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Biomedical subjects

K Kushida

Publications and source records attributed to K Kushida.

At least 91 records · Page 5Linked to original sources

Factors related to the parameters of ultrasound measurements in the early menopausal period.

Urinary deoxypyridinoline, serum osteocalcin (OC), and ultrasound (US) measurements were investigated in a premenopausal group and a postmenopausal group. In previous studies we reported the relation between each biochemical marker and each US parameter by simple regression analysis. However, in this study, multiple regression analysis of the US parameter, not only by biochemical markers but also by age and body mass index (BMI), were done to determine what fraction of the variation in the respective US values can be accounted for by these factors. Multiple regression analysis showed that age and serum OC were significant determinants for stiffness index, serum OC and BMI were significant determinants for speed of sound, age was a significant determinant for broadband ultrasound attenuation, although each US parameter can be explained by factors of approximately only 26-33%.

Amino Acids↗

Comparison of bone and total alkaline phosphatase activity on bone turnover during menopause and in patients with established osteoporosis.

OBJECTIVE: Recently, a bone alkaline phosphatase (AP) enzyme immunoassay (EIA) was developed for measurement of bone AP activity with a monoclonal antibody. We compared the clinical performance of bone AP (bAP) measured by EIA and total AP (tAP) to examine if bAP is preferable to tAP as a bone formation marker in the post-menopause and established osteoporosis. DESIGN AND PATIENTS: Serum was obtained from 50 pre- and 93 post-menopausal healthy women, and 54 osteoporotic patients with vertebral fractures and 57 patients with hip fracture. MEASUREMENTS: Total AP was measured spectrophotometrically with p-nitrophenyl phosphate as substrate. The intra- and inter-assay coefficients of variation were 0.7-1.8% and 0.6-1.1%, respectively. Bone AP activity (bAP) was measured by EIA kit, ALKPHASE-B (Metra Biosystems, Inc.) using a monoclonal antibody against human bone AP. The intra- and inter-assay CVs were 4.0-8.3% and 6.2-7.9%, respectively. RESULTS: The percentage mean increase of bAP (54.9%) in post-menopausal subjects over premenopausal subjects was higher than that of tAP (40.1%). In age-matched comparison, % mean increases were 57.5% for bAP and 35.3% for tAP. Z-score for bAP in post-menopausal subjects was significantly higher than that for tAP. However, there was no significant difference in Z-scores between tAP and bAP in osteoporotic patients with vertebral fractures or with hip fracture. The correlation coefficient of bAP with age (r = 0.316) was similar to that of tAP with age (r = 0.319). In post-menopausal subjects, there was no difference in the concentrations of tAP nor bAP among the groups in whom times since the menopause was 0-9 years, 10-19 years and more than 20 years. Bone AP was highly correlated to tAP in the normal subjects, the patients and the total study group. CONCLUSION: Preference can be given to bone AP by enzymatic immunoassay over total AP based on their clinical utility during the menopause; however, no preference can be given to bone AP over total AP in established osteoporosis.

Adult↗

Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis.

Pentosidine is one of the advanced glycation end-products and is formed by glycosylation and oxidation. The aim of this study is to investigate the relationship between serum and urinary pentosidine levels and the activity of rheumatoid arthritis (RA). Using HPLC with column switching, we measured pentosidine in serum and urine from 77 patients with RA and 62 normal control subjects. The clinical features, blood biochemistry and activity of inflammation were examined in RA patients. Serum and urinary pentosidine in RA were significantly higher than in controls. Pentosidine significantly correlated with age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor, joint score and Lansbury Index in RA. The levels of pentosidine were higher in patients with active RA than in those with inactive RA. Serum and urine levels of pentosidine correlated with the activity of RA, and serum and urinary pentosidine may be a significant and novel marker for evaluating the disease status and the activity of RA.

Adult↗

Neuropathic arthropathy caused by paraneoplastic sensory neuropathy. A case report.

