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HIV testing technologies after two decades of evolution.

Over the past two decades, HIV diagnostics have been essential in detecting and monitoring infection, and continue to play a major role in saving lives throughout the world. As technology evolved, screening, confirmatory, and HIV monitoring assays have been improved and offer better alternatives to address blood screening, surveillance, diagnosis, and patient management. Molecular methods are critical in detecting early infection and for managing patients on anti retroviral therapy whose viral infection may become resistant to therapy. In addition, modifications to conventional methods have introduced new assays, such as sensitive/less sensitive (detuned) assays that can estimate when someone was infected, thereby providing a useful tool for epidemiologic incidence estimates and enrollment into specific intervention programmes for recently infected persons. Many of the newly evolving technologies are essential for use in resource-limited countries because they can address cost issues, limited infrastructure, and a lack of formally trained personnel. Newer rapid HIV kits can be stored in a wide range of temperatures (2-30 degrees C) to address cold-chain issues, can use easily-collected fingerstick blood and oral fluids, and have one-step procedures that are relatively foolproof. Manual CD4 lymphocyte count assays that require only a light microscope and haemacytometer and more simple assays to estimate viral load are appropriate for developing countries where sophisticated instrumentation cannot be supported. Technologic advances with HIV diagnostics continue to address outstanding and new issues associated with diagnosis and the monitoring of infection by providing more simplified, cost-effective, and accurate testing throughout the world.

AIDS Serodiagnosis↗

[Influence of ambiant temperature on evolution of Schistosoma mansoni in the mouse (author's transl)].

Mice infested with Schistosoma mansoni are kept continuously in an ambiant temperature of 35 degrees C for different periods and at different stages of the infestation. The effects of the hyperthermia thus provoked are evaluated by counting adult parasites and pulmonary schistosomules. There is a very considerable decrease in the number of parasites present, probably due to the action of the higher temperature on the early migratory phase of the schistosomules.

Animals↗

Short- and long-term changes in proteome composition and kinetic properties in a culture of Escherichia coli during transition from glucose-excess to glucose-limited growth conditions in continuous culture and vice versa.

To investigate the ability of Escherichia coli K12 MG1655 to cope with excess and limitation of a carbon and energy source, we studied the changes in kinetic properties and two-dimensional (2D) gel protein patterns of an E. coli culture. The population was transferred from glucose-excess batch to glucose-limited continuous culture (D = 0.3 h(-1)), in which it was cultivated for 500 h (217 generations) and then transferred back to glucose-excess batch culture. Two different stages to glucose-limitation were recognized: a short-term physiological adaptation characterized by a general effort in enhancing the cell's substrate scavenging ability and mutations resulting in a population exhibiting increased glucose affinity. Physiological short-term adaptation to glucose-limitation was achieved by upregulation of 12 proteins, namely MglB, MalE, ArgT, DppA, RbsB, YdcS, LivJ (precursor), UgpB (precursor), AceA, AldA, AtpA and GatY. Eight of these proteins are periplasmic binding proteins of ABC transporters. Most of them are not involved in glucose transport regulons, but rather in chemotaxis and transport of other substrates, whereas MalE and MglB have previously been shown to belong to transport systems important in glucose transport under glucose-limited conditions. Evolution under low glucose concentration led to an up to 10-fold increase in glucose affinity (from a K(s) of 366 +/- 36 microg l(-1) at the beginning to 44 +/- 7 microg l(-1)). The protein pattern of a "500-h-old" continuous culture showed a highly increased expression of MglB and MalE as well as of the regulator protein MalI. When adapted cells taken from the "500-h-old" continuous culture were transferred to batch culture, an increased expression of MalE was observed, compared with cells from un-adapted batch-grown cells. Otherwise, no significant changes were observed in the protein pattern of batch-grown populations before and after 500 h of evolution in the glucose-limited continuous culture.

Biological Evolution↗

[Radiofrequency catheter ablation of ventricular tachycardia in patients with an implantable defibrillator. Long-term follow-up].

