PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes.

Scintigraphic imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) has demonstrated extensive losses of cardiac sympathetic neurons in idiopathic Parkinson's disease (IPD). In contrast, normal cardiac innervation has been observed in (123)I-MIBG studies of multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP). Consequently, it has been hypothesized that cardiac denervation can be used to differentiate IPD from MSA and PSP. We sought to test this hypothesis by mapping the distribution of cardiac sympathetic neurons in patients with IPD, MSA, and PSP by using PET and (11)C-meta-hydroxyephedrine ((11)C-HED). Also, the relationship between cardiac denervation and nigrostriatal denervation was investigated by measuring striatal presynaptic monoaminergic nerve density with PET and (11)C-dihydrotetrabenazine ((11)C-DTBZ). METHODS: (11)C-HED and (11)C-DTBZ scans were obtained for patients with IPD (n = 9), MSA (n = 10), and PSP (n = 8) and for age-matched control subjects (n = 10). Global and regional measurements of (11)C-HED retention were obtained to assess the extent of cardiac sympathetic denervation. (11)C-DTBZ binding was measured in the caudate nucleus, anterior putamen, and posterior putamen. RESULTS: As expected, extensive cardiac denervation was observed in several of the patients with IPD. However, substantial cardiac denervation was also seen in some patients with MSA and PSP. (11)C-DTBZ studies demonstrated striatal denervation in all patients with IPD and in most patients with MSA and PSP. No correlation was found between cardiac (11)C-HED retention and striatal (11)C-DTBZ binding. CONCLUSION: Cardiac sympathetic denervation was found to occur not only in IPD but also in other movement disorders, such as MSA and PSP. This finding implies that scintigraphic detection of cardiac sympathetic denervation cannot be used independently to discriminate IPD from other movement disorders, such as MSA and PSP. Cardiac sympathetic denervation was not correlated with striatal denervation, suggesting that the pathophysiologic processes underlying cardiac denervation and striatal denervation occur independently in patients with parkinsonian syndromes. These findings provide novel information about central and peripheral denervation in patients with neurodegenerative disorders.     

Identification of three FcR-positive T cell subsets (T gamma, T mu and T gamma mu) in the cerebrospinal fluid of multiple sclerosis patients

Proportions of T cells and T cell subsets, as identified by their Fc receptors (FcR) for IgM and IgG (Tmu and T gamma), were determined in the peripheral blood lymphocyte (PBL) and cerebrospinal fluid (CSF) lymphocyte populations in patients with multiple sclerosis (MS). On average, MS patients had 79% total T cells (62% of which were T gamma, 66% Tmu) in CSF lymphocytes compared to 66% total T cells (30% T gamma, 63% Tmu) in PBL. Normal age- and sex-matched controls PBL had 74% total T cells (20% T gamma, 54% Tmu). By direct observation using an indirect immunofluorescence assay, 41% of the CSF T gamma cells in MS patients bore receptors for IgM; these cells were designated T gamma mu and, according to the double-marker analysis, did not seem to correlate with disease stage. In MS PBL, 20% of T gamma cells were T gamma mu compared to 9% in the control PBL T gamma population. Thus, MS patients had a higher proportion of total T cells, T gamma cells and T gamma mu cells in their CSF than in their peripheral blood and than those populations found in normal control blood. The significance of this T gamma mu population for the continuing disease state in MS is discussed.     

Myoblasts fail to stimulate T cells but induce tolerance

Recent interest in myoblast transfer and in the use of myoblastsas vehicles in gene therapy has made it important to understandthe potential immunogenicity of allogeneic or neoantlgen-expresslngmyoblasts. Given the problems of producing a pure populationof myoblasts, In this study we used a tumour-derived musclecell line (TE671), with phenotyplc features of myoblasts, whichwe transfected to express HLA-DR1. However, this cell line wasunable to stimulate either established HLA-DR1-specific alloreactlveT cell clones or a primary alloresponse. Nor could it presenthaemagglutlnln peptide HA 306–324 to DR1-restricted, HA306–324-speciflc T cell clones or lines. Indeed, prelncubatlonwith DR1-expressing TE671 and HA 306–324 rendered suchT cells tolerant as Judged by their subsequent inability toproliferate in response to a DR1⁺ B cell line plus peptide HA306–324. These results imply that myoblasts do not providecostlmulatory signals, and are therefore unlikely to stimulateallospeclfic T cells following myoblasts transplantation orto initiate neoantlgen-speclfic immune responses following Invivo transfection.     

Construction of microcell hybrid panel containing differentNeo gene insertions in mouse chromosome 17 used for chromosome-mediated gene transfer

A panel of four microcell hybrids representing different sites of insertion of the exogeneous neogene into mouse chromosome 17 has been constructed. These constructions were based on a cotransfer of mouse chromosome 17 and neomycin resistance generated in a stepwise procedure involving (1) random insertion of the neogene into a primary cell hybrid containing mouse chromosome 17 in a hamster cell background, (2) microcell-mediated chromosome transfer (MMCT) to segregate mouse and hamster chromosomes, and (3) identification of the mouse chromosome containing cells using a novel cell dotting procedure for mass screening at the cell colony level by molecular hybridization. Using this panel of four microcell hybrids for chromosome mediated gene transfer (CMGT), we obtained one transformant containing a chromosome fragment derived from the t-complex region located on mouse chromosome 17. It is concluded that the specific chromosome based procedure used here to generate CMGT transfectants may provide a general means to produce large numbers of transfectants containing megabase fragments covering, in principle, all regions of a given chromosome.     

