Automatic assessment of levodopa-induced dyskinesias in daily life by neural networks.

We developed an objective and automatic procedure to assess the severity of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease during daily life activities. Thirteen patients were continuously monitored in a home-like situation for a period of approximately 2.5 hours. During this time period, the patients performed approximately 35 functional daily life activities. Behavior of the patients was measured using triaxial accelerometers, which were placed at six different positions on the body. A neural network was trained to assess the severity of LID using various variables of the accelerometer signals. Neural network scores were compared with the assessment by physicians, who evaluated the continuously videotaped behavior of the patients off-line. The neural network correctly classified dyskinesia or the absence of dyskinesia in 15-minute intervals in 93.7, 99.7, and 97.0% for the arm, trunk, and leg, respectively. In the few cases of misclassification, the rating by the neural network was in the class next to that indicated by the physicians using the AIMS score (scale 0-4). Analysis of the neural networks revealed several new variables, which are relevant for assessing the severity of LID. The results indicate that the neural network can accurately assess the severity of LID and could distinguish LID from voluntary movements in daily life situations.     

乳酸脱氢酶实验检测细胞新陈代谢的实验研究

目的 探索LDH实验检测细胞活力的可行性。方法 原代培养骨髓细胞和软骨细胞，用LDH实验测定上述两组细胞的活力，并与镜下活体观察到细胞的生长状况相比较。与目前比较成熟的测定细胞活力的MTS实验的测得的值相比较。结果 LDH实验对上述两组细胞的活力的测定结果与镜下活体观察到的结果相符合。与MTS实验的测得的结果经统计学处理无显著差异。结论 LDH实验可用于细胞活力的直接测定，而对活细胞的生存、繁殖无影响。     

Can a part of an inducer become incorporated into interferon?

Highly purified and concentrated interferons obtained from L cells or from mouse peritoneal leukocytes (MPL) after induction with³H-uridin labeled double-stranded RNA of f₂ phageE. coli (phage ds-RNA) were analysed by poly-acrylamide gel electrophoresis. A coincidence of the discrete radioactivity peak with one of the interferon activity peaks was demonstrated.     

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

BAG1 over-expression in brain protects against stroke

The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over-expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild-type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases.     

HIV testing within at-risk populations in the United States and the reasons for seeking or avoiding HIV testing

OBJECTIVES: We determined proportions of high-risk persons tested for HIV, the reasons for testing and not testing, and attitudes and perceptions regarding HIV testing, information that is critical for planning prevention programs. METHODS: Cross-sectional interview study of persons at high risk for HIV infection (men who have sex with men [MSM]; injection drug users [IDUs]; and heterosexual persons recruited from gay bars, street outreach, and sexually transmitted disease clinics) among six states participating in the HIV Testing Survey (HITS) in 1995 to 1996 (HITS-I) and 1998 to 1999 (HITS-II). RESULTS: Overall testing rates were lower in the HITS-I (1226/1599 [77%]) than in the HITS-II (1375/1711 [80%]) (p =.01). Persons <25 years old tested less frequently than those >or=25 years old (HITS-I: 71% vs. 78%, respectively, p=.007; HITS-II: 63% vs. 85%, respectively, p<.001). The main reasons for testing and not testing were the same in both surveys, but the proportions of reasons for not testing differed (e.g., "unlikely exposed to HIV" [HITS-I (17%) vs. HITS-II (30%), p<.0001], "afraid of finding out HIV-positive" [HITS-I (27%) vs. HITS-II (18%), p<.0001]). Attitudes regarding HIV testing differed among tested and untested respondents, especially among MSM. CONCLUSIONS: HIV testing rates were higher in the HITS-II, but testing rates decreased among the youngest respondents. Denial of HIV risk factors and fear of being HIV-positive were the principal reasons for not being tested. Availability of new HIV therapies may have contributed to decreased fear of finding out that one is HIV infected as a reason to avoid testing. The increased proportion of persons at risk who did not test because they believed they were unlikely to have been exposed highlights the need for prevention efforts to address risk perceptions.