INTRODUCTION AND OBJECTIVES: The frequent occurrence of ventricular tachycardia can be a serious problem for patients with an implantable defibrillator, and may necessitate adjuvant antiarrhythmic therapy or radiofrequency catheter ablation. We analyzed the long-term results obtained with this latter therapy in patients suffering from frequent or continuous ventricular tachycardia. PATIENTS AND METHOD: Eighteen ablation procedures were performed in 11 patients who had a defibrillator implanted because of previous syncopal ventricular tachycardia. All were men, aged 67.64 (5.87) years; 10 patients had had a myocardial infarction 15.50 (5.08) years earlier, and one suffered from arrhythmogenic right ventricular dysplasia. RESULTS: Electrophysiologically, treatment was initially successful in 8 patients (72.73%). After a follow-up period of 39.10 (24.70) months, the number of defibrillator discharges decreased significantly in all patients, from 52.82 (35.73) to 0.64 (1.03) (P=.001). During follow-up, ventricular tachycardia occurred in nine patients. In five, it took the same form as the ablated ventricular tachycardia. Six patients needed additional ablation procedures: two because of initial failure, three because of recurrence, and one because a different ventricular tachycardia occurred. In addition to the good electrophysiological results obtained, long-term clinical evolution was favorable in all patients. CONCLUSIONS: Radiofrequency ablation successfully disrupts frequent or continuous ventricular tachycardias and significantly reduces the defibrillator discharge rate even when ablation has failed electrophysiologically. It is particularly useful in these latter critical situations, in which other therapies are not sufficiently effective. Because our patients mainly had ischemic heart disease and were highly susceptible to new arrhythmias during follow-up, ablation complemented rather than replaced the implantable defibrillator.

Aged↗

Spatiotemporal evolution of soil pH and zinc after the Aznalcollar mine spill.

The residual pollution after the Aznalcóllar (southwestern Spain) pyrite mine spill is still a threat due to the continuing oxidation of sulfuric minerals. The objective of this paper was to analyze the combined effect of pyrite oxidation, sugar beet foam applications, and meteorological conditions on the spatiotemporal evolution of the pH and EDTA-extractable Zn concentration, using non co-located data from 11 sampling dates between June 1999 and March 2002. Median pH values ranged from 4.4 at the beginning of the monitoring period to 7.6 at the end, although values near 2.5 were observed throughout the entire period, despite of two sugar beet foam (SBF) applications. Zinc distributions were positively skewed and median concentrations ranged from 17 to 94 mg kg(-1). The inverse relationship between pH and Zn became weaker toward the end of the monitoring period as a consequence of the precipitation and posterior dissolution of newly formed minerals from the reaction products of the pyrite oxidation. Normal score maps showed that after the SBF applications only 0.5% of the monitored area was below the pH = 4 threshold, while on other dates up to one-third of the area remained below this value. The better performance of the second SBF application could be explained in terms of pyrite oxidation pathways and environmental conditions. From this analysis, with data obtained under uncontrolled field conditions, it is concluded that SBF should be applied before or during the wet and cold season to alleviate acidification, caused by the oxidation of pyrite or other sulfuric minerals.

Hydrogen-Ion Concentration↗

The carbonic anhydrases: widening perspectives on their evolution, expression and function.

Now, some 55 years after its discovery in bovine red cells, carbonic anhydrase (CA), in all its varied forms, continues to challenge and intrigue physiologists, biochemists and molecular geneticists. This is so because of an increasing awareness of the many apparently diverse functions of the different CA isozymes encoded by this large multigene family, the continuing discovery of new CA, or CA-related, genes, and the extensive variation in their hormonal control, cellular expression and subcellular localization.

Amino Acid Sequence↗

Metabolite channeling in the origin of life.

A central question in the origin of life concerns whether primitive metabolites and catalysts interacted randomly in solution, as often envisaged, or whether they were arranged from the start in ordered metabolic complexes. The latter possibility would be consistent with the hypothesis of metabolite channeling in extant cells, which holds that intermediates in many pathways are transferred directly, without diffusion, between pathway enzymes. A model on this basis is proposed in which life originated autotrophically de novo in metabolic complexes organized on FeS2 (pyrite) mineral surfaces. Because metabolites and catalysts arose at specific sites in these complexes, they could interact specifically with neighbouring species in evolving pathways prior to the existence of protein enzymes with precise substrate binding sites. In successive stages, RNA catalysts and protein enzymes could be incorporated in these arrays. The overall process may be viewed as a molecular analogue of embryonic development, with the formation and positioning of each new component continuously transforming the whole. A corollary of the hypothesis relates to the evolution of translation and the genetic code. By virtue of channeling, biosynthetically related amino acids (e.g., aspartic acid and threonine) would have arisen close together in the complex. A second premise is that tRNAs with similar base sequences, and thus similar anticodons, were also clustered together in the complex and channeled to adjacent sites. As a result of these combined effects, tRNAs with similar anticodons would necessarily have been positioned close to, and thus more likely to have been charged with, metabolically related amino acids. This mechanism affords a new rationale for the observed codon structure of the genetic code, in which biosynthetically related amino acids possess similar codons.

