Expression of p27kip1 and p53 in medulloblastoma: relationship with cell proliferation and survival

p27kip1 and p21cip1 are cyclin-dependent kinase (cdk) inhibitors which along with p53 play critical roles in the control of cell cycle progression. Accumulation of p27kip1 in post-mitotic neurons is a major event of neurogenesis. We hypothesized that a dysregulation of the expression of p53 and these cdk inhibitors underlies cellular proliferation in medulloblastomas, and tested this hypothesis by investigating p27kip1, p21cip1, Bcl2 and p53 immunoreactivity in 14 medulloblastoma tumors. We noted an inverse relationship between p27kip1 expression and cellular proliferation (MIB1). Focal islands of neuroblastic or glial differentiation expressed high levels of p27kip1, while the undifferentiated, highly-proliferative population of tumor cells showed no detectable p27kip1 expression, thus suggesting a role for p27kip1 in cell cycle control in medulloblastoma. In addition, there was no detectable p21cip1 expression in any of the medulloblastomas studied. The low level of apoptosis displayed by these tumors was not associated with the expression of Bcl-2. A significant relationship was found between detection of p53 protein and poor survival. Since, p21cip1 and p27kip1 are often co-expressed with other INK4 family of cdk inhibitors during the induction of cellular differentiation and are synergistic in their effect, a deregulation of their coordinate expression may underlie the lack of complete differentiation in medulloblastoma.     

Expression analysis of juvenile pilocytic astrocytomas by oligonucleotide microarray reveals two potential subgroups

Juvenile pilocytic astrocytoma (JPA) is one of the most common brain tumors in children. The expression profiles of 21 JPAs, determined using Affymetrix GeneChip U133A, were compared with subjects with normal cerebella. The genes involved in neurogenesis, cell adhesion, synaptic transmission, central nervous system development, potassium ion transport, protein dephosphorylation, and cell differentiation were found to be significantly deregulated in JPA. These 21 JPAs were further clustered into two major groups by unsupervised hierarchical clustering using a set of 848 genes with high covariance (0.5-10). Supervised analysis with Significance Analysis of Microarrays software between these two potential subgroups identified a list of significant differentially expressed genes involved in cell adhesion, regulation of cell growth, cell motility, nerve ensheathment, and angiogenesis. Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein-positively stained tumor cells may have a higher tendency to progress.     

In vivo administration of TNF-{alpha} prevents EMC-M virus induced viral encephalitis

EMC-M virus causes a monophasic paralytic syndrome characterizedby encephalltic lesions in the brain and patchy demyellnatinglesions in the spinal cord and nerve roots of BALB/c mice. Sincethe replication of EMC virus in vitro is inhibited by tumornecrosis factor (TNF)- we have studied the effect of in vivoadministration of this cytokine on the acute disease. Our studiesshow that periodic administration of TNF- to animals infectedwith EMC-M reduces viral titers in the brain, and decreasesthe degree of clinical paralysis and the severityof the inflammatorylesions in the brain.     

Female adolescents and the future of female genital mutilation/cutting: a report from an endemic area

BackgroundDespite collaborative efforts aimed at its eradication, Female Genital Mutilation/Cutting (FGM/C) continues in endemic areas.ObjectiveTo evaluate the experience and preparedness of female adolescents to protect their future daughters from FGM/C.MethodsA cross-sectional survey involving adolescent secondary school girls in North Central Nigeria. Participants were secondary school students who completed the study''s self-administered questionnaire after informed parental or participant''s consent. Data management was with SPSS 20.0 (IBM, USA), P-value <0.05 was significant.ResultsThere were 2000 participants aged 13–19 years (mean 15.56±1.75), prevalence of FGM/C was 35.0%, awareness was 86.1%, mutilation was performed between infancy and eight years of age (mean 3.85±3.24 years), 644(32.2%) desire to mutilatetheir future daughters, 722(36.1%) expressed support for FGM/C and 63.1% of victims of FM/C reported adverse post-mutilation experiences. Support for FGM/C was associated with low social class (P0.0010), opinion that FGM/C has benefit (P0.001) and desire to mutilate future daughters (P0.001) while awareness of efforts to eradicate FMG/C was 813(40.7%).ConclusionFGM/C remains prevalent with potential support for its continuation among female adolescents despite reported adverse post-mutilation experiences. The multi-pronged approach to eradicate FGM/C should prioritize re-orientation for adolescent girls, rehabilitation of mutilated girls and girl child formal education.     

Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations

PURPOSE： Traditional genetic approaches to identify gene mutations in cancer are expensive and laborious. Nonetheless, if we are to avoid rejecting effective molecular targeted therapies, we must test these drugs in patients whose tumors harbor mutations in the drug target. We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities.     

Increased blood-brain barrier permeability with thymidine phosphorylase deficiency

Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive multisystemic disorder caused by thymidine phosphorylase deficiency. Whereas the pathomechanism of the secondary mitochondrial dysfunction has been extensively studied, that of the leukoencephalopathy has not been elucidated. We hypothesized that the white matter hyperintensities on T2-weighted magnetic resonance images reflect disturbance of blood-brain barrier function. Albumin immunohistochemistry disclosed quantitative (p < 0.01) and qualitative differences between the mitochondrial neurogastrointestinal encephalomyopathy and control brains, indicating that loss of thymidine phosphorylase function impairs the integrity of the blood-brain barrier.     

Identification of the cholera diffusion process in Ibadan, 1971

The paper tries to examine and identify which spatial diffusion process was responsible for generating the pattern of cholera diffusion (an epidemic spread which was apparently wave-like) within Ibadan City in 1971. In this paper one of Moran's statistics, the BW join-count measure of spatial autocorrelation is employed. Five different plannar graphs are used in the study. The results show that contagion was apparent on the various models of spatial processes employed and on their different combinations. But it is the radial contact diffusion which was discovered to be most important in the spread of the epidemic. But even, though such a radial contact diffusion process was discovered to be the most important, during the advance and peak phases of the epidemic wave; as the epidemic intensity rose to a spread phase, a mixture of the various models became a best contributor to the contagion.