982 resultados para Dual Specificity Phosphatase 1


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BACKGROUND: The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration. METHODS: Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load <1000 copies/mL for > or =5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (> or =500 cells/microL was defined as a complete response, and <500 cells/microL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses. RESULTS: The median CD4 T cell count increased from 180 cells/microL at baseline to 576 cells/microL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau <500 cells/microL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders (P>.05). Older age (adjusted odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count <500 cells/microL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders (P<.001) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% sensitivity and 72% specificity. CONCLUSION: Individuals with incomplete CD4 T cell recovery to <500 cells/microL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes.

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Dental identification is the most valuable method to identify human remains in single cases with major postmortem alterations as well as in mass casualties because of its practicability and demanding reliability. Computed tomography (CT) has been investigated as a supportive tool for forensic identification and has proven to be valuable. It can also scan the dentition of a deceased within minutes. In the present study, we investigated currently used restorative materials using ultra-high-resolution dual-source CT and the extended CT scale for the purpose of a color-encoded, in scale, and artifact-free visualization in 3D volume rendering. In 122 human molars, 220 cavities with 2-, 3-, 4- and 5-mm diameter were prepared. With presently used filling materials (different composites, temporary filling materials, ceramic, and liner), these cavities were restored in six teeth for each material and cavity size (exception amalgam n = 1). The teeth were CT scanned and images reconstructed using an extended CT scale. Filling materials were analyzed in terms of resulting Hounsfield units (HU) and filling size representation within the images. Varying restorative materials showed distinctively differing radiopacities allowing for CT-data-based discrimination. Particularly, ceramic and composite fillings could be differentiated. The HU values were used to generate an updated volume-rendering preset for postmortem extended CT scale data of the dentition to easily visualize the position of restorations, the shape (in scale), and the material used which is color encoded in 3D. The results provide the scientific background for the application of 3D volume rendering to visualize the human dentition for forensic identification purposes.

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Human maltase-glucoamylase (MGAM) is one of the two enzymes responsible for catalyzing the last glucose-releasing step in starch digestion. MGAM is anchored to the small-intestinal brush-border epithelial cells and contains two homologous glycosyl hydrolase family 31 catalytic subunits: an N-terminal subunit (NtMGAM) found near the membrane-bound end and a C-terminal luminal subunit (CtMGAM). In this study, we report the crystal structure of the human NtMGAM subunit in its apo form (to 2.0 A) and in complex with acarbose (to 1.9 A). Structural analysis of the NtMGAM-acarbose complex reveals that acarbose is bound to the NtMGAM active site primarily through side-chain interactions with its acarvosine unit, and almost no interactions are made with its glycone rings. These observations, along with results from kinetic studies, suggest that the NtMGAM active site contains two primary sugar subsites and that NtMGAM and CtMGAM differ in their substrate specificities despite their structural relationship. Additional sequence analysis of the CtMGAM subunit suggests several features that could explain the higher affinity of the CtMGAM subunit for longer maltose oligosaccharides. The results provide a structural basis for the complementary roles of these glycosyl hydrolase family 31 subunits in the bioprocessing of complex starch structures into glucose.

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OBJECTIVE: The aim of this investigation was to assess soluble endoglin (sEng) and soluble fms-like tyrosine kinase-1 (sFlt1) as first-trimester serum markers to predict preeclampsia. STUDY DESIGN: First-trimester sera were obtained from 46 women with subsequent late-onset preeclampsia and from 92 controls. sEng and sFlt1 concentrations were determined immunoanalytically. Correlation analysis with inhibin A and placental growth factor levels was performed. RESULTS: sEng and sFlt1 serum concentrations were higher in women with subsequent preeclampsia than in controls (mean +/- SD, sEng: 5.57 +/- 1.18 ng/mL vs 5.02 +/- 1.01 ng/mL, P = .009; sFlt1: 1764 +/- 757 pg/mL vs 1537 +/- 812 pg/mL, P = .036). Sensitivities and specificities for predicting preeclampsia were 63% and 57% for sEng and 64% and 56% for sFlt1, respectively. When sEng and inhibin A were combined, the sensitivity increased to 68%, whereas the specificity was 61%. CONCLUSION: sEng and sFlt1 are increased in the first trimester in women with subsequent late-onset preeclampsia and might therefore prove useful to predict preeclampsia.

