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An incorrect definition of fitness revisited.

I have attempted to show that a certain mistaken definition of fitness, which surfaces occasionally, may turn out to have some merit. No claim is made that it is an improvement on, or should replace, the conventional definition of fitness; but it is different and has its own validity. Its generality is intriguing, its application is not limited either to selection or one locus models, and it may be easier to measure experimentally.

Biological Evolution↗

Evolution of biliary secretion during bile diversion in normal and two-thirds hepatectomized rats.

The effect of the interruption of the enterohepatic circulation on bile production in anesthetized rats both before and after two thirds partial hepatectomy (PH) was studied. Both in the control animals and in the different periods after PH, interruption of the enterohepatic circulation led to significant decreases in bile flow and bile acid and sodium output. The evolution of choleresis in all the experimental groups was seen to follow a parallel course to that of sodium output and showed qualitative and quantitative discrepancies with the behavior of bile acid output. The cumulative secretion of bile acids expressed per 100 g of body weight was comparable in the controls and at 384 h after PH, though only in the former did the bile acid circulating pool size seem to be depleted. This depletion was more delayed than that described for conscious nonfasting rats. At 96 and 384 h after PH both cumulative bile flow and cumulative sodium secretion expressed per gram of liver were greater than those of the control animals. The choleretic capacity of the bile acids and the bile acid independent fraction of bile flow were significantly modified in the different posthepatectomy periods.

Animals↗

Fumonisin toxicosis in swine: clinical and pathologic findings.

From a series of experimental studies with pigs (12-16 kg), either pulmonary edema or liver failure emerged as a distinct pathogenetic expression of fumonisin B1 (FB1) toxicosis. The primary determinant as to which pathogenetic consequence developed was the quantity (dose) of the mycotoxin fed or intubated per kilogram of body weight per day. Pigs intubated with a minimum of 16 mg FB1/kg/day developed severe interlobular edema with or without hydrothorax and variably severe pulmonary edema. Pigs intubated with < 16 mg FB1/kg/day or pigs fed diets containing 200 mg FB1/kg of feed developed marked icterus and hepatocellular necrosis. The spectrum of degrees of severity of pulmonary edema observed in the experimental pigs allowed rational speculation regarding evolution of the pathologic changes.

Animals↗

DNA-based therapeutics and DNA delivery systems: a comprehensive review.

The past several years have witnessed the evolution of gene medicine from an experimental technology into a viable strategy for developing therapeutics for a wide range of human disorders. Numerous prototype DNA-based biopharmaceuticals can now control disease progression by induction and/or inhibition of genes. These potent therapeutics include plasmids containing transgenes, oligonucleotides, aptamers, ribozymes, DNAzymes, and small interfering RNAs. Although only 2 DNA-based pharmaceuticals (an antisense oligonucleotide formulation, Vitravene, (USA, 1998), and an adenoviral gene therapy treatment, Gendicine (China, 2003), have received approval from regulatory agencies; numerous candidates are in advanced stages of human clinical trials. Selection of drugs on the basis of DNA sequence and structure has a reduced potential for toxicity, should result in fewer side effects, and therefore should eventually yield safer drugs than those currently available. These predictions are based on the high selectivity and specificity of such molecules for recognition of their molecular targets. However, poor cellular uptake and rapid in vivo degradation of DNA-based therapeutics necessitate the use of delivery systems to facilitate cellular internalization and preserve their activity. This review discusses the basis of structural design, mode of action, and applications of DNA-based therapeutics. The mechanisms of cellular uptake and intracellular trafficking of DNA-based therapeutics are examined, and the constraints these transport processes impose on the choice of delivery systems are summarized. Finally, the development of some of the most promising currently available DNA delivery platforms is discussed, and the merits and drawbacks of each approach are evaluated.

Antisense Elements (Genetics)↗

Image processing based on seeded spontaneous optical pattern formation by optoelectronic feedback.

