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At least 991 records · Page 55Linked to original sources
PubMed1985

A deletion adjacent to the maize transposable element Mu-1 accompanies loss of Adh1 expression.

Insertion of the maize transposable element Mu-1 into the first intron of the alcohol dehydrogenase locus (Adh1) of maize produced mutant Adh1-S3034 with 40% of the wild-type level of protein and mRNA. Continued instability at this locus resulted in secondary mutations with lower levels of protein expression. One of these, Adh1-S3034a, has no detectable ADH1 expression. This paper describes the precise nature of the changes in the Adh1 gene that gave rise to the S3034a allele. The Mu-1 element is still present in the mutant, but Adh1 sequences immediately adjacent to the element are deleted. The deletion starts precisely at the Mu-1 insertion site and extends 74 bp leftward removing part of the first intron, the intron:exon junction and 2 bp of the eleventh amino acid codon in the first exon of the gene. Tests for reversion within the somatic tissue of plants show that mutant S3034a, unlike its progenitor, is stably null for ADH1 activity.

Alcohol Dehydrogenase↗
PubMed2002

Methylation reveals a niche: stem cell succession in human colon crypts.

Little it known about human stem cells although they are likely to be the earliest progenitors of carcinomas. Just as methylation can substitute for mutations to inactivate tumor suppressor genes, methylation can also substitute for mutations in a phylogenetic analysis. This review explains why stem cell dynamics may be important to tumor progression and how methylation patterns found in a normal human colon can be used to reconstruct the behavior of crypt stem cells. Histories are recorded in sequences and strategies used to reconstruct phylogenies from sequences likely apply to methylation patterns because both exhibit somatic inheritance. Such a quantitative analysis of colon methylation patterns infers stem cells live in niches containing multiple 'stem' cells. Although niche stem cell numbers remain constant, clonal succession is inherent to niches because periodically progeny from a single stem cell become dominant. These niche succession cycles may potentially accumulate multiple alterations because they resemble superficially the clonal succession of tumor progression except that they occur invisibly in the absence of selection or phenotypic change. Alterations without immediate selective value may hitchhike passively in the stem cells that become dominant during niche succession cycles. The inherent ability of a niche to fix alterations (Muller's ratchet) is another potential mechanism besides instability and selection to sequentially accumulate multiple alterations. Many alterations found in colorectal tumors may reflect such occult clonal progression in normal colon.

Colon↗
PubMed2004

[Psychosomatic reactions comorbid with ischemic heart disease: psychogenically provoked infarctions and myocardial ischemia].

Ischemic heart disease (IHD) with psychogenic provoked myocardial infarctions (MI) and myocardial ischemic disease (MID) is considered as a psychosomatic disorder. Seventy patients, 17 female and 53 male, aged between 39-77 years, mean age 61.2 +/- 9.9 years, were observed. The presence of both somatic (prolonged atherosclerotic lesion of coronary arteries) and mental (personality disorders with symptoms of reactive lability under psychic trauma influence) predisposition is obligate for manifestation or exacerbation of this IHD type. It is suggested that atherosclerotic coronary vessels affection of heterogeneity may exist. Two types of vulnerability are described. In type 1 cardiovascular system exhibits selective sensitivity to the influence of obligate and of great personality significance cathatymic affect. A strict condition of its realization is amplification of negative emotions up to a level of pathological affective outbursts in the spectrum of paranoiac or explosive reactions. In these cases, IHD is characterized by a stable course (angina of high tensions, without instable anginal episodes etc). In type 2 cardiovascular system reveals vulnerability to negative emotions, the continuum of which is ended by polar pathological affects-cathatymic and anxiety. In contrast to cathatymic affect, a common feature of anxiety affect is a fast, like short-term emotional outburst, manifestation of instable, labile, dramatic external appearances (with tears, converse disorders etc). IHD symptom complex is distinguished by pronounced clinical manifestations (stenocardia of tension with progressive impairment of tolerability to loadings).

Adult↗
PubMed1995

Mutations in DNA mismatch repair genes are not responsible for microsatellite instability in most sporadic endometrial carcinomas.

