Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling.

Reproductive management is necessary to prevent deleterious genetic disorders in purebred dogs, but comprehensive studies aimed at prevention of multiple underlying genetic disorders in a single breed have not been performed. The aims of this study were to examine mutant allele frequencies associated with multiple genetic disorders, using Border collies as a representative breed, and to make recommendations for prevention of the disorders. Genotyping of known mutations associated with seven recessive genetic disorders was performed using PCR assays. More than half (56%) of the Border collies had no mutant alleles associated with any of the seven disorders, suggesting that these disorders can be removed from the population over several generations. Since frequencies of each mutant allele differed among disorders, reproductive management should be performed after the establishment of prevention schemes that are appropriate for each disorder, the type and specificity of genetic test available, and the effective population size in each breeding colony.

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.

Pilomatrix carcinoma of the axilla: CT and MRI features.

Pilomatrix carcinoma, a rare malignant soft tissue tumour, is the malignant variant of pilomatricoma. We report a case of pilomatrix carcinoma of the axilla. CT demonstrated a well-circumscribed, sand-like calcified mass. MRI showed diffusely inhomogeneous, mixed signal intensities with inhomogeneous enhancements. The MRI findings were different from those previously reported for pilomatricoma.

The preventive and interventional effects of raloxifene analog (LY117018 HCL) on osteopenia in ovariectomized rats.

The effects of LY117018 HCL (LY) treatment on bone metabolism, spine bone mineral density (BMD), bone mineral content (BMC), and serum cholesterol were studied in ovariectomized (OVX) rats. Experiment 1 was designed to observe the preventive effects of LY on bone loss due to ovariectomy (OVX; prevention study). The rats were divided into three groups: sham group, OVX + vehicle, and OVX + LY. LY was administrated at the same time of OVX. Experiment 2 was designed to investigate the interventional effects of LY on OVX rats with osteopenia (intervention study). The rats were divided into the sham and OVX groups, first. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into two groups: OVX + vehicle and OVX + LY. The longitudinal effects of LY on bone were studied by dual-energy X-ray absorptiometry and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. Urinary Pyr and Dpyr increased maximally at 6 weeks post-OVX, decreased at 12 and 18 weeks post-OVX, although the OVX rats had significantly higher levels of Pyr and Dpyr than the sham group during the experiment. LY was a very potent inhibitor of Pyr and Dpyr excretion while at the same time only partially reducing the bone loss in the high turnover phase at 6 weeks postovariectomy. However, at the later time points at 12 and 18 weeks, no further bone loss occurred in rats treated with LY, while the vehicle-treated group lost another 10% in spine BMD and BMC. LY also completely blocked further bone loss when used in an intervention protocol. LY significantly reduced serum cholesterol levels in OVX rats. The results suggest that LY is not fully protective during the early rapid bone loss phase, but the compound is fully protective during the later slow phase of bone loss in both the protocols.

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)

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.

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.

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.

Urinary bone resorption markers in patients with metabolic bone disorders.

Recently, urinary pyridinoline and deoxypyridinoline have been commonly employed as bone resorption markers. We studied these markers in 17 patients with hyperthyroidism, 15 undergoing long-term anticonvulsant drug therapy, and 28 with postmenopausal osteoporosis. Both markers had significantly higher levels than those in age-matched control groups. Values of urinary pyridinoline and deoxypyridinoline correlated well with urinary hydroxyproline levels in patients with hyperthyroidism (r = 0.856, p < 0.001 for pyridinoline and hydroxyproline; r = 0.919, p < 0.001 for deoxypyridinoline and hydroxyproline); however, poor correlations were observed, especially between urinary deoxypyridinoline and urinary hydroxyproline (r = 0.357, NS) in patients with postmenopausal osteoporosis. To compare the discriminatory ability of urinary pyridinoline and deoxypyridinoline, receiver operating characteristic (ROC) curves were generated for each of these patient groups using data from age-matched healthy females as the control group. The areas under the curves for both markers were 100.0% in hyperthyroidism. The areas under the curves for pyridinoline in patients undergoing long-term anticonvulsant drug therapy (mean +/- SE; 98.1 +/- 2.8%) and postmenopausal osteoporosis (77.9 +/- 5.7%) were significantly higher than those for deoxypyridinoline in anticonvulsant drug therapy (92.4 +/- 3.3%) and in osteoporosis (64.9 +/- 4.3%). Using data from premenopausal healthy females as the control group, areas under ROC curves for urinary pyridinoline (100.0%) and deoxypyridinoline (94.8 +/- 5.9%) were significantly higher than those for urinary hydroxyproline (73.8 +/- 9.4%) in patients undergoing long-term anticonvulsant drug therapy. In patients with postmenopausal osteoporosis, those for urinary pyridinoline (97.0 +/- 2.8%) were also significantly higher than those for urinary hydroxyproline (74.0 +/- 6.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian variation of urinary type I collagen crosslinked C-telopeptide and free and peptide-bound forms of pyridinium crosslinks.

