To cephalometrically compare the skeletal vertical and sagittal effects of TSME with those of RME protraction facemask therapy in Class III patients.
The sample of this retrospective study included ...104 patients (53 females, 51 males) with age ranging from 5 to 9 years, presenting a skeletal Class III relationship: 52 were treated with transverse sagittal maxillary expander (TSME) appliance (Group 1) and 52 with Hyrax rapid maxillary expander/facemask (RME/FM, Group 2). For each patient a lateral cephalogram was obtained before treatment (T0) and at the end of the retention period (T1). Changes in the two groups during the observation period were calculated, compared and statistically analysed with t-test.
TSME can produce skeletal changes and dento-alveolar modifications. RME in association with protraction facemask showed that after treatment the maxilla was moved significantly forward. The correction of the ANB angle was due to a change in mandibular position during treatment which showed a backward and downward rotation.
Both devices were effective in the treatment of subjects with skeletal Class III due to maxillary retrusion.
It recently was reported that Duchenne muscular dystrophy (DMD) patients and mdx mice have elevated levels of caveolin-3 expression in their skeletal muscle. However, it remains unknown whether ...increased caveolin-3 levels in DMD patients contribute to the pathogenesis of DMD. Here, using a genetic approach, we test this hypothesis directly by overexpressing wild-type caveolin-3 as a transgene in mice. Analysis of skeletal muscle tissue from caveolin-3- overexpressing transgenic mice reveals: (i) a dramatic increase in the number of sarcolemmal muscle cell caveolae; (ii) a preponderance of hypertrophic, necrotic, and immature/regenerating skeletal muscle fibers with characteristic central nuclei; and (iii) down-regulation of dystrophin and β -dystroglycan protein expression. In addition, these mice show elevated serum creatine kinase levels, consistent with the myo-necrosis observed morphologically. The Duchenne-like phenotype of caveolin-3 transgenic mice will provide an important mouse model for understanding the pathogenesis of DMD in humans.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Caveolin is a principal component of caveolae membranes. It has been demonstrated that the interaction of the caveolin scaffolding domain with signaling molecules can functionally inhibit the ...activity of these molecules. Taxol is an antitumor agent that suppresses microtubule dynamics and binds to microtubules thereby stabilizing them against depolymerization. The drug also has been implicated in the induction of apoptosis through activation of components in signal transduction cascades. Here we have investigated the role of caveolin in the development of drug resistance by examining the expression of caveolins in low- and high-level drug-resistant cell lines. Caveolin-1, but not caveolin-2, was upregulated in highly multidrug resistant SKVLB1 cells that express high levels of P-glycoprotein, and in low-level Taxol-resistant A549 cell lines that express low amounts of P-glycoprotein. Two drug-resistant A549 cell lines (one 9-fold resistant to Taxol and the other 1.5-fold resistant to epothilone B), both of which express no P-glycoprotein, demonstrate a significant increase in the expression of caveolin-1. These results indicate that in low-level epothilone B- or Taxol-resistant A549 cells, increased caveolin-1 expression occurs independently of P-glycoprotein expression. Electron microscopic studies clearly demonstrate the upregulation of caveolae organelles in Taxol-resistant A549 cells. Upregulation of caveolin-1 expression in drug-sensitive A549 cells was observed acutely beginning 48 h after incubation with 10 nM Taxol. Thus, caveolin-1 may play a role in the development of Taxol resistance in A549 cells.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Epidemiological and clinical studies show higher prevalence of amyotrophic lateral sclerosis (ALS) in males than in females and more severe lesions in androgen receptor (AR)‐expressing ...tissues. The AR gene contains a polymorphic CAG trinucleotide repeat, whose expansion over a certain threshold is toxic to motor neurons, causing spinal and bulbar muscular atrophy (SBMA).
Purpose and methods: We tested the hypothesis that the AR CAG repeat linked to SBMA is a risk factor for ALS. We analyzed AR CAG expansions in 336 patients with ALS and 100 controls.
Results: We found a negative association of AR CAG expansions with ALS susceptibility, clinical presentation, and survival.
Conclusions: Our findings do not support a role of the AR CAG repeat length in ALS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The environmental heterogeneity may reflect the different morphological and phenotypic traits of individuals belonging to a single species. We used 14 morphological traits of Mauritia flexuosa L.f. ...to understanding the relation between environment and phenotypic traits. Twenty-five fruits were collected from each of the 10 individuals sampled in each study site: Chapada dos Guimarães (CG), Vila Bela da Santíssima Trindade (VB), and Alta Floresta (AF). We analyzed the genetic divergence, using the standardized Euclidean distance, the sequential method of Tocher, unweighted pair group method with arithmetic mean (UPGMA), and the projection of the distances onto 2D plane, and calculated the relative importance of the traits evaluated. The analysis showed the partition of individuals into three main groups: Two groups comprising the majority of individuals. Fresh fruit weight, pulp rate, fresh pulp weight, and moisture rate were the traits that most helped explaining the difference between materials. The results shown in the current study evidenced the influence of these three different environments on the biometric traits of M. flexuosa. Such influence has led to the formation of Alta Floresta and Vila Bela da Santíssima Trindade individuals in different groups, whereas the Chapada dos Guimarães individuals were able to permeate the two other groups, although they showed stronger tendency to group with individuals from Vila Bela da Santíssima Trindade.
The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the ...relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers.
The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure.
The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
G protein-coupled receptors (GPCRs) mediate the action of many hormones, cytokines, and sensory and chemical signals. It is generally thought that receptor desensitization and internalization require ...occupancy and activation of the GPCR. PTH and PTHrP receptor (PTH1R) belongs to GPCR class B and is the major regulator of extracellular calcium homeostasis. Using kidney distal convoluted tubule cells transfected with a human PTH1R/enhanced green fluorescent protein fusion protein, quantitative, real-time fluorescence microscopy was used to analyze receptor internalization. In these cells, which are the target of the calcium-sparing action of PTH, PTH(1–34) activated adenylyl cyclase (AC) and phospholipase C (PLC) and PTH1R endocytosis. PTH(1–31), however, stimulated AC and PLC but not PTH1R endocytosis. Conversely, PTH(7–34) rapidly stimulated PTH1R internalization without activating AC or PLC. PTH(2–34) and (3–34) caused PTH1R internalization intermediate between PTH(1–34) and (7–34). PTH1R sequestration occurred in a dynamin- and clathrin-dependent manner. Directly activating AC inhibited PTH1R internalization in response to PTH(7–34). PTH1R endocytosis was sensitive to protein kinase C inhibition. PTH(1–34), (7–34), and (1–31) evoked PTH1R phosphorylation. Removal of most of the C terminus of the PTH1R eliminated receptor phosphorylation and the cAMP/protein kinase C sensitivity of internalization. PTH(1–34) and (7–34) internalized the truncated PTH1R with identical kinetics, and the response was unaffected by forskolin. Thus, the PTH1R C terminus contains regulatory sequences that are involved in, but not required for, PTH1R internalization. The results demonstrate that receptor activation and internalization can be selectively dissociated.
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