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Terms modified by CF Selected AbstractsFunctions of glutamate transporters in cerebellar Purkinje cell synapsesACTA PHYSIOLOGICA, Issue 1 2009Y. Takayasu Abstract Glutamate transporters play a critical role in the maintenance of low extracellular concentrations of glutamate, which prevents the overactivation of post-synaptic glutamate receptors. Four distinct glutamate transporters, GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3 and EAAT4, are distributed in the molecular layer of the cerebellum, especially near glutamatergic synapses in Purkinje cells (PCs). This review summarizes the current knowledge about the differential roles of these transporters at excitatory synapses of PCs. Data come predominantly from electrophysiological experiments in mutant mice that are deficient in each of these transporter genes. GLAST expressed in Bergmann glia contributes to the clearing of the majority of glutamate that floods out of the synaptic cleft immediately after transmitter release from the climbing fibre (CF) and parallel fibre (PF) terminals. It is indispensable to maintain a one-to-one relationship in synaptic transmission at the CF synapses by preventing transcellular glutamate spillover. GLT-1 plays a similar but minor role in the uptake of glutamate as GLAST. Although the loss of neither GLAST nor GLT-1 affects cerebellar morphology, the deletion of both GLAST and GLT-1 genes causes the death of the mutant animal and hinders the folium formation of the cerebellum. EAAT4 removes the low concentrations of glutamate that escape from uptake by glial transporters, preventing the transmitter from spilling over into neighbouring synapses. It also regulates the activation of metabotropic glutamate receptor 1 (mGluR1) in perisynaptic regions at PF synapses, which in turn affects mGluR1-mediated events including slow EPSCs and long-term depression. No change in synaptic function is detected in mice that are deficient in EAAC1. [source] Differential expression of TrkB isoforms switches climbing fiber-Purkinje cell synaptogenesis to selective synapse eliminationDEVELOPMENTAL NEUROBIOLOGY, Issue 10 2009Rachel M. Sherrard Abstract Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood. We assessed the role of cerebellar neurotrophins by examining tropomycin receptor kinase (Trk) receptor expression in the inferior olive and cerebellum between postnatal days (P)3-7, when CF-PC innervation changes from synapse formation to selective synapse elimination, and in a denervation-reinnervation model when synaptogenesis is delayed. Trks A, B, and C are expressed in olivary neurons; although TrkA was not transported to the cerebellum and TrkC was unchanged during innervation and reinnervation, suggesting that neither receptor is involved in CF-PC synaptogenesis. In contrast, both total and truncated TrkB (TrkB.T) increased in the olive and cerebellum from P4, whereas full-length and activated phosphorylated TrkB (phospho-TrkB) decreased from P4-5. This reveals less TrkB signaling at the onset of CF regression. This expression pattern was reproduced during CF-PC reinnervation: in the denervated hemicerebellum phospho-TrkB decreased as CF terminals degenerated, then increased in parallel with the delayed neosynaptogenesis as new CFs reinnervated the denervated hemicerebellum. In the absence of this signaling, CF reinnervation did not develop. Our data reveal that olivocerebellar TrkB activity parallels CF-PC synaptic formation and stabilization and is required for neosynaptogenesis. Furthermore, TrkB.T expression rises to reduce TrkB signaling and permit synapse elimination. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Hydrodynamic Modulation Voltammetry with a Dual Disk Chopped Flow-Microjet Electrode (CF-MJE)ELECTROANALYSIS, Issue 18 2003Nafeesa Simjee Abstract A novel form of hydrodynamic modulation voltammetry (HMV) is described, based on the periodic variation of mass transport in a microjet electrode (MJE) system, in combination with phase-sensitive detection techniques. In the configuration developed, a jet of solution is fired from a nozzle that is aligned directly over the surface of a dual disk Pt-Pt ultramicroelectrode (UME). The potential at each electrode is controlled separately. A rotating blade, positioned between the nozzle and the UME probe, is used to periodically interrupt flow to the electrode surface, resulting in modulation of the overall mass transfer rate between two defined extremes. The use of a dual disk UME enables two transport-limited current signals to be recorded simultaneously, one for the analyte of interest, and the other for a ,reference species' (oxygen for the studies described herein). The latter current response corresponds to the variation in mass transport rate in the chopped flow (CF) arrangement and is used as the signal for phase sensitive detection of the analyte current. Studies of potassium hexachloroiridate (III) [IrCl] oxidation in aqueous solution are used to demonstrate the capabilities of the technique. HMV in the CF-MJE arrangement allows quantitative concentration measurements, down to at least 5×10,7,M. [source] High phenotypic diversity in infecting but not in colonizing Staphylococcus aureus populationsENVIRONMENTAL MICROBIOLOGY, Issue 12 2007Christiane Goerke Summary In hostile environments diversity within a bacterial population may be beneficial for the fitness of the microbial community as a whole. Here we analysed the population diversity of Staphylococcus aureus in infecting and colonizing situations. In the study, performed independently in two German centres, the heterogeneity of the S. aureus population was determined by quantifying the occurrence of phenotypic variants (differences in haemolysis, pigmentation, colony morphology) in primary cultures from nose, oropharyngeal and sputum specimens from cystic fibrosis (CF) patients and in nose swabs from healthy S. aureus carriers. The proportion of heterogeneous samples, the number of clearly distinguishable isolates per sample and the qualitative differences between phenotypes was significantly higher in CF sputum specimens than in the other samples. The