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At least 793 records · Page 44Linked to original sources
PubMed1998

[Study of active myocardial damage in children with suspected myocarditis using antimyosin monoclonal antibodies (AMMoAb-111In)].

BACKGROUND: The study with monoclonal antimyosin antibody-111In has proved to be useful in the detection of the myocardial damage present in different processes. There is active myocardial damage and specific antimyosin uptake in myocarditis, as both experimental and clinical trials have shown. In experimental models the evolution of myocardial damage has been studied, where a parallelism between the histological changes of the myocardial damage and the evolution on the antimyosin uptake has been found. In clinical myocarditis it is difficult to do an histological follow up of the inflammatory process, and therefore the evolution of myocardial damage present in myocarditis is unknown. The antimyosin antibody images allow a non-invasive study of this evolution. OBJECTIVES: a) to study with monoclonal antimyosin antibody-111In, the myocardial damage present regarding the disease evolution in children with suspected clinical diagnosis of myocarditis; b) to evaluate the evolution of the active myocardial damage reflected on the changes on the monoclonal antimyosin antibody-111In uptake. METHODS: A study with monoclonal antimyosin antibody-111In was carried out on 43 children, 16 males and 27 females with a median age of 39 months (SD 48 m; range: 2-167) with suspected diagnosis of acute myocarditis defined as the presence of congestive cardiac failure or severe ventricular arrhythmia with less than 12 months of evolution. The image evaluation was done visually and through the heart to lung ratio. Twenty of these patients were also followed up with antimyosin antibody scan for a period of 19 +/- 9 months, and 3.8 +/- 1.7 studies were performed on them in this time. RESULTS: The prevalence of positive myocardial uptake was 83.72%. There is a negative correlation (r = -0.352; p < 0.02) between the evolution time of the process and the heart to lung ratio: patients studied before two months, have a higher heart to lung ratio and greater prevalence of positive studies than those studied later (heart to lung ratio 2.09 vs 1.74; p = 0.013; 90% vs 69.2%). Of the patients followed up with antimyosin antibody scans, 6 showed a clinical relapse which increased their heart to lung ratio. The other 14 showed an progressive decrease of the heart to lung ratio reaching normality in 14 +/- 6 months. CONCLUSIONS: a) the uptake intensity of monoclonal antimyosin antibody-111In, as a reflection of the myocardial damage, depends on the disease evolution time, as in the first two months is when the major damage happens; b) the uptake intensity slowly decreases, tending to normality around the 14th month, although this evolution may be altered by the appearance of relapses.

Antibodies, Monoclonal↗
PubMed1996

Theoretical approaches to the analysis of homeobox gene evolution.

The homeobox gene system presents a unique model for experimental and theoretical analyses of gene evolution. Homeobox genes play a role in patterning the embryonic development of diverse organisms and as such are likely to have been fundamental to the evolution of the specialized body plans of many animal species. The organization of Hox-genes in chromosomal, clusters in many species implicates gene duplication as a prominent mechanism in the evolution of this multigene family. I review here various theoretical analyses that have contributed to our understanding of the molecular evolution of this class of developmental control genes. This article also illustrates relationships between theoretical predictions and experimental studies and outlines future avenues for the evolutionary analysis of developmental systems.

Animals↗
PubMed1997

Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity.

Previous studies of attenuated simian immunodeficiency virus (SIV) vaccines in rhesus macaques have demonstrated the development of broad protection against experimental challenge, indicating the potential for the production of highly effective immune responses to SIV antigens. However, the development of this protective immune status was found to be critically dependent on the length of time postvaccination with the attenuated virus strain, suggesting a necessary maturation of immune responses. In this study, the evolution of SIV envelope-specific antibodies in monkeys experimentally infected with various attenuated strains of SIV was characterized by using a comprehensive panel of serological assays to assess the progression of antibodies in longitudinal serum samples that indicate the development of protective immunity. In parallel studies, we also used the same panel of antibody assays to characterize the properties of SIV envelope-specific antibodies elicited by inactivated whole-virus and envelope subunit vaccines previously reported to be ineffective in producing protective immunity. The results of these studies demonstrate that the evolution of protective immunity in monkeys inoculated with attenuated strains of SIV is associated with a complex and lengthy maturation of antibody responses over the first 6 to 8 months postinoculation, as reflected in progressive changes in antibody conformational dependence and avidity properties. The establishment of long-term protective immunity at this time in general parallels the absence of further detectable changes in antibody responses and a maintenance of relatively constant antibody titer, avidity, conformational dependence, and the presence of neutralizing antibody for at least 2 years postinoculation. In contrast to the mature antibody responses elicited by the attenuated SIV vaccines, the whole-virus and envelope subunit vaccines in general elicited only immature antibody responses characterized by poor reactivity with native envelope proteins, low avidity, low conformational dependence, and the absence of neutralization activity against the challenge strain. Thus, these studies establish for the first time an association between the effectiveness of experimental vaccines and the capacity of the vaccine to produce a mature antibody response to SIV envelope proteins and further indicate that a combination of several antibody parameters (including titer, avidity, conformational dependence, and virus neutralization) are superior to any single antibody parameter as prognostic indicators to evaluate candidate AIDS vaccines.

