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Possible Mechanisms Underlying (possible + mechanism_underlying)
Selected AbstractsCognitive visual dysfunctions in preterm children with periventricular leukomalaciaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2009ELISA FAZZI MD PHD Aim, Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method, We studied 22 children born preterm (12 males, 10 females; mean age at examination 8y, range 6,15y; mean gestational age 30wks, range 28,36wks) with periventricular leukomalacia, spastic diplegia, normal intelligence (mean Full-scale IQ 84; mean Verbal IQ 97; mean Performance IQ 74), and normal visual acuity, focusing on higher visual functions. Brain magnetic resonance images (MRI) were analysed to establish the presence of lesions along the primary optic pathway, in the occipitoparietal and occipitotemporal regions. Results, Most children displayed an uneven cognitive profile, with deficits in visual object recognition, visual imagery, visual,spatial skills, and visual memory, and sparing of visual associative abilities, non-verbal intelligence, and face and letter recognition. Conventional brain MRI did not document major alterations of parietal and temporal white matter, or cortical alteration of areas involved in visual associative functions. Interpretation, We suggest a widespread involvement of higher visual processing systems, involving both the ventral and dorsal streams, in preterm children with periventricular leukomalacia. The lack of major alterations on conventional MRI does not exclude the possibility of malfunctioning of higher visual processing systems, expressing itself through discrete CVDs. Possible mechanisms underlying these neuropsychological deficits are discussed. [source] The effects of adolescent cannabis use on educational attainment: a reviewADDICTION, Issue 11 2000Michael Lynskey This paper reviews research examining the link between cannabis use and educational attainment among youth. Cross-sectional studies have revealed significant associations between cannabis use and a range of measures of educational performance including lower grade point average, less satisfaction with school, negative attitudes to school, increased rates of school absenteeism and poor school performance. However, results of cross-sectional studies cannot be used to determine whether cannabis use causes poor educational performance, poor educational performance is a cause of cannabis use or whether both outcomes are a reflection of common risk factors. Nonetheless, a number of prospective longitudinal studies have indicated that early cannabis use may significantly increase risks of subsequent poor school performance and, in particular, early school leaving. This association has remained after control for a wide range of prospectively assessed covariates. Possible mechanisms underlying an association between early cannabis use and educational attainment include the possibility that cannabis use induces an 'amotivational syndrome' or that cannabis use causes cognitive impairment. However, there appears to be relatively little empirical support for these hypotheses. It is proposed that the link between early cannabis use and educational attainment arises because of the social context within which cannabis is used. In particular, early cannabis use appears to be associated with the adoption of an anti-conventional lifestyle characterized by affiliations with delinquent and substance using peers, and the precocious adoption of adult roles including early school leaving, leaving the parental home and early parenthood. [source] Relationships between the yield of perennial ryegrass and of small-leaved white clover under cutting or continuous grazing by sheepGRASS & FORAGE SCIENCE, Issue 3 2001T. A. Williams Seven varieties or advanced breeding lines of white clover (Trifolium repens L.), all of small leaf size, were grown separately in mixtures with perennial ryegrass (Lolium perenne L.) in an experiment encompassing three harvest years. Harvestable dry-matter (DM) yield measurements were taken of these mixtures and of perennial ryegrass monocultures under two management regimes: cutting and continuous sheep grazing. Considerable differences were observed in the harvestable DM yields of white clover, perennial ryegrass and total yields of the mixtures between plots containing different white clover varieties. White clover yields were generally higher under cutting, and perennial ryegrass yields were higher under grazing. The difference between perennial ryegrass yield in monoculture and in mixture was variable. In the second harvest year, a significant interaction effect was seen between management and white clover variety for white clover yield but not for