Neuropathic arthropathy of both knees after paraneoplastic sensory neuropathy developed in a 64-year-old woman. The patient was found to have small cell lung cancer 2 months after the onset of a sensory neuropathy that was diagnosed as paraneoplastic sensory neuropathy, a nonmetastatic neurologic complication in patients with malignancy. The onset of paraneoplastic sensory neuropathy was followed by the gradual onset of neuropathic arthropathy. This is the first well documented report on neuropathic arthropathy in a patient with paraneoplastic sensory neuropathy.

Carcinoma, Small Cell↗

Effect of thyroid hormone on bone and mineral metabolism in rat: evaluation by biochemical markers.

We evaluated the effects of the thyroid hormone on bone and mineral metabolism in rats using biochemical markers [pyridinoline (Pyr), deoxypyridinoline (Dpyr), Osteocalcin (OC), alkaline phosphatase (Alp)] and the measuring of bone mineral density (BMD). First, the rats were divided into three groups: 1) control group 2) The fifty micrograms group (T3-50) [It was given 50 micrograms/kg ip/day of triiod-l-thyronine (T3) for 2 weeks.] 3)The hundred micrograms group (T3-100) [It was given 100 micrograms/kg ip/day of T3 for 2 weeks.] Next, the rats were divided into two groups: 1)control group and 2)T3 group. The latter was given 100 micrograms/kg of T3 ip/day for 4 weeks. In experiment 1, Pyr and Dpyr levels in the T3 groups were significantly higher or well tended to be higher than those in the control group. OC levels in the T3 groups were significantly higher than in the control group until day 7. The Z-score of Pyr and Dpyr in T3-100 were two to thirteen times higher than those of OC and Alp. In experiment 2, Pyr and Dpyr levels in the T3 group were significantly higher or well tended to be higher than those in the control group. OC levels in the T3 group were significantly higher than those in the control group only on day 3. In the present study, the administering of T3 100 micrograms decreased both cortical (tibia) and trabecular (lumbar spine) BMDs in the rats. Bone resorption continued to increase after increased bone formation was reduced by T3 administration. Furthermore, bone resorption exceeded bone formation throughout T3 administration.

Alkaline Phosphatase↗

Short-term effect of parathyroidectomy on biochemical markers in primary and secondary hyperparathyroidism.

This study has been carried out in order to evaluate several bone metabolic markers after parathyroidectomy in patients with primary hyperparathyroidism (PHP) and secondary hyperparathyroidism (SHP). The subjects studied were 6 patients with PHP (5 females, 1 male, aged 64-83 years) and 5 patients with SHP on chronic maintenance hemodialysis with skeletal symptoms (2 females, 3 males, aged 57-67 years). In PHP, serum alkaline phosphatase (ALP) and procollagen type I carboxy-terminal propeptides (PICP) levels showed a trend to increase gradually after parathyroidectomy, changes which were statistically significant (ALP, p = 0.0375; PICP, p = 0.0006). The serum bone Gla protein (BGP) level showed no significant change throughout the pre- and postoperative periods (p = 0.7512). Urinary pyridinoline (Pyr.) and deoxypyridinoline (DPyr.) levels showed rapid decreases after parathyroidectomy (Pyr.; p = 0.0014, DPyr., p = 0.0087). In SHP, individual values of serum ALP in 3 patients with complete parathyroid resection and 1 patient with incomplete parathyroid resection showed a tendency to increase. Individual values of serum BGP and PICP increased after parathyroidectomy in 3 patients with complete parathyroid resection but not in the 2 patients with incomplete parathyroid resection. Individual values of the serum carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) level showed no certain trend. The results obtained after surgery indicate that there is a positive uncoupling of the two processes of bone remodeling, and serum PICP and urinary pyridinium cross-links are good specific markers for the evaluation of potential recovery of bone damage after parathyroidectomy.

Aged↗

Structural characterization of a novel glycoinositolphospholipid from the parasitic nematode, Ascaris suum.

