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Evaluation of 99mTc-dimercaptosuccinic acid renal uptake as an index of individual kidney function after acute ureteral obstruction and desobstruction. An experimental study in rats.

The evolution of the 99mTc-dimercaptosuccinic acid (DMSA) renal uptake is followed after ligation of the right ureter in rats. The DMSA uptake falls rapidly from 35% before ligation to 13% after 24 h, and decreases further to 1.5% after 31 days. The ligated ureter was desobstructed after 10, 17, 24 and 31 days, respectively, DMSA uptake was controlled 4, 11 and 18 days after desobstruction. In the first group, deobstruction after 10 days, the DMSA uptake rose from 7 to 15%, while in the fourth group it rose from 1.5 to 2%. It is concluded that DMSA uptake provides a reliable index for renal function after acute urinary tract obstruction in rats. If the DMSA uptake has fallen below 4% very little renal function can be expected to be regained, whereas above 4% the function can improve considerably.

Acute Disease↗

[Experimental cutaneous leishmaniasis. III. Histopathological aspects of the developmental behavior of the cutaneous lesion induced in Cebus apella (Primates: Cebidae) by Leishmania (Viannia) lainsoni, L. (V.) braziliensis and L. (Leishmania) amazonensis].

We have studied the histopathological aspects related to the evolution of cutaneous lesions experimentally produced in the monkey Cebus apella (Primates: Cebidae) by Leishmania (V.) lainsoni, L. (V.) braziliensis and L. (L.) amazonensis. Microscopical examination of a series of biopsies obtained from these animals showed the kinetics of the cutaneous lesions regarding three species of Leishmania inoculated, as follows: 1) an initial non-specific chronic inflammatory infiltrate; 2) macrophagic nodules; 3) necrosis of parasitized phagocytic cells; 4) epitheliode granuloma; 5) absorption of the necrotic area (sometimes forming "foreign-body granuloma"); 6) a non-specific residual inflammatory infiltration; and 7) cicatrization. These pathological processes are, of course, responsible for both development and resolution of the leishmaniotic lesion. We also discuss some immunopathological mechanisms probably related with the sequential events, and that could be also responsible for the different clinical aspects found in man.

Animals↗

MR imaging of acute experimental ischemia in cats.

The evolution of acute cerebral ischemia was documented by magnetic resonance (MR) imaging in 13 mongrel cats with occlusion of the middle cerebral artery through a transorbital approach. The animals were imaged under anesthesia at intervals from 30 min to 10 days after production of the lesion. An MR imager operating at 0.35 T was used with multislice, multi-spin-echo technique (TR = 500-2000 msec; TE = 28, 56 msec). The animals were sacrificed after imaging for pathologic correlation. Infarcts beyond 4 hr of age were visualized in all subjects. The earliest infarct was seen at 30 min (two cats) as an area of high signal intensity on T2-weighted images. In three other cats, however, 3-hr-old infarcts were not detectable. In one animal, a hemorrhage within a 1-week-old area of infarction was not characterized by MR imaging but was identified on CT scanning. The mass effect of the infarction appeared greatest at 2-4 days after infarction. The basal ganglia showed ischemic effects to best advantage. MR imaging offers previously unavailable sensitivity for the early noninvasive detection of cerebral ischemia in vivo.

Animals↗

[Evolution of venous cerebral infarction and brain edema--an experimental study of sagittal sinus obstruction].

Superior sagittal sinus with/without neighboring venous system of 36 mongrel cats were occluded by cyanoacrylate polymer after i.v. administration of Evans-blue (EB). Thereafter, the cats were sacrificed 1, 3, 6, 12, 24, 72 or 120 hours after sinus-vein occlusion. According to the degree of occluded region, the cats were divided into two groups; group A (GA) and B (GB). GA showed only superior sagittal sinus occlusion, while many cortical veins were also occluded in GB. No EB nor histological changes were found in 13 cats of GA and 4 sham operated cats, while EB distribution was observed in all 20 cats of GB. The other 3 cats of GA showed a little EB in gyrus lateralis. EB distribution of GB were divided into two types. Type 1 showed EB mainly in the cortical gray matter, while type 2 showed massive EB extravasation in the white matter as well. Edematous changes with gliosis in its resolution phase, were observed in type 1. In addition, EB free zone was formed along with U-fiber zone (cortico-medullary junction) in the cats of later phase (72 hours after occlusion). The findings of EB extension in the type 1 means the existence of blockage against edema evolution from cortex toward subcortical white matter. The cats of type 2 showed fulminant hemorrhagic changes which appeared depend on time interval. Although occurrence of pathological changes were rather earlier than that of cases of clinical cerebral sinus thrombosis, this pathological findings demonstrated the typical character of venous hemorrhagic infarction. In this paper, the similarity and difference between this model and clinical case of sinus-vein thrombosis were discussed. And the possible function of the U-fiber zone in the corticomedullary junction against edema evolution was suggested.