Animals↗
PubMed2005

Combination of computational prescreening and experimental library construction can accelerate enzyme optimization by directed evolution.

Chiral compounds can be produced efficiently by using biocatalysts. However, wild-type enzymes often do not meet the requirements of a production process, making optimization by rational design or directed evolution necessary. Here, we studied the lipase-catalyzed hydrolysis of the model substrate 1-(2-naphthyl)ethyl acetate both theoretically and experimentally. We found that a computational equivalent of alanine scanning mutagenesis based on QM/MM methodology can be applied to identify amino acid positions important for the activity of the enzyme. The theoretical results are consistent with concomitant experimental work using complete saturation mutagenesis and high-throughput screening of the target biocatalyst, a lipase from Bacillus subtilis. Both QM/MM-based calculations and molecular biology experiments identify histidine 76 as a residue that strongly affects the catalytic activity. The experiments demonstrate its important influence on enantioselectivity.

Amino Acid Substitution↗
PubMed2000

Rapid evolution of reproductive barriers driven by sexual conflict.

A growing amount of experimental data indicates extremely rapid evolution of traits and proteins related to fertilization in many diverging taxa. These data come from studies of sperm or pollen competition between closely related species, and from molecular studies of fertilization proteins. The positive selection for evolutionary novelty that appears to be acting on fertilization systems seems paradoxical because successful reproduction requires the close matching of female and male traits. It has been suggested that perpetual coevolution between the sexes can result from sexual conflict in mating. Sexual conflict occurs when characteristics that enhance the reproductive success of one sex reduce the fitness of the other sex. Numerous examples of sexual conflict resulting from sensory exploitation, polyspermy and the cost of mating have been discussed in detail. The potential for coevolution due to such conflict has been evaluated experimentally. Here I develop a simple mathematical model describing coevolutionary dynamics of male and female traits involved in reproduction. The model shows that continual change in such traits at a constant speed is expected whenever females (or eggs) experience fitness loss from having too many compatible males (or sperms). The plausibility of runaway coevolution increases with increasing population size. Rapid evolution of reproductive barriers driven by sexual conflict may explain increased speciation rates after colonization of new habitats ('adaptive radiation') and high species richness in resource-rich environments.

Animals↗
PubMed2006

Targeted deletion of MKK4 in cancer cells: a detrimental phenotype manifests as decreased experimental metastasis and suggests a counterweight to the evolution of tumor-suppressor loss.

Tumor-suppressors have commanded attention due to the selection for their inactivating mutations in human tumors. However, relatively little is understood about the inverse, namely, that tumors do not select for a large proportion of seemingly favorable mutations in tumor-suppressor genes. This could be explained by a detrimental phenotype accruing in a cell type-specific manner to most cells experiencing a biallelic loss. For example, MKK4, a tumor suppressor gene distinguished by a remarkably consistent mutational rate across diverse tumor types and an unusually high rate of loss of heterozygosity, has the surprisingly low rate of genetic inactivation of only approximately 5%. To explore this incongruity, we engineered a somatic gene knockout of MKK4 in human cancer cells. Although the null cells resembled the wild-type cells regarding in vitro viability and proliferation in plastic dishes, there was a marked difference in a more relevant in vivo model of experimental metastasis and tumorigenesis. MKK4(-/-) clones injected i.v. produced fewer lung metastases than syngeneic MKK4-competent cells (P = 0.0034). These findings show how cell type-specific detrimental phenotypes can offer a paradoxical and yet key counterweight to the selective advantage attained by cells as they experiment with genetic null states during tumorigenesis, the resultant balance then determining the observed biallelic mutation rate for a given tumor-suppressor gene.

Animals↗
PubMed1998

Evolution of satellite DNAs from the genus Palorus--experimental evidence for the "library" hypothesis.