heterogeneity of the S. aureus population could be correlated with high bacterial densities in the sputum samples. In patients co-infected with Pseudomonas aeruginosa lower S. aureus bacterial loads and less heterogeneity in the S. aureus population were observed. Typing of all S. aureus isolates from heterogeneous samples by pulsed-field gel electrophoresis or spa typing revealed that the bacteria were polyclonal in 30%, monoclonal with minor genetic alterations in 25% or not distinguishable in 69% of the specimens. Some specimens harboured monoclonal and polyclonal variants simultaneously. Importantly, differences in antibiotic susceptibility were detected in phenotypic S. aureus variants within a single specimen. Diversification of a S. aureus population is highly favoured during chronic CF lung infection, supporting the general hypothesis that maintenance of intrahost diversity can be of adaptive value, increasing the fitness of the bacterial community. [source] Worldwide distribution of Pseudomonas aeruginosa clone C strains in the aquatic environment and cystic fibrosis patientsENVIRONMENTAL MICROBIOLOGY, Issue 7 2005Ute Römling Summary Highly successful bacterial clones have the ability to effectively colonize environmental niches and patients. However, the factors which determine the complex interplay between the colonization of environmental niches and patients are mainly unknown. In this study we show that Pseudomonas aeruginosa clone C strains are distributed worldwide and highly prone to infect cystic fibrosis (CF) patients in Canada, England, France and Germany. In Hanover, Germany and Vancouver, Canada, clone C strains are highly prevalent in the CF patient community, although the mechanisms of acquisition may have been different. All clone C strains showed highly related macrorestriction fragment pattern of the whole genome as visualized by pulsed-field gel electrophoresis and harboured the 102 kbp plasmid pKLC102. Comparison of three prevalent P. aeruginosa clones with different distribution between the environment and patients revealed that neither enhanced biofilm formation nor antibiotic resistance was responsible for the spread of clone C. Clone M, which was highly prevalent in the clinical environment such as sanitary facilities, lacked motility, which could explain its relatively low prevalence in CF patients. Elucidation of the mechanisms which lead to the prevalence of clone C strain in patients and the environment requires the investigation of additional phenotypes. [source] Seasonal evaluation of reproductive status and exposure to environmental estrogens in hornyhead turbot at the municipal wastewater outfall of Orange County, CAENVIRONMENTAL TOXICOLOGY, Issue 5 2007Xin Deng Abstract Seasonal changes in developmental stages, condition factor (CF), gonadosomatic index, and plasma vitellogenin (Vtg) concentrations in male and female hornyhead turbot were examined at the wastewater outfall (T1) of the Orange County Sanitation District, and two farfield sites T11 (7.7 km northwest of the outfall) and Dana Point (35 km south of the outfall) between February 2005 and May 2006. Fish collected from the three sites exhibited male-oriented sex ratios. With few exceptions, developmental stages, CF, and GSI of both genders and plasma Vtg concentrations of females were not significantly different in samples collected from different sites at the same sampling period. More advanced gonad developmental stages and higher plasma Vtg concentrations in females were observed in August, indicating the seasonality of the reproductive cycle for this species. Plasma Vtg concentrations in males were observed in all of the sampling sites with the highest prevalence at T11 relative to T1 and Dana Point. The Vtg expression in males from the three sampling sites indicated widespread exposure to estrogenic compounds in waters of coastal California. However, the histopathological and reproductive relevance of the responses appeared to be insignificant and may not affect the population in these locations. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 464,471, 2007. [source] In vitro and in vivo estrogenicity and toxicity of o -, m -, and p -dichlorobenzeneENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2003Bram J. Versonnen Abstract The estrogenicity of o -, m -, and p -dichlorobenzene (DCB) was evaluated with a yeast estrogen screen (YES) and zebrafish (Danio rerio) vitellogenin (VTG) assays. With the YES, p -DCB and m -DCB were found to be estrogenic in a concentration-responsive manner. The relative potency measured with the YES (relative to 17,-estradiol) was 2.2 × 10,7 for p -DCB and 1.04 × 10,8 for m -DCB. Following acute toxicity tests with the zebrafish, plasma VTG production was measured to examine the in vivo estrogenic activity of the three compounds after a 14-d exposure. Adult zebrafish were exposed to different concentrations of o -, m - and p -DCB, ranging from 0.1 to 32 mg/L; ethynylestradiol ([EE2]; 5 ng/L, 10 ng/L, 50 ng/L, and 100 ng/L) was used as a positive control. After exposure, blood samples were taken and protein electrophoresis was performed to determine the relative VTG content. Gonadosomatic indices (GSI) and condition factors (CF) were also calculated. Elevated VTG levels and decreased female GSIs were found in fish exposed to ,5 ng EE2/L and in fish exposed to ,10 mg p -DCB/L. Low GSIs coincided with high levels of VTG in the blood of female zebrafish. This relation was not only found in fish exposed to EE2 but also in controls and fish exposed to DCB. Therefore, a direct or indirect effect of VTG on the GSI is suggested rather than a direct toxic effect of the tested compounds on the gonads. [source] Anticonvulsant Profile and Teratogenicity of N -methyl-tetramethylcyclopropyl Carboxamide: A New Antiepileptic DrugEPILEPSIA, Issue 2 2002Nina Isoherranen Summary: ,Purpose: The studies presented here represent our efforts to investigate the anticonvulsant activity of N -methyl-tetramethylcyclopropyl carboxamide (M-TMCD) and its metabolite tetramethylcyclopropyl carboxamide (TMCD) in various animal (rodent) models of human epilepsy, and to evaluate their ability to induce neural tube