Deletion of RBM and DAZ in azoospermia: Evaluation by PRINS

Molecular and cytogenetic studies from infertile men have shown that one or more genes controlling spermatogenesis are located in proximal Yq11.2 in interval 6 of the Y chromosome. Microdeletions within the azoospermia factor region (AZF) are often associated with azoospermia and severe oligospermia in men with idiopathic infertility. We evaluated cells from a normal‐appearing 27‐year‐old man with infertility and initial karyotype of 45,der(X)t(X;Y)(p22.3;p11.2)[8]/46,t(X;Y)(p22.3;p11.2)[12]. By fluorescence in situ hybridization with dual‐color whole chromosome paint probes for X and Y chromosomes, we confirmed the Xp‐Yp interchange. By primed in situ labeling, we identified translocation of the SRY gene from its original location on Yp to the patient's X chromosome at band Xp22. We also obtained evidence that the apparent marker was a der(Y) (possibly a ring) containing X and Y domains, and observed that the patient's genome was deleted for RBM and DAZ, two candidate genes for AZF. © 2001 Wiley‐Liss, Inc.     

Discrepancies between self-reported years of education and estimated reading level among elderly community-dwelling African-Americans: Analysis of the MOAANS data.

The influence of education on cognition has received a great deal of attention in the literature. Although there is general consensus regarding the importance of education on cognitive functioning, the extent to which self-reported level of education corresponds to true educational attainment remains unclear, especially in ethnic minority populations where equal access to education has not always been available. Several investigators have suggested that reading skill may serve as a quantitative estimate of true education experience. Among African-Americans, however, research has shown that self-reported educational level consistently over predicts estimated reading level. The current study analyzed the discrepancy between self-reported years of education completed and estimated reading level in a sample of community-dwelling, elderly African-Americans participating in Mayo's Older African Americans Normative Studies (MOAANS) (Lucas, J.A., Ivnik, R.J., Willis, F.B., Ferman, T.J., Smith, G.E., Parfitt, F.C., Petersen, R.C., & Graff-Radford, N.R. (2005). Mayo's Older African Americans Normative Studies: Normative data for commonly used clinical neuropsychological measures. The Clinical Neuropsychologist, 19, 162-183). In this sample, 29% of the participants read at a level that was 3 or more years below what would be expected based on self-report of education attained. This study also sought to evaluate the extent to which this discrepancy fluctuated as a function of demographic variables such as location of schooling (urban, suburban, rural; North vs. South), parental education and literacy, and percentage of segregation in schooling. Implications of these results are discussed, as are areas for further inquiry.     

The combined effect of psychotherapy and fluoxetine on obesity]

Obesity as psychosomatic disease is a mass phenomenon. The number of obese males (BMI > 30) became doubled in the last ten years. In the etiology of obesity play an important role the reactive obesity. In the background of "yo-yo syndrome" often could be found depression, or other psychotic disorder. The low self-esteem, body dissatisfaction, tension, anxiety disorders is well-known in a slimming diet. Obese subjects (n = 29) who were admitted on their request with a view to losing weight were examined (Hamilton Depressive Scala, Hamilton Anxietas Scala, Eating Attitude Test) Physical Conditioning and internal Medicine Department of National Sports Medicine Institute, Budapest. Among obesities with mild and severe depression as treatment of somatic complications was used fluoxetine, in severe cases and depression with severe anxiety was associated with supportive or cognitive-behavioral treatment. The prevalence of binge eating disorders were at 57% and bulimia nervosa was at 3% in using population (n = 29). Decreasing of anxiety and grade of depression significantly correlated with body mass index (p < 0.023, F = 1.997, p < 0.034, F = 3.131). The treatment of fluoxetine significantly correlated with body mass index (T1: p < 0.023, T2: p < 0.03, T3: p < 0.004). The patients indicated their well being as fluoxetine reduced eating, satiety and lower binges.     

多途径丝裂原激活的蛋白激酶介导一氧化氮引起的肝癌细胞凋亡

目的研究非离子型的diazeniumdiolate类一氧化氮供体引起肝癌细胞凋亡的分子机制.方法利用免疫印迹、免疫沉淀、凝胶阻滞实验研究一氧化氮供体处理Hep3B肝癌细胞后,丝裂原激活的蛋白激酶、AP-1的激活以及和Hep3B肝癌细胞凋亡的关系.结果一氧化氮可引起细胞外信号调节蛋白激酶、c-jun N末端激酶和p38激酶的激活,特别是细胞外信号调节的蛋白激酶的持续激活,其中细胞外信号调节的蛋白激酶和c-jun N末端激酶的特异的阻断剂U0126和JNK抑制剂Ⅱ可阻断AP-1的激活和Hep3B细胞的凋亡,而p38激酶的阻断剂SB203580不能阻断AP-1的激活和Hep3B肝癌细胞的凋亡.结论一氧化氮通过激活细胞外信号调节蛋白激酶、c-jun N末端激酶,进而激活AP-1而引起Hep3B肝癌细胞的凋亡.