perennial ryegrass yield. The relationship between clover yield and grass yield differed between the two management regimes. Under cutting, a negative correlation was observed, indicative of competitive effects. However, under grazing, no such correlation was seen. Possible mechanisms underlying these outcomes are discussed. [source] Low expression of the interleukin (IL)-4 receptor alpha chain and reduced signalling via the IL-4 receptor complex in human neonatal B cellsIMMUNOLOGY, Issue 1 2006Cuixia Tian Summary Diminished neonatal antibody responses following infection or immunization may stem in part from intrinsic characteristics of neonatal B cells. In this study, we used B-cell subset sorting combined with gene expression assays to investigate major differences in the expression of host genes in neonatal and adult naïve B cells. We discovered significantly reduced expression of the interleukin (IL)-4 receptor alpha chain and reduced IL-4-induced signalling in neonatal B cells. Neonatal naïve B cells were susceptible to more rapid and more profound levels of apoptosis when cultured in vitro. They also exhibited a limited response to IL-4 treatment compared with adult cells. The expression level of the IL-13 receptor alpha 1 chain, a key component of the IL-13 receptor/IL-4 type II receptor, and the response to IL-13 treatment for protection against apoptosis in neonatal B cells were similar to those of the adult B cells. These studies suggest a possible mechanism underlying the limited magnitude and durability of neonatal antibody responses. [source] Mutagenicity of non-homologous end joining DNA repair in a resistant subset of human chronic lymphocytic leukaemia B cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Ludovic Deriano Summary Non-homologous end joining (NHEJ) is an important determinant of genomic stability in mammalian cells. This DNA repair pathway is upregulated in a subset of B-cell chronic lymphocytic leukaemia (B-CLL) cells resistant to DNA damage-induced apoptosis. Using an in vitro assay for double-strand breaks (DSB) end ligation, we studied the fidelity of DSB repair in B-CLL cells which were resistant or sensitive to in vitro DSB-induced apoptosis with concomitant patients' resistance or sensitivity to chemotherapy, respectively. The fidelity of DNA repair was determined by DNA sequencing of polymerase chain reaction products cloned in pGEM-T vector. Sequence analysis of DNA end junctions showed that the frequency of accurate ligation was higher in sensitive B-CLL cells and control cell lines, than in resistant cells where end joining was associated with extended deletions. Upregulated and error-prone NHEJ in resistant cells could be a quite possible mechanism underlying both genomic instability and poor clinical outcome. [source] Efficacy of the Flashlamp-Pumped Pulsed-Dye Laser in Nonsurgical Delay of Skin FlapsDERMATOLOGIC SURGERY, Issue 7 2003Ali Riza Erçöçen MD Objective. The purpose of this article was to determine the effectiveness of laser delay by use of the flashlamp-pumped pulsed-dye laser operating at a wavelength of 585 nm; to elucidate the comparable or dissimilar macroscopic, microscopic, and hemodynamic changes between laser and surgical delay methods; and to clarify the possible mechanisms underlying the delay effect of laser. Methods. A standardized caudally based random dorsal rat flap model was used in this study: Acute random skin flaps served as control subjects (group 1). Surgical delay was employed by incision of lateral longitudinal borders both without (group 2) and with (group 3) undermining, and laser delay methods were performed by laser irradiation of both lateral longitudinal borders (group 4) and the entire surface (group 5) of the proposed flap. Evaluation was done by histologic examination, India ink injection, laser Doppler perfusion imaging, and measurement of flap survival. Results. Histologically, dilation and hypertrophy of subpapillary and subdermal vessels were evident in groups 2, 3, and 4; on the other hand, degranulation of mast cells in the vicinity of occluded vessels at the 1st hour of laser delay and a striking mast cell proliferation and degranulation in association with newly formed vessels (angiogenesis) at the 14th day of laser delay were prominent in group 5. India ink injections revealed longitudinally arranged large-caliber vessels and cross-filling between the vessels of adjacent territories in groups, 2, 3, and 4, but only small-caliber vessels in group 5. Compared with the acute flaps, both surgical and laser delay significantly increased the mean flap perfusion to the maximal levels after a 14-day delay period, and all delay procedures improved flap survival; the most significant increase in surviving area was observed in