This study was performed to investigate the circadian variation of urinary CrossLaps (CTx), which was the type I collagen peptide released during bone matrix degradation, and peptide-bound and free forms of urinary pyridinium crosslinks. Urine was obtained during the 24 h of the study in seven separate collections as follows: from 23:00 h to the first void (FV) followed by FV at 11:00, 11:00-14:00, 14:00-17:00, 17:00-20:00, 20:00-23:00, and 23:00 h to FV the next morning. Total, free, and peptide-bound pyridinoline (Pyr) and deoxypyridinoline (Dpyr) excretion measured by high-performance liquid chromatography (HPLC) and CTx measured by enzyme-linked immunosorbent assay in nine premenopausal women aged 22-40 years and nine osteoporotic women aged 65-83 years was analyzed. Among three parameters of Pyr measured by HPLC, a significant day and night difference was found only in total Pyr (21.9% higher at night than during the day in premenopausal women and 24.0% in osteoporotic women, whereas no significant day and night variation was found in free and peptide-bound Pyr in either group. In contrast, total and peptide-bound Dpyr were significantly (37.9% and 66.9%) higher at night than those during the day in premenopausal women (38.0%) and osteoporotic women (48.8%). For free Dpyr, there were no day and night differences in the two groups. The day and night variances were significantly greater in peptide-bound Dpyr than with total Dpyr in both groups. In urinary CTx, a significant circadian variation with a peak at night and a nadir at 17:00 h was found (p < 0.0001) (premenopausal was 54.0% higher at night than during the day; osteoporotic was 38.4%. In conclusion, urinary CTx represented remarkable circadian variation compared with urinary pyridinium crosslinks measured by HPLC. Furthermore, free pyridinium crosslinks did not undergo a circadian variation. Peptide-bound crosslinks might contribute mostly to the circadian variation of total excretion of pyridinium crosslinks.

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.

Risk factors for vertebral fractures in renal osteodystrophy.

We determined the prevalence of vertebral fractures in hemodialysis (HD) patients, investigated whether low bone mineral density (BMD) is predictive of vertebral fracture, and evaluated the effect of serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) levels on vertebral fracture. One hundred eighty-seven male HD patients were assessed for vertebral fractures, and lumbar-spine and total-body BMD were measured by dual-energy x-ray absorptiometory. Thirty-nine patients (20.9%) had vertebral fractures. Each standard deviation (SD) decrease in lumbar-spine BMD increased the age-adjusted odds ratio of vertebral fracture 2.0 times (95% confidence interval [CI], 1.4 to 2.0) and 1.6 times (95% CI, 1.1 to 1.6) for total-body BMD. The area under the receiver operating characteristic curve for lumbar-spine BMD was significantly greater than that for total-body BMD (P < 0.05). Patients with serum iPTH levels in the lowest tertile had a 2.4-fold greater risk for vertebral fracture than those in the middle tertile and a 1.6-fold greater risk than those in the highest tertile (P < 0.05). When the two criteria of lowest tertile of serum iPTH level and highest tertile of serum ALP level were combined, the prevalence of vertebral fractures was the greatest. Similarly, when the lowest tertile of serum iPTH level and lowest tertile of serum ALP level were combined, the prevalence was the second greatest among the combined groups according to tertiles of serum iPTH and ALP levels. We conclude that low lumbar-spine BMD might be a sensitive predictor of vertebral fracture in HD patients, and patients with relatively low iPTH levels would have a greater risk for vertebral fracture than those with hyperparathyroidism.

Fluorophores from aging human articular cartilage.

Human articular cartilages of various ages were digested with collagenase, and the fluorescence of the digests was measured as a function of age. At acidic pH, all collagenase-treated fractions were found to contain two main fluorophores with fluorescence maxima at 395 and 385 nm (excitation at 295 and 335 nm, respectively). Each fluorophore was isolated from the hydrolysate and its structure was deduced from spectral and chemical data. The 395/295 nm fluorophore was identified as pyridinoline, which is one of the non-reducible cross-linkages in collagen. The 385/335 nm fluorophore was identical to pentosidine, which was isolated from human dura mater and characterized by Sell and Monnier in 1989. Our results showed that the amount of pentosidine per collagen in human articular cartilage increases linearly with age (r = 0.929, p less than 0.005), while the amount of pyridinoline per collagen remained constant and was not correlated with age (r = 0.20). On the other hand, the amount of pentosidine per pyridinoline increased exponentially during life (r2 = 0.839, p less than 0.05).