Spontaneous optical pattern formation from an initial seed optical pattern in an optoelectronic system with optical diffractive feedback is investigated experimentally. We demonstrate that the temporal evolution of the spontaneously formed patterns exhibits a contrast enhancement effect, a spatial filtering effect, and filling of vacant space while the surrounding structures are maintained. These effects allow us to perform image processing of natural fringe patterns, i.e., in our experiments, fingerprint patterns. We also demonstrate image processing with defect invariance for fingerprint patterns.

Journal Article↗

[Biological features and experimental pathogenicity of Candida strains isolated by hemoculture at the Hospital Infantil de México "Federico Gómez"].

In a period of 15 months (1990-1991) it was carried out 5781 blood cultures in which 180 strains of yeast-like were isolated. 116 of these strains were selected for biochemical classification, cellular and colonial morphology and experimental determination of virulence in mice. Most of the strains were classified as Candida albicans (60%) and the others were C. tropicalis (15.5%); C. guillermondii (10.3%); T. glabrata (6.8%); Rhodotorula rubra (3.4%); Cryptococcus neoformans (2.58%) y C. parapsilosis (0.86%). C. albicans ATCC14053, y C. tropicalis ATCC14056 and T. glabrata ATCC15545 were employed as controls. The virulence test was performed using mice of 20-30 gr (4-6 weeks age) by intravenous injection in caudal vein with 0.5 ml of different suspension from 10(5) to 10(9) CFU/ml. Observation time was 10 days. Target organ was kidney by macro and microscopic observation of micro-abscess death. LD50 was estimated by the Reed-muench method. Intraspecific and interspecific differences were observed. It is more valid if we take into account that the experiment was done in homogenous population of host without risk factor which influences the human population in hospitals. Experimental virulence was compared with the evolution of diseases in the human host of which the strain was isolated.

Blood↗

Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers.

Studies of the deformation characteristics of single biological cells can offer insights into the connections among mechanical state, biochemical response and the onset and progression of diseases. Deformation imposed by optical tweezers provides a useful means for the study of single cell mechanics under a variety of well-controlled stress-states. In this paper, we first critically review recent advances in the study of single cell mechanics employing the optical tweezers method, and assess its significance and limitations in comparison to other experimental tools. We then present new experimental and computational results on shape evolution, force-extension curves, elastic properties and viscoelastic response of human red blood cells subjected to large elastic deformation using optical tweezers. Potential applications of the methods examined here to study diseased cells are also briefly addressed.

Elasticity↗

Recent studies on the developing human hepatocellular carcinoma.

From our knowledge of characteristic phenotypic changes of the preneoplastic lesions during the stepwise evolution of hepatocellular carcinoma (HCC) in experimental models, we are now beginning to define the structural, histochemical, biochemical, antigenic and molecular properties of early HCC and of the putative preneoplastic changes in human liver. Histological, ultrastructural, morphometric and immunohistochemical studies suggest that adenomatous nodules of regenerating and hyperplastic hepatocytes are more likely to represent direct precursors of HCC than dysplastic hepatocytes. Histochemical and immunomorphological investigations show appreciable functional and phenotypic heterogeneity of human HCC as previously recognized in experimental hepatocarcinogenesis. Studies of altered expression of oncogenes in the regenerating liver and HCC are beginning to define the molecular mechanisms in cell growth and malignant transformation. Although integration of Hepadna viral DNA sequences frequently occurs during persistent infection in man and animals, the exact mechanism of viral oncogenesis remains to be elucidated. It is likely that the development of monoclonal antibodies to surface antigens on transformed hepatocytes will be useful for exploring lineage relationships between the cell populations involved in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

[Actualities concerning frequency, etiopathogeny, and the diagnosis of temporomandibular osteoarthrosis].

On the basis of a vast reference list, and on the personal experience of the authors new opinions are presented, concerning the concept, the frequency, and the etiopathogeny of temporomandibular osteoarthrosis. Although the symptoms and signs of this morbid entity are frequently similar with those of other intracapsular affections, as a result of a combination of modern radiographic investigations (arthrotomography with double contrast, computerized scanner tomodensitometry, magnetic nuclear resonance), arthroscopy, macroscopic and microscopic examinations (biochemical analysis of the synovial fluid) it has become possible to make a positive diagnosis, as well as a differential one. The conclusions of the study have confirmed the evolution of a large number of experimental studies, both clinical and epidemiological, published in the specialized literature, which favor the detection and the removal of multiple risk factors involved in the development of this disease of degenerative origin, by a correct treatment, and by the use of prostheses.

