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Acute promyelocytic leukemia. M.D. Anderson Hospital experience.

Sixty patients with acute promyelocytic leukemia were treated between 1973 and 1984. The overall median survival was 16 months with a five-year survival rate of 31 percent. The complete remission rate was 53 percent and was similar whether they received amsacrine- or anthracycline-based regimens (60 percent versus 51 percent). The median remission duration was 29 months. At five years, 43 percent of patients with responses to treatment had continuous remission and 57 percent were alive. Salvage therapy produced remissions in 53 percent of patients during first relapse, with two long-term survivors after further consolidation with bone marrow transplantation. Early fatal hemorrhage associated with disseminated intravascular coagulopathy during induction therapy occurred in 16 patients (26 percent). Multivariate analysis of the pretreatment patient characteristics significantly associated with an increased risk of fatal hemorrhage identified four that have primary prognostic importance: thrombocytopenia, elevated absolute blast and promyelocyte counts, old age, and anemia. Patients having up to two unfavorable features had a low risk of fatal hemorrhage compared with those who had more than two (5 percent versus 58 percent; p less than 0.0001). Overall, patients who received heparin had a lower incidence of fatal hemorrhage than those who did not (19 percent versus 32 percent). Heparin therapy was not beneficial to those at low risk but was associated with a trend towards decreased hemorrhagic deaths among high-risk patients (45 percent versus 67 percent). Cytogenetic studies demonstrated the characteristic 15;17 translocation in 73 percent of patients with analyzable metaphases, whereas 12 percent had other karyotypic abnormalities. Remission induction was often associated with a gradual atypical morphologic evolution into remission without intermediate hypoplasia with the interim marrows showing a high proportion of blasts. It is concluded that acute promyelocytic leukemia is a unique disease with a high potential for cure. Knowledge of its prognosis using present frontline and salvage therapy, of the factors related to fatal hemorrhage, and of the unusual patient marrow profiles during remission induction may improve the therapeutic approach.

Aminoacridines↗

Parasite speciation within or between host species?--phylogenetic evidence from site-specific polystome monogeneans.

Partial nuclear 28S ribosomal RNA and mitochondrial cytochrome c oxidase subunit I (COI) gene sequences (953 and 385 nucleotides, respectively) of one fish monogenean (outgroup) and six polystome monogeneans (four Polystomoides spp. from the oral cavities and urinary bladders of freshwater turtles in Australia and Malaya, two Neopolystoma spp. from the urinary bladder and conjunctival sac of a freshwater turtle in Australia) were used to examine the question of whether congeneric species infecting different sites in the same host species have speciated in that host by adapting to different sites, or whether species infecting a particular site in one host have given rise to species infecting the same site in different hosts. Results show unequivocally that congeneric species infecting the same site, even of host species belonging to different suborders and occurring on different continents, are more closely related than congeneric species infecting different sites of the same host species. This is interpreted as meaning that speciation has not occurred in one host. Morphological evolution of polystomes has been very slow: few differences between species and even genera have evolved over a period of at least 150 Myr, and this is matched by low substitution rates of nucleotides, and the ambiguous position of species of different genera, depending on whether COI or 28S rDNA sequences are used.

Animals↗

Childhood cirrhosis associated with alpha-1-antitrypsin deficiency. A genetic, biochemical, and morphologic study.

A study of 27 relatives of a child with fatal hepatic cirrhosis due to homozygous Z variant alpha-1-antitrypsin deficiency revealed 15 members with heterozygous MZ phenotypes. Levels of circulating alpha-1-antitrypsin and trypsin-inhibiting capacity were shown to be unreliable in identifying the heterozygous state, Pi typing being necessary for definitive diagnosis. The morphologic evolution of the hepatic changes in this condition have been studied, and the importance of the PAS stain in identification of the characteristic cytoplasmic bodies is stressed.

Autopsy↗

Concentric hemorrhagic necrosis of the myocardium. A morphological and clinical study.