Inhibition of nitric oxide formation and superoxide generation during reduction of LY83583 by neuronal nitric oxide synthase.

6-Anilino-5,8-quinolinedione (LY83583) has been widely used as an agent to reduce levels of nitric oxide (NO)-dependent cGMP in tissues. We report here that suppression of NO formation and production of superoxide during enzymatic reduction of LY83583 by neuronal NO synthase appeared to be potentially involved in the pharmacological action caused by LY83583. LY83583 suppressed neuronal NO synthase activity of 20,000 x g rat cerebellar supernatant preparation in a concentration-dependent manner (IC50 value = 12.9 microM). A kinetic study revealed that LY83583 is a competitive inhibitor with respect to NADPH, with a Ki value of 2.57 microM. With purified neuronal NO synthase it was found that LY83583 was a potent inhibitor of NO formation by the enzyme and served as efficient substrate for reduction with a specific activity of 173 nmol of NADPH oxidized per mg of protein per minute. The reductase activity was stimulated about 19.8-fold by addition of CaCl2/calmodulin, indicating that the presence of CaCl2/calmodulin is essential to express maximal activity of LY83583 reduction. Although LY83583 was a good substrate for both NADPH-cytochrome P450 reductase (P450 reductase) and DT-diaphorase, these flavin enzymes-catalyzed reductions of LY83583 were less than the neuronal NO synthase-mediated reduction in the presence of CaCl2/calmodulin. Enzymatic generation of superoxide during reduction of LY83583 by neuronal NO synthase, P450 reductase or DT-diaphorase was confirmed by electron spin resonance (ESR) experiments. Thus the present results indicate that a benzoquinone derivative LY83583 appears to interact with the P450 reductase domain on neuronal NO synthase, resulting in inhibition of NO formation and superoxide generation, which is involved in suppression of intracellular cGMP content.

Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures.

We have evaluated the effect of aging, menopause, and osteoporosis on the measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144 postmenopausal healthy women, 74 patients with vertebral fractures and 61 patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age-related changes of alpha-CTx in healthy females show that the values were extremely high before the age of 16 years and decreased between ages 16 and 29, and that after the age of 40 years, the values tended to increase and to vary widely with age. In menopause, alpha-CTx in postmenopausal subjects was significantly higher than those in premenopausal subjects. There was no significant correlation between alpha-CTx and years since menopause in 102 postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher than those in the postmenopause group, but not significantly. Alpha-CTx in the hip fracture group were significantly higher than those in postmenopause and vertebral fracture groups. In age-matched comparisons, the values of the patients with vertebral fracture and the patients with hip fracture were significantly higher than those of corresponded age-matched postmenopausal women. Alpha-CTx well reflects an increase of bone resorption associated with bone modeling at childhood and high bone resorption after the menopause and higher bone resorption in osteoporotic patients with fractures.

Comparison of the analytical and clinical performance characteristics of an N-MID versus an intact osteocalcin immunoradiometric assay.

Osteocalcin is the most abundant non-collagenous protein in bone, reflecting its formation. It was reported that the instability of intact osteocalcin results from the cleavage of the C-terminal sequence of osteocalcin to produce a large N-terminal osteocalcin fragment. A two-site immunoassay for detecting both the N-terminal osteocalcin fragment and the intact osteocalcin was developed that were both independent of an unstable C-terminal sequence. The aim of this study is to investigate the performance of an N-MID osteocalcin immunoradiometric assay and to compare it with an intact osteocalcin assay. Ten serum samples were repeatedly frozen and thawed up to seven times. The variability of the values of N-MID osteocalcin was less than that of the intact osteocalcin. For stability of osteocalcin in serum after storage, the mean value of N-MID was 94. 3% of the initial value after 7 days at 4 degrees C, whereas the intact was 73.4%. The reduction of intact values were significantly larger than that of N-MID after 2, 5 and 7 days. At -30 degrees C, the values of N-MID did not change for up to 10 weeks. The concentrations of osteocalcin measured by an N-MID osteocalcin and an intact osteocalcin were investigated in 27 premenopausal subjects, 27 postmenopausal subjects, and 68 osteoporotic patients (23 with vertebral fractures and 45 with hip fractures). The percent mean increase of osteocalcin in postmenopausal subjects over premenopausal subjects was 98% in N-MID versus 42% in the intact assay. The z-scores of N-MID and intact showed similar results in all groups. N-MID osteocalcin significantly correlated with intact osteocalcin (r=0.755), and other biochemical markers for bone formation, such as bone specific alkaline phosphatase (r=0.606) and C-terminal propeptide of type I procollagen (PICP) (r=0.568). An N-MID IRMA had better stability during storage than intact and had the discriminative ability which is similar to the intact assay in postmenopause and osteoporosis. Therefore, an N-MID osteocalcin IRMA could improve the clinical utility and evaluation of osteocalcin.

Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis.

BACKGROUND: Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are alpha-CTx and beta-CTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We evaluated the effects of aging, menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. METHODS: In 79 premenopausal healthy women, 80 postmenopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures, s-CTx and urinary beta-CTx (u-betaCTx) were measured by ELISAs, and urinary alpha-CTx (u-alphaCTx) was measured by an RIA. RESULTS: In all subjects, s-CTx significantly correlated with both u-alphaCTx (r=0.54) and u-betaCTx (r=0.51). There was no significant difference among s-CTx, u-alphaCTx and u-betaCTx in the T-scores of the postmenopausal group over the premenopausal group. These findings indicate that the value of s-CTx, as well as urinary CTxs, reflected the increase of bone resorption associated with menopause with a high degree of sensitivity. Patients with vertebral fractures had moderately increased concentrations of bone resorption markers compared to age-matched healthy postmenopausal women (T-score; s-CTx: 0.8, u-alphaCTx: 0.9, u-betaCTx: 0.7), whereas bone resorption markers in hip fracture patients were greatly increased compared to healthy postmenopausal women (T-score; s-CTx: 1.1, u-alphaCTx: 1.3 u-betaCTx: 1.3). The T-scores of u-CTxs against the postmenopausal group in vertebral fracture group and in hip fracture group were not significantly different from those of s-CTx. CONCLUSIONS: s-CTx, as well as urinary CTxs, reflects the increase of bone resorption in patients with vertebral fractures and hip fractures.

Longitudinal study of age- and menopause-related metacarpal index changes in Japanese adult females.

To establish a comprehensive mode for cortical bone thinning rate, the metacarpal index (MCI) of the index finger of the nondominant hand was measured using computed X-ray microdensitometry. Statistical analysis was used to study the MCI data in relation to age and menopausal status. A total of 383 healthy Japanese women ranging in age from 30 to 79 yr were investigated in 1996 and 1999. The MCI was generally decreased by 1.11% per year. However, accelerative decreases of 1.78 and 2.05% per year were observed within both the age 50-59 yr group and the early postmenopausal period, respectively. In addition, analysis of age-based longitudinal data showed that the age-related loss of MCI in the age 50-59 yr category was significantly higher than that in the other age categories (p < 0.01), indicating that the changes in MCI were more dependent on menopausal status than on aging. Our study suggests that the cortical bone thinning rate is affected by both aging and menopausal status, but the latter may be a predominant factor.

Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fractures. Contact Ultrasound Bone Analyzer.

The purpose of this study was to assess the ultrasound (US) parameters measured by Contact Ultrasound Bone Analyser (CUBA) clinical system for discriminating the subjects with vertebral fractures from those without vertebral fractures. The subjects consisted of 114 postmenopausal women over age 50 (mean +/- SD: 72.2 +/- 8.7). Seventy-three had vertebral fractures (fracture group) and 41 had no vertebral fractures (control group). Values of all US parameters and bone mineral density (BMD) in the fracture group were significantly lower than those in the control group, even after adjusting for age. Areas under the receiver operating characteristic (ROC) curve was 0.768 +/- 0.056 (mean +/- SE) for broadband ultrasound attenuation (BUA) 0.828 +/- 0.045 for velocity of sound (VOS), 0.707 +/- 0.058 for lumbar spine, 0.872 +/- 0.050 for femur neck, 0.790 +/- 0.050 for trochanter, and 0.695 +/- 0.060 for Ward's triangle. There were no significant differences among the areas under the ROC curves in BUA, VOS, lumbar spine, femur neck, trochanter, and Ward's triangle. US parameters (BUA and VOS) had the same discriminatory power as spine and hip BMD for evaluating the vertebral fracture risk. As far as disadvantages of the use of BMD measurement against US measurement, US measurement is potentially useful for screening of vertebral fractures. However, the bias concerning the propotion of the number of patients with or without vertebral fractures could not be neglected in this study.

Structure of cervinomycin, a novel xantone antibiotic active against anaerobe and mycoplasma.

The structures of cervinomycins A1 (1) and A2 (2), a potent anti-anaerobic and anti-mycoplasmal antibiotic were investigated by means of recent NMR techniques of O-methyl ether (3) and C,O-dimethyl ether (4) obtained by methylation of 2 with CH3I in the presence of Ag2O. The antibiotic 2 posesses a polycyclic structure involving a xanthone skeleton. The structure of 1 was confirmed to be a hydroquinone of 2 from the evidences that oxidation of 1 with Ag2O and acetylation of 1 with (CH3CO)2O in pyridine afforded quantitatively 2 and triacetylcervinomycin A1 (7), respectively.