Long‐term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke

Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri‐infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri‐infarct striatum. Numbers of microglia expressing markers of antigen‐presenting cells (MHC‐II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short‐ and long‐term increase (at 1 and 6 weeks postinfarct) of insulin‐like growth factor‐1 (IGF‐1) gene expression was detected in SVZ tissue. Elevated numbers of IGF‐1‐expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF‐1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long‐term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. © 2008 Wiley‐Liss, Inc.     

DNA repair: from genome maintenance to biomarker and therapeutic target

A critical link exists between an individual's ability to repair cellular DNA damage and cancer development, progression, and response to therapy. Knowledge gained about the proteins involved and types of damage repaired by the individual DNA repair pathways has led to the development of a variety of assays aimed at determining an individual's DNA repair capacity. These assays and their use in the analysis of clinical samples have yielded useful though somewhat conflicting data. In this review article, we discuss the major DNA repair pathways, the proteins and genes required for each, assays used to analyze activity, and the relevant clinical studies to date. With the recent results from clinical trials targeting specific DNA repair proteins for the treatment of cancer, accurate, reproducible, and relevant analysis of DNA repair takes on an even greater significance. We highlight the strengths and limitations of these DNA repair studies and assays, with respect to the clinical assessment of DNA repair capacity to determine cancer development and response to therapy.     

Pindborg's tumor: a propos of a case

The calcifying epithelial odontogenic tumor was first described as an entity by Danish pathologist Jens Pindborg in 1955. It is an uncommon and locally invasive benign odontogenic tumor. The most characteristic findings are the presence of amyloid-like substance and calcified concentric liesegang rings.     

Euchromatic 16p+ heteromorphism: first report in North America

A heteromorphism of the short arm of 16 (16p+) was discovered in 2 unrelated infants. By G banding, the euchromatic variant appears as a light and a medium dark band just distal to the centromere. This results in an increase of the short arm by about 1/3. The same variant was present in the normal father and the normal paternal grandmother in one family and mildly retarded mother in the 2nd family. The anomalies of the 2 infants are not similar and are apparently unrelated to the 16p+ variant. Though the discovery of such euchromatic variants is highly significant for clinical diagnosis, their genetic significance and mode of origin remain to be elucidated.     

A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh

Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies. The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin (Hb) concentrations, micronutrient status, and growth among adolescent girls in rural Bangladesh. A total of 1125 girls (Hb > or = 70 g/L) enrolled in a randomized, double-blind, placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance. The beverage was provided at schools 6 d/wk for 12 mo. Concentrations of Hb and serum ferritin (sFt), retinol, zinc, and C-reactive protein were measured in venous blood samples at baseline, 6 mo, and 12 mo. In addition, weight, height, and mid-upper arm circumference (MUAC) measurements were taken. The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo (P < 0.01). Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia (Hb <120 g/L), iron deficiency (sFt <12 microg/L), and low serum retinol concentrations (serum retinol <0.70 micromol/L) (OR = 2.04, 5.38, and 5.47, respectively; P < 0.01). The fortified beverage group had greater increases in weight, MUAC, and BMI over 6 mo (P < 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the sFt level continued to increase (P = 0.01). The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh.     

Wavelets and functional magnetic resonance imaging of the human brain

The discrete wavelet transform (DWT) is widely used for multiresolution analysis and decorrelation or "whitening" of nonstationary time series and spatial processes. Wavelets are naturally appropriate for analysis of biological data, such as functional magnetic resonance images of the human brain, which often demonstrate scale invariant or fractal properties. We provide a brief formal introduction to key properties of the DWT and review the growing literature on its application to fMRI. We focus on three applications in particular: (i) wavelet coefficient resampling or "wavestrapping" of 1-D time series, 2- to 3-D spatial maps and 4-D spatiotemporal processes; (ii) wavelet-based estimators for signal and noise parameters of time series regression models assuming the errors are fractional Gaussian noise (fGn); and (iii) wavelet shrinkage in frequentist and Bayesian frameworks to support multiresolution hypothesis testing on spatially extended statistic maps. We conclude that the wavelet domain is a rich source of new concepts and techniques to enhance the power of statistical analysis of human fMRI data.     

Absence of Mycobacterium tuberculosis DNA in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVES--To determine whether Mycobacterium tuberculosis DNA can be detected in synovial fluid of patients with rheumatoid arthritis (RA). METHODS--The polymerase chain reaction was applied to cellular components of synovial fluid. RESULTS--No evidence of M tuberculosis DNA was found in synovial fluid from 31 patients with RA and 13 control patients. CONCLUSION--The findings do not support a role for persistent M tuberculosis infection in the pathogenesis of RA.     

Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis

BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.