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B6
Kinds of B6 Terms modified by B6 Selected AbstractsOccupational and systemic contact dermatitis with photosensitivitydue to vitamin B6CONTACT DERMATITIS, Issue 3 2001A. K. Bajaj [source] Mice Carrying the Szt1 Mutation Exhibit Increased Seizure Susceptibility and Altered Sensitivity to Compounds Acting at the M-ChannelEPILEPSIA, Issue 9 2004James F. Otto Summary:,Purpose: Mutations in the genes that encode subunits of the M-type K+ channel (KCNQ2/KCNQ3) and nicotinic acetylcholine receptor (CHRNA4) cause epilepsy in humans. The purpose of this study was to examine the effects of the Szt1 mutation, which not only deletes most of the C-terminus of mouse Kcnq2, but also renders the Chnra4 and Arfgap-1 genes hemizygous, on seizure susceptibility and sensitivity to drugs that target the M-type K+ channel. Methods: The proconvulsant effects of the M-channel blocker linopirdine (LPD) and anticonvulsant effects of the M-channel enhancer retigabine (RGB) were assessed by electroconvulsive threshold (ECT) testing in C57BL/6J- Szt1/+ (Szt1) and littermate control C57BL/6J+/+ (B6) mice. The effects of the Szt1 mutation on minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures were evaluated by varying stimulation intensity and frequency. Results:Szt1 mouse seizure thresholds were significantly reduced relative to B6 littermates in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Mice were injected with LPD and RGB and subjected to ECT testing. In the minimal clonic seizure model, Szt1 mice were significantly more sensitive to LPD than were B6 mice [median effective dose (ED50) = 3.4 ± 1.1 mg/kg and 7.6 ± 1.0 mg/kg, respectively]; in the partial psychomotor seizure model, Szt1 mice were significantly less sensitive to RGB than were B6 mice (ED50= 11.6 ± 1.4 mg/kg and 3.4 ± 1.3 mg/kg, respectively). Conclusions: These results suggest that the Szt1 mutation alters baseline seizure susceptibility and pharmacosensitivity in a naturally occurring mouse model. [source] Counting the COST: a European collaboration on the efficiency of psychotherapeutic treatment of patients with eating disordersEUROPEAN EATING DISORDERS REVIEW, Issue 3 2005Hans Kordy Abstract In 1993, a European collaboration on the efficiency of psychotherapeutic treatment of patients with Eating Disorders was initiated. The European Union supported it under the name COST Action B6 from 1994,2001. This unique opportunity to co-ordinate research and to exchange clinical experience eventually attracted more than 200 researchers and clinicians from 19 European countries. This is the first paper of a series of five through which we report on the general background, the organizational structure, the objectives, the design, the main findings, and specific methodological developments of COST Action B6. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Care provision for patients with eating disorders in Europe: what patients get what treatment where?EUROPEAN EATING DISORDERS REVIEW, Issue 3 2005Matthias Richard Abstract In this paper, we report on the similarities and differences between patients with eating disorders and the services provided to them across 80 centres participating in a European collaboration (COST Action B6). Differences in patient characteristics as well as differences in treatment regimen, especially length of treatment, are described. The relationship between patient characteristics, treatment setting and length of treatment is investigated by multilevel analysis. The findings show a rich diversity in service conditions and traditions across European countries. Patients with anorexia nervosa are mostly treated in inpatient settings, patients with bulimia nervosa are treated mostly as outpatients,with the exception of German-speaking countries. Day-patient settings were generally rare. Clinical characteristics of the patients,e.g. severity of symptoms or illness duration,contributed only little to the differences in treatment length (within as well as between centres), whereas organizational factors explained the largest proportion of between centre variability. The findings are discussed from a service research perspective. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Systemic IFN-, drives kidney nephritis in B6.Sle123 miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Anna-Marie Fairhurst Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source] IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007Alice Abstract The potent innate cytokines IL-12 and IL-18 are considered to be important antigen-independent mediators of IFN-, production by NK cells and T,lymphocytes. The present analysis addresses the physiological role of IL-12 and IL-18 in the generation of virus-specific CD8+ T cells. Both wt C57BL/6J (B6) mice and mice with disrupted IL-12p40 (IL-12p40,/,) or IL-18 (IL-18,/,) genes were infected with an influenza,A virus and the characteristics of the resultant epitope-specific CD8+ T cell responses were compared. While IL-12 appeared to have no notable effect on either virus growth or on CD8+ T cell response profiles, the absence of IL-18 was associated with delayed