Biomedical subjects

K Naruse

Publications and source records attributed to K Naruse.

At least 199 records · Page 11Linked to original sources

PubMed1993

Plateau pattern of afferent discharge rate from frog muscle spindles.

1. A characteristic plateau pattern was observed in the rate of afferent discharges during ramp-and-hold stretch of spindles isolated from semitendinosus muscles of frogs. The plateau pattern was more frequent in summer frogs (84%) than winter frogs (11%). 2. The plateau pattern consisted of a discharge rate around 120 imp/s at the end of dynamic stretch, followed by second and third steps of plateau rates around 60 and 40 imp/s, respectively. The intervals of impulses in lower steps were approximately n times those of the top step. 3. The plateau pattern was not sensitive to cutting extracapsular myelinated branches or lowering temperature from 23 to 12 degrees C. However, the number of the plateau was reduced in both cases. 4. Application of depolarizing current to the sensory terminal abolished the plateau pattern. In contrast, in spindles that did not show a plateau pattern, hyperpolarizing current induced such a pattern. 5. Calcium channel blockers and protein kinase C inhibitors abolished the plateau pattern. The plateau pattern could be established in quiescent spindles by drugs eliciting Ca2+ entry, raising cytosolic-free Ca2+, and activating protein kinase C. 6. The most striking aspect of the present study is the stability in the discharge rate at each step of the plateau, irrespective of different experimental conditions. This suggests that the spindle sensory terminal possesses a stable intrinsic rhythm generator in excitation, of which maximum frequency is 120 imp/s. The generator seems to be triggered by stretch stimulus and to be regulated by cytoplasmic Ca2+ and protein kinase C.

Afferent Pathways↗

PubMed1993

Molecular forms of atrial natriuretic factor in normal and failing human myocardium.

BACKGROUND: Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart. METHODS AND RESULTS: We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF. CONCLUSIONS: These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.

Adolescent↗

PubMed1993

Colocalization of immunoreactive endothelin-1 and neurohypophysial hormones in the axons of the neural lobe of the rat pituitary.

The intracellular localization of immunoreactive endothelin (ET)-1, and its colocalization with vasopressin (VP) and oxytocin (OT) in the rat neural lobe were investigated by immunogold techniques using specific antisera raised against ET-1, VP, and OT. There were two types of axons: the first contained VP-immunolabeled neurosecretory granules, and the second contained OT-immunolabeled neurosecretory granules. A considerable number of the neurosecretory granules in both types of axon were immunolabeled with antibodies against ET-1, although the VP-immunolabeled granules were more heavily labeled with anti-ET-1 antiserum than OT-immunolabeled ones. Double immunogold labeling clearly demonstrated the intragranular colocalization of immunoreactions for ET-1 and VP and that of immunoreactions for ET-1 and OT. These results suggest that ET in the neural lobe may be released concomitantly with neurohypophysial hormones. Its biological significance remains to be elucidated.

Animals↗

PubMed1993

Mechanics of patch clamped and intact cell-membranes in relation to SA channel activation.

Stretch activated (SA) channels are believed to be activated by tension in the membrane generated by membrane stretch. However, very few studies have been made on the quantitative estimation of the tension during membrane stretch. Here we present a method to evaluate the tension both in patch clamped and intact cell-membranes. The tension in patch clamped membranes was calculated from Laplace's law by knowing transmembrane pressure and the radius of patch-curvature. We also provide a simpler version for calculating the tension from the pressure and pipette radius. The tension in intact cell membranes was calculated from Hook's law based on the measurement of changes in cell surface area. The estimated tension required for activating SA channels in both types of membranes was found to be comparable suggesting that the SA channel acts as a physiological mechanotransducer in intact cells.

Animals↗

PubMed1993

[Involvement of stretch activated (SA) ion channels in cardiovascular responses to mechanical stimuli].