group 3, whereas the less significant increase in surviving area was in group 5. Conclusion. This study demonstrates that laser delay is as effective as surgical delay and that laser delay by lasering lateral borders leads to dilation and longitudinal rearrangement of the existing vessels rather than angiogenesis, whereas laser delay by lasering the entire surface results in delay effect by inducing angiogenesis due to activation and degranulation of the mast cells. [source] Heparan sulfate proteoglycans in experimental models of diabetes: a role for perlecan in diabetes complicationsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2001Karin Conde-Knape Abstract Proteoglycans are ubiquitous extracellular proteins that serve a variety of functions throughout the organism. Unlike other glycoproteins, proteoglycans are classified based on the structure of the glycosaminoglycan carbohydrate chains, not the core proteins. Perlecan, a member of the heparan sulfate proteoglycan (HSPG) family, has been implicated in many complications of diabetes. Decreased levels of perlecan have been observed in the kidney and in other organs, both in patients with diabetes and in animal models. Perlecan has an important role in the maintenance of the glomerular filtration barrier. Decreased perlecan in the glomerular basement membrane has a central role in the development of diabetic albuminuria. The involvement of this proteoglycan in diabetic complications and the possible mechanisms underlying such a role have been addressed using a variety of models. Due to the importance of nephropathy among diabetic patients most of the studies conducted so far relate to diabetes effects on perlecan in different types of kidney cells. The various diabetic models used have provided information on some of the mechanisms underlying perlecan's role in diabetes as well as on possible factors affecting its regulation. However, many other aspects of perlecan metabolism still await full elucidation. The present review provides a description of the models that have been used to study HSPG and in particular perlecan metabolism in diabetes and some of the factors that have been found to be important in the regulation of perlecan. Copyright © 2001 John Wiley & Sons, Ltd. [source] Ageing and the neutrophil: no appetite for killing?IMMUNOLOGY, Issue 4 2000S. Butcher Summary In the armoury of the immune system developed to combat the various micro-organisms that could invade the host, the neutrophil forms the first line of defence against rapidly dividing bacteria and fungi. However, as humans age they become more susceptible to infection with these microbes and this has been ascribed to a decline in immune status, termed immune senescence. Here we summarize the literature specifically concerning the attenuation of neutrophil function with age and the possible mechanisms underlying their reduced response to infectious agents. [source] ,-tocopherol, an exogenous factor of adult hippocampal neurogenesis regulationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Tiziana Cecchini Abstract In previous work, we found that adult hippocampal neurogenesis in rat is affected by vitamin E deficiency. Because vitamin E deficiency is a complex condition involving numerous biological systems, it is possible that its effect on postnatal new neuron production could be mediated by unknown changes in different factors that in turn play a role in this process. To clarify if vitamin E plays a direct role in regulating hippocampal neurogenesis, we studied the neurogenesis in adult control rats and in adult rats under supplementation with ,-tocopherol, the most important compound of vitamin E. The ,-tocopherol level in control and supplemented rats was monitored. Qualitative and quantitative analysis of cell proliferation and death was carried out and expression of immature neuron markers PSA-NCAM, TUC 4, and DCX was investigated in hippocampus dentate gyrus. ,-Tocopherol levels increased significantly in both plasma and brain after supplementation. Cell proliferation was inhibited in ,-tocopherol-supplemented rats, the number of dying cells was reduced, and the number of cells expressing the immature neuron markers was increased. The results obtained confirm and extend the idea that vitamin E is an exogenous factor playing a direct role in regulation of different steps of adult hippocampal neurogenesis. Some hypotheses about the possible mechanisms underlying the complex action of ,-tocopherol, related to its antioxidant and molecule-specific non-antioxidant properties, are proposed and discussed. © 2003 Wiley-Liss, Inc. [source] Areca nut extracts-activated secretion of leukotriene B4, and phosphorylation of p38 mitogen-activated protein kinase and elevated intracellular calcium concentrations in human polymorphonuclear leukocytesJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2007S.