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Biomedical subjects

N Kurihara

Publications and source records attributed to N Kurihara.

At least 181 records · Page 10Linked to original sources

Production of endothelin by cultured porcine endothelial cells: modulation by adrenaline.

Cultured porcine endothelial cells derived from aortas spontaneously released immunoreactive endothelin into the medium in a time-dependent manner. This release was completely inhibited by cycloheximide and is, therefore, directly related to de novo protein synthesis. The endothlin-induced release was further stimulated by adrenaline. Adrenaline-induced stimulation was completely inhibited by the alpha-adrenergic blocker phentolamine and was not inhibited by the beta-adrenergic blocker propranolol. Cycloheximide completely prevented the adrenaline-stimulated as well as the basal release. These results suggest that cultured endothelial cells release endothelin slowly but continuously and that this release can be stimulated by adrenaline via alpha-adrenergic receptors. We speculate that the endothelium generates vasoconstrictor signals through endothelin production, thus contributing to the regulation of vascular tone.

Animals↗

Effect of a new angiotensin converting enzyme inhibitor, cilazapril, on circulating atrial natriuretic factor during exercise in patients with essential hypertension.

In seven patients with mild to moderate essential hypertension, the effect of a new angiotensin converting enzyme (ACE) inhibitor, cilazapril, on atrial natriuretic factor (ANF) was examined at rest and during exercise. The exercise protocol consisted of three fixed workloads (25, 50 and 75W) every 4 min with the use of a sitting bicycle ergometer. Cilazapril reduced blood pressure without increasing the heart rate, both at rest and during exercise. The resting pre-exercise left ventricular ejection fraction was not altered. The plasma ANF level was increased by exercise, but at the 75-W workload it was decreased by cilazapril; the resting plasma ANF value was not altered. At the 75-W workload the plasma ANF level was inversely correlated to the left ventricular ejection fraction (n = 14, r = -0.64, P less than 0.01). These results suggest that the observed decrease in the plasma ANF level during exercise induced by cilazapril is, in part, related to an improvement in the cardiac overload, and that cilazapril may be effective in physically active hypertensive patients.

Angiotensin-Converting Enzyme Inhibitors↗

Glucocorticoids and dopamine-1 receptors on vascular smooth muscle cells.

The effect of glucocorticoids on the dopamine (DA)-mediated cyclic adenosine monophosphate (cAMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from renal arteries of 14-week-old Wistar-Kyoto rats by explant method. Micromolar concentrations of dexamethasone (DEX) pretreatment for 48 hours potentiated DA-mediated response without any change of affinity constant. However, micromolar concentrations of aldosterone pretreatment for 48 hours had almost no effect on DA-mediated response. The DEX-induced facilitation began at 6 hours and reached maximum at 24 hours after DEX administration in a dose-dependent manner. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twofold higher than that in control cells. Treatment of VSMC with DEX increased cholera toxin-stimulated and forskolin-stimulated adenylate cyclase activity. However, pertussis toxin treatment did not augment or reduce the effect of DEX treatment. These results suggest that glucocorticoids increase DA-mediated cAMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis and that the activation of the catalytic unit may play some role in this facilitation.

Adenylyl Cyclases↗

[Clinical application of sintered bone (II). Effects of collagen coating on implant materials in vitro].

In vitro studies with osteoblast-like cells, revealed that in addition to preventing the immediate outflow and promoting stabilization of implant materials, these cells have the additional effect of promoting the mending and early calcification by coating the materials with collagen. The materials used for the experiment were minute hydroxyapatite, beta-tricalcium phosphate and bovine sintered bone. To these, atelocollagen which is solble in pepsin extracted from calf corium and crosslinked by using ultraviolet rays was added. We observed the cells very closely after these materials were added to alpha-modified eagle's medium containing 10 mM beta-glycero phosphate, 10% fetal bovine serum and osteoblast-like cells and the cultures incubated at 37 degrees C and 5% CO2. After 14 and 21 days, cells were fixed and stained with Alizarin Red S and Von Kossa stains to measure calcification. As a result of the collagen coating, positive areas appeared and, compared to the control improvement of the early mending was apparent. The results suggest that by coating the materials with collagen, the osteoblast-like cells show better mending and early calcification.

