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Biomedical subjects

H Orimo

Publications and source records attributed to H Orimo.

At least 19 recordsLinked to original sources
PubMed1992

Vitamin K2 modulates proliferation and function of osteoblastic cells in vitro.

A human osteosarcoma cell line, HOS TE85 cells, and a mouse osteoblastic cell line, MC3T3-E1 cells, were cultured for 3 days in a medium containing various concentrations of menaquinone-4 (vitamin K2). As a result, the proliferation of HOS cells was suppressed by vitamin K2 in a dose dependent manner up to 56% of control by 10(-7)M of vitamin K2 and that of MC3T3-E1 cells was suppressed to 84% of control by 10(-6)M of vitamin K2. Vitamin K2 increased alkaline phosphatase activity in both kinds of cells. Warfarin counteracted the effect of vitamin K2 on osteoblastic cell proliferation. Our results show that vitamin K2 modulates proliferation and function of osteoblastic cells by some mechanisms including gamma-carboxylation system.

Animals↗
PubMed1992

Regulation of bone turnover and prevention of bone atrophy in ovariectomized beagle dogs by the administration of 24R,25(OH)2D3.

In order to determine whether the administration of 24R,25(OH)2D3 had any beneficial effect on the regulation of bone turnover and the prevention of bone atrophy, we examined beagles for 31 months after ovariectomy (OVX). Fourteen beagle dogs (8.54 +/- 1.22 kg body wt-b.w.) were divided into four groups. Group 1 (n = 3) was the sham, and Group 2 (n = 3) served as the OVX control. In Group 3 (n = 4) and Group 4 (n = 4), 24,25-dihydroxyvitamin D3(24R,25(OH)2D3) was given daily at dose levels of 2 and 10 mcg/kg B.W., respectively. In Group 4, the dose level was increased to 100 mcg/kg by 17 months. During the experiments, urinary hydroxyproline (U-HPr), serum chemistry, serum bone gla-protein (BGP), and vitamin D metabolite levels were monitored. At the end of the experiment, bone mineral content (BMC) in the 6th and 7th lumbar vertebrae and right femur was determined by single photon absorptiometry. The left iliac bone sample was obtained after tetracycline labeling, and undecalcified sections were observed. In Group 2, excretion of U-HPr increased after OVX and had reached a level of approximately twice the baseline values by 10 months; then it gradually came down to the original level. In Group 3, however, U-HPr excretion remained at the same level as the baseline value, as it did in Group 1. In Group 4, it was remarkably reduced down to 50-60% of the baseline values. Serum BGP level was markedly reduced in Group 4. Serum 24,25(OH)2D levels were markedly increased in Groups 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Osteonal remodeling and mechanical properties of the femoral cortex in rabbits treated with 24R,25(OH)2D3.

The increase of bone mass by therapeutics does not always mean the enhancement of bone quality. The purpose of this study is to clarify the changes of osteonal remodeling and the mechanical properties of femoral cortex in rabbits treated with 24R,25(OH)2D3. Fifteen NZW rabbits (3 kg B.W.) were divided into three groups of 5 animals each. Groups 1, 2, and 3 were given vehicle, 10 micrograms/kg, and 100 micrograms/kg 24R,25(OH)2D3, respectively, daily for 8 weeks. At the end of the experiment, the left femur was removed and bone mineral content (BMC) was measured with single photon absorptiometry. Serum 24,25(OH)2D concentrations reached levels of approximately 15 and 200 times that of the controls in groups 2 and 3, respectively. Neither 25(OH)D nor 1,25(OH)2D level showed any significant change in either group. Group 3 showed significant increase in mineral content and density in the epimetaphyseal regions, but the increase at the diaphyseal region did not reach a statistically significant level. Mechanical test for torsion was conducted for mid-cortical regions. After the test, bone pieces were bonded together with adhesive to reconstruct the original form, and undecalcified cross-sectional sections were made at the diaphyses. Fluorescent microscopy disclosed a marked reduction of remodeling in secondary osteonal bone area. The numbers for double-labeled osteons for groups 1, 2, and 3 were 2.47 +/- 0.819, 1.14 +/- 1.02* and 0.137 +/- 0.307* N/mm2, respectively, and the numbers for osteons with resorption lacunae were 1.37 +/- 0.721, 0.412 +/- 0.370* and 0.268 +/- 0.339** N/mm2, respectively. However, neither structural stiffness nor strength correlated with the indices of osteonal remodeling; instead, they were significantly correlated with bone mineral contents.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Characteristics of steroid hormone receptors in cultured MC3T3-E1 osteoblastic cells and effect of steroid hormones on cell proliferation.