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One dimensional magnetic photonic crystals (1D-MPC) are promising structures for integrated optical isolator applications. Rare earth substituted garnet thin films with proper Faraday rotation are required to fabricate planar 1D-MPCs. In this thesis, flat-top response 1D-MPC was proposed and spectral responses and Faraday rotation were modeled. Bismuth substituted iron garnet films were fabricated by RF magnetron sputtering and structures, compositions, birefringence and magnetooptical properties were studied. Double layer structures for single mode propagation were also fabricated by sputtering for the first time. Multilayer stacks with multiple defects (phase shift) composed of Ce-YIG and GGG quarter-wave plates were simulated by the transfer matrix method. The transmission and Faraday rotation characteristics were theoretically studied. It is found that flat-top response, with 100% transmission and near 45o rotation is achievable by adjusting the inter-defect spacing, for film structures as thin as 30 to 35 μm. This is better than 3-fold reduction in length compared to the best Ce-YIG films for comparable rotations, thus allows a considerable reduction in size in manufactured optical isolators. Transmission bands as wide as 7nm were predicted, which is considerable improvement over 2 defects structure. Effect of repetition number and ratio factor on transmission and Faraday rotation ripple factors for the case of 3 and 4 defects structure has been discussed. Diffraction across the structure corresponds to a longer optical path length. Thus the use of guided optics is required to minimize the insertion losses in integrated devices. This part is discussed in chapter 2 in this thesis. Bismuth substituted iron garnet thin films were prepared by RF magnetron sputtering. We investigated or measured the deposition parameters optimization, crystallinity, surface morphologies, composition, magnetic and magnetooptical properties. A very high crystalline quality garnet film with smooth surface has been heteroepitaxially grown on (111) GGG substrate for films less than 1μm. Dual layer structures with two distinct XRD peaks (within a single sputtered film) start to develop when films exceed this thickness. The development of dual layer structure was explained by compositional gradient across film thickness, rather than strain gradient proposed by other authors. Lower DC self bias or higher substrate temperature is found to help to delay the appearance of the 2nd layer. The deposited films show in-plane magnetization, which is advantageous for waveguide devices application. Propagation losses of fabricated waveguides can be decreased by annealing in an oxygen atmosphere from 25dB/cm to 10dB/cm. The Faraday rotation at λ=1.55μm were also measured for the waveguides. FR is small (10° for a 3mm long waveguide), due to the presence of linear birefringence. This part is covered in chapter 4. We also investigated the elimination of linear birefringence by thickness tuning method for our sputtered films. We examined the compressively and tensilely strained films and analyze the photoelastic response of the sputter deposited garnet films. It has been found that the net birefringence can be eliminated under planar compressive strain conditions by sputtering. Bi-layer GGG on garnet thin film yields a reduced birefringence. Temperature control during the sputter deposition of GGG cover layer is critical and strongly influences the magnetization and birefringence level in the waveguide. High temperature deposition lowers the magnetization and increases the linear birefringence in the garnet films. Double layer single mode structures fabricated by sputtering were also studied. The double layer, which shows an in-plane magnetization, has an increased RMS roughness upon upper layer deposition. The single mode characteristic was confirmed by prism coupler measurement. This part is discussed in chapter 5.

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This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the ventral retina and visual streak. In damaged regions, the outer nuclear layer was reduced in thickness or eliminated entirely, with a concomitant loss of immunoreactivity for rhodopsin. However, the magnitude of the effect varied between animals with the same IAA dose and survival time, suggesting individual differences in the bioavailability of the toxin. In all eyes, the inner retina remained intact, as judged by the thickness of the inner nuclear layer, and by the pattern of immunoreactivity for protein kinase C-alpha (rod bipolar cells) and calbindin D-28 (horizontal cells). Müller cell stalks became immunoreactive for glial fibrillary acidic protein (GFAP) even in IAA-treated retinae that had no signs of cell loss, indicating a response of the retina to the toxin. However, no marked hypertrophy or proliferation of Müller cells was observed with either GFAP or vimentin immunohistochemistry. Thus the selective, long lasting damage to the photoreceptors produced by this toxin did not lead to a reorganization of the surviving cells, at least with survival as long as 6 months, in contrast to the remodeling of the inner retina that is observed in inherited retinal degenerations such as retinitis pigmentosa and retinal injuries such as retinal detachment.