A novel glycosphingolipid containing inositol phosphate as an acidic group has been demonstrated in whole tissues of the porcine roundworm, Ascaris suum. The thin layer chromatographic pattern of the total acidic glycolipid revealed the presence of several components, of which a major component (named AGL) with positive reactions toward both orcinol-sulfuric acid (sugar) and molybdate (phosphate) spray reagents was isolated and purified by the use of successive column chromatography on DEAE-Sephadex and silicic acid (latrobeads). From structural studies including compositional sugar analysis, hydrogen fluoride degradation, methylation analysis, periodate oxidation, proton magnetic resonance spectroscopy and fast atom bombardment mass spectrometry, the structure of AGL was deduced to be Gal alpha 1-2Ins(1-->)-P-Cer. Aliphatic constituents were lignoceric acid and its 2-hydroxy homologue as the principal fatty acids, and octadecasphinganine and branched heptadecasphinganine as the major sphingoids.

Animals↗

Effect of physical activity as a caddie on ultrasound measurements of the Os calcis: a cross-sectional comparison.

This cross-sectional study investigated the effect of long-term activity as a caddie on ultrasonic properties of the os calcis. We measured 74 healthy women, age 20-59 years, who worked at a golf course as caddies. An age-matched control group of 433 healthy women, who were office workers or housewives, also were recruited for comparison. The ultrasound measurements were performed with an Achilles ultrasound densitometer. The quadriceps muscle strength and the hand grip strength were measured in a perimenopausal subgroup (45-59 years) of the caddies and a subgroup of controls matched for age, height, weight, and body mass index. Urinary pyridinoline and deoxypyridinoline were also measured in these perimenopausal subgroups. Caddies had significantly higher ultrasound values than controls in the 40-49 (stiffness index, 101.6 +/- 12.9% versus 87.9 +/- 11.9%; p < 0.0001) and 50-59 (stiffness index, 90.5 +/- 11.6% versus 77.2 +/- 11.6%; p < 0.0001) age-stratified groups. Quadriceps strength and grip strength were significantly higher in caddies than those in controls. In postmenopausal caddies, all ultrasound values were significantly higher than for controls. In caddies there were not significant decreases of any ultrasound values with postmenopausal age. Even for the subgroup within 3 years of menopause there were significant differences between caddies and controls (p < 0.01). There were no significant increases of pyridinoline and deoxypyridinoline after menopause in the caddies. We demonstrated that the caddies had higher ultrasound properties of the os calcis and lower bone resorption after menopause compared with controls.

Adult↗

The effect of cyclosporin A administration on bone metabolism in the rat evaluated by biochemical markers.

We investigated the effects of cyclosporin A (CsA), an immunosuppressive agent, on bone remodeling in 6 rats compared to 6 controls, using a histomorphometric technique and biochemical markers for bone metabolism. With an oral daily dose of 15 mg CsA/kg of body weight for 28 days, the trabecular bone volume in CsA administered rats was significantly lower than that in control rats, which indicates bone loss in CsA rats. In CsA rats, bone resorption increased, and urinary pyridinoline (Pyr) significantly increased on day 28 compared with control rats. In contrast, bone formation assessed by serum osteocalcin and osteoid volume had no remarkable changes. These results suggest that administration of CsA for 28 days induces bone loss due to uncoupling between bone resorption and bone formation.

Administration, Oral↗

The influence of aortic calcification on spinal bone mineral density in vitro.

We examined the influence of aortic calcification on the spine phantom bone mineral density (BMD). Soft X-ray photographs of human aortae were taken to calculate the percent calcification of aortic tissues. Human aorta laid on lumber spine phantom was placed in the bottom of 15 cm of water and BMD and bone mineral content (BMC) were measured in the anteroposterior view. Samples with severe aortic calcification (over 30%) caused a 2.5% increase of BMD. There might be a relatively small influence of aortic calcification on the value of L2-L4 BMD, but changes over time in a patient could falsely elevate values.

Absorptiometry, Photon↗

The effect of tamoxifen on bone metabolism and skeletal growth is different in ovariectomized and intact rats.

