Regional Specificity in Alterations of Rat Brain Copper and Catecholamines Following Perinatal Copper Deficiency

Abstract: Perinatal copper deficiency was studied in 1-month-old female and male Sprague-Dawley rat offspring to investigate regional changes in brain copper and catecholamine levels. Offspring of dams given the low copper treatment beginning at day 7 of gestation exhibited signs characteristic of deficiency such as impaired growth and 10-fold lower liver copper levels compared with copper-adequate controls. Regional analysis of brain copper by graphite furnace atomic absorption spectroscopy revealed uniform and severe reduction of copper to levels 20 ± 3% of controls in all regions, except the hypothalamus, where reductions to 56 and 28% of those in copper-adequate females and males, respectively, were measured. HPLC analysis revealed significant reductions in norepinephrine levels in cerebrum, midbrain, corpus striatum, cerebellum, and medulla-pons of copper-deficient offspring ranging between 39 and 67% of control values. There were no significant differences in norepinephrine concentration in the hypothalamus. There was a significant, one-third reduction of dopamine in the corpus striatum of copper-deficient male rats. Consistent with altered in vivo dopamine β-monooxygenase activity, there were five-, three-, and twofold elevations of dopamine in cerebellum, medulla-pons, and hypothalamus of copper-deficient rats. Spectrophotometric measurement of in vitro dopamine β-monooxygenase activity of brain and adrenal homogenates was higher in copper-deficient rats, confirming prior work. An explanation for the in vitro data is unclear. Changes in copper and catecholamine levels were influenced by diet and were regionally selective, especially in the hypothalamus.     

Comparison of prevalence of schizophrenia among residents of hostels for homeless people in 1966 and 1992.

OBJECTIVE--To determine whether the prevalence of schizophrenia among the homeless population of Edinburgh resident in hostels has changed between 1966 and 1992. DESIGN--Comparison of two cross sectional surveys. SETTINGS--Hostels for homeless people in Edinburgh. SUBJECTS--In 1966 a random sample of 98 residents of three common lodging houses. In 1992 a random sample of 198 residents of nine hostels. MAIN OUTCOME MEASURE--Prevalence of schizophrenia. RESULTS--The prevalence of schizophrenia in 1992 was 12/136 (9%) compared with 20/79 (25%) in 1966 (odds ratio 0.29; 95% confidence interval 0.13 to 0.62; P = 0.001). Adjustment for confounding by age, current hostel, and duration of unemployment by means of logistic regression produced an adjusted odds ratio of 0.22 (0.08 to 0.58). CONCLUSIONS--The prevalence of schizophrenia was lower in 1992 even after other changes in the population resident in hostels occurring between 1966 and 1992 were taken into account. The findings are not consistent with an increase in the prevalence of schizophrenia among homeless people despite a 66% reduction in adult psychiatric beds in the region during 1966-92.     

Monoclonal antibodies and idiotypic network activation for ovarian carcinoma

Antibodies can be processed by the B- and T-cell systems and may lead to a selective activation of the immune system. The network structure of the immune system implicates the possibility of a selective immunization by the activation of idiotypic cascades. In a retrospective analysis, patients with advanced ovarian carcinoma, who had received MAb, against the cancer-associated antigen CA125 for diagnostic purposes, were analyzed for the production of anti-idiotypic antibodies, survival rate, and immunological effects. Furthermore, we started a prospective and randomized study for ovarian cancer patients, using a different antigen, TAG72, for the induction of idiotypic cascades. Our first results on 58 patients with advanced ovarian carcinomas showed that the induction of anti-idiotypic-antibodies against OC125 mimicking the TAA Class III CA125 leads to a prolongation of the survival rate, and, in extended stages, to an induction of antitumoral immunity, and that the induction of idiotypic cascades is also possible for different antigens like TAG72. Summarizing the activation of idio-typic network cascades seems to be a very effective way of intervention in the immune system of patients with advanced stages of ovarian carcinoma. A prospective study of the adjuvant approach seems to be necessary.     

Phylogenetic analysis of a bacterial aerobic degrader of azo dyes.

