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Differential nucleosome positioning on Xenopus oocyte and somatic 5 S RNA genes determines both TFIIIA and H1 binding: a mechanism for selective H1 repression.

In Xenopus somatic cells histone H1 effects the transcriptional repression of oocyte type 5 S RNA genes, without altering the transcription of the somatic type 5 S RNA genes. Using an unambiguous nucleosome mapping method we find substantial differences between the multiple in vitro nucleosome positions on the two types of genes. These nucleosome positions determine both transcription factor and H1 binding, allowing TFIIIA to bind more efficiently to nucleosomes containing the somatic 5 S RNA gene than to nucleosomes on the oocyte 5 S RNA gene. Significantly, in a binding competition between TFIIIA and H1, TFIIIA preferentially binds to the somatic nucleosome whereas H1 preferentially binds to the oocyte nucleosome, excluding TFIIIA binding. These results strongly suggest that nucleosome positioning plays a key role in the regulation of transcription of 5 S RNA genes and provide a molecular mechanism for the selective repression of the oocyte 5 S RNA genes by H1.

Animals↗

Reprogramming a somatic nucleus by trans-modification activity in germ cells.

The germ cell lineage is totipotent insofar as it provides a link between an individual and the subsequent generations. There is a series of characteristic genomic modifications in germ cells that distinguish this lineage from somatic cells. These modifications include extensive demethylation of the genome, erasure of allele-specific methylation of imprinted loci and re-activation of the silent X chromosome. To test if this is an active process capable of reprogramming a somatic nucleus, we prepared germ cell-somatic cell hybrids. A dominant trans modification activity was detected in germ cells that was capable of inducing similar modifications in the somatic nucleus. This experimental system can therefore be used to study how determined cell state can be reversed by specific genomic modifications.

Animals↗

DNA fingerprinting: the utilization of minisatellite probes to detect a somatic mutation in the proteus syndrome.

Syndromes with localized or segmental abnormalities have been proposed to be the result of a somatic mutation leading to the presence of somatic mosaicism in the tissue. The Proteus syndrome, with its hemihypertrophy, macrodactyly and exostoses, has features which would indicate that the phenotype results from such events. The success of utilizing DNA fingerprint probes to detect somatic mutations in cancer raised the possibility that a similar approach might be successful in an investigation of two patients with the Proteus syndrome. Single band differences were detected with the probe 33.6 in a pair of monozygotic twins discordant for Proteus and in a comparison of tissue from normal and affected areas in another patient. These findings would appear to confirm the hypothesis that the Proteus syndrome results from a somatic mutation. Furthermore, the results indicate that DNA fingerprinting may offer a valuable technique for identifying probes for investigations of similar syndromes.

Abnormalities, Multiple↗

Neuronal mechanisms of pain with special emphasis on visceral and deep somatic pain.

Pain has several dimensions: the sensory-discriminative, the motivational-affective, the cognitive and the motor and autonomic dimension. Each dimension can be roughly identified with certain brain areas. The sensory-discriminative dimension is also called the "nociceptive dimension" or, briefly, "nociception". 1. Noxious stimuli applied to the skin appear to be encoded quite specifically by certain types of nociceptive afferent units with group III (A) and IV (C) fibers. The impulse activity of these cutaneous primary afferents converges on spinal "nociceptive-specific" neurones, most of which seem to be located in lamina I of the dorsal horn, and together with the nonnociceptive information from the skin on "wide-dynamic range" (multisensory) neurones in the grey matter, most of which are situated in lamina V, but some also in adjacent laminae and lamina I. 2. Many of these "nociceptive-specific" and "wide-dynamic range" neurones project with their axons through the anterolateral tract to the nucleus ventralis posterolateralis (VPL) of the thalamus and also to other thalamic nuclei, to the mesencephalon and to the reticular formation of the brain stem. In the VPL of the thalamus, most neurones with nociceptive input have a wide-dynamic range property, very few are nociceptive-specific. 3. Noxious events leading to deep somatic pain are encoded by thin myelinated (A delta) and unmyelinated afferent fibers (e.g., from skeletal muscle, tendon and joint capsule). Besides these deep somatic "nociceptive" afferent units, other nonnociceptive deep somatic afferent units with fine afferents have been claimed to exist and it is believed that these are involved in functions other than nociception. The specificity of responses of these afferents, with respect to the natural stimuli, is only relative. 4. For the viscera nociceptive spinal visceral afferents, which are only activated when injurious or potentially injurious events in the visceral domain (which may lead to pain) occur, cannot be unambiguously shown to exist. It seems more likely that the activity in the same population of spinal visceral afferents is involved in nociceptive as well as in nonnociceptive sensory functions, in the regulation of visceral organs and in various types of reflexes. 5. No neurones in the spinal grey matter have been found which specifically transmit and process information from fine deep somatic and spinal visceral afferents. This information seems to converge not only on many "wide-dynamic range" (multisensory) spinal neurones but also on some "nociceptive-specific" neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