Animals↗

[Distribution pattern of density in lumbar vertebra studied with computed tomography: a study of histogram plot].

The bone mineral status of the cancellous bone in the lumbar vertebrae was evaluated by analysing density histograms and measuring the mean density by computed tomography. The results obtained were as follows: (a) the distribution pattern of bone density in lumbar vertebrae revealed a normal distribution. (b) high correlation coefficients between peak density (r = -0.79) or mean density (r = -0.77) and age was obtained in males, whereas peak densities in females were maintained well at ages younger than 50 years and peak densities abruptly decreased after 50 years of age. Osteoporotic vertebrae, in which multiple osteosclerotic changes were observed, had several peak densities and did not show normal density distribution pattern. These results indicated that our methods combining analysis of density histograms and measurement of mean density are useful to evaluate the bone mineral status.

Absorptiometry, Photon↗

[A new computed tomography method for quantitative analysis of abdominal aortic atherosclerosis].

Clinical evaluation of aortic atherosclerosis has been most commonly performed by visual analysis of aortic calcification on conventional radiographs or X-ray CT. However, precise evaluation of the degree of calcification or mild changes with increasing age can be difficult by these methods of visual analysis. A new quantitative method of evaluating the abdominal aortic atherosclerosis using CT is reported. Target CT scans of the abdominal aorta were performed at the level of the 1st, 3rd and 4th lumbar vertebrae. Two circular regions of interest (ROI) were selected along the outer margin and inner margin of the abdominal aortic wall on CT images, since it was difficult to precisely trace the aortic wall. Histograms of CT value for each pixel were made from two ROIs. A histogram at the ROI of the outer margin was depicted using class values over the maximum CT value in histogram at the ROI of inner margin which indicated flowing blood. A sum of products of the value in each class by the number in that class was divided by the aortic diameter. The value thus obtained was defined as the atherosclerotic index (S.I.). Forty-five cases were studied with this method. Six cases were excluded because of artifacts. The remaining 39 cases (16 males, 23 females) were analyzed. S.I. increased with aging and was higher in men than in women. However, it increased more rapidly in women (8.68/year) than in men (2.73/year). Because this new method employed the CT value, it is more objectively quantitative than previous methods of visual analysis in evaluating abdominal aortic atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Evaluation of gallbladder emptying in patients with chronic liver disease by 99mTc-EHIDA hepatobiliary scintigraphy].

Gallbladder emptying after intramuscular injection of cerulein was investigated by 99mTc-EHIDA hepatobiliary scintigraphy in 23 patients with biliary disease, 55 patients with chronic liver disease, and 21 normal controls. The mean gallbladder ejection fraction in patients with gallstones and liver cirrhosis was significantly reduced compared with normal controls. (gallstones: 56.3 +/- 21.3%, LC with gallstones: 50.8 +/- 29.6%, LC without gallstones: 55.9 +/- 26.7%, vs. normal controls: 74.4 +/- 12.9%, p less than 0.01). The mechanism for sluggish gallbladder emptying in liver cirrhosis is unknown, however impaired emptying with bile stasis provides a potential pathophysiologic basis for the high frequency of pigment stones.

Adult↗

[IgG, IgA and IgM serum antibodies against lipopolysaccharide from Bacteroides intermedius in periodontal health and disease].

Serum antibody titers to lipopolysaccharide from Bacteroides intermedius (B. intermedius) and Bacteroides gingivalis (B. gingivalis) were measured by enzyme-linked immunosorbent assay in serum samples from subjects with healthy gingiva and patients with periodontitis. The IgG antibody titers to LPS from B. gingivalis were significantly higher in the patients group, compared with healthy controls. No such difference was found between IgG activity to LPS from B. intermedius in the healthy and the periodonitis. Likewise, no significant difference in specific IgA level was found between the group with healthy gingiva and the patients group, both in LPS from B. intermedius and B. gingivalis. The IgM antibody levels to LPS from B. intermedius and B. gingivalis were low in subjects of patients and controls.

