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PubMed1983

A method to detect tumors and presumed somatic mutations in mice.

A method was tested to detect both tumors and somatic mutations in mice. When HT-A/J F1 embryos were treated with ethylnitrosourea on day 11 of gestation, a single injection was enough to induce tumors and presumed somatic mutations of coat color in significantly high incidence. Urethane, treated in a similar way, induced somatic mutations and malformations in the offspring. Tumor incidence was also increased but was not significantly different from controls. Treatment on day 13 was too late to induce somatic mutations and malformations, while high incidence of tumors were induced.

Abnormalities, Drug-Induced↗
PubMed1992

Viscerosomatic convergence onto feline spinal neurons from esophagus, heart and somatic fields: effects of inflammation.

One objective of this study was to examine a mechanism for the inability of patients to distinguish esophageal pain from cardiac pain. Patients with esophageal disease and angina pectoris often perceive pain as originating from the same somatic fields. Another objective was to compare the effect of esophageal distension between animals with a non-inflamed or with an inflamed esophagus. For this study in anesthetized cats, we recorded extracellular action potentials from T2-T7 spinal neurons that responded to intraluminal distension of an untreated or a turpentine-inflamed distal esophagus. Threshold distension volumes were compared between these 2 groups of animals. Neurons also were examined for effects of intracardiac bradykinin injection and somatic stimuli. Results showed that spinal neurons responded to a smaller threshold distension volume when cells in animals with an inflamed distal esophagus were compared to cells in animals with a non-inflamed distal esophagus. Spinal neurons that received input from the distal esophagus also received convergent input from the heart and somatic fields. Our data supported the hypotheses that (1) referred pain from the distal esophagus resulted from activation of the same spinal neurons by visceral and somatic input, (2) pain originating from the distal esophagus and heart might be difficult to distinguish because of viscerosomatic and viscerovisceral convergence onto the same spinal neurons, and (3) an inflamed distal esophagus might be more sensitive to distension than a non-inflamed esophagus.

Afferent Pathways↗
PubMed1995

Somatic antigens of adult Dicrocoelium dendriticum recognised by bile antibodies of naturally infected cattle.

Bile samples, from slaughtered cattle harbouring between 120 and 280 adult lancet flukes, were used to investigate the range of somatic proteins inducing local antibody responses in naturally infected animals. Lancet fluke infections induced local (bile) antibody responses against Tris-buffered saline (TBS) soluble, sodium dodecyl sulphate (SDS) soluble and 2-mercaptoethanol (2-Me) soluble somatic proteins of adult Dicrocoelium dendriticum. IgA antibody isotypes predominated in the response against buffer-soluble somatic antigens, whereas SDS-soluble and 2-Me-soluble proteins induced similar level of both IgA and IgG1 antibodies. Analysis of the antigens recognised by particular isotype-specific bile antibodies suggests that different antigens preferentially induce isotype restricted antibody responses. The bile antibody response was highly species specific, only one antigen from somatic protein extracts of Fasciola hepatica being precipitated by bile samples showing the highest reactivity against D. dendriticum.

Animals↗
PubMed1988

Somatic cell genetics and the study of cholesterol metabolism.