We examined the binding characteristics of three kinds of steroid hormones--estrogen, androgen, and glucocorticoid--in cultured MC3T3-E1 mouse osteoblastic cells by whole-cell binding assay. The binding studies revealed the presence of a single class of high-affinity binding sites for [3H]17 beta-estradiol, [3H]mibolerone (a synthetic androgen), and [3H]triamcinolone acetonide (a synthetic glucocorticoid). The numbers of binding sites for these steroid hormones were found to be 4534 +/- 819, 14312 +/- 1884, and 24898 +/- 655 sites/cell; and the Kd values were 8.57 +/- 0.62 x 10(-10) M, 1.12 +/- 0.19 x 10(-9) M, and 6.08 +/- 1.24 x 10(-10) M, respectively. We also examined the effects of steroid hormones on the proliferation of MC3T3-E1 cells. 17 beta-estradiol significantly stimulated the proliferation of the cells (130-150% of control). Dihydrotestosterone also significantly stimulated the proliferation of the cells (115% of control); the effect was, however, much less potent than that of 17 beta-estradiol, although the number of binding sites was approximately three times more than that of 17 beta estradiol. Triamcinolone acetonide and dexamethasone had no effect on cell proliferation. These results suggest that estrogen and androgen act directly on osteoblastic cells through a receptor-mediated mechanism, and that androgen is much less potent than estrogen in stimulating the proliferation of MC3T3-E1 osteoblastic cells.

Animals↗
PubMed1992

Increased bone volume and reduced bone turnover in vitamin D-replete rabbits by the administration of 24R,25-dihydroxyvitamin D3.

To study the effect of a large dose of 24R,25(OH)2D3 on bone metabolism, we treated vitamin D-replete rabbits with the agent for eight weeks. Fifteen rabbits 20 weeks of age were divided into three groups of five animals each. Group I received only the vehicle; groups II and III were given the agent at doses of 10 micrograms/kg/d, and 100 micrograms/kg/d, respectively. Through the dosing period, serum calcium, phosphorus, alkaline phosphatase, and creatinine levels were not altered. By the end of the experiment, serum 1,25(OH)2D or serum 25(OH)D levels did not change, nor did the PTH level. Serum 24,25(OH)2D levels for groups I, II, and III were 5.25 +/- 3.40, 76.16 +/- 19.90 (p less than .01), and 199.0 +/- 30.90 (p less than .01) ng/ml, respectively. The bone mineral content (BMC) significantly increased in group III. The percentages of BMC increase in group III over group I were 14.5% on the femur, 34.1% (p less than .01) on the sixth lumbar vertebra, and 23.3% (p less than .05) on the seventh lumbar vertebra. A marked increase of bone mineral densities in the cancellous bone-rich regions was seen in group III. Bone histomorphometry on the seventh lumbar vertebra demonstrated that both the eroded surface and the osteoclast number were reduced and the surfaces indicating bone formation such as the osteoid surface and the tetracycline double labeled surface were also reduced. However, both the osteoid thickness and the mineral apposition rate increased and the mineral formation rate at the tissue level remained approximately equal to that in the control.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Soybean protein isolate and soybean lectin inhibit iron absorption in rats.

Inhibitory effects of soybean protein isolate (SPI) and soybean lectin on the intestinal absorption of nonheme iron were investigated by in vivo studies in rats. Rats fed the SPI-based diet absorbed significantly less iron than did control rats fed the casein-based diet. Supplementing the SPI diets with 8% D-galactose significantly increased the incorporation of iron into liver ferritin, although D-galactose did not significantly increase iron absorption. Heat treatment of SPI significantly increased iron absorption. Ascorbate did not enhance iron absorption in rats fed the SPI-based diet. The presence of lectin in an aqueous extract of SPI was suggested by hemagglutination activity as well as by immunoreactivity with soybean lectin antibody. Soybean lectin introduced into ligated segments of the upper small intestine of rats inhibited ferrous iron absorption. This inhibitory effect, especially in the mucosal uptake, was significantly improved by addition of N-acetyl-D-galactosamine to soybean lectin. Soybean lectin had no effect on ferric iron absorption. Our results suggest that a portion of the reduction in iron absorption in rats fed SPI may be due to lectins.