defects (NTDs) and neurotoxicity. Methods: The anticonvulsant activity of M-TMCD and TMCD was determined after intraperitoneal (i.p.) administration to CF#1 mice, and either oral or i.p. administration to Sprague,Dawley rats. The ability of M-TMCD and TMCD to block electrical-, chemical-, or sensory-induced seizures was examined in eight animal models of epilepsy. The plasma and brain concentrations of M-TMCD and TMCD were determined in the CF#1 mice after i.p. administration. The induction of NTDs by M-TMCD and TMCD was evaluated after a single i.p. administration at day 8.5 of gestation in a highly inbred mouse strain (SWV) that is susceptible to valproic acid,induced neural tube defects. Results: In mice, M-TMCD afforded protection against maximal electroshock (MES)-induced, pentylenetetrazol (Metrazol)-induced, and bicuculline-induced seizures, as well as against 6-Hz "psychomotor" seizures and sound-induced seizures with ED50 values of 99, 39, 81, 51, and 10 mg/kg, respectively. In rats, M-TMCD effectively prevented MES- and Metrazol-induced seizures and secondarily generalized seizures in hippocampal kindled rats (ED50 values of 82, 45, and 39 mg/kg, respectively). Unlike M-TMCD, TMCD was active only against Metrazol-induced seizures in mice and rats (ED50 values of 57 and 52 mg/kg, respectively). Neither M-TMCD nor TMCD was found to induce NTDs in SWV mice. Conclusions: The results obtained in this study show that M-TMCD is a broad-spectrum anticonvulsant drug that does not induce NTDs and support additional studies to evaluate its full therapeutic potential. [source] Time Trends in Incidence, Mortality, and Case-Fatality after First Episode of Status EpilepticusEPILEPSIA, Issue 8 2001Giancarlo Logroscino Summary: ,Purpose: Status epilepticus (SE) is a medical emergency associated with a high mortality. Clinical series have suggested that mortality after SE has decreased. No studies have systematically examined trends in incidence, mortality, and case fatality after SE in a well-defined population. Methods: All first episodes of SE receiving medical attention between January 1, 1935, and December 31, 1984, were ascertained through the Rochester Epidemiology Project Records-Linkage System and followed up until death or study termination (February 1, 1996). We calculated incidence rates in the 50-year period (1935,1984), while we considered mortality and case-fatality in the last 30-year period (1955,1984). Results: Incidence of SE increased over time to 18.1/100,000 (1975 through 1984). The increase was related to an increased incidence in the elderly and to the advent of myoclonic SE after cardiac arrest, a condition not seen in the early decades. In the last decade, ,16% of the incidence was due to myoclonic SE. The mortality rates increased from 3.6 per year in the decade 1955,1965 to 4.0/100,000 per year between 1975 and 1984. The 30-day case-fatality (CF) was unchanged, although a trend toward improvement was shown after excluding myoclonic SE. Conclusions: Incidence and mortality rates of SE have increased in the last 30 years. Case fatality remained the same. The increased incidence and mortality are due to the occurrence in the last decade of myoclonic SE after cardiac arrest. The mortality in the elderly was twice that of the youngest age group, across all study periods. Changes in the age and cause distribution of SE over time are responsible for the stable survivorship. There is improvement in survivorship in the last decade when myoclonic SE is excluded. [source] Ceramide in Pseudomonas aeruginosa infectionsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 10 2007Joachim Riethmüller Abstract Cystic fibrosis (CF), the most common autosomal recessive disorder, at least in western countries, is caused by mutations of the cystic fibrosis transmembranous conductance regulator (CFTR) molecule and affects approximately 80,000 patients in Europe and the USA. Most, if not all, CF patients develop a chronic pulmonary infection with Pseudomonas aeruginosa. At present it is unknown why CF patients are highly sensitive to P.,aeruginosa infections, and most importantly, no curative treatment for CF is available. P.,aeruginosa infection results in an activation of the enzyme acid sphingomyelinase which catalyzes the release of ceramide from sphingomyelin in the cell membrane. Ceramide forms large ceramide-enriched membrane domains that are required for internalization of bacteria, induction of cell death in infected cells and a controlled release of cytokines from infected cells. Ceramide-enriched membrane platforms seem to serve the reorganization of receptors and intracellular signaling molecules involved in the infection of mammalian cells with P.,aeruginosa. The significance of the acid sphingomyelinase and ceramide for the infection of mammalian cells with P.,aeruginosa was demonstrated on mice genetically deficient for the acid sphingomyelinase. Further studies with N.,gonorrhoeae, S.,aureus and rhinoviruses indicate that ceramide-enriched membrane domains are also important for the infection of mammalian cells with other bacterial and viral pathogens, suggesting a general role of these membrane domains in infectious biology. [source] Afferent,target interactions during olivocerebellar development: transcommissural reinnervation indicates interdependence of Purkinje cell maturation and climbing fibre synapse eliminationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Ann M. Lohof Abstract We have used a model of postlesional reinnervation to observe the interactions between synaptic partners during neosynaptogenesis to determine how the developmental states of the pre- and postsynaptic cells influence circuit maturation. After unilateral transection of the neonatal rat olivocerebellar pathway (pedunculotomy), axons from the remaining ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF) terminal arbors on Purkinje cells (PCs) at a later stage of development than normal. However, the significance of delayed CF-PC interactions on subsequent circuit maturation remains poorly defined. To examine this question, we recorded CF-induced currents in PCs and analysed PC morphology during the first two postnatal