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At least 541 records · Page 30Linked to original sources
PubMed1972

N.A.S. symposium: new evidence as the basis for increased efforts in cancer research.

Recent studies, primarily with mouse, rat, and chicken cells, have provided evidence to support the concept that vertebrates contain the genetic information for producing a type-C RNA tumor virus in an unexpressed form in their somatic cells as well as in their germ cells. This information, which our associates and we postulated has been part of the genetic makeup of vertebrates since early in evolution, can persist for hundreds of generations in cell culture without overt production of virus. It is proposed that the endogenous virogenes (the genes for the production of type-C viruses) and the oncogenes (that portion of the virogene responsible for transforming a normal cell into a tumor cell) are maintained in an unexpressed form by repressors in normal cells. Various agents, including radiation, chemical carcinogens, and, perhaps, exogenously added viruses, may transform cells by "switching on" the endogenous oncogenic information. Some other implications of the viral oncogene theory are presented.

Animals↗
PubMed1984

Human transferrin: cDNA characterization and chromosomal localization.

Transferrin (Tf) is the major iron binding protein in vertebrate serum. It shares homologous amino acid sequences with four other proteins: lactotransferrin, ovotransferrin, melanoma antigen p97, and HuBlym-1. Antigen p97 and the Tf receptor genes have been mapped on human chromosome 3. The goal of the study described here was to initiate the characterization of the Tf gene by identifying and characterizing its cDNA and mapping its chromosomal location. Recombinant plasmids containing human cDNA encoding Tf have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Within the 2.3 kilobase pairs of Tf cDNA analyzed, there is a probable leader sequence encoded by 57 nucleotides followed by 2037 nucleotides that encode the homologous amino and carboxyl domains. During evolution, three areas of the homologous amino and carboxyl domains have been strongly conserved, possibly reflecting functional constraints associated with iron binding. Chromosomal mapping by in situ hybridization and somatic cell hybrid analysis indicate that the Tf gene is located at q21-25 on human chromosome 3, consistent with linkage of the Tf, Tf receptor, and melanoma p97 loci.

Amino Acid Sequence↗
PubMed1987

Further characterization of the defects of skin fibroblasts from cancer patients.

We have previously shown that skin fibroblasts from breast cancer patients display abnormal growth properties when compared with cells from patients with benign breast lesions. In the present study, we shown that it is possible to define, within the patients previously analysed, a subgroup whose fibroblasts exhibit a significant fraction of cells still synthesizing DNA when growth curves reach a plateau. The phenomenon can also be detected in skin fibroblasts from patients with other types of cancer. In two instances detection of this defect preceded the discovery of the disease. The high percentage of labelled interphases when cell counts reach a plateau is not due to an increased duration of S phase, relative to total cell cycle duration. The data suggest that these cells are delayed in the G2 phase. This assay buttresses our previous results, which suggested that at least in some instances cancer is a systemic disease; it could be used for the screening of patients at high risk of cancer. Research on the patients' somatic cells could shed more light on the process leading to neoplasia, rather than the study of the tumour cells that have already gone through several steps of the evolution to malignancy.

Breast Neoplasms↗
PubMed1983

Conversion disorder following termination of pregnancy.

A variety of psychologic disorders may present as physical complaints without organic basis. As characterized by Sydenham over 300 years ago, such disorders "mimic all the physical disease to which man is heir." The case here presents the evolution of a conversion disorder (urinary retention) in response to a decision to terminate pregnancy. The predominant disturbance in a conversion disorder is an involuntary loss or alteration in somatic function that is temporally related with an environmental stressor. Conversion, as a defense mechanism, provides primary gain by keeping the conflict from the patient's awareness and secondary gains by generating environmental support and avoidance of undesired activities. Awareness of a patient's current life events, past responses to stress, and support systems is essential in order to recognize and manage this array of physical complaints of functional origin.

Abortion, Induced↗
PubMed1995

[The borders of hysteria].

Medical writing dealing with the nosology of hysteria has evolved through successive national and international classifications, while in parallel the expression of hysteria has changed with time, with cultural evolution and with increased medical knowledge. Hysteria, by definition, is distinguished both by psychic or physical symptoms reported or voluntarily induced by patients (simulation or pathomimic behaviour) and by somatic disorders having an underlying, associated organic pathology, favoured by an emotional context or a conflictual situation (psychosomatic disorders). The divergence, but above all the analogies between hysterical symptoms and such limits are underlined, showing the frequency of succession with time, associations and transitional forms ("somatisation disorder" of the DSM III, psychogenic pain, and psychosomatic disorders termed "psychofunctional").

