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Results for “somatic evolution”

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At least 55 records · Page 3Linked to original sources
PubMed1992

Experience of isolated sleep paralysis in clinical practice in Nigeria.

The supernatural fears associated with the experience of isolated sleep paralysis in the culture of developing countries is sometimes associated with the evolution of somatic symptoms of psychological origin in patients predisposed to neurotic illness. Patients rarely spontaneously volunteer these fears and doctors pay them scant attention. Illustrative case histories that demonstrate the dynamics of the clinical presentation, as well as the treatment approach, are highlighted. It is hoped that doctors in general medical practice and in psychological medicine in developing countries where belief in supernatural causation of illness is rife will consider these factors in order to provide more effective treatment.

Adult↗
PubMed1987

Facilitation of emergence of multidrug-resistant state by alteration of tumor environment: implications from competitive ecology models.

The presence of multidrug-resistant (MDR) cells in a solid tumor constitutes a major problem in cancer therapy. Current thinking suggests that the resistant phenotype arises de novo during the tumor's evolution via somatic mutation mechanisms. The proportion of MDR cells, once established, may be enriched during therapy as a consequence of differential cell kill. Michelson et al have developed mathematical models of these phenomena to gain an insight into the dynamics of clonal subpopulation emergence in general and MDR emergence in particular, and I now show that one unexpected consequence of therapy may be the facilitation of MDR emergence due to damage inflicted on the host. The therapeutic damage to the host is modeled as a decreased ability to carry a specific tumor burden.

Antineoplastic Agents↗
PubMed1987

Evolution of antibody variable region structure during the immune response.

The results reviewed above reveal that during the anti-Ars immune response of strain A mice a somatic process that results in the evolution of V region structure occurs. This process involves both the selection of V regions encoded by particular gene segment combinations as well as the selection of structural variants of these V regions produced by somatic mutation as the immune response progresses. As a result, both quantitative and qualitative changes in the V region population initially elicited by immunization take place. The structural and functional character of the immune V region repertoire appears to be largely determined by this process of "somatic evolution" occurring in the primary response.

Animals↗
PubMed1990

Parallel evolution of antibody variable regions by somatic processes: consecutive shared somatic alterations in VH genes expressed by independently generated hybridomas apparently acquired by point mutation and selection rather than by gene conversion.

We identified, in independently generated hybridoma antibodies, blocks of shared somatic alterations comprising four consecutive amino acid replacements in the CDR2s of their heavy chain variable regions. We found that the nucleotide sequences encoding the shared replacements differed slightly. In addition, we performed genomic cloning and sequencing analyses that indicate that no genomic sequence could encode the block of shared replacements in any one of the antibodies and thus directly serve as a donor by a recombinational process. Finally, in a survey of other somatically mutated versions of the same heavy chain variable gene, we found several examples containing one, two, or three of the shared CDR2 mutations in various combinations. We conclude that the shared somatic alterations were acquired by several independent events. This result, and the fact that the antibodies containing the four shared mutations were elicited in response to the same antigen and are encoded by the same VH and VK gene segments, suggests that an intense selection pressure has fixed the shared replacements by favoring the clonal expansion of B cells producing antibodies that contain them. The basis of this selection pressure is addressed elsewhere (Parhami-Seren, B., L. J. Wysocki, M. N. Margolies, and J. Sharon, manuscript submitted for publication).

Amino Acid Sequence↗
PubMed1980

Some mathematics of recombination: evolution of complexity and genotypic modification in somatic cells - a possible model for aging and cancer effects.

A plausible discrete time model is proposed, in an effort to explain genotypic modificaton via genetic recombination. The model is used in an effort to explain the evolution of macromolecular complexity. By macromolecular complexity we mean the evolution of a more complex form of a given protein or enzyme from its less-complex ancestors. The model is also used to draw some conclusions concerning the utility of recombination events in aging and carcinogenesis.

Aging↗
PubMed1992

Synapsis, recombination, and meiotic segregation in the mesquite lizard, Sceloporus grammicus, complex. II. Fission heteromorphism of the FM2 cytotype and evolution of chromosome 2.

