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Kinds of Kd Terms modified by Kd Selected AbstractsRefractory Progression of Coronary Aneurysms, a Case of Delayed Onset Kawasaki Disease as Depicted by Cardiac Computed Tomography AngiographyCONGENITAL HEART DISEASE, Issue 3 2010FACP, Shah Azmoon MD ABSTRACT Background., Kawasaki disease (KD) is an immune-mediated vasculitis of unknown etiology with self-limited clinical course that was first described in 1967 by Dr. Tomisaku Kawasaki. It is a disease of early childhood and rare past late adulthood but one that can have detrimental consequences when there is a delay in diagnosis and treatment. Cardiovascular complications causing increased morbidity and mortality may include coronary artery aneurysms, myocardial infarction, heart failure, arrhythmias, and peripheral artery occlusion. Case Presentation., Here, we present an atypical case of delayed onset KD in a young teenager. DS had visited three different emergency departments during the course of 2 weeks for unrelenting fevers. Despite multiple treatment protocols including immunoglobulin, steroids, and tumor necrosis factor-alpha antagonists, he continued to have progression of cardiovascular complications. While echocardiographic findings were suspicious for cardiac complications, a cardiac computed tomography (CT) angiography was able to clearly distinguish giant coronary aneurysms. Conclusion., Without prompt therapy, fever and manifestations of acute inflammation can last for several weeks to months with increased risk toward complications. The incidence of coronary artery aneurysms has been noted to be 25% in untreated patients with a mortality rate of up to 2%. Using low-dose protocols along with high spatial and temporal resolution of cardiac CT angiography may provide a useful and complimentary imaging modality in accurate diagnosis and follow-up of patients with KD. [source] Metacognition as a mediator of the effects of impairments in neurocognition on social function in schizophrenia spectrum disordersACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010P. H. Lysaker Lysaker PH, Shea AM, Buck KD, Dimaggio G, Nicolò G, Procacci M, Salvatore G, Rand KL. Metacognition as a mediator of the effects of impairments in neurocognition on social function in schizophrenia spectrum disorders. Objective:, This study explored whether Mastery, a domain of metacognition that reflects the ability to use knowledge about mental states to respond to psychological challenges, mediated the effects of neurocognition on the frequency of social contact and persons' capacity for social relatedness. Method:, Participants were 102 adults with schizophrenia or schizoaffective disorder. Neurocognition was represented by a single factor score produced by a principal components analysis of a neurocognitive test battery. Mastery was assessed using the metacognitive assessment scale and social functioning by the quality of life scale. Results:, Using structural equation modeling, specifically measured-variable path analysis, a mediational model consisting of neurocognitive capacity linked to mastery and capacity for social relationships and mastery linked with frequency of social contact and capacity for social relatedness showed acceptable fit to the observed data. This persisted after controlling for negative and cognitive symptoms. Conclusion:, Results suggest that certain forms of metacognition mediate the influence of neurocognition upon function in schizophrenia. [source] Type 1 diabetes and epilepsy: Efficacy and safety of the ketogenic dietEPILEPSIA, Issue 6 2010Anastasia Dressler Summary Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD. [source] The influence of concurrent anticonvulsants on the efficacy of the ketogenic dietEPILEPSIA, Issue 8 2009Peter F. Morrison Summary It is unknown if any particular anticonvulsants modify the likelihood of seizure reduction when used in combination with the ketogenic diet (KD). A retrospective study was performed of 217 consecutive children who started the KD from 2000,2007. Patients included did not have any changes to their anticonvulsant dose. Efficacy data at 3 months on the KD were analyzed with respect to the six most frequently used anticonvulsants in this cohort. A total of 115 patients were included. Children receiving phenobarbital in combination with the KD were significantly less likely to have a >50% seizure reduction (p = 0.003). Conversely, those receiving zonisamide in combination with the KD at onset were more likely to have a >50% reduction (p = 0.04). These results provide practical information to clinicians who are treating children receiving both the KD and anticonvulsants. [source] A blinded, crossover study of the efficacy of the ketogenic dietEPILEPSIA, Issue 2 2009John M. Freeman Summary Despite over 80 years of use, the ketogenic diet (KD) has never been tested in a blinded manner. Twenty children with intractable Lennox-Gastaut syndrome (LGS) were fasted 36 h and then randomized to receive the classic KD in conjunction with a solution containing either 60 g/day of glucose or saccharin. Parents and physicians were blinded to both the solution composition and level of ketosis. A crossover to the KD with the alternate solution occurred following the sixth day and a repeat fast. A 24-h electroencephalography (EEG) was obtained at baseline and after each arm. After administration of the solution, there was moderate evidence of a reduction in parent-reported seizures between the glucose and saccharin arms, with a median difference of 1.5 seizures