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  • 1
    Electronic Resource
    Electronic Resource
    A Heterogeneity in Serum Osteocalcin N-Terminal Fragments in Paget's Disease: A Comparison with Other Biochemical Indices in Pre- and Postmenopause (1998)
    Springer
    Calcified tissue international 63 (1998), S. 459-465 
    Details
    ISSN: 1432-0827
    Keywords: Key words: N-terminal osteocalcin — Heterogeneity — Paget's disease — Bone turnover — Pre- and postmenopause.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. An osteocalcin (OC) nitrogen (N)-terminal sandwich enzyme immunoassay that employs anit-N-20 (amino acids 1–20) polyclonal and monoclonal antibodies has been developed. This assay has demonstrated the existence of a heterogeneity in the OC N-terminal fragments observed in the serum of a patient with Paget's disease and a normal child. The elevation of the serum OC N-terminal value that occurs in Paget's disease was considered to be comparable to the serum alkaline phosphatase (ALP) elevations that also occur. The size of the peaks corresponding to N-terminal OC fragments in Paget's serum decreased 3 months after bisphosphonate treatment. Serum levels of OC N-terminals, and other biochemical indices, were determined for 67 premenopausal and 181 postmenopausal Japanese women. Serum OC N-terminal levels increased significantly (41.2%) in postmenopausal women compared with age-matched premenopausal women. These results strongly suggest that serum OC N-terminal levels reflect bone turnover rates when bone resorption is dominant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002239900558
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  • 2
    Electronic Resource
    Electronic Resource
    Down regulation of peroxisome proliferator-activated receptorγ expression by inflammatory cytokines and its reversal by thiazolidinediones (1999)
    Springer
    Diabetologia 42 (1999), S. 702-710 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Cloning ; PPARγ ; insulin resistance ; thiazolidinediones ; cytokines ; TNF-α ; rat ; adipocyte ; glucose uptake.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptorγ (PPARγ). We hypothesized that the anti-diabetic mechanism of thiazolidinediones depends on the quantity of PPARγ in the insulin resistant state in which inflammatory cytokines play a part. Methods. We isolated rat PPARγ1 and γ2 cDNAs and examined effects of various cytokines and thiazolidinediones on PPARγ mRNA expression in rat mature adipocytes. Results. Various inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6 and leukaemia inhibitory factor decreased PPARγ mRNA expression. In addition, hydrogen peroxide, lysophosphatidylcholine or phorbol 12-myristate 13-acetate also decreased the expression of PPARγ. The suppression of PPARγ mRNA expression caused by 10 nmol/l of TNF-α was reversed 60 % and 55 % by treatment with 10–4 mol/l of troglitazone and 10–4 mol/l of pioglitazone, respectively. The suppression of glucose transporter 4 mRNA expression caused by TNF-α was also reversed by thiazolidinediones. Associated with the change of PPARγ mRNA expression, troglitazone improved glucose uptake suppressed by TNF-α. Conclusion/interpretation. Our study suggests that inflammatory cytokines could be factors that regulate PPARγ expression for possible modulation of insulin resistance. In addition, we speculate that the regulation of PPARγ mRNA expression may contribute to the anti-diabetic mechanism of thiazolidinediones. [Diabetologia (1999) 42: 702–710]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051218
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  • 3
    Electronic Resource
    Electronic Resource
    Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity (1997)
    Springer
    Diabetologia 40 (1997), S. 1204-1210 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Leptin ; leptin receptor ; Ob-R ; obesity ; sequence variant.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3 ± 8.4 kg/m2). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa k /fa k) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85 %, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 ± 6.5 kg/m2) and 68 non-obese (BMI 21.6 ± 2.2 kg/m2) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects. [Diabetologia (1997) 40: 1204–1210]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050808
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  • 4
    Electronic Resource
    Electronic Resource
    Well-differentiated hepatocellular carcinoma: findings of US, CT, and MR imaging (1999)
    Springer
    Abdominal imaging 24 (1999), S. 392-397 
    Details
    ISSN: 1432-0509
    Keywords: Key words: Ultrasonography (US)—Computed tomography (CT)—Magnetic resonance (MR)—US, liver neoplasm—CT, liver neoplasm—MR, liver neoplasm.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: To elucidate the imaging characteristics of well-differentiated hepatocellular carcinomas (HCCs) on ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging. Methods: Ultrasonograms, CTs, and MR images of 18 histopathologically proven well-differentiated HCCs in 15 patients were reviewed. The findings of these images were correlated with histopathologic findings. Results: On US, seven tumors were depicted as a hyperechoic area and eight as a hypoechoic area. Three tumors were not visualized. On precontrast CT, four tumors were depicted as a low-density area, but 14 were not visualized. On conventional contrast-enhanced CT, 12 tumors were depicted as a low-density area but six were not visualized. On T1-weighted MR images, 10 tumors had high signal intensity and two had low signal intensity. Six tumors were not visualized. On T2-weighted MR images, five tumors had high signal intensity and two had low signal intensity. Eleven tumors were not visualized. Tumors with fatty change and/or clear cell formation were frequently hyperechoic on US and hyperintense on T1-weighted MR images. Conclusions: Well-differentiated HCCs show different findings on US, CT, and MR imaging. Therefore, reliable diagnosis of well-differentiated HCCs by these imaging techniques may be difficult.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002619900521
