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Biomedical subjects

C Christiansen

Publications and source records attributed to C Christiansen.

At least 181 records · Page 10Linked to original sources

Changes in the carboxyl-terminal propeptide of type I procollagen and other markers of bone formation upon five days of bed rest.

This study was performed in order to investigate the influence of skeletal unloading on the serum concentration of the carboxyl-terminal propeptide of type I procollagen (sPICP) and other markers of bone formation. Blood samples were taken every third hour from nine healthy premenopausal women (22-29 years) in two 24 h studies, before and at the end of five days of bed rest. Furthermore, a set of samples were taken 12 h apart after three days of bed rest. We measured sPICP, the serum concentration of intact and N-terminal-Mid fragment osteocalcin (sOC), and the serum concentration of alkaline phosphatase (sAP). During the five days of bed rest a gradual increase in sOC was observed, while sPICP gradually decreased. sAP was unchanged. Five days of best rest resulted in the following overall changes in the 24 h mean values: sPICP: -14% (p = 0.002); sOC: +9% (p = 0.009); sAP: -1% (not significant). The circadian patterns did not change significantly after bed rest. It is puzzling that the changes in the bone formation markers are of different magnitude, and for sPICP and sOC even in opposite directions. The increase in sOC may be caused by an increase in OC secretion by the osteoblasts or a release of bone-incorporated OC from resorbing sites; the accompanying decrease in sPICP may indicate that bone formation is actually transiently decreased after short term bed rest.

Adult↗

Osteoporosis: diagnosis and management today and tomorrow.

Osteoporosis is a disease in which low bone mass and microarchitectural deterioration of bone tissue lead to increased bone fragility and a consequent increase in fracture risk. The risk of developing osteoporosis can be assessed by determining the maximum density and strength achieved at maturity (peak bone mass) and the rate and duration of age-associated bone loss. The major cause of osteoporosis is estrogen withdrawal in women, most commonly associated with the menopause, but also with other causes of ovarian failure. Androgen insufficiency in men, although much less common, can also lead to osteoporosis. Measurements of bone mineral density (BMD) have been used to predict fractures, and current evidence suggests that fractures at any site can be predicted by taking measurements of BMD at any other site in the skeleton, using noninvasive techniques such as single or dual energy absorptiometry, quantitative computed tomography and ultrasound, a promising but experimental approach. Rapid bone loss at the start of the menopause is also an important contributing factor to the development of osteoporosis. Levels of biochemical markers of bone turnover in plasma and urine have been found to correlate with rapid and prolonged bone loss. Powerful new assays for estimating bone turnover have emerged and more are being developed. Various combinations of these biochemical tests may be used in conjunction with bone densitometry to predict future risk of osteoporosis and osteoporosis-related fractures. Furthermore, biochemical tests can also be useful in assessing response to therapy. Although many factors, including sex, race, heredity and lifestyle (e.g., calcium intake, minerals, nutrition and exercise), influence the risk of osteoporosis, i.e., they affect peak bone mass and subsequent bone loss, and are of little use in predicting future occurrence.

Biomarkers↗

Two-dimensional gel analysis of human endometrial proteins: cyclic changes in the expression of specific proteins during the normal menstrual cycle.

High resolution two-dimensional (2-D) gel electrophoresis was used to compare the patterns of [35S]methionine-labelled cellular proteins in endometrial tissue from healthy, normally menstruating women. Samples of endometrial tissue were incubated with [35S]methionine for 20 h, and total cell lysates were processed for 2-D gel electrophoresis. Using this technique it was possible to study proteins with iso-electric points (pI) ranging from 3.5 to 11 and relative molecular weights (M(r)) ranging from 10,000 to 300,000 Da. The fluorograms were compared by computer-aided analysis whereby a total of 1095 [35S]-labelled proteins were resolved on the iso-electric focusing gels (IEF, pI 3.5-7) and 488 on the non-equilibrium pH gradient electrophoresis (NEPHGE) gels (pI 6.5-11). Of the proteins on the IEF gels, 125 showed differential expression during the menstrual cycle. Of these, 36 were maximally expressed in proliferative phase endometrium, 26 in the interval phase and 63 in secretory and/or late secretory phase endometrium. Correspondingly, on the NEPHGE gels a total of 61 proteins exhibited cyclical variation, of which 30 were more prominent in proliferative phase, 13 in interval phase and 18 in secretory phase endometrium. This study shows that 2-D gel electrophoresis is eminently suited to the identification of proteins whose expression varies in a cyclical manner during the menstrual cycle. Further investigations should be carried out to isolate and characterize these proteins with the aim of establishing useful markers for specific endometrial phases of the menstrual cycle.

