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Long-term evolution of lymphocytes subsets after induction therapy based on continuous versus discontinuous administration of anti-thymocyte globulins in renal-transplant patients.

UNLABELLED: The aim of our retrospective study was to assess the long-term evolution of lymphocyte subsets after two modes of administration of anti-thymocyte globulin (ATG) after renal transplantation. METHODS: Before 1993, patients (group I, n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until the serum creatinine level became <150 micromol/L. After 1993, patients (group II, n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and, thereafter, doses were adapted to target a CD2 T-cell count <50/mm3. RATG cumulative dose was significantly higher among group I than group II (9.7 +/- 4.5 versus 7.4 +/- 3.2 mg/kg, P = .0002). RESULTS: In both groups, total lymphocyte and T lymphocyte subset (CD4, CD8, CD2, CD3) counts decreased significantly during the first month after transplantation, increasing slowly between the first month and the third year posttransplantation. Thereafter it rose rapidly, which was greater in group II. At last follow up, total lymphocyte, T lymphocyte subsets and NK cell counts were similar to those observed before transplantation. At all monitoring times, T lymphocyte, B lymphocyte, and NK cell counts were similar in both group, except for the total lymphocyte count at 6 months and CD4 T lymphocyte count at 1 year, which were significantly higher in group II compared to group I. CONCLUSION: Induction therapy based on continuous or discontinuous administration of ATG is associated with profound depletion of T, B, and NK cells during the first 3 years, followed by a progressive reconstitution of the lymphocyte pool after 5 years.

Antigens, CD↗

Assessing immunophenotyping performance: proficiency-validation for adopting improved flow cytometry methods.

BACKGROUND: The continuous improvement and evolution of immune cell phenotyping requires periodic upgrading of laboratory methods and technology. Flow cytometry laboratories that are participating in research protocols sponsored by the NIAID are required to perform "switch" studies to validate performance before methods for T-cell subset analysis can be changed. METHODS: Switch studies were conducted among the four flow cytometry laboratories of the Multicenter AIDS Cohort Study (MACS), comparing a 2-color, lyse-wash method and a newer, 3-color, lyse no-wash method. Two of the laboratories twice failed to satisfy the criteria for acceptable differences from the previous method. Rather than repeating more switch studies, these laboratories were allowed to adopt the 3-color, lyse no-wash method. To evaluate the impact of the switch to the new method at these two sites, their results with the new method were evaluated within the context of all laboratories participating in the NIH-NIAID-Division of AIDS Immunology Quality Assurance (IQA) proficiency-testing program. RESULTS: Laboratory performance at these two sites substantially improved relative to the IQA standard test results. Variation across the four MACS sites and across replicate samples was also reduced. CONCLUSIONS: Although switch studies are the conventional method for assessing comparability of laboratory methods, two alternatives to the requirement of repeating failed switch studies should be considered: (1) test the new method and assess performance on the proficiency testing reference panel, and (2) prior to adoption of the new methods, use both the old and the new method on the reference panel samples and demonstrate that performance with the new method is better according to standard statistical procedures. These alternatives may help some laboratories' transition to a new and superior methodology more quickly than if they are required to attempt multiple, serial switch studies.

Acquired Immunodeficiency Syndrome↗

Cosmetic minilaparoscopic cholecystectomy.

BACKGROUND: Since its introduction in 1987, the technique of laparoscopic cholecystectomy has continued to undergo evolution. One area of refinement has been the optimization of cosmetic results. Surgeons have reduced port size and number or both in attempts to achieve this goal. In this report, we describe a method of adjusting port position to obtain more discreet scars. METHODS: Minilaparoscopic cholecystectomy is performed using three 5-mm ports. One port is placed in the umbilicus. Instead of placing the two additional ports in the right subcostal and subxiphoid positions, they are moved to either side of midline at the level of the pubic hairline. RESULTS: The result is one scar hidden in the umbilicus, with the two other scars located below the bikini line. These scars are nearly undetectable when the patient is wearing minimal clothing. CONCLUSION: We conclude that, in addition to minimizing port size and number, positioning of ports can be used to optimize cosmetic results.