Animals↗

Hox gene duplication in fish.

The study of Hox gene clusters continues to serve as a paradigm for those interested in vertebrate genome evolution. Recent exciting discoveries about Hox gene composition in fishes challenges conventional views about vertebrate Hox gene evolution, and has initiated lively debates concerning the evolutionary events making the divergence of the major vertebrate lineages. Comparative analyses indicate that Hox cluster duplications occurred in early vertebrate evolution, and again within the order Cypriniformes of teleost fish. Loss of Hox genes was more widespread than duplication during fish evolution.

Animals↗

A knowledge-based system for assisted ventilation of patients in intensive care units.

The procedure for weaning a patient with respiratory insufficiency from mechanical ventilation may be complex and requires expertise obtained by long clinical practice. We designed a knowledge-based system for the management of patients receiving respiratory support and implemented a weaning procedure. The system is intended for patients whose spontaneous respiratory activity is assisted by a Hamilton Veolar ventilator delivering a positive pressure plateau during inspiration (Pressure Support Ventilation mode). Our closed-loop real-time system running on a Personal Computer continuously adapts the assistance provided by the ventilator to the patient's evolution, and indicates when the patient can be withdrawn from the ventilator. Three parameters are used to appreciate the 'respiratory comfort' of the patient: breathing frequency, which we consider the most informative index, tidal volume and end-tidal CO2 pressure. A preliminary study of 19 patients was performed to evaluate the ability of our system to adapt the assistance to the patient's needs, with the main objective of facilitating weaning by gradually lowering the level of assistance. In 10 of these patients, considered as good candidates for weaning on the strength of objective criteria, the system maintained the breathing pattern in a zone of comfort for 95% of the period of assisted ventilation and stated that they were 'weanable'. This was consistent with the clinical evolution of all 10 patients. These results show that such a system can provide effective management for mechanically ventilated patients.

Adult↗

Comparison of single current dipole and magnetic field tomography analyses of the cortical response to auditory stimuli.

Measurements of the magnetic field elicited by a 50 ms long auditory stimulus, from three normal subjects and one head injured subject, are used to estimate the three dimensional distribution of generators in the brain. The resulting images are compared with point source solutions obtained with the usual single current dipole fitting procedures, over a latency range which includes the extrema in the (average) measured signal. In all cases considered, 100 or so epochs time-locked to the stimulus were magnetically recorded. These were averaged, and then analyzed using two techniques; a new distributed current model known as Magnetic Field Tomography (MFT), and the standard single current dipole (SCD) model. Both methods provide estimates of the current generators in the brain. In two of the normal subjects, the MFT solutions are super-imposed onto Magnetic Resonance Images (MRI) of the relevant cortical area. The results show that when the SCD model provides a reasonable description of the data, the MFT estimate shows one dominant localized region in agreement with the current dipole position. In the MFT sequence of solutions the activity evolves smoothly; multiple areas of activity often arise as the focal activity in one region declines while focal activity in another region grows. In contrast the SCD solutions during these intermediate periods fit the data poorly, and may move erratically from one locale to another. We conclude that MFT seems to provide a reasonable description of the activity through cortical and subcortical regions. The evolution of activity, as derived from the average signal, can be traced continuously from the onset of the stimulus, not just at the peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

[Electron-beam CT-angiography in abdominal aortic aneurysms. Initial results].

PURPOSE: To evaluate the suitability of ultrafast electron-beam tomography (EBT) for the investigation of abdominal aortic aneurysms using CTA. METHODS: Thirty-one patients with suspected abdominal aortic aneurysm were investigated with EBT using an Evolution XP scanner (Siemens, Erlangen) with the newest software version 12.34 with continuous volume scanning of 140 images in 17 s. Collimation was 3 mm, table increment 4 mm with overlapping image reconstruction every 2 mm, exposure time 200 ms (124 mAs), resulting in a scan-range of 28 cm. A quantity of 80 ml contrast material was administered (flow 4 ml/s). Visualization of the abdominal aorta and its branches was performed with MIPs and shaded surface display. Evaluation of image quality was based on a four-step classification scale (1 = good, 4 = insufficient) for the demonstration of the abdominal aorta and the visceral, renal and iliac arteries. RESULTS: All EBT examinations demonstrated high and homogeneous density values along the whole vessel course with a mean density value of 258.7 +/- 47.3 HU for the abdominal aorta and the iliac arteries. Quality evaluation for the vessel demonstration showed mean values between 1.22 and 1.57 for the abdominal aorta and the visceral, renal and iliac arteries. CONCLUSIONS: EBT with 140 slices and slice reconstruction every 2 mm offers a high z-axis resolution resulting in high-quality CT angiographies of the whole abdominal aorta and its branches.

