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PubMed1984

Peptidergic pathways in the avian brain.

The results obtained by topographical studies on the immunoreactive peptide systems in the embryonic and adult avian brain (domestic fowl, domestic mallard, pigeon, Japanese quail, and zebra finch) can be realized only by means of phylogenetical comparisons. The comparative studies mainly demonstrate a fascinating constancy of the immunological properties and the spatial distribution of the neuropeptides. Independent of the development of the neopallium, and the increasing cerebral complexity, the spatial distribution of the neuropeptides, the location of their main perikaryal accumulations which are interconnected by immunoreactive fiber projections (and thereby forming widespread but continuous peptide systems) remain nearly unchanged during vertebrate evolution. The recognition of the neuropeptides as integral parts of the central nervous system is demonstrated by the fact that neuropeptidergic structures connect sensory inputs with central nervous areas as well as with the peripheral endocrinium.

Animals↗

PubMed1999

Arms Races, Conflict Costs and Evolutionary Dynamics.

In conflicts and fights, the winner is often determined by the difference in resource-holding potential, e.g. size, weaponry, strength (RHP). I model the evolution of RHP in a symmetric game with continuous strategies. I show that there is a convergence stable ESS level of RHP if the cost of the trait increases faster than linearly, and that this is the only solution if the cost increases fast enough with RHP. Otherwise with slowly increasing cost, the solution is a cyclically fluctuating level of RHP. It is also shown that if the cost increases linearly with RHP, the only solution to the game is neutrally stable cycles, the amplitude determined by the initial conditions. The cycles come about because in a population drawn into an arms race of RHP, individuals after a while suffer costs so high that mutants with the lowest possible armament level may invade. Copyright 1999 Academic Press.

Journal Article↗

PubMed1996

Human immunodeficiency virus replication in the presence of antiretroviral drugs: analogies to antineoplastic drug resistance.

There are many analogies between antineoplastic therapy and antiviral therapy. For each there may be sanctuary sites in which the drug is ineffective because of decreased accumulation of the active form of the drug or increased competition by naturally occurring inhibitors. These sanctuaries may be restricted to anatomic or biochemical subsets of the population. A knowledge of these sanctuaries is essential to an understanding of the failure of therapy and for the design of more effective treatments. Eradication of these sanctuary sites may be important because they may be responsible for the viral replication or tumor cell division that continues to generate the diversity that drives clonal evolution. Ultimately, diversity as a consequence of the accumulation of mutations results in the selection of resistant viral or tumor cell variants and the failure of drug therapy. Maximizing therapy in an attempt to diminish the rate of generation of this diversity may result in better clinical outcomes, including a delay in the generation of variants with genetic drug resistance.

Antineoplastic Agents↗

PubMed1994

Highly repetitive structure and its organization of the silk fibroin gene.

We have sequenced a number of cDNAs representing the Bombyx mori silk fibroin heavy chain transcript. These reveal that the central region of the fibroin gene is composed of alternate arrays of the crystalline element a and the noncrystalline element b. The core region is partitioned by a homogeneous nonrepetitive amorphous domain of around 100 bp in length. The element a is characterized by repeats of a highly conserved 18-bp sequence coding for perfect repeats of the unit peptide Gly-Ala-Gly-Ala-Gly-Ser. The element b is composed of repeats of a less-conserved 30-bp sequence which codes for a peptide similar to that in element a except in that (1) Ser is replaced by Tyr and (2) there are irregular substitutions of Ala to Val or Tyr. Therefore, the structure of the fibroin gene core consists of three-step higher-order periodicities. Heterogeneities in numbers of repeats are observed in each step of periodicity. Boundary sequence appeared in each periodicity to be quite homogeneous. Sequence analysis indicates that the unit sequences of elements a and b have homology to those of recombination hotspots reported in other genes and a recombination event may frequently occur between the misaligned sister chromatids, resulting in heterogeneities in repeat numbers and duplication or deletion of repetitive sequences. The repetitive superstructure of the fibroin gene may have been a result of continuous unequal crossovers in a primordial gene during evolution. A couple of important features of the fibroin protein were proved by the present nucleotide sequencing.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMedDate not supplied

A health-promotion perspective of urinary continence.