cDNA cloning of ECP40, an embryogenic-cell protein in carrot, and its expression during somatic and zygotic embryogenesis.

A cDNA of 1.2 kb was isolated from a cDNA library of embryogenic cells of carrot (Daucus carota L.) by use of nucleotide sequences that encode two internal amino-acid sequences of ECP40 (an embryogenic-cell protein with a relative molecular mass of 40,000). A genomic Southern blot using the cDNA as probe suggested that there are at least two genes for ECP40 in the carrot genome. The cDNA encoded an open reading frame of 306 amino acids, and the deduced amino-acid sequence was found to share two motifs, namely SSSSSSEDDGXGGRRKKGXXXKIKEKLXGG and EKKXXXDKIKXKLPG, with rab16 protein from rice and dehydrins from barley and maize. The level of expression of these proteins has been reported to be high during late embryogenesis and to be induced by a plant hormone, ABA. Accumulation of ECP40-specific transcripts started 18 days after flowering and continued until maturation of seeds, but the levels decreased within 24 h after imbibition. ECP40 and its mRNAs were detected in the endosperm and zygotic embryos of mature seeds by immunohistochemistry and in situ hybridization. Exogenous application of 0.1 mM ABA to carrot seedlings did not induce expression of the gene for ECP40, while drought treatment induced the accumulation of low levels of the mRNAs. During somatic embryogenesis, the mRNAs were found at high levels in embryogenic cells and at low levels in somatic embryos at the torpedo stage. Immunohistochemical analysis and in situ hybridization showed that both ECP40 and its transcripts were preferentially localized in the peripheral cells of the clusters of embryogenic cells. In somatic embryos, application of ABA resulted in increases in levels of mRNAs for ECP40 up to the levels in embryogenic cells, but no such increases were observed in ABA-treated embryogenic cells. The pattern of expression of the gene for ECP40 during somatic embryogenesis was basically the same as that of ECP31, another ABA-regulable embryogenic-cell protein of carrot, the presence of which has been correlated with the embryogenic competence of cultured cells (T. Kiyosue, S. Satoh, H. Kamada and H. Harada, Plant Physiol 95 (1991) 1077-1083). The various results together imply that a group of ABA-inducible genes is expressed in these embryogenic cells.

Amino Acid Sequence↗

Development of a culture specific (Nigeria) screening scale of somatic complaints indicating psychiatric disturbance.

In a pre-study it was seen that somatization complaints formed the basis of the distress of the mentally ill in Nigeria and there was need for somatic complaints to be employed in evolving a psychodiagnostic system which would lead to a better understanding of mental illness in Nigeria. In pursuit of this goal, some 65 somatic complaints were drawn from protocols of patients treated at the Psychiatric Hospital, Enugu, from 1978-1981. These complaints were administered in form of questions to 179 psychiatric patients and 349 students (normals) of the Institute of Management and Technology, Enugu. Forty-six of the 65 complaints distinguished male normals from the psychiatric patients and 30 items of the 65 distinguished the female normals from the female psychiatric patients at the 0.05 level or better. In a further step each subject was rated. A positive response to each of the discriminant items was scored as one point. The mean, standard deviation and cumulative frequency percentage of both groups were calculated. These values are recommended for use in discriminating normals from the mentally ill in Nigeria. This study is seen as a first step leading towards a much wider study involving somatizations in a psychodiagnostic endeavor, as well as throwing more light into the problem of classification of psychiatric disorders in Nigeria.