Antibodies, Bacterial↗

[Exercise induced hypoxemia and exercise tolerance in patients with COPD and the benefits of oxygen supplementation].

In order to evaluate the benefits of O2 supplementation during exercise, slowly incremental treadmill exercise tests were performed twice with 30 minutes interval rest in fourteen patients with severe COPD. The patients breathed room air. 31/min of compressed air by nasal prongs, and 31/min of supplemental oxygen in single blind fashion at random. The patients who developed arterial desaturation below 88% on exercise, group D, showed slight but significant increase in walked distance (397 m vs 424 m) and significant decrease in breathlessness (22.9 vs 16.9) on oxygen as compared to on air. On the other hand in patients without significant arterial desaturation, group S, there was no improvement in those parameters. The increase in walked distance on oxygen was closely related with the decrease in mean inspiratory flow (VT/Ti), blood lactate level, and CO2 production at identical work load. Plasma human atrial natriuretic peptide (h-ANP) levels in group D increased with exercise from a resting value of 27.6 +/- 6.9 to 44.0 +/- 9.0 on compressed air whereas the increase was significantly suppressed to 35.4 +/- 9.0 on oxygen. In group S there was no difference in the increase of plasma h-ANP levels between air and oxygen breathing during exercise (33.1 +/- 5.1 vs 31.9 +/- 9.6). A close correlation (r = 0.908) was found between mean pulmonary artery pressures and plasma h-ANP levels at rest and during exercise performed in four patients breathing air and oxygen. Those findings suggested that arterial plasma h-ANP levels reflected the right ventricular afterload and that they could be used to evaluate the effectiveness of O2-supplementation during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Generation of osteoclasts from isolated hematopoietic progenitor cells.

A variety of studies have shown that osteoclasts originate from bone marrow, but their exact progenitors and differentiation pathway remain unclear. The treatment of mice with a high dose of 5-fluorouracil (5-FU) results in an enrichment for primitive hematopoietic progenitors; using this procedure, we prepared a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro. When spleen cells from mice pretreated in vivo with 5-FU were cultured in the presence of methylcellulose medium containing recombinant interleukin-3 (rIL-3), small colonies consisting of blast cells with little sign of differentiation developed on day 7 of culture. We lifted these blast colonies, pooled them, and replated them as secondary methylcellulose cultures in the presence of rIL-3 and erythropoietin. Approximately 60% of the cells formed colonies comprising various combinations of neutrophils, macrophages, eosinophils, mast cells, megakaryocytes, and erythroblasts. We replated such blast cells into microtiter wells and cultured them in the presence of rIL-3 (100 U/mL) or recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) (100 U/mL) plus 1.25(OH)2D3 (10(-7) mol/L). Multinucleated cells appeared from day 14 of culture and approximately 100 giant cells per well were scored on day 21 of culture. Parathyroid hormone (1 U/mL) also induced the multinucleated cell formation. May-Grunwald-Giemsa staining revealed the large cells containing many nuclei in their cytoplasm, which is characteristic of bone-resorbing cells or osteoclasts. These cells showed a tartrate-resistant acid phosphatase (TRAP) activity. Calcitonin caused a striking shape change in these cells and suppressed the formation of multinucleated cells. Moreover, electron microscopy shows that these cells were able to resorb fetal calvariae. In the presence of r granulocyte-colony stimulating factor, r macrophage-colony stimulating factor, or r interleukin-6 plus 1.25(OH)2D3, formation of TRAP-positive multinucleated cells was lower compared with the support of rIL-3 or rGM-CSF. Mature macrophages collected from colonies did not form the multinucleated cells as described above, even in the presence of rIL-3 and 1.25(OH)2D3. Moreover, to exclude the possibility that osteoclasts generated from non-blast cells, we performed a cloning experiment from one isolated blast cell and demonstrated that single cells differentiate into osteoclasts or macrophages in the presence of rIL-3 with or without 1.25(OH)2D3. This system will provide a useful model for further analysis of osteoclast formation in vitro.

Animals↗

[A case of sarcoidosis beginning with extensive ground-glass pattern on chest X-ray, accompanied with high fever and eosinophilia].