weeks in control animals and following left unilateral inferior cerebellar pedunculotomy on postnatal day (P)3. Our results show that transcommissural olivary axons multiply-reinnervate PCs in the denervated hemisphere over 4 days following pedunculotomy. Each PC received fewer CFs than did age-matched controls and the maximal multi-reinnervation was reached on P7, 2 days later than in controls. Consequently, the onset of CF synapse elimination in reinnervated PCs was delayed, but then proceeded in parallel with controls so that all PCs were monoinnervated by P15. Furthermore, reinnervated PCs had delayed dendritic maturation and subsequent dendritic abnormalities consistent with the role of CF innervation in PC dendritic growth. Thus, within the olivocerebellar system, our data suggest that target neurons depend upon sufficient afferent investment arriving at the correct time for their normal development, and maturation of the target neuron regulates afferent selection and therefore circuit maturation. [source] Post-lesion transcommissural growth of olivary climbing fibres creates functional synaptic microzonesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Izumi Sugihara Abstract In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, postlesion plasticity may generate alternate paths, providing models to investigate reinnervating axon,target interactions. After unilateral transection of the neonatal rat olivocerebellar path, axons from the ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF)-like arbors on Purkinje cells (PCs). However, the synaptic function and extent of PC reinnervation remain unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and electrophysiological properties of reinnervating olivocerebellar axons were studied, using axonal reconstruction and patch-clamp PC recording of CF-induced synaptic currents. Reinnervated PCs displayed normal CF currents, and the frequency of PC reinnervation decreased with increasing laterality. Reinnervating CF arbors were predominantly normal but 6% branched within the molecular layer forming smaller secondary arbors. CFs arose from transcommissural olivary axons, which branched extensively near their target PCs to produce on average 36 CFs, which is six times more than normal. Axons terminating in the hemisphere developed more CFs than those terminating in the vermis. However, the precise parasagittal microzone organization was preserved. Transcommissural axons also branched, although to a lesser extent, to the deep cerebellar nuclei and terminated in a distribution indicative of the olivo-cortico-nuclear circuit. These results show that reinnervating olivocerebellar axons are highly plastic in the cerebellum, compensating anatomically and functionally for early postnatal denervation, and that this reparation obeys precise topographic constraints although axonal plasticity is modified by target (PC or deep nuclear neurons) interactions. [source] Switchable Fluorescent and Solvatochromic Molecular Probes Based on 4-Amino- N -methylphthalimide and a Photochromic DiaryletheneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2008Sergey F. Yan Abstract New fluorescent photochromic compounds (1 -H and 1 -Boc) have been synthesized and characterized in different solvents. The fluorescence emission can be switched "on" and "off" with visible light and UV, respectively, by means of the photochromic reaction. The emission wavelength and efficiency strongly depend on the polarity of the solvent. The compounds show a positive solvatochromic effect in the emission maxima, and their fluorescence quantum yield decreases as the solvent's polarity increases (from cyclohexane to dioxane). In solvents more polar than dioxane the emission is too weak and therefore undetectable, and thus 1 -H and 1 -Boc behave as "normal" photochromic compounds. The photochromic reaction is also sensitive to the environment. A decrease of more than an order of magnitude was found for the quantum yield of the colouring reaction (,OF,CF) for 1 -H in ethanol compared with cyclohexane, and an about threefold decrease in ,OF,CF was observed for the compound 1 -Boc in polar solvents (compared with apolar solvents). For both compounds the ring-opening reaction was found not to dependent on the solvent. The novel fluorescent molecular switches 1 -H and 1 -Boc are able to probe the polarity of their microenvironment. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Corrosion fatigue behaviour of a 15Cr-6Ni precipitation-hardening stainless steel in different tempersFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 6 2000C.-K. Lin Systematic fatigue experiments, including both high-cycle axial fatigue (S,N curves) and fatigue crack growth (FCG, da/dN,,K curves), were performed on a precipitation-hardening martensitic stainless steel in laboratory air and 3.5 wt% NaCl solution. Specimens were prepared in three tempers, i.e. solution-annealed (SA), peak-aged (H900) and overaged (H1150) conditions, to characterize the effects of ageing treatment on the corrosion fatigue (CF) resistance. S,N results indicated that fatigue resistance in all three tempers was dramatically reduced by the aqueous sodium chloride environment. In addition, the smooth-surface specimens in H900 temper exhibited longer CF lives than the H1150 ones, while those in SA condition stood in between. However, for precracked specimens, the H1150 temper provided superior corrosive FCG resistance than the other two tempers. Comparison of the S,N and FCG curves indicated that early growth of crack-like defects and short cracks played the major role in determining the CF life for smooth surface. The differences in the CF strengths for the S,N specimens of the given three tempers were primarily due to their inherent differences in resistance to small crack growth, as they were in the air environment. [source] Anaerobic culture conditions favor biofilm-like phenotypes in Pseudomonas aeruginosa isolates from patients with cystic fibrosisFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Che Y. O'May Abstract Pseudomonas aeruginosa causes chronic infections in the lungs of cystic fibrosis (CF) individuals and remains the leading