virus clearance from the lung and, despite normal numbers, a significantly reduced production of IFN-,, TNF-,, and IL-2 by epitope-specific CD8+ T cells. While this cytokine phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no evidence was seen for any additive effect. Together, our results suggest that IL-18, but not IL-12, induces optimal, antigen-specific production of key cytokines by CD8+ T cells for the efficient clearance of influenza virus from the lungs of infected mice. [source] Marginal zone B cell enrichment and strong follicular B cell reduction correlate with a delayed IgG response in a light chain diversity restricted mouse modelEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004Yacine Abstract Recently developed B6.,,,SEG mice (by crossing ,, and C57BL/6 mice congenic for the wild Mus spretus SEG strain , locus lacking genes coding for ,1 and ,3) have a very reduced light chain diversity. B6.,,,SEG mice produce only ,2 and ,x light chains. Regardless of their Igh haplotype, B6.,,,SEG mice show a restricted B cell distribution by light chain subtype with ,x dominance in all peripheral compartments except peritoneal cavity where ,2 is dominant. This distribution suggests that selection mechanisms act differently in different B cell compartments on ,2 and ,x bearing B cells. Sequence analysis before or following immunization did not reveal unusual mechanisms of diversification. B6.,,,SEG mice still respond to various challenging antigens using new Ab patterns. In particular, regardless of Igha or Ighb haplotypes, the anti-2,4-dinitrophenyl response is characterized by a restricted diversity for both heavy and light chains and a delayed IgG response when compared to B6 and B6.,, mice. We suggest that the delayed IgG response is due to the expansion of marginal zone B cells whereas follicular B cells are strongly reduced. [source] Fc,RIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune diseaseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2003Kaori Yajima Abstract MRL.Faslpr/lpr mice, a model for systemic lupus erythematosus (SLE) and arthritis in humans, have a Fas mutation that results in spontaneous development of systemic autoimmune diseases and a short life span. Half of them die by 5,6,months of age due to massive progression of systemic autoimmune diseases, such as lupus nephritis. However, C57BL/6 (B6).Faslpr/lpr strain does not develop such disorders within the normal life span, indicating that suppressor gene(s) in B6 mice may control the onset and exacerbation of disease. Here, we show that the gene for a unique inhibitory Fc receptor for IgG (Fc,RIIB) is a critical SLE suppressor. Fc,RIIB-deficient B6.Faslpr/lpr (B6.IIB,/,Faslpr/lpr) mice developed systemic autoimmune diseases, including anti-DNA and anti-type,II collagen autoantibodies and cryoglobulin production, immune complex glomerulonephritis and arthritis. They were short-lived, due to enhanced autoantibody production by B cells culminating in fatal lupus nephritis. Thus, Fc,RIIB deletion with Fas mutation is sufficient for the development of systemic autoimmunity in B6 mice. The inhibitory signaling cascade via Fc,RIIB may be critical for suppressing SLE in humans. [source] hypercloso -Hexa(amino)hexaboranes: Structurally Related to Known hypercloso -Dodecaboranes, Metastable with Regard to Their Classical CycloisomersEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 36 2009Wahid Mesbah Abstract B6(NMe2)6 (2a) is the first neutral hypercloso -hexaborane to be characterized by X-ray structural analysis. The geometry of 2a is in nice agreement with that of the Ci symmetric molecule computed at the B3LYP/6-311+G** level of theory. Two B3 triangles with long B···B distances in 2a are reminiscent of those in Hawthorne's benzyloxy-substituted hypercloso -dodecaboranes 6a,b. Upon heating to 200 °C, 2a transforms into Nöth's classical cyclohexaborane 1a. Computations at the B3LYP/6-311+G** + ZPE level of theory show 1a to be 21.6 kcal,mol,1lower in energy than 2a, that is, the latter is metastable. hypercloso -Hexaborane B6(NEt2)6 (2b), which was reported to be thermodynamically more stable than 1b, is computed to be 22.4 kcal,mol,1less stable than 1b. Pure 1b is shown here not to transform into 2b upon standing in solution, which is in contrast to reports in the literature for a mixture containing 1b. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Structural Characterization of N -Methylpyridoxine (MePN; PN = Vitamin B6) and Its Diorganotin Complexes [SnR2(MePN-H)]I (R = Me, Et, Bu and Ph)EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 15 2003José S. Casas Abstract For comparison with the corresponding pyridoxine complexes we have prepared dimethyl-, diethyl-, dibutyl- and diphenyltin(IV) complexes of N -methylpyridoxine (MePN). The compounds [SnMe2(MePN,H)]I (1), [SnEt2(MePN,H)]I (2), [SnBu2(MePN,H)]I (3) and [SnPh2(MePN,H)]I·H2O (4) were isolated and characterized by IR, Raman, Mössbauer, 1H, 13C and 119Sn NMR spectroscopy, and by EI and FAB mass spectrometry. The crystal structures of [HMePN]I and of compounds 1, 2·2H2O and 3 were determined by X-ray diffractometry. Their lattices contain dimeric [SnR2(MePN,H)]22+ units (R = Me, Et, Bu) in which two bridging-chelating methylpyridoxinato anions link pentacoordinate Sn atoms with coordination polyhedra closer to square pyramids than to trigonal bipyramids. NMR results show that the dimeric cations persist in (CD3)2SO. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Calcium taste preferences: genetic analysis and genome screen of C57BL/6J × PWK/PhJ hybrid miceGENES, BRAIN AND BEHAVIOR, Issue 6 2008M. G. Tordoff To characterize the genetic basis of voluntary calcium consumption, we tested C57BL/6J mice (B6; with low avidity for calcium), PWK/PhJ mice (PWK; with high avidity for calcium) and their F1 and F2 hybrids. All mice received a series of 96-h two-bottle preference tests with a choice between water and the following: 50 mm CaCl2, 50 mm calcium lactate, 50 mm MgCl2, 100 mm KCl, 100 mm NH4Cl, 100 mm NaCl, 5 mm citric acid, 30 ,m quinine hydrochloride and 2 mm saccharin. Most frequency distributions of the parental and F1 but not F2 groups were normally distributed, and there were few sex differences. Reciprocal cross analysis showed that B6 × PWK F1 mice had a non-specific elevation of fluid intake relative to PWK × B6 F1 mice. In the F2 mice, trait correlations were clustered among the divalent salts and the monovalent chlorides. A genome screen involving 116 markers showed 30 quantitative trait loci (QTLs), of which six involved consumption of calcium chloride or lactate. The results show pleiotropic controls of calcium and magnesium consumption that are distinct from those controlling consumption of monovalent chlorides or exemplars of the primary taste qualities. [source] Autism-like behavioral phenotypes in BTBR T+tf/J miceGENES, BRAIN AND BEHAVIOR, Issue 2 2008H. G. McFarlane Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms. [source] Genetic basis for the psychostimulant effects of nicotine: a quantitative trait locus analysis in AcB/BcA recombinant congenic miceGENES, BRAIN AND BEHAVIOR, Issue 7 2005K. J. Gill Genetic differences in sensitivity to nicotine have been reported in both animals and humans. The present study utilized a novel methodology to map genes involved in regulating both the psychostimulant and depressant effects of nicotine in the AcB/BcA recombinant congenic strains (RCS) of mice. Locomotor activity was measured in a computerized open-field apparatus following subcutaneous administration of saline (days 1 and 2) or nicotine on day 3. The phenotypic measures obtained from this experimental design included total basal locomotor activity, as well as total nicotine activity, nicotine difference scores, nicotine percent change and nicotine regression residual scores. The results indicated that the C57BL/6J (B6) were insensitive to nicotine over the entire dose,response curve (0.1, 0.2, 0.4 and 0.8 mg/kg). However, the 0.8-mg/kg dose of nicotine produced a significant decrease in the locomotor activity in the A/J strain and a wide and continuous range of both locomotor excitation and depression among the AcB/BcA RCS. Single-locus association analysis in the AcB RCS identified quantitative trait loci (QTL) for the psychostimulant effects of nicotine on chromosomes 11, 12, 13, 14 and 17 and one QTL for nicotine-induced depression on chromosome 11. In the BcA RCS, nicotine-induced locomotor activation was associated with seven putative regions on chromosomes 2, 7, 8, 13, 14, 16 and 17. There were no overlapping QTL and no genetic correlations between saline- and nicotine-related phenotypes in the AcB/BcA RCS. A number of putative candidate genes were in proximity to regions identified with nicotine sensitivity, including the ,2 subunit of the nicotinic acetylcholine receptor and the dopamine D3 receptor. [source] Stable generation of serum- and feeder-free embryonic stem cell-derived mice with full germline-competency by using a GSK3 specific inhibitorGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 6 2009Hiromu Sato Abstract C57BL/6 (B6)-derived embryonic stem (ES) cells are not widely used to generate knockout mice despite the advantage of a well-defined genetic background because of poor developmental potential. We newly established serum- and feeder-free B6 ES cells with full developmental potential by using leukemia inhibitory factor (LIF) and 6-bromoindirubin-3,-oxime (BIO), a glycogen synthase kinase-3 (GSK3) inhibitor. BIO treatment significantly increased the expression levels of 364 genes including pluripotency markers such as Nanog and Klf family. Unexpectedly, by aggregating or microinjecting those ES cells to each eight-cell-stage diploid embryo, we stably generated germline-competent ES-derived mice. Furthermore, founder mice completely derived from female XO, heterozygous, or homozygous mutant B6 ES cells were directly available for intercross breeding and phenotypic analysis. We hereby propose that serum- and feeder-free B6 ES cells stimulated with LIF plus GSK3 inhibitor are valuable for generating mouse models on B6 background. genesis 47:414,422, 2009. © 2009 Wiley-Liss, Inc. [source] Micronutrients and the risk of renal cell cancer: A case-control study from ItalyINTERNATIONAL JOURNAL OF CANCER, Issue 4 