Animals↗

Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution.

Surgical occlusion of the left coronary artery of the rat is a relatively simple, economical technique for producing experimental myocardial infarction (MI). Histologic study of 1- to 21-day-old MI in rats showed that following a mild and brief acute inflammatory response at the margins of the necrotic myocardium, there is chronic inflammation, vascular and collagenous proliferation, and resorption of necrostic tissue which progresses until scar formation is complete, usually by 21 days. From Day 1 to Day 21 the volume of infarcted myocardium decreases from 45.9 +/- 5.9% (mean +/- SEM) to 26.1 +/- 3.2% of the left ventricle and infarct thickness decreases from 1.30 +/- 0.06 mm to 0.47 +/- 0.02 mm. Concomitantly, the percent of the surface area of the left ventricle which is infarcted decreases insignificantly from 55.7 +/- 7.2% to 48.3 +/- 4.2%, indicating that the decrease in volume of the infarcted tissue occurs primarily as a result of thinning of the MI. This study provides qualitative and quantitative information on the natural history of MI in rats, which should be useful as a baseline for future studies.

Animals↗

Programming the Drosophila embryo.

A critical step in understanding the mechanisms of development is in defining the steps at the molecular, cellular, and organismal levels in the developmental program for a given organism-so that given the egg one can predict not only how the embryo will develop but also how that embryo evolved from its ancestors. Using methods employed by chemists and engineers in modeling hierarchical systems, I have integrated current theory and experiment into a calculational method that can model early Drosophila embryogenesis on a personal computer. This quantitative calculation tool is simple enough to be useful for experimentalists in designing experiments yet detailed enough for theoreticians to derive new insights on the evolution of developmental genetic networks. By integrating the strengths of theoretical and experimental methods into a single engineering model that can compute the cascade of genetic networks in a real organism, I provide a new calculational tool that can apply current theory to current experimental data to study the evolution of developmental programs.

Animals↗

The dynamic evolution of the power exponent in a universal growth model of tumors.

We have previously reported that a universal growth law, as proposed by West and collaborators for all living organisms, appears to be able to describe also the growth of tumors in vivo after an initial exponential growth phase. In contrast to the assumption of a fixed power exponent p (assumed by West et al. to be equal to 3/4), we propose in this paper a dynamic evolution of p, using experimental data from the cancer literature. In analogy with results obtained by applying scaling laws to the study of fragmentation of solids, the dynamic behaviour of p is related to the evolution of the fractal topology of neoplastic vascular systems. Our model might be applied for diagnostic purposes to mark the emergence of an efficient neo-angiogenetic structure if the results of our in silico experiments are confirmed by clinical observations.

Humans↗

[Comparative study of the evolution of inflammatory colitis treated with an elemental diet, glutamine and 5-ASA. An experimental study in rats].

The objective of the present investigation was to study the evolution of untreated inflammatory disease of the colon as compared to disease treated with an elemental diet plus glutamine, with 5-ASA and with a combination of the three. A total of 120 female Wistar-Tecpar rats aged 180 days and weighing on average 290 g were studied. Inflammatory disease of the colon was induced with 10% acetic acid and the animals were divided at random into four groups of 30 rats each. Group A, which received a standard diet and no type of treatment, was used as control. Group B received an elemental diet supplemented with glutamine. Group C received a standard diet and daily 5-ASA enemas, 15 mg/ml. Group D received an elemental diet supplemented with glutamine plus daily 5-ASA enemas. Ten animals were picked at random from each group and sacrificed on the 7th, 14th and 21st days of treatment after intravenous injection of Evans blue for visualization of the damaged areas. Changes in weight and the macroscopic aspects of the abdominal cavity and the colon were evaluated and the involved segment was resected for macroscopic and microscopic analysis. The highest weight loss occurred in group D animals on the 14th and 21st days. The number of complications was larger in group A animals, with intestinal perforation, peritonitis and death (P = 0.0053). Complications were of equal intensity in groups B and C and no complications were detected in group D. Macroscopic evaluation showed a lower frequency of ulcers on the 7th day in group B (P = 0.0113) and D (P = 0.0294). Group D animals showed a significantly reduced frequency of ulcers on the 14th day (P = 0.0140). Microscopic examination showed a better evolution in groups B (P = 0.0113) and D (P = 0.0294) on the 7th day and in group D on 14th day (P = 0.0105) compared to A. We conclude that the combination of an elemental diet containing glutamine and treatment with 5-ASA leads to more rapid healing of the colon lesions induced by 10% acetic acid in rats.

Animals↗

Assessing the likelihood of recurrence during RNA evolution in vitro.