Animals↗
PubMed1992

Inhibition of mouse alveolar macrophage production of tumor necrosis factor alpha by acute in vivo and in vitro exposure to tobacco smoke.

We investigated the effects of tobacco smoke exposure on the production of tumor necrosis factor alpha (TNF alpha) by alveolar macrophages (AM) in mice (C57BL/6). The results obtained are as follows: (1) In vivo tobacco smoke exposure caused a significant decrease in the production of TNF alpha by AM with the stimulation of lipopolysaccharide (LPS; control group: 19.32 +/- 5.52 U/ml, smoked group: 4.28 +/- 0.98 U/ml; p less than 0.05). (2) In vitro exposure of AM to tobacco smoke extracts (water-soluble extracts) also caused a decrease in the production of TNF alpha up to 93% of control with stimulation of LPS (p less than 0.05) without any decrease in cellular viability. We concluded that the production of TNF alpha by AM was impaired by smoking via direct action of the factors present in tobacco smoke.

Animals↗
PubMed1992

Genetic and environmental factors of bone mineral density indicated in Japanese twins.

To evaluate the effects of genetic and environmental factors on the bone mass, we determined the bone mineral density (BMD) in the total body, the lumbar spine and in the femoral neck in 23 Japanese twin pairs including 21 monozygotic (MZ) pairs, applying dual-energy X-ray absorptiometry. In MZ pairs aged 20-49 years, highly significant intraclass correlation coefficients, ranging from 0.775 to 0.926, were observed at several sites, including the lumbar spine and the femoral neck, which suggests considerable contributions of genetic factors to the BMD. Neither intraclass correlation coefficients nor intrapair differences were found to change with increasing age in the present analysis. In female MZ pairs, exercises both at the present time and in the past were correlated with the BMD at several sites as well as body mass index in multiple regression analyses.

Absorptiometry, Photon↗
PubMed1992

Quantitative assessment of dyspnea during exercise before and after bullectomy for giant bulla.

Incremental exercise testing using a cycle ergometer was performed in eight patients with giant bulla before and after bullectomy to assess dyspnea. There was a significant positive linear relationship between dyspnea expressed in the Borg scale (BS) and oxygen consumption (VO2) during exercise in all subjects. From these correlations, we introduced the following three new parameters for quantitative assessment of dyspnea: the Borg scale slope (BSS); the threshold load of dyspnea (TLD); and the breakpoint load of dyspnea (BLD), representing the slope of the regression line, onset of dyspnea on the regression line, and the maximum oxygen consumption before the subjects interrupted exercise, respectively. After surgery, the BSS showed marked decrease, and the TLD and BLD showed significant increase. Therefore, the reduction in the dyspnea with peak exercise after surgery was thought to be, at least in part, based on the delay of dyspnea onset, the decrease in dyspnea sensitivity, and the improvement in exercise capacity. The improvement in dyspnea during exercise in patients with giant bulla after surgery was extensively evaluated by newly introduced parameters based on BS-VO2 regression line.

Blister↗
PubMed1992

Accuracy and reliability of quantitative measurement of coronary arterial stenosis by videodensitometry on coronary angiogram.

This study was undertaken to investigate the accuracy and reliability of videodensitometry (VDM) in measuring the magnitude of coronary arterial stenosis on coronary angiogram (CAG). CAG taken after administration of sublingual nitroglycerin was analyzed with VDM (XR-70 Coronary Analyzer, Vanguard). The magnitude of stenosis in coronary segments with four different classes of stenosis was consecutively measured 10 times by the same observer, and the values were 89.0 +/- 1.4, 70.9 +/- 2.1, 59.5 +/- 2.5, and 22.8 +/- 3.4%. The coefficients of variation (CVs), indicating intraobserver variability, were low for severe to moderate lesions (1.6, 2.9, and 4.3%, respectively), but was higher for low-grade lesions (14.8%). When the same lesions were measured by 2 observers, the measurements were highly correlated (r = 0.971, p < 0.01). The results of VDM were consistent with those of conventional gross examination for moderate to severe lesions, and the discrepancy was mainly found in low-grade lesions. The magnitude of stenosis of the same lesion was measured from the right and the left anterior oblique views, and the cineangle was found not to affect the results of VDM. Moreover, cardiac cycle did not affect the videodensitometric measurements of % area stenosis. In order to further investigate the accuracy of VDM, the magnitude of stenosis was measured in nine phantom arteries, and the value measured by VDM significantly correlated with the actual stenosis (r = 0.969, p < 0.001). These results indicate that the values of coronary arterial stenosis on CAG measured by VDM are accurate and clinically acceptable, even though variability is somewhat high for low grade lesions. VDM may be useful for evaluation of the outcome of PTCA and the anti-atherogenic action of some agents.