Cardiovascular system exhibits various responses to mechanical stimulations. Overload in heart induces arrhythmias or hypertrophy. Increases in blood flow or blood pressure elicit vessel dilation via an activation of endothelial cells. Although the molecular mechanism of these responses are unclear, the evidence has been accumulated that the stretch activated (SA) ion channel acts as a primary sensor for mechanical stimuli. In this article, cardiovascular responses to mechanical stimuli have been summarized and the possible role of SA channels is discussed.

Animals↗

PubMed1993

High plasma concentrations of endothelin-like immunoreactivities in patients with hepatocellular carcinoma.

The plasma levels of endothelin-like immunoreactivities (ET-IR) of patients with hepatocellular carcinoma (HCC) were compared with those of patients with liver cirrhosis (LC), using a specific radioimmunoassay for endothelin-1. The mean concentration of plasma ET-IR of 21 HCC patients (30.3 +/- 8.5 pg/ml, n = 21) (means +/- SD) was markedly higher than those in LC (22.1 +/- 4.7 pg/ml, n = 16) (p < 0.01), which were also elevated compared with those in normal subjects (9.4 +/- 1.6 pg/ml, n = 91). Moreover, the level of plasma ET-IR reflected the tumor size of HCC patients, which was estimated by the ultrasonic and computed tomographic examinations. Although there was no relation to other biochemical parameters indicating liver function or tumor markers such as alpha-fetoprotein, a good positive correlation was obtained between plasma ET-IR and C-reactive protein (CRP) concentrations of HCC patients (r = 0.805, p < 0.01). We measured the tissue contents of ET-IR in HCC and its adjacent LC tissue, but failed to find any significant difference between the mean content of HCC (0.50 +/- 0.38 ng/g) and LC (0.44 +/- 0.28 ng/g). The endothelial cell damage due to cancer growth may not be responsible for the high concentrations of plasma ET-IR of HCC, because plasma thrombomodulin concentrations were not correlated with plasma ET-IR levels in HCC patients. Our study implies that the high plasma concentration of ET-IR is pathogenomonic to HCC, although the site of production is still debatable.

Aged↗

PubMed1992

Histological study on ouabain immunoreactivities in the mammalian hypothalamus.

The endogenous digitalis-like factor (EDLF) which has recently been purified from human plasma and identified as 'ouabain', a cis-trans-cis steroid of plant origin, is thought to be similar to the hypothetical humoral factor, 'endogenous digitalis-like substance (EDLS)'. In order to examine the hypothesis that EDLS is produced in the hypothalamus, we prepared an ouabain-specific antibody, and applied it to rat and macaque brains. Ouabain immunoreactivities were observed in the hypothalamus of both species. The immunopositive neurons were distributed in paraventricular and supraoptic nuclei, and some other hypothalamic regions. Their nerve fibers were seen abundantly in the hypothalamo-neurohypophysial regions. These results strongly support the possibility of existence of cis-trans-cis steroid including EDLF in mammalian brain.

Animals↗

PubMed1992

A highly repetitive interspersed sequence isolated from genomic DNA of the Medaka, Oryzias latipes, is conserved in three other related species within the genus Oryzias.

A highly repeated interspersed sequence (OLR1) was isolated from a genomic DNA library of the Medaka, Oryzias latipes. The OLR1 was about 160 base pairs (bp) in length. As judged from the results of colony hybridization experiments, OLR1 is one of the major repeated DNA sequences in the Medaka genome and is present in every 136 kb on average. Results of Southern and colony-hybridization analyses indicate that OLR1 is a small interspersed repetitive element (SINE). OLR1-related sequences were conserved in other three species (O. luzonensis, O. curvinotus, and O. mekongnensis) within the genus Oryzias as a repetitive sequence. These results lend support at the DNA level to the hypothesis that these four species form one group in the genus Oryzias, as has been suggested from an analysis of their karyotypes (Magtoon and Uwa, '85, Proc. Jpn. Acad., Ser. B, 61:157-160).

Animals↗

PubMed1992

Differential responses of Ca-activated K channels to bradykinin in sensory neurons and F-11 cells.

