Molecular internalization of a region of myelin basic protein

The conformation of myelin encephalitogenic or basic protein (BP) was investigated with a double-antibody radioimmunoassay by studying the reaction of BP or its fragments with antibodies produced in two rabbits against peptide 43-88 linked to rabbit serum albumin. Both antisera reacted well with peptide 43-88 but showed little or no reaction with BP. Absorption of these antisera with a BP-immunoadsorbent did not remove the antibody activity against peptide 43-88. Within the region of peptide 43- 88 it was shown that peptides 68-88 and 79-88 gave an equivalent or better reaction than peptide 43-88, whereas peptides 43-67 and 64-73 had very little reactivity. In the BP fragments containing region 43-88, peptide 1-88 showed the best reactivity, peptide 20-166 showed minimal reactivity, while peptide 1-115 showed none. These data document the internal position of at least a portion of peptide 43-88 and all of residues 79-88 in the BP molecule. The much greater reactivity of peptide 1-88 as compared to peptide 1-115 suggests that the region or a portion of the region of BP containing residues 89- 115 participates in the conformational alignment of BP restricting access to peptide 79-88. After absorption with BP, neither of the antisera prepared to peptide 43-88 reacted with PNS myelin in fixed tissue sections but continued to react with CNS myelin in similarly treated sections. The present findings demonstrate the need to consider the role of shielded antigenic determinants in the investigation of antigens or of immune responses.     

The (not necessarily) convoluted role of basal radial glia in cortical neurogenesis

Recent advances in cell labeling and imaging techniques have dramatically expanded our knowledge of the neural precursor cells responsible for corticogenesis. In particular, radial glial cells are now known to generate several classes of restricted progenitors and neurons. While radial glial cells in the ventricular zone have received the most attention, it has become increasingly clear that a distinct subclass of radial glial cells situated in the subventricular zone (SVZ) and intermediate zone also play an important role in corticogenesis. These delaminated radial glial cells, which lack an apical process attached to the ventricular surface but maintain a basal process, were discovered over 3 decades ago. Recently, they have been further characterized as cortical progenitors and renamed outer, intermediate, or basal radial glia (bRG). Some of these studies indicated that bRG abundance in the outer SVZ (oSVZ) is correlated with enhanced gyrencephaly, particularly in primates and especially human, and therefore suggested that bRG may be responsible for the emergence and evolution of cerebral convolutions. In this issue of Cerebral Cortex, 2 papers provide new information about bRG in common marmosets, a near-lissencephalic primate, and in agouti, a near-gyrencephalic rodent (Garcia-Moreno et al. 2011; Kelava et al. 2011). They demonstrate that bRG are abundant and proliferate in inner as well as oSVZ, in both species. Together, these findings indicate that bRG and the oSVZ might not be correlated with gyrification or phylogeny. Rather, differential regulation of bRG and other progenitor types may enhance the adaptability and diversity of cortical morphogenesis.     

Tpr homologs in Treponema paraluiscuniculi Cuniculi A strain

Treponema paraluiscuniculi, the etiologic agent of rabbit venereal syphilis, is morphologically indistinguishable from Treponema pallidum subsp. pallidum (T. pallidum), the human syphilis treponeme, and induces similar immune responses and histopathologic changes in the infected host. Because of their high degree of relatedness, comparative studies are likely to identify genetic determinants that contribute to pathogenesis or virulence in human syphilis. The tpr (Treponema pallidum repeat) genes are believed to code for potential virulence factors. In this study, we identified 10 tpr homologs in Treponema paraluiscuniculi Cuniculi A strain and determined their sequence architecture. Half of this group of paralogous genes were predicted to be nonfunctional due to the presence of frameshifts and premature stop codons. Furthermore, the immune response against the T. paraluiscuniculi Tpr homologs in long-term-infected rabbits was studied by enzyme-linked immunosorbent assay and lymphocyte proliferation assay, showing that TprK is the only target of the antibody and T-cell responses during experimental infection and emphasizing the importance of this putative virulence factor in venereal treponematosis.     