Humans↗
PubMed1997

Genomic structure and chromosomal localization of the gene encoding translin, a recombination hotspot binding protein.

Human Translin is a novel DNA end binding protein that specifically recognizes consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments, in human lymphoid neoplasms. We have recently cloned a full-length human Translin cDNA using peptide sequence information obtained from the purified protein. From comparisons of the amino acid sequences in humans and other vertebrates, we conclude that Translin has been highly conserved during evolution, especially at the leucine zipper motif and the basic region, which is thought to be the DNA binding domain. Analysis of the human and mouse Translin genes revealed that they have identical genomic structures consisting of six exons, five introns, and a GC-rich upstream region. In situ hybridization and physical mapping of somatic cell hybrids allowed localization of the gene to human chromosome 2q21.1.

Amino Acid Sequence↗
PubMed2007

Somatic microindels: analysis in mouse soma and comparison with the human germline.

Microindels, defined as mutations that result in a colocalized microinsertion and microdeletion with a net gain or loss of between 1 and 50 nucleotides, may be an important contributor to cancer. We report the first comprehensive analysis of somatic microindels. Our large database of mutations in the lacI transgene of Big Blue((R)) mice contains 0.5% microindels, 2.8% pure microinsertions, and 11.5% pure microdeletions. There appears to be no age, gender, or tissue-type specificity in the frequency of microindels. Of the independent somatic mutations that result in a net in-frame insertion or deletion, microindels are responsible for 13% of protein expansions and 6% of protein contractions. These in-frame microindels may play a crucial role in oncogenesis and evolution via "protein tinkering" (i.e., modest expansion or contraction of proteins). Four characteristics suggest that microindels are caused by unique mechanisms, not just simple combinations of the same mechanisms that cause pure microinsertions and pure microdeletions. First, microinsertions and microdeletions commonly occur at hotspots, but none of the 30 microindels are recurrent. Second, the sizes of the deletions and insertions in microindels are larger and more varied than in pure microdeletions and pure microinsertions. Third, microinsertions overwhelmingly repeat the adjacent base (97%) while the insertions in microindels do so only infrequently (17%). Fourth, analysis of the sequence contexts of microindels is consistent with unique mechanisms including recruitment of translesion DNA synthesis polymerases. The mouse somatic microindels have characteristics similar to those of human germline microindels, consistent with similar causative mechanisms in mouse and human, and in soma and germline.

Age Factors↗
PubMed1996

How rapidly does the human mitochondrial genome evolve?

The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard phylogenetic approaches. The nucleotide sequence of the D-loop region of the mitochondrial genome was determined for 45 members of a large matrilineal Leber hereditary optic neuropathy pedigree. Two germ-line mutations have arisen in members of one branch of the family, thereby leading to triplasmic descendants with three mitochondrial genotypes. Segregation toward the homoplasmic state can occur within a single generation in some of these descendants, a result that suggests rapid fixation of mitochondrial mutations as a result of developmental bottlenecking. However, slow segregation was observed in other offspring, and therefore no single or simple pattern of segregation can be generalized from the available data. Evidence for rare mtDNA recombination within the D-loop was obtained for one family member. In addition to these germ-line mutations, a somatic mutation was found in the D-loop of one family member. When this genealogical approach was applied to the nucleotide sequences of mitochondrial coding regions, the results again indicated a very rapid rate of evolution.

Child↗
PubMed1986

The molecular evolution of the immune response: idiotope-specific suppression indicates that B cells express germ-line-encoded V genes prior to antigenic stimulation.