The nonapeptide bradykinin (BK) excites a subset of dorsal root ganglion (DRG) neurons with putative nociceptive functions by stimulating an inward cation current. In addition, BK stimulates various intracellular signaling pathways including an elevation of intracellular Ca2+. In a DRG neuron x neuroblastoma hybrid cell (F-11), BK stimulates similar increases in intracellular [Ca2+] and inward current but also elicits a large transient outward current through Ca(2+)-activated K channels. We have investigated the mechanisms underlying differential expression of outward current responses in the two cell types at the single channel level. Although K(Ca) channel activity appears in inside-out patches from both cells exposed to Ca2+, BK applied to the extrapatch membrane of cell-attached patches activates K(Ca) channels in F-11 but not DRG neurons. Whereas single K(Ca) channels are quantitatively similar in terms of conductance, voltage-dependence, and sensitivity to tetraethylammonium, they differ in sensitivity to intracellular Ca2+. Channel activation in both cells requires at least four Ca2+ ions, but half-maximal activation occurs at slightly higher [Ca2+] for DRG neurons. The shift in the Ca2+ dose-response curve combined with the steep [Ca2+] dependence of channel open probability makes it less likely that a BK-induced rise in internal [Ca2+] induced will trigger a transient outward current and resultant hyperpolarization in a DRG neuron.

Animals↗

PubMed1992

Endothelin stimulates aldosterone secretion in vitro from normal adrenocortical tissue, but not adenoma tissue, in primary aldosteronism.

In addition to vasoconstriction, endothelin (ET) has been reported to show various endocrine actions in animals. However, no data have emerged concerning the effect of ET on adrenal function in humans. We, therefore, investigated the effects of ET on aldosterone and cortisol secretion from adrenocortical tissues obtained from normal subjects (n = 6) and patients with primary aldosteronism (n = 5). Adrenal tissue slices were incubated at 37 C for 120 min in modified Krebs-Ringer solution containing glucose and HEPES. ET increased aldosterone secretion from normal adrenocortical tissue in a dose-dependent manner, with an ED50 of 0.036 nmol/L, although the maximum response was small compared with that to angiotensin-II. ET also stimulated aldosterone secretion from tissues adjacent to the adenoma, but not from the adenoma, in patients with primary aldosteronism. The effects of ET on aldosterone secretion were significantly suppressed by calcium channel blockade with nicardipine. ET did not affect cortisol secretion from the adrenal tissues. These results suggest that ET is one of the factors that regulates aldosterone secretion in humans.

Adenoma↗

PubMed1992

Endothelin-3 immunoreactivity in gonadotrophs of the human anterior pituitary.

Endothelin (ET), originally discovered in vascular endothelial cells, has also been demonstrated in nonvascular tissues. The present study was undertaken to elucidate the presence of ET in the human pituitary. The avidin-biotin complex method with antiserum to ET-1 (and ET-2) or ET-3 was used to identify ET in human pituitaries obtained by autopsy. ET-3 immunoreactivity was found in the cytoplasm of large ovoid cells of the anterior pituitary. Using the double staining method, the cells containing ET-3 immunoreactivity were differentiated from cells containing ACTH, TSH beta, GH, PRL, and protein S-100. By staining with anti-LH beta antiserum in adjacent sections and using the double staining method, the cells were identified as gonadotrophs. No staining was observed in the posterior pituitary. In addition, no ET-1 (and ET-2) immunoreactivity was detected. The specific localization of ET-3 immunoreactivity in the gonadotrophs of the human pituitary suggests a possible role of ET-3 in the regulation of anterior pituitary function.

Adolescent↗

PubMed1992

A patient with a prolactinoma associated with an aldosterone producing adrenal adenoma: differences in dopaminergic regulation of PRL and aldosterone secretion.