Endometrial carcinoma is the second most common tumor type in women with hereditary nonpolyposis colorectal carcinoma. Microsatellite instability (MI) has been observed in the inherited (hereditary nonpolyposis colorectal carcinoma-associated) form of endometrial carcinoma as well as in approximately 20% of presumably sporadic cases. Recent studies suggest that MI in many cell lines or xenografts derived from sporadic colorectal carcinomas is not attributable to mutations in four known human DNA mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, and hPMS2). Mutational analyses of these four MMR genes in endometrial carcinomas have not been previously reported. We analyzed nine sporadic MI-positive primary endometrial carcinomas for mutations in the above four MMR genes. Mutations were detected in two tumors (in hMSH2), and both of the mutations were acquired somatically. Immunohistochemical staining revealed a lack of expression of hMSH2 protein in the two tumors containing hMSH2 mutations. Our data suggest that mutations in these four known DNA MMR genes are not responsible for MI in the majority of sporadic endometrial carcinomas displaying this phenotype.

Adult↗
PubMedDate not supplied

[Determination of mutation frequency at loci of glycophorin A and T-cell receptor: study of Chernobyl AES accident cleanup workers].

The frequencies of somatic mutations at loci of glycophorin A (GPA) and T-cell receptor (TCR) were determined in control unexposed donors and Chernobyl clean up workers, who received low doses of irradiation up to 0.25 Gy. High variability of mutant rates for two investigated genes was shown in the clean up workers. No significant difference in the GPA (NO) mutant frequencies was observed between the clean up workers and control donors (p > 0.05), though there is a tendency for increasing the GPA mutation rate in the clean up workers. Meanwhile, the TCR mutation rate was significantly increased the clean up workers (p < 0.01), perhaps because of acceleration of spontaneous mutagenesis and possible genome instability. Persons with elevated levels of mutations at two loci can present a group at high risk in respect to oncological diseases.

Adult↗
PubMed2004

Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.

In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the release of chemical mediators from MCs, the pathologic infiltration of neoplastic MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis might regress spontaneously. Systemic mastocytosis (SM) is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the majority of such patients. The natural clinical course in SM is variable. Whereas most patients remain at the indolent stage for many years, some have aggressive SM (ASM) at diagnosis. Other patients have an associated clonal hematologic non-MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant characterized by circulating MCs and fatal disease progression. The diagnoses of ASM, SM-AHNMD, and MCL might be confused with a variety of endocrinologic, vascular, or immunologic disorders. It is therefore of particular importance to be aware of the possibility of an underlying (malignant) MC disease in patients with unexplained vascular instability, unexplained (anaphylactoid) shock, idiopathic flushing, diarrhea, headache, and other symptoms that might be mediator related. An important diagnostic clue in such cases is an increased serum tryptase level. The current review provides an overview of mastocytosis and its subvariants and a practical guide that might help to delineate mastocytosis from unrelated systemic disorders.

Adult↗
PubMed1997

Insertions of a novel class of transposable elements with a strong target site preference at the r locus of maize.

The r locus of maize regulates anthocyanin synthesis in various tissues of maize through the production of helix-loop-helix DNA binding proteins capable of inducing expression of structural genes in the anthocyanin biosynthetic pathway. The complex r variant, R-r: standard (R.r), undergoes frequent mutation through a variety of mechanisms including displaced synapsis and crossing over, and intrachromosomal recombination. Here we report a new mechanism for mutation at the R-r complex: insertion of a novel family of transposable elements. Because the elements were first identified in the R-p gene of the R-r complex, they have been named P instability Factor (PIF). Two different PIF elements were cloned and found to have identical sequences at their termini but divergent internal sequences. In addition, the PIF elements showed a marked specificity of insertion sites. Six out of seven PIF-containing derivatives examined had an element inserted at an identical location. Two different members of the PIF element family were identified at this position. The seventh PIF-containing derivative examined had the element inserted at a distinct position within r. Even at this location, however, the element inserted into a conserved target sequence. The timing of PIF excision is unusual. Germinal excision rates can range up to several percent of progeny. Yet somatic sectors are rare, even in lines exhibiting high germinal reversion rates.

Anthocyanins↗
PubMed2002

[Depression and Parkinson's Disease: study of a series of 135 Parkinson's patients].

