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[Analysis of loco-regional control rate, metastatic remission and survival in 178 breast cancer patients treated by radical modified mastectomy and post-operative irradiation (author's transl)].

178 cases of post-operative irradiation for breast cancer (145 T1, T2, T3 and 33 T4) are analyzed. According to the surgical procedure there are 146 cases of radical modified mastectomy (Patey) and 32 cases of radical mastectomy (Halsted). The axillary status reveals 50% of involved nodes, but radiotherapy has been systematic on chest wall and supra-clavicular, parasternal, axillary lymph nodes areas. Loco-regional failures are only situated on chest wall (3,9%) and in the supraclavicular area (1,7%). The five year actuarial rate of locoregional control is 93% and 98% if we exclude 7 locoregional failures contemporaneous or consecutive to a metastatic evolution. The five year actuarial rate of metastatic remission for patients with negative axillary nodes (N-) is 83% against 55% for N+ (p < 0,001). The five year actuarial survival rate is 92% (N-) and 64% (N+) (p < 0,001). We discuss about indications of selective irradiation of chest wall and parasternal area for patients with negative axillary nodes and also about post-operative immuno-suppression, and chronology of chemotherapy.

Adult↗

[Controversies in the management of operated pituitary macroadenomas].

BACKGROUND AND PURPOSE: Complete resection of a pituitary adenoma is feasible in almost 50 to 70% of cases. Dealing with the remnant is still controversial. Three positions can be discussed: second stage operation, radiation therapy, clinical and radiological follow-up. METHODS: Among 108 pituitary macroadenomas operated on during the last 10 years, 54 patients (50%) with partially removed tumors were studied. Three cases best illustrating the evolution of these remnants are reported. RESULTS: Late MRI performed 4 to 6 months postoperatively is more valuable than early MRI in the evaluation of these remnants, which can remain stable for a long period of time without any adjuvant treatment. CONCLUSION: MRI should be performed 4 to 6 months postoperatively. Rather than performing radiation therapy systematically for asymptomatic patients, these patients should be followed up at regular intervals and treated only in case of regrowth of the tumor.

Adenoma↗

Masticatory function and post-Pleistocene evolution in Nubia.

The present research focuses on craniofacial variation in Nubia over approximately 10,000 years. Samples were grouped according to their temporal location and subsistence pattern, and represent a transition from a hunting-gathering adaptation (Mesolithic) to a transitional hunting-gathering-agricultural adaptation (A-C Group) and finally to a fully agricultural adaptation (Meroitic/X-Group/Christian). The purposes were: (1) to compare the Mesolithic sample with the later Nubian populations; and (2) to evaluate further the hypothesis that change in Nubian craniofacial morphology was due to changing functional demands associated with the progressive change in subsistence adaptation and associated behavior. The results tend to support recent views that the Nubian Mesolithic population is probably ancestral to later Nubian groups, and that the masticatory-functional hypothesis can best account for craniofacial change among the Nubians since 12,000 B.P. According to this hypothesis systematic reduction in functional demand placed on the masticatory complex from the Mesolithic led, secondarily, to an alteration of the growth of the maxillomandibular complex such that the face became progressively less robust and more inferoposteriorly located relative to the cranial vault. Both the increase in the height of the vault relative to its length, producing a more "globular" appearance, and the reduction in dental size were tertiary, compensatory responses to altered facial size and position.

Biological Evolution↗

Specialization in pyramidal cell structure in the sensory-motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys.

The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species.

Animals↗

Population genetics of transposable DNA elements. A Drosophila point of view.

