The −22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer’s disease in Poland

Summary. The –22c/t polymorphism in the promoter of the presenilin 1 gene is associated with increased risk for Alzheimerrc="/content/t4jrt50ymupwrc0r/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">s disease (AD) in some populations. It was shown that –22c allele is connected with two-fold decrease in promoter activity. We studied the impact of the polymorphism in groups of Polish late-onset and early-onset AD patients. Our results suggest that –22c/t polymorphism is not connected with AD in Polish population. The –22t allele showed a high degree of linkage disequilibrium with –2797 insertion of 13rc="/content/t4jrt50ymupwrc0r/xxlarge8201.gif" alt="thinsp" align="MIDDLE" BORDER="0">bp. An additional –2923g/t polymorphism is also not connected with –22c/t and is not a risk factor for AD.     

Stroke causes a transient imbalance of interhemispheric information flow in EEG during non-REM sleep

Objective

Large-scale connectivity, especially interhemispheric connections, plays a crucial role for recovery after stroke. Here we used methods from information theory to characterize interhemispheric information flow in wake- and sleep-EEG after cerebral ischemia.

Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis

BACKGROUND & AIMS: We tested whether the attenuation of experimental colitis by live probiotic bacteria is due to their immunostimulatory DNA, whether toll-like receptor (TLR) signaling is required, and whether nonviable probiotics are effective. METHODS: Methylated and unmethylated genomic DNA isolated from probiotics (VSL-3), DNAse-treated probiotics and Escherichia coli (DH5 alpha) genomic DNA were administered intragastrically (i.g.) or subcutaneously (s.c.) to mice prior to the induction of colitis. Viable or gamma-irradiated probiotics were administered i.g. to wild-type mice and mice deficient in different TLR or in the adaptor protein MyD88, 10 days prior to administration of dextran sodium sulfate (DSS) to their drinking water and for 7 days thereafter. RESULTS: Intragastric and s.c. administration of probiotic and E. coli DNA ameliorated the severity of DSS-induced colitis, whereas methylated probiotic DNA, calf thymus DNA, and DNase-treated probiotics had no effect. The colitis severity was attenuated to the same extent by i.g. delivery of nonviable gamma-irradiated or viable probiotics. Mice deficient in MyD88 did not respond to gamma-irradiated probiotics. The severity of DSS-induced colitis in TLR2 and TLR4 deficient mice was significantly decreased by i.g. administration of gamma-irradiated probiotics, whereas, in TLR9-deficient mice, gamma-irradiated probiotics had no effect. CONCLUSIONS: The protective effects of probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon. TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because nonviable probiotics are equally effective.     

Molecular localization of human IgG anti-F(ab′)2 reactivity with variable- and constant-region λ light-chain epitopes

Human IgG antibodies reacting with antigenic determinants on F(abrc="/content/lmvu5683039277r6/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">)₂ fragments represent generic antiidiotypic antibodies present in the serum of normal individuals. Additionally, the titers of these antibodies in the sera of patients with systemic lupus erythematosus (SLE) are inversely related to disease activity. Because these autoantibodies recognize predominantly light chain-related epitopes, especially rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0"> type, we synthesized constant (C)_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">}- and variable (V)_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">}-related overlapping 7-mer peptides on polypropylene pins to determine anti-F(abrc="/content/lmvu5683039277r6/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">)₂-reactive epitopes on humanrc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0"> light chains. ELISA reactivity of affinity-purified anti-F(abrc="/content/lmvu5683039277r6/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">)₂ antibodies obtained from normal individuals and from patients with SLE, as well as murine anti-human light-chain monoclonal antibodies specific for C_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">} and V_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">} subgroup-related determinants, was tested using the overlapping 7-mers of humanrc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0"> light-chain sequence. The patterns of reactivity against C_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">}-related peptides were similar in both normal and SLE-derived anti-F(abrc="/content/lmvu5683039277r6/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">)₂ antibodies. However, reactivity profiles against V_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">}-related peptides were distinctively different between the normal and the SLE-associated anti-F(abrc="/content/lmvu5683039277r6/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">)₂ autoantibodies. A decrease in reactivity among the SLE IgG anti-F(abrc="/content/lmvu5683039277r6/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">)₂ antibodies was noted for particular amino acid V_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">} complementarity-determining region (CDR) residues, including glycine at positions 27 and 54, alanine at 16 and 37, and tyrosine at 28 and 91. This different pattern of reactivity from normal may indicate that in SLE there is a failure of antiidiotypic control mechanisms, as reflected by a defect in production of antibody to immunodominant V_{rc="/content/lmvu5683039277r6/xxlarge955.gif" alt="lambda" align="BASELINE" BORDER="0">} CDR residues.     