Froty-nine cases of concentric hemorrhagic necrosis of the left ventricular myocardium were reviewed in a series of 97 autopsy studies in patients subjected to cardiopulmonary bypass for various types of cardiac surgery. The gross and microscopic findings were analyzed in order to define the morphologic evolution of the lesion. The extent of involvement was graded by gross examination of serial transverse sections of the heart. Microscopically there were five major histologic changes, probably representing the sequential evolution of the lesion, i.e., contraction bands, subendocardial hemorrhages, coagulative necrosis, healing by granulation tissue, and fibrosis. The location of the lesion conincided with the vulnerable region of the microcirculation. Owing to the implementation of new surgical techniques, the cases were subdivided into two groups, one covering the period from 1963 to 1970 and the other , 1971 to 1974. Concentric hemorrhagic necrosis was less frequent in the more recent group, but when it was present it was more pronounced in the individual heart. The lesion in the earlier group was milder but demonstrated a higher incidence of platelet microthrombi in the heart. In the recent cases concentric hemorrhagic necrosis tended to be more diffuse in aortocoronary bypass than in valvular replacement surgery. We discuss one possible explanation for the development of this lesion, i.e., transient hypoxemia occurring at the time of cardiopulmonary bypass, followed by reperfusion and accelerated necrosis with hemorrhage.

Adult↗

Evolving patterns of tissue composition in benign prostatic hyperplasia as a function of specimen size.

The tissue composition in 36 transurethral resections and four prostate enucleations for benign prostatic hyperplasia (BPH) was quantitated by computerized morphometric techniques using 15 morphologic categories. Data were compared between seven consecutive weight ranges. Nodules of glandular and/or stromal tissue comprised only 5% of tissue in the smallest resections, while bladder neck and anterior fibromuscular tissue represented more than half the specimen. Non-nodular prostatic tissue from the transition zone was the dominant resected component in all but the largest specimens (enucleations) where nodules comprised most of the tissue. Though nodules comprised only 22% of the largest transurethral resections, their contribution to hyperplasia increased more rapidly than any other component. Glandular nodules with a high ratio of epithelium to stroma dominated at all weight ranges. It was concluded that tissue resected for BPH is quite heterogeneous, that nodules comprise most of the tissue only in specimens over 50 g in weight, and that the most common hyperplastic component is histologically normal tissue. Benign prostatic hyperplasia undergoes morphologic evolution with increasing weight, and epithelial-rich nodules are the most rapidly evolving component.

Aged↗

Effects of axotomy, deafferentation, and reinnervation on sympathetic ganglionic synapses: a comparative study.

The main physiological and morphological features of the synapses in the superior cervical ganglia of mammals and the last two abdominal ganglia of the frog sympathetic chain are summarized. The effects of axotomy on structure and function of ganglionic synapses are then reviewed, as well as various changes in neuronal metabolism in mammals and in the frog, in which the parallel between electrophysiological and morphological data leads to the conclusion that a certain amount of synaptic transmission occurs at "simple contacts." The effects of deafferentation on synaptic transmission and ultrastructure in the mammalian ganglia are reviewed: most synapses disappear, but a number of postsynaptic thickenings remain unchanged. Moreover, intrinsic synapses persist after total deafferentation and their number is strongly increased if axotomy is added to deafferentation. In the frog ganglia, the physiological and morphological evolution of synaptic areas is comparable to that of mammals, but no intrinsic synapses are observed. The reinnervation of deafferented sympathetic ganglia by foreign nerves, motor or sensory, is reported in mammals, with different degrees of efficiency. In the frog, the reinnervation of sympathetic ganglia with somatic motor nerve fibers is obtained in only 20% of the operated animals. The possible reasons for the high specificity of ganglionic connections in the frog are discussed.

Afferent Pathways↗

Parvalbumin immunoreactivity during the development of the cerebellum of the rainbow trout.

