Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

原癌基因蛋白质C-erbB-2在乳腺良恶性病变中表达的意义

目的:检测原癌基因蛋白质C-erbB-2在乳腺良恶性病变中的表达及意义.方法:对111例乳腺良恶性病变的石蜡切片标本进行免疫组织化学染色.结果:乳腺良恶性病变中乳腺导管内乳头状瘤病的C-erbB-2阳性率为31.3%,与乳腺纤维腺病和纤维腺瘤比较差异有显著性(P<0.01),乳腺癌C-erbB-2的阳性率为74.3%,与良性病变比较差异有显著性(P<0.01);乳腺癌C-erbB-2表达与肿瘤大小和组织学分级呈正比(P<0.05),与激素受体(ER、PR)水平及5年生存期呈反比(P<0.05),与淋巴结是否转移无关.结论:C-erbB-2表达的乳腺导管内乳头状瘤病容易癌变,C-erbB-2过度表达的乳腺癌组织分化差、生存期短、预后不好.C-erbB-2 可作为判定乳腺导管内乳头状瘤病早期癌变及乳腺癌预后的有效指标.     

Hepatitis C associated with Guillain-Barré syndrome

ABSTRACT— Hepatitis C is frequently associated with immune-mediated diseases, such as cryoglobulinemia. Guillain-Barré syndrome is an acute demyelinating neuropathy of probable immune pathogenesis. We describe two patients with Guillain-Barré syndrome, and associated chronic hepatitis C, the second one previously treated with interferon. The link between both conditions may be hepatitis C being the trigger of this immune polyneuropathy. Guillain-Barré syndrome should be added to the list of conditions associated with hepatitis C.     

Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma retinol binding protein.

Using Rbp4-null mice as models, we have established for the first time the kinetics of the spermatogenetic alterations during vitamin A deficiency (VAD). Our data demonstrate that the VAD-induced testicular degeneration arises through the normal maturation of germ cells in a context of spermatogonia differentiation arrest. They indicate that retinoic acid (RA) appears dispensable for the transition of premeiotic to meiotic spermatocytes, meiosis, and spermiogenesis. They confirm that RA plays critical roles in controlling spermatogonia differentiation, spermatid adhesion to Sertoli cells, and spermiation, and suggest that the VAD-induced arrest of spermatogonia differentiation results from simultaneous blocks in RA-dependent events mediated by RA receptor gamma (RARgamma) in spermatogonia and by RARalpha in Sertoli cells. They also provide evidence that expression of major RA-metabolizing enzymes is increased in mouse Sertoli cells upon VAD and that vitamin A-deficient A spermatogonia differ from their RA-sufficient counterparts by the expression of the Stra8 gene.     

Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an anaerobic physical exercise program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 M was seen after a program of anaerobic physical exercise. This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.Abbreviations BCM Body cell mass - HIV Human immunodeficiency virus type 1 - NAC N-Acetyl-cysteine     

Analysis of tetanus toxin peptide/DR recognition by human T cell receptors reconstituted into a murine T cell hybridoma

We have previously reported that human T cell receptors (TcR) selected in the class II-restricted (HLA-DRB1*1302) response to a tetanus toxin peptide (tt830-843) frequently used the Vβ2 germ-line segment which paired with several Vα segments and that the putative CDR3 of both α and β chains showed remarkable heterogeneity. To analyze the structural basis for recognition of the tt830-843/DR complex, five of these TcR were reconstituted into a murine T cell hybridoma, 58 α^?β^?, by expressing the human α and β variable regions joined to the mouse α and β constant regions, respectively. The chimeric TcR, expressing the same Vβ germ-line segment (Vβ2), two expressing Vα21.1, twoVα17.1 and one Vα8.1 were shown to have the expected antigen specificity and DR restriction. Two lines of evidence suggested that the putative CDR3, although not conserved in these TcR, played a key role in recognition. First, two TcR with identical V germ-line segments but distinct CDR3 showed large differences in their capacity to react with the ligand. Second, interchanging the α and β chains from tt830-843/DR1302-specific TcR which differed in their CDR3 sequences invariably led to loss of recognition. We also asked whether germ-line Vα17.1 could functionally replace Vα21.1, as they appear to be related in their primary sequence. However, as in the case of CDR3 exchanges, Vα replacement abrogated TcR reactivity. Taken together, these data underline the fine interdependence of the structural components of the TcR binding site in defining a given specificity. Four of the TcR studied displaying promiscuous recognition were also tested against different DR alleles and site-directed mutants. The results of these experiments suggested that, in spite of their structural heterogeneity, anti-tt830-843 TcR may have a similar orientation with respect to the peptide/DR complex. The reconstitution system described herein should represent a valuable tool for detailed studies of human TcR specificity.     

CD4+ T-cell lymphopenia in Q fever endocarditis.