Adult↗

Why the back of the child?

An international congress about "the back of children and teenagers and the prevention of backache" was held in March 1999 in Grenoble (France). Beside specific low back pain following progressive and growth diseases, special attention was paid to non-specific low back pain (LBP). Some epidemiological data show a high incidence of LBP during and after the rapid growth phase, with the concomitant possibility of continued or recurrent evolution. MRI studies reveal frequent signs of disc degeneration: they start after the growth phase, spread during adolescence and are often correlated with backache. An immunohistological study seems to confirm the presence of degenerative-type alterations and changes in collagen in the vertebral plates and nucleus of juvenile spine. These data must be confirmed, and their relation to natural history and prognosis of juvenile LBP have to be clarified by longitudinal studies.

Adolescent↗

DNA distribution and respiratory activity of Spodoptera frugiperda populations infected with wild-type and recombinant Autographa californica nuclear polyhedrosis virus.

Spodoptera frugiperda cells were infected with a wild-type Autographa californica nuclear polyhedrosis virus and with a recombinant Autographa californica nuclear polyhedrosis virus. The recombinant virus was derived from the wild-type virus and produced beta-galactosidase instead of polyhedrin. The changes in cell size, cell growth, viability, DNA distribution, and respiratory activity were followed through the time course of the infection. The DNA content as measured by flow cytometry of infected cells increased to approximately 1.8 times the value of uninfected cells and the distributions of single-cell DNA content of the infected cells were strongly deformed. Early in the infection the respiratory activity passed through a maximum. The mitochondrial activity based on Rhodamine 123 labelling of cells infected with the recombinant virus, as determined by flow cytometry, also passed through a maximum at 24 h post infection while the mitochondrial activity of cells infected with the wild-type virus continued to increase. Evolution of single-cell mitochondrial activity was different in uninfected populations and in populations infected with wild-type and with recombinant virus. In all experiments performed, the recombinant virus influenced cell behavior and the measured parameters earlier than the wild-type virus. The influence of the multiplicity of infection was stronger for the wild-type virus than for the recombinant virus.

Animals↗

The importance of resolution in the clinical application of breast sonography.

Although in use for over thirty years, breast ultrasound continues a steady evolution both in technological development and in clinical application. It is now firmly established as a first line diagnostic modality to be used in conjunction with x-ray mammography. Its ability to provide qualitatively different parenchymal information in a slice-type, or tomographic format with excellent resolution makes it a clinically important instrument. The ultimate goal, however, still lies ahead. This is the detection and characterization of small masses within the breast, coupled with the ability to determine whether these foci are benign or malignant. This will likely involve not only scanners with better resolution, but also those, such as doppler, with the ability to obtain functional information as well.

Adult↗

Reconstructing the diversification of subtilisins in the pathogenic fungus Metarhizium anisopliae.

Fungi secrete subtilisin proteinases to acquire nutrients and breach host barriers. Here we sought a global characterization of the diversity of subtilisins in the insect pathogen Metarhizium anisopliae. Expressed sequence tag (EST) analyses showed that a broad host range strain of M. anisopliae sf. anisopliae (strain 2575) expressed 11 subtilisins during growth on insect cuticle, the largest number of subtilisins reported from any fungus. Polymerase chain reaction amplified 10 of their orthologs from a second strain with multiple hosts (strain 820) and seven from the locust specialist M. anisopliae sf. acridum (strain 324). Analyses based on sequence similarities and exon-intron structure grouped M. anisopliae subtilisins into four clusters-a class I ("bacterial") subtilisin (Pr1C), and three clusters of proteinase K-like class II subtilisins: extracellular subfamily 1 (Pr1A, Pr1B, Pr1G, Pr1I and Pr1K), extracellular subfamily 2 (Pr1D, Pr1E, Pr1F and Pr1J) and an endocellular subtilisin (Pr1H). Phylogenetic analysis of homologous sequences from other genera revealed that this subdivision of proteinase K-like subtilisins into three subfamilies preceded speciation of major fungal lineages. However, diversification has continued during the evolution of Metarhizium subtilisins with evidence of gene duplication events after divergence of M. anisopliae sf. anisopliae and M. anisopliae sf. acridum. Comparing alignments and nonsynonymous/synonymous rates for Pr1 isoenzymes within a lineage and between lineages showed that while overall divergence of subtilisins followed neutral expectations, amino acids involved in catalysis were under strong selective constraint. This suggests that each Pr1 paralog contributes to the pathogens fitness. Furthermore, homology modeling predicted differences between the Pr1's in their secondary substrate specificities, adsorption properties to cuticle and alkaline stability, indicative of functional differences.