per day (p = 0.07). There was no reduction in the number of EEG-identified events, with a median reduction of 7 events per day (p = 0.33). Ketosis was not completely eliminated in the glucose-added arm. [source] History of the ketogenic dietEPILEPSIA, Issue 2008James W. Wheless Summary Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the ketogenic diet (KD) was introduced by modern physicians as a treatment for epilepsy in the 1920s. For two decades this therapy was widely used, but with the modern era of antiepileptic drug treatment its use declined dramatically. By the end of the twentieth century this therapy was available in only a small number of children's hospitals. Over the past 15 years, there has been an explosion in the use, and scientific interest in the KD. This review traces the history of one of the most effective treatments for childhood epilepsy. [source] Medium-chain triglyceride (MCT) ketogenic therapyEPILEPSIA, Issue 2008Yeou-mei Christiana Liu Summary The medium-chain triglyceride diet (MCTD) is a variant of the classic 4:1 ketogenic diet (KD) introduced in 1971 by Huttenlocher as an attempt to improve the palatability of the KD by allowing more carbohydrates yet preserving ketosis. Although initially found to be equally effective as the classic KD, use of the MCTD declined because of frequent gastrointestinal side effects such as cramps, diarrhea, and vomiting. Recently, we have used the MCTD in more than 50 patients. We have found excellent seizure control, similar to the classic KD, and with careful monitoring, we have encountered minimal side effects. The MCTD should remain a viable dietary option for children with refractory epilepsy who have large appetites, can tolerate more calories, or cannot accept the restrictions of the classic KD. [source] The Modified Atkins DietEPILEPSIA, Issue 2008Eric H. Kossoff Summary In 2003, a case series was published describing the benefits of a less restrictive ketogenic diet (KD) started as an outpatient without a fast and without any restrictions on calories, fluids, or protein. This "Modified Atkins Diet" (MAD) restricts carbohydrates to 10 g/day (15 g/day in adults) while encouraging high fat foods. Now 5 years later, there have been eight prospective and retrospective studies published on this alternative dietary therapy, both in children as well as adults. In these reports, 45 (45%) have had 50,90% seizure reduction, and 28 (28%) >90% seizure reduction, which is remarkably similar to the traditional KD. This review will discuss basics and tips to best provide the MAD, evidence for its efficacy, suggestions about the role of ketosis in dietary treatment efficacy, and its side effect profile. Lastly, the possible future benefits of this treatment for new-onset seizures, adults, neurologic conditions other than epilepsy, and developing countries of the world will be discussed. [source] Peroxisome proliferator-activated receptor alpha and the ketogenic dietEPILEPSIA, Issue 2008Tim Cullingford Summary Peroxisome proliferator-activated receptor alpha (PPAR,) is a drug/fatty acid-activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPAR, in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action. [source] The contribution of norepinephrine and orexigenic neuropeptides to the anticonvulsant effect of the ketogenic dietEPILEPSIA, Issue 2008David Weinshenker Summary The ketogenic diet (KD) is a high-fat, low-carbohydrate, low-protein diet used to treat refractory epilepsy. Despite its efficacy and many years of investigation, the mechanism by which the KD exerts its anticonvulsant effect remains controversial and poorly understood. The purpose of this article is to review the available data considering two classes of molecules that may contribute to the anticonvulsant effect of the KD: norepinephrine and the orexigenic neuropeptides galanin and neuropeptide Y. [source] Current Treatment of Myoclonic Astatic Epilepsy: Clinical Experience at the Children's Hospital of PhiladelphiaEPILEPSIA, Issue 9 2007Sudha Kilaru Summary:,Purpose: Myoclonic astatic epilepsy (MAE) is a generalized epilepsy of early childhood. Little is known about the use of newer antiepileptic treatments (AET) in MAE. The purpose of this study was to describe the characteristics, treatment, and outcome of a contemporary MAE cohort exposed to the new generation AET. Methods: Charts of subjects with MAE treated between 1998 and 2005 were reviewed. Results: Twenty-three subjects (19 boys), with a median (range) follow-up of 38 (2, 86) months were identified. Thirty-nine percent had a family history of epilepsy, and 39% had family history of febrile seizures. Age at seizure onset was a median of 36 (12,24) months. Initial EEG was normal in 30%. When seizures ceased, EEG background and epileptiform abnormalities persisted in 17 and 58%, respectively. On average, each subject was exposed to five AET. The most frequently used AET was valproate (83%). Seizure freedom occurred spontaneously in three subjects, with ethosuximide and levetiracetam in one each, valproate and lamotrigine in two each, topiramate in three and the ketogenic diet (KD) in five subjects. By 36 months after seizure onset, 67% achieved seizure freedom. At the last visit, 43% were developmentally normal, 52% had mild, and 5% had moderate cognitive disabilities. Time to seizure freedom did not correlate with cognitive outcome. Conclusions: The new generation of AET may offer significant benefit to children with MAE. The KD was the most effective AET in this series, and perhaps should be considered earlier in