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Biomedical subjects

N Kurihara

Publications and source records attributed to N Kurihara.

At least 163 records · Page 9Linked to original sources
PubMed1990

IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release.

IL-6 enhances the differentiation of pluripotent hematopoietic stem cells but predominantly affects the differentiation of hematopoietic cells in the granulocyte-macrophage lineage. We have previously shown that multinucleated cells (MNC) with many features of the osteoclast phenotype form in long term human marrow cultures. Addition of rhIL-6 (10 to 100 pg/ml) to these cultures significantly increased MNC formation, with greater than 80% of the MNC expressing an Ag that cross-reacts with the mAb 23c6. This antibody preferentially binds to osteoclasts. rhIL-6 did not enhance MNC formation in marrow cultures treated with 1,25 dihydroxyvitamin D3, a potent stimulator of MNC formation, but significantly increased the percentage of MNC that cross-reacted with the 23c6 mAb. Addition of antihuman IL-1 to cultures treated with rhIL-6 totally inhibited the increase in MNC formation stimulated by rhIL-6. In contrast, anti-IL-1 did not affect MNC formation stimulated by 1,25 dihydroxyvitamin D3. Further, conditioned media from marrow cultures exposed to rhIL-6 contained elevated levels of IL-1 beta (500 pg/ml compared to 23 pg/ml in control cultures 15 h after IL-6 addition). These results suggest that the capacity of rhIL-6 to stimulate formation of MNC which cross-react with 23c6 is mediated by induction of release of IL-1 beta.

Antibodies, Monoclonal↗
PubMed1990

Prostaglandin E2 inhibits formation of osteoclastlike cells in long-term human marrow cultures but is not a mediator of the inhibitory effects of transforming growth factor beta.

Prostaglandins are important local regulators of bone cell function and have been shown to have multiple effects on osteoclasts. Using a human bone marrow culture system in which multinucleated cells with osteoclast characteristics form, we have recently shown that TGF-beta is a potent inhibitor of osteoclastlike cell formation and appears to act at several stages of their development. Because it has been suggested that the effects of TGF-beta are mediated via a prostaglandin-dependent mechanism, we determined the effects of prostaglandin E2 (PGE2) on total and osteoclastlike cell formation (detected by reactivity with the 23c6 monoclonal antibody, which identifies osteoclasts) in human marrow cultures and tested whether prostaglandin synthesis was responsible for the inhibitory effects of TGF-beta on multinucleated cell formation. These studies show that PGE2 is a potent inhibitor of both 23c6-positive and negative multinucleate cell formation in human marrow cultures and that the effects of TGF-beta on multinucleated cell formation are not mediated by PGE2.

Bone Marrow Cells↗
PubMed1990

Endothelin stimulates release of atrial natriuretic factor in anesthetized rats.

The present study was designed to examine the effect of synthetic rat endothelin, a novel potent vasoconstrictor isolated from endothelial cells, on the release of immunoreactive atrial natriuretic factor (ir-ANF) in anesthetized rats. Systemic blood pressure and plasma ir-ANF concentration were measured at 1, 3, 5, 15, 30, and 60 minutes after rat endothelin administration (0.01, 0.10, 1.00 nmol/kg body weight [BW]). Administration of rat endothelin caused a long-lasting increase in mean blood pressure and produced a dose-dependent increase in plasma ir-ANF that peaked 5 minutes after the injection and remained higher than the basal value 60 minutes after the injection. These data suggest that administration of pharmacological doses of rat endothelin produces a profound release of ir-ANF into the circulation, which may cause vasodilation and diuresis to antagonize the effect of endothelin.

Animals↗
PubMed1990

Interferons-alpha and -gamma inhibit interleukin-1 beta-stimulated osteoclast-like cell formation in long-term human marrow cultures.

