HBs antigen in the blood donors of Calvados. Epidemiologic study and surveillance of the patients

175 Chronic HBs Ag carriers have been discovered in the blood donors of the Calvados blood transfusion center from 1971 to 1979. 72 of them (41%) gave their consent for a clinical and biological study at the end of 1979, after receiving a convocation letter. This work had two aims: - to study the epidemiological factors in this population. - to evaluate the clinical and biological consequences of persistent antigenemia. 1. Epidemiological Study. Most results agree with the literature (higher prevalence in male, age, stay in endemic countries) but some results disagree for several reasons: our donors are all volunteers, HBs Ag prevalence is low in our region, most of the patients are caucasian and with life conditions and habits which may explain some particularities in contagion. Furthermore, the relative number of blood donors found every year as chronic HBs Ag carriers, does not increase in our country. 2. The Clinical and Biological follow-up of 62 HBs Ag carriers (alcoholics excluded) was carried out for 4,3 years on average. No patients developed clinical and biological features of chronic liver disease. After a mean term follow-up, we conclude that the asymptomatic HBs Ag carriers state seems not to be of bad prognostic. Since long term complications cannot be excluded, the follow-up of these patients must be maintained.     

Causal Regularities in the Biological World of Contingent Distributions

Former discussions of biological generalizations have focused on the question of whether there are universal laws of biology. These discussions typically analyzed generalizations out of their investigative and explanatory contexts and concluded that whatever biological generalizations are, they are not universal laws. The aim of this paper is to explain what biological generalizations are by shifting attention towards the contexts in which they are drawn. I argue that within the context of any particular biological explanation or investigation, biologists employ two types of generations. One type identifies causal regularities exhibited by particular kinds of biological entities. The other type identifies how these entities are distributed in the biological world.     

Non-linear and parametric resonance in the organs of hearing and sight in man

Nonharmonic and parametric resonance in man's hearing and sight organs are considered. For the first time for combination tones omega 2-omega 1 and 2 omega 1-omega 2 arising in hearing organs under low intensities of an acoustic signal the parametric equations are suggested to explain the properties of these tones. On the basis of the experimental data of the nonharmonic sight the scheme of cis-trans-isomerization of the chromophore group (retinal) of visual pigments under simultaneous absorption of two infrared photons is suggested. Possible appearance of nonharmonic resonances in other biological systems is analysed.     

The cladistic solution to the species problem

The correct explanation of why species, in evolutionary theory, are individuals and not classes is the cladistic species concept. The cladistic species concept defines species as the group of organisms between two speciation events, or between one speciation event and one extinction event, or (for living species) that are descended from a speciation event. It is a theoretical concept, and therefore has the virtue of distinguishing clearly the theoretical nature of species from the practical criteria by which species may be recognized at any one time. Ecological or biological (reproductive) criteria may help in the practical recognition of species. Ecological and biological species concepts are also needed to explain why cladistic species exist as distinct lineages, and to explain what exactly takes place during a speciation event. The ecological and biological species concepts work only as sub-theories of the cladistic species concept and if taken by themselves independently of cladism they are liable to blunder. The biological species concept neither provides a better explanation of species indivudualism than the ecological species concept, nor, taken by itself, can the biological species concept even be reconciled with species individualism. Taking the individuality of species seriously requires subordinating the biological, to the cladistic, species concept.     

Biological oscillators can be stopped—Topological study of a phase response curve

Many biological oscillators are stable against noise and perturbation (e.g. circadian rhythms, biochemical oscillators, pacemaker neurons, bursting neurons and neural networks with periodic outputs). The experiment of phase shifts resulting from discrete perturbation of stable biological rhythms was developed by Perkel and coworkers (Perkel et al., 1964). By these methods, they could get important insights into the entrainment behaviors of biological rhythms. Phase response curves, which are measured in these experiments, can be classified into two types. The one is the curve with one mapping degree (Type 1), and the other is that with zero mapping degree (Type 0) (Winfree, 1970). We define the phase response curve mathematically, and explain the difference between these two types by the homotopy theory. Moreover, we prove that, if a Type 0 curve is obtained at a certain magnitude of perturbation, there exists at least one lower magnitude for which the phase response curve cannot be measured. Some applications of these theoretical results are presented.     

