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PubMed1995

Computer simulation modelling and visualization of 3D architecture of biological tissues. Simulation of the evolution of normal, metaplastic and dysplastic states of the nasal epithelium.

Recent technical improvements, such as 3D microscopy imaging, have shown the necessity of studying 3D biological tissue architecture during carcinogenesis. In the present paper a computer simulation model is developed allowing the visualization of the microscopic biological tissue architecture during the development of metaplastic and dysplastic lesions. The static part of the model allows the simulation of the normal, metaplastic and dysplastic architecture of an external epithelium. This model is associated to a knowledge base which contains only data on the nasal epithelium. The latter has been well studied by numerous authors and its lesional states are well known. An inference engine allows the initialization of the static model parameters. A statistical comparison between simulated epithelia and real epithelia is achieved by adjusting the parameter values during the simulation. The dynamic part of the model allows the simulation of a growth process on a 3D representation based on the static model. The main hypothesis is that nasal epithelium is submitted to a continuous transformation from normal to cancer through metaplasia and dysplasia. The evolution of each cell (represented by its nucleus) depends on its local environment and also on its heritage from its mother-cell. Simulation of tissue renewal of the nasal pseudostratified epithelium has been achieved. The evolution from normal to hyperplasia has been simulated. After modification of the cell cycle modelling, the simulation of the development of metaplastic foci has been obtained.

Cell Cycle↗

PubMed1967

Changing man.

The human condition is changing both culturally and biologically. Although the cultural evolution overshadows the biological, the two are connected by feedback relationships; culture has a biological foundation. Natural selection continues to operate in modern mankind, but its action ought to be supplemented by artificial selection. The problems of the management of human evolution are, however, as much sociological as they are biological. The success of any eugenical program depends on the creation of favorable conditions for human development and self-actualization. In particular, the urgency of the problem of uncontrolled overpopulation exceeds at present that of genetic improvement. Contrary to the alarmist views of some biologists, the evolutionary perspectives for the human species may be regarded as favorable, although, of course, subject to improvement. Man should be the maker of his history, including his evolutionary history. The trend toward increasing social mobility and equality of opportunity may have desirable genetic effects because of the positive assortative mating which it encourages. It makes possible the realization of many hitherto concealed genetically conditioned talents and aptitudes. Rapid progress of both molecular and organismic, Cartesian and Darwinian, biology gives hope of development of new and powerful methods of genetic engineering, control of gene action, betterment of the environment, and improved understanding of the evolutionary processes in the living world, including man.

Biological Evolution↗

PubMed2005

Acute intramural hematoma of the aorta: a mystery in evolution.

BACKGROUND: The definition, prevalence, outcomes, and appropriate treatment strategies for acute intramural hematoma (IMH) continue to be debated. METHODS AND RESULTS: We studied 1010 patients with acute aortic syndromes who were enrolled in the International Registry of Aortic Dissection (IRAD) to delineate the prevalence, presentation, management, and outcomes of acute IMH by comparing these patients with those with classic aortic dissection (AD). Fifty-eight (5.7%) patients had IMH, and this cohort tended to be older (68.7 versus 61.7 years; P<0.001) and more likely to have distal aortic involvement (60.3% versus 35.3%; P<0.001) compared with 952 patients with AD. Patients with IMH described more severe initial pain than did those with AD but were less likely to have ischemic leg pain, pulse deficits, or aortic valve insufficiency; moreover, they required a longer time to diagnosis and more diagnostic tests. Overall mortality of IMH was similar to that of classic AD (20.7% versus 23.9%; P=0.57), as was mortality in patients with IMH of the descending aorta (8.3% versus 13.1%; P=0.60) and the ascending aorta (39.1% versus 29.9%; P=0.34) compared with AD. IMH limited to the aortic arch was seen in 7 patients, with no deaths, despite medical therapy in only 6 of the 7 individuals. Among the 51 patients whose initial diagnostic study showed IMH only, 8 (16%) progressed to AD on a serial imaging study. CONCLUSIONS: The IRAD data demonstrate a 5.7% prevalence of IMH in patients with acute aortic syndromes. Like classic AD, IMH is a highly lethal condition when it involves the ascending aorta and surgical therapy should be considered, but this condition is less critical when limited to the arch or descending aorta. Fully 16% of patients have evidence of evolution to dissection on serial imaging.