Immune cell products can have major effects on bone remodeling. Cytokines, such as interleukin-1 (IL-1), are potent stimulators of bone resorption, whereas interferon-gamma (IFN-gamma) inhibits bone resorption stimulated by these factors. Bone resorption is a result of either increased numbers of osteoclasts, increased activity of individual osteoclasts, or both. Recently, we have shown that human recombinant IFN-gamma is a potent inhibitor of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced formation of multinucleated cells (MNC) that express the osteoclast phenotype. However, it is unknown if other IFNs share this capacity to inhibit MNC formation. Therefore, we tested the effects of natural IFNs-alpha and -gamma and Escherichia coli-derived recombinant human IFN-gamma on MNC formation and on granulocyte-macrophage (CFU-GM) colony formation (an early osteoclast precursor) in human marrow cultures treated with IL-1 beta or CSF-GM, respectively, to determine their effects on human osteoclast formation. Each type of IFN inhibited CFU-GM colony formation similarly in a dose-dependent fashion, with 50% inhibition seen at 64-250 U/ml. Natural or recombinant IFN-gamma inhibited IL-1 beta-stimulated MNC formation in a dose-dependent manner with an ID50 of 1-16 U/ml. IFN-alpha was more potent than IFN-gamma, with an ID50 of less than 1 U/ml. Furthermore, both IFN-alpha and -gamma inhibited fusion of precursors of these multinucleated cells. These data demonstrate that IFNs-alpha and -gamma inhibit MNC formation by inhibiting the growth of precursors for these cells as well as their subsequent fusion.

Bone Marrow↗
PubMed1990

Effect on atrial natriuretic peptides of chronic treatment with alpha-methyldopa and hydralazine in spontaneously hypertensive rats.

The present study was designed to examine the effect of antihypertensive therapy on plasma and atrial concentration of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR) by using alpha-methyldopa and hydralazine. Methyldopa and hydralazine treatment reduced blood pressure (P less than .05, P less than .05, respectively); however, ventricular weight was reduced by methyldopa (P less than .05) but not by hydralazine. Plasma ANP concentration in untreated SHR was higher than that observed in Wistar-Kyoto rats (WKY). Methyldopa treatment decreased plasma ANP concentration, but hydralazine treatment did not. Moreover, plasma ANP concentration and ventricular weight were positively correlated in untreated and treated SHR. The left atrial ANP concentration in untreated SHR was lower than that observed in WKY. Methyldopa treatment increased left atrial ANP concentration, but hydralazine treatment did not. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that a decrease in plasma ANP concentration by methyldopa treatment is, in part, associated with the decline of ANP release from the heart due to the reductions of blood pressure and cardiac hypertrophy.

Animals↗
PubMed1990

Endothelin does not affect intracellular calcium ion concentration in the platelets of rats.

We recently demonstrated that porcine endothelin increases intracellular calcium ion concentration ([Ca2+]i) in monolayers of cultured vascular smooth muscle cells isolated from rat renal arteries. The present study was designed to examine the effect of porcine endothelin on [Ca2+]i in the platelets of rats. [Ca2+]i was serially measured with the fluorescent dye, fura 2, and the photoprotein, aequorin. Endothelin (10(-9) mol/L, 10(-8) mol/L, and 10(-7) mol/L) did not induce any change in [Ca2+]i in the platelets of rats while thrombin (2 U/mL) dramatically increased [Ca2+]i as measured by these methods. Our results indicate that [Ca2+]i in rat platelets is not influenced by porcine endothelin.

Aequorin↗
PubMed1990

[A case of septicemia due to Capnocytophaga ochracea beginning post radiation therapy for lung cancer].

A 46-year-old man was admitted to our hospital on Mar. 16, 1988 with the chief complaint of productive cough. The chest roentgenogram and tomogram showed a tumorous shadow in the right upper lobe, accompanied with stenosis of the trachea and the right main bronchus. Bronchofiberscopic examination confirmed a nodular tumor protruding into the lower part of the trachea from the right lateral wall and nearly complete obstruction of the right main bronchus. Pathological specimen obtained by transbronchial biopsy revealed "low differentiated adenocarcinoma". It was highly suspected that the primary lung cancer had directly invaded the trachea and the right main bronchus. His symptoms and roentgenological findings remarkably improved after radiation therapy. He was discharged on May 12. On Sep. 14, he was admitted to our hospital again because of hoarseness, general fatigue and increasing dyspnea. The chest CT demonstrated severe stenosis of the trachea, which was treated with another radiation therapy. Although his symptoms diminished, he had a sudden onset of high fever on Oct. 15. Immediately a blood culture and transtracheal aspiration (TTA) were performed. Gram-negative bacilli were isolated from the blood culture four days later. The administration of fosfomycin and tobramycin was started. However he died because of massive hemoptysis on Oct. 23. Several days after the death, an isolated strain was identified as Capnocytophaga ochracea by the biochemical characteristics. Culture of sputum obtained by TTA was negative for Capnocytophaga ochracea. Septicemia due to Capnocytophaga spp. is very rare and only one case (due to Capnocytophaga sputigena) has been reported until now in Japan. Our patient is thought to be the first case of septicemia due to Capnocytophaga ochracea in Japan.