cause of morbidity and mortality associated with the disease. Biofilm growth and phenotypic diversification are factors thought to contribute to this organism's persistence. Most studies have focused on laboratory isolates such as strain PAO1, and there are relatively few reports characterizing the properties of CF strains, especially under decreased oxygen conditions such as occur in the CF lung. This study compared the phenotypic and functional properties of P. aeruginosa from chronically infected CF adults with those of strain PAO1 and other clinical non-CF isolates under aerobic and anaerobic culture conditions. The CF isolates overall displayed a reduced ability to form biofilms in standard in vitro short-term models. They also grew more slowly in culture, and exhibited decreased adherence to glass and decreased motilities (swimming, swarming and twitching). All of these characteristics were markedly accentuated by anaerobic growth conditions. Moreover, the CF strain phenotypes were not readily reversed by culture manipulations designed to encourage planktonic growth. The CF strains were thus inherently different from strain PAO1 and most of the other non-CF clinical P. aeruginosa isolates tested. In vitro models used to research CF isolate biofilm growth need to take the above properties of these strains into account. [source] Evidence for non-genomic transmission of ecological information via maternal behavior in female ratsGENES, BRAIN AND BEHAVIOR, Issue 1 2007J. McLeod Maternal behavior is flexible and programs offspring development. Using a novel manipulation, we demonstrate that rat maternal behavior is sensitive to ecologically relevant stimuli. Long-Evans hooded rat dams (F0) and pups were exposed to a predator condition (cat odor) or a control condition (no odor) for 1 h on the day of parturition. Predator-exposed F0 dams displayed significantly more maternal behavior (licking/grooming, arched-back nursing) relative to control-exposed dams across five subsequent observation days. Female offspring (F1) were raised to adulthood, bred and maternal behavior was observed. F1 dams reared by a predator-exposed F0 dam displayed significantly higher maternal behavior relative to F1 dams reared by a control-exposed F0 dam across 5 days of observation. Increased levels of maternal behavior in predator-reared (PR) F1 dams were evident even in F1 females that had been cross-fostered (CF) from a control-exposed F0 dam, suggesting a non-genomic transmission of increased levels of maternal behavior. Lactating PR F1 dams had significantly elevated estrogen receptor , and , mRNA in the medial preoptic area relative to control-reared (CR) F1 dams. Furthermore, among CR F1 dams, there was no significant difference between those dams that had been CF from predator-exposed F0 dams and those that had been sham CF. These results support the hypothesis that flexible rat maternal behavior can shape offspring development according to current environmental conditions. The results also suggest that estrogen signaling may be part of an epigenetic mechanism by which changes in maternal behavior are passed from F0 to F1 dams. [source] Cluster headache: the challenge of clinical trials.HEADACHE, Issue 3 2003K Moore Curr Pain Headache. Rep 2002 Feb;6(1):52-56 The design and execution of clinical trials poses special problems for cluster headache. Although there is less inter-individual and intra-individual variability of attacks than seen with migraine, the brevity of attacks, spontaneous remissions unrelated to treatment, and the relative rarity of cluster headaches challenge investigators. The International Headache Society has developed guidelines that represent a compromise between scientific rigor and practicality. Only injectable sumatriptan for acute attacks and verapamil for prophylaxis have demonstrated a robust therapeutic effect in controlled clinical trials. Comment: Kenneth Moore raises important methodological considerations. It is possible to undertake crossover trials comparing different active treatments? He is correct in his assertion that few agents show robust efficacy. A major issue relates to the proportion of patients with episodic versus chronic cluster headache where efficacy of active treatments can vary. For example, oral zolmitriptan was effective against placebo only in those patients with episodic disease (Bahra A, Gawel MJ, Hardebo JE, Millson DS, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54:1832-1839). And a set of small studies on melatonin and cluster demonstrate the problems Dr. Moore describes. In one study (Leone M, D'Amico D, Moschiano F, Fraschini F, Busonne G. Metalonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996;16:494-496), the melatonin worked only in episodic, not chronic cluster patients. In the second study (Prinsheim T, Magnoux E, Dobson CF, Hamel E, Aube M. Melatonin as adjuctive therapy in the prophylaxis of cluster headache: a pilot study. Headache. 2002;42:787-792), melatonin did not work better than placebo in either episodic or chronic cluster patients. Furthermore, the paper abstracted above by Torelli and Manzoni suggests that episodic cluster may progress to chronic cluster as a result of extrinsic factors such as smoking. Finally, there are ethical issues in placebo-controlled cluster studies, given the severity of the pain and the availability of effective acute and chronic treatments. As noted above, Dr. Peter Goadsby points out the need to persevere with these studies to find nonvasoactive treatments for patients with cluster headache. DSM and SJT [source] What is the perceived nature of parental care and support for young people with cystic fibrosis as they enter adult health services?HEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 1 2010Nicola Iles RN MSc Abstract The majority of those diagnosed with cystic fibrosis (CF) now live to adulthood. In response to increased survival age, transition services have been developed to ensure smooth transfer from paediatric to adult specialist healthcare, although the majority of treatment and care continues to be delivered in the home. However, little is known about how young adults and staff conceptualise