The purposes of this article are to discuss continence in older adults from a public health perspective, to expand a previously reported conceptual model of continence health promotion, and to provide a primary prevention focus to nursing research efforts regarding continence. The conceptual model shows that there has been a strong interest in secondary and tertiary prevention strategies, but little interest in primary prevention. Use of the matrix allows the nurse researcher identify primary, secondary, or tertiary prevention research questions and the target population for study. Historically, nurses have had a central role in the care and management of incontinent people. Nurses will continue to play a critical role in the evolution of research-based practice that includes identification of risks, health promotion, and preventive nursing strategies.

Aged↗

PubMed1994

Autonomic responses correlate to motor anticipation.

New findings have stated that autonomic nervous system (ANS) functioning may reflect some cognitive processes observed in real time analysis. Four ANS variables plus instantaneous heart rate and respiratory frequency were quantified by original techniques and indices on 11 subjects during a coincidence-anticipation task, performed on a computer screen under six different, randomly-presented modalities (3 modalities describing the spot moving along a parabola at 2 speeds). Tonic levels and phasic responses corresponding to each trial were recorded continuously. Results showed that skin resistance tonic level evolution gave evidence of vigilance changes. Thus, performance can be related to subjects' vigilance. An autonomic response was always observed during performance of an anticipation task. The six task modalities were distinguished by performance values. Simultaneously recorded ANS responses fully differentiated these same modalities for 10 subjects out of 11. These ANS responses were furthermore related to performance. Ten subjects out of 11 possess at least one Autonomic variable which can differentiate the six task modalities, confirming Lacey's hypothesis on ANS preferential response, and suggesting ANS specificity. ANS functioning may reveal some brain functions through a specific autonomic channel, characterizing each subject. The behavioral output of an individual may thus be reflected by such a functioning.

Adolescent↗

PubMed1989

Epidemiology and mechanisms of antimicrobial resistance.

Bacterial evolution and the emergence of antimicrobial drug resistance continue to interfere with the successful treatment of infections by both community- and hospital-based physicians. Resistance has emerged to even the newer, most potent antimicrobial agents. Although generalizations can be made about the appropriateness of antimicrobial agents on the basis of published susceptibility patterns, significant regional, demographic, and interinstitutional variables exist that require each hospital to establish its own antibiotic data base and antibiogram. In particular, multiresistant pathogens occur infrequently in acute care community hospitals compared with tertiary care centers. Important clinical factors that promote the emergence of drug-resistant flora include prolonged therapy, the persistence of foreign bodies, sequestra, or prostheses, and the inadequate surgical debridement of necrotic tissue or abscesses. Antibiotic resistance may occur through changes in the permeability of the cell wall or outer membrane, by alteration of the antimicrobial binding or target site, and by inactivation or modification of the drug by bacterial enzymes. These mechanisms are reviewed. In particular, gram-negative beta-lactamases, methicillin-resistant staphylococci, multiresistant enterococci, and the emergence of fluoroquinolone resistance are discussed in detail.

Anti-Bacterial Agents↗

PubMed1987

Bridging the gap: the village health worker as the cornerstone of the primary health care model.

The Alma-Ata Conference in 1978 reiterated the goal of 'Health for All by the Year 2000' and declared primary health care (PHC) the vehicle through which this lofty goal was to be achieved. National governments were recognized as responsible agents for developing and implementing PHC plans. The emphasis on community-oriented delivery of care places great importance on the village health worker (VHW), the individual who serves as the 'interface' between the formal health care system and the community. Despite the acknowledged importance of the VHW role, the question of whether the PHC model, with the VHW as the cornerstone can be effectively implemented without a "fundamental shift of wealth and power" (Sidel) continues to be asked. This paper examines the evolution and current status of the VHW role in Costa Rica, Nicaragua and Columbia, three Latin American nations which have adopted the PHC model. The authors discuss the evolution of the PHC model in each country with particular reference to the occurrence or non-occurrence of fundamental changes in the society. The conclude that the primary determiner of successful implementation of PHC is a national commitment to PHC including recognition of the importance of community participation which is best achieved through reliance on the village health worker.