Valvular endocarditis is the most serious complication of chronic Q fever, an infectious disease due to Coxiella burnetii. Although its pathogenesis is poorly understood, the role of the immune system has been evoked. The aim of this study was to investigate lymphocyte subsets in the peripheral blood of infected patients by analyzing the distribution of T- and B-lymphocyte subsets. Since various infectious diseases have been found to be associated with modified antigen expression, we also measured the antigen density of the main lymphocyte markers by quantitative flow cytometry. The absolute values of CD3+ T cells and CD19+ B cells were lower in infected subjects than in controls. The decrease in the CD4+ T-cell count was more pronounced than that in the CD8+ T-cell count, leading to a significantly lower CD4/CD8 ratio in patients. The decreases in CD4+ T cells and CD19+ B cells were correlated with levels of C. burnetii-specific immunoglobulin G, showing that CD4+ lymphopenia is related to the activity of chronic Q fever. Quantitation of antigen expression on lymphocytes showed that CD3, CD4, CD8, and CD19 were expressed similarly in patients and controls. In contrast, CD2 and CD11a expression levels, which are both related to naive and memory phenotypes, were modified in patients. The study of CD45RO and CD45RA expression by CD4+ T cells provided evidence that lymphopenia preferentially affected unprimed lymphocytes.     

Human Annexin Ⅴ在不同胎盘中的表达的定量分析

目的观察人膜联蛋白Ⅴ(Human Annexin Ⅴ,HAⅤ)在乙肝病毒感染胎盘、正常中、晚孕胎盘及早孕绒毛中的表达并探讨其意义.方法用SP法检测HBsAg阳性孕妇足月分娩胎盘、HBV血清标志物阴性的正常早孕、中孕和足月胎盘各20例HAⅤ的表达、分布并进行定量分析.结果中孕、足月胎盘和HBV感染的胎盘组织中HAⅤ呈不均一的棕黄色颗粒状染色,泛存在于胎盘组织各类细胞胞浆、胞膜和核膜上.滋养细胞呈强阳性染色,绒毛间质细胞和毛细血管内皮细胞呈弱阳性染色.早孕绒毛HAⅤ棕黄色颗粒主要分布于外层滋养细胞的胞浆、胞膜和核膜上,最内层滋养细胞和间质偶见表达;比较HBV感染组和正常足月组胎盘HAⅤ表达的量,前者的平均灰度比后者明显增高,差异具有显著性(P＜0.01),中孕组与足月组HAⅤ表达的量没有差别(P＞0.05),早孕和中孕组、足月组HAⅤ表达的量的比较,前者显著低于后两者(P＜0.05).结论HAⅤ可能作为受体介导了HBV对胎盘的感染.     

Affective temperaments in clinically-well subjects in Turkey: initial psychometric data on the TEMPS-A

BACKGROUND: This is a first attempt to evaluate the reliability and factor structure replicability of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) in its Turkish Version. The questionnaire is a self-report 110-item measure that postulates five affective temperaments-the depressive, cyclothymic, irritable, hyperthymic, and anxious-which embody both strengths and liabilities along affective lines. METHODS: The questionnaire was administered to 658 clinically-well subjects in a Turkish university circle. We undertook item analysis and test-retest reliability. We then examined internal consistency through factor analysis with PCA rotation. RESULTS: We found good to excellent test-retest reliability (0.73-0.91), and internal consistency (0.77-0.85). We deleted 10 items with factor loading <0.20 for their own subscales, resulting in a questionnaire with 99 items. Despite considerable overlap between depressive and cognitive anxiety traits, a distinct "nervous"-anxious factor emerged as well, and the hypothesized (original English) 5-factor structure of the TEMPS-A was supported. Cut-offs for each temperament were based on z-scores higher than +2S.D. Dominant irritable (3.7%), nervous-anxious (3.7%) and depressive (3.1%) temperaments were the most common in this population, whereas dominant cyclothymic (1.7%) and hyperthymic (1.2%) temperaments were relatively uncommon. These temperaments tended to lose their intensity with age. As expected, women scored significantly higher on the nervous-anxious, and men on the hyperthymic temperaments. LIMITATIONS: The sample was composed of younger subjects with higher education than the general population of Turkey. Although the distribution of the scores for each of the temperaments deviated somewhat from normal curves, for heuristic reasons we did attempt to provide prevalence rates based on z-scores. CONCLUSION: In this preliminary version of the TEMPS-A, we have retained 100 (of the original 110) traits loading >0.20. Some deleted items referred to sleep, others appeared socially desirability traits in the Turkish culture endorsed by many subjects. Nonetheless, item analyses within each factor revealed traits indicative of personal assets (specific to each temperament) along with those which might represent vulnerability to affective illness. This is in line with the hypothesized original theoretical framework of the senior authors. Even in this "first pass," in its Turkish version the TEMPS-A is a reliable and valid instrument. Further refinement of the instrument will require the study of a nationally representative sample in Turkey.