A 62-year-old woman was admitted to our hospital with a chief complaint of dyspnea on effort. Her temperature was 38 approximately 39 degrees C. Eosinophilia was seen in peripheral blood and the chest roentgenogram showed bilateral extensive ground-glass pattern, accompanied by air bronchogram. The extensive shadow fitted the description of "unstable shadow." Transbronchial lung biopsy specimens demonstrated the formation of non-caseating epithelioid cell granulomas with severe alveolitis and exudative change in alveolar spaces. In bronchoalveolar lavage fluid (BALF), the total cell count was normal but the lymphocyte population was increased to 28%. Pathological findings were suggestive of either sarcoidosis or hypersensitivity pneumonitis. Prednisolone therapy was started. As a result, her symptoms rapidly disappeared and the chest roentgenogram showed remarkable improvement for a short period. However skin lesions on bilateral lower extremities appeared after approximately one month from discontinuation of prednisolone. Skin biopsy specimens showed non-caseating epithelioid cell granulomas leading to the final diagnosis of sarcoidosis. About one month after the appearance of the skin lesion, the chest roentgenogram findings deteriorated. At this time, the BALF eosinophil population surprisingly increased to 24.9%. Chest roentgenogram showed rapid improvement again by administration of prednisolone. This case was considered to be a unique case of sarcoidosis from the point of view of the chest roentgenogram pattern, eosinophilia, clinical course and presence of severe alveolitis with exudative change in alveolar spaces.

Alveolitis, Extrinsic Allergic↗

[A case of chronic obstructive pulmonary disease associated with central alveolar hypoventilation diagnosed by exercise test].

We report a case of chronic obstructive pulmonary disease associated with central alveolar hypoventilation diagnosed by exercise test. A 61-year-old man with chronic obstructive pulmonary disease was admitted to our hospital because of respiratory failure caused by bacterial pneumonia. After recovery from pneumonia, we examined his functional ventilatory response to incremental exercise. Exercise was discontinued because of his maximal target heart rate, and there was no complaint of dyspnea throughout the exercise test. Although the patient had enough ventilatory reserve during exercise (VEmax/MVV = 50%), there was a marked progressive retention of carbon dioxide disproportionate to the extent of his air flow obstruction. Moreover the patient was able to reduce the carbon dioxide tension to a subnormal level by voluntary hyperventilation, and his ventilatory response to carbon dioxide and mouth occlusion pressure at rest was significantly diminished as compared with normal subjects. These findings suggest that this patient has several features compatible with central alveolar hypoventilation. Exercise test was useful for the diagnosis as well as exercise prescription because the patient could develop dangerous hypoxemia without alarming symptoms like dyspnea.

Exercise Test↗

Effects of diastereoisomers of 1,25-dihydroxyvitamin D3-26,23-lactone on alkaline phosphatase and collagen synthesis in osteoblastic cells.