treatment. [source] Efficacy and Tolerability of the Ketogenic Diet According to Lipid:Nonlipid Ratios,Comparison of 3:1 with 4:1 DietEPILEPSIA, Issue 4 2007Joo Hee Seo Summary:,Purpose: The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1. Methods: Seventy-six patients with refractory childhood epilepsy were randomly placed into two groups and were started on KD diets with nonlipid:lipid ratios of either 3:1 or 4:1. Antiepileptic efficacy and diet tolerability were evaluated 3 months after initiating the diet. Patients showing seizure-free outcome with the 4:1 diet were changed to the 3:1 diet, and those without a seizure-free outcome on the 3:1 diet were changed to the 4:1 diet, for three more months, after which time their progress was monitored. Results: (1) Antiepileptic efficacy was higher for the 4:1 than the 3:1 diet (p < 0.05). Twenty-two (55.0%) of 40 patients on the 4:1 diet and 11 (30.5%) of 36 patients on the 3:1 diet became seizure free. Seizure reduction of over 90% was observed in 2 (5.0%) patients on the 4:1 diet, and 2 (5.6%) on the 3:1 diet. (2) Dietary tolerability was better for the 3:1 than the 4:1 diet. Gastrointestinal symptoms were observed in 5 (13.9%) patients with the 3:1 diet and 14 (35.0%) patients with the 4:1 diet (p < 0.05). (3) For seizure-free patients who started on the 4:1 diet, antiepileptic efficacy was maintained after changing to the 3:1 diet, while 10 (83.3%) of 12 patients who were not seizure free with the 3:1 diet showed increased seizure reduction after changing to the 4:1 diet. (4) Complications from the KD and laboratory data were not significantly different between the two groups. Conclusions: The 4:1 KD showed greater antiepileptic efficacy than the 3:1 diet with higher seizure-free outcome. In most cases, seizure free outcome was maintained even after changing the ratio to 3:1. Dietary tolerability was better in the 3:1 diet than the 4:1 with less frequent gastrointestinal symptoms. [source] Selenium Deficiency Associated with Cardiomyopathy: A Complication of the Ketogenic DietEPILEPSIA, Issue 4 2003A. G. Christina Bergqvist Summary: ,Purpose: The ketogenic diet (KD) is an efficacious treatment for intractable epilepsy, associated with infrequent side effects. The KD is known to be deficient in most vitamins and minerals and may be deficient in trace minerals. We report biochemical selenium deficiency in nine patients on the KD, including one who developed cardiomyopathy. Methods: A whole-blood selenium level was obtained on the symptomatic patient after noting the patient's poor appearance on physical examination. Children already treated and children beginning the KD were then evaluated prospectively for selenium status by measuring whole-blood or serum selenium as part of routine laboratory evaluation every 3 months. Results: The index case had no detectable whole-blood selenium. Cardiac physical examination and ECG were normal, but the echocardiogram revealed cardiomyopathy. Thirty-nine additional children had the selenium status evaluated. Eight had selenium levels below the normal range (six initially, and two developed low selenium levels on serial testing). They were referred for cardiology evaluations, which were normal. Selenium supplementation improved levels in all children. Low levels were seen in some children after only a few months of treatment. Conclusions: The nutrient adequacy of the currently used KD has not been fully evaluated. The nutrient content of KD with usual supplements may not meet Recommended Dietary Allowances (RDA) for selenium and may not provide other trace minerals in adequate amounts. At our center, selenium deficiency was found in 20% of the patients evaluated. Screening for selenium deficiency is suggested if the patient KD regimen does not meet ,75% of the RDA or if the child is symptomatic. Nutrient supplementation should provide adequate trace elements for children treated with the KD. The KD requires close monitoring of the overall nutritional status. [source] General Anesthesia and the Ketogenic Diet: Clinical Experience in Nine PatientsEPILEPSIA, Issue 5 2002Ignacio Valencia Summary: ,Purpose: To determine if children actively on the ketogenic diet (KD) can safely undergo general anesthesia (GA) for surgical procedures. Methods: The records of children treated with the KD at Children's Hospital (Boston, Massachusetts) from 1995 to the present were reviewed. The charts of children who had received GA while on the diet were evaluated with regard to demographics, procedure information, anesthesia records, blood chemistries, and perioperative course. Of 71 children on the KD during the period of the study, nine (12.7%) had procedures requiring GA while on the diet. Results: Nine children received GA for surgical procedures ranging from central line placement to hemispherectomy while on the KD. At the time of GA, the children ranged from age 1 to 6 years, and had been on the KD for 2,60 months. The patients received carbohydrate-free intravenous solutions perioperatively. Anesthesia duration ranged from 20 min to 11.5 h; for longer procedures, serum pH, glucose, and electrolyte levels were monitored. Serum glucose levels remained stable in all patients, but serum pH typically decreased; the largest reduction was to 7.16. In three procedures, patients received intravenous bicarbonate because of level of acidosis. There were no perioperative complications. Conclusions: Children on the KD can safely undergo GA for surgical procedures. Although serum glucose levels appear to remain stable, serum pH or bicarbonate levels