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Biomedical subjects

K Kushida

Publications and source records attributed to K Kushida.

At least 109 records · Page 6Linked to original sources
PubMed1995

Quantitation of the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta with dystrophic calcification.

Pyridinoline and, its minor analogue deoxypyridinoline, are trifunctional crosslinks of mature collagen in the connective tissues. Pentosidine, a new type of fluorescent crosslink, is possibly one of the senescent crosslinks but its function and metabolism are still unclear. In this study, we quantitated the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta which were obtained from 21 autopsy cases. In each case, the existence of dystrophic calcification in the aorta and complications (diabetes, chronic renal failure and hypertension) were examined. The determination of the content of the three crosslinks was carried out using high performance liquid chromatography (HPLC) analysis. In calcified lesions, the amount of deoxypyridinoline/collagen showed a decrease and the amount of deoxypyridinoline/pyridinoline showed a prominent decrease compared to those in non-calcified lesions (deoxypyridinoline/collagen, P < 0.005; deoxypyridinoline/pyridinoline, P < 0.0001). In non-calcified lesions without complications, the amount of pentosidine/pyridinoline and that of pentosidine/deoxypyridinoline significantly increased with age (pentosidine/pyridinoline, r = 0.704, P < 0.05; pentosidine/deoxypyridinoline, r = 0.624, P < 0.05). This result suggests a possible relationship between dystrophic calcification and crosslink formation of collagen in human aorta.

Age Factors↗
PubMed1995

Assessment of spine bone mineral density in ovariectomized rats using DXA.

Measurements of lumbar spine (L1-L6) bone mineral density (BMD) and bone mineral content (BMC) of Wistar rats were obtained by dual energy X-ray absorptiometry (DXA) (QDR-1000W, Hologic Inc., Waltham, MA) to estimate reproducibility and investigate age-related changes. In addition we evaluated the accuracy of the technique in female rats. The coefficients of variation (CV) for spine BMD measurements were found to range from 0.73-1.04 in vivo and from 0.36-1.56 in vitro. The in vitro measurements were performed in a 3 cm deep water bath to stimulate an equivalent tissue thickness. Spine BMC, measured in vivo and in vitro correlated closely with the subsequently determined ash weights (r2 = 0.87 and 0.97, respectively). We examined age-related spine BMD by DXA. A relatively constant increase in spine BMD was observed from 6 weeks to 22 weeks; spine BMD remained stable between 22 and 58 weeks. No peak was observed in spine BMD. To evaluate the effect of estrogen deficiency on animals of different ages, we measured spine BMD weekly in female rats subjected to ovariectomy (OVX) or sham operation at 8 and 23 weeks of age. The spine BMDs in each OVX rat were significantly lower than that of the controls. In the 23-week-old rats, bone loss was quite rapid for the first 3 weeks of observation and stable afterward. The BMD of 8-week-old OVX rats increased with body size. We conclude that DXA allows the observation of age-related changes in the spine BMD of rats with great precision.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients.

Recently, the biochemical markers for bone metabolism have been developed and are expected to reflect the minor change of bone turnover. We compared bone formation markers: alkaline phosphatase-(Alp), bone gla-protein(BGP), carboxy-terminal propeptide of type I collagen(PICP); and bone resorption markers: carboxy-terminal telopeptide of type I collagen(ICTP), pyridinoline(Pyr), deoxypyridinoline(Dpyr) to see if they reflected the effects of aging and menopause in 95 premenopausal and 66 postmenopausal healthy subjects. We also compared the bone turnover in 29 vertebral osteoporosis patients. All markers except ICTP significantly increased with age in the healthy subjects. Alp, BGP, PICP, Pyr, and Dpyr were significantly higher in the postmenopausal group than in the premenopausal group. BGP, Pyr, and Dpyr in premenopausal subjects in their 50s were already significantly increased compared with BGP, Pyr, and Dpyr in premenopausal subjects in their 30s and 40s. To evaluate the discrimination power of the six markers in the postmenopausal subjects and in patients with osteoporosis, the z scores of six markers were calculated against the premenopausal group. z-scores of bone resorption markers(ICTP, Pyr, and Dpyr) were much higher than those of bone formation markers (Alp, BGP, and PICP) in patients with osteoporosis, even though z-scores of bone resorption markers were similar to those of bone formation markers in postmenopausal subjects. In conclusion, Alp, BGP, PICP, Pyr, and Dpyr had good performance in postmenopausal status. Resorption markers increased more than formation markers in osteoporosis subjects, and the bone turnover in osteoporosis subjects was more uncoupled than in postmenopausal subjects.