Aged↗

Full-genome analysis of resistance gene homologues in rice.

The availability of the rice genome sequence enabled the global characterization of nucleotide-binding site (NBS)-leucine-rich repeat (LRR) genes, the largest class of plant disease resistance genes. The rice genome carries approximately 500 NBS-LRR genes that are very similar to the non-Toll/interleukin-1 receptor homology region (TIR) class (class 2) genes of Arabidopsis but none that are homologous to the TIR class genes. Over 100 of these genes were predicted to be pseudogenes in the rice cultivar Nipponbare, but some of these are functional in other rice lines. Over 80 other NBS-encoding genes were identified that belonged to four different classes, only two of which are present in dicotyledonous plant sequences present in databases. Map positions of the identified genes show that these genes occur in clusters, many of which included members from distantly related groups. Members of phylogenetic subgroups of the class 2 NBS-LRR genes mapped to as many as ten different chromosomes. The patterns of duplication of the NBS-LRR genes indicate that they were duplicated by many independent genetic events that have occurred continuously through the expansion of the NBS-LRR superfamily and the evolution of the modern rice genome. Genetic events, such as inversions, that inhibit the ability of recently duplicated genes to recombine promote the divergence of their sequences by inhibiting concerted evolution.

Amino Acid Sequence↗

Microdialysis techniques in the study of brain and skeletal muscle.

Traditionally, plasma measurements have been used to monitor metabolic events and the actions of hormones that are actually taking place within tissue beds that are anatomically separated from the vascular compartment. It is generally assumed that the extracellular fluid (ECF) within metabolically active tissues is composed of substrates and hormones in concentrations that closely approximate those in plasma. Indeed, this view is implicit in non-steady-state tracer calculations. However, through the use of microdialysis techniques in the study of tissue metabolism this view is being challenged. Our data suggest that there may be substantial concentration gradients for a variety of fuels between plasma and ECF, i.e. fuels (e.g. glucose) removed from the circulation being lower and fuels (e.g. glycerol, lactate, some amino acids) produced by tissues being higher than plasma levels. In short, the metabolic milieu seen by individual tissues (and hormone receptors?) may, at least in some instances, be strikingly different from that in plasma, and as a result, plasma measurements by themselves may not appropriately define the contributions of specific tissues to metabolic events, and overlook the importance of metabolic processes which are largely restricted to individual tissue beds. Through the use of microdialysis as a means of directly sampling ECF from metabolically important body tissues and with the evolution of its use in animal and human research, this technique will continue to offer exciting new insights into tissue metabolism and to investigate fundamental issues that cannot be addressed by other methods.

Brain↗

First results of computerised tomographic angiography using electron beam tomography.

The aim of this study was to evaluate the suitability of electron beam tomography (EBT) with fast continuous volume scanning for CT angiography (CTA) in chest and abdomen. An Evolution XP EBT scanner with a new software version (12.34) was used. One hundred forty images per study can be acquired in 17 s using 3-mm collimation and overlapping image reconstruction. Study protocols for five different clinical applications of EBT CTA were established and evaluated. The EBT CTA technique was performed in 155 patients. High- and homogeneous density values were achieved along the whole course of the vessels; the mean density in the aorta was > 240 HU. Coeliac axis, superior and inferior mesenteric artery, renal and lumbar arteries were visualised in all cases. Maximum intensity projection and shaded surface display reconstruction demonstrated the relation between aneurysm and aortic branches very well due to an excellent resolution along the z-axis. In large scan volumes overlapping image reconstruction demonstrated better resolution along the z-axis than is available with helical CT. The EBT CTA technique proved to be very well suited excellent suitability for evaluation of pulmonary vessels. Compared with helical CT, EBT CTA offers a shorter scan time, which allows higher contrast enhancement in pulmonary vessels. The identification of intraluminal emboli and mural thrombi has improved. The EBT CTA technique is a very reliable tool for evaluation of aortic disease and pulmonary vessels.