Adult↗

Neurasthenia and depression: a study of somatization and culture in China.

The author reviews conceptual and empirical issues regarding the interaction of neurasthenia, somatization and depression in Chinese culture and in the West. The historical background of neurasthenia and its current status are discussed, along with the epidemiology and phenomenology of somatization and depression. Findings are presented from a combined clinical and anthropological field study of 100 patients with neurasthenia in the Psychiatry Outpatient Clinic at the Hunan Medical College. Eighty-seven of these patients made the DSM-III criteria of Major Depressive Disorder; diagnoses of anxiety disorders were also frequent. Forty-four patients were suffering from chronic pain syndromes previously undiagnosed, and cases of culture-bound syndromes also were detected. For three-quarters of patients the social significances and uses of their illness behavior chiefly related to work. Although from the researcher's perspective 70% of patients with Major Depressive Disorder experienced substantial improvement and 87% some improvement in symptoms when treated with antidepressant medication, fewer experienced decreased help seeking, and a much smaller number perceived less social impairment and improvement in illness problems (the psychosocial accompaniment of disease including maladaptive coping and work, family and school problems). These findings are drawn on to advance medical anthropology and cultural psychiatry theory and research regarding somatization in Chinese culture, the United States and cross culturally. The author concludes that though neurasthenia can be understood in several distinctive ways, it is most clinically useful to regard it as bioculturally patterned illness experience (a special form of somatization) related to either depression and other diseases or to culturally sanctioned idioms of distress and psychosocial coping.

Adolescent↗

Submodality and columnar organization of the second somatic sensory area in cats.

Electrophysiological responses of 519 single and 405 multiple neurons located in the distal forelimb zone of the second somatic sensory cortex (SII) of 11 intact cats were characterized according to their submodality and receptive field properties. In 4 of these animals, 46 single and 134 multiple neuronal responses were studied after transection of the dorsal columns contralateral to the cortical recording sites. Receptive field positions overlapped considerably in SII during orthogonal electrode penetrations, but were shifted during tangential penetrations. Analysis of the receptive field positions for neurons encountered in tangential penetrations indicated that receptive fields rarely overlapped when the neurons were separated by more than 750 microns. Using a variety of hand-held stimuli, neuronal responses were assessed according to several criteria including: velocity, adaptation, following rate, spontaneous activity, and whether the response was elicited by stimulating hairs, skin, claws, or deep tissue. Based on these parameters, it was possible to discern several types of neuronal responses in SII. Among these, over 60% of the neurons in our sample responded best to movement of hairs. A smaller number of neurons responded as though they received inputs from Pacinian receptors or rapidly adapting receptors in the glabrous skin. In about 20% of the single neuron sample, it was not possible to identify a selective adequate stimulus, however, these cells responded to somatic stimuli, such as taps. Approximately 5% of the neurons could not be driven with somatic sensory stimuli. Following dorsal column lesions, some neurons in SII still responded to cutaneous stimulation, primarily hair movement. Most SII neurons were more difficult to drive, the responses were more sluggish and receptive fields were less well-defined. A greater proportion of single neuron responses (greater than 60%) could not be activated by any type of somatic sensory stimulus. These results indicate that the dorsal columns provide a potent, but not exclusive, source of afferent input to SII.

Afferent Pathways↗

Ultrastructure of germ cells and adjacent somatic cells correlated to initiation of meiosis in the fetal pig.