the nature of the parental role after young people have left paediatric care. The aim of this study is to explore the nature of parental support that is perceived to be available at this time. As part of a larger study of transitional care, semi-structured interviews were conducted with 50 young people with CF aged 13,24 years (32 with experience of transition and/or adult CF services) and 23 specialist healthcare professionals (14 working in adult care) across two CF centres in Southeast England. Interviews took place in young people's homes or within CF services, using a topic guide and were recorded, transcribed and analysed thematically. Four domains of perceived parental support were identified by the young people interviewed, with varying degrees of continuity into adult care: (1) Providing non-clinical practical and emotional support; (2) Acting as ,troubleshooters' in times of health-related crisis; (3) Working in partnership with offspring in ongoing disease management in the home and clinic; (4) Acting as ,protectors' of their children. Young people and service staff expressed tensions in managing parental involvement in post-paediatric consultations and the degree to which parents should be aware of their offspring's deteriorating health and social concerns. Parental anxiety and over-involvement was perceived by many young people and staff as unsupportive. We suggest that although health and social care providers are mindful of the tensions that arise for those leaving paediatric services, the place of parental support in adult care is currently contentious for these ,new' ageing populations. [source] Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosisHEPATOLOGY, Issue 6 2004Jeffery L. Smith Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas,liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P = .04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P < .05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD. (HEPATOLOGY 2004;39:1673,1682.) [source] Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosisHEPATOLOGY, Issue 2 2000Nils Kinnman M.D. The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the ,F508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of ,F508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease. [source] Evaluation and use of a synthetic quality control material, included in the European external quality assessment scheme for cystic fibrosis,HUMAN MUTATION, Issue 8 2008Sarah Berwouts Abstract Assuring high quality within the field of genetic testing is fundamental, as the results can have considerable impact on the patient and his or her family. The use of appropriate quality control (QC) samples is therefore essential. Diagnostic laboratories mainly use patient samples as QC material, which of course include a maximum of two mutations per sample. Bearing in mind that some assays (such as for cystic fibrosis [CF] testing) can test for more than 100 mutations, multiplex QC materials including more than two mutations could save valuable time and reagents. Based on this need, synthetic multiplex controls have been developed by Maine Molecular Quality Controls, Inc. (MMQCI) for CF. A synthetic control, containing six homozygous mutations and one polymorphism for CF transmembrane conductance regulator (CFTR), was evaluated by distributing it through the CF external quality assessment (EQA) scheme, along with the EQA samples in 2005. A total of 197 participants returned results of the yearly EQA scheme and 133 laboratories participated in the evaluation of the synthetic sample. Respectively, 76% and 73% of the participants were assigned as successful. This evaluation study revealed that the multiplex QC material performed well in the majority of assays and could be useful in method validation, as a tool to challenge interpretation skills, and as potential proficiency testing (PT) material. Hum Mutat 0, 1,8, 2008. © 2008 Wiley-Liss, Inc. [source] N-terminal CFTR missense variants severely affect the behavior of the CFTR chloride channel,HUMAN MUTATION, Issue 5 2008G.G. Gené Abstract Over 1,500 cystic fibrosis transmembrane conductance regulator (CFTR) gene sequence variations have been identified in patients with cystic fibrosis (CF) and related disorders involving an impaired function of the CFTR chloride channel. However, detailed structure,function analyses have only been established for a few of them. This study aimed evaluating the impact of eight N-terminus CFTR natural missense changes on channel behavior. By site-directed mutagenesis, we generated four CFTR variants in the N-terminal cytoplasmic tail (p.P5L, p.S50P, p.E60K, and p.R75Q) and four in the first transmembrane segment of membrane-spanning domain 1 (p.G85E/V, p.Y89C, and p.E92K). Immunoblot analysis revealed that p.S50P, p.E60K, p.G85E/V, and p.E92K produced only core-glycosylated proteins. Immunofluorescence and whole cell patch-clamp confirmed intracellular retention, thus reflecting a defect of CFTR folding and/or trafficking. In contrast, both p.R75Q and p.Y89C had a glycosylation pattern and a subcellular distribution comparable to the wild-type CFTR, while the percentage of mature p.P5L was considerably reduced, suggesting a major biogenesis flaw on this channel. Nevertheless, whole-cell chloride currents were recorded for all three variants. Single-channel patch-clamp analyses revealed that the channel activity of p.R75Q appeared similar to that of the wild-type CFTR, while both p.P5L and p.Y89C channels displayed abnormal gating. Overall, our results predict a major impact of the CFTR missense variants analyzed, except p.R75Q, on the CF phenotype and highlight the importance of the CFTR N-terminus on channel physiology. Hum Mutat 29(5), 738,749, 2008. © 2008 Wiley-Liss, Inc. [source] A T3 allele in the CFTR gene exacerbates exon 9 skipping in vas deferens and epididymal cell lines and is associated with Congenital Bilateral Absence of Vas Deferens (CBAVD),HUMAN MUTATION, Issue 1 2005Antoine Disset Abstract The different alleles at the (TG)m(T)n polymorphic loci at the 3, end of the human CFTR intron 8 determine the efficiency by which exon 9 is spliced. We identified a novel TG12T3 allele