Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

JOAQUIM L. REIS, M.D., PH.D.,1,2 JORGE CORREIA-PINTO, M.D., PH.D.,3,4 MARIANA P. MONTEIRO, M.D., PH.D.,1 MADALENA COSTA, B.SC.,1 AND GROVER M. HUTCHINS, M.D.5 1Department of Anatomy, Abel Salazar Institute for the Biomedical Sciences and Unit for Multidisciplinary Biomedical Research, University of Porto; 2Department of Neurosurgery, Santo António General Hospital; 4Department of Pediatric Surgery, São João Hospital, Porto; 3Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; and 5Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland Object. Myelomeningocele (MMC) is a primary neurulation defect that is associated with devastating neurological disabilities in affected newborns. To better characterize the in utero neurodegenerative process of MMC, the authors investigated the changes in vascular organization, apoptosis, and the presence of inflammatory cells during gestation by using a mutant mouse model of MMC. Methods. The curly tail/loop tail (ct/lp) mutant mouse model of MMC was chosen to obtain fetuses at different stages of gestation. Mouse fetuses harboring MMC were harvested by caesarean section at embryonic Days 14.5, 16.5, and 18.5 (complete mouse gestation at 19 days, 6 mice/group); littermate fetuses with the same gestational age but without an MMC were used as controls. Samples of the MMC placode or normal spinal cord were stained for immunocytochemical labeling with caveolin antibody (endothelium marker) and activated caspase-3 antibody (apoptosis marker). Samples were morphometrically analyzed with a computer-assisted image analyzer. Results. The MMC mice presented with an increase in vascular density from embryonic Days 16.5–18.5 and an enhanced number of apoptotic cells at embryonic Day 18.5, compared with controls. There were scarce signals of an inflammatory reaction in the MMC placode, as a few infiltrating neutrophils were seen only at embryonic Day 18.5. Conclusions. Fetal placodes in MMC mice showed evidence of increased vascular density since embryonic Day 16.5 and increased apoptosis at embryonic Day 18.5. These new data support the view that in utero changes of the MMC placode, occurring during the last stages of gestation, contribute to the neuropathological manifestations in fullterm newborns with MMC. (DOI: 10.3171/PED/2008/2/8/150

The Role of Interferon Regulatory Factor-1 and Interferon Regulatory Factor-2 in IFN-γ Growth Inhibition of Human Breast Carcinoma Cell Lines

Interferon (IFN) regulatory factor-1 (IRF-1) and IRF-2 play opposing roles in the regulation of many IFN-γ-inducible genes. To investigate the signal transduction pathway in response to IFN-γ in light of differences in growth effects, we selected four human breast carcinoma cell lines based on a spectrum of growth inhibition by IFN-γ. MDA468 growth was markedly inhibited by IFN-γ, and it showed substantial induction of IRF-1 mRNA but little IRF-2 induction. SKBR3 showed little growth inhibition and little induction of IRF-1 mRNA but significant induction of IRF-2 mRNA. HS578T and MDA436 growth inhibition and IRF-1/IRF-2 induction were intermediate. All four cell lines showed intact receptor at the cell surface and Stat1 translocation to the nucleus by immunostaining. By EMSA, there were marked differences in the induced ratio of IRF-1 and IRF-2 binding activity between the cell lines that correlated with growth inhibition. Finally, antisense oligonucleotides specific for IRF-1 attenuated IFN-γ growth inhibition in MDA436 and MDA468, confirming the direct role of IRF-1 in IFN-γ growth inhibition. Induction of IRF-1 causes growth inhibition in human breast cancer cell lines, and induction of IRF-2 can oppose this. The relative induction of IRF-1 to IRF-2 is a critical control point in IFN-γ response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63111/1/10799900360708623.pd

The neurotropic black yeast Exophiala dermatitidis has a possible origin in the tropical rain forest

The black yeast Exophiala dermatitidis is known as a rare etiologic agent of neurotropic infections in humans, occurring particularly in East and Southeast Asia. In search of its natural habitat, a large sampling was undertaken in temperate as well as in tropical climates. Sampling sites were selected on the basis of the origins of previously isolated strains, and on the basis of physiological properties of the species, which also determined a selective isolation protocol. The species was absent from outdoor environments in the temperate climate, but present at low abundance in comparable habitats in the tropics. Positive outdoor sites particularly included faeces of frugivorous birds and bats, in urban as well as in natural areas. Tropical fruits were found E. dermatitidis positive at low incidence. Of the human-made environments sampled, railway ties contaminated by human faeces and oily debris in the tropics were massively positive, while the known abundance of the fungus in steam baths was confirmed. On the basis of the species' oligotrophy, thermotolerance, acidotolerance, moderate osmotolerance, melanization and capsular yeast cells a natural life cycle in association with frugivorous animals in foci in the tropical rain forest, involving passage of living cells through the intestinal tract was hypothesized. The human-dominated environment may have become contaminated by ingestion of wild berries carrying fungal propagule

GPs' perspectives on preventive care for older people: a focus group study

BACKGROUND Preventive care traditionally aims to prevent diseases or injuries. For older people, different aims of prevention, such as maintenance of independence and wellbeing, are increasingly important. AIM To explore GPs' perspectives on preventive care for older people. DESIGN AND SETTING Qualitative study comprising six focus groups with GPs in the Netherlands. METHOD The focus-group discussions with 37 GPs were analysed using the framework analysis method. RESULTS Whether or not to implement preventive care for older people depends on the patient's individual level of vitality, as perceived by the GP. For older people with a high level of vitality, GPs confine their role to standardised disease-oriented prevention on a patient's request; when the vitality levels in older people fall, the scope of preventive care shifts from prevention of disease to prevention of functional decline. For older, vulnerable people, GPs expect most benefit from a proactive, individualised approach, enabling them to live as independently as possible. Based on these perspectives, a conceptual model for preventive care was developed, which describes GPs' different perspectives toward older people who are vulnerable and those with high levels of vitality. It focuses on five main dimensions: aim of care (prevention of disease versus prevention of functional decline), concept of care (disease model versus functional model), initiator (older persons themselves versus GP), target groups (people with requests versus specified risk groups), and content of preventive care (mainly cardiovascular risk management versus functional decline). CONCLUSION GPs' perspectives on preventive care are determined by their perception of the level of vitality of their older patients. Preventive care for older people with high levels of vitality may consist of a standardised disease-oriented approach; those who are vulnerable will need an individualised approach to prevent functional decline.Public Health and primary careGeriatrics in primary car

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)