Acute Disease↗

PubMed1990

The involucrin genes of pig and dog: comparison of their segments of repeats with those of prosimians and higher primates.

The involucrin genes of the dog and the pig have been cloned and sequenced. Like the corresponding genes of the prosimians, each contains a homologous segment of short tandem repeats at the same position in the coding region. However, the codon sequence of the repeats in the prosimians differs significantly from that of the nonprimate mammals. This evolution has been brought about by a combination of genetic modifications (selective deletions, mutations, and gene conversions). In the anthropoids, this segment of repeats was replaced by a modern one differing in location, sequence, and repeat length. In several of its properties the modern segment has continued the prosimian trend away from the nonprimates. The overall direction of the evolution of this segment has therefore been maintained even though there have been sudden changes in the evolutionary processes acting on the gene.

Animals↗

PubMed2001

On the origin and evolution of the human immunodeficiency virus (HIV).

The human AIDS viruses--HIV-1 and HIV-2--impose major burdens on the health and economic status of many developing countries. Surveys of other animal species have revealed that related viruses--the SIVs are widespread in a large number of African simian primates where they do not appear to cause disease. Phylogenetic analyses indicate that these SIVs are the reservoirs for the human viruses, with SIVsm from the sooty mangabey monkey the most likely source of HIV-2, and SIVcpz from the common chimpanzee the progenitor population for HIV-1. Although it is clear that AIDS has a zoonotic origin, it is less certain when HIV-1 and HIV-2 first entered human populations and whether cross-species viral transmission is common among primates. Within infected individuals the process of HIV evolution takes the form of an arms race, with the virus continually fixing mutations by natural selection which allow it to escape from host immune responses. The arms race is less intense in SIV-infected monkeys, where a weaker immune response generates less selective pressure on the virus. Such a difference in virus-host interaction, along with a broadening of co-receptor usage such that HIV strains are able to infect cells with both CCR5 and CXCR4 chemokine receptors, may explain the increased virulence of HIV in humans compared to SIV in other primates.

Animals↗

PubMed1999

[Sudden death by sleep apnea syndrome associated with myxedema. A case report and a review of the literature].

The case is presented of a 48-year old, slightly overweight, brachymorphic male affected by undiagnosed myxedema, admitted for nocturnal dyspnea present for several years but worsened in the last few weeks. At the age of 19, a paranoid schizophrenia diagnosis was indicated leading to repeated admissions to psychiatric hospitals and continued pharmacological therapy. His sensorium was lucid albeit with a slight psycho-motor slowing down; pharyngeal edema and macroglossia were also apparent, blood O2 saturation was 97%. After the first emergency exams, a hypothyroid condition associated with multinodular goiter and tracheal dislocation was found. Administration of triiodothyronine p.o. and hydrocortisone i.v. was thus initiated. In the doubt of sleep apnea syndrome (SAS) occurrence, pulse oximetry was performed, but after 7 hours, the patient suddenly deceased. Data showed waves of deep O2 desaturation secondary to periods of prolonged apnea. A literature review shows that such a case has never been reported. A posteriori analysis of the patient's clinical management indicates that the obstructive form of SAS, associated with myxedema is a condition which needs to be promptly diagnosed; due to the possible seriousness of its functional evolution, the need for intensive or sub-intensive therapy, with continuous nasal airway positive pressure or with oro-tracheal intubation and assisted ventilation, should be carefully taken into consideration; continuous cardiac monitoring should also be carried out, given the risk for acute coronary complications and ventricular arrhythmias in the early phases of substitutive therapy with thyroid hormone.

Death, Sudden↗

PubMed2004

Are residues in a protein folding nucleus evolutionarily conserved?