in a congenital bilateral absence of vas deferens (CBAVD) patient who carries a [TG11T7; p.Phe508Cys; p.Met470Val] haplotype on the other chromosome. To better understand the complex regulation of exon 9 splicing, we analyzed the levels of correctly spliced CFTR transcripts in six CFTR-expressing epithelial cell lines derived from lung, colon, testis, vas deferens, and epididymis transiently transfected with four CFTR minigenes (pTG11T7, pTG12T7, pTG12T5, and pTG12T3). In this work, we show that a decrease in the Ts at the polymorphic locus in a TG12 background determines a cell-type dependent reduction in exon 9+ transcripts that is not related to the basal splicing efficiency in the cell line. These data emphasize the role of the T5 allele in CBAVD and identify the T3 allele as a severe cystic fibrosis (CF) disease-causing mutation. Finally, UV cross-linking experiments demonstrated that tissue-specific trans -acting splicing factors do not contribute to the different patterns of exon 9 splicing found between the cell lines. However, we observed that lower numbers of Ts can alter the binding of TDP-43 (TDP43 or TARDBP) to its specific target ug12 in a tissue-specific manner. Our results support the idea that the ratio of general splicing factors plays a role in the tissue variability of exon 9 alternative splicing. Hum Mutat 25:72,81, 2005. © 2004 Wiley-Liss, Inc. [source] Three phosphor plate systems and film compared for imaging root canalsINTERNATIONAL ENDODONTIC JOURNAL, Issue 4 2001A. C. Shearer Abstract Aim The aim of this study was to compare three phosphor plate intraoral imaging systems (Digora (DA), Digident (DT), Denoptix (DX)) and E-speed conventional film (CF) for the imaging of root canals. Methodology Sixty extracted permanent teeth were exposed using CF, DA, DT and DX. The length of root canal visible from its most apical extent to a line drawn at the level of the cementoenamel junction was measured and this was expressed as a percentage of the distance between the radiographic apex and the cementoenamel line. All images were examined concurrently by two examiners. Films were viewed under standardized conditions and DA, DT and DX images were viewed directly from the monitor screen. The images on the monitor were enhanced to give the subjectively clearest image. Results The mean percentage of canal visible on CF was 90%, DA 78%, DT 81% and DX 83%. The difference was significant for CF,DA (P < 0.001) and CF,DT (P = 0.001). There was no statistically significant difference for CF,DX or between any of the three phosphor plate imaging systems. Conclusions It is concluded that a greater length of root canal was visible on conventional film than on three phosphor plate imaging systems and that this may be of clinical significance. [source] Kinetic and mechanistic investigation into the influence of chelate substituents on the substitution reactions of platinum(II) terpyridine complexesINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 12 2008Deogratius Jaganyi The substitution kinetics of the complexes [Pt{4,-(o -CH3 -Ph)-terpy} Cl]SbF6 (CH3PhPtCl(Sb)), [Pt{4,-(o -CH3 -Ph)-terpy}Cl]CF3SO3 (CH3PhPtCl(CF)), [Pt(4,-Ph-terpy)Cl]SbF6 (PhPtCl), [Pt(terpy)Cl]Cl·2H2O (PtCl), [Pt{4,-(o -Cl-Ph)-terpy}Cl]SbF6 (ClPhPtCl), and [Pt{4,-(o -CF3 -Ph)-terpy}Cl]SbF6 (CF3PhPtCl), where terpy is 2,2,:6,,2,-terpyridine, with the nucleophiles thiourea (TU), N,N,-dimethylthiourea (DMTU), and N,N,N,,N,-tetramethylthiourea (TMTU) were investigated in methanol as a solvent. The substitution reactions of the chloride displacement from the metal complexes by the nucleophiles were investigated as a function of nucleophile concentration and temperature under pseudo-first-order conditions using the stopped-flow technique. The reactions followed the simple rate law kobs = k2[Nu]. The results indicate that the introduction of substituents in the ortho position of the phenyl group on the ancillary ring of the terpy unit does influence the extent of ,-backbonding in the terpy ring. This controls the electrophilicity of the platinum center, which in turn controls the lability of the chloro-leaving group. The strength of the electron-donating or -withdrawing ability of the substituents correlates with the reactivity of the complexes. Electron-donating substituents decrease the rate of substitution, whereas electron-withdrawing substituents increase the rate of substitution. This was supported by DFT calculations at the B3LYP/LACVP+** level of theory, which showed that most of the electron density of the HOMO is concentrated on the phenyl ligand rather than on the metal center in the case of the strongest electron-withdrawing substituent in CF3PhPtCl. The opposite was found to be true with the strongest electron-donating substituent in CH3PhPtCl. Thiourea was found to be the best nucleophile with N,N,N,,N,-tetramethylthiourea being the weakest due to steric effects. The temperature dependence studies support an associative mode of activation. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 808,818, 2008 [source] Hard palate perforation: an unusual finding in paracoccidioidomycosisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2001Luiz G. M. Castro MD A 36-year-old black man presented to his dermatologist in May 1996 complaining of mucosal lesions in the mouth, as well as perforation of the hard palate. The lesions had started approximately 7 months before and had worsened gradually. Other complaints included odynophagia, dysphagia, mild dyspnea, and dry cough. The patient was in good general health, but reported a 3 kg weight loss over the previous semester. The hard and soft palate presented erythematous ulcers with a finely granulated base and irregular, but clearly defined margins. A perforation (diameter, 0.5 cm) of the hard palate was seen in the center of the ulcerated region (Fig. 1). Direct examination of 10% KOH cleared specimens showed typical double-walled, multiple budding yeast structures. Paracoccidioidomycosis (PCM) serologic reactions tested positive for double immunodiffusion (DI), complement fixation (CF) 1 : 256 and counterimmunoelectrophoresis (CIE) 1 : 128. Hematoxylin and eosin-stained sections of oral lesions