The ultrastructure of female and male germ cells and associated somatic cells were studied in morphologically sex differentiated fetal pig gonads from day 27 to day 95 post insemination. Before meiosis starts in the ovary, the organelles of germ cells and somatic cells of both sexes are poorly developed. In oocytes in leptotene stage, the endoplasmic reticulum attains close proximity to the plasma membrane forming characteristic contact areas which in addition are only seen in male germ cells of the same age. As meiosis progresses, the organelles of the oocyte increase in number and degree of differentiation. In particular the ER is prominent in the diplotene stage. At midgestation the male germ cells become polarized, the organelles gathering at one side of the nucleus. In the granulosa cells the number and extension of organelles increase concomitantly with the oocytes proceeding through meiosis. The Sertoli cells grow progressively complex in shape, with numerous mitochondria and a prominent ER, whereas the Golgi complex remains poorly developed. Small dense bodies are present both in germ cells and somatic cells. They are electron dense, membrane bounded, rounded or elongated granules often connected with endoplasmic reticulum. No activity of peroxidase, catalase or acid phosphatase could be traced in the granules, making them improbable candidates as peroxisomes or lysosomes. Their number is high in all germ cells and somatic cells on day 27 post insemination and in germ cells in leptotene stage.

Animals↗

Cell type determines plastid transmission in tomato intergeneric somatic hybrids.

Mesophyll (M)- and suspension culture (S)-derived protoplasts of both Lycopersicon esculentum, tomato, and its wild relative Solanum lycopersicoides were fused as S + M, M + M and S + S combinations, respectively, to resolve the role of parental cell types in determining cpDNA transmission to intergeneric somatic hybrid plants. The mesophyll cpDNA was preferentially transmitted to 96% of the plants, each regenerated from a separate callus, in M + S and S + M fusion combinations. In contrast, for the M + M combination there was an equable distribution of either tomato cpDNA or that of S. lycopersicoides among the 34 hybrid plants. The number of plastids or proplastids in mesophyll or suspension protoplasts was not a factor regulating cpDNA transmission. Mesophyll or suspension protoplasts of both fusion partners had comparable frequencies of either plastid type with a mean of 23. The biased transmission of plastids from the mesophyll parent in somatic hybrid plants of S + M and M + S combinations appears to be due to differential multiplication of plastids, possibly conditioned by an unequal input of the nucleoids found in plastids versus proplastids. In the M + M fusion, plastid and nucleotide input and subsequent plastid multiplication are apparently equal, and when combined with random sorting out leads to an equal distribution of parental cpDNAs in the regenerated somatic hybrid plants. For the S+S combination, 22 somatic hybrid plants have exclusively tomato cpDNA, an outcome that is not readily explained by donor cell input.

Cell Fusion↗

Somatization, distress and chronic pain.

The two defining features of somatization are numerous self-reported physical symptoms and excessive health care seeking. This may be due to a lowered perceptual threshold for perceiving and reporting bodily symptoms, amplification or misinterpretation of those symptoms, or underlying psychiatric disturbance. Recurrent pain is the most common somatic symptom reported. True somatization disorder is very rare (< 1%) and requires a DSM-III-R diagnosis of at least 13 different physical symptoms which cannot be explained by, or are in gross excess of physical findings, and have caused the patients to seek health care or alter their lifestyles. However, researchers have argued that a spectrum of severity for somatization exists, and this is supported by epidemiological research. Available data also indicate that behavioural interventions may show long-term cost-effectiveness in the management of chronic pain. Chronic pain dysfunction appears to place a disproportionate burden on overall health care expenditure for chronic pain patients.

Chronic Disease↗

Analyses of deoxycytidylate deaminase molecular forms in human-mouse and monkey-mouse somatic cell hybrids.