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BACKGROUND: Renal calcium stones and hypercalciuria are associated with a reduced bone mineral density (BMD). Therefore, the effect of changes in calcium homeostasis is of interest for both stones and bones. We hypothesized that the response of calciuria, parathyroid hormone (PTH) and 1.25 vitamin D to changes in dietary calcium might be related to BMD. METHODS: A single-centre prospective interventional study of 94 hyper- and non-hypercalciuric calcium stone formers consecutively retrieved from our stone clinic. The patients were investigated on a free-choice diet, a low-calcium diet, while fasting and after an oral calcium load. Patient groups were defined according to lumbar BMD (z-score) obtained by dual X-ray absorptiometry (group 1: z-score <-0.5, n = 30; group 2: z-score -0.5-0.5, n = 36; group 3: z-score >0.5, n = 28). The effect of the dietary interventions on calciuria, 1.25 vitamin D and PTH in relation to BMD was measured. RESULTS: An inverse relationship between BMD and calciuria was observed on all four calcium intakes (P = 0.009). On a free-choice diet, 1.25 vitamin D and PTH levels were identical in the three patient groups. However, the relative responses of 1.25 vitamin D and PTH to the low-calcium diet were opposite in the three groups with the highest increase of 1.25 vitamin D in group 1 and the lowest in group 3, whereas PTH increase was most pronounced in group 3 and least in group 1. CONCLUSION: Calcium stone formers with a low lumbar BMD exhibit a blunted response of PTH release and an apparently overshooting production of 1.25 vitamin D following a low-calcium diet.

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BACKGROUND: Natural xenoreactive antibodies (Abs) directed against the Bdi-epitope (Gal alpha 1-3Gal beta) on the cells of non-primate mammals take part in hyperacute rejection of xenotransplanted organs. We found that some Abs, which were one-step affinity purified on Bdi-Sepharose, cross-reacted with the disaccharide Gal alpha 1-4GlcNAc beta. The epitope Gal alpha 1-4GlcNAc has not been identified on mammals or bacterial polysaccharides yet. METHODS: To isolate the antibodies of the corresponding specificity the disaccharide was immobilized on Sepharose and antibodies were affinity purified from pooled serum of blood group O individuals. RESULTS: These one-step purified Abs cross-reacted with Bdi, but after a prior absorption step on Bdi-Sepharose no cross-reactivity with Bdi was observed any longer. Surprisingly, the quantity of anti-Gal alpha 1-4GlcNAc isolated from the same serum pool, 4-7 microg/ml, was equal to that of anti-Bdi or more. Independently of ABO blood groups all the tested healthy donors had anti-Gal alpha 1-4GlcNAc Abs at a similar level. Monospecific anti-Gal alpha 1-4GlcNAc Abs were not cytotoxic towards porcine cells. CONCLUSIONS: 1. The actual concentration of monospecific, xenoreactive Gal alpha 1-3Gal beta Abs in blood may be considerably lower than the value referred to in the literature for 'anti-alpha Gal' or 'anti-Galili' antibodies. 2. Anti-Gal alpha 1-4GlcNAc Abs seem not to be important for xenotransplantation.

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This study defines the feasibility of utilizing three-dimensional (3D) gradient-echo (GRE) MRI at 1.5T for T(2)* mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T(2)* mapping without gadolinium-enhancement utilizing a 3D-GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual-flip-angle 3D-GRE sequence for dGEMRIC T(1) mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T(1) and T(2)* findings were subsequently correlated. There were significant differences between volunteers and patients in normally-rated cartilage only for T(1) values. Both T(1) and T(2)* values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T(2)* (T(1)) (P < 0.05). High intraclass correlation was noted for both T(1) and T(2)*. Correlation factor was 0.860 to 0.954 (T(2)*-T(1) intraobserver) and 0.826 to 0.867 (T(2)*-T(1) interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T(2)* mapping at 1.5T.