Protein is the working molecule of the cell, and evolution is the hallmark of life. It is important to understand how protein folding and evolution influence each other. Several studies correlating experimental measurement of residue participation in folding nucleus and sequence conservation have reached different conclusions. These studies are based on assessment of sequence conservation at folding nucleus sites using entropy or relative entropy measurement derived from multiple sequence alignment. Here we report analysis of conservation of folding nucleus using an evolutionary model alternative to entropy-based approaches. We employ a continuous time Markov model of codon substitution to distinguish mutation fixed by evolution and mutation fixed by chance. This model takes into account bias in codon frequency, bias-favoring transition over transversion, as well as explicit phylogenetic information. We measure selection pressure using the ratio omega of synonymous versus non-synonymous substitution at individual residue site. The omega-values are estimated using the PAML method, a maximum-likelihood estimator. Our results show that there is little correlation between the extent of kinetic participation in protein folding nucleus as measured by experimental phi-value and selection pressure as measured by omega-value. In addition, two randomization tests failed to show that folding nucleus residues are significantly more conserved than the whole protein, or the median omega value of all residues in the protein. These results suggest that at the level of codon substitution, there is no indication that folding nucleus residues are significantly more conserved than other residues. We further reconstruct candidate ancestral residues of the folding nucleus and suggest possible test tube mutation studies for testing folding behavior of ancient folding nucleus.

Amino Acid Sequence↗

PubMed2006

Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 evolution.

The error-prone replication of human immunodeficiency virus type 1 (HIV-1) enables it to continuously evade host CD8+ T-cell responses. The observed transmission, and potential accumulation, of CD8+ T-cell escape mutations in the population may suggest a gradual adaptation of HIV-1 to immune pressures. Recent reports, however, have highlighted the propensity of some escape mutations to revert upon transmission to a new host in order to restore efficient replication capacity. To more specifically address the role of reversions in early HIV-1 evolution, we examined sequence polymorphisms arising across the HIV-1 genome in seven subjects followed longitudinally 1 year from primary infection. As expected, numerous nonsynonymous mutations were associated with described CD8+ T-cell epitopes, supporting a prominent role for cellular immune responses in driving early HIV-1 evolution. Strikingly, however, a substantial proportion of substitutions (42%) reverted toward the clade B consensus sequence, with nearly one-quarter of them located within defined CD8 epitopes not restricted by the contemporary host's HLA. More importantly, these reversions arose significantly faster than forward mutations, with the most rapidly reverting mutations preferentially arising within structurally conserved residues. These data suggest that many transmitted mutations likely incur a fitness cost that is recovered through retrieval of an optimal, or ancestral, form of the virus. The propensity of mutations to revert may limit the accumulation of immune pressure-driven mutations in the population, thus preserving critical CD8+ T-cell epitopes as vaccine targets, and argue against an unremitting adaptation of HIV-1 to host immune pressures.

CD8-Positive T-Lymphocytes↗

PubMed2004

Deletion 6p23 and add(11)(p15) leading to NUP98 translocation in a case of therapy-related atypical chronic myelocytic leukemia transforming to acute myelocytic leukemia.

A NUP98 gene translocation occurring with a del(6p23) and an add(11)(p15) was determined in a 61-year-old patient with therapy-related atypical chronic myelocytic leukemia after complete remission from acute promyelocytic leukemia that eventually underwent clonal evolution and transformed to CD56-positive acute myelocytic leukemia (French-American-British classification M0). Precise chromosome analysis by G-banding, spectral karyotyping analysis, and dual-color fluorescence in situ hybridization showed this abnormality as 46,XY,del(6)(p23),add(p15). ish del(6)(NUP98-,D6Z1+),der(7)(NUP98+,D7Z1+),der(11)(NUP98+,D11Z1). A split signal of NUP98 was observed in 68.4% of the 117 cells analyzed, which clearly indicated that the NUP98 partially translocated to chromosome 7. However, the potential fusion partner of the NUP98 was not HOX family or DEK. The fusion gene has not been found by a differential display method. The significance of simultaneously combined del(6)(p23), which also has been reported with secondary leukemogenesis, has not been elucidated. Additional karyotype abnormalities evolved increasingly, and leukocytosis with blasts with more complex karyotypic abnormalities appeared 5 months later. Careful and continuous analysis of karyotype change clarified the process of the clonal evolution after NUP98 translocation. Further investigation of molecular characterization of this NUP98 translocation and interaction with 6p23 abnormalities might be worthwhile for understanding leukemogenesis.

