Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed endogenous GH secretory dynamics and MCRs by a novel quantitative deconvolution technique in 20 boys with idiopathic short stature (ISS) and 35 boys of normal stature in Tanner stage I of puberty. We tested the null hypotheses that 1) ISS is not associated with any alterations in the frequency, mass, amplitude, or duration of spontaneous GH secretory bursts and/or the 24-h GH production rate; and 2) the half-life of endogenous GH is not altered in ISS. The boys with ISS had a mean (+/- SEM) bone age of 8.0 +/- 0.42 yr and a chronological age of 10 +/- 0.50 yr. The latter was similar to the chronological (and bone) age of the normal boys of 9.8 +/- 0.23 (and 9.3 +/- 0.34) yr. Mean height SD scores were significantly lower in ISS boys, viz. -2.7 +/- 0.15 in ISS vs. +0.34 +/- 0.13 in normal boys (P less than 0.001). Plasma insulin-like growth factor-I concentrations were similar in the two groups, as were (24-h) mean serum GH concentrations, viz. 3.5 +/- 0.29 micrograms/L in ISS and 4.1 +/- 0.49 micrograms/L in normal boys (P = NS). Deconvolution analysis revealed that the mean number of GH secretory events per 24 h was similar in normal and ISS boys, viz. 9.6 +/- 0.76 (normal) vs. 8.4 +/- 0.55 (ISS), and that there was no significant difference in mean GH interburst intervals. The amplitude, mass, and duration of computer-resolved GH secretory bursts also did not differ in normal and ISS boys. The half-lives of endogenous GH were estimated to be 16 +/- 0.77 min in the ISS and 18 +/- 0.93 min in the control boys (P = NS). The calculated daily GH secretion rate per unit distribution volume was not significantly reduced in ISS, i.e. 194 +/- 19 micrograms/L.day in ISS vs. 177 +/- 19 micrograms/L.day in control boys. Moreover, daily GH secretion rates corrected for body mass index (weight/height2) in the twp groups were not significantly different. In summary, the present cohort of boys with ISS manifested no significant alterations in GH secretory burst frequency, duration, mass, or amplitude or in the half-life of endogenous GH compared to normal boys in Tanner stage I of pubertal development. Indeed, whether daily GH secretion rates are expressed per unit distribution volume or per unit body mass index, groups of boys with ISS and normal height controls secrete similar total amounts of GH. We conclude that the overall dynamics of GH secretion and clearance in boys with ISS considered as a whole cannot be distinguished readily from physiological patterns observed in prepubertal boys of normal height.
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PMID:Properties of spontaneous growth hormone secretory bursts and half-life of endogenous growth hormone in boys with idiopathic short stature. Genentech Collaborative Group. 154 38

Six patients (21-50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatotropin, 0.04-0.1 U.kg.body wt-1.day-1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0 +/- 0.6 (SEM)% and 3.8 +/- 1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were -2.4 +/- 0.6% and -1.9 +/- 0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean +2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.
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PMID:Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. 162 80

This study aimed to determine the longitudinal changes in serum zinc concentrations and the relationship between serum alkaline phosphatase (AP) activity and serum zinc concentrations in small preterm infants. The total serum AP and serum zinc concentrations were determined serially at 3, 6, 9, and 12 months in 72 infants with mean (+/- SEM) birth weights of 1000 +/- 29 g and gestational ages of 28.6 +/- 0.3 weeks. Twenty-four of 72 infants had radiographic evidence of rickets and/or fractures (R/F). In infants with R/F, group mean (+/- SEM) serum AP (371 +/- 42 U/L) and serum zinc (12.5 +/- 1.0 mumol/L) concentrations were significantly higher at 3 months compared with infants in the non-R/F group (193 +/- 12 U/L and 9.6 +/- 0.3 mumol/L, respectively). During the study, the serum AP concentrations decreased, and the serum zinc concentrations increased; both stabilized after 6 months. The serum AP concentrations were not related to the serum zinc concentrations. We speculate that in preterm infants, an increased bone turnover and a release of tissue (bone) zinc may contribute to the higher group mean serum AP and serum zinc concentrations at the time of diagnoses in infants with R/F compared with those infants without R/F.
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PMID:Serum alkaline phosphatase and serum zinc concentrations in preterm infants with rickets and fractures. 281 63