Somatic and meiotic chromosomal and synaptonemal complex techniques were used to characterize the chromosomal complement and to study the fission heteromorphism of chromosome 4 in the FM2 cytotype of Sceloporus grammicus. Analysis of silver-stained somatic metaphases revealed that the nucleolar organizer region in this cytotype is located at the distal end of a pair of medium-sized acrocentric chromosomes, rather than on the largest acrocentric chromosomal pair, as previously reported. This condition is hypothesized to be the result of at least two sequential rearrangements. Analysis of surface-spread zygotene and pachytene nuclei indicated that the components of the chromosome 4 trivalent initiated synapsis at their distal telomeric regions. Although synapsis of the fission trivalent was synchronous with that of the homomorphic autosomal pairs, completion of synapsis was delayed in the trivalent. Associations between the fission trivalent and other autosomal or sex-chromosomal elements occurred in approximately one third of the pachytene nuclei examined. Analysis of secondary spermatocytes (metaphase II configurations) revealed low levels of nondisjunction in fission heterozygotes. These analyses indicate that FM2 individuals heterozygous for the fission rearrangement of chromosome 4 suffer no meiotic deficit.

Animals↗
PubMed1996

The mutation rate and cancer.

The selection of advantageous mutations underlies tumorigenesis. The growth of a tumor is therefore a form of evolution at the somatic level, in which the population is comprised of individual cells within the tumor. Models of tumorigenesis have considered the relative importance of mutation and selection. We show that selection is more important than an increased mutation rate in the growth of a tumor. Some cancers may acquire a "mutator phenotype," probably leading to faster growth, but mutator phenotypes are not necessary for carcinogenesis.

Biological Evolution↗
PubMed1993

Affinity maturation of lymphocyte receptors and positive selection of T cells in the thymus.

In this review we have re-evaluated the dominant paradigm that TcR V genes do not somatically mutate. We highlight the many structural and functional similarities between Ig and TcR antigen-specific receptors on B and T cells. We have reviewed the factors influencing the somatic and germline evolution of IgV regions in B cells, have evaluated in detail various models which could be invoked to explain the pattern of variation in both transcribed and non-transcribed segments of germline IgV-gene DNA sequences, and applied this perspective to the TcR V beta and V alpha genes. Whilst specific TcRs recognize a complex of a short antigenic peptide bound to MHC Class I or II glycoprotein, and Ig receptors can recognize both oligopeptides and conformational determinants on undegraded polypeptides, they both employ heterodimer variable regions (Fabs) utilizing all three CDRs in epitope binding. We conclude that a plausible case can be made for the possibility that rearranged TcR V genes may undergo some type of somatic hypermutation process during T-cell development in the thymus (concurrent with or after the positive selection phase) thus allowing a repertoire of TvR alpha beta heterodimers to be both positively and negatively selected by the same set of ligands (self MHC + self peptide) in the thymus.

Animals↗
PubMedDate not supplied

[Psychoneuroimmunological connections (II)].

Complementary neuro-endocrine-immune data, concomitant and successive lesions at the central nervous and immune systems as well as clinical interferences make possible the use of psychoimmunology in the various aspects of the diagnostic and therapeutic process. This paper makes references to the hypotheses regarding the share the immunobiological factors have in the pathogenesis of schizophrenic psychoses, affective disturbances, psychotic production consecutive to infections and/or febrile processes. The influence of psychic state on the evolution od some somatic affections with immunopathological determinism is also discussed.

Blood-Brain Barrier↗
PubMed1988

The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution.

