Physiological regulation of transgene expression by a lentiviral vector containing the A2UCOE linked to a myeloid promoter.

Protection against epigenetic silencing is a desirable feature of future gene therapy vectors, in particular for those applications in which transgene expression will not confer growth advantage to gene-transduced cells. The ubiquitous chromatin opening element (UCOE) consisting of the methylation-free CpG island encompassing the dual divergently transcribed promoters of the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) has been shown to shield constitutive active heterologous promoters from epigenetic modifications and chromosomal position effects. However, it is unclear if this element can be used to improve expression from tissue-specific enhancer/promoters, while maintaining tissue specificity in hematopoietic cells. Here, we evaluated the potential of the A2UCOE in combination with the myeloid-specific myeloid related protein 8 (MRP8) promoter to target transgene expression specifically to myeloid cells in vitro and in vivo from a self-inactivating lentiviral vector. The inclusion of the A2UCOE did not interfere with specific upregulation of MRP8 promoter activity during myeloid differentiation and mediated sustained and vector copy-dependent expression in myeloid cells. Notably, the A2UCOE did not protect the MRP8 promoter from methylation in the P19 embryonal carcinoma cell line, suggesting that this element maintains the inherent epigenetic state and transcriptional activity of cellular promoters in their native configuration. Thus, the A2UCOE could represent a useful protective genetic element in gene therapy vectors, ensuring physiological transcriptional regulation of tissue-specific promoters independent of the chromosomal integration site.

Use of competing conceptions of risk in animal agriculture.

This study considers a theory of risk as a means of coping with risk and uncertainty that have become a growing reality for animal agriculture. Microbial contaminations of food, waste management, animal products in the human diet, and transmissible spongiform encephalopathies (TSE) incorporate different conceptions of risk and require different approaches to handling the uncertainty involved. A dichotomous schema is suggested to assist understanding risk that may be adapted to recognizing and handling risk. The polar aspects of the proposal are the probabilistic approach at one end and the contextual understanding at the other. Probabilist conceptions of risk presume that risk is determined by probability and consequence. Contextual conceptions presume that management, law, regulation, media, and public perceptions, as well as the severity of the consequence, will figure prominently in decision making in the face of uncertainty. Relative emphasis on probabilistic characteristics shapes distinct understandings of risk that can be plotted between the poles. We are proposing that these conceptualizations need not be issues only for debate but also for recognition of the probabilistic or contextual nature of the risk. Specific actions and policy may be constructed on the basis of the conceptualization. The bovine spongiform encephalopathy/new variant Creutzfeldt-Jakob disease complex is examined philosophically and methodologically as a contextual challenge to animal agriculture and associated industries. As such, the TSE serve as a case study of effective application of risk theory to risks in animal agriculture.

Interests and values in the Recommended Dietary Allowances and nutritional guidelines for Americans.

Evidence is provided showing that interests, values and belief systems have affected the development of Recommended Dietary Allowances (RDAs) and nutrition guidelines for Americans in the past and can be expected to do so in the future. The conflicts of the 1980s relative to the nutritional guidelines for Americans and the RDAs illustrate the tension among values that can parallel a conflict of interests. In the conflicts of the 1980s, we saw an apparent conflict between those policies that attempt to optimize outcomes for a large class of affected parties and those policies that attempt to establish constraints on actions which appear to threaten individual autonomy and freedom of choice. The former approach derives from utilitarian, consequential moral philosophy which evaluates policies by evaluating costs and harms, and weighing them against benefits to all parties. The latter has its strongest advocates in contemporary libertarianism which takes individual freedom to be the bottom line. Ethical vegetarianism, a belief system which would limit RDAs and guidelines to those that can be translated to vegan and other vegetarian diets, has been a more recent entry into the discussions. Such human value issues suggest that a set of RDAs or of nutrition guidelines is analogous to and may be considered to be an ethic. An ethic is a theory reached via the method of reflective equilibrium that is a coherent ordered triple set of beliefs: a set of considered moral judgments, a set of moral principles, and a set of relevant scientific background theories. The reasoning, however, can become circular and unsound when the considered moral judgments, moral principles and relevant background are not independent sources of information. If they are mixed or, for example, an intuition is mistaken for a scientific conclusion, the reasoning can be flawed.

[Stripping the Giacomini vein--pathophysiologic necessity or phlebosurgical games?]. / Stripping der Giacominivene--pathophysiologische Notwendigkeit oder phlebochirurgische Spielerei?