In six anuric haemodialysed patients, aluminium and iron mass transfer were determined 48 hours after 40 and 80mg/kg body weight desferrioxamine intravenous infusion. All patients were aluminium overloaded (mean +/- SEM: 2.91 +/- 1.05 mumol/g wet tissue bone) and two had high plasma ferritin. Haemodialysis and haemofiltration were performed using a highly permeable membrane. The adequate dose of desferrioxamine for aluminium removal is 40mg/kg, since aluminium mass transfer induced by haemodialysis and haemofiltration (47.4 and 40 mumol/session) are not significantly different from that obtained with 80mg/kg. Iron removal is dose related in high plasma ferritin concentration patients: 50 and 100 mumol/session with haemodialysis and 29 and 175 mumol/session with haemofiltration after 40 and 80mg/kg body weight respectively.
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PMID:Concomitant removal of aluminium and iron by haemodialysis and haemofiltration after desferrioxamine intravenous infusion. 399 42

In order to determine the effects of exercise on the calcium status of selected axial and appendicular bones of mature rats, female Sprague-Dawley rats (8-9 mo.) were divided into three groups including, two months (E2, n = 8) or four months (E4, n = 9) of exercise, and four month sedentary controls (S, n = 10). Exercise consisted of treadmill running for 1 hr/day, 5 days/wk at a speed of 14.1 m/min and 8 degrees elevation. After sacrifice all femurs, tibia/fibula complexes, ribs (T7), and vertebrae (T7) were excised, cleaned, weighed and measured for length and volume. After freeze-drying and bone hydrolysis in 5N HCl, total bone calcium contents and concentrations were determined spectrophotometrically. The acid soluble, appendicular bone calcium contents of the E4 group were significantly greater than S for the femur and tibia respectively: E4 = 159.78 +/- 3.44 mg (mean +/- SEM), 129.46 +/- 4.87 mg; S = 140.03 +/- 5.04 mg, 110.40 +/- 4.71 mg. Bone calcium concentration (mg/g dry bone) also was significantly greater in the tibia/fibulas, ribs and vertebrae of the E4 group than the S group. With respect to other training-induced effects, the oxygen carrying capacity of the blood, as well as the heart and lung DNA and protein concentrations did not change after four months of exercise training. Within four months, moderate exercise can increase the calcium deposition in the bones of mature, female rats.
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PMID:Increased bone calcium following endurance exercise in the mature female rat. 404 48

Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, intact cells were used, nuclear uptake of 1,25-dihydroxy[23,24(n)3-H]cholecalciferol [1,25(OH)2[3H]D3) was temperature-dependent, optimal at 45 min at 37 degrees C, and saturable. In competition experiments with other calciferols, the 1,25(OH)2[3H]D3 uptake showed specificity indistinguishable from that reported for 1,25(OH)2D3 receptors from calciferol target tissues. Analysis of 1,25(OH)2[3H]D3 nuclear uptake in fibroblast strains from six normal adults (four male, two female) yielded an average binding capacity (R0) of 10,600 +/- 2,000 (SEM) nuclear sites per cell and an apparent dissociation contant (Kd) of 0.50 +/- 0.07 (SEM) x 10(-9) M. Donor sex, donor age, or anatomic site of origin of the cell line did not affect the characteristics of uptake. Similar nuclear uptake was demonstrable with cultured MCF-7 cells (derived from human breast cancer) when assayed in the same fashion. When hypertonic extracts of nuclei obtained from skin fibroblasts incubated with 1,25(OH)2[3H]D3 were subjected to centrifugation on sucrose gradients, a single peak of radioactivity sedimented at approximately 3 S; when excess 1,25(OH)2D3 was coincubated during the cellular uptake phase, this 3S peak was not observed. Molybdate was an essential buffer component for receptor stabilization during cell fractionation and sedimentation analysis. In summary, by using fibroblasts cultured from normal human skin, we have identified a process of nuclear uptake of 1,25(OH)2[3H]D3 with the affinity, saturability, and specificity characteristics of a steroid hormone--receptor interaction. This method should be useful in studying 1,25(OH)2D3 recept physiology in cells from normal persons as well as in cells from patients who have disorders in the responsiveness of calciferol target tissues.
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PMID:Nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in dispersed fibroblasts cultured from normal human skin. 626 80