OBJECTIVE: The prevalence of depression in Parkinson's disease (PD) raises the issues of the difficulties of diagnosing the condition and of the relationships between depression and the natural history of the disease. METHODS: A cohort of 135 consecutive patients with idiopathic PD underwent psychiatric (DSM-III-R, Goldberg depression scale), neurological (distinguishing "axial" signs from other signs of parkinsonism), and neuropsychological (particularly frontal tests) evaluations. RESULTS: Depression is present in more than half of the patients and it seems to be more frequent in patients with the akinetic and fluctuating forms of the disease. The subjects who are depressed do not have a greater degree of cognitive impairment, but their scores on frontal tests are higher. Moreover, the axial signs of the disease (postural instability, axial rigidity) are more severe in depressed parkinsonians suggesting a link between depression and the non-dopaminergic lesions of the disease. Even though slowness, appetite and sleep disturbances, and fatigue may be encountered in non-depressed parkinsonian patients, separation of the parkinsonian population into subgroups shows that certain symptoms are never seen in parkinsonians who are not depressed: it is thus evident that "the impression that life is not worth living", "the hopelessness", "the impression of being worthless and incompetent", "the low level of energy", "the morning sadness" are characteristic of parkinsonian depression. Parkinsonian depression has two major clinical forms. The first one is associated with a greater number of somatic manifestations: sleep disturbances, morning fatigue. corresponding to more severe depression with hopelessness and loss of self confidence. The second exhibits few somatic manifestations with apathy and slowness as frequent complaints. CONCLUSIONS: This study defines the symptoms of parkinsonian depression which should be better recognised in order to be treated. The link between depression and axial signs of the disease may explain why L-dopa and dopaminergic agonists improve the motor signs of depression without influencing depressive manifestations in most cases.

Aged↗
PubMed2002

Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA.

Genetic integrity is crucial to normal cell function, and mutations in genes required for DNA replication and repair underlie various forms of genetic instability and disease, including cancer. One structural feature of intact genomes is runs of homopolymeric dC/dG. Here we describe an unusual mutator phenotype in Caenorhabditis elegans characterized by deletions that start around the 3' end of polyguanine tracts and terminate at variable positions 5' from such tracts. We observed deletions throughout genomic DNA in about half of polyguanine tracts examined, especially those containing 22 or more consecutive guanine nucleotides. The mutator phenotype results from disruption of the predicted gene F33H2.1, which encodes a protein with characteristics of a DEAH helicase and which we have named dog-1 (for deletions of guanine-rich DNA). Nematodes mutated in dog-1 showed germline as well as somatic deletions in genes containing polyguanine tracts, such as vab-1. We propose that DOG-1 is required to resolve the secondary structures of guanine-rich DNA that occasionally form during lagging-strand DNA synthesis.

3' Flanking Region↗
PubMed1994

Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus.

The retinoblastoma tumor suppressor gene (RB1) is inactivated in hereditary and sporadic forms of retinoblastoma as well as in a number of other sporadic tumors. The majority of human pituitary tumors have been shown to be monoclonal neoplasms, suggesting that 1 or more somatic mutations are involved in the clonal expansion of a single progenitor cell. Recently, a high percentage of transgenic mice containing a disrupted RB1 allele have been shown to develop pituitary tumors. To investigate whether RB1 inactivation contributes to the development of human pituitary adenomas, we searched for loss of heterozygosity (LOH) within the RB1 gene locus in a variety of human pituitary adenomas. We screened 34 adenomas for LOH using a polymerase chain reaction (PCR)-based microsatellite polymorphic marker at the RB1 gene locus. In addition, a variable number of tandem repeat markers from within the RB1 gene was also used to search for LOH in 14 tumors. We found no LOH or microsatellite instability at the RB1 locus in any of the informative cases (30 of 34). Additionally, we showed that 4 representative adenomas from female patients are monoclonal in origin using a PCR-based clonality analysis assay. We conclude that the RB1 gene shows no LOH in a variety of human pituitary adenomas and that PCR-based microsatellite markers can serve as a useful tool for LOH analysis in human pituitary tumors.

Adenoma↗
PubMed2005

Telomerase and cancer stem cells.

Telomerase is critical for the integrity of stem cell compartments. Mutations in telomerase components lead to telomere shortening and hematopoietic stem cell failure in autosomal dominant dyskeratosis congenita and aplastic anemia. Telomerase activity is readily detected in most cancers but not in adult somatic cells. The telomere hypothesis for cancer states that telomerase is reactivated in late stages of carcinogenesis. However, recent evidence has suggested a stem cell origin for certain cancers, implying that the genetic alterations that lead to cancer accumulate in tissue-specific stem cells and not in adult somatic cells. In these cancers, stem cells would already have telomerase and it would not need to be reactivated. Here, we reconsider the telomere hypothesis in view of this evidence and propose that, rather than telomerase reactivation, enzyme activity may increase in later stages of carcinogenesis due to increased expression or efficient assembly of telomerase components. Understanding these mechanisms will refine approaches to telomerase inhibition in cancer.

Dyskeratosis Congenita↗
PubMed1994

Telomere dynamics in an immortal human cell line.