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RATIONALE AND OBJECTIVES: The aim of this study was to measure the radiation dose of dual-energy and single-energy multidetector computed tomographic (CT) imaging using adult liver, renal, and aortic imaging protocols. MATERIALS AND METHODS: Dual-energy CT (DECT) imaging was performed on a conventional 64-detector CT scanner using a software upgrade (Volume Dual Energy) at tube voltages of 140 and 80 kVp (with tube currents of 385 and 675 mA, respectively), with a 0.8-second gantry revolution time in axial mode. Parameters for single-energy CT (SECT) imaging were a tube voltage of 140 kVp, a tube current of 385 mA, a 0.5-second gantry revolution time, helical mode, and pitch of 1.375:1. The volume CT dose index (CTDI(vol)) value displayed on the console for each scan was recorded. Organ doses were measured using metal oxide semiconductor field-effect transistor technology. Effective dose was calculated as the sum of 20 organ doses multiplied by a weighting factor found in International Commission on Radiological Protection Publication 60. Radiation dose saving with virtual noncontrast imaging reconstruction was also determined. RESULTS: The CTDI(vol) values were 49.4 mGy for DECT imaging and 16.2 mGy for SECT imaging. Effective dose ranged from 22.5 to 36.4 mSv for DECT imaging and from 9.4 to 13.8 mSv for SECT imaging. Virtual noncontrast imaging reconstruction reduced the total effective dose of multiphase DECT imaging by 19% to 28%. CONCLUSION: Using the current Volume Dual Energy software, radiation doses with DECT imaging were higher than those with SECT imaging. Substantial radiation dose savings are possible with DECT imaging if virtual noncontrast imaging reconstruction replaces precontrast imaging.

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BACKGROUND: All site-specific interactions between HIV type-1 (HIV-1) subtype, human leukocyte antigen (HLA)-associated immune selection and integrase inhibitor resistance are not completely understood. We examined naturally occurring polymorphisms in HIV-1 integrase sequences from 342 antiretroviral-naive individuals from the Western Australian HIV Cohort Study and the Swiss HIV Cohort Study. METHODS: Standard bulk sequencing and sequence-based typing were used to generate integrase sequences and high-resolution HLA genotypes, respectively. Viral residues were examined with respect to drug resistance mutations and CD8(+) T-cell escape mutations. RESULTS: In both predominantly subtype B cohorts, 12 of 38 sites that mediate integrase inhibitor resistance mutations were absolutely conserved, and these included the primary resistance mutations. There were 18 codons with non-primary drug resistance-associated substitutions at rates of up to 58.8% and eight sites with alternative polymorphisms. Five viral residues were potentially subject to dual-drug and HLA-associated immune selection in which both selective pressures either drove the same amino acid substitution (codons 72, 157 and 163) or HLA alleles were associated with an alternative polymorphism that would alter the genetic barrier to resistance (codons 125 and 193). The common polymorphism T125A, which was characteristic of non-subtype B and was also associated with carriage of HLA-B*57/*5801, increased the mutational barrier to the resistance mutation T125K. CONCLUSIONS: Primary integrase inhibitor resistance mutations were not detected in the absence of drug exposure in keeping with sites of high constraint. Viral polymorphisms caused by immune selection and/or associated with non-subtype B might alter the genetic barrier to some non-primary resistance-associated mutations.

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BACKGROUND:Accurate quantification of the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance in patients who are receiving antiretroviral therapy (ART) is difficult, and results from previous studies vary. We attempted to assess the prevalence and dynamics of resistance in a highly representative patient cohort from Switzerland. METHODS:On the basis of genotypic resistance test results and clinical data, we grouped patients according to their risk of harboring resistant viruses. Estimates of resistance prevalence were calculated on the basis of either the proportion of individuals with a virologic failure or confirmed drug resistance (lower estimate) or the frequency-weighted average of risk group-specific probabilities for the presence of drug resistance mutations (upper estimate). RESULTS:Lower and upper estimates of drug resistance prevalence in 8064 ART-exposed patients were 50% and 57% in 1999 and 37% and 45% in 2007, respectively. This decrease was driven by 2 mechanisms: loss to follow-up or death of high-risk patients exposed to mono- or dual-nucleoside reverse-transcriptase inhibitor therapy (lower estimates range from 72% to 75%) and continued enrollment of low-risk patients who were taking combination ART containing boosted protease inhibitors or nonnucleoside reverse-transcriptase inhibitors as first-line therapy (lower estimates range from 7% to 12%). A subset of 4184 participants (52%) had >or= 1 study visit per year during 2002-2007. In this subset, lower and upper estimates increased from 45% to 49% and from 52% to 55%, respectively. Yearly increases in prevalence were becoming smaller in later years. CONCLUSIONS:Contrary to earlier predictions, in situations of free access to drugs, close monitoring, and rapid introduction of new potent therapies, the emergence of drug-resistant viruses can be minimized at the population level. Moreover, this study demonstrates the necessity of interpreting time trends in the context of evolving cohort populations.