Paget's disease is a human bone dysplasia with a probable viral origin. SEM studies on anorganic and acid etched biopsies confirm the osteocondensation and the structural and textural abnormalities (presence of woven bone). Corrosion casts revealed a complex scaffolding structure of vascular channels. On resting fronts, the domains are small and irregular and surfaces are different from human fetal woven bone. Mineralizing fronts extend largely on bone surfaces and present evidence of abnormal thickness. Resorption surfaces extend irregularly in multiple directions and are often found unusually deep. Irregularity of osteoclastic lacunae was also evidenced. This SEM study suggests that an osteoblastic qualitative dysfunction could be associated with the osteoclastic changes.
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PMID:Paget's disease of bone. A scanning electron microscopic study. 637 Dec 59

Renal osteodystrophy is an important complication in patients with end-stage renal disease on maintenance dialysis. The aim of this study was to compare the biochemical markers of bone formation (serum collagen type I C-terminal propeptide) and resorption (serum deoxypyridinoline - DPD - and pyridinoline - PYR) with the bone mineral density (BMD) at lumbar spine, femoral neck, and forearm in patients with end-stage renal disease on haemodialysis (HD) versus continuous ambulatory peritoneal dialysis (CAPD). Fifty-nine adult patients, 45 on CAPD (18 females, 27 males) and 14 on HD (2 females, 12 males), were studied. The mean age was 44 +/- SEM 1.6 and 54.4 +/- 4.8 years, respectively. No significant differences in serum calcium, phosphorus, creatinine, and parathyroid hormone were found between patients on HD and CAPD in predialysis samples. Serum urea was significantly lower (p = 0.02) in the CAPD group. Serum PYR (nmol/l) and DPD (nmol/l) were significantly higher in patients on HD as compared with those on CAPD: 105 +/- 23.3 versus 43.7 +/- 3.47 (p = 0.007) and 31.0 +/- 2.4 versus 24.4 +/- 1.4 (p = 0.027), respectively. The results were still significantly higher in the HD patients following correction for serum creatinine and body mass index. There was a close correlation between dialysate DPD and creatinine in both dialysis modalities (HD r = 0.9, CAPD r = 0.76). The clearance of DPD did not differ significantly between the CAPD membrane and the HD membrane (p = 0.22). Serum collagen type I C-terminal propeptide was not significantly different between the HD and CAPD patients. The results were unaffected following correction for age and gender. The BMD was measured in 38 (65%) of the patients (HD n = 8, CAPD n = 30) by dual-energy X-ray absorptiometry and expressed as 'Z' scores. This was reduced at all sites in the patients with end-stage renal disease. The BMD was significantly lower at the ultradistal forearm (mostly trabecular bone) in HD patients as compared with CAPD patients (n = 0.02). A similar trend was observed at the lumbar spine, although the results failed to reach significance. In the whole population (n = 38), linear regression analysis revealed a significant negative correlation between BMD at the ultradistal forearm and serum PYR (r = -0.35, p = 0.04) and DPD (r = -0.33, p = 0.049). Combined measurements of BMD and biochemical markers of bone resorption may have potential in the identification of patients at high risk of bone loss who may require further evaluation of bone remodeling by bone histomorphometry.
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PMID:Comparison of the humoral markers of bone turnover and bone mineral density in patients on haemodialysis and continuous ambulatory peritoneal dialysis. 1202 25