The effects of tamoxifen (TAM) treatment on bone metabolism and skeletal growth were studied in sexually mature intact or ovariectomized (OVX) rats. Experiment 1 was designed to observe the effects of TAM on bone metabolism and skeletal growth in intact rats and included two groups: (1) intact plus vehicle and (2) intact plus TAM. Experiment 2 was designed to investigate the effects of TAM on OVX rats and included the other two groups: (3) OVX plus vehicle and (4) OVX plus TAM. Serum calcium osteocalcin and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured serially before and after TAM treatment for 6 weeks in order to monitor bone turnover. Bone mineral density (BMD) and bone mineral content (BMC) of excised right femora and lumbar vertebrae were determined by dual energy X-ray absorptiometry (DXA). To examine the effect of TAM on skeletal growth, the conventional parameters of femora and the histology of right tibiae were also measured. TAM did not induce significant change in the biochemical markers in intact rats during the 6-week experiment. Bone mass and skeletal growth were not changed by TAM treatment in intact rats. However, TAM treatment reduced the increase in serum osteocalcin and urinary pyridinium cross-links from 1 week to 6 weeks postovariectomy in the OVX rats. TAM inhibited the skeletal growth in OVX rats, because TAM treatment shortened femoral length and decreased the cell number in the growth plate in OVX rats in this study. Our findings indicate that TAM exerts an effect of estrogen agonist on bone metabolism and skeletal growth in OVX rats, however, it does not affect them in intact rats.

Animals↗

Concentrations of pyridinoline and deoxypyridinoline in joint tissues from patients with osteoarthritis or rheumatoid arthritis.

OBJECTIVE: To assess the usefulness of pyridinoline (Pyr) and deoxypyridinoline (Dpyr), intermolecular crosslinks of collagen, as markers in the evaluation of arthritis, by studying their distribution in tissues from knee joints. METHODS: Joint tissues (cartilage, bone, synovium) were obtained during operation from 10 patients with osteoarthritis (OA) and 10 patients with rheumatoid arthritis (RA). Synovium was also obtained from 10 non-arthritic (NA) subjects. Hydroxyproline was measured in hydrolysed tissue samples and converted to an equivalent collagen content. The amounts of Pyr and Dpyr crosslinks measured in the hydrolysed samples using a fluorescence technique were expressed as mumol/mol of collagen. RESULTS: Pyr and Dpyr were distributed in all three tissues, but in different amounts. The ratio of the contents of Pyr and (Pyr:Dpyr) was 50:1 in cartilage, 3:1 in bone, and 25:1 in synovium. OA cartilage had a greater Dpyr content than the RA cartilage, but there was no other significant difference in the contents of Pyr and Dpyr and the ratio Pyr:Dpyr in the joint tissues from patients with OA or RA. In synovium, there was no significant difference between the contents of Pyr and Dpyr and the Pyr:Dpyr ratio among OA, RA, and NA tissues. CONCLUSION: Both Pyr and Dpyr were located in cartilage, bone, and synovium. A significant amount of Pyr and Dpyr in these joint tissues, especially in synovium, may contribute to the urinary excretion of those crosslinks that is observed in arthritis.

Adolescent↗

Analysis of urinary pyridinoline and deoxypyridinoline in patients undergoing long-term anticonvulsant drug therapy.

Urinary pyridinoline and deoxypyridinoline were analyzed in 23 patients undergoing long-term anticonvulsant drug therapy and compared with those in an age-matched control group, which consisted of 218 healthy premenopausal women. Values of urinary pyridinoline and deoxypyridinoline in the patient group were significantly higher than those in the control group. However, mean serum levels of alkaline phosphatase in the patient group were within the control range. Our data demonstrate that bone resorption is accelerated by long-term anticonvulsant drug therapy and there may be an imbalance between bone resorption and bone formation in the patient group.

Adult↗

Effects of 2 years' treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study.

