones along intrafusal fibres are discussed.

Adenosine Triphosphatases↗

Immunohistochemical study on human atrial natriuretic polypeptide in the ventricle of hearts with endocardial fibroelastosis.

The presence and distribution of human atrial natriuretic polypeptide (ANP) were investigated immunohistochemically in the ventricles of hearts of 14 cases with endocardial fibroelastosis and 15 cases with noncardiac disease in children. Paraffin sections of autopsied hearts with endocardial fibroelastosis were stained with polyclonal antibodies against human alpha-ANP. Immunoreactive myocytes were clearly demonstrated in the ventricles of 10 hearts with endocardial fibroelastosis. The distribution of ANP-positive cells was most frequent in the inner one-third of the left ventricle. No ANP immunoreactivity was detected in any heart in cases with noncardiac disease. The left ventricular volume index of hearts with ANP-positive cells was larger than that with ANP-negative cells. The mean diameter of ANP-positive myocytes was greater than that of ANP-negative myocytes. These results suggest that ANP expression in ventricular myocytes is related to severe dilatation of the ventricular cavity and to development of myocardial hypertrophy in endocardial fibroelastosis.

Atrial Natriuretic Factor↗

Intracellular formation and release of angiotensins from juxtaglomerular cells.

Evidence accumulates that intrarenal angiotensin II (Ang II) plays important roles in the regulation of renal functions. To determine the mechanism and site of the intrarenal formation of Ang II, we employed histochemical, cell biological and ex vivo perfusion methods. Immunohistochemical studies have revealed the co-existence of renin and Ang II in juxtaglomerular (JG) cells, and electron microscopic studies and subcellular organelle fractionation have demonstrated the localization of renin and angiotensin in renin granules. Cloned and cultured renin-containing cells derived from rat kidney were also found to contain renin, ACE, and Ang I and Ang II. The subcellular fractionation of renin granules from rat kidney homogenate demonstrated the presence of Ang I and Ang II in the renin granule fractions. The findings suggest the formation of both angiotensins in JG cells. To study the release of Ang I and Ang II, we determined the release of these peptides from isolated rat kidney perfused with Krebs-Ringer buffer at a constant pressure. Release of both peptides was stable for as long as two hours in the absence of angiotensinogen in the perfusion medium. There was a positive correlation between renin secretion rate and Ang I secretion rate, and also between Ang I secretion rate and Ang II secretion rate. Since the perfusate does not contain angiotensinogen, these results lead to the hypothesis that Ang II is formed in JG cells in the kidney and is directly secreted with renin into plasma or the interstitial fluid, and that Ang II formed in the kidney cells may participate in various renal functions along with Ang II produced in the plasma.

Angiotensin I↗

Effects of endothelin on renal regional blood flow in dogs.

The effects of intrarenal infusion of endothelin on renal blood flow were investigated in anesthetized dogs. Endothelin produced a biphasic change in the renal blood flow (RBF): an initial, transient increase followed by a marked, long-lasting decrease. The changes in the RBF were parallel to those in the renal cortical blood flow, whereas the changes in the medullary blood flow were less prominent. These results suggest that endothelin affects RBF, preferentially in the renal cortex.

Anesthesia↗

Radioimmunoassay for endothelin and immunoreactive endothelin in culture medium of bovine endothelial cells.

Using a synthetic 21-residue endothelin as antigen, we have produced an antiserum for endothelin and developed a specific and sensitive radioimmunoassay (RIA) for endothelin. The minimum detection limit of the RIA was 1 pg/tube. Immunoreactive (ir-) endothelin was extracted from the culture medium by Bondelute C8 column. The ir-endothelin in the culture medium of endothelial cells (EC) from bovine pulmonary artery and carotid artery was 1.48 ng/ml and 3.31 ng/ml, respectively. Reverse-phase high performance liquid chromatography coupled with the RIA revealed that ir-endothelin in the culture medium comprised one major component corresponding to synthetic endothelin. In addition, the cultured EC of bovine pulmonary artery were specifically stained by immunohistochemical technique. These results suggest that endothelin could be produced in the EC of the pulmonary and carotid arteries besides the aorta. The RIA presented in this study could be an useful tool to investigate the pathophysiologic significance of endothelin.

Animals↗

Discovery of atrial natriuretic factor in the brain: its characterization and cardiovascular implication.

1. We have devised a radioimmunoassay for atrial natriueretic factor (ANF). Its application to rat brain extract led to the discovery of ANF in the brain. In addition to the hypothalamus and the pontine medullary region, it was widely distributed. 2. ANF in the brain is stored in a low molecular weight form, in contrast to pro-ANF in the atria. Thus, the processing of pro-ANF in the bran neuronal cells is different from that in the atria. 3. ANF was found in the anterior and posterior lobes of the pituitary, the peripheral ganglia, adrenergic neurons, and the adrenal medulla. 4. Brain ANF suppressed stimulated dipsogenesis, basal and stimulated vasopressin release, and angiotensin II-stimulated pressor effects. 5. ANF in the peripheral neuronal system inhibits catecholamine synthesis and release. Thus, central ANF functions to reduce the peripheral fluid volume and vascular tone in concert with the peripheral ANF.

Animals↗