Amino Acid Sequence↗

Otolaryngology in the information age: enabling technologies for the future of surgery. Enabling technologies for the future of surgery.

Enabling technologies for the future, whether exemplified by endoscopic, minimally invasive, or microdexterity systems or surgical and nonsurgical image-guided procedures, continue with an evolution so rapid that before one change has been accepted and perfected, another even more dramatic change promises to replace it. These information-based surgical and procedural interventions are just now becoming accepted standards of surgical, radiologic, and medical practice, and yet the promise of more advanced technologies blurs even these new boundaries, constantly redefining the concept of "surgery." It is essential that otolaryngologists, as part of the broader spectrum of physicians, understand these changes and prepare to adapt and improve each and every one of their technical and cognitive skills.

Computer Simulation↗

Swine production.

The US swine industry is large and growing. The quantity of pork desired by consumers of US pork is growing at the rate of 1.5%/y. New production systems and new technology have enabled production per sow to grow at a rate of 4% annually in recent years. Consequently, the number of sows in the United States is declining. Because productivity growth is outpacing demand growth, the deflated price of hogs and pork is declining. Hog production and prices continue to exhibit strong seasonal and cyclic patterns. Pork production is usually lowest in the summer and highest in the fall. Production and prices tend to follow 4-year patterns. The US swine industry continues to evolve toward fewer and larger producers who rely on contracts for both hog production and marketing. In 2000, over half of the hogs marketed were from approximately 156 firms marketing more than 50,000 head annually. These producers finished 60% of their production in contract facilities. Over 90% of their marketings were under contract or were owned by a packer. These producers expressed a high level of satisfaction with hog production. Both they and their contract growers were satisfied with production contracts. These large producers were satisfied with their marketing contracts and planned to continue them in the future. The hog industry has changed a great deal in the last decade. There is little reason to believe this rapid rate of change will not continue. This swine industry is highly competitive and profit driven. Profit margins are too small to allow producers the luxury of ignoring new technology and innovative production systems. Consequently, hog production will continue its rapid evolution from traditional agriculture to typical industry.

Animal Husbandry↗

A combined evolution method for associative memory networks.

In the study of associative memory networks, the updating rule remains unchanged during neuron evolution. When evolution stops at an undesired minimum, simulated annealing is used to resolve the problem. In this paper, a combined neuron evolution method based on a multipath network architecture is presented. It is shown that, by controlling the evolution path, the probability that evolution terminates in undesired, minima is significantly reduced. Once evolution is trapped in an undesired minimum with respect to one path, the method seeks an alternative path to carry on the evolution. The process continues until a desired minimum is reached. Visual examples are used to demonstrate the performance of the method.

Journal Article↗

Advances in surface plasmon resonance biosensor analysis.

The number and diversity of surface plasmon resonance (SPR) biosensor applications continue to increase. Evolutions in instrument and sensor chip technology, experimental methodology, and data analysis are making it possible to examine a wider variety of biomolecular interactions in greater mechanistic detail. SPR biosensors are poised to make a significant impact in basic research and pharmaceutical discovery.

Animals↗

Suicide attempts, plans, and ideation in culturally diverse sites: the WHO SUPRE-MISS community survey.