The regulation of cholesterol biosynthesis by extracellular cholesterol occurs both in whole animal tissue and in permanent somatic cell lines in culture. Permanent mammalian cells lines, under optimized growth conditions, are easily manipulated both biochemically and genetically. The Chinese hamster ovary cell line (CHO-K1) is the most widely used cell line for genetic studies. CHO-K1 is a pseudo-diploid mammalian cell exhibiting a short doubling time and a relatively high plating efficiency. Somatic cell mutants can be generated through mutagenesis and also by drug adaptation. Following mutagenesis, auxotrophs may be isolated either by selection or by screening. Most selection procedures for mutants of cholesterol metabolism must be done in serum depleted of cholesterol which requires the endogenous biosynthetic pathway to be intact. Mutants failing to produce cholesterol do not replicate their DNA and exhibit reduced concentrations of cholesterol in their membranes. BUdR and polyene antibiotics have both been used to select against the wild-type cells which incorporate these compounds and are killed, allowing the survival of the mutant cells. Both mevalonate and cholesterol auxotrophs have been isolated with the BUdR technique and have proven useful for elucidation of the early steps in cholesterol biosynthesis, particularly for the ratelimiting enzyme HMG-CoA reductase. Somatic cell fusion of a mutant and wild-type cell followed by chromosomal segregation, routinely used to map human genes, has also been used to map the human gene for HMG-CoA synthase. Such hybrids also provide valuable information on the dominance or recessivity of a specific lesion. DNA-mediated gene transfer into somatic cell mutants allows the selection of DNA sequences which complement the mutation, and is also useful for analysis of regions of regulatory significance. Mutants, resistant to the regulatory effects of oxygenated sterols, can be isolated following mutagenesis. Mutants of this type vary the lipid content of their membranes in response to cholesterol concentration in the medium. All such mutants tested exhibit a pleiotropic regulatory effect on more than one enzyme in the cholesterol biosynthetic pathway. Adaptation to drugs such as compactin and mevinolin, which inhibit HMG-CoA reductase, have been used to produce mutants which overexpress enzymes in the pathway. These amplified cells are useful sources of specific mRNAs for construction of cDNA libraries and gene isolation. Structure-function relationships of membrane sterols can be studied in cholesterol auxotrophs where changes in acyl-chain ordering can be manipulated by exogenous sterols in the medium.

Animals↗
PubMed1990

Antidromic firing occurs spontaneously on thalamic relay neurons: triggering of ectopic action potentials by somatic intrinsic burst discharges.

Possible dynamic relationships between orthodromically conducted somatic bursts and antidromic impulses arising from presynaptic endings of thalamocortical neurons were explored. Evoked or spontaneous bursts were recorded from 125 identified thalamic relay neurons in 36 anesthetized rats using extracellular microelectrodes. Evoked bursts were obtained by electrical stimulation of either the neocortex or the peripheral activation field. Spontaneous antidromic firing appeared only during periods of (or an expected) rapid somatic intrinsic burst discharge. Ectopic axonal impulses occurred either separately, or clustered in doublets or triplets having relatively long-lasting intervals; these slow bursts represented a proportion of about 12% of evoked and 20% of spontaneous whole bursts. Separate ectopic action potentials could also appear several milliseconds after rapid bursts, producing peculiar long last-interval bursts; about 15% of the whole bursts were of this long interval type. The probability that an ectopic axonal impulse will occur after a rapid burst increases with the number of its action potentials, suggesting that the duration of orthodromic burst firing might contribute to the triggering of ectopic impulses. For 52% of the neurons tested, the activation threshold of their axon terminals decreased just before or immediately after rapid somatic bursts. Since no excitability changes were observed in thalamocortical axons of the white matter, the ectopic action potential generators were probably located on presynaptic endings. During a transient deafferentation of thalamic neurons induced by intrathalamic microinjection of a magnesium solution, neither burst activity nor spontaneous antidromic firing were observed, suggesting that thalamic orthodromic burst discharges are required for presynaptic impulse generation. In conclusion, somatic intrinsic bursts traveling orthodromically along thalamocortical axons might be involved in triggering presynaptic impulses on parent and possibly on nearby thalamic cells. Since a spontaneous antidromic action potential is able to trigger a rapid burst [Pinault (1988) Eur. J. Neurosci. Suppl. P. 246; Pinault and Pumain (1989) Neuroscience 31, 625-637], it is postulated that excitatory interactions between presynaptic endings might be involved in intrinsic burst synchronization processes.

Action Potentials↗
PubMed1990

Induction of somatic sensory inputs to the lateral geniculate nucleus in congenitally blind mice and in phenotypically normal mice.