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Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.

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The aim of this study was to determine the influence of individual factors on differences in bone mineral density (BMD) using dual X-ray absorptiometry pencil beam (PB) and fan beam (FB) modes in vivo and in vitro. PB.BMD and FB.BMD of 63 normal Caucasian females ages 21-80 yr were measured at the lumbar spine and hip. Residuals of the FB/PB regression were used to assess the impact of height, weight, adiposity index (AI) (= weight/height(3/2)), back tissue thickness, and PB.BMD, respectively, on FB/PB difference. The Hologic Anthropomorphic Spine Phantom (ASP) was measured using the PB and FB modes at two different levels to assess the impact of scanning mode and focus distance. The European Spine Phantom (ESP) prototype, a geometrically well-defined phantom with known vertebral densities, was measured using PB and FB modes and analyzed manually to determine the impact of bone density on FB/PB difference and automatically to determine the impact of edge detection on FB/PB difference. Population BMD results were perfectly correlated, but significantly overestimated by 1.5% at the lumbar spine and underestimated by 0.7% at the neck, 1.8% at the trochanter, and 2.0% at the total hip, respectively, when using the FB compared with PB mode. At the lumbar spine, the FB/PB residual correlated negatively with height (r = 0.34, p < 0.01) and PB.BMD (r = 0.48, p <: 0. 0001) and positively with AI (r = 0.26, p < 0.05). At the hip, residual of trochanter correlated positively with weight (r = 0.36, p < 0.01) and AI (r = 0.36, p < 0.01). The FB mode significantly increased ASP BMD by 0.7% compared with PB. Using the FB mode, increasing focus distance significantly (p < 0.001) decreased area and bone mineral content, but not BMD. By contrast, increasing focus distance significantly decreased PB.BMD by 0.7%. With the ESP, the PB mode supplied accurate projected are of the bone (AREA) results but significant underestimation of specified BMD in the manual analysis. The FB mode significantly underestimated PB. AREA by 2.9% but fitted specified BMD quite well. FB/PB overestimation was larger for the low-density (+8.7%) than for the high-density vertebra (+4. 9%). The automated analysis resulted in more than 14% underestimation of PB. AREA (low-density vertebra) and an almost 13% overestimation of PB.BMD (high-density vertebra) using FB. In conclusion, FB and PB measurements are highly correlated at the lumbar spine and hip with small but significant BMD differences related to height, adiposity, and BMD. In clinical practice, it can be erroneous to switch from one method to another, especially in women with low bone density.

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To assess the effect of age and disease on mineral distribution at the distal third of the tibia, bone mineral content (BMC) and bone mineral density (BMD) were measured at lumbar spine (spine), femoral neck (neck), and diaphysis (Dia) and distal epiphysis (Epi) of the tibia in 89 healthy control women of different age groups (20-29, n = 12; 30-39, n = 11; 40-44, n = 12; 45-49, n = 12; 50-54, n = 12; 55-59, n = 10; 60-69, n = 11; 70-79, n = 9), in 25 women with untreated vertebral osteoporosis (VOP), and in 19 women with primary hyperparathyroidism (PHPT) using dual-energy x-ray absorptiometry (DXA; Hologic QDR 1000 and standard spine software). A soft tissue simulator was used to compensate for heterogeneity of soft tissue thickness around the leg. Tibia was scanned over a length of 130 mm from the ankle joint, fibula being excluded from analysis. For BMC and BMD, 10 sections 13 mm each were analyzed separately and then pooled to define the epiphysis (Epi 13-52 mm) and diaphysis area (Dia 91-130 mm). Precision after repositioning was 1.9 and 2.1% for Epi and Dia, respectively. In the control group, at any site there was no significant difference between age groups 20-29 and 30-39, which thus were pooled to define the peak bone mass (PBM).(ABSTRACT TRUNCATED AT 250 WORDS)