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PubMed1995

[Introduction to index of the failing heart syndrome].

On the occasion of the 42nd Scientific Meeting of the Japanese College of Cardiology, a presentation of the methods of the recognition or some indices of heart failure was given to encourage comprehensive discussion of failing heart syndrome. During the last 10 years, several multicenter, randomized, placebo-controlled studies of the efficacy and safety of drugs in patients with heart failure have been performed in western countries, resulting in the evolution of a new concept of heart failure based on pathophysiologic and therapeutic approaches. However, many trials of new drugs for heart failure shown to be efficacious in western countries have failed to be effective in Japan. The reasons for this discrepancy might be based on differences of the causes of chronic heart failure, but also on differences in understanding. All Japanese cardiologists know that the prevalence of left ventricular failure evolving rapidly after acute myocardial infarction in Japan is far less common than in western countries. Recent evolution of pathophysiologic concepts of heart failure is derived from the experimental and clinical observations of myocardial failure. The effects of mechanical overload on failing heart might be an unfashionable topic now, but in Japan, all factors affecting failing heart should be carefully considered when heart failure is treated, because the controlling factor inducing heart failure is hard to identify.

Heart Failure↗

PubMedDate not supplied

[Hygienic aspects of aerobic fermentation of urban waste in the Tunisian context].

The use of the aerobic fermentation (composting) as an alternative of the landfilling of the municipal solid wastes was studied in a pilot plant in the District of Tunis. The effectiveness of the composting, by the windrow turning technical, in producing sanitized compost was considered. Fecal coliforms, fecal streptococcis and E. coli were used as an indicator organism. In addition, the evolution of the process was monitored using sporogenous bacteria. Under the experimental conditions, approximately five logarithmic unit reduction of fecal indicators was noted after a 60 days composting.

Aerobiosis↗

PubMed1996

[Elucidation of the mechanism of fertilization and clinical application of assisted reproductive technology].

Fertilization is the process including many events such as maturation of egg and sperm, attachment, binding, acrosomal reaction, penetration, fusion, cortical reaction, zona reaction and nuclear fusion of both gamete, whereby individual gametes from the female and male unite to create offspring. Although the reason for mechanism of fertilization is still not clearly understood, this process may accelerate the rate adaptation in evolution. In this special lecture, I would like to present our experimental and clinical results especially concerning with morphological, physiological, biochemical and molecular approach on the mechanism of fertilization. 1. Development and maturation of follicles and oocytes. It is well known that pituitary FSH, LH control the ovarian function. Follicular development and ovum maturation are also controlled by both pituitary gonadotropins and local factors such as autocrine and paracrine agents. When hMG is injected during 1-6 day of menstrual cycle, several dominant follicles are developed. If hMG is injected after selection of dominant follicles, only one dominant follicle develop in the ovary. When PMS-treated immature rats were injected with immature or mature follicle fluids, rats injected with mature follicular fluid showed strongly suppress in the ovarian weights and numbers of ovulated follicles. Also mature follicle suppress aromatization from and androstenedione to estradiol. These findings mean that mature follicular fluid contains inhibitory factors. Apoptosis of granulosa cells and follicular steroids are related to fertilization. 2. Intracellular calcium of oocyte. Intracellular calcium concentration is known to start to increase in a periodic manner after fertilization in oocytes of mammalians. In 65% of tested mouse oocytes, fertilization occurred during 4 hours observation after sperm insemination in vitro. An initial long lasting intracellular calcium concentration was observed and followed by periodic manner. This calcium oscillation is inhibited by calcium blockers such as verpamil and nifedipine, but increased by high concentration of extracellular calcium concentration in the medium. Role of increase of intracellular calcium are understood to prevent polysperm and activate metabolism of oocytes. 3. Glucose metabolism of oocytes. Mouse embryo utilizes pyruvate as an essential nutrient until the 8-cell stage, and glucose thereafter. We have devised non-radiometrie and enzymatic microassay method to measure glucose, deoxyglucose, deoxyglucose 6-phosphate incorporated into individual mouse oocytes and preimplantation embryo. In parallel, the activities of several enzymes of glycolytic pathway were also determined. In this study, glucose metabolism is necessary to develop in fertilized ova with changing activity of enzymes. 4. Molecular bases of ovarian fluid. The zona pellucida ZP is involved in a number of events in fertilization, all these fertilization events occur in the oviduct. Oviductal glycoprotein 200-240 KD has been identified from oviductal zona pellucida. Monoclonal antibody of oviductal glycoprotein reacted with ZP of oviductal egg but not with the ovarian egg. Anti-ZPO antibody inhibit to bind sperm to ZP. Sequences in mouse and hamster oviduct specific glycoprotein are estimated, this glycoprotein mRNA was observed in only oviduct by northern blotting method. These molecular gene expression was observed by in situ hybridization in the oviduct of estrous cycle of hamster. 5. Microinsemination of sperm. Microinsemination of sperm into oocyte is widely used in clinical medicine. Sperm penetration assay (hamster test) is useful method to estimate fertilization capacity of sperm. But immotile sperm cannot estimate it. So modified micro sperm penetration assay was established to estimate fertilization capacity of sperm by using micro-manipulator. Subzonal sperm injection (SUZI) and intracytoplasmic sperm injection (ICSI) promotes fertilization and cleavage rate in immotile