Adult↗
PubMed1995

Plasma pentosidine levels in uremic patients before and after hemodialysis.

Pentosidine, a fluorescent cross-link, is one of the advanced glycosylation end-products. It accumulates in human tissues, plasma and urine in diabetic and uremic patients. Using SP-Sephadex C-25 in the pretreatment for reversed-phase HPLC, we determined pentosidine levels in plasma before and after hemodialysis using cuprophane membranes from 18 patients (9 diabetic, 9 nondiabetic) with end-stage renal disease, as well as examined the hemodialysis efficiency of plasma pentosidine. We also measured beta 2-microglobulin levels in plasma before and after hemodialysis. The values of plasma pentosidine did not significantly change after hemodialysis. Also, plasma beta 2-microglobulin was not removed by hemodialysis. Hemodialysis efficiency of plasma pentosidine and beta 2-microglobulin was nil. In addition, there was a significant correlation between plasma levels of pentosidine and beta 2-microglobulin before hemodialysis in 116 uremic patients. The results indicated that hemodialysis could not eliminate pentosidine from plasma; therefore, pentosidine retention by the diseased kidney might be a major cause of elevated levels of pentosidine with uremia.

Arginine↗
PubMed1995

Analysis of junctional sequences of T cell receptor gamma chain transcripts in gamma delta T cells from rheumatoid synovial fluid.

OBJECTIVE: We previously reported the predominance of the V gamma 3 gene in synovial fluid mononuclear cells (SFMC) from patients with rheumatoid arthritis (RA); the V gamma 3 gene is rare in normal peripheral blood mononuclear cells (PBMC). Our objective was to sequence the nucleotide composition of the junctional region of gamma chain transcripts expressed in gamma delta T cells from RA SFMC and normal PBMC. METHODS: cDNA from RA SFMC and normal PBMC were amplified by polymerase chain reaction, and the nucleotide sequences of amplified clones were determined. We compared the frequencies of V gamma-J gamma rearrangements in inframe (functional) and out of frame (nonfunctional) V gamma transcripts to determine the effect of intrinsic gene rearrangement on the expressed repertoire. RESULTS: Most V gamma genes, including V gamma 9, both inframe and out of frame, were rearranged to the J1/J2 genes, indicating that the intrinsic rearrangement may be influential in molding the mature functional gamma delta T cell repertoire. V gamma 9 transcripts in RA SFMC predominantly used J1/J2, as opposed to JP in normal PBMC. Most N regions displayed extensive diversity in both RA SFMC and normal PBMC, but some functional V gamma 9 transcripts of RA SFMC from one patient showed an identical junctional sequence, and 2 functional clones from different RA SFMC showed an identical junctional sequence, implying that the V gamma 9-J1/J2 transcripts could be controlled by antigenic selection. CONCLUSION: These results demonstrate that the prominent occurrence of the J1/J2 genes in all V gamma genes and the oligoclonality of functional V gamma 9 transcripts, in addition to the predominance of the V gamma 3 gene, are striking features of gamma chain transcripts in RA SFMC:

Aged↗
PubMed1994

Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders.

OBJECTIVE: To determine the content of two crosslinks, pyridinoline (a mature crosslink) and pentosidine (a senescent crosslink), in human articular cartilage, and to examine the effect of bone and joint disorders on the content of those crosslinks in articular cartilage. METHODS: After pretreatment with SP-Sephadex C-25, high-performance liquid chromatography was conducted on a hydrolysate of human articular cartilage from 53 patients with one of the following diseases: osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, femoral head necrosis, and renal osteodystrophy (ROD). RESULTS: Pyridinoline levels were either unchanged with age or were slightly decreased in elderly patients. Pentosidine levels increased with age in the entire patient population. There was no significant difference in the pyridinoline content among the study groups, but there was a significant difference in pentosidine content (P < 0.001). ROD patients had the highest mean level of pentosidine (407 mumoles/mole of hydroxyproline), and RA patients had a higher mean level than age-matched OA patients (214 versus 103 mumoles/mole of hydroxyproline). CONCLUSION: Bone and joint disorders do not affect the pyridinoline content in articular cartilage, but they do not affect the pentosidine content.

Adult↗
PubMed1994

The effect of menopause on biochemical markers and ultrasound densitometry in healthy females.