Disc polyacrylamide gel electrophoresis (disc PAGE) analyses have revealed that mouse, human, and monkey cytosal deoxycytidylate (dCMP) deaminases differ in electrophoretic mobility, so that mixtures of mouse and human, mouse and monkey and human and monkey enzymes can be separated. To learn whether the genes for dCMP deaminase and thymidine (dT) kinase are genetically linked, disc PAGE analyses of cytosol fractions from human-mouse and monkey-mouse somatic cell hybrids were carried out. The interspecific somatic cell hybrids were derived from the fusion of cytosol dT kinase deficient mouse cells with cytosol dT kinase-positive human and monkey cells: they contained mostly mouse chromosomes and a few primate chromosomes, including the determinant for primate cytosol dT kinase. The disc PAGE analyses demonstrated that the human-mouse and monkey-mouse somatic cell hybrids contained a dCMP deaminase activity with an electrophoretic mobility characteristic of mouse dCMP deaminase. Enzymes with electrophoretic mobilities characteristic of human and monkey dCMP deaminases were not demonstrable. these findings suggest that primate cytosol dT kinase and dCMP deaminase are coded on different chromosomes, or that the formation in hybird cells of an active primate dCMP deaminase is suppressed. Chick-mouse somatic cell hybrids containing chick but not mouse cytosol dT kinase were also analyzed, but it was not possible to establish whether the enzyme was of murine or avian origin because of the similarity in electrophoretic mobility between the chick and mouse enzymes. Human and mouse cells contained low levels of mitochondrial dCMP deaminase activity. In contrast to dT kinase isozymes, however, mitochondrial and cytosol dCMP deaminases were electrophoretically indistinguishable.

Aminohydrolases↗

The voluntary control of heart rate under differential somatic restraint.

The purpose of this investigation was to test the hypothesis that subjects (Ss) can exert voluntary, bidirectional heart rate (HR) control in the absence of concomitant changes in respiration rate (RR) and muscle activity (chin EMG). Feedback-assisted HR control was studied under four experimental conditions involving increasing levels of somatic restraint: (a) No somatic controls, (b) RR pacing, (c) EMG feedback, to maintain constant muscle activity, and (d) RR pacing plus EMG feedback. Fifteen Ss, eight females and seven males, were assigned to each of these four conditions (N = 60). The HR control task involved ten increase and ten decrease trials in random order, each lasting 60 sec and preceded by a 60-sec resting baseline period. The results indicated that Ss produced significant HR increases (Xdelta = +3.4 bpm), but were unable to effect decreases (Xdelta = -.3 bpm). Furthermore, the magnitude of the obtained HR changes did not differ by experimental condition, i.e., by level of somatic restraint. While concomitant bidirectional RR changes were found, the pacing procedure effectively reduced, and on HR increase trials, nearly eliminated, RR involvement. No increases in EMG activity were found on HR increase trials for any of the four experimental conditions, whereas all groups showed some EMG decreases on HR deceleration trials. With respect to the question of somatic mediation of autonomic control, it is concluded that HR increases produced under paced respiration "favor" an interpretation of unmediated HR acceleration.

Biofeedback, Psychology↗

Somatic sensations and psychological distress among students in Britain and Pakistan.

This is a cross-cultural study reporting the prevalence of somatic sensations in matched populations of students in Leeds (U.K.) and Lahore (Pakistan). A new self-report questionnaire, the Bradford Somatic Inventory (BSI), was employed together with the General Health Questionnaire (GHQ-28). There was no statistically significant difference between the two populations in mean endorsement rates but females from both ethnic groups demonstrated a higher prevalence of reported somatic sensations and had higher GHQ scores than males. The frequency hierarchy of endorsed items was similar in both groups. This study provides no support for the notion that Asian subjects generally experience more somatic sensations associated with psychological distress than Western subjects. Differences in the endorsement rates of particular items were evident and these are discussed.

Affective Symptoms↗

Clinical application of somatic gene therapy in inborn errors of metabolism.