The incidence of aberrant innervation of the lateral geniculate nucleus by ascending somatic sensory axons was examined following injections of wheat germ agglutinin conjugated with horseradish peroxidase into the dorsal column nuclei of adult mice which were: (1) normal; (2) normal, but bilaterally enucleated on the day of birth; (3) normal, but received a large unilateral lesion of the rostral cortex on the day of birth; (4) normal, bilaterally enucleated, as well as unilaterally lesioned in the rostral cortex on the day of birth; (5) homozygous for an ocular retardation mutation (orj/orj); or (6) homozygous for the orj mutation and received a large unilateral lesion of the rostral cerebral cortex on the day of birth. In the phenotypically normal animals which were untreated, no somatic sensory inputs enter into the dorsal lateral geniculate nucleus. A few labeled axons enter into and arborize within the dorsal lateral geniculate nucleus in normal animals which received bilateral enucleations or unilateral rostral cortical lesions on the day of birth. However, in congenitally blind animals and in phenotypically normal animals which received bilateral enucleations as well as unilateral rostral cortical lesions on the day of birth, a significant number of labeled axons enter into and arborize within the dorsal lateral geniculate nucleus. Among all these experimental groups, the densest innervation of the lateral geniculate nucleus occurred in congenitally blind animals which received rostral cortical lesions on the day of birth. In these, robust arborizations of labeled somatic sensory axons occupy a substantial extent of the lateral geniculate nucleus. These results not only demonstrate that ascending somatic sensory axons can be rerouted to the lateral geniculate nucleus, but also indicate that the ability of a thalamic afferent pathway to undergo extensive reorganization and to innervate inappropriate thalamic targets following early perturbations is not unique to the retinal projection (in which this has previously been demonstrated), and may be a more general characteristic of the major thalamic afferent systems.

Animals↗
PubMed1989

Emotional and somatic consequences of binge episodes.

The present study investigated emotional and somatic consequences of the daily eating episodes of 19 bulimics, 15 bingers, and 20 normal control subjects. For 1 week, subjects rated 21 emotional and somatic states immediately following all eating episodes and 1 h later. Results indicated that bulimics and bingers reported significantly greater negative and somatic consequences immediately following their binge episodes than normal eaters following all of their eating episodes. For both groups, these negative emotional consequences persisted over time. Following nonbinge episodes, only bulimics reported experiencing significantly greater negative emotions than normal controls. Comparisons of the binge and nonbinge episodes of the bulimics and bingers indicated that binge episodes are followed by greater immediate and delayed negative and somatic consequences than nonbinge episodes. Furthermore, the positive emotions that occur immediately after a binge significantly decrease in intensity within 90 min after the episode. Theoretical and clinical implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1986

Relationships between psychological symptoms, somatic complaints and menopausal status.

The importance of distinguishing climacteric symptoms from other psychological and somatic complaints has been repeatedly stressed, but as yet no detailed guidelines are available to assist the clinician in the day-to-day management of patients. Previous epidemiological surveys of climacteric symptoms have been criticised because of inadequate methodology. We have attempted to overcome most of these problems and to provide a more detailed analysis of the relationships between menopausal status and psychological and somatic symptoms. Eight hundred and fifty pre-, peri- and post-menopausal women, aged 45-65 yr, took part in a cross-sectional survey of general health, psychosocial factors and current symptomatology. They were a non-menopause clinic sample and were blind to the purpose of the study. Using a principal components analysis, the relationships between symptoms were examined. Certain psychological and somatic symptoms occurred together in specific clusters. Some of these symptom clusters, e.g., vasomotor symptoms and sexual difficulties, were best predicted solely by menopausal status, while others, such as psychological and somatic symptoms, were more clearly associated with psychosocial factors. On the basis of these results, guidelines for the assessment of climacteric and post-menopausal women can be suggested.