Urinary pyridinoline (pyr) and deoxypyridinoline (dpyr) are new markers for bone resorption, and serum osteocalcin reportedly indicates osteoblastic activity. Recently, a new ultrasound bone densitometer instrument has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index. The effects of menopause on biochemical markers and ultrasound densitometry were investigated in 40 healthy females, 36-39 years, with regular menstruation, and in 117 healthy perimenopausal females, 47-57 years, who were divided into a premenopausal group and a postmenopausal group. Significantly elevated values of pyr, dpyr, and serum osteocalcin were found for the postmenopausal group as a whole compared with the premenopausal group. We examined postmenopausal groups 48-57 years of age stratified into 2-year intervals (within 2 years of the menopause, 2-4 years postmenopause and 4-6 years postmenopause). Elevated values of urinary pyr, dpyr, and serum osteocalcin were evident even in the first 2 years postmenopause compared with the premenopausal group, and these higher values were exhibited until 6 years after menopause. We found a significant decrease in SOS, BUA, and stiffness index of the postmenopausal group as a whole, compared with those of the premenopausal group. SOS, BUA, and stiffness index of the group within 2 years of menopause significantly decreased compared with those of the premenopausal group. The Z-scores of the increase in biochemical markers and the decrease in stiffness index in the postmenopausal group were approximately 0.7-1.3 compared with the premenopausal group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Metacarpal bone mass in normal and osteoporotic Japanese women using computed X-ray densitometry.

The metacarpal bone mineral density (BMD) and metacarpal index (MCI) of the second metacarpal bone were measured by computed X-ray densitometry (CXD) (Teijin Ltd., Tokyo), which we have established with the development of microdensitometry of radiographs. In this study, we evaluated the basic attributes of this CXD method and determined the age-related changes in both metacarpal measurements in normal Japanese women. The precision in vivo was measured in eight subjects. The precision errors [coefficient of variation (CV)] were 0.2-1.2% CV for metacarpal BMD and 0.4-2.0% CV for MCI, respectively. We have obtained low precision error and more rapid analysis, within 3 minutes respectively, compared with the previous methods. Age-related changes in the metacarpal measurements were evaluated in 1438 normal women. Both measurements showed the most significant decrease in the sixth decade of life. The rate of decrease in the sixth decade was 1.6%/year for metacarpal BMD and 1.5%/year for MCI. On comparison between metacarpal BMD by CXD and spine BMD using dual energy X-ray absorptiometry (DXA) in 248 normal women with and without menstruation, the two measurements were found to be similarly decreased in the subjects within 5 years after menopause. There was also no significant difference in the Z-score between metacarpal BMD and spine BMD within 5 years after menopause. These results indicate that early postmenopausal bone loss occurs not only in the spine but also in the metacarpal bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Ultrasound bone densitometry of the os calcis in Japanese women.

The velocity (SOS), attenuation slope (BUA) and stiffness index in the os calcis were measured using the 'Achilles' ultrasound bone densitometer (Lunar, Madison, WI). We evaluated the basic attributes of this ultrasound bone densitometer, and showed the age-related changes in ultrasound values in normal Japanese women. The precision was measured in vivo on ten occasions over a 2-week period in 5 subjects. The short-term precision errors (CVs) in vivo were 0.6% for stiffness index, 0.3% for SOS and 1.0% for BUA. Spine, femur neck and total body BMD using dual X-ray absorptiometry (DXA) were highly correlated with stiffness index (r = 0.80, 0.77 and 0.78, respectively) in 194 subjects. Ultrasound values for patients with osteoporosis were significantly lower than those for the normal controls. The Z-score compared with young normals was significantly higher for spine bone mineral density (-4.4) than for stiffness index (-3.5); BUA and SOS gave significantly lower Z-scores -2.9 and -3.0, respectively). Ultrasound values were also lower compared with age-matched normal controls. The Z-score for stiffness index (-2.1) was significantly superior to that for either SOS or BUA (-1.5). Age-related change in ultrasound values was evaluated in 842 normal women. There was a decline in stiffness index of about 24% from the values in young adulthood to those of women in their seventies, about 75% of which occurred from age 44-49 years onward. These findings seem to indicate that the menopause affected the change in ultrasound values.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Urinary pyridinoline and deoxypyridinoline in prostate carcinoma patients with bone metastasis.

