Molecular analysis of neocortical layer structure in the ferret

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals, however, is unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for 15 layer‐enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: 1) Many but not all layer markers tested show similar patterns of layer‐specific gene expression between mouse and ferret cortex, supporting the view that layer‐specific cell type identity is conserved at a molecular level across mammalian superorders; 2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layers 5 and 6 into 5a, 5b, 6a, and 6b are also conserved between rodents and carnivores; 3) Variations in layer‐specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; 4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so‐called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell‐type comparisons across mammals. J. Comp. Neurol. 518:3272–3289, 2010. © 2010 Wiley‐Liss, Inc.     

Cost-effectiveness,cost-utility,and cost-benefit studies in rheumatology: a review of the literature, 2001-2002

Economic analyses of prevention and treatment interventions in rheumatology are potentially powerful tools for evaluating many complex decisions facing clinical and public policy makers. Cost-effectiveness, cost-utility, and cost-benefit analyses allow for the assessment of the trade-offs between expended resources and expected health benefits. This review describes 12 cost-effectiveness analyses done in the past year. Each relates to a different intervention for a variety of rheumatologic conditions including osteoporosis, rheumatoid arthritis, the use of cyclooxygenase-II inhibitors, infected total joint replacements, back pain, and Lyme disease. While cost-effectiveness analyses of the use of the new biologic agents in rheumatoid arthritis have been presented at national meetings, these have yet to be published. Proper use of cost-effectiveness analysis could provide valuable evidence about treatment decisions for clinical and public policy makers in rheumatology.     

Squamous cell carcinoma of breast--report of two case

Squamous cell carcinoma is an extremely rare variant of breast cancer. Presence of unequivocal squamous differentiation should be observed to diagnose a case as squamous cell carcinoma of breast since focal squamous metaplasia is frequently seen in common variants of breast carcinoma. We report here two cases of squamous cell carcinoma of breast, one a primary metaplastic type and the other one metastatic from a carcinoma of the cervix.     

Alcohol functionality in the fatty acid backbone of sphingomyelin guides the inhibition of blood coagulation

Cell-surface sphingomyelin (SM) inhibits binary and ternary complex activity of blood coagulation by an unknown mechanism. Here we show the OH functionality of SM contributes in forming the close assembly through intermolecular H-bond and through Ca²⁺ chelation, which restricts the protein–lipid/protein–protein interactions and thus inhibits the coagulation procedure.

Cell-surface sphingomyelin (SM) inhibits binary and ternary complex activity of blood coagulation.     

MTHFR 677C-->T and 1298A-->C polymorphisms: evaluation of maternal genotypic risk and association with level of neural tube defect

BACKGROUND: Neural tube defects (NTDs) are common birth defects (1 in 1,000) leading to significant morbidity and mortality. Periconceptional folic acid supplementation helps in prevention of 70% of NTDs. Recently, polymorphisms in genes encoding enzymes of the folate pathway have been implicated in causation of NTDs. Since the closure of neural tube occurs at multiple sites, the etiology of defect at different sites may be different - which explains the failure of folic acid supplementation to prevent all NTDs. METHODS: Molecular analysis of methylenetetrahydrofolate reductase polymorphisms was carried out using polymerase chain reaction and restriction enzyme digestion. We studied the association of these polymorphisms in mothers with a previous child with NTD and further refined the risk by stratification based on level of defect. RESULTS: The frequency of 677C-->T homozygotes was higher in mothers with a previous child with NTD than the controls (OR = 1.6 (0.38-6.7), 95% CI, p = 0.72) but the difference was statistically insignificant. There was a significant difference in frequency of T alleles among mothers with a previous child with a 'lower' type of defect compared to controls (OR = 2.15 (1.13-4.1), 95% CI, p = 0.02). We did not find any significant association of 1298A-->C polymorphism with the level of NTDs. CONCLUSIONS: We conclude that in the North Indian population, the 677C-->T allele of the MTHFR gene may be associated with the occurrence of a lower type of NTD. This points towards the differential role of thermolabile MTHFR at different sites of neural tube closure.     

Impairment of natural killer cell activity in Indian kala-azar: restoration of activity by interleukin 2 but not by alpha or gamma interferon.

Indian kala-azar patients have normal numbers of peripheral blood NK cells but impaired functional activity due to decreased binding and lysis of target cells. This impairment of NK activity could not be corrected by exogenous recombinant human alpha or gamma interferon. However, recombinant human interleukin 2 was able to restore this activity by augmenting conjugate formation and lysis of target cells.     

Barriers to community integration for participants in community-based psychiatric rehabilitation

This pilot study examined barriers to community integration for adults with serious mental illness (SMI) enrolled in a community-based psychiatric rehabilitation program. Program staff administered a self-report scale to 135 adults (mean age = 43.3 years, 53% men, 65.1% White). Staff completed the same measure. Individuals with mental illness and staff differed significantly in their reports of the type, number, F (1, 73) = 29.25, P < .0001, and severity (F (1, 176) = 43.53, P < .0001) of barriers to community integration. Clinicians should assist adults with SMI to identify relevant barriers, and participate in treatment planning and outcome evaluation.