Par6alpha signaling controls glial-guided neuronal migration

Neuronal migrations along glial fibers provide a primary pathway for the formation of cortical laminae. To examine the mechanisms underlying glial-guided migration, we analyzed the dynamics of cytoskeletal and signaling components in living neurons. Migration involves the coordinated two-stroke movement of a perinuclear tubulin 'cage' and the centrosome, with the centrosome moving forward before nuclear translocation. Overexpression of mPar6alpha disrupts the perinuclear tubulin cage, retargets PKCzeta and gamma-tubulin away from the centrosome, and inhibits centrosomal motion and neuronal migration. Thus, we propose that during neuronal migration the centrosome acts to coordinate cytoskeletal dynamics in response to mPar6alpha-mediated signaling.     

Corpus callosum morphometry: comparison of fresh brain,preserved brain and magnetic resonance imaging values

In recent years interest in the anatomy of corpus callosum (CC) has led to a number of studies on morphometric analysis of CC, either in vivo on magnetic resonance imaging (MRI) or on preserved (formalin-fixed) cadaveric brain specimens. There are very few reports comparing the values obtained by both these methodologies, and to the authors' knowledge no study of CC morphometry in fresh (unfixed) autopsy brains has been done. Morphometric measurements of the CC were done on fresh autopsy brains ( n  = 15), preserved cadaveric brains ( n  = 44) and MRI scans ( n  = 30) in adults (age range: 20–60 years) of both sexes without any intracranial brain pathology, in north-west Indian subjects. Most of the CC measurements were found to be more in the fresh autopsy brain group as compared to the preserved cadaveric brain and MRI group. The distance between the splenium and superior colliculus in the fresh autopsy brain group was almost twice that in the other two groups. In addition, there was a similarity between the preserved cadaveric brain and MRI values for most of the parameters, but the distances between the genu and fornix and between the genu and anterior commissure were larger in the MRI group as compared to the other two groups. The present data may be of value in studying deviations from the normal in various disease processes as well in surgical planning of intraventricular and callosal pathologies.     

Alkali-free bioactive glasses for bone tissue engineering: a preliminary investigation

An alkali-free series of bioactive glasses has been designed and developed in the glass system CaO-MgO-SiO₂-P₂O₅-CaF₂ along the diopside (CaMgSi₂O₆)-fluorapatite (Ca₅(PO₄)₃F)-tricalcium phosphate (3CaO·P₂O₅) join. The silicate network in all the investigated glasses is predominantly coordinated in Q² (Si) units, while phosphorus tends to remain in an orthophosphate (Q⁰) environment. The in vitro bioactivity analysis of glasses has been made by immersion of glass powders in simulated body fluid (SBF) while chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. Some of the investigated glasses exhibit hydroxyapatite formation on their surface within 1-12 h of their immersion in SBF solution. The sintering and crystallization kinetics of glasses has been investigated by differential thermal analysis and hot-stage microscopy, respectively while the crystalline phase evolution in resultant glass-ceramics has been studied in the temperature range of 800-900 °C using powder X-ray diffraction and scanning electron microscopy. The alkaline phosphatase activity and osteogenic differentiation for glasses have been studied in vitro on sintered glass powder compacts using rat bone marrow mesenchymal stem cells. The as-designed glasses are ideal candidates for their potential applications in bone tissue engineering in the form of bioactive glasses as well as glass/glass-ceramic scaffolds.     

Hormonal effects on the immunocytochemical location of 3',5'-cyclic adenosine monophosphate-dependent protein kinase in rat tissues

Homogeneous preparations of type I and type II regulatory subunits (RI and RII, respectively) of cAMP-dependent protein kinase (cAMP kinase) were utilized as antigens to obtain isozyme specific antisera. Injections of pure catalytic subunit (C) from the type I isozyme resulted in antisera that reacted with C subunit obtained from either isozyme type. Cross-reactivity of the antisera raised against isolated subunits of the kinase was assessed by immunodiffusion analysis and by measuring the cAMP binding and phosphotransferase activities of the subunits after immunoprecipitation. These antisera were used to localize subunits of type I and type II cAMP kinases in rat skeletal muscle, liver, and adrenal by using indirect immunofluorescence and immunoperoxidase techniques. Specificity of the immunofluorescence was shown by absorption of the antisera with pure homologous antigens. In skeletal muscle, both R and C subunits of the type I and type II cAMP kinases were localized in the area of the sarcoplasmic reticulum and in periodic crossbands. Specific fluorescence for these components was observed in both isotropic and anisotropic band regions of the sarcomere. Densitometric determinations of immunoperoxidase staining revealed a larger amount of RI, RII, and C subunits in the isotropic band than in the anisotropic band regions. In liver, C, RI, and RII subunits were distributed both in cytoplasmic and nuclear areas and along plasma membranes of hepatocytes; however, there were qualitative differences observed among these various subcellular sites. With each antiserum, fluorescence was blocked by prior absorption with homologous antigen. After treatment of rats with glucagon, dramatic changes in the relative distribution patterns of C and RII were noted in the nucleus. In the adrenal gland, RI, RII, and C subunits were localized in both cytoplasmic and nuclear areas, and an apparent redistribution of these subunits occurred after treatment of (dexamethasone-suppressed) rats with ACTH. The application of this immunocytochemical approach provides a tool for examining and monitoring the subcellular distribution of these components of cAMP kinase in biological systems.     