We have isolated and determined the DNA sequences of the human somatic cytochrome c gene (HCS) and 11 processed pseudogenes. HCS is the functional homologue to the previously characterized rat somatic gene because it correctly encodes the human heart protein, is present in single copy in the human genome, is nearly identical in both size and intron/exon structure to rodent somatic genes, and shares a high degree of sequence homology with its rat counterpart including a well-conserved promoter region (77% over 250 nucleotides). In contrast to the rodent system, however, where the known pseudogenes all originated from a locus encoding the present day cytochrome c, the human pseudogenes are of two types. A predominant class of older pseudogenes came from a progenitor of HCS that encoded an ancestral form of the protein, while a second group of only a few young pseudogenes originated from a recent parent of HCS that encoded the current cytochrome c polypeptide. These two distinct classes of human pseudogenes provide a molecular record of the history of cytochrome c evolution in primates and demarcate a short period of rapid evolution of the functional gene.

Animals↗
PubMed1989

Protein evolution on rugged landscapes.

We analyze a mathematical model of protein evolution in which the evolutionary process is viewed as hill-climbing on a random fitness landscape. In studying the structure of such landscapes, we note that a large number of local optima exist, and we calculate the time and number of mutational changes until a protein gets trapped at a local optimum. Such a hill-climbing process may underlie the evolution of antibody molecules by somatic hypermutation.

Biological Evolution↗
PubMed1991

Psychological factors related to prehospital delay during acute myocardial infarction.

BACKGROUND: Prior studies have had difficulty identifying factors that significantly explain patients' delay in responding to symptoms of acute myocardial infarction (AMI). METHODS AND RESULTS: We therefore examined factors affecting the time between symptom onset and hospital arrival for 103 AMI patients admitted to a Detroit metropolitan hospital between October 1989 and January 1990. Variables evaluated included demographic and medical history factors, psychological characteristics of somatic and emotional awareness, and type A behavior. The mean prehospital delay time was 9.0 +/- 10.8 hours (median, 5.0 hours; range, 0.25-62.0 hours). Delay time was not significantly associated with demographic or medical history categories or with type A behavior. Of study variables that can be identified prior to evolution of an AMI, somatic and emotional awareness were the only factors significantly predictive of delay time. Patients who were more capable of identifying inner experiences of emotions and/or bodily sensations sought treatment significantly earlier than patients with low emotional or somatic awareness (low emotional awareness median delay, 12.8 hours; high emotional awareness median delay, 3.8 hours; low somatic awareness median delay, 7 hours; high somatic awareness median delay, 4 hours). CONCLUSIONS: Variations in sensitivity to bodily sensations and emotions appear to play an important role in treatment seeking and thus potentially in treatment outcome for AMI patients. Assessment of these characteristics in patients with coronary risk factors could allow early identification of persons at risk of excessive delay in responding to symptoms of AMI.

Attitude to Health↗
PubMed1982

Changes in gene order and gene expression.

Studies on changes in gene position in germ line and somatic cell chromosomes during evolution and differentiation have led biologists to abandon the static view of chromosomes as invariant linear arrays of hereditary information. Prokaryotic cells contain several classes of DNA insertion elements which move from place to place in the genome and mediate chromosome rearrangements. Similar elements exist in a wide variety of eukaryotic organisms (yeasts, insects, plants, and vertebrates). In addition, both reversible and irreversible changes of chromosome primary structure provide developmental controls on gene activity in bacteria, bacteriophages, yeasts, trypanosomes, and mammalian lymphocytes. At least five recombination mechanisms are known to catalyze chromosome changes: 1) general homologous, 2) site-specific reciprocal, 3) illegitimate, 4) DNA splicing, and 5) replicative. Various combinations of these mechanisms can explain many different chromosome rearrangements and changes in gene dosage. Changes in gene position can alter gene expression in many ways, some of which we understand (such as insertional mutation and inversion of coding and regulatory sequences) and some of which are still unexplained. The activities of DNA insertion elements and somatic rearrangement systems are subjects to controls at several levels by specific regulatory systems, natural selection, and connection to cell lineage. Despite the recent increase in knowledge about the biological importance of changes in gene order on chromosomes, there are far more questions than answers, particularly about the mechanisms that coordinate recombination events and cell division in higher organisms.

Animals↗
PubMed1987

Germ cell-somatic cell relationships: a comparative study of intercellular junctions during spermatogenesis in selected non-mammalian vertebrates.