Antibodies expressed by the immune B cell population are characterized by variable region amino acid substitutions resulting from somatic nucleotide replacement (somatic mutation). This is not true of antibodies expressed by the "naive" B cell population. It is at present unclear whether this discrepancy is due to the preferential clonal selection of a pre-existing subpopulation of naive B cells that express variable regions altered via nucleotide replacement, or whether the process of nucleotide replacement occurs only during the antigen-dependent stages of B cell differentiation. To address this question we have used anti-idiotypic suppression to functionally delete B cells that express particular variable-region structures from the antigen-responsive repertoire. Suppression of the major cross-reactive idiotype (IdCR) expressed in strain A mice in response to p-azophenylarsonate (Ars) was induced using the monoclonal anti-IdCR antibody AD8. The idiotope recognized by AD8 is easily destroyed by alteration of IdCR variable-region structure via nucleotide replacement. The IdCR anti-Ars immune repertoire is characterized by antibodies that lack the AD8-cognate idiotope due to nucleotide replacement. However, complete suppression of the IdCR could reproducibly be achieved by administration of AD8 prior to Ars immunization. This result indicates that all IdCR-expressing B cells also express the AD8-cognate idiotope prior to immunization. Thus, somatic nucleotide replacement must occur exclusively during the antigen-dependent stages of B cell differentiation in this system.

Animals↗
PubMed2004

Comprehensive scanning of somatic mitochondrial DNA alterations in acute leukemia developing from myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by ineffective hematopoiesis resulting in refractory cytopenias. Transformation resulting in acute myeloblastic leukemia is the final stage in the multistep process of MDS evolution. Functional relevant mutations of mitochondrial DNA (mtDNA) have been related to sideroblastic anemia and MDS. To investigate the role of mtDNA in malignant transformation to acute leukemia, we used high-resolution techniques such as single-strand conformational polymorphism and fluorescence sequencing for investigation of the whole mitochondrial genome from blood cells of 10 patients with MDS. Functionally relevant point mutations in mitochondrial RNA and polypeptide-encoding genes were detected in 50% of patients with MDS. Their increasing mutation load connects MDS and the developing acute myeloid leukemias. Several point mutations of mtDNA, including secondary point mutations for Leber's hereditary optic neuropathy, occur in one bone marrow and may synergically affect bone marrow stem cells by an apoptotic pathway.

Acute Disease↗
PubMed2001

A conflict between two evolutionary levels in trees.

Due to the lack of germ line segregation in plants, it is possible to consider plant evolution (but not the evolution of most animals) as being composed of two evolutionary levels: 1. Intra-organism, in which the replicating unit is a part of the tree (e.g. a branch), reproduction is asexual, mutations are somatic, and selection operates only upon traits relevant to vegetative growth. 2. Inter-organism, in which the replicating unit is the whole tree, reproduction is sexual, and selection operates upon all the traits. In this work, a case of a conflict between these two levels is studied. The dynamics of a mutation, which is advantageous on the branch level but harmful for the whole tree, are discussed for a one-locus two-allele model. Several cases are considered: dominant, partially dominant, and haploid. Necessary and sufficient conditions for fixation of such a mutation are found. The model predicts that as the longevity of a tree species increases, the trees are expected to be more strongly shifted from their optimal growth-to-reproduction ratio towards growth, and resource allocation between branches and other tree parts is expected to be shifted in favor of the branches. Traditional approach, considering the second level only, is justified as a limit case for short longevity.

Biological Evolution↗
PubMed1999

Improvement of depression following transcranial magnetic stimulation.

Psychiatry as a field was transformed by the discovery and introduction of electroconvulsive therapy (ECT) as a treatment in the early part of this century. ECT demonstrated that depression was a disease of the brain and that it could be treated with a direct brain intervention. Psychiatry's evolution continued in 1958 with the discovery of the antidepressant activity of the monoamine oxidase inhibitors. Interestingly, although the area of neuropsychopharmacology has continued to advance, the realm of physical somatic interventions in psychiatry has lagged behind. With perhaps the exception of light therapy, there were no advances in somatic interventions in psychiatry. However, in 1985, Barker et al. developed a brief high intensity electromagnet capable of depolarizing cortical neurons, called transcranial magnetic stimulation (TMS). There has been much interest in the past 10 years in whether TMS might have antidepressant actions, similar to ECT but without causing a seizure and with no apparent cognitive side effects. This review examines the basic principles underlying TMS, and describes how TMS differs from electrical stimulation and the other uses of magnets.

Cerebral Cortex↗
PubMed1984

ERV3, a full-length human endogenous provirus: chromosomal localization and evolutionary relationships.