Rapid advances in recombinant DNA and gene transfer technologies provide the potential for somatic gene therapy of inborn errors of metabolism in which the genetically defective function will be restored by transfer of a normal gene into somatic cells. The therapeutic potential and safety of gene therapy has been explored in cultured cells and experimental animals, but therapeutic clinical trials have not yet been proposed or performed. The technologies which may make somatic gene replacement therapy feasible need to be considered and criticised from a clinical perspective. Clinical trials will be necessary to determine the efficacy of somatic gene therapy and address concerns about safety.

Animals↗

hMLH1 and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer patients.

Much is known about the role of germline inactivation in mismatch repair (MMR) genes in hereditary non-polyposis colorectal cancer (HNPCC), but the impact of somatic MMR gene changes on sporadic colorectal cancer remains to be elucidated. In hereditary cases the hMLH1 and hMSH2 genes were shown to have a great importance, and in order to examine the somatic inactivation mechanisms of the two MMR genes hMLH1 and hMSH2 we screened 37 Hungarian sporadic colorectal cancer patients for allelic imbalance (AI), microsatellite instability (MSI), hMLH1 promoter hypermethylation and somatic mutations. Thirteen of the examined tumours (35%) were characterized by low-level MSI and none of the cases belonged to the high MSI group. Nine (24%) and seven (19%) cases had AI at the hMLH1 and hMSH2 genes, respectively. Seven tumours (19%) showed dense promoter hypermethylation of hMLH1, but only two patients had somatic mutations, one for each MMR gene. According to our study on this limited set of cases the most prominent mismatch repair inactivation mechanism in sporadic colorectal cancer patients is the hMLH1 promoter hypermethylation which may have a role in the carcinogenesis of sporadic colorectal cancer.

Adaptor Proteins, Signal Transducing↗

Antinociceptive effects of epidural and intravenous ketamine to somatic and visceral stimuli in rats.

PURPOSE: To evaluate the antinociceptive effect of epidural and intravenous ketamine on somatic and visceral stimuli and to address the emergency reaction. METHODS: Rats were randomly allocated into nine groups (n = 6); five groups with chronically implanted epidural catheters received saline or 0.5, 1, 2 and 4 mg. kg-1 ketamine epidurally, four groups received saline, or 1, 5 and 10 mg. kg-1 ketamine i.v. To assess somatic and visceral antinociceptive effects, tail flick (TF) test and colorectal distension (CD) test were carried out, respectively. Emergence reactions were graded. Maximal possible effects (% MPE) were calculated. RESULTS: Epidural ketamine increased % MPE in both tests in a dose-dependent fashion for 30 min (vs saline group, P < 0.05). Epidural ketamine 0.5 mg. kg-1 produced an increase in % MPE in the CD test (P < 0.05) but failed in the TF test. Intravenous ketamine, 10 mg. kg-1, produced 100 +/- 0 (mean +/- SE) % MPE in the CD test but 36 +/- 15% MPE in the TF test. Dose response curves indicated greater visceral antinociception than somatic. All rats showed emergence reactions following intravenous ketamine 10 and 5 mg. kg-1. CONCLUSION: Both epidural and intravenous ketamine produce greater antinociceptive effects to visceral than to somatic stimulation, and that epidural ketamine has a low incidence of emergence reactions.

Analgesics, Non-Narcotic↗

Behavioural/emotional symptoms among 8-9-year-old children with somatic symptoms or illnesses as reported by their teacher.

The aim of this study was to assess children's behavioural/emotional symptoms at school and to compare these symptoms of somatically healthy children with those of children with somatic illnesses or symptoms. The Rutter Teacher Questionnaire (RB2) was used for measuring psychiatric symptoms in 5813 children aged 8-9 years. The parents reported the somatic symptoms and illnesses of their children during the previous 12 months. One hundred and sixty one children had a marked or serious chronic illness, 292 had a mild chronic illness, and 92 had one or several symptoms. The findings suggest that boys with a marked or serious chronic somatic illness are prone to manifest psychiatric symptoms in their interactions with peers and teachers at school and that boys with a mild chronic illness have less psychiatric symptoms than healthy boys.

Child↗