Adult↗

Human endometrial proteins with cyclic changes in the expression during the normal menstrual cycle: characterization by protein sequence analysis.

Endometrial proteins showing cyclic expression during the normal menstrual cycle were localized on two-dimensional (2-D) electrophoresis gels separating proteins with isoelectric points (pl) ranging from 3.5 to 7 and relative molecular weights ranging from 10 to 300 kDa. Menstrual cycle-related proteins were excised from several 2-D gels, concentrated by one-dimensional (1-D) sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, and cleaved in situ by trypsin. The tryptic fragments were extracted and separated by reverse phase high performance liquid chromatography (RP-HPLC). Finally, the partial amino-terminal amino acid sequence of selected tryptic fragments were determined for each protein. We aimed at characterizing the 21 menstrual cycle-related proteins that were visible on silver-stained 2-D electrophoresis gels. Of the proteins being maximally synthesized in the proliferative phase endometrium, we identified proteins associated mainly with the cytoskeleton: vimentins, keratin, tropomyosin and tubulin, but also proteins such as proliferating cell nuclear antigen and beta-galactoside binding lectin. The partial amino acid sequences for another two proteins did not match any protein sequence in the Protein Identification Resource (PIR) and Swissprot databases. In the group of proteins having maximal synthesis in the secretory phase endometrium, we identified creatine kinase chain B and an isocitrate dehydrogenase-homologous protein, both of which are involved in energy metabolism. However, we also identified the annexin IV precursor, the 14-3-3 protein homologue also called stratifin or the epithelial cell marker protein 1 and the 21K tumour protein. Finally, four of the proteins were present in too low amounts to allow characterization. Interestingly, most of the identified proteins have not previously been described as having a menstrual cycle-related synthesis in the human endometrium. It may be considered that the concentration of some of the cycle-related proteins may be used in clinical situations to reflect specific endometrial phases.

Amino Acid Sequence↗

Body composition and serum lipids in female runners: influence of exercise level and menstrual bleeding pattern.

The impact of running and menstrual disturbances on regional and total body fat distribution and serum lipids was investigated in 205 women. Body composition was measured by dual-energy X-ray absorptiometry. The total fat mass in the elite runners was approximately half of the normally active's (7.3 [0.48] kg vs. 14.3 [0.49] kg, P < 0.001) (mean [SEM]). The difference was most pronounced in the abdomen (fat percentage 9.7 [0.85]% vs. 22.0 [0.88]%, P < 0.001). The elite runners tended to have a more favourable lipid profile than the normally active (NS). A significant relation was found between lipoproteins and body fatness. In comparison with the regularly menstruating runners (n = 93), the 13 runners with amenorrhea tended to have less body fat and slightly less favourable lipid profiles (NS). In conclusion, regular exercise was associated with a low abdominal fat percentage, which may affect cardiovascular risk beneficially. Running-associated menstrual dysfunctions were not significantly related to a specific body composition or serum lipid profile.

Body Composition↗

Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment.

An enzyme-linked immunosorbent immunoassay (ELISA) for a new marker of bone resorption (CrossLaps) was evaluated. The ELISA procedure determines degradation products of type I collagen in urine. Values obtained in the ELISA and in pyridinoline by high pressure liquid chromatography were correlated after a correction for creatinine. A high correlation was found (r = 0.77; n = 81). A group of postmenopausal women (n = 180) showed an increase of more than 70% compared to values in premenopausal women (n = 104). Hydroxyproline was increased by 23%, osteocalcin by 52%, pyridinoline by 31%, and deoxypyridinoline by 50%. A highly significant decrease (60.7%) in the CrossLaps values was seen after 12 months in samples from patients receiving hormone replacement therapy compared to a placebo group. The spontaneous bone loss in an untreated group of women was determined by repeated forearm bone mass measurement over 24 months. Baseline values obtained in the CrossLaps ELISA were correlated to the rate of loss, yielding a highly significant r value of -0.61, indicating that CrossLaps might be a useful parameter for assessment of the risk of osteoporosis in postmenopausal women.

Amino Acid Sequence↗

Insulin-like growth factors I and II in healthy women with and without established osteoporosis.

We measured serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) by radioimmunoassay in 107 healthy women aged 28-78 years and in 116 women with established osteoporosis. The women with established osteoporosis were randomized to a 1-year double-blind, placebo-controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p < 0.001) as compared to women above that age. For women more than 35 years of age, we found no correlation between IGF-I and age (r = 0.02). Correspondingly, we found no significant changes in serum IGF-I in 10 women, who were followed with serial measurements of IGFs every 3 months from 2 years before to 1 year after menopause; IGF-II revealed no correlation with age (r = 0.04). In the group of 116 women with established osteoporosis, IGF-I was 30% lower (p < 0.01) as compared to a group of 19 height-, weight- and age-matched nonfractured women (mean age 64 years). The IGF-II levels were equal in the two groups. Over the 1-year therapeutic intervention period, an increase in IGF-I of 13-15% (p < 0.05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis.