2007Cristina Bosetti Abstract The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41,0.75), and vitamin C (OR = 0.72, 95% CI = 0.54,0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59,1.08) for retinol, 0.82 (95% CI = 0.61,1.10) for ,-carotene, 0.90 (95% CI = 0.68,1.20) for ,-carotene, 0.94 (95% CI = 0.73,1.21) for ,-criptoxanthin, 0.85 (95% CI = 0.63,1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57,1.01) for vitamin D, 0.75 (95% CI = 0.55,1.01) for thiamine, 0.88 (95% CI = 0.66,1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64,1.13), 0.85 (95% CI = 0.64,1.12) for folate and 0.80 (95% CI = 0.60,1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC. © 2006 Wiley-Liss, Inc. [source] Paresthesias Developing in an Elderly Patient after Chronic Usage of Nitrofurantoin and Vitamin B6JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2003Rhodora A. Lacerna MD No abstract is available for this article. [source] Effects of high-level dietary B-vitamins on performance, body composition and tissue vitamin contents of growing/finishing pigsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2007B. M. Böhmer Summary Forty-eight growing pigs were randomly assigned to five dietary groups and penned individually. They received a diet based on barley, wheat, corn and soya bean meal according to requirement. The experimental groups were supplemented with 400% or 800% of vitamins B2, B6 and pantothenic acid, or 400% or 800% of biotin, while all other vitamins were administered according to requirement. Growth performance, carcass characteristics, aspartate aminotransferase (AST), and content of vitamins in blood, liver and muscles were recorded. Growth performance showed no influence of supplementation, while backfat thickness in the group with 800% B2/B6/pantothenic acid was significantly higher. Content of B2 in blood, liver and muscle was similar in all groups. Content of B6 in blood and liver showed significant differences according to supplementation. The content of vitamin B6 in muscle in the experimental groups was significantly higher than that in the control group. The content of pantothenic acid in blood and muscle in the experimental groups was significantly higher, while in liver all groups were significantly influenced by the supplementation level. Biotin content in liver showed no influence, but the content in plasma was significantly higher in the experimental groups and the content in muscle was significantly higher according to supplementation. The activity of AST showed no significant influence of the dietary vitamin level, but it was obviously decreased in the groups supplemented with biotin. The findings indicate that the dietary supplementation of vitamin B2, B6, pantothenic acid and biotin could not improve performance, but the contents in blood, liver and muscle. [source] Kinetics of microbial hydrogenation of free linoleic acid to conjugated linoleic acidsJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2008H. Xu Abstract Aims:, To investigate the ability of selected probiotic bacterial strains to produce conjugated linoleic acid (CLA) and also to estimate the biohydrogenation kinetics of Lactobacillus acidophilus on the production of CLA from free linoleic acid (LA). Methods and Results:, Six probiotic bacteria, Lact. paracasei, Lact. rhamnosus GG, Lact. acidophilus ADH, and Bifidobacterium longum B6, Lact. brevis, and Lact. casei, were used to examine their ability to convert LA to CLA. LA tolerance was evaluated by addition of different LA concentrations in MRS broth. Lact. acidophilus showed the major tolerant to LA and the greatest CLA-producing ability (36,48 ,g ml,1 of CLA). The rate-controlling steps were k2 and k1 for the addition of 1 and 3 mg ml,1 of LA, respectively. The percentage of CLA conversion was higher in MRS broth supplemented with 1 mg ml,1 (65%) than 3 mg ml,1 (26%). Conclusion:, The results provide useful information and new approach for understanding the biohydrogenation mechanisms of CLA production. Significance and Impact of the Study:, This study would help elucidate the pathway from LA to stearic acid (SA), known as biohydrogenation. In addition, the use of selected probiotic bacteria might lead to a significant improvement in food safety. [source] Enzyme Replacement Therapy for Murine Hypophosphatasia,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008José Luis Millán PhD Abstract Introduction: Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5,-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6 -dependent seizures. There is no established medical treatment. Materials and Methods: Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2,/,), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, ,CT, and histomorphometry. Results:Akp2,/, mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions: Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2,/, mice. [source] QTL Analysis of Trabecular Bone in BXD F2 and RI Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Abbey L Bower Abstract A sample of 693 mice was used to identify regions of the mouse genome associated with trabecular bone architecture as measured using ,CT. QTLs for bone