Humans↗

Correlation between tissue damage and malondialdehydemia in mice infected with Trypanosoma cruzi.

Evolution of the acute phase of experimental Chagas' disease was correlated with tissue damage and plasma levels of malondialdehyde. Heart lesions were quantified by the Tissue Damage Unit (TDU) and malondialdehydemia (MDA) by the colorimetric determination of malondialdehyde. The binary correlations were: C(X,Y) = 0.965 (P less than 0.001); C(Y,Z) = 0.784 (P less than 0.01); and C(X,Z) = 0.824 (P less than 0.01), where X = days of infection, Y = TDU means and Z = MDA means. These results show a positive correlation between the duration of the acute phase of experimental Chagas' disease and TDU, and between the duration and MDA. The methods for measuring tissue damage and MDA are shown to be simple and adequate for monitoring tissue aggression in the protozoosis studied.

Animals↗

[Humoral study of human parasitic diseases. Interest of ELIEDA. (Enzyme--linked--immuno--electro--diffusion--assay) (author's transl)].

In order to sensitize the reaction of immuno-electro-diffusion (IED) and to define the class of immuno-globulins implied in the antigen-antibody reaction, we have completed the technique of IED by coupling it to an enzymatic technique. In such a way the immune complexes are treated by enzyme labeled antibodies specific to each class of immunoglobulin. This association realizes the technique of ELIEDA (enzyme-linked-immuno-electro-diffusion-assay). The sensitivity and the specificity of this method allow the follow up of the qualitative evolution of antibodies during natural or experimental parasitic diseases.

Counterimmunoelectrophoresis↗

Experimental investigations in prolonged myocardial ischaemia. Note II. Biology of the myocardial fiber during permanent ischaemia.

The dynamics of morphologic and biochemical lesions of the myocardial fiber during the first ten days after an experimental myocardial infarction showed an unequal evolution of the lesional picture in the ischaemic area, the intervention of lysosomal hydrolases and the reactions of inflammatory fibrocollagen substitution. Morphologic aspects in the areas neighbouring the infarction and other myocardial areas are discussed.

Animals↗

Cushing, Cutler and the mitral valve.

Because of the over-all excellent results in the correction of many cardiac disorders which have accrued during the past several years, it is easy to take for granted the long and often painful evolution of surgery of the heart. Experimental work on the creation of valvular lesions and attempts at their repair stem back for a century, although it took until the 1920's before a few intrepid surgeons considered such procedures for clinical use. It is of interest that early attempts on repair of mitral stenosis, both in laboratory animals and in patients, were undertaken by Cushing and Cutler, two surgical innovators who succeeded each other as Moseley Professors of Surgery at the Peter Bent Brigham Hospital. Such early efforts in surgical manipulation of the heart opened the way for the refinements of modern cardiac surgery that have become routine.

Animals↗

[Acute neutropenia in adult severe bacterial infections. Six cases (author's transl)].

A transient neutropenia (duration : less than 48 hours) occurred in 6 patients with severe bacterial infections. The bone marrow myeloïd cellularity was high or normal; a maturation arrest of the myeloïd cells - at a variable stage - was present in each case, as well as circulating granulocyte precursors. Other causes of neutropenia were excluded. A general survey of the literature is made and the mechanisms of this bacterial neutropenia are considered : bone marrow failure seems mostly improbable ; the few previously reported cases, the experimental bacterial neutropenias, the peculiar, transient, evolution we observed, all favor a peripheral mechanism ; the bacterial infection seems to act by; two ways : in septicemia (especially during septic shock) by enhancing leucocyte margination along vascular walls ; in large septic foci (mostly pulmonary) by an important destruction of polymorphonuclear neutrophils. Such bacterial infections share a bad prognosis but the neutropenia itself needs no specific treatment.