Aged↗
PubMed1988

Genomic multipotentiality of differentiated somatic cells.

Nuclear transplantations from several differentiated somatic cell types into amphibian oocytes and eggs revealed that their genome contains the genes required for the development of prefeeding tadpoles. In addition, erythrocyte nuclei directed the formation of feeding tadpoles (independent organisms) that advanced to larval stages with hind limb buds. Thus, the genome of several differentiated somatic cell types can undergo widespread activation and specify a multiplicity of cell types. Although evidence for the genetic totipotency of differentiated somatic cells is lacking, we speculate that the genetic totipotency of at least some differentiated somatic cell types still remains a tenable hypothesis.

Amphibians↗
PubMed1995

Mechanism of somatic mitochondrial DNA mutations associated with age and diseases.

Mitochondrial DNA (mtDNA) that codes protein subunits essential for the maintenance of mitochondrial ATP synthesis system acquires mutations at a much higher rate than that in nuclear DNA. Recent study has revealed that somatically acquired mutations such as deletions in mtDNA are caused mainly by oxygen free-radical damage. Cumulative accumulation of these somatic mutations during the life of an individual causes bioenergetic deficit leading to cell death and normal ageing. The base-sequencing of the entire mtDNA from 48 individuals revealed that germ-line point mutations accelerate extensively the somatic oxygen free-radical damage and the deletions leading to generation of more than a hundred kinds of mtDNA minicircle. These accelerated somatic mutations are expressed as premature ageing of the patients with degenerative diseases. Comprehensive analyses of the entire mtDNA, including the total base-sequencing and the total deletion correlating with oxygen free-radical damage, has revealed a clear relationship between the genotype and its phenotype, such as the severity of clinical symptoms and the survival time of the patients. Extensive generation of mtDNA minicircles caused by the oxygen free radical implies a close relations between the redox mechanism of ageing and the programmed cell-death machinery.

Aging↗
PubMed2006

The role of neuroticism and perceived school-related stress in somatic symptoms among students in Norwegian junior high schools.

The present study investigated the role of neuroticism and perceived school-related stress in somatic symptoms among a sample of 327 (167 females and 160 males) students in two Norwegian junior high schools. The results suggest that the role of neuroticism on somatic symptoms may be overestimated, and that the role of stress may be underestimated if neuroticism, stress and somatic symptoms are measured at the same time. In this study, both neuroticism and perceived school-related stress were found to be significantly associated with somatic symptoms.

Adolescent↗
PubMed2006

Targeting cellular memory to reprogram the epigenome, restore potential, and improve somatic cell nuclear transfer.