in the proximal tibial metaphysis were identified on several chromosomes indicating regions containing genes that regulate properties of trabecular bone. Introduction: Age-related osteoporosis is a condition of major concern because of the morbidity and mortality associated with osteoporotic fractures in humans. Osteoporosis is characterized by reduced bone density, strength, and altered trabecular architecture, all of which are quantitative traits resulting from the actions of many genes working in concert with each other and the environment over the lifespan. ,CT gives accurate measures of trabecular bone architecture providing phenotypic data related to bone volume and trabecular morphology. The primary objective of this research was to identify chromosomal regions called quantitative trait loci (QTLs) that contain genes influencing trabecular architecture as measured by ,CT. Materials and Methods: The study used crosses between C57BL/6J (B6) and DBA/2J (D2) as progenitor strains of a second filial (F2) generation (n = 141 males and 148 females) and 23 BXD recombinant inbred (RI) strains (n , 9 of each sex per strain). The proximal tibial metaphyses of the 200-day-old mice were analyzed by ,CT to assess phenotypic traits characterizing trabecular bone, including bone volume fraction, trabecular connectivity, and quantitative measures of trabecular orientation and anisotropy. Heritabilities were calculated and QTLs were identified using composite interval mapping. Results: A number of phenotypes were found to be highly heritable. Heritability values for measured phenotypes using RI strains ranged from 0.15 for degree of anisotropy in females to 0.51 for connectivity density in females and total volume in males. Significant and confirmed QTLs, with LOD scores ,4.3 in the F2 cohort and ,1.5 in the corresponding RI cohort were found on chromosomes 1 (43 cM), 5 (44 cM), 6 (20 cM), and 8 (49 cM). Other QTLs with LOD scores ranging from 2.8 to 6.9 in the F2 analyses were found on chromosomes 1, 5, 6, 8, 9, and 12. QTLs were identified using data sets comprised of both male and female quantitative traits, suggesting similar genetic action in both sexes, whereas others seemed to be associated exclusively with one sex or the other, suggesting the possibility of sex-dependent effects. Conclusions: Identification of the genes underlying these QTLs may lead to improvements in recognizing individuals most at risk for developing osteoporosis and in the design of new therapeutic interventions. [source] Mapping Quantitative Trait Loci for Vertebral Trabecular Bone Volume Fraction and Microarchitecture in Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Mary L Bouxsein Abstract BMD, which reflects both cortical and cancellous bone, has been shown to be highly heritable; however, little is known about the specific genetic factors regulating trabecular bone. Genome-wide linkage analysis of vertebral trabecular bone traits in 914 adult female mice from the F2 intercross of C57BL/6J and C3H/HeJ inbred strains revealed a pattern of genetic regulation derived from 13 autosomes, with 5,13 QTLs associated with each of the traits. Ultimately, identification of genes that regulate trabecular bone traits may yield important information regarding mechanisms that regulate mechanical integrity of the skeleton. Introduction: Both cortical and cancellous bone influence the mechanical integrity of the skeleton, with the relative contribution of each varying with skeletal site. Whereas areal BMD, which reflects both cortical and cancellous bone, has been shown to be highly heritable, little is known about the genetic determinants of trabecular bone density and architecture. Materials and Methods: To identify heritable determinants of vertebral trabecular bone traits, we evaluated the fifth lumbar vertebra from 914 adult female mice from the F2 intercross of C57BL/6J (B6) and C3H/HeJ (C3H) progenitor strains. High-resolution ,CT was used to assess total volume (TV), bone volume (BV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp), and number (Tb.N) of the trabecular bone in the vertebral body in the progenitors (n = 8/strain) and female B6C3H-F2 progeny (n = 914). Genomic DNA from F2 progeny was screened for 118 PCR-based markers discriminating B6 and C3H alleles on all 19 autosomes. Results and Conclusions: Despite having a slightly larger trabecular bone compartment, C3H progenitors had dramatically lower vertebral trabecular BV/TV (,53%) and Tb.N (,40%) and higher Tb.Sp (71%) compared with B6 progenitors (p < 0.001 for all). Genome-wide quantitative trait analysis revealed a pattern of genetic regulation derived from 13 autosomes, with 5,13 quantitative trait loci (QTLs) associated with each of the vertebral trabecular bone traits, exhibiting adjusted LOD scores ranging from 3.1 to 14.4. The variance explained in the F2 population by each of the individual QTL after adjusting for contributions from other QTLs ranged from 0.8% to 5.9%. Taken together, the QTLs explained 22,33% of the variance of the vertebral traits in the F2 population. In conclusion, we observed a complex pattern of genetic regulation for vertebral trabecular bone