Bone metastases from prostate carcinoma are predominantly osteoblastic. Recently, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been employed as indicators of bone resorption. In this study, we evaluated urinary Pyr and Dpyr levels in 19 prostate carcinoma patients, of whom 12 had bone metastasis and seven had not, and 11 age-matched control subjects. There was a significant difference in Pyr levels between the control group and the patients with metastasis (mean +/- s.d., 19.5 +/- 7.2 vs 73.3 +/- 67.1 nmol mmol-1 creatinine, P < 0.05). The mean level of Dpyr in the patients with metastasis (10.8 +/- 8.0 nmol mmol-1 creatinine) was significantly higher than that in the control group (3.1 +/- 2.1 nmol mmol-1 creatinine, P < 0.01), and also higher than that in the patients without metastasis (3.5 +/- 1.9 nmol mmol-1 creatinine, P < 0.05). There was no significant difference in Pyr and Dpyr levels between the control group and the patients without metastasis. These results suggest that bone resorption is also accelerated in prostate carcinoma patients with bone metastasis.

Aged↗
PubMed1994

Cross-reactivity and neutralizing ability of monoclonal antibodies against microcystins.

Monoclonal antibodies (MAbs) against the microcystin-leucine-arginine variant (MCYST-LR), a cyclic peptide toxin of the freshwater cyanobacterium Microcystis aeruginosa, were prepared from cloned hybridoma cell lines. The specificity of the MAbs and their ability to neutralize the toxin were investigated by an indirect enzyme-linked immunosorbent assay (ELISA) and by a neutralizing test in mice, respectively. All MAbs reacted with MCYST-LR and also with the microcystin-arginine-arginine variant (MCYST-RR), 3,7-didesmethylmicrocystin (MCYST-3, 7-dDMLR) and 7-desmethylmicrocystin (MCYST-7-DMLR). Furthermore, the antibodies reacted with cell-extracts of toxic and non-toxic M. aeruginosa strains. The MAbs can apparently recognize the common configuration, but not the variant-specific structure, in the microcystin molecules. The non-toxic strains apparently contain some substance(s) related antigenically to microcystin. The in vivo toxin-neutralizing ability of MAbs was minimal.

Animals↗
PubMed1994

Proton magnetic resonance spectroscopy of cerebrospinal fluid as an aid in neurological diagnosis.

The proton magnetic resonance (1H-NMR) spectra were obtained from 38 cerebrospinal fluid (CSF) samples from 34 patients with various central nervous system (CNS) diseases and the H2O signals were reduced by the presaturation method. A doublet signal for CH3 protons of lactate, as well as a singlet one for alpha-CH proton of glucose, were clearly detected in all the spectra obtained. The relative lactate concentration values were calculated on the basis of the glucose concentrations which had been measured by a routine laboratory method in the hospital and the ratios of the peak heights (lactate CH3/glucose alpha-CH). In the CSF samples examined, the relative lactate values semi-quantitatively determined in this way were clearly elevated in cerebral infarction and bacterial meningitis, but not in other disorders including viral meningitis. On the other hand, one CSF component whose enhancement was found only in a sample from a hepatic encephalitis patient was identified as glutamine from the double quantum filtered-shift correlation spectrum. These results suggest that 1H-NMR spectroscopy of CSF can become a powerful aid in biochemical diagnosis of CNS diseases.

Adult↗
PubMed1994

Creatine kinase isoenzyme BB increased in serum and tumor tissue of patients with giant cell tumor of bone.

Increased creatine kinase isoenzyme BB (CK-BB) has been observed in sera from patients with brain injuries and occasionally in sera from patients with malignancy. We report here that, in two patients with giant cell tumor of bone (GCT), preoperative serum CK-BB increased to approximately 20 and 90 U/L, but in postoperative serum the CK-BB decreased to normal values. That the tumors contained CK-BB was indicated by electrophoretic analysis and immunohistochemical staining. Furthermore, serum CK-BB was detectable in five additional cases of GCT and in cultured tumor cells from a patient with GCT by an electrophoretic method. These results suggest that CK-BB may be a marker for GCT.

Adult↗
PubMed1994

[Pharmacologic therapy of osteoporosis].