Specialized germ cell-somatic cell relationships were surveyed in the testis of species representative of four classes of non-mammalian vertebrates. Desmosome-like junctions were present in all classes studied. In the teleost fish studied (bluegill; Lepomis macrochirus), small, infrequent desmosomes, seen between the spherical cyst cells and spermatocytes, were characterized by poorly represented subsurface densities. In the bullfrog (Rana catesbeiana), similar desmosome-like junctions were found between cyst cell processes and spermatocytes. Reptilian (turtle; Pseudameys scripta) desmosome-like junctions between Sertoli cells and germ cells were heterogeneous and more numerous than those junctions found in fish and amphibians. In general, the reptilian desmosome-like junctions were extensive structures displaying 10 nm filaments associated with the Sertoli cell component of the junctions. Regions within the desmosome where the two plasma membranes converged suggested that gap junctions were a component of the desmosome-like junctions. "Desmosome-gap" junctions persisted in turtle spermatids for sometime after nuclear elongation had commenced. In birds (chicken; Gallus domesticus), "desmosome-gap" junctions, similar to those seen in turtles were described between both spermatocytes and Sertoli cells, and spermatids and Sertoli cells. These junctions were frequently lined by saccules of endoplasmic reticulum. The presence of gap junctions suggest the evolution of mechanisms for somatic cell-germ cell communication although more species should be examined to confirm this hypothesis.

Animals↗
PubMed1988

Conserved organization of the human and murine T-cell receptor beta-gene families.

Generation of an immune response depends on the interaction of haematopoietic cell types, among which T cells and their receptors are of central importance. The T-cell receptor is a heterodimer consisting of disulphide-linked alpha and beta-chains, each chain divided into variable (V) and constant (C) regions. The beta-chain is encoded by the rearrangement of separate variable (V beta), diversity (D beta) and joining (J beta) gene segments during T-cell differentiation. To examine the mechanisms of somatic DNA rearrangement and evolution of the beta-gene segments, we have constructed a physical map of the human T-cell receptor beta-chain family containing 40 V beta gene segments as well as both C beta gene clusters. A comparison of the published nucleotide sequences of human and murine V beta gene segments reveals 12 examples of gene segments sharing 65% or more interspecies homology. The relative order of these human and murine V beta gene segment homologues is also conserved along the chromosome, apart from more extensive human gene duplication, presumably as a consequence of constraints imposed on evolutionary mechanisms operating to diversify these gene families or of selective pressures operating to maintain order.

Animals↗
PubMed1996

Molecular cloning of mouse somatic and testis-specific H2B histone genes containing a methylated CpG island.

We have isolated a mouse testis-specific H2B histone gene based on the unusual methylation of the CpG island of rat testis-specific H2B gene in somatic tissues. After digestion of genomic DNA with the methylation-sensitive restriction enzyme Hha I, we found that, among 10-20 copies of mouse H2B histone genes, at least three copies are methylated in somatic tissues, but not in testis. Cloning and sequence analysis of two methylated H2B genes revealed that one gene, MTH2B, is strikingly similar to the testis-specific histone H2B (TH2B) gene of rat and the other, psH2B, is a pseudogene of the somatic-type H2B gene. Northern blot analysis revealed that the expression of the MTH2B gene is testis-specific. During spermatogenesis, the MTH2B gene is expressed predominantly in pachytene spermatocytes, as observed in the expression of rat TH2B gene. Interestingly, the MTH2B gene is largely unmethylated in embryonic stem cells, but methylated in F9 embryonal carcinoma cells. The psH2B pseudogene is methylated in somatic tissues and F9 cells, but only partially methylated in embryonic stem cells. Methylation of the psH2B pseudogene seems to be attributed to its location within the context of repetitive sequences including the B1 element. The unmethylation of both H2B histone genes in the testis explains how CpG islands of those histone genes can be maintained during evolution despite heavy methylation in somatic tissues.

Amino Acid Sequence↗