The Giacomini vein is present in 2.5%-10% of all patients having a phlebography because of varicosis. In a patient analysis of the last 5 years 129 patients were detected with a Giacomini vein (2.5%) out of a total of 5132 patients with varicosis. This vein was found in a significantly higher number of patients with a combined insufficiency of the long and short saphenous vein (p = 0.0001). An analysis of the different insufficiency patterns showed a Giacomini vein in 80% of insufficiency of grade I of the long and short saphenous vein. Likewise, this vein could be detected in more than half of the cases with complete insufficiency of both venous trunks (51%) as well as in 55% of the patients with a short saphenous vein insufficiency of grade III and an incomplete insufficiency of the long saphenous vein. On the other hand, there was no connection between insufficiency of the long saphenous vein, incomplete insufficiency of the short saphenous vein and the presence of the Giacomini vein. From these results we draw the conclusion that the Giacomini vein is a pathophysiologic connection between the two providing areas and thus transfers the insufficiency from one vascular system to the other. It hereby enhances the combined varicosis of both trunks as well as the formation of relapses. Therefore the Giacomini vein should always be stripped or removed by exeresis.

Construction of science for animal agriculture.

Current animal science research is dominated by disciplinary studies that are experimentally controlled and statistically analyzed. Research in animal science is also placed predominantly within a hierarchy of biological sciences ranging through molecular mechanisms, cells, organ systems, organisms, life systems, ecosystems, and human systems. In the main, disciplinary and applied animal investigations differ from each other only in that they are conducted within different biological work boundaries. Both are largely reductionist and often fragmentary. Animal science, however, has two sets of constituents, the scientific community and external interests, and both are legitimate. External interests will judge the research according to how well it contributes to a hierarchy of functional and practical knowledge instead of the biological. The functional hierarchy of inquiry ranges through validation of ideas; actions; tactics of management; strategies and systems of production; agrospheres including land and water resources, landscapes, human capital, and community; and the anthrosphere including consumers, food product chains, and global markets. More interconnection of the biological and biophysical research with functional knowledge is needed but may be limited by insufficient theoretical development of the new contributing disciplines such as molecular biology, system science, and those represented by the functional hierarchy, and recruitment of specialized scientists who often lack practical experience in agriculture and the food system. Multiple opportunities for intervention of animal agriculture exist, and multiple disciplines including the new biological and functional disciplines will be needed to provide what will be perceived to be the full scope of animal science research.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-gammaglobulin factors in human sera revealed by enzymatic splitting of anti-Rh antibodies. Vox Sang 1963;8:133-52.

Human sera were found that contained antibody activity which caused agglutination of red cells or particles sensitized with immunoglobulin G that had first been degraded by pepsin proteolysis. The agglutinating activity was specific for a determinant that was not present on the untreated, native immunoglobulin. It was found most frequently in sera from rheumatoid arthritis patients and its titre showed some correlation with disease activity.

EEG profile of three different extractions of Ginkgo biloba.

Two experiment were conducted to assess the electroencephalographic effects of (1) three different dosages of a total extract of Ginkgo biloba (EGb 761, Tebonin) and (2) three different extractions of G. biloba (Tebonin and two fractions from it). The medicament was tested against placebo using a double-blind cross-over design in 12 normal healthy males for each experiment. Medication was administered for 3 days preceding the recording sessions. 25 parameters were computed from the EEG spectra. Medication-related effects were obtained for most of the power measures, whereas dominant frequencies of the respective frequency band remained largely unchanged. The differences between the EEG effects of the two studies are critically discussed.

[Automatic (computer-assisted) EEG analysis in comparison with visual EEG analysis in patients following minor cranio-cerebral trauma (a follow-up study)]. / Die automatische (computergestützte) EEG-Analyse im Vergleich zur visuellen EEG-Analyse bei Patienten nach leichtem Schädelhirntrauma (Verlaufsuntersuchung).

The study was designed to examine the clinical applicability and use of computer-assisted EEG-analysis in comparison to visual EEG-analysis in patients with minor head injuries. For this in 31 patients the following examinations were performed within the first 24 hours, one, three and eight weeks after traumatization: EEG, neurological examination and standardized evaluation of subjective complaints. The EEG was analysed visually as well as computer-assisted. The results were compared to the neurological findings and subjective complaints. Reversible posttraumatic EEG-changes were observed in 50% of all patients. The results of computer-analysis and visual analysis were equivalent in respect to baseline-activity (as one of the main characteristic EEG-features). Furthermore, based on computer-assisted analysis a discriminant function is provided, which is of diagnostic and prognostic value in the single patient. We conclude that the computer-assisted EEG-analysis can be a useful alternative in EEG-routine diagnosis after minor head injuries.