The distribution of parvalbumin immunoreactivity in the developing cerebellum of the rainbow trout was studied by using a specific monoclonal antibody and the avidin-biotin peroxidase method. Parvalbumin immunoreactivity was absent during the embryonic development of the cerebellum. The first immunoreactive elements, identified by their localization and posterior morphological evolution as immature Purkinje cells, appeared at 6 days posthatching in the presumptive corpus cerebelli and lobus vestibulolateralis. The labeling extended throughout the cerebellum following a caudorostral gradient, and in 21 days alevins, parvalbumin immunoreactive Purkinje cells were also observed in the valvula cerebelli. The appearance of parvalbumin-immunostaining in the Purkinje cells was not simultaneous; the labeling was observed initially in the cell body, extending gradually to the dendritic branches and finally to the axon. From 1 year onwards, parvalbumin immunoreactive terminal puncta from the Purkinje cell axons were observed surrounding the cell bodies of eurydendroid cells, that were parvalbumin immunonegative in all developmental stages studied. The spatio-temporal pattern of parvalbumin immunoreactivity in the rainbow trout cerebellum is different to previous observations in the cerebellum of amniotes.

Animals↗

Deletions of 17p are associated with transition from early to advanced colorectal cancer.

Several chromosome defects parallel morphologic evolution in colorectal tumor progression. Allelic losses in the short arm of chromosome 17, the majority encompassing the 17p13.3 band, have been found in advanced cancer in the absence of TP53 mutations, suggesting that loss of genes in this chromosome region is relevant for tumorigenesis. The aim of this study was to investigate 17p13.3 deletions throughout the colorectal tumor progression using two-color fluorescence in situ hybridization. Histologic sections from 20 colorectal adenomas containing early invasive carcinoma were analyzed by interphase fluorescence in situ hybridization using a centromeric probe for chromosome 17 simultaneously with a subtelomeric probe mapping to the 17p13.3 band. Separate evaluation was made for sectors corresponding to adenoma tissue with low-grade dysplasia, high-grade dysplasia, and early cancer. The same technique was also used in 20 cases of advanced adenocarcinoma of the large bowel. Loss of one centromeric signal was observed in 20, 40, 50, and 10% of low-grade dysplasia, high-grade dysplasia, early cancer, and advanced cancer, respectively (P<0.02 early vs. advanced cancer). Subtelomeric 17p deletions were seen in 60% of advanced cancer and in 15% of early cancer (P<0.01). These findings indicate that loss of genes from the 17p13.3 chromosome region may play an important role in sustaining the transition from early to advanced cancer in colorectal tumor progression.

Adenocarcinoma↗

Morphologic study of the glenoid in primary glenohumeral osteoarthritis.

We studied the natural course and the possibility of making a prognostic classification of glenoid morphology in primary glenohumeral osteoarthritis (GHOA). For this purpose, serial computed tomography scans of 113 osteoarthritic shoulders were reviewed. The position of the humeral head with respect to the glenoid seems to be an important predictor of the glenoid morphologic evolution. Three main glenoid types were defined: Type A, Type B, Type C. Type A (59%) was marked by a well-centered humeral head and a balanced distribution of strengths against the surface of the glenoid. The symmetric erosion was explained by the absence of subluxation. In Type B (32%), the posterior subluxation of the humeral head was responsible for the asymmetric load against the glenoid and was implicated in the development of primary GHOA, particularly the exaggerated posterior wear pattern. Type C (9%) was defined by a glenoid retroversion of more than 25 degrees, regardless of erosion; retroversion was primarily of dysplastic origin and explained the early event of osteoarthritis. In primary GHOA, this classification of the glenoid can discriminate retroversion between posterior erosion and dysplasia.

Aged↗

Cherubism. Histo-enzymological and ultrastructural study.