Acute Disease↗

Stretching and tilting of material lines in turbulence: the effect of strain and vorticity.

The Lagrangian evolution of infinitesimal material lines is investigated experimentally through three dimensional particle tracking velocimetry (3D-PTV) in quasihomogeneous turbulence with the Taylor microscale Reynolds number Re(lambda)=50. Through 3D-PTV we access the full tensor of velocity derivatives du(i)/dx(j) along particle trajectories, which is necessary to monitor the Lagrangian evolution of infinitesimal material lines l. By integrating the effect on l of (i) the tensor du(i)/dx(j), (ii) its symmetric part s(ij), (iii) its antisymmetric part r(ij), along particle trajectories, we study the evolution of three sets of material lines driven by a genuine turbulent flow, by "strain only," or by "vorticity only," respectively. We observe that, statistically, vorticity reduces the stretching rate l(i)l(j)s(ij)/l2, altering (by tilting material lines) the preferential orientation between l and the first (stretching) eigenvector lambda1 of the rate of strain tensor. In contrast, s(ij), in "absence" of vorticity, significantly contributes to both tilting and stretching, resulting in an enhanced stretching rate compared to the case of material lines driven by the full tensor du(i)/dx(j). The same trend is observed for the deformation of material volumes.

Journal Article↗

Differential expression of sonic hedgehog immunoreactivity during lesion evolution in autoimmune encephalomyelitis.

The signaling molecule Sonic hedgehog (Shh) is involved in several processes of central nervous system development. Recent reports indicate that Shh expression plays a role also in certain pathologic conditions in the adult brain, including multiple sclerosis and its animal model. However, the role of Shh signaling in immune-mediated demyelinating disease remains still uncertain. The aim of our study was to investigate the distribution pattern of Shh immunoreactivity (Shh-IR) during lesion evolution in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), a model strongly mimicking multiple sclerosis. MOG-EAE was actively induced in DA rats. Histologic evaluation was performed with light and confocal microscopy on paraffin-embedded central nervous system sections from days 20 to 120 after active immunization. Shh-IR was present within the lesions of MOG-EAE during all stages of lesion evolution. The highest staining intensity for Shh was found in remyelinating lesions. In actively demyelinating, inactive demyelinated lesions, and in remyelinating lesions, Shh-IR was detected in macrophages, endothelium, and astrocytes. Shh-IR in axons was exclusively present in remyelinating lesions. Although the exact molecular mechanisms of the Shh-signaling pathway in experimental autoimmune encephalomyelitis are yet to be determined, our findings may imply a role of Shh signaling in facilitating remyelination.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Natural history of experimental intracerebral hemorrhage: sonography, computed tomography and neuropathology.

The evolution of intracerebral hemorrhage was investigated in a canine model by high resolution sonography, computed tomography (CT), and neuropathologic examination. In 12 dogs, a parietal lobe hematoma was introduced by craniotomy. The sonographic appearance of acute hemorrhage was characteristic and consisted of a sharply circumscribed, homogeneous, highly echogenic lesion, the size and shape of which correlated closely to the area of increased density seen on the CT scan. This changed within 3-4 days to an echogenic rim surrounding a hypoechoic center. Histologically, this change corresponded to a loss of integrity of individual red blood cells. This occurred earliest in the hemorrhage center causing a hypoechoic center, while intact red blood cells at the periphery accounted for the echogenic rim. Shortly after the red blood cells lost their biconcave shape they began to lose their hemoglobin causing the hemorrhage to become isodense with surrounding brain on the CT scan. Faint contrast enhancement by CT was noted at this early stage and was related primarily to a mononuclear perivascular infiltrate at the edge of the hemorrhage. A collagen capsule formed around the hemorrhage over a 2 week period. This capsule slowly replaced intact red cells as the cause of the now shrinking echogenic rim. This capsule was also responsible for the increasing ring contrast enhancement around the resolving hemorrhage. The sequence of image changes seen on both CT and sonography in this experimental model closely resembled the findings seen in intracerebral hemorrhage in patients.

Animals↗