Adenocarcinoma↗
PubMed1990

Identification of committed mononuclear precursors for osteoclast-like cells formed in long term human marrow cultures.

Nonadherent marrow mononuclear cells enriched for hematopoietic progenitor cells were cultured in semisolid medium with recombinant human granulocyte-macrophage colony-stimulating factor for 9 days to form colony forming unit-granulocyte macrophage (CFU-GM) colonies. 1,25-Dihydroxyvitamin D was then gently layered over the cultures. After 2 weeks, approximately 30% of the colonies that formed were composed of cells with a unique polygonal morphology. One hundred percent of the polygonal cells in these colonies crossreacted with the monoclonal antibody 23c6, which preferentially recognizes osteoclasts. Homogenous populations of these polygonal cells formed multinucleated cells (MNC) in suspension culture, 100% of which cross-reacted with the 23c6 monoclonal antibody, and greater than 90% of the MNC contracted in response to calcitonin. Approximately 20% of these MNC formed resorption lacunae on calcified matrices. These results suggest that 1) early osteoclast precursors are derived from CFU-GM, the committed granulocyte-macrophage progenitor; 2) committed mononuclear osteoclast precursors have a distinct polygonal morphology and cross-react with monoclonal antibodies that recognize mature osteoclasts; and 3) these mononuclear precursors are capable of forming multinucleated cells which fulfill the functional criteria for osteoclasts.

Antibodies, Monoclonal↗
PubMed1990

Sequential expression of phenotype markers for osteoclasts during differentiation of precursors for multinucleated cells formed in long-term human marrow cultures.

Long-term human marrow cultures form multi-nucleated cells (MNC) which express the osteoclast phenotype. Mononuclear precursors for these MNC can be identified and highly enriched. We tested early (bipotent) and late (unipotent) precursors of these MNC for expression of several osteoclast differentiation markers: 1) the osteoclast vitronectin receptor, identified by the 23c6 monoclonal antibody, 2) the vacuolar-type proton pump, identified by the E11 monoclonal antibody, and 3) the calcitonin (CT) receptor, by autoradiography with 125I-labeled salmon calcitonin. We wished to determine if the proton pump was expressed in cells in long term marrow cultures and if its expression correlated with expression of the CT receptor and the vitronectin receptor. About 30% of early precursor cells reacted with the 23c6 monoclonal antibody, but none expressed CT receptors or showed amplified proton pump expression. The CT receptor and amplified proton pump expression were detected first on the late precursor, a stage in which every cell reacted strongly with the 23c6 monoclonal antibody. Over 80% of MNC formed from these late precursors expressed abundant CT receptors, and all MNC expressed the vitronectin receptor and showed amplified proton pump expression. In contrast, macrophage polykaryons and mononuclear macrophages formed in vitro failed to express the osteoclast vitronectin and CT receptors and expressed the proton pump at levels indistinguishable from those of surrounding cells.

Biomarkers↗
PubMed1990

Endothelin-induced renal vasoconstriction and increase in cytosolic calcium in renal vascular smooth muscle cells.