The 3 cases of cherubism reported affected the mandible. They were all studied by means of histo-enzymological and ultrastructural methods. This study demonstrated 3 stages in the morphological evolution of the disease, corroborated by clinical data. The 1st stage was characterized by an osteolytic granuloma with round, fusiform and giant-cells and a high level of activity of acid phosphatase. The 2nd stage showed repair with proliferation of highly active fibroblasts (increase in activity of leucine aminopeptidase). The 3rd stage exhibited an osteogenesis with high activity of alkaline phosphatase and ATPase. The pathogenesis of this rare osteodysplasia is discussed.

Adolescent↗

A molecular phylogeny of the neotropical butterfly genus Anartia (Lepidoptera: Nymphalidae).

While Anartia butterflies have served as model organisms for research on the genetics of speciation, no phylogeny has been published to describe interspecific relationships. Here, we present a molecular phylogenetic analysis of Anartia species relationships, using both mitochondrial and nuclear genes. Analyses of both data sets confirm earlier predictions of sister species pairings based primarily on genital morphology. Yet both the mitochondrial and nuclear gene phylogenies demonstrate that Anartia jatrophae is not sister to all other Anartia species, but rather that it is sister to the Anartia fatima-Anartia amathea lineage. Traditional biogeographic explanations for speciation across the genus relied on A. jatrophae being sister to its congeners. These explanations invoked allopatric divergence of sister species pairs and multiple sympatric speciation events to explain why A. jatrophae flies alongside all its congeners. The molecular phylogenies are more consistent with lineage divergence due to vicariance, and range expansion of A. jatrophae to explain its sympatry with congeners. Further interpretations of the tree topologies also suggest how morphological evolution and eco-geographic adaptation may have set species range boundaries.

Animals↗

Temporal comparison of Broad-Complex expression during eggshell-appendage patterning and morphogenesis in two Drosophila species with different eggshell-appendage numbers.

A central question in biology is how developmental mechanisms are altered to bring about morphological evolution. Drosophilids boast a remarkable diversity in eggshell-appendage number-from as few as one to as many as nine, depending on the species. Appendage patterning in Drosophila melanogaster is well characterized, inviting candidate-gene-based approaches that identify the developmental mechanisms underlying Drosophilid eggshell diversity. Previous studies show that a combination of Epidermal growth factor receptor (EGFR) and TGFbeta/BMP2,4 Decapentaplegic (DPP) signaling determines appendage fate in D. melanogaster. Broad-Complex expression integrates EGFR and DPP signaling and predicts future appendage position. Here we present our confocal analyses of BR-C immunofluorescence and appendage morphogenesis in Drosophila melanogaster (two appendages) and Drosophila virilis (four appendages). Our comparison suggests that differences in BR-C patterns among Drosophilids may be strongly influenced by anterior-posterior information.

Animals↗

A molecular evolutionary framework for the phylum Nematoda.

Nematodes are important: parasitic nematodes threaten the health of plants, animals and humans on a global scale; interstitial nematodes pervade sediment and soil ecosystems in overwhelming numbers; and Caenorhabditis elegans is a favourite experimental model system. A lack of clearly homologous characters and the absence of an informative fossil record have prevented us from deriving a consistent evolutionary framework for the phylum. Here we present a phylogenetic analysis, using 53 small subunit ribosomal DNA sequences from a wide range of nematodes. With this analysis, we can compare animal-parasitic, plant-parasitic and free-living taxa using a common measurement. Our results indicate that convergent morphological evolution may be extensive and that present higher-level classification of the Nematoda will need revision. We identify five major clades within the phylum, all of which include parasitic species. We suggest that animal parasitism arose independently at least four times, and plant parasitism three times. We clarify the relationship of C. elegans to major parasitic groups; this will allow more effective exploitation of our genetic and biological knowledge of this model species.

Animals↗

DNA phylogeny of the extinct marsupial wolf.