Eubacterial consensus oligonucleotide primers were used to amplify by polymerase chain reaction the nearly full-length 16S rRNA gene of isolate C7, a gram-negative rod capable of aerobic degradation of azo dyes. The DNA product was cloned and sequenced. Phylogenetic analysis based upon this DNA sequence places C7 within the alpha subdivision of proteobacteria, most closely related to Caulobacter subvibrioides. The phospholipid fatty acid pattern resembles that of caulobacters, with monounsaturated 16- and 18-carbon fatty acids predominating. C7 is unusual in having a monounsaturated branched fatty acid in the phospholipids and exclusively 2-hydroxy fatty acids in the lipid-extracted residue. This organism is of potential use in bioreactors operated for azo dye degradation.     

PocketOptimizer 2.0: A modular framework for computer-aided ligand-binding design

The ability to design customized proteins to perform specific tasks is of great interest. We are particularly interested in the design of sensitive and specific small molecule ligand-binding proteins for biotechnological or biomedical applications. Computational methods can narrow down the immense combinatorial space to find the best solution and thus provide starting points for experimental procedures. However, success rates strongly depend on accurate modeling and energetic evaluation. Not only intra- but also intermolecular interactions have to be considered. To address this problem, we developed PocketOptimizer, a modular computational protein design pipeline, that predicts mutations in the binding pockets of proteins to increase affinity for a specific ligand. Its modularity enables users to compare different combinations of force fields, rotamer libraries, and scoring functions. Here, we present a much-improved version––PocketOptimizer 2.0. We implemented a cleaner user interface, an extended architecture with more supported tools, such as force fields and scoring functions, a backbone-dependent rotamer library, as well as different improvements in the underlying algorithms. Version 2.0 was tested against a benchmark of design cases and assessed in comparison to the first version. Our results show how newly implemented features such as the new rotamer library can lead to improved prediction accuracy. Therefore, we believe that PocketOptimizer 2.0, with its many new and improved functionalities, provides a robust and versatile environment for the design of small molecule-binding pockets in proteins. It is widely applicable and extendible due to its modular framework. PocketOptimizer 2.0 can be downloaded at https://github.com/Hoecker-Lab/pocketoptimizer .     

Entwicklungsgeschichtliche untersuchungen an einer Blattmutante vonHyoscyamus niger L.

Summary The leaf shape of the mutantfiliformis (fil) ofHyoscyamus niger L. is strongly modified by external factors (like nutrition and light) as well as by the height of insertion. The name filiformis refers to thread-like leaves which always occur in the inflorencence; they may also be formed in the vegetative region, especially under short day conditions. Other leaves may have a small rhombic blade or a larger blade with irregular edges and deep incisions. Even pinnate leaves have been found. In contrast to the leaves of normalHyoscyamus, all mutant leaves (hypsophylls included) have a stalk-like basal portion that seems to be homologous to the basal part of the normal blade. This mutant is caused by one recessive factor which is linked neither toann nor topall.the submarginal initials of the normalHyoscyamus blade were always found dividing according to the periclinal-anticlinal type, while in the mutant the activity of the submarginal initials frequently resulted in a primarily biseriate mesophyll (so-called double-edged segmentation).This is apparently the first time that gene control of the mode of submarginal blade growth has been observed. Further differences between mutant and normalHyoscyamus concern the venation, the lengths of palisade cells and of stomata guard cells, the frequency of stomata per mm², and the thickness of the blade.

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A measuring device for calculating electrical impedance of the heart in clinical conditions]

Changes in the electrical impedance of tissue can indicate structural changes. This suggests a technique for the noninvasive detection of allograft rejection after heart transplantation. The direct electrical connection to the heart and the application of a measuring current to the myocardium requires a high standard of safety. A device was developed for measuring cardiac impedance using a sinusoidal current of 20 microA at a frequency of 15 kHz. The control logic ensures a slow current onset and also an immediate cessation in case of conductor fracture or excessive voltage. Initial results in patients with normal recovery after heart transplantation revealed a rapid drop in impedance to about 70% of the initial value in the 1st 48 hours and then a stable course. In the sole rejection episode observed so far, the impedance increased again to 85% of the initial value. This paper discusses the technical safety requirements and the design of the device, and presents initial results of clinical examinations.