The effects of the four diastereoisomers of 1,25-dihydroxyvitamin D3-26,23-lactone (1,25-(OH)2D3-26,23-lactone) on alkaline phosphatase (AP) activity and collagen and noncollagen protein synthesis were examined in cultures of the osteoblastic clone MC3T3-E1 cell line. The four lactone diastereoisomers had little effect on the protein and DNA content of the cells. The 23(S),25(S)- and 23(R),25(R)-1,25-(OH)2D3-26,23-lactones increased AP activity in a linear dose-dependent fashion. Maximal effects were observed at 100 and 1000 pg/ml, respectively. In contrast, the naturally occurring 23(S),25(R)-, 1,25-(OH)2D3-26,23-lactone and the 23(R),25(S)-1,25-(OH)2D3-26,23-lactone showed biphasic stimulatory effects on AP activity. At both 80 and 10,000 pg/ml, they stimulated maximum increases in alkaline phosphatase activity. At 80 pg/ml the 23(S),25(R)- and 23(R),25(S)-isomers stimulated an increase in collagen synthesis, while at 10,000 pg/ml these isomers and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) did not. Moreover, these two isomers (at 10,000 pg/ml) plus insulin or dexamethasone had an additive effect on AP activity, but not at 80 pg/ml. At 80 pg/ml but not at 10,000 pg/ml, the 23(S),25(R)-isomer had an additive effect on AP activity with the simultaneous addition of 25-hydroxyvitamin D3. Relative to 1,25-(OH)2D3, the binding affinities of 23(S),25(S)-, 23(R),25(R)-, 23(S),25(R)- and 23(R),25(S)-1,25-(OH)2D3-26,23-lactones were calculated to be 1/13.0, 1/131.8, 1/805.2, and 1/1083.3, respectively. No metabolites could be detected in the medium when [1-3H]23(S),25(R)-1,25-(OH)2D3-26,23-lactone (the naturally occurring diastereoisomer) was added to the cultures. However, the stimulative effects of 1,25-(OH)2D3 and the 23(S),25(R)-isomer at both concentrations were completely abolished by L-1-tosyl-amido-2-phenylethyl chloromethyl ketone. These results indicate that 1,25-(OH)2D3-lactone has a stimulative effect on osteoblastic cell functions in vitro. The naturally occurring 23(S),25(R)-1,25-(OH)2D3-lactone acts biphasically and may act on bone metabolism in vivo, possibly through a 1,25-(OH)2D3-receptor-mediated pathway.

Alkaline Phosphatase↗

Effect of long-term treatment with diltiazem on atrial natriuretic peptides in spontaneously hypertensive rats.

The present study was designed to examine the possible effect of long-term treatment with diltiazem on plasma and atrial concentrations of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR). Diltiazem treatment reduced blood pressure and ventricular weight in SHR. Plasma ANP concentration in untreated SHR was higher than Wistar-Kyoto rats (WKY). Diltiazem treatment decreased plasma ANP concentration in SHR near to the level of WKY; moreover, plasma ANP concentration was correlated with blood pressure and ventricular weight in treated and untreated SHR. Left atrial ANP concentration in untreated SHR was lower than WKY. Diltiazem treatment increased left atrial ANP concentration in SHR, but this effect was not noted in WKY. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that the prevention of an increase in plasma ANP by diltiazem treatment may be, in part, attributed to the improvement of cardiac overload induced by reductions in blood pressure and cardiac hypertrophy.

Animals↗

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells.

Vitamin D3 and its hormonally active metabolite 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can be metabolized to a number of daughter metabolites, including 1 alpha,25-(OH)2D3-26,23-lactone; this latter compound has four diastereoisomers. The 23(S),25(R)-lactone (naturally occurring) and the 23(R),25(S)-1 alpha,25-(OH)2D3-26,23-lactone are both known to be able to inhibit bone resorption induced by 1 alpha,25-(OH)2D3 under in vivo or in vitro conditions. To understand the mechanism of the inhibitory action of these two isomers on bone resorption we investigated the effects of 1 alpha,25-(OH)2D3-26,23-lactone on unfractionated mouse bone marrow cells in vitro. The addition of 1 alpha,25-(OH)2D3 to these cultures dose-dependently stimulated the formation of multinucleated cells over a range of 10(-9) - 10(-7) M. The 23(S),25(S)- and 23(R),25(R)-1 alpha,25-(OH)2D3-26,23-lactones also increased the number of multinucleated cells, whereas the 23(S),25(R)- and 23(R),25(S)-1 alpha,25-(OH)2D3-26,23-lactones failed to do so. In addition, these latter two diastereomers inhibited the 1 alpha,25-(OH)2D3 stimulation of multinucleated cell formation, although the 23(S),25(S)- and 23(R),25(R)-1 alpha,25-(OH)2D3-26,23-lactones and 24R,25-(OH)2D3 did not. These multinucleated cells responded to calcitonin and contained tartrate-resistant acid phosphatase, both of which are characteristic of osteoclasts. The present data suggest that inhibition of multinucleated cell formation is the mechanism by which the 23(S),25(R)- or 23(R),25(S)-1 alpha,25-(OH)2D3-26,23-lactone inhibits bone resorption induced by 1 alpha,25-(OH)2D3.

Acid Phosphatase↗