Does smoking protect from Alzheimer's disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history

The objective of this report is to investigate whether smoking exerts any influence on the number of senile plaques and Alzheimer neurofibrillary tangles. A retrospective study was based on unselected consecutive autopsy findings on the brains of 301 patients aged 65 years or older examined at the Institute of Pathology, Basel. Brains were investigated according to a fixed protocol. Histological examination was performed on 15 paraffin-embedded tissue blocks per brain using staining with silver impregnation specific for Alzheimer neurofibrillary tangles and for senile plaques, and Alzheimer-type changes were quantified. Retrospective assessment of smoking history was also based on a fixed protocol. Statistical analysis of the relationship between the smoking habits and the amount of Alzheimer-type changes was performed and included analysis of 72 age- and sex-matched smoker-nonsmoker pairs from within the total of 301 cases to compensate for variations in these changes due to age/sex alone. The influence of smoking on the total of 301 cases cannot be proven statistically. But a protective action against senile plaque formation could be demonstrated in 28 age matched pairs of smoking-nonsmoking women. Furthermore a positive correlation between the amount of smoking and the neurofibrillary changes as expressed in Braak stages in smokers of both sexes was present. Thus, there seems to be an influence of nicotine on the structural alterations of Alzheimer's disease which can exert itself in opposite directions.     

Small‐Molecule Inhibitors of AF6 PDZ‐Mediated Protein–Protein Interactions

PDZ (PSD‐95, Dlg, ZO‐1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ‐mediated protein–protein interactions has important implications in disease‐related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1‐fused gene from chromosome 6), which is an essential component of cell–cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile‐Gln‐Ser‐Val‐Glu‐Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6–Bcr interaction and interfere with epidermal growth factor (EGF)‐dependent signaling.     

Toxicity characterization of complex mixtures using biological and chemical analysis in preparation for assessment of mixture similarity

In the United States, several proposed approaches for using bioassays for the risk assessment of complex hazardous mixtures require that selected mixtures be "sufficiently similar" to each other. The goal of this research was to evaluate the utility of a protocol using in vitro bioassays and chemical analysis as a basis for assessing mixture similarity. Two wood preserving wastes (WPWs) containing polycyclic aromatic hydrocarbons and pentachlorophenol were extracted and fractionated to generate potentially similar mixtures. Chemical analysis was conducted using gas chromatography/mass spectrometry. Genotoxicity was evaluated using the Salmonella/microsome and Escherichia coli prophage induction assays. The crude extract of one WPW was also tested in the chick embryotoxicity screening test (CHEST) assay. The CHEST assay provided the most sensitive measurement of toxicity. Overall, the biological potency of the samples was not well correlated with predicted potency based on chemical analysis. Although several mixtures appeared similar based on chemical analysis, the magnitude of the response in bioassays was often dissimilar. Fractionation was required to detect the genotoxicity of mixture components in vitro. The results confirm the need for an integrated protocol, combining chemical analysis, fractionation, and biological testing to characterize the risk associated with complex mixtures.     

Hypertrophic cardiomyopathy: spontaneous course

Hypertrophic cardiomyopathy is a relatively rare (prevalence approximately 0.2%), primary myocardial disorder with an autosomal pattern of inheritance, characterized by mostly asymmetric left ventricular hypertrophy with myocyte and myofibrillar disarray. To date, about 34 mutations of the beta-cardiac myosin heavy chain gene have been described and shown to have prognostic implications. The disease has an annual mortality rate of 3%, related to both sudden cardiac death and progressive systolic dysfunction. Not only diastolic but also progressive systolic dysfunction with cavity dilatation occurs in a minority of patients with severe hypertrophy during the long-term course. Sudden death often occurs in young, asymptomatic or mildly symptomatic patients. The degree of hypertrophy and the presence of a pressure gradient are of little prognostic significance. Nonsustained ventricular tachycardia is associated with a poor prognosis in the presence of a history of syncope.     

Rosalind Picard: Affective Computing

User Modeling and User-Adapted Interaction -     

An Efficient Algebraic Algorithm for the Geometric Completion to Involution

 We describe an adaption of a differential algebraic completion algorithm for linear systems of partial differential equations that allows us to deduce intrinsic differential geometric information like the number of prolongations and projections needed for the completion. This new hybrid algorithm represents a much more efficient realisation of the classical Cartan–Kuranishi completion than previous purely geometric ones. A classical problem in geometric completion theory is the existence of δ-singular coordinate systems in which the algorithms do not terminate. We develop a new and a very simple criterion for δ-singularity based on a comparison of the Janet and the Pommaret division. This criterion can also be used for the direct construction of δ-regular coordinates. Received: July 28, 2000; revised version: October 16, 2001     

Tilidine does not affect human sphincter of Oddi motility--a randomized, controlled study

AIM: To investigate the effects of intravenous pentazocine and tilidine on sphincter of Oddi motility. METHODS: Twenty patients with suspected sphincter of Oddi dysfunction were enrolled in a prospective, double-blind study. Sphincter of Oddi motility was assessed by means of endoscopic manometry after injection of 0.9% saline, as well as after randomized dosing with either 30 mg pentazocine i.v. (n = 10) or 50 mg tilidine i.v. (n = 10). RESULTS: Pentazocine significantly increased the sphincter of Oddi baseline pressure from 32 +/- 21 mmHg (saline) to 41 +/- 19 mmHg (P = 0.002), whereas tilidine did not alter the sphincter baseline pressure (34 +/- 15 mmHg saline vs. 36 +/- 16 mmHg tilidine, P = 0.16). Furthermore, pentazocine increased the phasic sphincter contraction amplitude (108 +/- 16 mmHg saline vs. 121 +/- 18 mmHg pentazocine, P = 0.004), but tilidine was without any effect (125 +/- 24 mmHg saline vs. 125 +/- 21 mmHg tilidine, P = 0.93). The phasic sphincter of Oddi contraction frequency and duration were not influenced either by pentazocine or by tilidine. CONCLUSION: In contrast to 30 mg of pentazocine, 50 mg of tilidine does not affect sphincter of Oddi motility. Therefore, tilidine can be used during endoscopic manometry and for analgesia in pancreatobiliary disease.     

Troponin-T: improved diagnostic assessment of myocardial damage in childhood

Troponin-T (cTnT) as a marker of myocardial damage is well established in adults, but not yet in children. cTnT was measured in 85 children (aged 1 day-204 months, mean 46 months). Twenty-five children were non-surgical patients, with possible myocardial damage suspected on clinical grounds. The other 60 patients had cardiac surgery leading to a defined myocardial damage. In these children, troponin-T (cTnT), creatine kinase activity (CK), creatine kinase-MB activity (CK-MB), and creatine kinase-MB-Mass (CK-MB-Mass) were measured preoperatively and 3-4 times during the first 55 postoperative h. Except in four children with probable preoperative myocardial damage, all troponin-T values were in the normal range (< 0.1 microg/l). All children with intracardiac surgery showed a postoperative increase in troponin-T. Children with extracardiac surgery of the great vessels showed no postoperative increase of troponin-T. For the assessment of myocardial damage, troponin-T was more specific and more sensitive than the other markers tested, troponin-T might significantly improve the diagnostic assessment of myocardial damage in children.