should be monitored because of the risk of metabolic acidosis. [source] IRAK-4 kinase activity-dependent and -independent regulation of lipopolysaccharide-inducible genesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008Magdalena Koziczak-Holbro Abstract IRAK-4 kinase inactive (IRAK-4 KD) knock-in mice display defects in TLR- and IL-1 receptor signaling and are resistant to LPS-induced shock. In the present study we examined the LPS-induced response in IRAK-4 KD mice in more detail. We show that IRAK-4 kinase activity is required for certain aspects of TLR-mediated signaling but not for others. We found that IRAK-4 KD cells displayed reduced JNK and p38 signaling, while NF-,B was activated to a normal level but with delayed kinetics compared to wild-type cells. TLR4-mediated IRF3 activation was intact in these cells. Comprehensive analysis of expression of LPS-inducible genes by microarray demonstrated that IRAK-4 KD cells were severely impaired in the expression of many pro-inflammatory genes, suggesting their dependence on IRAK-4 kinase activity. In contrast, the expression of a subset of LPS-induced genes of anti-viral response was not affected by IRAK-4 kinase deficiency. Additionally, we demonstrate that LPS-activated early expression and production of some cytokines, e.g., TNF-,, is partially induced in the absence of IRAK-4 kinase activity. This suggests that the partially unaffected TLR4-mediated signaling could still drive expression of these genes in early phases and that IRAK-4 kinase activity is important for a more sustained anti-bacterial response. See accompanying commentary http://dx.doi.org/10.1002/eji.200838161 [source] Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivoFEBS JOURNAL, Issue 2 2010Eric Calvo Aegyptin is a 30 kDa mosquito salivary gland protein that binds to collagen and inhibits platelet aggregation. We have studied the biophysical properties of aegyptin and its mechanism of action. Light-scattering plot showed that aegyptin has an elongated monomeric form, which explains the apparent molecular mass of 110 kDa estimated by gel-filtration chromatography. Surface plasmon resonance identified the sequence RGQOGVMGF (where O is hydroxyproline) that mediates collagen interaction with von Willebrand factor (vWF) as a high-affinity binding site for aegyptin, with a KD of approximately 5 nm. Additionally, aegyptin interacts with the linear peptide RGQPGVMGF and heat-denatured collagen, indicating that the triple helix and hydroxyproline are not a prerequisite for binding. However, aegyptin does not interact with scrambled RGQPGVMGF peptide. Aegyptin also recognizes the peptides (GPO)10 and GFOGER with low affinity (,m range), which respectively represent glycoprotein VI and integrin ,2,1 binding sites in collagen. Truncated forms of aegyptin were engineered, and the C-terminus fragment was shown to interact with collagen and to attenuate platelet aggregation. In addition, aegyptin prevents laser-induced carotid thrombus formation in the presence of Rose Bengal in vivo, without significant bleeding in rats. In conclusion, aegyptin interacts with distinct binding sites in collagen, and is useful tool to inhibit platelet,collagen interaction in vitro and in vivo. Structured digital abstract ,,MINT-7299280, MINT-7299290: Collagen (uniprotkb:P02461) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by enzyme linked immunosorbent assay (MI:0411) ,,MINT-7298991, MINT-7299153, MINT-7299208: Collagen (uniprotkb:P02452) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by surface plasmon resonance (MI:0107) ,,MINT-7299266: Collagen (uniprotkb:P02452) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by fluorescence microscopy (MI:0416) ,,MINT-7299256: Collagen (uniprotkb:P02452) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by solid phase assay (MI:0892) [source] Molecular cloning of the ecdysone receptor and the retinoid X receptor from the scorpion Liocheles australasiaeFEBS JOURNAL, Issue 23 2007Yoshiaki Nakagawa cDNAs of the ecdysone receptor and the retinoid X receptor were cloned from the Japanese scorpion Liocheles australasiae, and the amino acid sequences were deduced. The full-length cDNA sequences of the L. australasiae ecdysone receptor and the L. australasiae retinoid X receptor were 2881 and 1977 bp in length, respectively, and the open reading frames encoded proteins of 560 and 414 amino acids. The amino acid sequence of the L. australasiae ecdysone receptor was similar to that of the ecdysone receptor-A of the soft tick, Ornithodoros moubata (68%) and to that of the ecdysone receptor-A1 of the lone star tick, Amblyomma americanum (66%), but showed lower similarity to the ecdysone receptors of Orthoptera and Coleoptera (53,57%). The primary sequence of the ligand-binding region of the L. australasiae ecdysone receptor was highly homologous to that of ticks (85,86%). The amino acid sequence of the L. australasiae retinoid X receptor was also homologous to the amino acid sequence of ultraspiracles of ticks (63%) and insects belonging to the orders Orthoptera and Coleoptera (60,64%). The identity of both the L. australasiae ecdysone receptor and the L. australasiae retinoid X receptor to their lepidopteran and dipteran orthologs was less than 50%. The cDNAs of both the L. australasiae ecdysone receptor (L. australasiae ecdysone receptor-A) and the L. australasiae retinoid X receptor were successfully translated in vitro using a rabbit reticulocyte lysate system. An ecdysone analog, ponasterone A, bound to L. australasiae ecdysone receptor-A (KD = 4.2 