Colombia↗

PubMed1996

A practical guide to assessment of ventricular diastolic function using Doppler echocardiography.

Doppler assessment of diastolic function has become a standard part of routine echocardiographic examination and imparts information relevant to a patient's functional class, management and prognosis. This review describes the Doppler patterns of diastolic function relative to physical signs and physiology. A continuum of doppler patterns of diastolic function exists, including normal diastolic function, impaired relaxation, pseudonormal filling, restriction, constriction and tamponade. These patterns evolve from one to another in a single individual, with changes in disease evolution, treatment and loading conditions. New applications of continuous wave Doppler, color Doppler M-mode and Doppler tissue imaging are refining our understanding of diastolic function.

Diastole↗

PubMed2006

Thymus-homing precursors and the thymic microenvironment.

T cells develop in the thymus from precursors that are generated in the bone marrow and continuously seed the thymus through the blood. During evolution, 'outsourcing' the development of one blood lineage, namely the T-cell lineage, to an anatomically distinct hematopoietic organ required the generation of migratory precursors in the bone marrow, their homing to specialized, precursor-retaining thymic niches and their subsequent differentiation. Niche building and precursor homing are therefore intricately linked and should be viewed in context. In this review, we discuss recent findings on the developmental and genetic events that prepare the thymic epithelial microenvironment for its complex tasks, and highlight recent progress in the definition of the thymus-settling cells and the homing process that leads them into the thymus.

Animals↗

PubMed2026

Long-term clinical and genomic surveillance of rare respiratory enterovirus C types in France, 2013-2025.

INTRODUCTION: Rare enterovirus types assigned to species C (EV-C) display respiratory tropism and may be associated with neurological involvement, which display similarities to EV-D68 disease. PATIENTS AND METHODS: We conducted continuous enterovirus/rhinovirus (EV/RV) surveillance between 2013 and 2025, including systematic EV/RV screening of all respiratory samples and reflex VP4/VP2 sequencing (a total of 5855 samples). When an EV-C strain was detected, the VP1-coding and complete genome sequence was sequenced to investigate phylogenetic relationships and to identify any recombinant forms. RESULTS: Over the 13-year period, 30 EV-C infections were identified from respiratory samples, with 23 cases (77%) detected between 2013 and 2018. EV-C105 was the most frequent type (n = 11), followed by EV-C104 (n = 8), EV-C109 (n = 6), and EV-C117 (n = 5). We also document the first detection of EV-C117 in France and only the second case reported in Europe since its initial description in 2011 in Lithuania. Clinical data were available for 25 patients, of whom 19 (76%) were children. Respiratory symptoms predominated (17/25, 68%), and 7 patients presented with lower respiratory tract infections. Hospitalization was required in 18 cases (72%), including three with ICU admissions (12%). Nearly half of the patients (12/25, 48%) had at least one risk factor for severe respiratory disease. Across all respiratory EV-C types, recovered sequences clustered with contemporary global strains. CONCLUSIONS: This long-term surveillance highlights the sustained circulation of multiple respiratory EV-C types in France and underscores the need for continued clinical and genomic monitoring to assess the evolution and pathogenic potential of these enteroviruses.

Complete genome characterization↗

PubMed1985

Stability of atrial sensing and pacing after dual chamber pulse generator implantation.

The continued efficacy of dual chamber pacing is predicated on the stability of both atrial and ventricular electrodes. The introduction of the tined atrial J lead has decreased the incidence of atrial lead dislodgment, allowing for continued effective sensing and pacing. To study the evolution of atrial pacing and sensing threshold, 54 patients with identical pulse generators and atrial electrodes were evaluated for 58 +/- 29 weeks (mean +/- SD). Immediately after pacemaker implantation in 39 patients, the amplitude of the atrial signal was measured by programming the pulse generator to the lowest sensitivity that assured pacing in the atrial synchronous mode. Three levels of atrial sensing were possible: high (0.5 mV), intermediate (1.3 mV) and low (2.5 mV) sensitivity. Three patients had a high, 16 patients had a medium and 20 patients had a low atrial sensitivity. The P wave amplitude and slew rate measured on a physiologic recorder did not differ significantly between the latter two groups. The atrial charge threshold increased from 1.8 +/- 1.3 microcoulombs (microC) to a maximal value of 2.5 +/- 1.3 microC, 3 days to 1 week after implantation (p = 0.02). This remained elevated for 1 to 3 months (p = 0.05) and then decreased, remaining stable over the ensuing year. The atrial sensitivity for the group with noninvasive measurement did not change significantly, although there was considerable patient variation. For 54% of the patients, atrial sensing remained stable or improved. In 26% of the patients, further programming to higher sensitivity settings ws required. In the remaining 20% of the patients, the atrial sensitivity setting fluctuated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2005