The phylogenetic affiliation of the extinct marsupial wolf (Thylacinus cynocephalus), which once was widespread in Australia, has been uncertain. On the basis of morphology, some systematists argue that the thylacine was most closely related to an extinct group of South American carnivorous marsupials, the borhyaenids, whereas others consider it to be closer to Australian carnivorous marsupials. Here we use direct sequencing by means of the polymerase chain reaction (PCR) to compare 219 bases of mitochondrial (mt) DNA from museum specimens of the marsupial wolf and representatives of six genera of extant marsupials. In agreement with the results of an antigenic study of albumin, our genetic data suggest that the marsupial wolf was more closely related to other Australian marsupial carnivores than to those of South America. Thus, the marsupial wolf represents an example of convergent morphological evolution to South American carnivorous marsupials as well as to true wolves.

Amino Acid Sequence↗

The earliest known fully quadrupedal sirenian.

Modern seacows (manatees and dugongs; Mammalia, Sirenia) are completely aquatic, with flipperlike forelimbs and no hindlimbs. Here I describe Eocene fossils from Jamaica that represent nearly the entire skeleton of a new genus and species of sirenian--the most primitive for which extensive postcranial remains are known. This animal was fully capable of locomotion on land, with four well-developed legs, a multivertebral sacrum, and a strong sacroiliac articulation that could support the weight of the body out of water as in land mammals. Aquatic adaptations show, however, that it probably spent most of its time in the water. Its intermediate form thus illustrates the evolutionary transition between terrestrial and aquatic life. Similar to contemporary primitive cetaceans, it probably swam by spinal extension with simultaneous pelvic paddling, unlike later sirenians and cetaceans, which lost the hindlimbs and enlarged the tail to serve as the main propulsive organ. Together with fossils of later sirenians elsewhere in the world, these new specimens document one of the most marked examples of morphological evolution in the vertebrate fossil record.

Animals↗

The genetics and evo-devo of butterfly wing patterns.

Understanding how the spectacular diversity of colour patterns on butterfly wings is shaped by natural selection, and how particular pattern elements are generated, has been the focus of both evolutionary and developmental biologists. The growing field of evolutionary developmental biology has now begun to provide a link between genetic variation and the phenotypes that are produced by developmental processes and that are sorted by natural selection. Butterfly wing patterns are set to become one of the few examples of morphological diversity to be studied successfully at many levels of biological organization, and thus to yield a more complete picture of adaptive morphological evolution.

Animals↗

Long-term outcome of adult acute leukemia patients who are alive and well 2 years after autologous blood or marrow transplantation.

We studied the long-term outcome of 87 adults with acute leukemia (age 15-59 years at transplant, median 27; 44 myeloid, 42 lymphoblastic, one biphenotypic) who were alive in continuous remission 2 years after a marrow (n = 74) or blood stem cell (n = 13) autograft. Nine relapsed 25-50 months (median 38) after transplantation. Five relapses were straightforward with no karyotypic or morphologic evolution of the original disease. Four recurrences were unusual, with development of myelodysplasia (n = 3) or myeloproliferative disease (n = 1). Five patients died of relapsed disease and four are still alive. Two patients died of complications related to the transplant, and one of ischemic heart disease. Seventy-nine patients (91%) are alive in remission 24-149 months (median 67) after transplantation (75 in continuous remission and four after further therapy) with Karnofsky scores of 80-100% (median 100%). The 8-year probabilities of survival, toxic death, and relapse (from the 2-year mark) are 89%, 3% and 12%. Eleven (12%) survivors had creatinine levels of >110 micromol/l (one more than double), and 14 (16%) had bilirubin levels of >17 mmol/l (one more than double) at the last follow-up. None of the following factors was found to be predictive for survival, non-relapse death, or relapse from the 2-year mark in multivariate analysis: age, sex, type of leukemia, disease stage, diagnosis, conditioning, origin of cells, and nucleated cell dose. We conclude that adult patients with acute leukemia who are alive and well 2 years following an autograft have a high probability of being cured, and the incidence of long-term liver and kidney dysfunction measured by serum bilirubin and creatinine is low.

Acute Disease↗