Successful cloning by somatic cell nuclear transfer (SCNT) is thought to require reprogramming of a somatic nucleus to a state of restored totipotentiality [Dean, W., Santos, F., Reik, W., 2003. Epigenetic programming in early mammalian development and following somatic cell nuclear transfer. Semin. Cell. Dev. Biol. 14, 93-100; Jouneau, A., Renard, J.P., 2003. Reprogramming in nuclear transfer. Curr. Opin. Genet. Dev. 13, 486-491; ]. Though SCNT-induced reprogramming is reminiscent of the reprogramming that occurs after fertilization, reprogramming a differentiated nucleus to an embryonic state is delayed and incomplete in comparison (for review, see ). This is likely due to the existence of an epigenetic-based cellular memory, or program, that serves to regulate global patterns of gene expression, and is the basis of a genome defense mechanism that silences viruses and transposons. The mechanisms of this memory include CpG methylation and modification of histones. Recent evidence by Feng et al. [Feng, Y.-Q., Desprat, R., Fu, H., Olivier, E., Lin, C.M., Lobell, A., Gowda, S.N., Aladjem, M.I., Bouhasira, E.E., 2006. DNA methylation supports intrinsic epigenetic memory in mammalian cells. PLOS Genet. 2, 0461-0470], using a transgenic experimental system, indicates that these marks may be acquired in more than one order and thus, silent heterochromatic structure can be initiated by either methylation of CpG dinucleotides or by histone modifications. In this system, however, CpG methylation appears to differ from histone modifications because it bestows a persistent epigenetic, or cellular, memory. In other words, CpG methylation can independently confer cellular memory, whereas histone modifications appear to be limited in this capacity. Therefore, in the context of genomic reprogramming induced by SCNT, efficient demethylation is likely a key (if not the only) rate-limiting step to improving the efficiency and outcomes of SCNT cloning. This review discusses the possibility of targeting cellular memory, and in particular inducing demethylation of a somatic nucleus prior to nuclear transfer, to enable reprogramming events typically carried out by oocyte factors and thereby improve developmental competence of SCNT-reconstructed embryos. Several recent published reviews of SCNT, cellular reprogramming and genomic demethylation served as valuable sources for the authors and are recommended as supplemental reading. These include the following: Bird, A., 2002. DNA methylation patterns and epigenetic memory. Gen. Dev. 16, 6-21; Grafi, G., 2004. How cells dedifferentiate: a lesson from plants. Dev. Biol. 268, 1-6; Latham, K.E., 2005. Early and delayed aspects of nuclear reprogramming during cloning. Biol. Cell 97, 119-132; Lyko, F., Brown, R., 2005. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J.Natl. Cancer Inst. 97, 1498-1506; Morgan, H.D., Santos, F., Green, K., Dean, W., Reik, W., 2005. Epigenetic reprogramming in mammals. Hum. Mol. Gen. 14, R47-R58; Szyf, M., 2005. DNA methylation and demethylation as targets for anticancer therapy. Biochemistry 70, 533-549; Buszczak, M., Spradling, A.C., 2006. Searching chromatin for stem cell identity. Cell 125, 233-236; Gurdon, J.B., 2006. From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Annu. Rev. Cell. Dev. Biol. 22, 1-22; Yoo, C.B., Jones, P.A., 2006. Epigenetic therapy of cancer: past, present and future. Nat. Rev. 5, 37-50.

Animals↗
PubMed2006

Individual reactivity to the open-field predicts the expression of stress-induced behavioural and somatic pain sensitisation.

Posttraumatic stress disorder (PTSD) is the fourth most common psychiatric disorder. It is associated with somatic complaints like pain problems. Only a proportion of persons exposed to traumatic events develop PTSD. Several factors, like genetic predisposition, stressor intensity, cognitive appraisal mechanisms and coping processes influence the likelihood of developing PTSD after exposure to a trauma. We used a single session of footshocks in rats, an animal model with a high degree of validity for PTSD, to study whether individual behavioural traits predict long-term stress-induced sensitisation of behavioural responsivity and somatic pain sensitivity and therefore can act as a vulnerability factor. Rats were selected for low (LA) and high (HA) open-field locomotor reactivity and then underwent a single session of footshocks. Two to 5 weeks after footshocks, behavioural sensitisation was investigated using a noise challenge, an electrified prod challenge and a forced swim test. Somatic pain sensitivity was measured using a tail-immersion test. During exposure to noise in a novel cage, footshocked rats showed increased immobility compared to controls, which was significantly greater in LA than in HA rats. Footshocked rats showed increased burying in the electrified prod challenge and no effect was found in the forced swim test. Footshocks caused hyperalgesia in LA rats, but hypoalgesia in HA rats. We conclude that low open-field locomotor reactivity predicts the degree of stress-induced behavioural sensitisation and the direction of altered somatic pain sensitivity, suggesting that an anxiety-prone personality or passive coping style may increase the risk of developing stress-related psychosomatic disorders.

Animals↗
PubMed2006

Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years.

Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. In this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G>T transitions and 1 G>A) and one in codon 13 (G>A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2. The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal cancer of later age of onset.