Reconstitution of a defunct glycolytic pathway via recruitment of ambiguous sugar kinases.

During a recent investigation of the persistence of substrate ambiguity in contemporary enzymes, we identified three distinct ambiguous sugar kinases embedded within the modern Escherichia coli genome [Miller, B. G., and Raines, R. T. (2004) Biochemistry 43, 6387-6392]. These catalysts are the YajF, YcfX, and NanK polypeptides, all of which possess rudimentary glucokinase activities. Here, we report on the discovery of a fourth bacterial kinase with ambiguous substrate specificity. AlsK phosphorylates the glucose epimer, d-allose, with a k(cat)/K(m) value of 6.5 x 10(4) M(-)(1) s(-)(1). AlsK also phosphorylates d-glucose, with a k(cat)/K(m) value that is 10(5)-fold lower than the k(cat)/K(m) value displayed by native E. coli glucokinase. Overexpression of the alsK gene relieves the auxotrophy of a glucokinase-deficient bacterium, demonstrating that weak enzymatic activities derived from ambiguous catalysts can provide organisms with elaborated metabolic capacities. To explore how ambiguous catalysts are recruited to provide new functions, we placed the glucokinase-deficient bacterium under selection for growth at the expense of glucose. Under these conditions, the bacterium acquires a spontaneous mutation in the putative promoter region of the yajF gene, a locus previously shown to encode a sugar kinase with relaxed substrate specificity. The point mutation regenerates a consensus sigma(70) promoter sequence that leads to a 94-fold increase in the level of yajF expression. This increase provides sufficient glucokinase activity for reconstitution of the defunct glycolytic pathway of the bacterial auxotroph. Our current findings indicate that ambiguous enzymatic activities continue to play an important role in the evolution of new metabolic pathways, and provide insight into the molecular mechanisms that facilitate the recruitment of such catalysts during periods of natural selection.

Adaptation, Physiological↗

PubMed2002

Statistical techniques for the analysis of change in longitudinal studies of the menopause.

OBJECTIVE: Critical review of statistical techniques used to analyze data from longitudinal studies. METHOD: Literature search and classification of statistical methods and their utilization evaluated against known underlying assumptions. RESULTS: One hundred and twenty-three papers found: 1. cross-sectional reduction of data (56%); 2. multifactorial techniques (26%); 3. repeated measurement analysis of variance (14%); 4. other (time series and structural equation modelling) (4%). CONCLUSIONS: Cross-sectional reduction violates underlying statistical assumptions. A simple and powerful technique is to mean values prior to and following an event such as the final menstrual period. To allow for the influence of multiple factors, linear regression is preferred to logistic regression where continuous data are available. For more information about evolution in time, more complex techniques are needed. A suitable technique is repeated measurement multivariate analysis of variance using a number of contrasts to estimate various effects. Split plot or randomized block designs cannot be recommended as they violate compound symmetry assumptions. For series involving more than 100 observations for each subject, time series and spectral analysis techniques should be considered. Structural equation modelling is recommended for examination in detail of a range of factors that may influence the studied end-point, the presence of feedback and of latent or non-measurable variables.

Adult↗

PubMed1989

Effect of sulphate on glutamate synthesis by intact spinach (Spinacia oleracea) chloroplasts.