The integration of transfected plasmid DNA at the telomere of chromosome 13 in an immortalized simian virus 40-transformed human cell line provided the first opportunity to study polymorphism in the number of telomeric repeat sequences on the end of a single chromosome. Three subclones of this cell line were selected for analysis: one with a long telomere on chromosome 13, one with a short telomere, and one with such extreme polymorphism that no distinct band was discernible. Further subcloning demonstrated that telomere polymorphism resulted from both gradual changes and rapid changes that sometimes involved many kilobases. The gradual changes were due to the shortening of telomeres at a rate similar to that reported for telomeres of somatic cells without telomerase, eventually resulting in the loss of nearly all of the telomere. However, telomeres were not generally lost completely, as shown by the absence of polymorphism in the subtelomeric plasmid sequences. Instead, telomeres that were less than a few hundred base pairs in length showed a rapid, highly heterogeneous increase in size. Rapid changes in telomere length also occurred on longer telomeres. The frequency of this type of change in telomere length varied among the subclones and correlated with chromosome fusion. Therefore, the rapid changes in telomere length appeared occasionally to result in the complete loss of telomeric repeat sequences. Rapid changes in telomere length have been associated with telomere loss and chromosome instability in yeast and could be responsible for the high rate of chromosome fusion observed in many human tumor cell lines.

Cell Line, Transformed↗
PubMed1975

Loss of agglutinating specificity in stock cultures of Rhizobium meliloti.

Several strains of Rhizobium meliloti which have been subcultured for 23-33 years have changed from being markedly specific in their somatic agglutination reactions to become widely cross-reactive. On the other hand a fresh collection of the same species obtained from naturally nodulated, field-grown plants revealed the high degree of agglutinating specificity which had previously characterised the old cultures. Attempts to reselect a specific substrain from old cross-agglutinating cultures by six plant passages, or to detect change to cross reactivity by ten successive subcultures of recent isolates were unsuccessful. However, one strain, isolated in 1939, was recently found to contain both specific and cross-reactive substrains. Practically all the cultures, both old and recent, showed considerable mutability in colony characteristics but none of these was consistently correlated with cross agglutinability. Instability in 6.4% (w/v) NaCl was characteristic of the cross-agglutinating cultures. Cross reactivity was associated with a shared lipopolysaccharide antigen (LPS) which appeared to be obscured by an outer antigen in most strains still showing specific agglutinability. In the exceptional case of strain SU27, agglutination could be attributed to its specific LPS.

Agglutination↗
PubMed2001

The association between sporadic somatic parental aneuploidy and chromosomally abnormal placentae in habitual abortions.

To determine whether there is a correlation between the proportion of aneuploid cells in peripheral lymphocytes and the karyotype of the abortus in recurrent miscarriage. 40 couples with recurrent miscarriage and their abortuses were cytogenetically analyzed according to the analysis of 60 cells per proband. Women were divided into two groups according to the proportion of chromosomally abnormal cells in the abortus. Chromosomal analysis was performed using G-banding with trypsin-Giemsa in parental peripheral blood and in the abortus. 20 of the 40 abortuses had a chromosomally abberant karyotype. 65% of parents aborting an embryo with with an increased proportion of chromosomally aberrant cells, had more than 10% aneuploid cells in their peripheral lymphocytes. However, only 12.5% of couples aborting an embryo with chromosomally normal cells had increased rates of aneuploidy. An increased proportion of aneuploid cells was found in the lymphocytes of recurrently aborting couples who repeatedly abort chromosomally abnormal fetuses. Mitotic instability in the lymphocytes may indicate a predisposition to instability at meiosis leading to a chromosomal abberations in the embryo and its subsequent abortion.

Abortion, Habitual↗
PubMedDate not supplied

[Chromosomal and ontogenetic instability in sibling species of common vole (Microtus arvalis group): comparative aspects].

Populations of chromosomal sibling species Microtus arvalis and Microtus rossiaemeridionalis were studied in Ural region in habitats affected by high radiation and the control ones. Frequency of chromosome disturbances in the marrow cells and fluctuating asymmetry (FA) of 8 craniometric characters were investigated. In impact populations the frequency of chromosome aberration was very high. Such frequency was also maintained in the offspring of the first laboratory generation of M. arvalis. In natural and control populations of both species frequently occurred individuals with anomalies in sex chromosome. Individuals of M. rossiaemeridionalis from Totsky radioactive region (forest-steppe zone) were characterized by very high integrative FA in comparison with control populations (southern taiga). At the same time neighboring impact and control populations of M. arvalis from southern taiga did not differ in this character. Despite the high level of caryotype divergence M. arvalis and M. rossiaemeridionalis showed similarity in mutation process that causes chromosome disturbances in somatic and germinative cells. Probably the level of FA of measured characters in both species is connected rather with geographical location than with man influence.