nm), but not to L. australasiae retinoid X receptor. The L. australasiae retinoid X receptor did not enhance the binding of ponasterone A to L. australasiae ecdysone receptor-A, although L. australasiae retinoid X receptor was necessary for the binding of L. australasiae ecdysone receptor-A to ecdysone response elements. [source] Encapsulation and release of a fluorescent probe, khusimyl dansylate, obtained from vetiver oil by complex coacervationFLAVOUR AND FRAGRANCE JOURNAL, Issue 1 2008A. S. Prata Abstract The essential oil of vetiver [Vetiveria zizanoides (L.) Nash ex. Small] is widely used in the perfume industry, owing to its pleasant, long-lasting, woody aroma. If this substance can be encapsulated in microparticles so that its release can be controlled, the effective duration of its properties should be extended for a much longer period of time. The present study was thus designed to investigate the encapsulation of this vetiver essential oil in microparticles. Since the detection of the effective release of such a complex mixture from these microparticles into the receiving medium can be problematic, an identifiable probe can be released with it to facilitate evaluation of the progression of the release process. Zizanoic acid is one of the compounds found in vetiver oil which depreciates its sensorial quality. This acid was thus extracted and reduced to the corresponding alcohol, khusimol, which was combined with dansyl chloride to form a fluorescent ester, khusimyl dansylate (KD). The vetiver oil and the fluorescent probe were then encapsulated (100:1) in microparticles produced by the complex coacervation of gum Arabic and gelatin. The microparticles showed spherical shape, multinuclear distribution of the core material and high encapsulation efficiency (95%). Two versions of these microparticles, moist and freeze-dried ones, were tested for the release of the KD into an ethanol medium. The moist particles released the whole KD after 5 h, although only 80% of the fluorescent probe was released with the freeze-dried microparticles at that time, probably due to the constriction caused by freeze-drying. The release of the components of vetiver oil, under the same experimental conditions, was followed, in parallel, by gas chromatography and the results obtained were compared and discussed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Br/Cl signature of hydrothermal fluids: liquid,vapour fractionation of bromine revisitedGEOFLUIDS (ELECTRONIC), Issue 2 2006A. LIEBSCHER Abstract Br/Cl ratios of hydrothermal fluids are widely used as geochemical tracers in marine hydrothermal systems to prove fluid phase separation processes. However, previous results of the liquid,vapour fractionation of bromine are ambiguous. Here we report new experimental results of the liquid,vapour fractionation of bromine in the system H2O,NaCl,NaBr at 380,450°C and 22.9,41.7 MPa. Our data indicate that bromine is generally more enriched than chlorine in the liquid phase. Calculated exchange coefficients KD(Br-Cl)liquid-vapour for the reaction Brvapour + Clliquid = Brliquid + Clvapour are between 0.94 ± 0.08 and 1.66 ± 0.14 within the investigated P,T range. They correlate positively with DClliquid-vapour and suggest increasing bromine,chlorine fractionation with increasing opening of the liquid,vapour solvus, i.e. increasing distance to the critical curve in the H2O,NaCl system. An empirical fit of the form KD(Br-Cl)liquid-vapour = a*ln[b*(DClliquid-vapour,1) + e1/a] yields a = 0.349 and b = 1.697. Based on this empirical fit and the well-constrained phase relations in the H2O,NaCl system we calculated the effect of fluid phase separation on the Br/Cl signature of a hydrothermal fluid with initial seawater composition for closed and open adiabatic ascents along the 4.5 and 4.8 J g,1 K,1 isentropes. The calculations indicate that fluid phase separation can significantly alter the Br/Cl ratio in hydrothermal fluids. The predicted Br/Cl evolutions are in accord with the Br/Cl signatures in low-salinity vent fluids from the 9 to 10°N East Pacific Rise. [source] Functional and structural analysis of five mutations identified in methylmalonic aciduria cbIB type,HUMAN MUTATION, Issue 9 2010Ana Jorge-Finnigan Abstract ATP:cob(I)alamin adenosyltransferase (ATR, E.C.2.5.1.17) converts reduced cob(I)alamin to the adenosylcobalamin cofactor. Mutations in the MMAB gene encoding ATR are responsible for the cblB type methylmalonic aciduria. Here we report the functional analysis of five cblB mutations to determine the underlying molecular basis of the dysfunction. The transcriptional profile along with minigenes analysis revealed that c.584G>A, c.349-1G>C, and c.290G>A affect the splicing process. Wild-type ATR and the p.I96T (c.287T>C) and p.R191W (c.571C>T) mutant proteins were expressed in a prokaryote and a eukaryotic expression systems. The p.I96T protein was enzymatically active with a KM for ATP and KD for cob(I)alamin similar to wild-type enzyme, but exhibited a 40% reduction in specific activity. Both p.I96T and p.R191W mutant proteins are less stable than the wild-type protein, with increased stability when expressed under permissive folding conditions. Analysis of the oligomeric state of both mutants showed a structural defect for p.I96T and also a significant impact on the amount of recovered mutant protein that was more pronounced for p.R191W that, along with the structural analysis, suggest they might be misfolded. These results could serve as a basis for the implementation of pharmacological therapies aimed at increasing the