Absorptiometry, Photon↗
PubMed1992

Age-related changes in GSH content of eyes in mice--a comparison of senescence-accelerated mouse (SAM) and C57BL/J mice.

1. Age-related changes in glutathione (GSH) content of eye lenses were investigated in senescence-accelerated mouse (SAM) and C57BL/J mice. 2. The decrease of GSH content with aging is markedly observed in SAM strains. 3. The oxidized glutathione (GSSG) content of eyes increased significantly with aging in SAM. 4. Ophthalmic changes, including cataract, increased with age in SAM alone. 5. The decrease of GSH content and the increase of GSH oxidation may be involved in the pathogenesis of cataract in SAM.

Aging↗
PubMed1992

[Pharmacokinetics and clinical efficacy of ciprofloxacin in aged patients with chronic respiratory diseases].

Pharmacokinetics and clinical efficacy of ciprofloxacin (CPFX) were investigated in aged patients with chronic respiratory diseases. Serum and sputum concentrations of CPFX were determined upon oral administration of 200 mg CPFX in 6 aged patients with chronic respiratory diseases (mean age = 78.8 +/- 3.2 years, 2 cases diagnosed chronic obstructive pulmonary disease with pneumonia, 3 cases were diagnosed bronchiectasis with acute exacerbation, and 1 case diagnosed chronic lung abscess). Maximal serum concentrations in these patients were 0.88-1.29 micrograms/ml (mean = 1.08 micrograms/ml). Thus, maximal serum concentrations of CPFX after oral administration in these aged patients were slightly lower than those in young subjects. However, peak sputum levels of CPFX following oral administration of 200 mg CPFX ranged from 0.53 to 1.47 micrograms/ml at 1-4 hours. These sputum concentrations of the 6 patients were sufficiently high for the inhibition of most infecting organisms in vitro. Clinical responses to CPFX in these 6 patients were good in 5, fair in 1, with an efficacy rate of 100%. Upon administration of CPFX, these 6 patients did not show any adverse reactions. These results suggest that oral administration of CPFX may keep effective levels in serum and sputum over 3 hours in aged patients with chronic respiratory diseases, and good clinical responses should be obtained without side effects in such patients.

Aged↗
PubMed1992

[Purification and characterization of the membrane associated calmodulin from the human placenta].

The protein with the most predominant Ca2+ binding activity in membrane fractions of the human placenta was purified to electrophoretical homogeneity. This protein was identified as the membrane bound form of calmodulin based on the immunological cross reactivity and a number of biochemical properties. The membrane fraction of the human placenta contained 8.3% of the total cellular calmodulin activity. Approximately 2/3 of the membrane associated calmodulin was extracted by incubation with a Ca2+ chelating agent, EGTA, suggesting that this form of calmodulin is bound reversibly to membrane proteins in a Ca2+ dependent manner. However, the rest of the membrane associated calmodulin could not be extracted by EGTA treatment. The EGTA nonextractable calmodulin appears to be embedded in the membrane matrix.

Calcium-Binding Proteins↗
PubMed1991

A new murine model of aging lung: the senescence accelerated mouse (SAM)-P.

The senescence accelerated mouse (SAM) has recently been characterized as a unique model to investigate age-related disorders, including amyloidosis, cataract, osteoporosis and dementia. However, little is known as to the properties of the lung in these animals. Tobacco smoke is also associated with enhanced loss of elastic recoil and the development of emphysema. We have attempted to examine morphological as well as biochemical changes of the distal lung in SAM-P/2, as the senescence-prone series and SAM-R/1, as the senescence-resistant series. The animals were intermittently exposed to tobacco smoke or air by Hamburg II machines for 5 weeks. Then both groups of animals were killed for histologic and biochemical study. Compared with SAM-R/1, SAM-P/2, even with air exposure, showed a higher value of the mean linear intercept without alveolar wall destruction. It became even greater due to tobacco exposure with emphysematous change. Tobacco exposure accumulated inflammatory cells into alveoli in SAM-P/2, but not in SAM-R/1. Oxygen radical generation by those cells was also higher in SAM-P/2. Analysis of bronchoalveolar lavage fluid in SAM-P/2 after tobacco exposure disclosed increases in albumin content, total protein content and elastase-like activity. There were decreases in the ratio of elastase inhibitory capacity (EIC) to trypsin inhibitory capacity (TIC), contents of glutathione and total free thiol groups. Moreover, SAM-P/2 showed significantly lower EIC/TIC ratio in serum, even with air exposure, than that of SAM-R/1. These results indicate that SAM-P/2 can be a good model for the study of natural evolution of the aging lung as well as its susceptibility to tobacco smoke in the development of emphysema.