Animals↗
PubMed2001

Multiple substrates of late-onset dementia: implications for brain protection.

Age is the single most important risk factor for progressive dementia in populations worldwide. In developed countries the prevalence of dementia is estimated to be 3-5% at age 65 years and expected to double every decade thereafter. Although there is ageing-related attrition of neural tissue accompanied by profound changes in brain glia, marked neuronal loss and severe cognitive impairment are associated with pathological changes. Accelerated somatic ageing of the vasculature comprising endothelial and smooth muscle cells and slowed glial replacement are also likely to pre-dispose to degenerative processes. Approximately 90% of patients with late-onset dementia have neuropathological features of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or vascular dementia (VaD), alone or in combination. Both AD and DLB reveal extensive amyloid beta deposition within senile plaques. Neurofibrillary tangles evident as tau pathology are much reduced in DLB where symptoms may be more related to cholinergic transmitter abnormalities than structural pathology. Depletion of brain acetylcholine is also encountered in VaD, which like AD and DLB may respond to cholinergic therapy. Cerebrovascular pathology, ischaemic brain damage and neurovascular instability resulting in cerebral hypoperfusion appears fundamental in the pathogenesis of late-onset dementia. The apolipoprotein E epsilon 4 allele, a major genetic susceptibility factor for AD also associated with cardiovascular pathology, may contribute to neurodegenerative changes through vascular mechanisms. The interrelationships of these multiple substrates of late-onset dementia have major implications for neuroprotective and disease slowing therapies. Measures that improve cardiovascular function and increase brain perfusion would be useful to attenuate cognitive decline.

Age of Onset↗
PubMed1984

Construction of human T-cell hybrids with helper function.

Human T-cell hybrids with helper activity were obtained after fusion of phytohemagglutinin-activated normal human T cells with a 6-thioguanine-resistant, aminopterin-sensitive human T-cell line. This mutant line, designated CEM-T15, was derived from the human T-cell line CEM after mutagenesis with ethyl methanesulfonate. The polyethylene glycol induced fusion and the selection in hypoxanthine- aminopeterin -thymidine medium were performed by modification of standard somatic cell hybridization techniques. After fusion, the strategy for selecting hybrids consisted in screening growing cultures for the presence of cells expressing the OKT3 cell surface differentiation antigen. OKT3 was chosen because it is present in 85-95% of normal human T cells but absent from CEM-T15 cells. Thus, OKT3+ cells growing 5-7 weeks after fusion most likely represented hybrids between normal T cells (OKT3+) and continuously growing CEM-T15 cells (OKT3-). Several of the hybrids were tested for their capacity to promote pokeweed mitogen-induced antibody production by B cells. These experiments demonstrated that many of the hybrids had helper activity. Periodical testing of these uncloned hybrids for helper activity revealed functional instability, with most of the hybrids losing helper activity after 20 weeks of continuous culture. However, early and repeated cloning of the same hybrids resulted in a series of hybrid clones with helper activity still present more than 8 months after fusion. In more recent fusions, we have demonstrated that human helper hybrids producing helper factor(s) can also be obtained. These and similar hybrids with different functions will be of considerable importance in further studies of the immunobiology of human T lymphocytes.

Antigens, Surface↗
PubMed2003

Heterogeneity of proteolytic enzyme activities in milk samples of different somatic cell count.

Milk contains the alkaline proteinase plasmin and lysosomal proteinases; the significance of the latter is ill-defined. The objective of this study was to investigate composition and activities of several different proteolytic enzymes in milk samples of varying somatic cell count (SCC). Increasing milk SCC was correlated with increased plasmin, cathepsin D and cysteine protease activities, with concomitant increases in proteolysis in milk. Addition of plasmin inhibitors confirmed the heterogeneity of proteinase activities in milk, as urea-PAGE analysis of milk samples showed casein hydrolysis in milk after 7 d storage even in samples with inhibitors added; extent and heterogeneity of proteolysis was correlated with milk SCC. Rennet coagulation properties were not significantly correlated with SCC, or activities of measured enzymes. Milk of increasing SCC also exhibited decreased physical stability during incubation of milk at 37 degrees C. Pasteurized milk was more stable than raw milk, suggesting that the enzyme(s) or mechanisms leading to such instability are impaired by pasteurization. Overall, milk has a very heterogeneous proteolytic enzyme population, with a higher significance of non-plasmin enzymes, such as cathepsin D and cysteine proteinases, than perhaps previously recognised.

Animals↗