residual activity of this type of mutations. Hum Mutat 31:1033,1042, 2010. © 2010 Wiley-Liss, Inc. [source] One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B,HUMAN MUTATION, Issue 1 2003Ali R. Afzal Abstract Autosomal recessive Robinow syndrome (RRS) is a severe skeletal dysplasia with short stature, generalized limb shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. The gene encoding receptor orphan receptor tyrosine kinase 2 (ROR2) is located on chromosome 9q22 and homozygous loss-of-function mutations in this gene are responsible for RRS. Moreover, knocking out the mouse Ror2 gene causes mesomelic dwarfism in the homozygous state, with almost identical features to recessive Robinow syndrome. The protein product of this gene is a cell membrane receptor, containing distinct motifs including an immunoglobulin-like (Ig) domain, a Frizzled-like cysteine-rich domain (FRZ or CRD), and a kringle domain (KD) in the extracellular region; and an intracellular region with tyrosine kinase (TK), serine/threonine-rich, and proline-rich structures. The extracellular motifs of the ROR2 protein are known to be involved in protein,protein interactions. The tyrosine kinase domain is involved in an as yet uncharacterized signaling pathway. Interestingly, heterozygous mutations in ROR2 have recently been shown to give rise to autosomal dominant brachydactyly type B1 (BDB1). This condition is characterized by terminal deficiency of fingers and toes. A variety of mutations have been reported in ROR2. Here, these genetic defects are compiled and possible genotype,phenotype correlations are discussed. Hum Mutat 22:1,11, 2003. © 2003 Wiley-Liss, Inc. [source] Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Patrizia Formichi Globoid cell leukodystrophy or Krabbe disease (KD), is a hereditary disorder caused by galactosylceramidase deficiency. Progressive accumulation of psychosine is considered to be the critical pathogenetic mechanism of cell death in the Krabbe brain. Psychosine mechanism of action has not been fully elucidated. It seems to induce apoptosis in oligodendrocytes through a mitochondrial pathway and to up-regulate inflammatory cytokines production resulting in oligodendrocyte loss. Our aim was to evaluate the role of psychosine in apoptotic cell death and inflammatory response in a group of patients affected by KD using peripheral blood lymphocytes (PBLs) and peripheral blood mononuclear cells (PBMCs) as a cellular model. PBLs from KP and healthy controls were exposed to 20 µM psychosine and analysed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy. Our results showed that psychosine induces apoptosis in PBLs through a mitochondrial pathway, but the apoptotic response was quite low especially KP. The role of psychosine in the up-regulation of cytokines (TNFalpha, IL8 and MCP1) has been evaluated by ELISA in PBMCs from KP and controls after stimulation with LPS and phytohemagglutinin. Both in basal condition and after LPS stimulation, cells from KP showed a significant increase in TNF-, production, reduced MCP1 levels and no modification in IL8. These results indicate that lymphomonocytes from KP had a basal proinflammatory pattern that was amplified by psychosine. In conclusion, the reduced apoptotic response and the atypical cytokine production observed in our experiments, suggest an involvement of inflammatory pattern in immune peripheral cells of KP. J. Cell. Physiol. 212:737,743, 2007. © 2007 Wiley-Liss, Inc. [source] AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunctionAGING CELL, Issue 4 2010Subat Turdi Summary Aging is associated with myocardial dysfunction although the underlying mechanism is unclear. AMPK, a key cellular fuel sensor for energy metabolism, is compromised with aging. This study examined the role of AMPK deficiency in aging-associated myocardial dysfunction. Young or old wild-type (WT) and transgenic mice with overexpression of a mutant AMPK ,2 subunit (kinase dead, KD) were used. AMPK , isoform activity, myocardial function and morphology were examined. DCF and JC-1 fluorescence probes were employed to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (,,m), respectively. KD mice displayed significantly reduced ,2 but not ,1 AMPK isoform activity at both ages with a greater effect at old age. Aging itself decreased ,1 isoform activity. Cardiomyocyte contractile function, intracellular Ca2+ handling, and SERCA2a levels were compromised with aging, the effects of which were exacerbated by AMPK deficiency. H&E staining revealed cardiomyocyte hypertrophy with aging, which was more pronounced in KD mice. TEM micrographs displayed severe disruption of mitochondrial ultrastructure characterized by swollen, irregular shape and disrupted cristae in aged KD compared with WT mice. Aging enhanced ROS production and reduced ,,m, the effects of which were accentuated by AMPK deficiency. Immunoblotting data depicted unchanged Akt phosphorylation and a significant decrease in mitochondrial biogenesis cofactor PGC-1, in aged groups. AMPK deficiency but not aging decreased the phosphorylation of ACC and eNOS. Expression of membrane Glut4 and HSP90 was decreased in aged KD mice. Moreover, treatment of the AMPK activator metformin attenuated aging-induced cardiomyocyte contractile defects. Collectively, our data suggest a role for AMPK deficiency in aging-induced cardiac dysfunction possibly through disrupted mitochondrial function and ROS production. [source] CHARACTERISTICS OF MUSCLE FROM TWO SPECIES OF BIGEYE SNAPPER, PRIACANTHUS TAYENUS AND PRIACANTHUS MACRACANTHUSJOURNAL OF