This study was designed to investigate the effects of the potent vasoconstrictor, endothelin, on renal hemodynamics in rats in vivo, and in addition, to measure intracellular calcium ion ([Ca2+]i) in monolayers of renal vascular smooth muscle cells in culture using the fura-2 method. Endothelin (1 nmol) dramatically decreased renal blood flow from 7.0 +/- 0.5 ml/min to 2.6 +/- 1.0 ml/min, whereas it increased mean arterial pressure from 100 +/- 2 mmHg to 113 +/- 7 mmHg. These alterations persisted over 20 minutes in conscious and almost unrestrained rats. Endothelin (10(-8)-10(-7) mol/l) immediately increased [Ca2+]i, although the increase by endothelin (10(-9) mol/l) was relatively slow. The increase persisted in the presence of 1 mmol/l extracellular calcium. In the absence of extracellular calcium, only a small, transient increase of [Ca2+]i was observed. These results indicate that endothelin produces renal vasoconstriction and increases the [Ca2+]i in cultured renal vascular smooth muscle cells. The latter effect is dependent mainly on extracellular calcium.

Animals↗
PubMed1990

[Chemical constituents of some biodegradable liquid scintillators].

Chemical constituents of the commercially available "biodegradable" liquid scintillator solvents were elucidated by means of GC/MS analysis etc., as either the mixture of monosubstituted benzenes with the alkyl chain of carbon 10 to 13, or 1-(3,4-dimethylphenyl)-1-phenyl-ethane.

Biodegradation, Environmental↗
PubMed1990

Abnormal hepatobiliary clearance of 99mTc-N-(2,6-diethylphenylcarbamoylmethyl)iminodiacetic acid in the altered state of thyroid--by an analysis of deconvolution method.

Hepatobiliary clearance of 99mTc-EHIDA was investigated in cases with altered thyroid function by deconvolution method. The results indicated that mean hepatic transit time of all control subjects revealed less than 10 minutes. On the other hand, mean hepatic transit time of cases with altered thyroid function revealed prolonged more than 13 minutes. Cases especially showing an elevated serum concentration of TSH compared with normal range (4.6 microU/ml) had a tendency of a high incidence of markedly prolonged mean hepatic transit time. These results suggest that thyroid hormone may influence on the hepatic metabolism of hepatobiliary radiopharmaceuticals. This phenomenon also could partly explain the cause of liver dysfunction seen in subjects with altered states.

Adult↗
PubMed1990

Exercise performance and limiting factors in patients with chronic lung diseases.

To demonstrate the clinical usefulness of the treadmill exercise test in patients with chronic lung diseases (CLD), 272 consecutive tests done from Jan. 1986 to Dec. 1988 were analyzed. The subjects mainly consisted of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). With the present incremental treadmill protocol the maximal stage attained by a patient or distance walked were closely related to the patient's maximal oxygen uptake. Comparing symptoms and cardio-pulmonary response, and exercise performance between patients with COPD and those with ILD, there was an evident difference in the exercise limiting factor (s): in the former ventilatory limitation was the most important whereas in the latter gas exchange and oxygen transport was critical. Assessment of breathlessness during the exercise test using the Borg scale was useful in evaluating various therapeutic modalities such as oxygen supplementation. In conclusion, the exercise performance in patients with CLD was properly assessed with the present treadmill protocol and the information derived thereby was of great clinical significance.

Exercise Test↗
PubMed1990

[Hepatic mean transit time of 99mTc-EHIDA estimated by deconvolution analysis].

Clinical usefulness of mean transit time (MTT) through the liver was evaluated by deconvolution analysis using 99mTc-EHIDA hepatobiliary scintigraphy in 82 patients with various hepatobiliary diseases and 18 normal controls. Initial transfer factor was also obtained according to the method of Rutland. Results obtained were as follows. 1) Effect of the age on MTT was not observed in normal controls. 2) MTT in left lobe of normal controls was significantly prolonged compared with that of right lobe (P less than 0.01). This kind of difference was not observed in patients with liver cirrhosis. 3) MTT in patients with obstructive jaundice, chronic liver diseases, liver cirrhosis at decompensative state and primary biliary cirrhosis was significantly prolonged compared with that in normal controls (P less than 0.01). 4) MTT in patients with liver cirrhosis at compensative state showed normal values, although blood clearance rate in those patients was significantly decreased (P less than 0.05). 5) Positive correlation was observed between MTT and values of T-Bil, ALP, LAP, and gamma-GTP. Negative correlation was observed between MTT and value of cholinesterase. 6) Initial transfer factor correlated with blood clearance rate. (r = 0.76, P less than 0.01). 7) Initial transfer factor in left lobe of normal controls was significantly decreased compared with that of right lobe (P less than 0.01). This kind of difference was not observed in patients with liver cirrhosis. 8) Initial transfer factor in patients with liver cirrhosis in both compensative and decompensative states and PBC was significantly decreased compared with that in normal controls. Estimation of MTT and initial transfer factor could be a useful parameters to assess transfer function of the liver.