Evaluation and outcome of patients with syncope

We studied 433 patients with syncope to derive insights into the diagnostic evaluation and outcome of patients with this common problem. This study shows that the etiology of syncope was not found in approximately 41% of patients. When a cause of syncope was determined, it was most frequently established on the basis of initial history, physical examination and an electrocardiogram (EKG). Furthermore, many of the other entities (e.g., aortic stenosis, subclavian steal) were suggested by findings on the history and physical examinations that required directed diagnostic testing. Initial EKG was abnormal in 50% of patients but led to a cause of syncope infrequently (less than 7%). Prolonged electrocardiographic monitoring, which has assumed a central role in the evaluation of syncope, led to a specific cause in only 22% of patients. Other tests were less often helpful in assigning a cause of syncope. At 5 years, the mortality of 50.5% in patients with a cardiac cause of syncope was significantly higher than the 30% mortality in patients with a noncardiac cause or 24.1% in patients with an unknown cause. At 5 years, a mortality of 50.5% in patients with a cardiac cause of syncope was noted. There were 54 actual deaths in this group as compared to 10.7 expected deaths based on 1980-86 mortality data from Allegheny County, PA (standardized mortality ratio = 5.02). At 5 years, a 33.1% incidence of sudden death was noted in patients with cardiac cause of syncope, as compared with 4.9% in patients with a noncardiac cause and 8.5% in patients with an unknown cause. Mortality and sudden death remained significant for the first 3 years after which the survival curves were parallel. A cardiac cause of syncope was an independent predictor of sudden death and mortality. Recurrences were common but were not associated with an increased risk of mortality or sudden death. Major vascular events were also more frequent in patients with cardiac causes of syncope. The results of this study will be helpful in designing future studies to evaluate the usefulness of newer diagnostic techniques. Furthermore, short- and long-term outcome data will be useful in planning intervention strategies in these patients.     

Erectile Dysfunction Precedes and Is Associated with Severity of Coronary Artery Disease among Asian Indians

IntroductionErectile dysfunction (ED) and coronary artery disease (CAD) often share common risk factors, and there is growing evidence that ED might serve as a clinical marker for cardiovascular disease. Despite rising trends of CAD in Asian Indians, limited data are available on the prevalence of ED and its correlation with CAD severity in such patients.AimTo study the prevalence of ED in Asian Indian patients undergoing coronary angiography and to assess if the severity of ED correlates with angiographic severity of CAD.MethodsIn all patients undergoing coronary angiography, ED was assessed using the International Index of Erectile Function‐5 questionnaire.Main Outcome Measures and ResultsAmong 175 male patients, ED was present in 70%; patients with ED had a higher incidence of multivessel CAD (80% vs. 36%, P 0.001), diffuse CAD (81% vs. 34%, P 0.001), and higher number of mean coronary vessels involved compared with those without ED. Those with severe ED had higher prevalence of multivessel CAD and higher number of mean coronary vessels involved compared with those with milder grades of ED. Onset of symptoms of ED preceded symptoms of CAD by a mean of 24.6 months in 84% of patients. The presence of severe ED was associated with a 21‐fold higher risk of having triple‐vessel disease (odds ratio [OR] 21.94, 95% confidence interval [CI] 3.41–141.09, P = 0.001) and an 18‐fold higher risk of having diffuse angiographic CAD (OR 17.91, 95% CI 3.11–111.09, P = 0.001).ConclusionAsian Indians with angiographic CAD frequently have ED; symptoms of ED precede that of CAD in most patients. Incidence of multivessel and diffuse CAD is significantly more common in patients with ED. It is important for physicians to be aware of the close relationship between the two conditions so that patients with ED can have optimal risk stratification for concomitant CAD whenever required.