FOOD BIOCHEMISTRY, Issue 4 2002SOOTTWAT BENJAKUL ABSTRACT Composition and some properties of muscle from two species of bigeye snapper, P. tayenus and P. macracanthus, were investigated. Both species had a similar composition with the same myofibrillar protein content. However, muscle proteins from P. tayenus had higher thermal stability than those from P. macracanthus, as indicated by the higher enthalpy for transitions as well as the lower inactivation rate constant (KD). Upon 15 days of iced storage, natural actomyosin Ca2* -ATP ase and Mg2+ -Ca2+ -ATPase activities decreased, whereas Mg2+ -EGTA-ATPase activity increased, suggesting the denaturation of myosin, actomyosin and troponin/tropomyosin complexes, respectively. Increased surface hydrophobicity and decreased sulfhydryl groups indicated the denaturation possibly occurred via hydrophobic interaction and disulfide formation. Heading and eviscerating offish retarded the denaturation and physicochemical changes of proteins during iced storage. The results indicated that a rapid and proper post harvest handling was of importance to maintain the muscle quality of bigeye snapper. [source] Technical Approach to Simplify the Purification Method and Characterization of Microbial Transglutaminase Produced from Streptoverticillium ladakanumJOURNAL OF FOOD SCIENCE, Issue 1 2000M.-L. Ho ABSTRACT: In order to fast and economically purify MTGase from Streptoverticillium ladakanum, a stepwise elution method was developed and compared with linear gradient elution method. MTGase was purified to electrophoretical homogeneity by using CM Sepharose CL-6B and Blue Sepharose Fast Flow chromatographies by linear gradient or stepwise methods. The recovery of MTGase by linear gradient and stepwise methods were 68.4% and 81.0%, respectively. The optimal temperature and pH were 40 °C and 5.5, respectively. It was stable at pH 5.0 to 7.0 and had a rate constant (KD) of 6.21 °o 10 -5 min -1 for thermal inactivation at 45 °C. The purified MTGase was activated by K+ Na+, Ca2+, Mn2+, and Mg2+, not affected by Fe3+, EDTA, but inhibited by Cu2+, Zn2+, Hg2+, Ni2+, Co2+, Cd2+, PCMB, NEM, IAA, and PMSF. A simple stepwise method was developed for the purification of MTGase from S. ladakanum. [source] Efficacy of dietary treatments for epilepsyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 2 2010E. G. Neal Abstract The ketogenic diet (KD) is a high fat, restricted carbohydrate regime that has been used as a treatment for seizures since the 1920s, when it was designed to induce a similar metabolic response to fasting. A modification of this early classical version of the KD was introduced in the 1970s using medium chain triglycerides as an alternative fat source. More recently, two alternative, less-restrictive dietary treatments have been developed: the modified Atkins diet and the low glycaemic index diet. There are many case reports and observational studies reporting successful use of the KD, and a growing number of studies reporting similar success with the modified Atkins protocol. A recent randomised controlled trial has shown a significant benefit of the KD compared to no change in treatment. The use of these dietary therapies in the UK is supported by literature evidence, although often is limited by a lack of resources; increasing awareness and knowledge is fundamental to ensure availability for those individuals with intractable epilepsy who may benefit from them. [source] Synthesis of [18F]3-[1-(3-fluoropropyl)-(S)-pyrrolidin-2-ylmethoxy]pyridine ([18F]NicFP): a potential ,4,2 nicotinic acetylcholine receptor radioligand for PETJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2003Filip Dumont Abstract Nicotinic acetylcholine receptors are widely distributed throughout the human brain and are believed to play a role in several neurological and psychiatric disorders. In order to identify an effective PET radioligand for in vivo assessment of the ,4,2 subtype of nicotinic receptor, we synthesized [18F]3-[1-(3-fluoropropyl)-(S)-pyrrolidin-2-ylmethoxy]pyridine (NicFP). The in vitro KD of NicFP was determined to be 1.1 nM, and the log P value obtained by HPLC analysis of the unlabelled standard was found to be 2.2. The radiosynthesis of [18F]NicFP was carried out by a nucleophilic substitution reaction of anhydrous [18F]fluoride and the corresponding mesylate precursor. After purification by HPLC, the radiochemical yield was determined to be 11.3±2.1% and the specific activity was 0.47±0.18 Ci/,mol (EOS, n = 3). The time of synthesis and purification was 99±2 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright © 2003 John Wiley & Sons, Ltd. [source] A new formulation of garnet,clinopyroxene geothermometer based on accumulation and statistical analysis of a large experimental data setJOURNAL OF METAMORPHIC GEOLOGY, Issue 7 2009D. NAKAMURAArticle first published online: 13 JUL 200 Abstract Published experimental data including garnet and clinopyroxene as run products were used to develop a new formulation of the garnet,clinopyroxene geothermometer based on 333 garnet,clinopyroxene pairs. Only experiments with graphite capsules were selected because of difficulty in estimating the Fe3+ content of clinopyroxene. For the calibration, a published subregular-solution model was adopted to express the non-ideality of garnet. The magnitude of the Fe,Mg excess interaction parameter for clinopyroxene (WFeMgCpx), and differences in enthalpy and entropy of the Fe,Mg exchange reaction were regressed from the accumulated experimental data set. As a result, a markedly negative