volume fraction and microarchitecture using the F2 intercross of the C57BL/6J and C3H/HeJ inbred mouse strains and identified a number of QTLs, some of which are distinct from those that were previously identified for total femoral and vertebral BMD. Identification of genes that regulate trabecular bone traits may ultimately yield important information regarding the mechanisms that regulate the acquisition and maintenance of mechanical integrity of the skeleton. [source] Genetically Based Influences on the Site-Specific Regulation of Trabecular and Cortical Bone Morphology,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Stefan Judex Abstract The degree of site-specificity by which genes influence bone quantity and architecture was investigated in the femur of three strains of mice. Morphological indices were highly dependent on both genetic makeup as well as anatomical location showing that the assessment of bone structure from a single site cannot be extrapolated to other sites even within a single bone. Introduction: The identification of genes responsible for establishing peak BMD will yield critical information on the regulation of bone quantity and quality. Whereas such knowledge may eventually uncover novel molecular drug targets or enable the identification of individuals at risk of osteoporosis, the site-specificity by which putative genotypes cause low or high bone mass (and effective bone morphology) is essentially unknown. Materials and Methods: ,CT was used to determine morphological and microarchitectural features of the femora harvested from three genetically distinct strains of 4-month-old female mice, each with distinct skeletal mass (low: C57BL/6J [B6], medium: BALB/cByJ [BALB], high: C3H/HeJ [C3H]). Two trabecular regions (distal epiphysis and metaphysis) were considered in addition to four cortical regions within the metaphysis and diaphysis. Results and Conclusions: Comparing morphological properties of the different trabecular and cortical femoral regions between the three strains of mice, it was apparent that high or low values of specific parameters of bone morphology could not be consistently attributed to the same genetic strain. Trabecular metaphyseal bone volume, for instance, was 385% larger in C3H mice than in B6 mice, yet the two strains displayed similar bone volume fractions in the epiphysis. Similarly, BALB mice had 48% more trabecular bone than C3H mice in the epiphysis, but there were no strain-specific differences in cortical bone area at the diaphysis. These data suggest that the genetic control of bone mass and morphology, even within a given bone, is highly site-specific and that a comprehensive search for genes that are indicative of bone quantity and quality may also have to occur on a very site-specific basis. [source] Congenic Strains of Mice for Verification and Genetic Decomposition of Quantitative Trait Loci for Femoral Bone Mineral Density,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003Kathryn L Shultz Abstract Peak femoral volumetric bone mineral density (femoral bone mineral density) in C57BL/6J (B6) 4-month-old female mice is 50% lower than in C3H/HeJ (C3H) and 34% lower than in CAST/EiJ (CAST) females. Genome-wide analyses of (B6 × C3H)F2 and (B6 × CAST)F2 4-month-old female progeny demonstrated that peak femoral bone mineral density is a complex quantitative trait associated with genetic loci (QTL) on numerous chromosomes (Chrs) and with trait heritabilities of 83% (C3H) and 57% (CAST). To test the effect of each QTL on femoral bone mineral density, two sets of loci (six each from C3H and CAST) were selected to make congenic strains by repeated backcrossing of donor mice carrying a given QTL-containing chromosomal region to recipient mice of the B6 progenitor strain. At the N6F1 generation, each B6.C3H and B6.CAST congenic strain (statistically 98% B6-like in genomic composition) was intercrossed to obtain N6F2 progeny for testing the effect of each QTL on femoral bone mineral density. In addition, the femoral bone mineral density QTL region on Chr 1 of C3H was selected for congenic subline development to facilitate fine mapping of this strong femoral bone mineral density locus. In 11 of 12 congenic strains, 6 B6.C3H and 5 B6.CAST, femoral bone mineral density in mice carrying c3h or cast alleles in the QTL regions was significantly different from that of littermates carrying b6 alleles. Differences also were observed in body weight, femoral length, and mid-diaphyseal periosteal circumference among these 11 congenic strains when compared with control littermates; however, these latter three phenotypes were not consistently correlated with femoral bone mineral density. Analyses of eight sublines derived from the B6.C3H-1T congenic region revealed two QTLs: one located between 36.9 and 49.7 centiMorgans (cM) and the other located between 73.2 and 100.0 cM distal to the centromere. In conclusion, these congenic strains provide proof of principle that many QTLs identified in the F2 analyses for femoral bone mineral density exert independent effects when transferred and expressed in a common genetic background. Furthermore, significant differences in femoral bone mineral density among the congenic strains were not consistently accompanied by changes in body weight, femur length, or periosteal circumference. Finally, decomposition of QTL regions by congenic sublines can reveal additional loci for phenotypes assigned to a QTL region and can markedly refine genomic locations of quantitative trait loci, providing the opportunity for candidate gene testing. [source] Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidantsAGING CELL, Issue 4 2009Sang-Kyu Park Summary We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S. Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl- l -carnitine and tempol were as effective as CR in the heart, and ,-lipoic acid and coenzyme Q10 were as effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis. [source] Improving the Stability of Probiotic Bacteria in Model Fruit Juices Using Vitamins and AntioxidantsJOURNAL OF FOOD SCIENCE, Issue 5 2010N.P. Shah Abstract:, This study examined the survival of probiotic bacteria in a model fruit juice system. Three different strains of probiotic bacteria were used in this study: HOWARU,Lactobacillus rhamnosus,HN001, HOWARU,Bifidobacterium lactis,HN001, and,Lactobacillus paracasei,LPC 37. The probiotic bacteria were inoculated into model juice with various vitamins and antioxidants, namely white grape seed extract, green tea extract, vitamin B2, vitamin B3, vitamin B6, vitamin C, and vitamin E. The model juice without any additives was used as a control. Their viability was assessed on a weekly basis using plate count method. The model juice was made with sucrose, sodium citrate, citric acid powder, and distilled water and was pasteurized before use. Our findings showed that probiotic bacteria did not survive well in the harsh environment of the model fruit juice. However, the model juice containing vitamin C, grape extract, and green tea extract showed better survival of probiotic bacteria. The model juice containing grape seed extract, green tea extract, and vitamin C had the same initial population of 8.32 log CFU/mL, and at the end of the 6-wk storage period it had an average viability of 4.29 log CFU/mL, 7.41 log CFU/mL, and 6.44 log CFU/mL, respectively. Juices containing all other ingredients tested had viable counts of <10 CFU/mL at the end of the 6-wk storage period. [source] Novel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin AJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2001Rie Unno Abstract Background and Aims: We have previously reported that cluster of differentiation (CD)4+ T cells induced autoimmune liver diseases in mice with graft-versus-host reaction (GVHR) because of major histocompatibility complex (MHC) class II disparity. To analyze the progression of the autoimmune-related mechanism in the liver, concanavalin A (Con A) was injected in mice undergoing GVHR. The aim of this study is to clarify whether Con A deteriorates murine hepatic lesions induced by GVHR, and to elucidate the participation of the cytokines of liver-infiltrating CD4+ T cells. Methods: Mice (F1; B6.C-H-2bm12× B6) were intravenously injected with B6 T spleen cells. Concanavalin A (15 mg/kg) was administrated 5 days after cell transfer. We examined serum transaminase, antimitochondrial antibodies (AMA), antinuclear antibodies (ANA) and histological changes. Liver-infiltrating CD4+ T cells were sorted and their cytokine mRNA expression was examined by the use of reverse transcription,polymerase chain reaction (RT-PCR). Results: Graft-versus-host reaction + Con A mice revealed an elevated serum transaminase, elevated AMA and ANA titers, increased periportal cellular infiltration, piecemeal necrosis and bridging necrosis in the liver. In this group, interferon (IFN)-, mRNA expression was more elevated than it was in the GVHR mice. However, there was no difference in the expression of interleukin (IL)-10 mRNA between the two groups. Conclusion: The results suggest that Con A deteriorates the GVHR-induced hepatic lesions, and IFN-, and IL-10 of CD4+ T cells might be implicated in the progression of autoimmune-related hepatic lesions. This model might offer an aspect for the investigation of progressive mechanisms in T-cell- mediated hepatobiliary injury. [source] Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapyJOURNAL OF INTERNAL MEDICINE, Issue 5 2002T. Apeland Abstract. Apeland T, Mansoor MA, Seljeflot I, Brønstad I, Gøransson L, Strandjord RE (Rogaland Central Hospital, Stavanger; and Ullevål University Hospital, Oslo; Norway). Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy. J Intern Med 2002; 252: 456,464. Objectives. Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. Design. Longitudinal and open intervention study. Setting. Two dialysis units in the County of Rogaland. Subjects. All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. Interventions. After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. Main outcome measures. Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins , markers of endothelial activation and (iii) serum malondialdehyde (S-MDA) , a marker of oxidative stress and lipid peroxidation. Results. The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). Conclusions. Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance. [source] REVIEW: Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and EJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Reynold Spector Abstract With the application of genetic and molecular biology techniques, there has been substantial progress in understanding how vitamins are transferred across the mammalian blood,brain barrier and choroid plexus into brain and CSF and how vitamin homeostasis in brain is achieved. In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood,brain barrier or choroid plexus. Then the vitamins are accumulated by brain cells by separate, specialized systems. This review focuses on six vitamins (B1, B3, B6, pantothenic acid, biotin, and E) and the newer genetic information including relevant ,knockdown' or ,knockout' models in mice and humans. The overall objective is to integrate this newer information with previous physiological and biochemical observations to achieve a better understanding of vitamin transport and homeostasis in brain. This is especially important in view of the newly described non-cofactor vitamin roles in brain (e.g. of B1, B3, B6, and E) and the potential roles of vitamins in the therapy of brain disorders. [source] Workshop 5: NAAG and NAALADase: Functional Properties in the Central and Peripheral Nervous SystemJOURNAL OF NEUROCHEMISTRY, Issue 2002D. Bacich Glutamate carboxypeptidase II (GCPII, also known as N-acetylated-alpha-linked acidic dipeptidase or NAALADase) knockout (KO) mice were generated by inserting a GCPII targeting cassette containing a PGK-Neo resistance marker and stop codons in exons 1 and 2, and removal of exons 1 and 2 intron/exon boundary sequence. Embryonic stem cells were injected into C57BL6 blastocysts, and chimeric offspring born. Germline transmission was confirmed by mating the chimeras to generate heterozygous KO mice. Crossing heterozygous mice generated F2 generation mice homozygous for the null mutant, as confirmed by loss of GCPII protein. NAAG hydrolyzing activity was minimal (0.07 pmol/mg/min) in KO tissue, with normal levels (4.82 pmol/mg/min) in wild types and intermediate levels (1.73 pmol/mg/min) in heterozygotes. Preliminary neuropathy experiments showed KO mice are less affected by nerve-crush and recover faster from the damage-induced neuropathy, as indicated by EMG recording and nerve morphology. Similarly, GCPII KO mice subjected to high dose vitamin B6 displayed less severe neuropathy than wild types, as indicated by reduced sensory nerve conduction velocity and morphological deficits. Also, in a transient middle cerebral artery occlusion model, GCPII KO mice were significantly more resistant to the effects of cerebral ischemia than their wildtype littermates. Findings support GCPII involvement in stroke and in mediating chronic neuropathic conditions and suggest GCPII inhibitors may be useful in treatment of brain ischemia as well as peripheral neuropathies. [source] Adolescent C57BL/6J (but not DBA/2J) Mice Consume Greater Amounts of Limited-Access Ethanol Compared to Adults and Display Continued Elevated Ethanol Intake into AdulthoodALCOHOLISM, Issue 4 2010Eileen M. Moore Background:, Alcohol use is common during the adolescent period, a time at which a number of crucial neurobiological, hormonal, and behavioral changes occur (Spear, 2000). In order to more fully understand the complex interaction between alcohol use and these age-typical neurobiological changes, animal models must be utilized. Rodents experience a developmental period similar to that of adolescence. Although rat models have shown striking adolescent-specific differences in sensitivity to ethanol, little work has been done in mice despite the fact that the C57BL/6J (B6) and DBA2/J (D2) mice have been shown to markedly differ in ethanol preference drinking and exhibit widely different sensitivities to ethanol. Methods:, The current study examined ethanol intake in adolescent and adult B6 and D2 mice using a limited access alcohol exposure paradigm called Drinking in the Dark (DID). Additionally, the effect of adolescent (or adult) ethanol exposure on subsequent adult ethanol intake was examined by re-exposing the mice to the same paradigm once the adolescents reached adulthood. We hypothesized that adolescent (P25,45) mice would exhibit greater binge-like alcohol intake compared to adults (P60,80), and that B6 mice would exhibit greater binge-like alcohol intake compared to D2 mice. Moreover, we predicted that relative difference in binge-like alcohol intake between adolescents and adults would be greater in D2 mice. Results:, Adolescent B6 mice consumed more ethanol than adults in the DID model. There was no difference between adolescent and adult D2 mice. Conclusions:, This work adds to the literature suggesting that adolescents will consume more ethanol than adults and that this exposure can result in altered adult intake. However, this effect seems largely dependent upon genotype. Future work will continue to examine age-related differences in ethanol intake, preference, and sensitivity in inbred mouse strains. [source] | |||||||||||||||||||||||||||||||