This paper is an attempt to bring together the various, dispersed data published in the literature on insertion polymorphism of transposable elements from various kinds of populations (natural populations, laboratory strains, isofemale and inbred lines). Although the results deal mainly with Drosophila, data on other organisms have been incorporated when necessary to illustrate the discussion. The data pertinent to the regions of insertion, the rates of transposition and excision, the copy number regulation, and the degree of heterozygosity were analysed in order to be confronted with the speculations made with various theoretical models of population biology of transposable elements. The parameters of these models are very sensitive to the values of the transposable element characteristics estimated on populations, and according to the difficulties of these estimations (population not at equilibrium, particular mutations used to estimate the transposition and excision rates, trouble with the in situ technique used to localize the insertions, undesired mobilization of TEs in crosses, spontaneous genome resetting, environmental effects, etc.) it cannot be decided accurately which model better accounts for the population dynamics of these TEs. Tendencies, however, emerge in Drosophila: the copia element shows evidence for deficiency of insertions on the X chromosomes, a result consistent with selection against mutational effects of copia insertions; the P element repartition does not significantly deviate from the neutral assumption, in spite of a systematic copy number of insertions higher on the X than on the autosomes. Data on other elements support either the neutral model of TE containment, neither of the two models, or both. Prudence in conclusion should then be de rigueur when dealing with such kind of data. Finally the potential roles of TEs in population adaptation and evolution are discussed.

Animals↗

A comparison of genetic variation in two sibling species pairs of haplodiploid insects.

Sibling species pairs of sweat bees (Halictus confusus and H. tumulorum) and pine sawflies (Neodiprion pratti and N. maurus) were surveyed for genetic variability using enzyme electrophoresis. Levels of heterozygosity were found to be within the ranges earlier recorded for Hymenoptera. Expected heterozygosities were not significantly higher in the sawflies than in the sweat bees. Estimates of genetic identity between the sibling species were not lower than those generally found for diplodiploid insect species: no evidence was found for an increased rate of evolution in these haplodiploids. Genetic identity data among populations of H. confusus and between Halictus species were within the range expected for conspecific populations and sibling species, respectively. In Neodiprion all genetic distances were low but the two populations of N. pratti had similar genetic distances as each did to N. maurus, indicating the necessity for further systematic studies of the genus.

Animals↗

Fetal alcohol syndrome: historical perspectives.

Fetal alcohol syndrome (FAS), the most severe manifestation of the adverse effects of alcohol on foetal development, was first described in the French medical literature by Lemoine et al. in 1968 [Les Gfants des parents alcholiques: anomalies observes a propos de 127 cas (The children of alchoholic parents: anomalies observed in 127 cases). Quert in Medicine 8, 476-482]. Five years later, Jones et al., 1973. Pattern of malformation in offspring of chronic alcholic mothers. Lancet 1, 1129-1267] were the first to delineate systematically the association between maternal alcohol abuse and a specific pattern of birth defects and to provide diagnostic criteria for this condition. Several diagnostic systems have since been developed with a view to capturing the wide spectrum of physical and behavioral anomalies resulting from prenatal alcohol exposure. The purpose of the current paper is to outline the evolution of FAS as a medical diagnosis.

Female↗

Phylogenomic inference of protein molecular function: advances and challenges.

MOTIVATION: Protein families evolve a multiplicity of functions through gene duplication, speciation and other processes. As a number of studies have shown, standard methods of protein function prediction produce systematic errors on these data. Phylogenomic analysis--combining phylogenetic tree construction, integration of experimental data and differentiation of orthologs and paralogs--has been proposed to address these errors and improve the accuracy of functional classification. The explicit integration of structure prediction and analysis in this framework, which we call structural phylogenomics, provides additional insights into protein superfamily evolution. RESULTS: Results of protein functional classification using phylogenomic analysis show fewer expected false positives overall than when pairwise methods of functional classification are employed. We present an overview of the motivations and fundamental principles of phylogenomic analysis, new methods developed for the key tasks, benchmark datasets for these tasks (when available) and suggest procedures to increase accuracy. We also discuss some of the methods used in the Celera Genomics high-throughput phylogenomic classification of the human genome. AVAILABILITY: Software tools from the Berkeley Phylogenomics Group are available at http://phylogenomics.berkeley.edu

Algorithms↗

Genetic clues to dispersal in human populations: retracing the past from the present.