Satellite DNA profiles have been characterized in the congeneric species Palorus ratzeburgii, Palorus subdepressus, Palorus genalis, and Palorus ficicola (Coleoptera, Insecta), each of which contains a single, A + T-rich satellite DNA comprising a considerable portion of the genome (20%-40%). These satellites exhibit insignificant mutual sequence similarity. Using PCR assay, it has been shown that all four sequences are present in each of the tested Palorus species: one of them is amplified into a high copy number or a major satellite, while the three others are in the form of low-copy-number repeats estimated to make up approximately 0.05% of the genome. Each of the four satellites is interspecifically high conserved concerning the sequence, monomer length, and tandem repeat organization. Major, as well as low-copy-number, satellites are colocalized in the regions of pericentromeric heterochromatin on all chromosomes of the complement. The low-copy-number satellites are dispersed between the large arrays of the major satellite over the whole heterochromatic block. Our results explain satellite DNA evolution, confirming the hypothesis that related species share a "library" of conserved satellite sequences, some of which could be amplified into a major satellite. Due to the evolutionary dynamics of satellite DNAs, the content of the "library" is variable; the elimination of some sequences parallels the creation of the new ones. Quantitative changes in satellite DNAs, induced by occasional amplification of satellite repeat from the "library", could possibly occur in the course of the speciation process, thus forming a species-specific profile of satellite DNAs.

Animals↗
PubMedDate not supplied

Evolution and development of gastropod larval shell morphology: experimental evidence for mechanical defense and repair.

The structural diversity of gastropod veliger larvae offers an instructive counterpoint to the view of larval forms as conservative archetypes. Larval structure, function, and development are fine-tuned for survival in the plankton. Accordingly, the study of larval adaptation provides an important perspective for evolutionary-developmental biology as an integrated science. Patterns of breakage and repair in the field, as well as patterns of breakage in arranged encounters with zooplankton under laboratory conditions, are two powerful sources of data on the adaptive significance of morphological and microsculptural features of the gastropod larval shell. Shells of the planktonic veliger larvae of the caenogastropod Nassarius paupertus [GOULD] preserve multiple repaired breaks, attributed to unsuccessful zooplankton predators. In culture, larvae isolated from concentrated zooplankton samples rapidly repaired broken apertural margins and restored the "ideal" apertural form, in which an elaborate projection or "beak" covers the head of the swimming veliger. When individuals with repaired apertures were reintroduced to a concentrated mixture of potential zooplankton predators, the repaired margins were rapidly chipped and broken back. The projecting beak of the larval shell is the first line of mechanical defense, covering the larval head and mouth and potentially the most vulnerable part of the shell to breakage. Patterns of mechanical failure show that spiral ridges do reinforce the beak and retard breakage. The capacity for rapid shell repair and regeneration, and the evolution of features that resist or retard mechanical damage, may play a more prominent role than previously thought in enhancing the ability of larvae to survive in the plankton.

Animals↗
PubMedDate not supplied

Experimental duck hepatitis B virus infection: pathology and evolution of hepatic and extrahepatic infection.

Seventy, 1-day-old ducklings inoculated intraperitoneally with duck hepatitis B virus and 30 controls have been studied over a 2-year period. Infection with duck hepatitis B virus occurred in all inoculated ducks, although this was not associated with clinical morbidity. Duck hepatitis B virus DNA was first detected in liver on Day 3, in pancreatic acinar cells on Day 4, serum on Day 6, splenic red and white pulp on Day 7 and in the renal glomurulus on Day 14, using a combination of dot, Southern blot and in situ hybridization techniques. Peak levels of circulating virus, as determined by DNA polymerase levels, occurred 1 to 4 weeks postinoculation. Mild degrees of portal inflammation were seen in sections of liver tissue in both infected and control ducks. However, moderately severe inflammatory changes were present in 8 of 22 infected birds compared with 0 of 18 controls (p less than 0.025). Appearance of this inflammatory infiltrate 6 weeks postinoculation coincided with a decrease in levels of duck hepatitis B virus DNA in hepatocytes and within the pancreatic acinar cells. At the same time, duck hepatitis B virus DNA became increasingly localized to the splenic germinal centers, and viral DNA was first detected in pancreatic islet cells. No histological changes accompanied the extra-hepatic tissue infection. The sequence and significance of duck hepatitis B virus infection in liver and extra-hepatic tissues is discussed in relation to the pathogenesis of hepatitis B virus infection in man.

Animals↗
PubMed1989

Evolution of the temporal contraction sequence after acute experimental myocardial infarction.