Matrix extracellular phosphoglycoprotein (MEPE) is expressed exclusively in osteoblasts, osteocytes and odontoblasts with markedly elevated expression found in X-linked hypophosphatemic rickets (Hyp) osteoblasts and in oncogenic hypophosphatemic osteomalacia (OHO) tumors. Because these syndromes are associated with abnormalities in mineralization and renal phosphate excretion, we examined the effects of insect-expressed full-length human-MEPE (Hu-MEPE) on serum and urinary phosphate in vivo, (33)PO(4) uptake in renal proximal tubule cultures and mineralization of osteoblast cultures. Dose-dependent hypophosphatemia and hyperphosphaturia occurred in mice following intraperitoneal (IP) administration of Hu-MEPE (up to 400 microg kg(-1) 31 h(-1)), similar to mice given the phosphaturic hormone PTH (80 microg kg(-1) 31 h(-1)). Also the fractional excretion of phosphate (FEP) was stimulated by MEPE [65.0% (P < 0.001)] and PTH groups [53.3% (P < 0.001)] relative to the vehicle group [28.7% (SEM 3.97)]. In addition, Hu-MEPE significantly inhibited (33)PO(4) uptake in primary human proximal tubule renal cells (RPTEC) and a human renal cell line (Hu-CL8) in vitro (V(max) 53.4% inhibition; K(m) 27.4 ng/ml, and V(max) 9.1% inhibition; K(m) 23.8 ng/ml, respectively). Moreover, Hu-MEPE dose dependently (50-800 ng/ml) inhibited BMP2-mediated mineralization of a murine osteoblast cell line (2T3) in vitro. Inhibition of mineralization was localized to a small (2 kDa) cathepsin B released carboxy-terminal MEPE peptide (protease-resistant) containing the acidic serine-aspartate-rich motif (ASARM peptide). We conclude that MEPE promotes renal phosphate excretion and modulates mineralization.
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PMID:MEPE has the properties of an osteoblastic phosphatonin and minhibin. 1496 9

The beneficial skeletal effects of menopausal estrogen replacement therapy (HRT) are well documented. The role of secondary mineralization of bone as a determinant of bone quality is now well established in postmenopausal women treated with bisphosphonates or SERMs. The aim of present study was to investigate the effect of conventional and high doses of estrogen on the main parameters reflecting the degree of mineralization of bone (DMB). Bone biopsies were obtained from 20 women with osteopenia or osteoporosis before and after 24 months (18 to 38 months) of conventional HRT, and from 19 women who had received high doses of estradiol (implant 100 mg every 3-6 months for 1.5-20 years). DMB parameters (mean DMB, DMB Freq. Max. and Heterogeneity Index of the individual distributions of DMB) were measured using quantitative microradiography in cortical, cancellous, and total bone and expressed as g mineral/cm(3) bone. Values obtained in women before HRT were lower than those reported in pre- and postmenopausal control women. After conventional HRT, there was an increase in mean DMB (total bone) of 4.4 +/- 1.9% (mean +/- SEM) versus pre-treatment values (4.1 +/- 2.1% in cortical bone, 4.5 +/- 2.3% in cancellous bone); these differences did not reach statistical significance (P = 0.055). Results were similar for DMB Freq. Max. but Heterogeneity Index was not significantly changed. After high dose estradiol therapy, mean DMB (total bone) was 6.9 +/- 1.9% higher than in untreated women (8.6 +/- 2.1% in cortical bone, 6.5 +/- 2.1% in cancellous bone); this difference was statistically significant (P </= 0.03). Results were similar for DMB Freq. Max. but once again Heterogeneity Index was not significantly modified. The increases in mean DMB were due to a shift of the curves towards high DMB with a decrease of the low DMB values, as confirmed by the absence of changes in the Heterogeneity Index. Estrogen therapy is associated with an increased degree of mineralization of bone induced by a prolongation of secondary mineralization, similar to that observed with other antiresorptive agents. However, this increase was about two-fold lower than that observed after alendronate therapy (10 mg/day/3 years) in postmenopausal osteoporotic women.
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PMID:Influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women. 1577 81


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