Ongoing debate about proper interpretation of DNA sequence polymorphisms and their ability to reconstruct human population history illustrates a important change in perspective that we have achieved in the past 20 years of population genetics. To what extent does the history of a locus represent the history of a population? Tools originally developed for molecular systematics, where genetic lineages have been separated by speciation events, are routinely applied to the analysis of variation within our species, with conflicting results. Because of automated technologies and linkage analysis, we are poised to harvest a wealth of information about our past, if we are successful in moving beyond a current polarization regarding models of human evolution. Rather than just suggesting that true resolution will only come by considering fossil or archaeological evidence, the realistic and appropriate application of genetic models for analysis of population structure is also necessary. Three examples from different dispersal events are highlighted here.

Animals↗

How many genes can make a cell: the minimal-gene-set concept.

Several theoretical and experimental studies have endeavored to derive the minimal set of genes that are necessary and sufficient to sustain a functioning cell under ideal conditions, that is, in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. A comparison of the first two completed bacterial genomes, those of the parasites Haemophilus influenzae and Mycoplasma genitalium, produced a version of the minimal gene set consisting of approximately 250 genes. Very similar estimates were obtained by analyzing viable gene knockouts in Bacillus subtilis, M. genitalium, and Mycoplasma pneumoniae. With the accumulation and comparison of multiple complete genome sequences, it became clear that only approximately 80 genes of the 250 in the original minimal gene set are represented by orthologs in all life forms. For approximately 15% of the genes from the minimal gene set, viable knockouts were obtained in M. genitalium; unexpectedly, these included even some of the universal genes. Thus, some of the genes that were included in the first version of the minimal gene set, based on a limited genome comparison, could be, in fact, dispensable. The majority of these genes, however, are likely to encode essential functions but, in the course of evolution, are subject to nonorthologous gene displacement, that is, recruitment of unrelated or distantly related proteins for the same function. Further theoretical and experimental studies within the framework of the minimal-gene-set concept and the ultimate construction of a minimal genome are expected to advance our understanding of the basic principles of cell functioning by systematically detecting nonorthologous gene displacement and deciphering the roles of essential but functionally uncharacterized genes.

Cells↗

[Belief in magic and magical medicine. Characteristics of its origin and consolidation in folk medicine for animal medical science].

In the evolution of mankind and therefore in the veterinary historiography as well you can find the belief in magic and in magic medicine. In the primitive society our early forefathers began with the magic medicine by domestication and the applying of magic medicine also to animals. Because of witch-hunt and printing the belief in magic was systematized and authorized in the veterinary medicine. With the freedom of trade in the second half of the 19th century the belief in magic and magic medicine flourished also in Germany.

Animals↗

Acute lymphoblastic leukemia and the lymphoblastic lymphomas of childhood.

Recent advances in diagnosis, treatment, and tumor biology of the lymphoid blastic malignancies have challenged historical concepts and created a need for revised classification of these diseases. The authors review this material and present a classification relevant to current therapeutic protocols and available biological data. Further advances in understanding of these diseases can be anticipated, with possible further evolution of classification. The exact clinical role of sensitive studies to monitor residual disease during and after treatment remains to be established. These diseases may present difficult differential diagnostic problems. The importance of accurate diagnosis cannot be overemphasized, as highly successful but divergent treatments have evolved for these various hematopoietic diseases. Diagnostic problems are usually resolved with systematic analysis including careful morphology, cytochemistry, immunologic analysis, and addition of EM and other studies in selected circumstances.

Bone Marrow↗

Molecular systematics and biogeography of the southern South american freshwater "crabs" Aegla (decapoda: Anomura: Aeglidae) using multiple heuristic tree search approaches.