The effect of infarct maturation on the temporal sequence of contraction within infarct zones has not previously been described. Accordingly, the time-varying pattern of contraction within ischemic/infarct zones was studied with use of cross-sectional echocardiography in 17 dogs at 10 min to 6 weeks after acute experimental myocardial infarction. Left ventricular short-axis images were digitized from end-diastole to end-systole and endocardial fractional radial change along 36 evenly spaced rays was calculated. The circumferential extent of dyskinesia and the number of rays that exhibited maximal dyskinesia were determined for each decile of the normalized contraction sequence. Between 10 min and 1 week after infarction, the greatest circumferential extent of dyskinesia occurred between the 3rd and 4th deciles of the normalized contraction sequence. However, as the infarct matured, the greatest spatial expanse of dyskinesia was noted to occur progressively earlier in the contraction sequence (second decile at 6 weeks), and the extent of mid- to late-systolic dyskinesia decreased markedly. Whereas end-systolic dyskinesia was present in 30% to 50% of ischemic/infarct zone rays from 10 min to 48 h, end-systolic dyskinesia was no longer observed at 6 weeks. Similarly, the maximal amplitude of dyskinesia was most commonly observed during midsystole from 10 min to 48 h, but occurred progressively earlier as the infarct matured, falling during the first decile at 6 weeks after infarction. These data suggest that maximal circumferential extent and amplitude of dyskinesia occur progressively earlier in the systolic contraction sequence as the infarct matures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Evolution of blood parameters during weight loss in experimental obese Beagle dogs.

The effects of weight loss on hormonal and biochemical blood parameters were measured monthly [carnitine, creatinine, urea, free T4 (fT4), total T4 (TT4), plasma alkaline phosphatases (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), potassium and total proteins] or bimonthly [cholesterol, triglycerides, non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I), glucose, insulin] in eight obese Beagles dogs fed either a high protein dry diet, DP (crude protein 47.5%, on dry matter basis) or a commercial high fibre diet, HF (crude protein 23.8%, crude fibre 23.3%). The dogs were allotted to two groups according to sex and body weight (BW) and they were respectively fed with the DP or the control HF diet during 12-26 weeks, until they reach their optimal BW. The plasma basal triglycerides and cholesterol concentrations were decreased by the two diets but the difference was only significant for the DP diet. The plasma mean NEFA concentration increased regularly over the period with the HF diet, without significant difference between the two diets. No effect of diet or weight loss was observed on plasma carnitine, urea, creatinine, ALP, AST, ALT, potassium, TT4, FT4, IGF-I, glucose and insulin. Weight loss induced a decrease in fT4 plasma concentration (p < 0.001). The high protein diet allowed a safe weight loss.

Animals↗
PubMed1983

Immediate and long-term evolution of the blood-venous graft interface. Experimental study in dogs.

Endothelial damage and repair in autogenous saphenous vein grafts was evaluated serially from 30 s to 9 months after implantation into the femoral arteries of 25 dogs. Light and scanning electron microscopy, quantitative morphometry and cytochemistry with specific rabbit antidog factor VIII-related antigen were used. These studies demonstrate: (1) early complete endothelial cell desquamation both on the venous graft and adjacent artery apparently related to dissection and suture; (2) differing early platelet activation on the venous and adjacent arterial wall, platelet aggregates were noted on the adjacent artery, whereas only adhesive platelets are noted on the exposed vein graft; (3) endothelial reconstitution being initiated after 10-15 days but not reaching completion even 9 months after implantation; (4) a mediointimal proliferation which is a constant feature. A unique cell possessing both fibroblastic and myocytic characteristics takes part in the process.

Animals↗
PubMed1981

Cardiomyopathy of doxorubicin in experimental animals, Factors affecting the severity, distribution and evolution of myocardial lesions.

Heart lesions induced in mice, rats, rabbits and dogs by Doxorubicin administered i.v. according to various schedules were studied by light and electron microscopy Vacuolization of myocardial cytoplasm due to distention of the sarcoplasmic reticulum, the T-tubule system and the Golgi vesicles was one of the most common findings. Myocytolysis, clumping and loss of fibrils, fragmentation of sarcomeres, swelling of mitochondria and an increase in lysosomes and residual bodies were also observed. The severity of the cardiomyopathy, quantitatively evaluated by a score system, proved to be dose-dependent. Cardiomyopathy was more severe when the treatment was given in a short period by administration of high doses than when the same cumulative dose was administered as low doses repeated for a long period. The left atrium was more severely affected than the ventricles when high doses were given, whereas it was less affected in animals given low doses. The cardiomyopathy was less severe in animals receiving the same dose in a high volume of solvent and during a long perfusion time. Threshold doses were needed both to induce the cardiomyopathy and to establish it as a progressive disease.

Animals↗