Animals↗

PubMed1995

Emergency medical dispatching by general practitioners in Brussels.

The objective of this study was to introduce general practitioners (GPs) to the existing emergency medical services (EMS) system, in order to improve the response to emergency residential calls. The study was based in Brussels, which has 1 million residents. A GP dispatcher (GPD) was placed in the emergency dispatch centre, with a stand-by GP, together with adequate equipment, at his or her immediate disposal. A comparative evaluation was conducted in 1994 to measure the changes brought by the availability of a stand-by GP to the emergency medical dispatching performed by the GPD in an experimental zone (EZ) in comparison with a control zone (CZ). The evolution between a first period at the beginning of the year and a second period in September was also analysed. In total, 1059 residential emergency calls were included in the study. The amount of missing data in the filing cards, collaboration between the emergency medical dispatcher (EMD) and the GPD, and evaluation of the emergency levels were improved by training the GPD and the stand-by GP. Intervention times of the stand-by GP varied according to the level of the emergency. The sending of supplementary assistance after dispatching an EMS ambulance, a stand-by GP or a GP of an on-call service was significantly different in the EZ compared with the CZ. The percentage of EMS ambulances and GPs sent increased. The evolution between the two periods was characterized in the CZ by the disappearance of the supplementary assistance performed by the stand-by GP or by the GP of the on-call service and in the EZ by a slight but not significant increased use of the mobile intensive care units (MICUs) for initial assistance. A stand-by GP was used in about 10% of the cases as supplementary assistance. A large number of non-vital urgent complaints arrive at the dispatch centre. The availability of a stand-by GP does not cause an increase (rather a decrease) in MICU use in initial care and supplementary assistance. It causes a decrease in the total EMS ambulances and transport to hospital and an increase in the use of EMS ambulances and stand-by GP as supplementary assistance. Following stand-by GP intervention, only 25% of visited people are hospitalized. Introduction of GPs is relevant because they are used to discerning critical events from a large number of non-critical disorders. The GPD can adapt the emergency medical dispatching by using a stand-by GP, without compromising the medical assistance to vital emergencies.

Belgium↗

PubMed2003

Position specific variation in the rate of evolution in transcription factor binding sites.

BACKGROUND: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. RESULTS: Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. CONCLUSION: As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA.

Artifacts↗

PubMed2001

Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut.

We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

Adaptation, Physiological↗

PubMed2002

Nonlinear features of two-plasmon decay in a long-scale-length plasma.

A transparent model of two-plasmon decay in a spatially homogeneous or long-scale-length plasma, reproducing the main experimentally observed nonlinear features, is presented. Secondary coupling between the plasma waves and the ion-acoustic waves, including their frequency mismatch, proves to be the principal saturation mechanism of the instability. The wave amplitude time evolution and spectra as well as the hot-electron generation properties are compared to the experimental data.

Journal Article↗

PubMed2003

First-order character of the smectic-A to chiral nematic transition in chiral liquid-crystal mixtures.

An investigation into the smectic-A to chiral nematic (N'A) transition in liquid crystals is presented by using adiabatic scanning calorimetry (ASC). It is predicted theoretically that chirality drives this transition to first order. This transition is studied in mixtures of the nonchiral liquid crystal octyloxycyanobiphenyl (8OCB) and the chiral 4-(2-methylbutyl)-4(')-cyanobiphenyl (CB15), a system with a large (chiral) nematic region that widens upon increasing the chiral (CB15) fraction. An ASC measurement on pure 8OCB showed no evidence for a latent heat, in agreement with previous ac calorimetric studies, with an upper boundary for the latent heat (if any) of 1.8 J/kg. Since pure 8OCB has no measurable latent heat, and taking into account the widening of the chiral nematic region, the possibility of a continuous to first-order crossover due to the coupling of the nematic and the smectic order parameters, as occurring in several cases of smectic-A to nematic (NA) transitions, can be excluded. However, for all examined mixtures a latent heat could be determined at the smectic-A to chiral nematic transition. This confirms theoretical predictions of the first order character of this transition. Quantitatively, theoretical predictions of the evolution of the entropy discontinuities and latent heats of this transition were not consistent with the experimental results. It was further observed that the transition temperature decreases linearly in agreement with theoretical predictions and a previous ac calorimetric study. Finally, it was observed that the pretransitional specific heat capacity shows an interesting evolution upon increasing chiral fraction, and it may be concluded that any theoretical model based on Landau theory is not sufficient to describe this transition.