Recently new heuristic genetic algorithms such as Treefinder and MetaGA have been developed to search for optimal trees in a maximum likelihood (ML) framework. In this study we combined these methods with other standard heuristic approaches such as ML and maximum parsimony hill-climbing searches and Bayesian inference coupled with Markov chain Monte Carlo techniques under homogeneous and mixed models of evolution to conduct an extensive phylogenetic analysis of the most abundant and widely distributed southern South American freshwater"crab,"the Aegla(Anomura: Aeglidae). A total of 167 samples representing 64 Aegla species and subspecies were sequenced for one nuclear (28S rDNA) and four mitochondrial (12S and 16S rDNA, COI, and COII) genes (5352 bp total). Additionally, six other anomuran species from the genera Munida,Pachycheles, and Uroptychus(Galatheoidea), Lithodes(Paguroidea), and Lomis(Lomisoidea) and the nuclear 18S rDNA gene (1964 bp) were included in preliminary analyses for rooting the Aegla tree. Nonsignificantly different phylogenetic hypotheses resulted from all the different heuristic methods used here, although the best scored topologies found under the ML hill-climbing, Bayesian, and MetaGA approaches showed considerably better likelihood scores (Delta> 54) than those found under the MP and Treefinder approaches. Our trees provided strong support for most of the recognized Aegla species except for A. cholchol,A. jarai,A. parana,A. marginata, A. platensis, and A. franciscana, which may actually represent multiple species. Geographically, the Aegla group was divided into a basal western clade (21 species and subspecies) composed of two subclades with overlapping distributions, and a more recent central-eastern clade (43 species) composed of three subclades with fairly well-recognized distributions. This result supports the Pacific-Origin Hypothesis postulated for the group; alternative hypotheses of Atlantic or multiple origins were significantly rejected by our analyses. Finally, we combined our phylogenetic results with previous hypotheses of South American paleodrainages since the Jurassic to propose a biogeographical framework of the Aegla radiation.

Animals↗

Viral evolution and insects as a possible virologic turning table.

Three lines of observation demonstrate the role of arthropods in transmission and evolution of viruses. a) Recent outbreaks of viruses from their niches took place and insects have played a major role in propagating the viruses. b) Examination of the list of viral families and their hosts shows that many infect invertebrates (I) and vertebrates (V) or (I) and plants (P) or all kingdoms (VIPs). This notion holds true irrespective of the genome type. At first glance the argument seems to be weak in the case of enveloped and non-enveloped RNA viruses with single-stranded (ss) segmented or non-segmented genomes of positive (+) or negative polarity. Here, there are several families infecting V or P only; no systematic relation to arthropods is found. c) In the non-enveloped plant viruses with ss RNA genomes there is a strong tendency for segmentation and individual packaging of the genome pieces. This is in contrast to ss+ RNA animal viruses and can only be explained by massive transmission by seed or insects or both, because individual packaging necessitates a multihit infection. Comparisons demonstrate relationships in the nonstructural proteins of double-stranded and ss+ RNA viruses irrespective of host range, segmentation, and envelope. Similar conclusions apply for the negative-stranded RNA viruses. Thus, viral supergroups can be created that infect V or P and exploit arthropods for infection or transmission or both. Examples of such relationships and explanations for viral evolution are reviewed and the arthropod orders important for cell culture are given.

Amino Acid Sequence↗

Evolution of the diatoms (Bacillariophyta). II. Nuclear-encoded small-subunit rRNA sequence comparisons confirm a paraphyletic origin for the centric diatoms.

A phylogeny of the diatoms was inferred from comparisons of nuclear-encoded small subunit ribosomal RNA coding regions using maximum likelihood, weighted maximum parsimony, and neighbor-joining distance methods with Jukes and Cantor, Kimura, Gamma, van de Peer, and LogDet evolutionary models. Analyses of 30 taxa in 11 orders recovered two clades (Clades I and II). Neither of these clades correspond to the three classes of diatoms presently recognized or to the traditionally recognized radially symmetrical centric diatoms or bilaterally symmetrical pennate diatoms. All analyses show that the centric diatoms are a paraphyletic lineage. Tests of alternative phylogenies that address existing hypotheses regarding diatom systematics with the maximum likelihood and maximum parsimony methods support the two clades. Clade I is defined by centric diatom orders with specialized tubes, termed labiate processes, located peripherally in the cell wall. Clade II contains (1) bi(multi)polar centric diatoms with centrally located labiate processes, (2) centric diatoms with other central tubes termed strutted processes, and (3) pennate diatoms. Morphological evidence from fossil assemblages and cytological architecture support the results of the molecular analyses, whereas morphological features of extant diatoms are too derived to resolve the deeper branches in the tree.