BACKGROUND: The objectives were to assess thoughts about suicide, plans to commit suicide and suicide attempts in the community, to investigate the use of health services following a suicide attempt, and to describe basic socio-cultural indices of the community. METHOD: The community survey was one component of the larger WHO multisite intervention study on suicidal behaviours (SUPRE-MISS). In each site, it aimed at randomly selecting and interviewing at least 500 subjects of the general population living in the catchment area of the emergency department where the intervention component of the study was conducted. Communities of eight SUPRE-MISS sites (in Brazil, China, Estonia, India, Iran, South Africa, Sri Lanka, and Viet Nam) participated plus two additional sites from Australia and Sweden conducting similar surveys. RESULTS: Suicide attempts (0.4-4.2%), plans (1.1-15.6%), and ideation (2.6-25.4%) varied by a factor of 10-14 across sites, but remained mostly within the ranges of previously published data. Depending on the site, the ratios between attempts, plans, and thoughts of suicide differed substantially. Medical attention following a suicide attempt varied between 22% and 88% of the attempts. CONCLUSIONS: The idea of the suicidal process as a continuous and smooth evolution from thoughts to plans and attempts of suicide needs to be further investigated as it seems to be dependent on the cultural setting. There are indications, that the burden of undetected attempted suicide is high in different cultures; an improved response from the health sector on how to identify and support these individuals is needed.

Adult↗

Viruses and microRNAs.

The discovery of RNA interference and cellular microRNAs (miRNAs) has not only affected how biological research is conducted but also revealed an entirely new level of post-transcriptional gene regulation. Here, I discuss the potential functions of the virally encoded miRNAs recently identified in several pathogenic human viruses and propose that cellular miRNAs may have had a substantial effect on viral evolution and may continue to influence the in vivo tissue tropism of viruses. Our increasing knowledge of the role and importance of virally encoded miRNAs will probably offer new insights into how viruses that establish latent infections, such as herpesviruses, avoid elimination by the host innate or adaptive immune system. Research into viral miRNA function might also suggest new approaches for treating some virally induced diseases.

Animals↗

Biosynthetic Ca2+/Sr2+ exchange in the photosystem II oxygen-evolving enzyme of Thermosynechococcus elongatus.

The thermophilic cyanobacterium, Thermosynechococcus elongatus, has been grown in the presence of Sr2+ instead of Ca2+ with the aim of biosynthetically replacing the Ca2+ of the oxygen-evolving enzyme with Sr2+. Not only were the cells able to grow normally with Sr2+, they actively accumulated the ion to levels higher than those of Ca2+ in the normal cultures. A protocol was developed to purify a fully active Sr(2+)-containing photosystem II (PSII). The modified enzyme contained a normal polypeptide profile and 1 strontium/4 manganese, indicating that the normal enzyme contains 1 calcium/4 manganese. The Sr(2+)- and Ca(2+)-containing enzymes were compared using EPR spectroscopy, UV-visible absorption spectroscopy, and O2 polarography. The Ca2+/Sr2+ exchange resulted in the modification of the EPR spectrum of the manganese cluster and a slower turnover of the redox cycle (the so-called S-state cycle), resulting in diminished O2 evolution activity under continuous saturating light: all features reported previously by biochemical Ca2+/Sr2+ exchange in plant PSII. This allays doubts that these changes could be because of secondary effects induced by the biochemical treatments themselves. In addition, the Sr(2+)-containing PSII has other kinetics modifications: 1) it has an increased stability of the S3 redox state; 2) it shows an increase in the rate of electron donation from TyrD, the redox-active tyrosine of the D2 protein, to the oxygen-evolving complex in the S3-state forming S2; 3) the rate of oxidation of the S0-state to the S1-state by TyrD* is increased; and 4) the release of O2 is slowed down to an extent similar to that seen for the slowdown of the S3TyrZ* to S0TyrZ transition, consistent with the latter constituting the limiting step of the water oxidation mechanism in Sr(2+)-substituted enzyme as well as in the normal enzyme. The replacement of Ca2+ by Sr2+ appears to have multiple effects on kinetics properties of the enzyme that may be explained by S-state-dependent shifts in the redox properties of both the manganese complex and TyrZ as well as structural effects.