A simple model can unify a broad range of phenomena in retinotectal map development

A paradigm model system for studying the development of patterned connections in the nervous system is the topographic map formed by retinal axons in the optic tectum/superior colliculus. Starting in the 1970s, a series of computational models have been proposed to explain map development in both normal conditions, and perturbed conditions where the retina and/or tectum/superior colliculus are altered. This stands in contrast to more recent models that have often been simpler than older ones, and tend to address more limited data sets, but include more recent genetic manipulations. The original exploration of many of the early models was one-dimensional and limited by the computational resources of the time. This leaves open the ability of these early models to explain both map development in two dimensions, and the genetic manipulation data that have only appeared more recently. In this article, we show that a two-dimensional and updated version of the XBAM model (eXtended Branch Arrow Model), first proposed in 1982, reproduces a range of surgical map manipulations not yet demonstrated by more modern models. A systematic exploration of the parameter space of this model in two dimensions also reveals richer behavior than that apparent from the original one-dimensional versions. Furthermore, we show that including a specific type of axon?Caxon interaction can account for the map collapse recently observed when particular receptor levels are genetically manipulated in a subset of retinal ganglion cells. Together these results demonstrate that balancing multiple influences on map development seems to be necessary to explain many biological phenomena in retinotectal map formation, and suggest important constraints on the underlying biological variables.     

Ambulatory blood pressure monitoring: assessing the diurnal variation of blood pressure

The purposes of this paper are to examine the effects of activity, situation of measurement, mood, and occupation on the daily variation of blood pressure and to discuss the potential utility of ambulatory blood pressure monitoring in physical anthropological studies. The subjects of the blood pressure variability study are 125 men who were referred to the Hypertension Center at New York Hospital--Cornell Medical Center for evaluation of hypertension. There were 1,386 blood pressure measurements from these subjects available for study, which were taken using noninvasive ambulatory blood pressure monitoring techniques. Pressures were transformed to z scores using the subject's daily mean pressure and standard deviation to assess the relative elevation during the experience of the various factors. The results show that activity and mood are the most significant sources of blood pressure variation (P less than .005) and are additive. Occupation, which may be an indicator of social class in this population, also modified the mood effects. Because ambulatory blood pressure monitors obtain many readings over a day under a variety of circumstances, their use can improve epidemiological and human biological studies of the inheritance and variability of blood pressure. Ambulatory blood pressure monitoring is an important new tool in the study of human biological variation.     

Predicting Biological Invasions

There are various approaches to explain the mechanisms of biological invasions. It is possible (1) to focus on the characteristics of invading species and (2) on those of the ecosystems invaded, (3) to investigate the relationship between these two factors (key–lock approach), or (4) to differentiate the invasion process in time. Each of these approaches may serve to improve the understanding of some aspects of biological invasions, and each of them is in some way suitable for the purpose of predicting invasions. We discuss the usefulness and the limitations of these approaches, focusing on case studies from central Europe. An example of the fourth approach, a model of steps and stages of plant invasions that describes the invasion process in greater detail, illustrates some general limitations in predicting biological invasions. This revised version was published online in July 2006 with corrections to the Cover Date.     

Duffy blood group and hemoglobin variants

Summary Data on a sample of 809 Afro-Americans indicated that there is no association between Duffy null (a^-, b^-) blood type and sickle cell trait. The results further rule out close linkage as an alternative hypothesis to explain the reported association between these loci in areas where falciparum and vivax malaria are endemic and indicate that, even if the two loci are independent or loosely linked, direct evidence of the selection favoring AS Fy^-Fy^- individuals must come from populations where mixed malaria infections occur. Stratification, as an explanation for the reported association, is also discussed.     

A phylogenetic and geotectonic scenario to explain the biogeography of the Lophopidae (Hemiptera, Fulgoromorpha)

The Lophopidae are found in South America, Africa, Australia, India and Southeast Asia. This distribution appears to be typically Gondwanan, triggered by tectonic events beginning over 100 Ma. However, within the Fulgoromorpha, the lophopids are considered to be relatively recently. In this study, biological, geological and phylogenetic information is evaluated to provide a parsimonious explanation for the distribution of the group and its geographic region of ancestral origin. The Lophopidae can be divided into four monophyletic groups. The ancestors of two groups appear to have originated somewhere along the western Pacific island arc system. Another group appears to have an origin in Southeast Asia. A reliable explanation for the ancestral origin of the fourth group was not possible because it consists of only one genus present in Central and South America. A biogeographic map of the two groups of lophids of the western Pacific island arc is concordant with their phylogeny based on biological and morphological data. Based on this finding, the best explanation for the origin and evolution of the Lophopidae and their current distribution of these lophopids is through vicariance. Similar types of eco-evolutionary events explain radiation and distribution of the Lophopidae, in general.     