value was obtained for the Fe,Mg excess interaction parameter of clinopyroxene (WFeMgCpx = , 3843 J mol,1). The pressure correction is simply treated as linear, and the difference in volume of the Fe,Mg exchange reaction was calculated from a published thermodynamic data set and fixed to be ,120.72 (J kbar,1 mol,1). The regressed and obtained thermometer formulation is as follows: where T = temperature, P = pressure (kbar), A = 0.5 Xgrs (Xprp , Xalm , Xsps), B = 0.5 Xgrs (Xprp , Xalm + Xsps), C = 0.5 (Xgrs + Xsps) (Xprp , Xalm), Xprp = Mg/(Fe2+ + Mn + Mg + Ca)Grt, Xalm = Fe/(Fe2+ + Mn + Mg + Ca)Grt, Xsps = Mn/(Fe2+ + Mn + Mg + Ca)Grt, Xgrs = Ca/(Fe2+ + Mn + Mg + Ca)Grt, XMgCpx = Mg/(Al + Fetotal + Mg)Cpx, XFeCpx = Fe2+/(Al + Fetotal + Mg)Cpx, KD = (Fe2+/Mg)Grt/(Fe2+/Mg)Cpx, Grt = garnet, Cpx = clinopyroxene. A test of this new formulation to the accumulated data gave results that are concordant with the experimental temperatures over the whole range of the experimental temperatures (800,1820 °C), with a standard deviation (1 sigma) of 74 °C. Previous formulations of the thermometer are inconsistent with the accumulated data set; they underestimate temperatures by about 100 °C at >1300 °C and overestimate by 100,200 °C at <1300 °C. In addition, they tend to overestimate temperatures for high-Ca garnet (Xgrs , 0.30,0.50). This new formulation has been tested against previous formulations of the thermometer by application to natural eclogites. This gave temperatures some 20,100 °C lower than previous formulations. [source] Reactions leading to the formation and breakdown of stilpnomelane in the Otago Schist, New ZealandJOURNAL OF METAMORPHIC GEOLOGY, Issue 4 2000G. Li Semi-pelitic rocks ranging in grade from the prehnite,pumpellyite to the greenschist facies from south-eastern Otago, New Zealand, have been investigated in order to evaluate the reactions leading to formation and breakdown of stilpnomelane. Detrital grains of mica and chlorite along with fine-grained authigenic illite and chlorite occur in lower-grade rocks with compactional fabric parallel to bedding. At higher grades, detrital grains have undergone dissolution, and metamorphic phyllosilicates have crystallized with preferred orientation (sub)parallel to bedding, leading to slaty cleavage. Stilpnomelane is found in metapelites of the pumpellyite,actinolite facies and the chlorite zone of the greenschist facies, but only rarely in the biotite zone of the greenschist facies. Illite or phengite is ubiquitous, whereas chlorite occurs only rarely with stilpnomelane upgrade of the pumpellyite-out isograd. Chemical and textural relationships suggest that stilpnomelane formed from chlorite, phengite, quartz, K-feldspar and iron oxides. Stilpnomelane was produced by grain-boundary replacement of chlorite and by precipitation from solution, overprinting earlier textures. Some relict 14 Å chlorite layers are observed by TEM to be in the process of transforming to 12 Å stilpnomelane layers. The AEM analyses show that Fe is strongly partitioned over Mg into stilpnomelane relative to chlorite (KD,2.5) and into chlorite relative to phengite (KD,1.9). Modified A,FM diagrams, projected from the measured phengite composition rather than from ideal KAl3Si3O10(OH)2, are used to elucidate reactions among chlorite, stilpnomelane, phengite and biotite. In addition to pressure, temperature and bulk rock composition, the stilpnomelane-in isograd is controlled by variations in K, Fe3+/Fe2+, O/OH and H2O contents, and the locus of the isograd is expected to vary in rocks of different oxidation states and permeabilities. Biotite, quartz and less phengitic muscovite form from stilpnomelane, chlorite and phengite in the biotite zone. Projection of bulk rock compositions from phengite, NaAlO2, SiO2 and H2O reveals that they lie close to the polyhedra defined by the A,FM minerals and albite. Other extended A,FM diagrams, such as one projected from phengite, NaAlO2, CaAl2O4, SiO2 and H2O, may prove useful in the evaluation of other low-grade assemblages. [source] Oligohis-tags: mechanisms of binding to Ni2+ -NTA surfacesJOURNAL OF MOLECULAR RECOGNITION, Issue 4 2009Steven Knecht Abstract Since immobilized metal ion affinity chromatography (IMAC) was first reported, several modifications have been developed. Among them, Ni2+ immobilized by chelation with nitrilotriacetic acid (NTA) bound to a solid support has become the most common method for the purification of proteins carrying either a C - or N -terminal histidine (His) tag. Despite its broad application in protein purification, only little is known about the binding properties of the His-tag, and therefore almost no thermodynamic and kinetic data are available. In this study, we investigated the binding mechanism of His-tags to Ni2+ -NTA. Different series of oligohistidines and mixed oligohistidines/oligoalanines were synthesized using automated solid-phase peptide synthesis (SPPS). Binding to Ni2+ -NTA was analyzed both qualitatively and quantitatively with surface plasmon resonance (SPR) using commercially available NTA sensor chips from Biacore. The hexahistidine tag shows an apparent equilibrium dissociation constant (KD) of 14,±,1,nM and thus the highest affinity of the peptides synthesized in this study. Furthermore, we could demonstrate that two His separated by either one or four residues are the preferred binding motifs within hexahis tag. Finally, elongation of these referred motifs decreased affinity, probably due to increased entropy costs upon binding. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||||||||