During the course of NH4+ (or NO2-)-plus-alpha-oxoglutarate-dependent O2 evolution in spinach (Spinacia oleracea) chloroplasts, glutamate was continuously excreted out of the chloroplasts. Under these conditions, for each molecule of NO2- or NH4+ which disappeared, one molecule of glutamate accumulated in the medium and the concentration of glutamate in the stroma space was maintained constant. SO4(2-) (or SO3(2-) behave as inhibitors of NH4+ incorporation into glutamate by intact chloroplasts. This considerable inhibition of glutamate synthesis by SO4(2-) was correlated with a rapid decline in the stromal Pi concentration. The reloading of stromal Pi with either external Pi or PPi4- relieved SO4(2-)-induced inhibition of glutamate synthesis by intact chloroplasts. It was concluded that SO4(2-) induced a rapid efflux of stromal Pi out of the chloroplast, leading to a limitation of ATP synthesis and therefore to an arrest of ATP-dependent glutamine synthetase functioning.

Brassica↗

PubMed2006

Extensive individual variation in L1 retrotransposition capability contributes to human genetic diversity.

Despite being scarce in the human genome, active L1 retrotransposons continue to play a significant role in its evolution. Because of their recent expansion, many L1s are not fixed in humans, and, when present, their mobilization potential can vary among individuals. Previously, we showed that the great majority of retrotransposition events in humans are caused by highly active, or hot, L1s. Here, in four populations of diverse geographic origins (160 haploid genomes), we investigated the degree of sequence polymorphism of three hot L1s and the extent of individual variation in mobilization capability of their allelic variants. For each locus, we found one previously uncharacterized allele in every three to five genomes, including some with nonsense and insertion/deletion mutations. Single or multiple nucleotide substitutions drastically affected the retrotransposition efficiency of some alleles. One-third of elements were no longer hot, and these so-called cool alleles substantially increased the range of individual susceptibility to retrotransposition events. Adding the activity of the three elements in each individual resulted in a surprising degree of variation in mobilization capability, ranging from 0% to 390% of a reference L1. These data suggest that individual variation in retrotransposition potential makes an important contribution to human genetic diversity.

Alleles↗

PubMed2002

Nimesulide-induced severe hemolytic anemia and acute liver failure leading to liver transplantation.

We present the case of a 63-year-old woman who had undergone 7 months of treatment with Nimesulide (100 mg/b.i.d.) for symptomatic osteoarthritis. The patient was admitted to our unit with a clinical picture of progressive jaundice over 3 weeks. Clinical and analytical studies revealed acute liver failure, this being confirmed by liver biopsy, which showed submassive necrosis. Serological tests for different viral agents causing hepatitis were all negative. In addition, she presented a picture of severe haemolytic anaemia resistant to several treatments and needed multiple transfusions. Twenty-three days after admission, the patient presented hepatic encephalopathy and received an orthotopic liver transplant on day 25. The evolution after transplantation was good and the patient continues in good health with no evidence of haemolysis almost 2 years later. Liver toxicity due to Nimesulide is well known, but to our knowledge the occurrence of haemolytic anaemia has not been related to this drug previously. For these reasons, Nimesulide has been restricted or removed from the market in several countries in recent months.

Anemia, Hemolytic↗

PubMed2006

Ion regulation in invertebrates: molecular and integrative aspects.

The subject of ion regulation in invertebrates is discussed, using a variety of invertebrate model species and approaches that range from the whole-organism level to tissue, subcellular, and molecular levels to illustrate the future direction of the field. These organisms inhabit a variety of aquatic, freshwater, and terrestrial environments, showing specific adaptations to each environment. This overview discusses mechanisms of metal detoxification and the presence of Cl-ATPase in marine organisms to avoid excess intracellular Cl(-); Ca(2+) regulation and endocrine aspects of adaptations to transitional (semiterrestrial) environments; adaptations to Ca(2+)-poor freshwater, particularly the reabsorption of Ca(2+) through specific transporters found in the urine; and finally, ionoregulatory mechanisms for life on land, such as Ca(2+) conservation during molting in isopods and the presence of K(+) channels in insect Malpighian tubules. Convergent mechanisms for dealing with similar problems in dissimilar habitats are discussed, taking into consideration that invertebrates will continue to serve as model systems for the evolution of ionoregulation in different habitats.

Adaptation, Physiological↗