Flagellar filaments of the deep-sea bacteria Idiomarina loihiensis belong to a family different from those of Salmonella typhimurium

The helical filaments of the bacterial flagella so far studied seem to be universal in the bacterial kingdom. Despite the variation in flagellin molecular masses, which range from 24 kDa to 62 kDa in different species, there are only two forms: either the so-called Normal (left-handed) or the Curly (right-handed). The Normal and Curly helical forms are asymmetric; the two characteristic helical parameters, which are the pitch and diameter, of Normal filaments are twice those of Curly filaments. Both the universality of these two helical forms and their asymmetry are biological puzzles. We found that the marine bacteria Idiomarina loihiensis have flagella with left-handed Curly-like filaments. Analysis of the polymorphic forms under different pH conditions showed that the Curly-like filaments are actually Normal filaments having a smaller pitch and diameter than those of Salmonella typhimurium. A minor modification of Calladine's model for a filament lattice can explain the variant helical forms. Pseudomonas aeruginosa filaments also belong to the family of I.loihiensis filaments. Thus, there are at least two families of flagella filaments.     

Loosening of the phage structure in a low ionic strength environment

Structural parameters of phage T7 were compared in two frequently use Tris buffers of high and low ionic strength, in order to explain the different biological activity and drug-binding characteristics.Characteristics of the whole phage geometry were obtained by viscosimetry, static and quasi-elastic light-scattering and small-angle X-ray scattering. The latter method revealed dissimilarities in the intraphage DNA compactness, consistent with the findings of the optical absorption melting studies.Alterations in the particle dimensions determined in the same sample by different methods are discussed, and a model is constructed to explain the structural modifications that occur on lowering the ionic strength.     

Review: the potential impact of surface crystalline states of titanium for biomedical applications

In many biomedical applications, titanium forms an interface with tissues, which is crucial to ensure its long-term stability and safety. In order to exert control over this process, titanium implants have been treated with various methods that induce physicochemical changes at nano and microscales. In the past 20?years, most of the studies have been conducted to see the effect of topographical and physicochemical changes of titanium surface after surface treatments on cells behavior and bacteria adhesion. In this review, we will first briefly present some of these surface treatments either chemical or physical and we explain the biological responses to titanium with a specific focus on adverse immune reactions. More recently, a new trend has emerged in titanium surface science with a focus on the crystalline phase of titanium dioxide and the associated biological responses. In these recent studies, rutile and anatase are the major two polymorphs used for biomedical applications. In the second part of this review, we consider this emerging topic of the control of the crystalline phase of titanium and discuss its potential biological impacts. More in-depth analysis of treatment-related surface crystalline changes can significantly improve the control over titanium/host tissue interface and can result in considerable decreases in implant-related complications, which is currently a big burden on the healthcare system.     

Biochemical and molecular modeling analysis of the ability of two p-aminobenzamidine-based sorbents to selectively purify serine proteases (fibrinogenases) from snake venoms

Snake venoms contain several trypsin-like enzymes with equivalent physicochemical characteristics and similar inhibition profiles. These are rather difficult to separate by classical purification procedures and therefore constitute a good model for affinity chromatography analysis. Some of these trypsin homologues present fibrinogenase activity, mimicking one or more features of the central mammalian coagulation enzyme, thrombin. It was previously demonstrated that a number of amidine derivatives are able to interact specifically with some of these serine proteases. To understand the enzyme-sorbent interactions we have investigated the ability of two commercially available benzamidine affinity matrices to purify thrombin-like serine proteases (TLSP) with similar biological properties from two snake venoms (Bothrops jararacussu and Lachesis muta rhombeata). Curiously, each sorbent retained a single but distinct TLSP from each venom with high yield. Molecular modeling analysis suggested that hydrophobic interactions within a specific region on the surface of these enzymes could be generated to explain this exquisite specificity. In addition, it was demonstrated that a specific tandem alignment of the two benzamidine sorbents enables the purification of three other enzymes from B. jararacussu venom.     

Mining the Human Phenome Using Allelic Scores That Index Biological Intermediates

It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach''s properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.     

How the spleen reshapes and retains young and old red blood cells: A computational investigation

The spleen, the largest secondary lymphoid organ in humans, not only fulfils a broad range of immune functions, but also plays an important role in red blood cell’s (RBC) life cycle. Although much progress has been made to elucidate the critical biological processes involved in the maturation of young RBCs (reticulocytes) as well as removal of senescent RBCs in the spleen, the underlying mechanisms driving these processes are still obscure. Herein, we perform a computational study to simulate the passage of RBCs through interendothelial slits (IES) in the spleen at different stages of their lifespan and investigate the role of the spleen in facilitating the maturation of reticulocytes and in clearing the senescent RBCs. Our simulations reveal that at the beginning of the RBC life cycle, intracellular non-deformable particles in reticulocytes can be biomechanically expelled from the cell upon passage through IES, an insightful explanation of why this peculiar “pitting” process is spleen-specific. Our results also show that immature RBCs shed surface area by releasing vesicles after crossing IES and progressively acquire the biconcave shape of mature RBCs. These findings likely explain why RBCs from splenectomized patients are significantly larger than those from nonsplenectomized subjects. Finally, we show that at the end of their life span, senescent RBCs are not only retained by IES due to reduced deformability but also become susceptible to mechanical lysis under shear stress. This finding supports the recent hypothesis that transformation into a hemolyzed ghost is a prerequisite for phagocytosis of senescent RBCs. Altogether, our computational investigation illustrates critical biological processes in the spleen that cannot be observed in vivo or in vitro and offer insights into the role of the spleen in the RBC physiology.     