Aging↗
PubMed1991

Effect of parathyroid hormone on release of interleukin 1 and interleukin 6 from cultured mouse osteoblastic cells.

This study was undertaken to examine the possibility that parathyroid hormone promotes the production of interleukin 1 and 6 in MC3T3-E1 osteoblastic cells derived from mouse calvaria. The cells were incubated in serum-free medium with or without synthetic human parathyroid hormone(1-34). The concentrations of interleukin 1 and 6 in the culture medium were determined by using specific bioassay. The cells cultured without parathyroid hormone for 24 hr released both of interleukins, and parathyroid hormone stimulated the release in a dose-dependent manner. When the cells were cultured with 10(-6) M parathyroid hormone, the release of both interleukins from the cells remained higher than control up to 144 hr. These results suggest that interleukin 1 and 6 release stimulated by parathyroid hormone may be involved in the bone resorbing activity of the hormone.

Animals↗
PubMed1991

[The effect of estrogen and, sex-steroids and thyroid hormone preparation on bone mineral density in senile osteoporosis--a comparative study of the effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on senile osteoporosis].

In order to assess the effect of sex steroids on bone mineral density in Japanese with senile osteoporosis, the bone mineral density in 1/3 distal site of radius was measured serially before and after treatment for 2 years using single photon absorptiometry. Sixty seven old females with senile osteoporosis were divided into 4 groups, Group 1 (n = 28, mean age; 74.4 +/- 1.3 y.o., mean +/- SEM) was the control group, Group 2 (n = 14, mean age; 73.7 +/- 1.7 y.o.) was treated with 0.5-1.0 micrograms/day of 1 alpha -OHD3, Group 3 (n = 12, mean age; 75.4 +/- 2.9 y.o.) was treated with conjugated estrogen (Premarin) in a dose of 0.3125 mg/day (3 approximately 4 weeks administration followed by 1 week rest) and Group 4 (n = 13, mean age; 76.4 +/- 1.8 y.o.) was treated with sex-steroids (pregnenolone : androstenedione : androstenediol : testosterone : estrone = 1.0 mg : 1.0 mg : 0.5 mg : 0.1 mg : 5 micrograms/tablet) and thyroid hormone (thyroid-sicca 7.5 mg/tablet) preparation in a dose of 2 tablets/day. When the radial bone mineral density (RMD) before the treatment was taken as 100%, RMDs of each group at 6, 12, 18 and 24 months were 96.4 +/- 3.1%, 97.3 +/- 2.0%, 93.7 +/- 2.1% and 96.1 +/- 1.8% in Group 1, 100.8 +/- 2.8%, 106.4 +/- 2.1%, 101.3 +/- 3.4% and 108.8 +/- 2.9% in Group 2, 103.0 +/- 2.8%, 106.2 +/- 3.5%, 105.9 +/- 4.3% and 100.2 +/- 4.7% in Group 3, 105.3 +/- 2.2%, 104.7 +/- 2.3%, 112.6 +/- 6.4% and 112.1 +/- 6.7% in Group 4, respectively. Therefore, significant increases in RMD were observed in Groups 2, 3 (transient) and 4 when compared with Group 1. In Group 3, serum level of parathyroid hormone (PTH) was significantly (p less than 0.05) increased from 0.28 +/- 0.03 ng/ml before the treatment to 0.55 +/- 0.15 ng/ml at 24 months after the treatment. In Group 2, transient (6 months after the treatment) but significant (p less than 0.01) increase in urinary Ca/Creatinine ratio from 0.15 +/- 0.04 to 0.20 +/- 0.03 was found. Serum A1-P activities in Group 4 was shown to increase transiently from 131 +/- 10 IU to 151 +/- 12 IU (p less than 0.05) at 6 months and to 158 +/- 13 IU (p less than 0.01) at 12 months followed by subsequent decrease to 135 +/- 6 IU at 18 months and 133 +/- 10 IU at 24 months after the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