A two-year double-blind study monitored and evaluated the effects of 1 alpha-hydroxy vitamin D3 (1 alpha(OH)D3) on the lumbar (L2-4BMD) and total body bone mineral densities (TBBMD) and occurrence of fracture in 113 female osteoporotic patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 (n = 57) or a placebo (n = 56) with calcium supplementation in both groups. L2-4BMD increased 1.81.% and 2.32% after one and 2 years in the 1 alpha (OH)D3 group, but decreased 1.89% (P < 0.05) and 0.28% in the placebo group. A significant difference (P < 0.01) existed between the two groups after one year. TBBMD decreased significantly in the placebo group by 3.34% (P < 0.01) and 3.52% after one and 2 years. Six new fractures occurred in the control group, but only two in the 1 alpha(OH)D3 group (Odd's ratio = 0.343, 95% confidence range; 0.0648-1.815). There were no serious adverse effects of the 1 alpha(OH)D3 treatment. It was concluded that two-year treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease in TBBMD. Although it was not significant, new fracture occurrence in the 1 alpha(OH)D3 group was around 1/3 of that in the control group.

Alkaline Phosphatase↗

Direct quantification of pentosidine in urine and serum by HPLC with column switching.

Concentrations of pentosidine, an advanced glycation end product, are increased in aging, diabetes mellitus, and uremia. Using HPLC with column switching, we developed a direct method of measuring pentosidine in urine and serum. We inject the sample directly onto a gel-filtration precolumn, select ("heart-cut") the eluate fraction containing pentosidine, and introduce this fraction into a reversed-phased column by use of a switching valve. The recovery rate of the complete method was 97.7-99.9%. The intraassay CV was 5.7%, and the interassay CV was 5.8%. The calibration curve showed significant linearity (r = 0.998, P = 0.0001). We examined urinary concentrations of pentosidine in 12 diabetic patients (mean +/- SD, 8.7 +/- 2.3 micromol/mol of creatinine), 32 patients with chronic renal failure (CRF; 36.1 +/- 39.0), 19 osteoporotic patients (7.9 +/- 5.3), and 29 healthy control subjects (5.2 +/- 2.3). In CRF, urinary pentosidine in the patients undergoing hemodialysis was significantly higher than in CRF patients not being treated by hemodialysis (mean, 58.1 vs 18.2; P <0.001). Also, concentrations of urinary and serum pentosidine were significantly correlated (r = 0.797, P = 0.0011). Because this method does not require pretreatment of samples, it is convenient and useful for measuring urinary and serum pentosidine.

Adult↗

Direct measurement of crosslinks, pyridinoline, deoxypyridinoline, and pentosidine, in the hydrolysate of tissues using high-performance liquid chromatography.

Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are mature crosslinks which maintain the structure of the collagen fibril. Pentosidine (Pen) is a senescent crosslink and one of the advanced glycation end products. We developed a direct and one-injection method to measure Pyr, Dpyr, and Pen in the hydrolysate of tissues using reversed-phase high-performance liquid chromatography. Using a linear gradient of acetonitrile and a cleaning step, the objective crosslinks were well separated and continuously and automatically assayed. Recovery rates of Pyr, Dpyr, and Pen were 95-116, 94-110, and 92-120%, respectively (n = 5). The intraassay coefficients of variation for Pyr, Dpyr, and Pen were 5.3, 5.8, and 4.3%, respectively (n = 5), and the interassay coefficients of variation for Pyr, Dpyr, and Pen were 3.5, 4.6, and 5.7%, respectively (n = 5). Linear regression analysis showed the linearity (r = 0.999) of calibration line for each Pyr, Dpyr, and Pen. We measured the content of these crosslinks in the tissues from the young and old subjects. There was no difference in the content of Pyr and Dpyr between the young and the old group. On the other hand, the content of Pen in the old group was extremely higher than that in the young group. We demonstrated the direct method for measuring two kinds of major crosslinks which have different characters and believe that this method will be useful in determining the content of these crosslinks in tissues under various conditions.

Adolescent↗