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  • 5
    Electronic Resource
    Electronic Resource
    Measurement of Intact Rat Osteocalcin in Osteoblast (ROS17/2.8) Cells and in Ovariectomized Rats with a Sandwich Enzyme Immunoassay (1996)
    Springer
    Calcified tissue international 59 (1996), S. 283-290 
    Details
    ISSN: 1432-0827
    Keywords: Key words: Intact rat osteocalcin — ROS17/2.8 — Ovariectomized rat — Bone turnover.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. We developed a sandwich enzyme immunoassay system for intact rat osteocalcin to improve the region specificity for the detection of this molecule. We synthesized two peptides of N-terminal 20 residues and C-terminal 10 residues of rat osteocalcin. After conjugating these peptides with carrier protein, we obtained anti-N- and anti-C-terminal rat osteocalcin antibodies in rabbits raised against these two peptides, respectively. By using these antibodies, we measured intact rat osteocalcin levels in a two-site immunoassay manner. These antibodies did not show the cross-reactivity to human osteocalcin. The immunoreactive peak corresponding to the intact molecules was detected by our intact osteocalcin method after high-performance liquid chromatographic fractionation of osteocalcin fragments in plasma from uremic rats. Furthermore, the intact rat osteocalcin was stable over 8 hours at 25°C. Intact rat osteocalcin levels extracellularly secreted from ROS 17/2.8 cells were measured by this method, showing time- and dose-dependent significant increases when administered 1,25(OH)2D3. The inhibition for the secretion of intact osteocalcin by actinomycin D was also detected quantitatively with this method. In ovariectomized rats, intact osteocalcin levels in plasma were acutely elevated after ovariectomy, and its elevation was significantly depressed by 17β-estradiol administration. These data suggest that this sandwich method is able to measure the intact form of osteocalcin secreted by osteoblasts. As the antibodies identify the specific regions of osteocalcin molecule, this method would be useful for sensitive estimation of bone turnover for various experimental conditions in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002239900124
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  • 6
    Electronic Resource
    Electronic Resource
    Local Bone Turnover in the Metaphysis of the Proximal Tibia and the Lumbar Vertebra During the Early Periods After Ovariectomy in Rats (1996)
    Springer
    Calcified tissue international 58 (1996), S. 52-59 
    Details
    ISSN: 1432-0827
    Keywords: Key words: Histomorphometry — Osteoclast — Bone formation rate — Intact osteocalcin — Tartrate-resistant acid phosphatase.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. To clarify the local changes in bone formation and resorption during the early period after ovariectomy (OVX), 200 SD rats, 4 months of age, underwent OVX or sham surgeries and seven to nine rats from each group were terminated at 1, 3, 7, 11, 15, 19, 23, 28, 35, 63, and 91 days postsurgery after tetracycline labeling. Serum intact osteocalcin levels were measured. Undecalcified sections of the 5th lumbar body (L5) and the right proximal tibia were measured for trabecular bone area, the labeled perimeters and the interlabeling distances after Villanueva's staining. On the 4th lumbar body (L4) and the left proximal tibia, undecalcified sections were measured for the trabecular osteoclast by tartrate-resistant acid phosphatase staining. The uterine horns were atrophied on the 3rd postovariectomy day (day 3). Serum osteocalcin levels increased on day 7 and reached the highest value on day 23. In either L5 or the metaphysis of the proximal tibia, trabecular bone volume (BV/TV) significantly decreased on day 15. The trabecular bone loss on day 28 was approximately 50% in the tibia and 15% in the L5. In either the lumbar or the tibia, osteoclast numbers significantly increased at day 3, and peaked between days 15 and 23. In the tibia, however, the bone formation rates (BFR/BS) were significantly reduced on the 3rd and 7th postsurgical days compared with the start value for both the OVX and sham groups. The BFR/BS values in L5 did not decrease during the first 7 days in either group. The BFR/BS values were then increased for both L5 and the tibia after day 7. These data clearly demonstrated that the local bone turnover 7 days post-OVX was identical in the proximal tibia and the lumbar vertebra. In the proximal tibia, however, it may be suggested that the increased bone resorption and reduced formation within 7 days after OVX due to the combined effects of both an estrogen deficiency and the surgical intervention would possibly play a critical role in the greater magnitude of the trabecular bone loss.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002239900010
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