Angiography↗

Electrophysiological and sleep alterations in experimental mouse rabies.

Changes in the spontaneous brain electrical activity and sleep organization were investigated in 5 mice strains during the evolution of experimental fixed rabies infection. Cortical electrodes were chronically implanted for continuous EEG recording and spectral analysis until death. Three evolutionary phases were individualized. The initial phase exhibited alterations of sleep stages, REM sleep disappearance, pseudoperiodic facial myoclonus and first clinical signs. The mature phase was characterized by a generalized EEG slowing (2-4 cycles/s). The terminal phase occurring with extinction of hippocampal rhythmic slow activity showed a flattening of cortical activity. The brain electrical activity ceased about 30 min before the cardiac arrest. Paroxysmal activities appeared during the course of the disease as bursts of rhythmic slow waves, pseudoperiodic spikes or occasionally ictal epileptic discharges. Spectral analysis revealed a progressive and characteristic clustering of the EEG frequency band power values. The spread of infection in the CNS was monitored by specific immunofluorescence studies which revealed the presence of rabies virus antigen in the pons, the cerebellum, the thalamus and the cortex during the initial phase. The pyramidal field of the hippocampus was infected during the mature phase but the gyrus dentatus was never infected even at the terminal phase. These studies show that particular neuronal functions are impaired during rabies virus infection suggesting that neuronal alterations may be involved in the pathogenic mechanisms leading to lethality.

Animals↗

Genetic and antigenic analyses of influenza A (H1N1) viruses, 1986-1991.

Eighteen strains of human influenza A (H1N1) viruses isolated between August 1986 and January 1991 were analyzed in this study. Examination of the total viral genome of 12 strains by T1 mapping revealed that considerable genetic heterogeneity exists among these viruses. Partial sequencing of each of the non-HA RNA segments of 4 viruses having divergent T1 oligonucleotide maps indicated that only one was a reassortant virus that had genes from both the influenza A (H1N1) and (H3N2) subtypes. This reassortant obtained its PB2 gene from a virus of the H3N2 subtype and the other 7 RNA segments from an H1N1 parent. Sequencing studies of the HA1 domains of the hemagglutinin (HA) genes of these 18 strains revealed that although these viruses are antigenically similar to the reference strains A/Taiwan/1/86 and A/Singapore/6/86, 7 conserved amino acid substitutions that are shared by recently isolated H1N1 viruses have occurred in the main stream of evolution of the H1N1 subtype. Our data indicate that: (1) Genetic reassortment continues to contribute to genetic variability of H1N1 viruses. (2) Genetic variants of non-reassortant H1N1 viruses are co-circulating in the world. (3) The HA's of recent H1N1 viruses are related to those of the 1986 reference strains. (4) Although there has been little detectable antigenic variability, the HA genes of human epidemic influenza A (H1N1) viruses have continued to evolve at an evolutionary rate similar to that for the H1N1 and H3N2 viruses analyzed previously.

Amino Acid Sequence↗

The American dominative medical system as a reflection of social relations in the larger society.

Expanding upon Navarro's analysis of the American biomedical sector, I argue that the phenomenon of medical pluralism has historically and continues to reflect class, racial/ethnic, and gender relations in American society. The evolution of the American medical system is traced from a relatively pluralistic one in the nineteenth century to a dominative one in the twentieth century. While legitimation and even professionalization of various alternative medical systems supports the assertion that the dominance of biomedicine is delegated rather than absolute, these processes reflect the growing accommodation on the part of alternative practitioners to the reductionist disease theory which is compatible with capitalist ideology.

Chiropractic↗

Selective evolutionary pressure from the tissue microenvironment drives tumor progression.

Cells grow within defined environmental niches and are subject to microenvironmental control. Outside of their niche, the environment is hostile, the normal cells lack appropriate survival signals which leads to anoikis. During tumor development and progression, malignant cells must escape the local tissue control and resist anoikis. The inherent genetic instability of tumor cells makes their phenotype very plastic, which changes under continuous environmental selection pressure. In this way the microenvironment drives the somatic evolution of the tumor. In the current review, we assess how this environmental selection pressure fits into the classical scheme of tumor progression.

Animals↗