Adult↗
PubMed2005

The relationship between somatic and emotional stimuli: a comparison between adolescents with temporomandibular disorders (TMD) and a control group.

The overall purpose of this study was to determine whether adolescents with chronic temporomandibular disorder (TMD) pain are more sensitive to all types of somatic and emotional stimuli compared with a matched healthy control group. Sixty adolescents, 8 boys and 52 girls ranging from 12 to 18 years, participated in the study. Thirty of the subjects exhibited TMD, reporting pain of at least 3 months duration. The age- and gender-matched control group consisted of 30 dental recall patients who reported TMD pain less than once a week. All participants completed a 40-item questionnaire comprising 10 items each of pleasant and aversive qualities crossed with somatic and emotional forms of stimuli. The items, a selection of a broad range of familiar stimuli by a panel of experts, were rated based on intensity of experience (0-10, numerical rating scale). Well-fitting items that formed a valid construct within each of the four domains were selected using Rasch analysis. The results showed that adolescents with TMD pain reported significantly greater sensitivity (p<0.05) to aversive somatic and pleasant somatic stimuli than the controls. The differences between groups for the aversive emotional and pleasant emotional stimuli were non-significant. These findings suggest that chronic TMD pain states in adolescents are accompanied by amplification of bodily, but not purely emotional stimuli and that cognitive systems are implicated, not only an alteration of the nociceptive systems.

Adolescent↗
PubMed2004

Identification of somatic and anxiety symptoms which contribute to the detection of depression in primary health care.

Somatic symptoms and anxiety symptoms are often disregarded in the detection of depression in primary care. The present investigation examined to what extent somatic and anxiety symptoms recorded with the Composite International Diagnostic Interview-Primary Health Care Version (CIDI-PHC) can improve the detection of depression as compared to the General Health Questionnaire-12-item version alone. Data from the World Health Organization study on Psychological Problems in General Health Care were used. The study sample consisted of primary care attenders from 15 centres from all over the world who underwent a psychiatric examination with the CIDI-PHC. Medically unexplained somatic symptoms (back pain, feelings of heaviness/lightness in parts of the body, periods of bodily weakness, seizures/convulsions, permanent tiredness, exhaustion after a minimum of effort) and-to a smaller extent-diverse anxiety symptoms (e.g. feelings of anxiousness/nervousness, feelings of tension, difficulties relaxing) significantly contributed to the detection of depression in a logistic regression analysis. The results confirm the observation that in primary care somatic symptoms play an important role in the manifestation of depressive disorders. The items investigated herein could prove beneficial for future depression screening instruments to improve the detection of depressive disorders in primary care.

Anxiety Disorders↗
PubMed2005

Molecular mechanisms controlling germline and somatic stem cells: similarities and differences.

Germline and somatic stem cells are distinct types of stem cells that are dedicated to reproduction and somatic tissue homeostasis, respectively. Extensive studies on these two stem cell types in different organisms over the past few years have revealed some commonalities in the mechanisms controlling their self-renewal and differentiation. Furthermore, germline or somatic cells in various organisms and sexes also exhibit their own unique ways of regulating stem cell function. By understanding these similarities and differences we might gain a better insight into how stem cells are regulated in general and how germline and somatic stem cell types are regulated differently.

Animals↗
PubMed2026

Origins and timing of somatic variants in the brain.

Somatic variants accumulate in human brain cells throughout the lifespan. Variant allele fraction has traditionally been used as a proxy for both the developmental timing of somatic variants and their functional effect, based on the assumption that earlier mutations are shared by larger cell populations and therefore have greater potential for severe phenotypes. However, recent discoveries challenge this simplified model. Variables such as developmental bottlenecks, lineage restriction, and cellular and molecular context play critical roles in shaping the distribution and functional impact of somatic variants in the brain. These insights support a shift toward a context-dependent framework for interpreting somatic mosaicism.

Humans↗