Calcium↗

Managed care under siege.

Managed Care Organizations (MCOs) are frequently criticized for their marketing mistakes. Often that criticism is leveled against an implicit benchmark of an ideal competitive market or an ideal system of government provision. But any accurate assessment in the choice of health care organizations always requires a comparative measure of error rates. These are high in the provision of health care, given the inherent uncertainties in both the cost and effectiveness of treatment. But the continuous and rapid evolution of private health care mechanisms is, in the absence of regulation, more likely to secure access and contain costs than any system of government regulation. State regulation is subject to the risk of capture and to the sluggish and acquisitive behavior of state run monopolies. The proposed fixes for the MCOs (rights to specialists, access to physicians outside the network, guaranteed emergency room access) are likely, when imposed from without, to cost more than they are worth. The long-term risk is that markets will fail under regulation, paving the way for greater losses from massive government control of the health care delivery system.

Benchmarking↗

Development of trauma care systems.

The modern-day history of trauma care system development encompasses a 45-year period. This report provides a timeline that highlights significant organizational and legislative initiatives that established the foundation of the current trauma system in the United States. The rationale for moving toward a public health approach in addressing trauma system development is explored and supported. Finally, the present-day issues confronting continued trauma system evolution and future opportunities are presented.

History, 20th Century↗

A test of the systems analysis underlying the scientific theory of Ayurveda's Tridosha.

A previous paper hypothesized that the tridosha of Ayurveda--vata, pitta, and kapha--constitute regulatory systems respectively controlling input/output, turnover, and storage; functions systems analysis identifies as fundamental to all open systems. This would make them universal properties of all living organisms, as Ayurveda itself maintains. This paper proposes independent scientific evidence for the proposed identification of the doshas and for the systems analysis on which it is based. In particular, it points to coenzyme A, a key component of fatty acid metabolism. Its universal presence in all cells implies that it is an evolutionary invariant ant that the biochemical pathway on which it lies must be exceptionally significant. The systems analysis shows that the pathway connects the cellular functions of energy turnover and energy storage, fundamental to the overall strategy of cell regulation. This, combined with the requirement for the pathway's close regulation, makes it effectively impossible to replace coenzyme A by a combination of simultaneous mutations or sequence of mutations and it should indeed remain invariant during evolution. The universality of coenzyme A is therefore consistent with its identified role, and supports the systems analysis identifying the doshas. Their systems functions survive developmental transformations of evolution with recognizable continuity. By virtue of that, vata, pitta, and kapha can be identified with them in all species.

Coenzyme A↗

Sleep research in affective illness: state of the art circa 1987.

Future sleep research in affective illness will probably continue the current evolution beyond cross-sectional to longitudinal studies, and beyond a largely descriptive emphasis to the testing of specific hypotheses and predictions derived from models of the pathophysiology of depression. These models are and will be variously neurochemical, chronobiological, genetic, and developmental in nature. Adequate testing of these models and predictions from them will require the use of pharmacologic and naturalistic probes and the use of sophisticated CNS imaging techniques. These probes will help further characterize the physiology of depression under conditions of disequilibrium or perturbation, such as following sleep deprivation, REM deprivation, phase advancement of the major sleep period, or the administration of antidepressant drugs with specific monoaminergic activity. Concurrently, if one is to understand further whether the sleep abnormalities of depression are part of a larger circadian rhythm disturbance, investigations will necessarily include 24-h measures of sleep-wake activity, psychomotor activity, and probably core body temperature rhythm under constant routine conditions. A complementary point of view would suggest that more intensive investigative efforts be focused on the first 100 min of sleep at night, since it is the first NREM-REM cycle that seems to show the greatest and most specific deviation in depressed patients from normal controls. Efforts to characterize further this part of the 24-h cycle, with respect to age- and gender-related variance as well as responses to physiologic, hormonal, pharmacologic, and naturalistic probes, are strongly warranted.

Aging↗