Chromosome Deletion↗

PubMedDate not supplied

Spontaneous rupture of the esophagus: report of two cases.

OBJECTIVE: To study the diagnosis, prognosis and management of spontaneous rupture of the esophagus. DESIGN: This is a retrospective study through the analysis of two cases with delayed diagnosis and subsequent treatment at the Track Surgery Service. LOCALE: The study was performed at the Thoracic Surgery Unit of the Hospital do Servidor Público Estadual Francisco Morato de Oliveira in the city of São Paulo. This is a specialized service. PARTICIPANTS: The two patients reported on had suffered spontaneous rupture of the esophagus. They were transferred to the Thoracic Surgery Unit because of the worsening of their condition in the previous institution which they had been admitted into. MEASUREMENT: The two patients with esophagus pleural fistula received similar treatment, initially advocated by Kanashin in Russia and Hauer-Santos in the United States, which consists of washing the fistula and using continuous pleural aspiration. RESULTS: Although both patients had to spend a long period of time in hospital, their evolution was satisfactory with the treatment adopted, and the fistula closed. CONCLUSION: The authors conclude that the method of lavage of the mediastinum and continuous pleural aspiration, in patients who after spontaneous rupture of the esophagus developed a pleural esophagus fistula due to belated diagnosis, is an alternative and satisfactory therapy. Furthermore, in order to have the best outcome, an early diagnosis is recommended and thoracostomy as the surgical procedure, with primary suture.

Aged↗

PubMed1998

Evolution of angiosperms via modulation of antagonisms.

The controversies concerning the evolutionary mechanisms of flowering plants continue unabated in spite of the current trends toward the analysis of macromolecular data and of the growing body of distributional micromolecular data. The usual narrative approach to this latter effort is here replaced by a novel technique, quantitative phytochemistry. An evolutionary outline emerges and reveals modulation of antagonisms as the fundamental mechanism of angiosperm evolutionary ecology. Origin or operation of many systems can be rationalized analogously. It is concluded that the impact of opposing features possesses universal relevance.

Biological Evolution↗

PubMed2003

Chromosome instability in cancer: how, when, and why?

The majority of malignant tumors exhibit complex genomic aberrations, and it has been suggested that an elevated rate of chromosome mutation is present in neoplastic cells. This chromosomal evolution is probably initiated at a preinvase stage and then proceeds continuously but at variable rates during tumor progression. Even though the initiating events may vary among neoplasms, the end point is often a similar set of cytogenetic and cytological events. These include an excessive shortening of telomeric repeats, disrupting the normal mitotic process and triggering chromosomal breakage-fusion-bridge events and gross genomic imbalances. Telomere dysfunction may also cause a failure of cytokinesis, resulting in tetraploidization and the accumulation of supernumerary centrosomes. In turn, this could cause multipolar cell division and gross aberrations in chromosome number. Several well-known cancer risk factors could contribute to these processes. For instance, breakage-fusion-bridge instability can be induced directly by clastogenic substances, whereas papilloma virus infection has been shown to dysregulate centrosome function. A prerequisite for the induction of chromosome instability through these mechanisms is partial inactivation of the DNA damage response and the mitotic checkpoint functions. Also, overexpression of telomerase appears to play a crucial role for moderating the rate of chromosomal evolution.

Chromosome Aberrations↗

PubMed2003

[Spectroscopic study on the time evolution behaviors of the laser-induced air plasma].