Journal Article↗

PubMed1999

[Trypanocidal effect of cysteine protease inhibitors in vitro and in vivo in experimental Chagas disease].

Endemic in most American countries, Chagas' disease causes high morbidity and mortality. Recent experimental and clinical evidence shows the importance of chemotherapy in both the acute and chronic phases of this disease. However, treatment is yet limited by the toxicity associated to available drugs. This review describes the design, evolution, and selection of dipeptides that interrupt the intracellular cycle of T. cruzi and cure acute experimental infections in laboratory animals. Peptido-mimetic inhibitors specifically bind cruzain, a T. cruzi cystein protease. The inhibitors cause alterations in the Golgi complex and ER, accumulation of unprocessed enzyme within Golgi cisternae, and decrease of mature cruzain within lysosomes. The most effective compound, N-Pip-F-hF-VS phi, cured an acute lethal infection in experimental animals. Myocardial lesions, lymphocyte infiltration and intracellular amastigote clusers were absent in treated animals. Preliminary toxicology and pharmacokinetic analyses suggest the lack of toxicity associated to high doses and prolonged treatment regimes. Protease inhibitors may soon become good chemotherapeutic alternatives for acute and chronic Chagas' disease.

Acute Disease↗

PubMed2000

Gene function.

The problem of gene function--of the relationships between hereditary material and the characteristics of organisms--preceded the rediscovery of Mendel's laws and accompanied the development of genetics in the XXth century. Molecular biologists replaced the simple gene-character relationship by two relationships: the first, between genes and proteins, was well defined, whereas the second between proteins and the complex structural and functional characteristics of organisms remained unknown. I will describe in this article the experimental approaches which helped to characterize during the last twenty years the relationships between proteins and characters. Four principles of macromolecular organization emerged from these studies: conservation of the elementary components during evolution, existence of pathways and networks, pleiotropy and redundancy. These principles are the explanation of the surprising experimental observations that have been made in recent years. The existence of these principles makes problematic any prediction on the consequences of gene modification. It both sounds the death-knell of the simplistic reductionist approach of many biologists, whereby genes were considered as responsible for specific functions, and definitely prevents the distribution of genes in separate, well defined categories.

Animals↗

PubMed2002

Sperm-female coevolution in Drosophila.

Rapid evolution of reproductive traits has been attributed to sexual selection arising from interaction between the sexes. However, little is known about the nature of selection driving the evolution of interacting sex-specific phenotypes. Using populations of Drosophila melanogaster selected for divergent sperm length or female sperm-storage organ length, we experimentally show that male fertilization success is determined by an interaction between sperm and female morphology. In addition, sperm length evolution occurred as a correlated response to selection on the female reproductive tract. Giant sperm tails are the cellular equivalent of the peacock's tail, having evolved because females evolved reproductive tracts that selectively bias paternity in favor of males with longer sperm.

Animals↗

PubMed2004

Electrorheological properties and microstructure of silica suspensions.

We present experimental and theoretical results on the electrorheological response and microstructure of colloidal suspensions composed of silica nanoparticles dispersed in a silicon oil, as a function of electric field strength and silica water content. Using small-angle neutrons scattering experiments, we determined the evolution of the static structure factor of the suspensions when an electric field is applied. Experimental data were fitted with model calculations using the Percus-Yevick solution for Baxter's hard-sphere adhesive potential. The obtained stickiness parameter is directly related to the polarization interactions that depend on the water content of silica particles. The influence of the polarization interparticle potential on the rheology of the silica dispersions was investigated in a second time. A microscopic theory for the shear viscosity of adhesive hard-sphere suspensions was successfully used which describes the steady shear viscosity of suspension in terms of the fractal concept.