Serum contains a potent factor that decreases β-adrenergic receptor-stimulated L-type Ca2+ current in cardiac myocytes

L-type Ca²⁺ current (I _Ca) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I _Ca induced by rc="/content/k5r60324572t2275/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenergic stimulation (isoprenaline 2· 10^–7 M) could be completely antagonized by diluted sera (1rc="/content/k5r60324572t2275/xxlarge8758.gif" alt="ratio" align="BASELINE" BORDER="0">100 v/v). Half-maximal inhibition of rc="/content/k5r60324572t2275/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-receptorstimulated I _Ca occurred at about 1rc="/content/k5r60324572t2275/xxlarge8758.gif" alt="ratio" align="BASELINE" BORDER="0">1000. Basal I _Ca was not affected by serum. Atropine in a concentration (10^–6M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2·10^–6 M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10^–4 M) pipette solution, potentiated I _Ca was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits rc="/content/k5r60324572t2275/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-receptor-stimulated adenylyl cyclase via G_iprotein.A preliminary report of this work has appeared in abstract form [11]     

Isoenzymes of γ-glutamyl transpeptidase in liver diseases

Summary A new method for the separation of isoenzymes ofrc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-glutamyl-transpeptidase is described, using electrophoresis on acetate cellulose gel and a developing solution composed byrc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-glutamylrc="/content/q6471173jl0r5j00/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-naphthylamide, and a colored diazonium compound.The method permits the separation of up to four different isoenzymes, which we calledrc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-GT₁,rc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-GT₂,rc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-GT₃,rc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-GT₄, the first two showing an electrophoretic migration similar to that ofrc="/content/q6471173jl0r5j00/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"> ₁- andrc="/content/q6471173jl0r5j00/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"> ₂-globulins and the other two to that ofrc="/content/q6471173jl0r5j00/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-globulins.The present technique has proved its usefulness in detecting isoenzymes in serum with values of totalrc="/content/q6471173jl0r5j00/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-glutamyl-transpeptidase higher than 80 U/L.The application of this method in 52 patients with different types of biliary obstruction and hepatocellular damage has shown that it provides new possibilities in differential diagnosis.     

Acid maltase deficiency in non-identical adult twins

Summary Acid maltase deficiency is described in non-identical adult twins. The onset of the disease can be traced into late infancy; the clinical picture is one of severe muscular dystrophy; respiratory insuficiency was the cause of death in one case. The autopsy showed the central nervous system, heart and liver to be spared. Glycogen filled vacuoles are found in skin, mesenchymal cells, small nerves and skeletal muscles. The light microscopic study of 9 different muscles showed extremely variable involvement ranging from normal appearance to overt vacuolization. A 6–20% residual acid rc="/content/k5004455r269313n/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-glucosidase activity was found in visceral organs, cultured fibroblasts and in some skeletal muscles. No satisfactory explanation can be given why this generalized acid rc="/content/k5004455r269313n/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-glucosidase deficiency produces a selective involvement of skeletal muscles. If compared with infantile AMD (Pompe's disease) our cases have a much higher residual acid rc="/content/k5004455r269313n/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-glucosidase activity and show the presence of an antigenically detectable protein.From our study and from a similar report in the literature (de Barsy et al., 1975), it appears that a combined approach of light microscopy, electron microscopy and biochemical analysis (determination of acid rc="/content/k5004455r269313n/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-glucosidase) is necessary to make a diagnosis of AMD in adults.Dr. Th. de Barsy is a Research Fellow of the rc="/content/k5004455r269313n/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Fonds National de la Recherche Scientifiquerc="/content/k5004455r269313n/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">.     

蜂胶毛胶中总黄酮、高良姜素和白杨素含量分析

目的：建立蜂胶毛胶中总黄酮以及高良姜素、白杨素含量测定方法,测定不同基原毛胶中上述各指标的含量。方法：以芦丁为对照品,采用uV法测定总黄酮含量,检测波长为415nm;用HPLC同时测定高良姜素、白杨素含量,采用Welchrom C18柱,以甲醇-0．15％磷酸溶液梯度洗脱,检测波长为268nm。结果：总黄酮在0～1．248mg线性关系良好,r=0．9999（n=6）,平均回收率为98．82％,RSD=1．45％。高良姜素、白杨素分别在0．089～0．4450,0．115～0．580μg线性关系良好,r均达到1．000,平均回收率分别为99．03％、99．32％,RSD分别为1．10％、1．72％。结论：该方法准确、可靠、简便易行,可用于蜂胶毛胶的定量分析,为蜂胶毛胶、其提取物以及蜂胶制品的质量评价和控制提供了依据。