showed an ulcer covered by a fibrous leukocytic crust, with a lymphoplasmacytic infiltrate, as well as multinuclear giant cells containing round bodies with a double membrane. Gomori,Grocott staining showed budding and blastoconidia suggestive of PCM. Lung computed tomography (CT) exhibited findings consistent with pulmonary PCM. Diagnosis of the chronic multifocal form of PCM with oral and pulmonary manifestations was established. Drug therapy was initiated with ketoconazole (KCZ) 200 mg twice daily, which led to clinical cure in approximately 2 months. Serum antibody values rose 30 days after institution of therapy (CIE 1 : 256; CF 1 : 512), peaking at day 60 (CIE 1 : 1024; CF 1 : 1024). Three months later the daily dose was reduced to 200 mg and titers declined slowly. The diameter of the perforation remained unchanged (Fig. 2). The hard palate perforation was corrected with a palatoplasty 27 months after initiation of drug therapy (Fig. 3). KCZ was discontinued when serologic cure was achieved after 34 months of treatment (DI weakly positive; CIE 1 : 8; CF not measurable). The patient was discharged 46 months after the first visit. Figure 1. Ulcers with a finely granulated base on the hard palate with irregular but clearly defined margins. A perforation (diameter, 0.5 cm) of the hard palate is seen in the center of the ulcerated region Figure 2. Clinical aspect after 2 months of oral ketoconazole 200 mg twice daily. Resolution of ulceration was evident, but the diameter of the perforation remained unchanged Figure 3. Final result of palatoplasty to cover hard palate perforation [source] Influence of natural and controlled fermentations on , -galactosides, antinutrients and protein digestibility of beans (Phaseolus vulgaris L.)INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 4 2008Emire Admassu Shimelis Summary The influence of natural fermentation (NF) and controlled fermentation (CF) in diminishing the content of antinutrients, , -galactosides and increments in in vitro protein digestibility was investigated. The dry bean (Phaseolus vulgaris) flour was the substrate used in this research study. A decrease in raffinose oligosaccharide, antinutritional components and pH was observed in both types of fermentation. The natural lactic fermentation of ground beans produced significant increase (P < 0.05) in protein digestibility. For all varieties of beans, raffinose concentration reduced significantly to an undetectable level after 96 h of NF. CF did not have any significant effect on the reduction of the , -galactosides content of the flours during fermentation. NF is an inexpensive method by which consumers can obtain good-quality protein. Both types of fermentation diminish antinutrients and improve the nutritional value of the bean flour, and indicate the potential to use bean flour as an ingredient for fabricated foods. [source] Analysis of DEFB1 regulatory SNPs in cystic fibrosis patients from North-Eastern ItalyINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010L. Segat Summary Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5,-untranslated region of the DEFB1 gene (namely g-52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g-20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients. [source] Equivalent orbitals for multiconfigurational spin-tensor electron propagator method (MCSTEP): The vertical ionization potentials of B, NO, CF, and OFINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 6 2008Dongxia Ma Abstract The multiconfigurational spin tensor electron propagator method (MCSTEP) was developed as an implementation of electron propagator/single particle Green's function methods for ionization potentials (IPs) and electron affinities (EAs). MCSTEP was specifically designed for open shell and highly correlated (nondynamically correlated) initial states. For computational efficiency the initial state used in MCSTEP is typically a small complete active space (CAS) multiconfigurational self-consistent field (MCSCF) state. If in a molecule there are some degenerate orbitals which are not fully or half occupied, usual MCSCF calculations will make these orbitals inequivalent, i.e., the occupied ones will be different from the nonoccupied ones, so that the degeneracy is broken. In this article, we use a state averaged MCSCF method to get equivalent orbitals for the initial state and import the integrals into the subsequent MCSTEP calculations. This gives, in general, more reliable MCSTEP vertical IPs. © 2008 Wiley Periodicals, Inc., 2008 [source] Combined S99/RB51 antigen for complement fixation test for serological diagnosis of brucellosis in cattle and sheepJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2002R. Adone Aims: To assess the efficiency of a single antigen for the complement fixation (CF) test, prepared by combining Brucella abortus smooth strain 99 (S99) with Brucella abortus rough strain RB51(RB51), in detecting cattle and sheep infected or vaccinated with Brucella spp. Methods and Results: Serum samples from B. abortus -infected and RB51-vaccinated cattle were tested by the CF test using S99, RB51 and the combined S99/RB51 as antigens. Likewise, serum samples from Brucella melitensis -infected, RB51-vaccinated and Brucella ovis- infected sheep were tested by the CF test using S99, RB51, hot saline (HS) and combined S99/RB51 as antigens. Comparative analysis of the CF results showed that no reduction of sensitivity or specificity occurs when S99/RB51 antigen is used instead of specific antigens used separately. Conclusions: The results of this study indicated that combined S99/RB51 antigen used in the CF test, because of its specificity and sensitivity, could be used in animal brucellosis surveillance systems to improve the efficiency of the preliminary screening of herds. Significance and Impact of the Study: This study proposes an improved antigen for the CF test for the epidemiological survey of animal brucellosis. It could represent advantages over standard protocols because of its ability to detect antibody responses following infection or vaccination withBrucella strains of rough and smooth phenotype. [source] | |||||||||||||||||||||||||||||||||||||||||||