Adult↗
PubMed1989

Effect of salt-loading on erythrocyte deformability in spontaneously hypertensive and Wistar-Kyoto rats.

Effects of salt-loading on erythrocyte and erythrocyte ghost deformabilities were measured by laser diffractometry using a flat cell and a helium-neon laser in spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). Salt-loading did not affect the deformability of erythrocytes in SHR and WKY, although a significantly reduced deformability was observed in salt-loaded SHR compared with values in control WKY and salt-loaded WKY (p less than 0.05, p less than 0.05, respectively). In contrast, salt-loading significantly reduced the deformability of erythrocyte ghosts in WKY and SHR (p less than 0.05, p less than 0.05, respectively). Our results suggest that salt-loading reduces erythrocyte membrane viscoelasticity in both WKY and SHR, and that the observed reduction of ghost deformability induced by salt-loading may influence the peripheral circulation.

Animals↗
PubMed1989

Possible involvement of atrial natriuretic factor in the antihypertensive action of a high-calcium diet in spontaneously hypertensive and Wistar-Kyoto rats.

The present study was designed to determine the possible involvement of atrial natriuretic factor (ANF) in the hypotensive action of a high-calcium diet. The effects of increased dietary calcium (2.9% calcium, HCa) on blood pressure, urinary sodium excretion, and ANF were examined in 30 spontaneously hypertensive rats (SHR) and 30 Wistar-Kyoto rats (WKY). Control groups of 30 SHR and 30 WKY were fed normal calcium lab chow (0.4% calcium, NCa). The HCa diet reduced blood pressure and serum phosphorus concentration and increased urinary excretion of sodium and calcium in SHR and WKY. The HCa diet also caused a sustained increase in plasma ANF concentration and, finally, a decrease in atrial ANF concentration in both groups. A significant inverse correlation was observed between ANF concentrations in plasma and atria of the four experimental groups. Plasma ANF concentration was positively correlated with daily calcium consumption, and blood pressure was inversely correlated with daily calcium consumption in HCa- and NCa-SHR groups and in HCa- and NCa-WKY groups, respectively. Furthermore, a significant inverse correlation between blood pressure and plasma ANF concentration was observed in SHR groups and in WKY groups, respectively. The observed sustained increment in endogenous plasma ANF concentration, which is probably caused by increased secretion from the atrium, may contribute, in part, to the blood-pressure-lowering effects of the HCa diet.

Animals↗
PubMed1989

Prolonged blood pressure elevation after endothelin administration in bilaterally nephrectomized rats.

The hemodynamic effect of a novel potent vasoconstrictive peptide (endothelin) on systemic blood pressure was studied in bilaterally nephrectomized and sham-operated rats under conscious and almost unrestrained condition. Following bolus IV administration of porcine endothelin, plasma endothelin concentration was measured by radioimmunoassay. After a transient decline, blood pressure was gradually elevated by endothelin administration. At 20, 30, and 40 minutes after injection, blood pressure was significantly elevated in bilaterally nephrectomized rats compared with sham-operated rats. Arterial plasma endothelin concentrations increased and rapidly decreased after injection in both rat groups. Bilateral nephrectomy significantly delayed the disappearance of endothelin from the plasma. These results suggest that the kidney plays a role in the plasma clearance of IV bolus endothelin administration and that the prolonged plasma half-life of endothelin is in part associated with the prolonged blood pressure elevation after endothelin administration in bilaterally nephrectomized rats.

Animals↗