Animals↗

Long-term evaluation of the replacement of the trachea with an autologous aortic graft.

BACKGROUND: Tracheal reconstruction after extensive resection remains a challenge in thoracic surgery. The goal of this experimental study was to analyze the long-term evolution of tracheal replacement using an autologous aortic graft. METHODS: In 21 sheep, a 5-cm segment of the cervical trachea was replaced by a segment of the descending thoracic aorta that was reconstructed to a prosthetic graft. Because of the airway collapse reported in a previous series, a permanent (n = 13) or temporary (n = 8) stent was systematically placed in the lumen of the graft. Clinical, bronchoscopic, and histologic examinations were performed up to 3 years after implantation. RESULTS: All animals survived the operation with no paraplegia. In the group with a permanent stent, three complications occurred: one stent displacement, one laryngeal edema, and one infection. Stent removal was tolerated after 6 months in the group with a temporary stent. Histologic examination showed a progressive transformation of the arterial segment into first extensive inflammatory tissue with a squamous epithelium, and after 6 to 36 months well-differentiated tracheal tissue including a continuous mucociliary epithelium and regular rings of newly formed cartilage. CONCLUSIONS: An autologous aortic graft used as a substitute for extensive tracheal replacement in sheep remained functional for periods up to 3 years. The progressive transformation of the graft into a structure resembling tracheal tissue seems to be a key factor in long-term patency. The mechanism of this regenerative process and the possibility of using arterial homografts, which would make clinical application easier, remain to be evaluated.

Animals↗

Influence of shape and energy anisotropies on the phase diagram of discotic molecules.

We present Monte Carlo simulations of discotic molecules using the Gay-Berne potential with shape (kappa) and energy (kappa(')) anisotropies. Following the previous work of Bates and Luckhurst [J. Chem. Phys. 104, 6696 (1996)] at kappa=0.345, kappa(')=0.2 when we determine the sequence of different phases at the same reduced pressure P(*)=50, we find an additional phase at low temperatures corresponding to an orthorhombic crystalline phase and we characterize it. Keeping the shape anisotropy fixed at kappa=0.2, we determine the evolution of the phase diagram with varying energy anisotropy. At high kappa('), low anisotropy, the system is not able to build columns while at low kappa('), the system exhibits both orthorhombic crystal as well as hexagonal liquid crystal phases over a wide range of pressures and temperatures. The domain of stability of the nematic phase is found to systematically shift towards higher pressures as kappa(') decreases.

Journal Article↗

Classification of phospholipases A2 according to sequence. Evolutionary and pharmacological implications.

The sequences of 32 phospholipases A2 (EC 3.1.1.4) were systematically compared on the basis of polypeptide chain length and similarity at selected amino acid positions around the active site. Two difference matrices were constructed and the various groupings present in the data were expressed in dendrogram form. The two methods of comparison yielded different results, and this is seen as a consequence of separate aspects of phospholipase evolution being highlighted in each case. It appears that, although Elapid snake venom phospholipases are very similar in terms of overall conformation, the area around their active sites distinguishes them into two major groups, namely the Asian Elapids and the marine/Australasian Elapids. Further, the Asian Elapids seem to have active-site vicinities which are closer to those in the mammalian pancreatic phospholipases. The relevance of the classifications to structure/activity relationships (especially beta-neurotoxicity) and phospholipase evolution is discussed.

Amino Acid Sequence↗