Adult↗

Measurement of a more stable region of osteocalcin in serum by ELISA with two monoclonal antibodies.

Intact human osteocalcin purified from femoral bones as well as tryptic fragments of the intact molecule [amino acids (aa) 1-19, 20-43, and 45-49] were used to raise and screen monoclonal antibodies (MAbs). A two-site ELISA for measurement of human osteocalcin in serum was developed with use of these MAbs. A MAb recognizing midregion human osteocalcin (aa20-43) was used as capture antibody, and an NH2 terminus (aa7-19)-specific peroxidase-conjugated MAb was used for detection. Human osteocalcin obtained from bone was used for calibration, and parallelism was observed for osteocalcin from serum samples, NH2-terminal midfragments (aa1-43), and synthetic human osteocalcin. Both inter- and intraassay variations were < 7%. Serum osteocalcin in healthy premenopausal women (n = 49) was 18.3 +/- 4.2 micrograms/L (mean +/- SD) and 28.6 +/- 9.7 micrograms/L in early postmenopausal women (n = 114). The mean serum concentration (n = 10) decreased by 10% after 7 days of storage at 4 degrees C, whereas the concentration of intact human osteocalcin was reduced 63%. The N-MID ELISA and an IRMA measuring intact human osteocalcin were used to monitor the effect of hormone replacement therapy in a retrospective study. A significant decrease to the premenopausal concentration was detected only in the N-MID ELISA.

Antibodies, Monoclonal↗

Cost-effectiveness of fracture prevention in established osteoporosis.

This study presents the results of a computer simulation model for calculating the cost-effectiveness and cost-utility of treating patients with established osteoporosis in order to reduce the risk of fractures. The results are based on Swedish data for risk of fracture and costs. The treatment intervention modelled is based on treatment of a 62-year-old woman with established osteoporosis. The cost per hip fracture avoided is 350,000 SEK, assuming a 50% reduction in the risk of fracture due to 5 years of treatment. A sensitivity analysis for changes in the cost and effectiveness of treatment, the risk of fracture and the discount rate is performed. The cost per life-year gained and the cost per quality-adjusted life-year (QALY) gained is presented to enable comparison of the cost-effectiveness of treating osteoporosis with that of other health care interventions. A comparison between treating the same woman for osteoporosis and mild hypertension shows a cost per life-year gained of 220,000 SEK and 128,000 SEK respectively. Cost per QALY gained is very similar for the two interventions: 105,000 SEK and 103,000 SEK respectively. This model provides a tool to enable clinicians, administrators and health policy makers to analyze and understand the economic aspects of a major health policy issue.

Computer Simulation↗

The response to treatment of overweight in postmenopausal women is not related to fat distribution.

OBJECTIVE: To investigate whether fat distribution or sex hormone status in overweight postmenopausal women do influence the response to treatment of overweight. DESIGN: Longitudinal, clinical intervention study of a 4.2 MJ diet daily with or without exercise. SUBJECTS: 98 healthy, overweight, postmenopausal women (age: 49-58 y, BMI: 25-42 kg/m2). MEASUREMENTS: Various fatness and fat distribution parameters (by dual-energy x-ray absorptiometry and anthropometry), sex hormone-binding globulin (SHBG), sex hormones, and the resting energy expenditure (REE) at baseline and after 3 months. RESULTS: Reductions in weight and fat were independent of the initial fat distribution and the REE, but were significantly associated with high initial SHBG levels. Furthermore, loss of fat was significantly and independently associated with increases in SHBG and reductions in central fat distribution. CONCLUSION: Postmenopausal women with an android and gynoid fat distribution respond with similar weight loss to treatment of overweight. Furthermore, a more healthy, less android, fat distribution and sex hormone status may be achieved with increasing weight loss.

Absorptiometry, Photon↗

Complete DNA sequence of yeast chromosome II.

In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.

Base Composition↗

[Bone metabolism in female runners. Menstruation disorders are frequent among long-distance runners, but the bone mass is not influenced, with the exception of runners with amenorrhea].