A patient with a rare combination of prolactinoma and aldosterone producing adrenal adenoma (APA) was reported in relation to studies concerning dopaminergic regulation of PRL and aldosterone secretion. The patient is a 38-year-old female with plasma PRL and aldosterone concentrations (PAC) of 563 ng/ml and 54 ng/dl, respectively. A bolus of 10 mg of metoclopramide significantly increased plasma PRL in 6 normal subjects and in 4 patients with APA, whereas the responses were blunted in 7 patients with prolactinoma and in our patient. The response of aldosterone to metoclopramide was less than that of PRL, but similar in all studied subjects, indicating that the dopaminergic inhibition of aldosterone secretion is less than that of PRL in normal subjects and did not change in patients with APA or prolactinoma. Oral administration of 2.5 mg of bromocriptine suppressed plasma PRL significantly in all the subjects studied, but did not produce any consistent changes in PAC. Discrepancies in the response of PRL and aldosterone to metoclopramide and to bromocriptine suggest a difference in the dopaminergic regulation of PRL and aldosterone secretion in both normal subjects and patients with prolactinoma and APA. It is unlikely that reduced dopaminergic inhibition is the basis for hypersecretion of PRL and aldosterone in our patient.

Adenoma↗

PubMed1992

Increased plasma endothelin in NIDDM patients with retinopathy.

OBJECTIVE: To elucidate the significance of ET in diabetic microvascular disease. RESEARCH DESIGN AND METHODS: We determined plasma levels of ir-ET-1 in 25 NIDDM patients without hypertension and/or renal dysfunction. RESULTS: The plasma levels of ir-ET-1 in NIDDM patients with simple (n = 8) and proliferative (n = 8) retinopathy were 0.58 +/- 0.04 pM and 0.60 +/- 0.04 pM, respectively, which were significantly higher than those in normal, nondiabetic subjects (0.24 +/- 0.02 pM [n = 31]) and NIDDM patients without retinopathy (0.30 +/- 0.05 pM [n = 9]). CONCLUSIONS: These results suggest that plasma ET-1 is related to diabetic microvascular disease.

Biomarkers↗

PubMed1992

Endothelin-specific antibodies decrease blood pressure and increase glomerular filtration rate and renal plasma flow in spontaneously hypertensive rats.

OBJECTIVE: Studies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGN: The technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the contribution of endothelin to the in vivo control of blood pressure and renal hemodynamics. METHODS: Endothelin-specific antibodies were administered intravenously into anesthetized SHR and Wistar-Kyoto (WKY) rats, and the effects upon blood pressure and renal function (renal plasma flow and glomerular filtration rate) assessed. Using the same antibodies, baseline plasma levels of endothelin in both strains of rats were determined by radioimmunoassay. RESULTS: Infusion of endothelin-specific antibodies into SHR decreased mean arterial pressure by approximately 10% and renal vascular resistance and renal vascular resistance by approximately 35%. Glomerular filtration rate and renal plasma flow both increased by approximately 50% over control. In contrast, infusion of normal rabbit serum into SHR or of endothelin-specific antibodies into WKY rats did not result in any significant change in renal hemodynamics or arterial blood pressure. Baseline plasma levels of immunoreactive endothelin in SHR were significantly lower than those in WKY rats. CONCLUSION: These results suggest that endothelin plays an important role in the modulation of systemic blood pressure and renal function in SHR.

Animals↗

PubMed1992

[A randomized study of pirarubicin (THP) versus adriamycin (ADM) for intravesical instillation therapy against superficial bladder cancer].

To determine the antitumor action by intravesical instillation prior to transurethral resection TUR, a randomized study on pirarubicin (THP) versus adriamycin (ADM) was performed for superficial, papillary and initially detected bladder cancers with participation of 21 Urological Clinics in 3 Tokai Prefectures. The instillation dose of 500 micrograms/ml was given 3 times per week for 3 weeks in both THP (n = 33) and ADM (n = 30) groups. The complete and partial response rates were 56.3% in THP group and 26.7% in ADM group. THP instillation was more effective against multiple tumors than a single tumor, stage Ta than T1 and grade G1 than G2 and G3. However, these findings were not statistically significant. Untoward effects were mainly bladder irritability and its frequency was 60.6% in the THP group and 23.3% in the ADM group. Contracted bladder was found in 2 of the 33 patients in the THP group and 2 of the 30 patients in the ADM group. The antitumor effect of a half dose of THP was equivalent to that of one dose of ADM, and the THP group showed a twofold higher frequency of side effects. Therefore, a clinical trial should be made comparing the effect of 500 micrograms/ml of THP and that of 1,000 micrograms/ml of ADM.