Recurrence is the possibility of resulting in the same endpoint multiple times when a living system is allowed to evolve repeatedly starting from a given initial point. This concept is of concern to both evolutionary theoreticians and molecular biologists who use nucleic acid selection techniques to mimic biotic and computorial processes in the test tube. Using the continuous in vitro evolution methodology, many replicate experimental evolutionary lineages with populations of catalytic RNA were performed to gain insight into the parameters that could affect recurrence. The likelihood that the same genotype will result in parallel trials of an evolution experiment in vitro depends on several factors, including the phenotype under selection, the size and composition of the initial diverse pool of nucleic acids used in the experiment, the degree of mutation possible during the experiment, the shape of the fitness landscape through which the population evolves, and the strategies used to invoke selection and to search the landscape, among others. By considering these factors, it can be predicted that recurrence is more likely when a small, wild-type-based starting pool is used with efficient selection and search strategies involving little online mutagenesis within a rugged adaptive landscape with a strong local optimum. The recurrence experiments performed here on the 150-nucleotide ligase ribozyme demonstrate that it repeatedly jumps from one peak in a fitness landscape to another, apparently hurdling a deep fitness valley. These predictions can and should be tested by additional multiple replicates of actual evolution experiments in the laboratory.

Base Sequence↗

Phenotypic divergence along lines of genetic variance.

Natural populations inhabiting the same environment often independently evolve the same phenotype. Is this replicated evolution a result of genetic constraints imposed by patterns of genetic covariation? We looked for associations between directions of morphological divergence and the orientation of the genetic variance-covariance matrix (G) by using an experimental system of morphological evolution in two allopatric nonsister species of rainbow fish. Replicate populations of both Melanotaenia eachamensis and Melanotaenia duboulayi have independently adapted to lake versus stream hydrodynamic environments. The major axis of divergence (z) among all eight study populations was closely associated with the direction of greatest genetic variance (gmax), suggesting directional genetic constraint on evolution. However, the direction of hydrodynamic adaptation was strongly associated with vectors of G describing relatively small proportions of the total genetic variance, and was only weakly associated with gmax. In contrast, divergence between replicate populations within each habitat was approximately proportional to the level of genetic variance, a result consistent with theoretical predictions for neutral phenotypic divergence. Divergence between the two species was also primarily along major eigenvectors of G. Our results therefore suggest that hydrodynamic adaptation in rainbow fish was not directionally constrained by the dominant eigenvector of G. Without partitioning divergence as a consequence of the adaptation of interest (here, hydrodynamic adaptation) from divergence due to other processes, empirical studies are likely to overestimate the potential for the major eigenvectors of G to directionally constrain adaptive evolution.

Adaptation, Biological↗

Measurement of gouy phase evolution by use of spatial mode interference.

An experimental technique to observe and accurately measure the Gouy phase evolution of Hermite-Gaussian modes is presented. Because of the unique features of spatial mode interference frequency-locking error signals, we are able to readily perform explicit measurement of the Gouy phase in a simple and highly accurate manner. We present these data and discuss the technique and its implications.

Journal Article↗

Machines for automated evolution experiments in vitro based on the serial-transfer concept.

Two machine setups for automated evolution experiments in vitro are described. Both machines enable the monitoring of growing populations of RNA or DNA molecules in real time using high-sensitivity glass fiber laser fluorimeters and an automated sample handling facility for volumes in the microliter range. Growth conditions are kept constant by means of the serial-transfer technique, that is, the successive transfer of a small fraction of a growing population into a fresh solution containing no individuals prior to the transfer. The serial transfer technique was modified to work with large populations and constant growth conditions. In the single-channel evolution machine isothermal amplification reactions (Qbeta-system, 3SR, NASBA, SDA) are monitored successively in single test tubes. This machine is particularly well suited for the investigation of optimal adaptation to altered environmental conditions, as is experimentally demonstrated in the evolution of an RNA quasi-species using ribonuclease A as the selection pressure. The new variant of RNA appeared very rapidly (within approximately 80 generations) without stable intermediates, and it was selected by steadily increasing the RNaseA concentration during the serial-transfer experiment. The other machine, which is described in the second part of this article, is a consequent extension of the single-channel machine, and was designed to allow the multichannel detection of up to 960 samples simultaneously. Thus, high-throughput screening can be applied to evolution experiments. In addition to monitoring isothermal amplification reactions, it is also possible to follow PCR amplifications through thin plastic foils. Initial experiments have demonstrated the suitability of the apparatus for uniformly processing samples and for performing thermocycling.

Base Sequence↗

Evolution of the cellular response in P2-induced experimental allergic neuritis.

We examined the development of the inflammatory cellular response and demyelination in P2 protein-induced experimental allergic neuritis (EAN). Collections of inflammatory cells were first identified in nerve roots 14 days after immunization. Ia+ cells predominated in the evolving lesions and T-helper cells were the dominant T-cell type with T-suppressor/cytotoxic cells appearing later in the course of the disease. Vesiculation, the earliest change seen in the myelin sheath, appeared before the wave of cellular infiltration. These results indicate that myelin injury precedes inflammation in P2 protein-induced EAN, and provide further evidence that this disorder is indistinguishable from EAN induced with whole peripheral nerve myelin.

Animals↗