-L. Hung Background and Objective:, Polymorphonuclear leukocytes are the major source of leukotriene B4, which is synthesized via the 5-lipoxygenase pathway. Activation of the 5-lipoxygenase pathway is regulated by intracellular calcium and the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The impact of areca nut extracts on the biosynthesis of leukotriene B4 by human polymorphonuclear leukocytes was evaluated, and some of the possible mechanisms underlying the responses were examined. Material and Methods:, Polymorphonuclear leukocytes were treated with various concentrations of areca nut extracts. The concentrations of leukotriene B4 released into the supernatants were evaluated using enzyme immunoassay. The phosphorylation of p38 MAPK was monitored using immunoblotting, and the cytosolic calcium kinetics were assessed fluorometrically using Fura-2. Results:, Exposure of polymorphonuclear leukocytes to areca nut extracts led to a dose-dependent increase in the production of leukotriene B4, with levels peaking at 30 min and decreasing thereafter. Areca nut extracts enhanced the phosphorylation of p38 MAPK, an enzyme known to activate 5-lipoxygenase. Incubation with areca nut extracts also resulted in a rapid elevation of intracellular calcium concentrations in polymorphonuclear leukocytes. The induction of leukotriene B4 by areca nut extracts was suppressed with the p38 MAPK inhibitor, SB203580, or with the intracellular calcium chelator, BAPTA-AM. Conclusion:, The interaction of areca nut extracts with polymorphonuclear leukocytes activated the arachidonic acid metabolic cascade. Incubation of polymorphonuclear leukocytes with areca nut extracts resulted in the activation of intracellular events, such as phosphorylation of p38 MAPK and Ca2+ mobilization, involved in the release of pro-inflammatory lipid mediators. The results of this study emphasize the potential importance of polymorphonuclear leukocytes as a source of leukotriene B4, which may modulate the inflammatory response in areca chewers. [source] Translational regulation of a novel testis-specific RNF4 transcriptMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2003Raffaela Pero Abstract The RING-finger protein SNURF/RNF4, a modulator of both steroid receptor dependent and basal transcription, is expressed at very high levels in testis and at much lower levels in several other tissues. In somatic tissues, the RNF4 gene is expressed as a 3-kb transcript while an additional shorter sized transcript (1.6 kb) was found in mouse testis. In murine germ cells, RNF4 protein expression is strongly modulated during progression of spermatogonia to spermatids, with a peak in spermatocytes. The expression of 3-kb transcript correlated with protein levels in the different germ cell populations. Conversely, the 1.6-kb transcript was abundantly and specifically expressed in spermatids, in which RNF4 protein was detected at very low levels. We have then examined possible mechanisms underlying this discrepancy. Primer extension and RNase protection analyses demonstrated that the 1.6- and 3.0-kb transcripts originate from the same promoter, encode for the same protein and differ in the 3, UTR. In vitro assays showed that protein degradation is not involved in the regulation of RNF4 protein level. Finally, polysome analysis revealed that only a slight fraction of the testis-specific transcript is engaged in translation, thus providing a feasible mechanism for the quantitative differences of RNF4 mRNA and protein levels. Present results demonstrate that RNF4 short transcript is poorly translated suggesting that this mechanism could be essential for normal spermatogenesis. Mol. Reprod. Dev. 66: 1,7, 2003. © 2003 Wiley-Liss, Inc. [source] Probiotics: Immunomodulation and Evaluation of Safety and EfficacyNUTRITION REVIEWS, Issue 1 2006Janine Ezendam PhD The intake of probiotics has been associated with beneficial effects on the immune system, such as improved disease resistance and diminished risk of allergies. This review gives an overview of the immunomodulatory effects of probiotics investigated with in vitro assays, experimental animal models, and clinical trials, and explores possible mechanisms underlying the immunomodulatory effects. Immunomodulation, however, is not always beneficial and might induce detrimental effects; therefore, a scheme is proposed for benefit-risk assessment of immunomodulation by probiotics. Within this scheme, expert judgment based on data derived from a panel of in vitro assays, animal models, and clinical trials should lead to conclusions on efficacy and safety aspects of probiotics. [source] | |||||||||||||