Journal Article↗

PubMed1996

Animal flight mechanics in physically variable gas mixtures

Empirical studies of animal flight performance have generally been implemented within the contemporary atmosphere. Experimental alteration of the physical composition of gas mixtures, however, permits construction of novel flight media and the non-invasive manipulation of flight biomechanics. For example, replacement of atmospheric nitrogen with various noble gases results in a tenfold variation in air density at a constant oxygen concentration. Such variation in air density correspondingly elicits extraordinary biomechanical effort from flying animals; hummingbirds and euglossine orchid bees hovering in such low-density but normoxic mixtures have demonstrated exceptionally high values for the mechanical power output of aerobic flight muscle. As with mechanical power, lift coefficients during hovering increase at low air densities in spite of a concomitant decline in the Reynolds number of the wings. The physical effects of variable gas density may also be manifest in morphological and physiological adaptations of animals to flight across altitudinal gradients. Global variation in atmospheric composition during the late Paleozoic may also have influenced the initial evolution and subsequent diversification of ancestral pterygotes. For the present-day experimenter, the use of physically variable flight media represents a versatile opportunity to explore the range of kinematic and aerodynamic modulation available to flying animals.

Journal Article↗

PubMed2004

Evolution: sexual arms races.

The reproductive interests of males and females usually differ, resulting in sexual conflict. Recent studies in which experimental selection trials were carried out under conditions of either 'high' or 'low' sexual conflict show that conflict can promote speciation and reduce female reproductive success.

Animals↗

PubMed2004

Origins of introns based on the definition of exon modules and their conserved interfaces.

Central to the unraveling of the early evolution of the genome is the origin and role of introns. The evolution of the genome can be characterized by a continuous expansion of functional modules that occurs without the interruption of existing processes. The design-by-contract methodology of software development offers a modular approach to design that seeks to increase flexibility by focusing on the design of constant interfaces between functional modules. Here, it is shown that design-by-contract can offer a framework for genome evolution. The definition of an ancient exon module with identical splice sites leads to a relatively simple sequence of events that explains the role of introns, intron phase differences and the evolution of multi-exon proteins in an RNA world. An interaction of the experimentally defined six-nucleotide splicing consensus sequence together with a limited number of primitive ribozymes can account for a rapid creation of protein diversity.

Animals↗

PubMed1993

[The structural and functional classification and evolution of cytokines].

According to the type of secondary structure, cytokines are classified into three categories: alpha-spiral (IFNs-alpha, beta, omega, gamma; ILS-2, 3,4,5,6,7,9; CSFs-G, M, GM, MGF, PDGF), beta-structural (ILs-1 alpha, beta, TNFs-alpha, beta, FGF) and (alpha + beta)-structural proteins (IL-8, IFN-gamma IP-10, PF-4, bTG, GRO, 9E3). According to the type of tertiary structure, alpha-spiral proteins are grouped into IFN- and IL-2-like families and beta-structural ones into IL-1-, and TNF-like families. Two subfamilies can be identified in the IFN-like family. Theoretical and experimental evidence suggests that the genes IFNs are products of divergent or convergent evolution towards the gene of the ancient intracellular protein alpha-prothymosine, which is evolutionally in turn associated with the L7/I1 protein of two ribosomes. It is suggested that the proteins of the immunoglobulin superfamily, including cytokine receptors descended from the ancient proteins of the unicellular organisms molecular shaperons.

Amino Acid Sequence↗

PubMed1988

Sequential analysis of experimental autoimmune thyroiditis induced by neonatal thymectomy in the Buffalo strain rat.

We have studied the evolution of thyroiditis induced by neonatal thymectomy in Buffalo strain rats, with particular emphasis on the thyroid lymphocytic infiltrate. The earliest change was increased endothelial Ia expression, and infiltration of the thyroid at 5 weeks by ED1- and ED2-positive macrophages and B and T cells. The T cells comprised equal numbers of Ox 8 (T cytotoxic/suppressor)- and W3/25 (T helper)-positive cells. Ia-positive thyroid follicular cells were seen only in the presence of a T-cell infiltrate. Thyroglobulin antibody levels, thyroid weight, thyroid follicular cell Ia expression, and lymphocytic infiltration of the thyroid were maximal between Weeks 12 and 24, and impairment of macrophage function by injection of silica at this time produced amelioration of disease. The thyroid weight returned to control levels by Week 34 and Ia expression by thyroid cells disappeared. Circulating Ox 8-positive T cells were reduced between Weeks 12 and 24 and by Week 34 had returned to control levels. Our results indicate that the mononuclear infiltrate precedes thyroid follicular cell Ia expression and macrophages play an important role in perpetuating thyroiditis. Recovery from disease is accompanied by a return to normal in circulating suppressor/cytotoxic T cells.

Animals↗

PubMed2026

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy↗