Aplastic anemia with fetallike erythropoiesis following androgen therapy

A 43/4-yr-old black girl with acquired aplastic anemia had an increase in total hemoglobin (Hb) from 4.5 to 16.8 g/dl and fetal hemoglobin (HbF) from 0.8 g/dl (18.8%) to 9.6 g/dl (60.2%) following combined androgen-adrenal steroid therapy. Discontinuation of the drugs was followed by a decline in both HbF and total Hb. Reinstitution of the combined steroids prompted a second rise in total and fetal hemoglobin. During these responses the subject's erythrocytes exhibited an increased i antigen score and a low level of red cell carbonic anhydrase. The glycine:alanine ratio at position 136 of the gamma chains of HbF was of the fetal type (proportion of chains with glycine residues, 0.74). Hemoglobin A2 was low (0.4%). The synthesis of alpha and non-alpha chains was balanced. These results indicate that the stimulation of red cell proliferation in this subject, in response to androgen therapy, resulted in the production of cells with several characteristics of "fetal" erythrocytes.     

Prevalence of asymptomatic left ventricular systolic dysfunction in hypertensive Nigerians: echocardiographic study of 832 subjects

Background

We sought to determine the prevalence of echocardiographically determined left ventricular systolic dysfunction in asymptomatic hypertensive subjects seen in Abeokuta, Nigeria.

Methods

Echocardiography was performed in 832 consecutive hypertensive subjects referred for cardiac evaluation over a three-year period.

Results

Data were obtained in 832 subjects (50.1% women) aged 56.0 ± 12.7 years (men 56.9 ± 13.3 years, women 55.0 ± 12.0 years, range 15–88). The prevalence of left ventricular systolic dysfunction (LVSD) was 18.1% in the study population (mild LVSD = 9.6%, moderate LVSD = 3.7% and severe LVSD = 4.8%). In a multivariate analysis, male gender, body mass index and LV mass were the predictors of LVSD.

Conclusion

Significant numbers of hypertensive subjects in this study had varying degrees of left ventricular systolic dysfunction. Early introduction of disease-modifying drugs in these patients, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers may retard or prevent the progression to overt heart failure.     

Essential role of Shp2-binding sites on FRS2alpha for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells

Mammalian corticogenesis occurs through a complex process that includes neurogenesis, in which neural progenitor cells proliferate, differentiate, and migrate. It has been reported recently that neurogenesis occurs in the subventricular zone (SVZ), a region previously thought to be the primary site of gliogenesis. It has been recognized that in the SVZ, intermediate progenitor cells, derived from radial glial cells that are multipotent neural stem cells, produce only neurons. However, the molecular mechanisms underlying the regulation of neural stem cells and intermediate progenitor cells as well as their contribution to overall corticogenesis remain unknown. The docking protein FRS2alpha is a major mediator of signaling by means of FGFs and neurotrophins. FRS2alpha mediates many of its pleiotropic cellular responses by recruiting the adaptor protein Grb2 and the protein tyrosine phosphatase Shp2 upon ligand stimulation. Here, we report that targeted disruption of Shp2-binding sites in FRS2alpha leads to severe impairment in cerebral cortex development in mutant mice. The defect in corticogenesis appears to be due at least in part to abnormalities in intermediate progenitor cells. Genetic evidence is provided that FRS2alpha plays critical roles in the maintenance of intermediate progenitor cells and in neurogenesis in the cerebral cortex. Moreover, FGF2-responsive neurospheres, which are cell aggregates derived from neural stem/progenitor cells (NSPCs), from FRS2alpha mutant mice were smaller than those of WT mice. However, mutant NSPCs were able to self-renew, demonstrating that Shp2-binding sites on FRS2alpha play an important role in NSPC proliferation but are dispensable for NSPC self-renewing capacity after FGF2 stimulation.     

Spinal cord compression due to metastatic disease: diagnosis with MR imaging versus myelography

To determine the efficacy of magnetic resonance (MR) imaging and myelography for the diagnosis of spinal cord compression due to metastatic disease, the authors prospectively examined 70 patients who had known or suspected spinal involvement by malignancy. Most MR examinations consisted of T1-weighted sagittal imaging of the entire spine, with additional sequences as needed for clarification. Extradural masses were found in 46 patients, 25 of whom had cord compression. For extradural masses causing cord compression, the sensitivity and specificity of MR imaging was .92 and .90, respectively, compared with .95 and .88 for myelography. For extradural masses without cord compression the sensitivity and specificity of MR imaging was .73 and .90, versus .49 and .88 for myelography. MR imaging was much more sensitive for metastases to bone (.90 vs .49), as expected. MR imaging is an acceptable alternative to myelography for diagnosing spinal cord compression and is preferable as a first study because it is noninvasive and better tolerated.