Administration, Intravesical↗

PubMed1991

Atrial natriuretic peptide and brain natriuretic peptide coexist in the secretory granules of human cardiac myocytes.

To elucidate the intracellular localization of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human cardiac myocytes, an immunocytochemical study was carried out by a double immunogold technique using antisera highly specific for ANP and BNP. Surgical and autoptic tissue specimens of human heart were studied. In the atrial myocytes, ANP was localized in almost all of the secretory granules, whereas BNP was colocalized with ANP in some of the granules. Although very few secretory granules were observed in ventricular myocytes, colocalization of ANP and BNP was basically the same as in atrial myocytes. No immunoreactive products were found in the control studies. These results suggest that secretion of BNP is under a regulatory mechanism similar to that of ANP.

Atrial Natriuretic Factor↗

PubMed1991

Immunoreactive endothelin in plasma of nonmammalian vertebrates.

Immunoreactive endothelin (ir-ET) was estimated in plasma of nonmammalian vertebrates, using radioimmunoassay (RIA) for endothelin-1 (ET-1). Blood samples were collected from unanesthetized animals. Plasma ET was determined by RIA after extraction. Plasma levels of ir-ET were 0.7 +/- 0.2 pg/ml (n = 6) in the hagfish Eptatretus burgeri, 4.3 +/- 0.9 pg/ml (n = 5) in the banded dogfish Triakis scyllia, 3.6 +/- 0.8 pg/ml (n = 3) in the common Japanese conger Conger myriaster, 9.6 +/- 1.4 pg/ml (n = 7) in the carp Cyprinus carpio, 6.4 +/- 0.8 pg/ml (n = 5) in the bullfrog Rana catesbeiana, 6.7 +/- 0.6 pg/ml (n = 3) in the soft-shelled turtle Trionyx sinensis japonica, and 3.3 +/- 0.6 pg/ml (n = 8) in the Japanese quail Coturnix coturnix japonica. The dilution curves of the plasma extracts from each species almost paralleled the standard curve for ET-1. Analysis of the plasma extracts of the carp by reverse-phase high-performance liquid chromatography revealed that ir-ET consisted of three components, a predominant peak being located at the elution position of synthetic ET-1. The present results demonstrate clearly that an ET-1-like substance circulates in blood of nonmammalian vertebrates, suggesting an endocrine function of the peptide in these species.

Animals↗

PubMed1991

Plasma immunoreactive endothelin, but not thrombomodulin, is increased in patients with essential hypertension and ischemic heart disease.

To ascertain an involvement of vascular endothelial cells in cardiovascular disease, we have determined plasma levels of two endothelium-derived substances, endothelin (ET) and thrombomodulin (TM), in essential hypertension (EH) and ischemic heart disease. Plasma ET was determined by radioimmunoassay (RIA) after extraction. Plasma TM levels were determined by enzymunoimmunoassay. Plasma ET levels were significantly elevated in patients with EH involving target organ damage, vasospastic angina pectoris (VSA), and acute myocardial infarction (AMI), especially in those associated with cardiogenic shock. There was a weak but significant correlation between plasma ET levels and serum creatinine concentration in patients with EH. Plasma ET levels were elevated even before the coronary spasm in patients with VSA, whereas they did not show any further increase during the spasm. In contrast, plasma TM levels in patients with EH and VSA did not show a significant difference from that in normal subjects. These results suggest that ET plays an important role in the pathophysiology of EH and ischemic heart disease, and also that increases in plasma ET cannot be simply attributed to a leakage of the peptide from the injured endothelial cells.

Angina Pectoris↗