The purpose of the study was to investigate the prevalence of exercise-related menstrual and sex hormonal disturbances and the effect of exercise on bone mass and metabolism in female runners at various training levels. Two hundred and five premenopausal women (running 0-140 km a week) were recruited from a large population of female runners, who had responded to a questionnaire regarding exercise habits. Maximum oxygen uptake was determined by treadmill testing. Gynaecological status was assessed on entries in a menstrual calendar and by transvaginal ultrasonography; and sex hormonal status was measured three times with 10-day intervals. Bone mass was measured in the lumbar spine, proximal femurs and total body by dual energy x-ray absorptiometry, and in the forearm by single photon absorptiometry. Bone turnover was assessed by plasma osteocalcin, serum alkaline phosphatase, and urinary calcium and hydroxyproline. The results showed that sex hormonal disturbances were significantly related to training intensity. Compared with the normally active women, the baseline levels and fluctuations of oestradiol and progesterone in the elite runners were reduced by up to 25-44%, (0.01 < p < 0.05). The prevalence of amenorrhoea increased from 1% in the normally active to 11% in the elite runners. No statistically significant relation was found between running activity and bone mass or bone turnover. However, the group of amenorrhoeic runners had a 10% reduction in lumbar bone mass as compared to the normally menstruating runners (p < 0.05), but the bone turnover was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Physical exercise as a supplement to diet. Effect on body composition, resting metabolic rate and cardiovascular risk factors in postmenopausal overweight women].

One hundred and twenty-one healthy, overweight, postmenopausal women were randomly assigned to three groups: controls (no intervention), a 4200 kJ/day diet, or 4200 kJ/day diet with combined aerobic and anaerobic exercise, for 12 weeks. One hundred and eighteen women completed the study. The loss of weight was similar in the two intervention groups, but compared with the diet-only group, the diet-plus-exercise group lost significantly more fat (7.8 vs 9.6 kg) and no lean tissue mass (1.2 vs 0.0 kg). The resting metabolic rate was increased in the diet-plus-exercise group as compared to the controls (11% vs 4%, p < 0.009). The cardiovascular risk factors (serum lipids and lipoproteins (except high density lipoprotein), systolic blood pressure, and the waist-to-hip ratio) decreased significantly in both intervention groups, as compared to the controls. There were no consistent, major differences between groups in changes in total body, spinal, or forearm bone mineral density. In conclusion, overweight postmenopausal women benefit from addition of combined aerobic and anaerobic exercise to an energy-restrictive diet.

Aged↗

Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks.

This study was performed to investigate whether the circadian variation in urinary pyridinium crosslinks is related to physical activity, age, the menopause, and asymptomatic osteopenia. We measured urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatinine (D-Pyr/Cr) in 9 healthy premenopausal women in two 27 h studies, before and at the end of 5 days of total bed rest. Both Pyr/Cr and D-Pyr/Cr showed highly significant circadian variations, with the peak at night and the nadir during the day (p < 0.001). The 5 days of complete bed rest produced no changes in the circadian pattern, but a general increase of 28% was observed in pyridinium crosslinks. A group of 12 healthy, early postmenopausal women (aged 55 +/- 2 years), 12 healthy, elderly postmenopausal women (aged 73 +/- 1 years), and 12 elderly osteopenic but otherwise healthy women (aged 73 +/- 1 years) were also studied for 27 h. All three groups showed highly significant (p < or = 0.001) circadian variations in the urinary excretion of pyridinium crosslinks. As expected, both Pyr/Cr (p < 0.05) and D-Pyr/Cr (p < 0.001) increased at the time of menopause, but the circadian variations in Pyr/Cr and D-Pyr/Cr were similar in all groups studied. We conclude that the circadian variation in the urinary excretion of pyridinium crosslinks is independent of physical factors. Furthermore, the circadian variation in pyridinium crosslinks was not related to age, menopausal status, or asymptomatic osteopenia.

Adult↗

Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry.

Total and regional bone mineral density (BMD) of the proximal femur was measured by DXA in 1238 healthy white women. In the 389 premenopausal women, aged 21-54 years, no bone loss was observed before the menopause, except in the femoral neck and Ward's triangle, in which BMD decreased by 0.3%/year (SEE 0.2-0.9%/year, p < 0.001) and 0.6%/year (SEE 0.4-0.8%/year, p < 0.001), respectively. In the postmenopausal women aged 48-75 years, there was a highly significant exponential decay in BMD with age and years since menopause (YSM) in all regions (-0.58 < r < -0.48, p < 0.001). However, YSM was a better predictor of BMD than age. The decrease in BMD in the first 5 years postmenopause reached values of 9-13%. The estimated bone loss after 20 years was 17-30%, greatest in Ward's triangle and smallest in the intertrochanteric region. BMD correlated highly significantly with BMI (0.26 < r < 0.48, p < 0.001). In conclusion, the present study indicates a stable premenopausal bone mass of the proximal femur and a postmenopausal bone loss, which is influenced mainly by YSM within the first 10-15 years after menopause. BMD correlated with body mass index (BMI) in the postmenopausal years, confirming that low BMI constitutes a potential risk factor for osteoporosis.

Absorptiometry, Photon↗