The time-resolved spectra of the air-breakdown plasma produced by the 1.06 microns beam of a Nd:YAG laser were investigated by using the time-delayed spectra and the spectral line evolution methods. The time evolutions of the short wavelength band and long wavelength band of the continuous spectra of the air-breakdown plasma have been measured. The result shows that the decay rates of both bands are slowing down 0.5 microsecond after the excitation of the plasma, and the attachment and the detachment of free electrons by O2 in the plasma could be the reason for this behavior. The results of the time-resolved measurements of the line spectra show that most of the line spectra have the evolution time longer than their lifetimes, and the evolutions of some line spectra take a fashion of "decay-grow-decay". We consider these evolution behaviors of the line spectra to be related to various recombination processes and the energy transfer processes of the decaying plasma.

Air↗

PubMed2004

Reversion of CTL escape-variant immunodeficiency viruses in vivo.

Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations in a heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage to new animals. We therefore infected macaques with a cloned SIV bearing escape mutations in three immunodominant CTL epitopes, and followed viral evolution after infection. Here we show that each mutant epitope sequence continued to evolve in vivo, often re-establishing the original, CTL-susceptible sequence. We conclude that escape from CTL responses may exact a cost to viral fitness. In the absence of selective pressure upon transmission to new hosts, these original escape mutations can be lost. This suggests that some HIV CTL epitopes will be maintained in human populations.

AIDS Vaccines↗

PubMed1991

Long-term EEG monitoring in the early premature: developmental and chronobiological aspects.

Long-term cassette EEG monitoring in the neonatal intensive care unit has established prognostic criteria regarding the developmental outcome by quantifying seizure activity. The clinical significance of the organization of continuous and discontinuous EEG patterns in the early premature is still an open question. This report presents quantified EEG data from repeated 24 h records during the first week of life in premature infants (conceptional age less than 32 weeks) with and without ultrasound evidence of intracerebral hemorrhage. The repartition and evolution of EEG background activity is not a reliable parameter regarding pathology. The continuity index is rather a maturational variable and its ultradian fluctuation is an early expression of the "basic rest activity cycle" (BRAC) rhythm.

Aging↗

PubMed1995

Update on current techniques of myocardial protection.

The spectrum of strategies for myocardial protection has led to the artificial creation of adversarial positions in regard to warm versus cold blood cardioplegia, antegrade versus retrograde delivery, and intermittent versus continuous perfusion. This report reviews the background for the aforementioned methods, that has led to the evolution of an integrated myocardial management technique that combines the advantages of the aforementioned methods to compensate for their individual shortcomings. This approach coordinates the myocardial protective strategies with the continuity of the operation so that the surgical procedure is never interrupted. It provides unimpaired vision, avoids unnecessary ischemia and cardioplegic overdose, allows aortic clamping as soon as cardiopulmonary bypass is started, permits aortic unclamping and discontinuation of bypass shortly after the technical procedure is completed, and minimizes the ration of ischemia and cardiopulmonary bypass. The preliminary results in 1,474 patients from four centers with surgeons participating in the infrastructure of this method are presented.

Aorta↗

PubMed1997

Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

Animals↗

PubMed1981

Ontophyletics of the nervous system: eyeless mutants illustrate how ontogenetic buffer mechanisms channel evolution.

Genetics and molecular biology have shown the mechanisms that allow the genome to provide both the continuity and the variation from generation to generation within a phylogeny. Embryology and developmental biology show the mechanisms that turn the genome into an organism. Mutations, the basis for evolutionary change, cannot in themselves ensure concordance between their products and the products of unchanged genes. Thus, mutations will not necessarily produce a viable organism. On the other hand, ontogenetic buffer mechanisms normally maintain concordance in the developing organism. In addition, ontogenetic buffer mechanisms can integrate discordant mutations into viable organisms that can then be perpetuated during evolution. The evolutionary role of one ontogenetic buffer mechanism, compensatory innervation, is well illustrated in the anopthalmic mutant mouse. In the anopthalmic mouse, a single gene mutation removes afferent axons of the dorsal lateral geniculate nucleus, and compensatory innervation by another population of axons ensures that the dorsal lateral geniculate remains integrated into the central nervous system. Within each organism's ontogeny is a hierarchy of sources of compensatory innervation, and this hierarchy will determine how any particular deafferentating mutation will be buffered. In this way, an ontogeny can channel the phylogeny of which it is a member.

Animals↗