[Event-related potentials in psychiatry--methodologic principles]. / Ereigniskorrelierte Potentiale in der Psychiatrie--Methodische Grundlagen.

The methodological requirements for the use of event-related brain potentials (ERPs) in psychiatry are critically reviewed. In particular the development of psychophysiological models is considered as essential for a functional interpretation of ERP-experiments. In addition problems of signal-analysis and clinical diagnosis relevant to ERP-research in psychiatry are briefly discussed. The logic of ERP-research in psychiatry is illustrated by a series of dichotic listening experiments.

Neurophysiological assessment of early hepatic encephalopathy.

The spontaneous EEG, pattern reversal VEPs, and the P300 wave were studied in patients with liver cirrhosis and early stages of hepatic encephalopathy (HE). The sensitivities of the different neurophysiological methods in the early stages of hepatic encephalopathy were compared with each other and with several neuropsychological tests. P300 latency was shown to be the most appropriate neurophysiological method for detection of early HE. The diagnostic sensitivity of the P300 latency resembled that of the number connection test (NCT). These results are discussed with regard to methodological considerations and the clinical use of both methods.

Positron emission tomography in neuropsychiatric lupus erythematosus.

We performed positron emission tomography (PET) using 18F-labeled 2-F-2-deoxyglucose in 13 patients with systemic lupus erythematosus (SLE). Ten of them had clinical signs of central nervous system involvement (NP-SLE). All patients with neurologic symptoms showed pathologic changes on PET, always in accordance with the clinical state. Three patients without neuropsychiatric manifestations had normal PETs. Computed tomography of the brain and magnetic resonance imaging proved to be less sensitive to both presence and localization of CNS lesions. We conclude that the combination of PET and MRI constitutes the most useful diagnostic procedure for NP-SLE.

Finite-element analysis of vibrational modes in piezoelectric ceramic disks.

The natural vibrational modes of axially symmetric piezoelectric ceramic disks have been calculated by the finite-element method. The disks are of the type used as active elements in compressional wave ultrasonic transducers, and are electrically polarized in thickness with full electrodes on the disk's major faces. To optimize disk geometry for ultrasonic transducer application, the dependence of the vibrational modes on the disk diameter-to-thickness ratio for ratios from 0.2 (a tall cylinder) to 10.0 (a thin disk) has been studied. Series and parallel resonance frequencies for each of the modes are determined through an eigenfrequency analysis, and effective electromechanical coupling coefficients are calculated. The modal displacement fields in the disk are calculated to determine the physical nature of each mode. An analysis of the complete spectrum of piezoelectrically active modes as a function of diameter-thickness ratio is presented for the ceramic PZT-5H, including and identification of radial, edge, length expander, thickness shear, and thickness extensional vibrations. From this analysis, optimal diameter-to-thickness ratios for good transducer performance are discussed.

Intravenous treatment of chronic peripheral occlusive arterial disease: a double-blind, placebo-controlled, randomized, multicenter trial of pentoxifylline.

A multicenter, prospective, placebo-controlled, double-blind trial was conducted to investigate the efficacy of intravenous infusion therapy with pentoxifylline over fourteen days in patients suffering from angiographically confirmed chronic peripheral occlusive arterial disease, Fontaine stage II, with at least a six-month history. After a washout phase of one week, the patients received in accordance with a randomization scheme either an i.v. infusion of 300 mg of pentoxifylline (15 mL ampoules) or 15 mL of a 0.9% NaCl solution in 250 mL of 5% laevulose, administered over three hours twice daily. The main efficacy parameters were treadmill-assessed initial claudication distance (ICD) and absolute claudication distance (ACD). Baseline testing revealed a mean ICD of 131 m in the pentoxifylline group and 126 m in the placebo cohort; mean ACD values were 239 m and 225 m respectively. The group of patients treated with pentoxifylline (n = 75) displayed a significantly greater improvement (p less than 0.0001) in ICD (+70%) and ACD (+60%) than the placebo group did (+33%) and 32%, respectively) (n = 79). The infusions were well tolerated in both groups.

Effects of a cholinergic nootropic (WEB 1881 FU) on event-related potentials recorded in incidental and intentional memory tasks.

In a double-blind placebo-controlled randomized study the influence of a cholinergic nootropic (WEB 1881 FU) on event-related brain potentials (ERPs) related to memory performance was investigated. Two different encoding modes were imposed on the subjects, who had to memorize word lists. No significant drug effects were obtained on memory performance and the ERP-concomitant of encoding, the Dm, while ERP effects related to memory were clearly present. However, the two dosages of the drug significantly influenced the overall amplitude of the late cognitive ERP components, suggesting its effect on cognitive processes.