The influence of basal metabolic rate on blood pressure among indigenous Siberians

Hypertension is an important global health issue and is currently increasing at a rapid pace in most industrializing nations. Although a number of risk factors have been linked with the development of hypertension, including obesity, high dietary sodium, and chronic psychosocial stress, these factors cannot fully explain the variation in blood pressure and hypertension rates that occurs within and between populations. The present study uses data collected on adults from three indigenous Siberian populations (Evenki, Buryat, and Yakut [Sakha]) to test the hypothesis of Luke et al. (Hypertension 43 (2004) 555-560) that basal metabolic rate (BMR) and blood pressure are positively associated independent of body size. When adjusted for body size and composition, as well as potentially confounding variables such as age, smoking status, ethnicity, and degree of urbanization, BMR was positively correlated with systolic blood pressure (SBP; P < 0.01) and pulse pressure (PP; P < 0.01); BMR showed a trend with diastolic blood pressure (DBP; P = 0.08). Thus, higher BMR is associated with higher SBP and PP; this is opposite the well-documented inverse relationship between physical activity and blood pressure. If the influence of BMR on blood pressure is confirmed, the systematically elevated BMRs of indigenous Siberians may help explain the relatively high blood pressures and hypertension rates documented among native Siberians in the post-Soviet period. These findings underscore the importance of considering the influence of biological adaptation to regional environmental conditions in structuring health changes associated with economic development and lifestyle change.     

2,4-diamino-7-hydroxy-pteridines, a new class of catabolites of methotrexate

Methotrexate remains a commonly used drug in the chemotherapy of various malignancies. The known catabolites are 7-hydroxy-methotrexate, formed in the liver, and diamino-methyl-pteroic acid formed in the gut. We report for the first time evidence that 2,4-diamino-7-hydroxy-pteridine derivatives are present in the biological fluids of patients on high-dose methotrexate protocols. So far, two major derivatives have been identified as 2,4-diamino-6-hydroxymethyl-7-hydroxy-pteridine and 2,4-diamino-6-methyl-7-hydroxy-pteridine. In regard to the actual knowledge of the catabolism of pteridines, these compounds are presumably formed by intestinal bacteria during enterohepatic circulation of the drug. Their slow clearance from the body raises the question of possible interference of these compounds on pteridine-dependent enzymes, which might explain in part some of the toxic effects of methotrexate.     

Pentaschistis (Poaceae) diversity in the Cape mediterranean region: habitat heterogeneity and climate stability

Aim To evaluate the role of habitat heterogeneity on species richness and turnover in the mega species‐rich Cape Floristic Region (Cape), the mediterranean region of southern Africa. Location The Cape and Drakensberg regions of southern Africa. Methods Bioclimatic data were used to estimate habitat amount and habitat heterogeneity in the Cape and Drakensberg regions; these data were then used to explain the patterns of species diversity in the Pentaschistis clade (Poaceae) in these two regions. Habitat variables were used to create ‘bioclimatic units’ to characterize 1′× 1′ cells in southern Africa and to describe the niches of species. Using these bioclimatic units, the niche and range sizes of species in the two regions were compared. A phylogram was used to test for age and lineage effects. Results Pentaschistis species diversity and turnover are higher in the Cape than the Drakensberg. There is no significant difference in the habitat amount and heterogeneity between the two regions. Species occupy the same range of estimated niche sizes, yet there are significantly more range‐restricted Pentaschistis species in the Cape. Main conclusions The roles of age‐ and lineage‐related effects are rejected; biodiversity differences lie in the regions. Current macrohabitat does not explain the differences in biodiversity between the two regions. The larger number of range‐restricted species in the Cape cannot be explained by dispersal mechanism or the occupation of range‐restricted habitats. Species of Pentaschistis and other Cape clades share characteristics associated with species from historically climatically stable areas, and palaeoclimatic and palaeontological evidence indicates the Cape climate has been more stable than the Drakensberg climate throughout the Pleistocene. We conclude that the corresponding lack of extinction might have allowed an accumulation of species in the Cape. Similar climatic and biological evidence for the south‐west Australian Floristic and Mediterranean regions indicate that the same mechanism might explain the high species richness of these mediterranean regions.