This paper reviews the pharmacologic therapies for the prevention and the treatment of osteoporosis. Vitamin D metabolites, estrogen, estrogen-progestin, calcitonin and ipriflavone are effective regimens for the prevention of bone loss and the treatment of osteoporosis. Since estrogen deficiency is the main cause for postmenopausal osteoporosis, estrogen supplementation is the most effective therapy for postmenopausal osteoporosis. Estrogen progestin combination therapy is one of the most potent therapies to increase both cortical and trabecular bone mass. Vitamin D has efficacy on increasing intestinal calcium absorption and decreasing fracture rate in osteoporotic patients. Calcitonin inhibits osteoclastic bone resorption and also has inherent analgesic properties. Several studies have suggested that new delivery systems of estrogen (transdermal) and calcitonin (transnasal) are effective in osteoporosis. Recent studies revealed that bisphosphonate and hPTH (1-34) were new potent agents for the treatment of osteoporosis. Bisphosphonate would be effective to osteoporosis by reducing bone resorption. hPTH may have a primary action to increase bone formation. Treated patients should be monitored using bone mineral density and biochemical markers for evaluating the response to therapy.

Bone Density↗
PubMed1993

Bone density and body composition on the Pacific rim: a comparison between Japan-born and U.S.-born Japanese-American women.

Bone mineral density (BMD) of total body, spine, and proximal femur and the percentage of body fat in 151 U.S.-born Japanese-American women and 137 Japan-born immigrant Japanese-American women living in San Diego, California were measured using dual-energy x-ray absorptiometry. These data were compared with unpublished data from Japanese women obtained in previous studies in Hamamatsu, Japan. The age-adjusted BMD for the spinal level, femoral neck, Ward's triangle, trochanter, and total body, respectively, of U.S.-born Japanese-American women were 10.2, 9.8, 9.9, 9.2, and 2.7% higher than those of native Japanese women. The U.S.-born Japanese-American women had significantly higher body fat than immigrant Japanese-American women. Furthermore, the immigrant women had higher BMD and higher body fat than their native Japanese counterparts; however, no significant total-body BMD differences were found among the three groups after age, height, and weight were adjusted. The U.S.-born Japanese-American women had BMD values equivalent to those of white normals at the spine and femur. Significant life-style differences between U.S.-born and immigrant Japanese-American women were noted. Weight, exercise, early menarche, and years of lifetime estrogen exposure correlated positively with BMD. The significant negative correlates of BMD were age, smoking, and percentage of body fat. Our study presents data suggesting that immigration to the United States has produced a higher BMD in Japanese-American women that is attributable to changes in life-style and diet.

Absorptiometry, Photon↗
PubMed1993

The Maillard protein cross-link pentosidine in urine from diabetic patients.

The Maillard protein cross-link pentosidine is a fluorescent condensation product of lysine, arginine and ribose. It accumulates in human tissues with age, and the accumulation process is accelerated in the tissues of diabetic patients. Using SP-Sephadex C-25 in the pretreatment for HPLC, we examined levels of pentosidine in urine without hydrolysis (free form) and levels of pentosidine in urine after hydrolysis (total forms), from 23 diabetic patients and 21 control subjects. The mean percentages of the values of free form per total forms (+/- SD) were 89 +/- 15% in diabetic patients, 88 +/- 16% in control subjects and 89 +/- 15% in total populations of diabetic patients and control subjects. There was a significant correlation between the values of free form and total forms in diabetic patients (r = 0.983, p = 0.0001), in control subjects (r = 0.820, p < 0.02) and in total populations of diabetic patients and control subjects (r = 0.951, p = 0.0001). The mean level of pentosidine per mol creatinine (+/- SD) was significantly elevated in urine from diabetic patients as compared to the level in control subjects (8.8 +/- 4.3 mumol/mol creatinine vs 4.2 +/- 1.4 mumol/mol creatinine, p = 0.0001 in free form; 10.1 +/- 5.3 mumol/mol creatinine vs 4.7 +/- 1.4 mumol/mol creatinine, p = 0.0001 in total forms). These results demonstrate that urinary pentosidine, especially in free form, could be a useful marker for the assessment of diabetes and diabetic complications.

Aged↗
PubMed1993

Exercise therapy for osteoporosis.

Our experimental and clinical studies lead to the following conclusions: 1. The amount of exercise that has a favorable effect on bone tissue differs between males and females among individuals. 2. An appropriate amount of exercise has a favorable influence not only on weight-bearing bone but also on non-weight-bearing bone, provided there is a sufficient intake of calcium. 3. Exercise may prevent the bone loss in osteoporosis, but an increase in bone mass cannot be expected. The major aim is to increase bone mass before the achievement of peak bone mass in order to prevent osteoporosis. However, suitable weight-bearing exercise in osteoporosis is useful for the prevention of falls which may result in fractures, to increase muscle strength, to improve walking balance and coordination, and to prevent orthostatic hypotension.

Adult↗