A full-length human endogenous provirus termed ERV3 was isolated from a human fetal recombinant DNA library by low stringency hybridization with two probes: baboon endogenous virus LTR; and a pol-env subclone from the endogenous chimpanzee provirus, CH2. DNA sequencing within the clone and comparisons with other retroviruses revealed that ERV3 contains gag and pol gene sequences that are significantly related to those of mammalian type C retroviruses and previously described human endogenous proviruses. The ERV3 genome was determined to reside at a single locus on human chromosome 7 using a panel of rodent X human somatic cell hybrids.

Amino Acid Sequence↗
PubMed1989

The murine retinoblastoma homolog maps to chromosome 14 near Es-10.

Restriction fragment length variants have been exploited to map genetically Rb-1, the murine homolog of the human retinoblastoma gene. Rb-1 localized to mouse chromosome 14 on the basis of results from analysis of somatic cell hybrids. In an interspecific backcross involving Mus spretus, Rb-1 and the murine homolog of the human esterase D gene (ESD), which we refer to here as Esd, were inseparable. Furthermore, the strain distribution patterns of Rb-1 and Es-10 are the same in 31 of 32 recombinant inbred strains. Close linkage of the chromosome 14 morphological marker hairless (hr) to Rb-1 is also implied. These results localize Rb-1 on the mouse linkage map and provide close genetic markers to follow Rb-1 in somatic as well as in germline genetic experiments. Additionally, the results suggest that Es-10 is the murine homolog of ESD and provide further evidence for linkage conservation during mammalian evolution.

Animals↗
PubMed2006

Fish transposons and their potential use in aquaculture.

A large part of repetitive DNA of vertebrate genomes have been identified as transposon elements (TEs) or mobile sequences. Although TEs detected to date in most vertebrates are inactivated, active TEs have been found in fish and a salmonid TE has been successfully reactivated by molecular genetic manipulation from inactive genomic copies (Sleeping Beauty, SB). Progress in the understanding of the dynamics, control and evolution of fish TEs will allow the insertion of selected sequences into the fish genomes of germ cells to obtain transgenics or to identify genes important for growth and/or of somatic cells to improve DNA vaccination. Expectations are high for new possible applications to fish of this well developed technology for mammals. Here, we review the present state of knowledge of inactive and active fish TEs and briefly discuss how their possible future applications might be used to improve fish production in aquaculture.

Animals↗
PubMed1995

Hypothesis: a memory lymphocyte-specific soma-to-germline genetic feedback loop.

Analysis of recently published DNA sequence data obtained for related germline Ig variable (IgV) genetic elements of several vertebrate species revealed the presence of a number of extremely non-random patterns of sequence variability among these genes. Strikingly, the patterns were also observed in two sets of chicken IgV pseudogenes. Since the observed patterns are clearly incompatible with existing theories of multigene family evolution, a new model that can account for all of the data is presented in this paper. The model is a modification and extension of an earlier proposed mechanism whereby somatically expressed genes can be returned to the germline by endogenous retroviruses that may act as soma-to-germline genetic vectors. The mechanism described proposes that the interactions that may result in the soma-to-germline transfer of somatically selected IgV genes occur in the epididymis of the male reproductive tract and are restricted to memory lymphocytes. This mechanism makes a number of predictions that are amenable to experimental testing. From the data presently available in the literature it is not possible to extend the mechanism to the female reproductive tract.

Animals↗
PubMed1982

Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae.

In the mouse, most anti-PC antibody is found in one of the three murine anti-PC idiotype families: T15, M603, or M511. The antibodies within each of these idiotypic families have characteristic fine specificities for phosphorylcholine (PC)-analogues. In this paper we compare the ability of hybridoma IgM anti-PC antibodies of the three idiotype families to protect mice from fatal infection with S. pneumoniae. Antibody bearing the T15 idiotype was approximately 8 times as effective as antibody with the M603 idiotype and approximately 30 times as protective as antibody with the M511 idiotype. Reports by others have shown that the heavy chains of virtually all mouse anti-PC antibodies are produced by translocation of a single variable region gene and that the direct translation of this gene (in the absence of somatic mutations) results in heavy chains characteristic of the T15 idiotype. Thus, our findings suggest that the T15 germ line heavy chain variable region gene may have been selected through evolution to code for antibody binding PC-containing pathogens such as S. pneumoniae. Our observations may also explain the existence of regulatory mechanisms that result in maintenance of T15 idiotype expression in murine anti-PC immune responses.

Animals↗