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Somatic and vagal afferent convergence on solitary tract neurons in cat: electrophysiological characteristics.

Electrophysiological characteristics are described for 67 neurones localized to subnuclei of the solitary tract or the area of the dorsal motor nucleus of the vagus in alpha-chloralose-anesthetized, paralysed cats which received vagal and hindlimb sural or peroneal nerve excitation. The peroneal and sural nerves were stimulated in an exposed hindlimb preparation; the ipsilateral vagus was stimulated at the cervical level. Compound action potentials were recorded from all three nerves. Neurons were recorded with extracellular microelectrodes from the brain stem solitary area contralateral to the stimulated somatic nerves. Ninety-one percent of the recorded neurons were spontaneously active. Eighteen percent and 5% of the neurons received only peroneal or sural excitation, respectively, while 59% of the neurons received convergent peroneal and sural excitation. Thirty-nine of the 67 neurons were also tested for vagal input of which 41% responded with excitation. All of the neurons tested for vagal input also received converging excitation from one or both of the somatic nerves. Thirty-one percent of the vagal-excited neurons received converging input from both the peroneal and sural nerves. The combined mean minimal conduction velocity for peroneal and sural input was 31 +/- 1 m/s (mean +/- 1 S.E., range 9-54 m/s). Thirty-six percent of the peroneal and 31% of the sural afferents were Group II fibers. Significant periods of inhibition of spontaneous neuronal spike activity followed peroneal and sural excitation in 43 and 39% of the neurons, respectively. In many neurons, both excitation and inhibition of spike activity could be elicited at stimulus intensities as low as 1.2 times threshold for the lowest threshold fibers in each nerve. Somatic nerve-induced inhibition of spontaneous neuron activity without prior excitation was also observed. These results suggest that neurons of the solitary tract nuclei receive Group II and Group III somatic afferents which converge on neurons also receiving excitatory vagal input. Consequently, somesthetic and kinesthetic as well as visceral receptor activation may directly modulate solitary tract neurons. A possible conclusion is that the nucleus tractus solitarius is the initial central site of mediation of somatosympathetic reflexes. Modulation of the nucleus tractus solitarius by somatic afferents may then adjust sympathetic tone, via modulation of other medullary centers, in visceral and somatic tissues to match somatic metabolic needs.

Action Potentials↗

Somatic pain sensitivity during formation and healing of acetic acid-induced gastric ulcers in conscious rats.

A classical feature of visceral pain is its referring to somatic locations. Gastric ulcer is a source of visceral pain. In the present study we investigated whether gastric ulcers may trigger the changes in somatic nociception. For this aim somatic pain sensitivity was estimated under conditions of gastric ulcer development and healing. Gastric ulcers were induced by luminal application of 60% acetic acid under surgical conditions. Control rats were subjected to the same surgical procedure, but with the application of saline instead of the acid. Somatic pain sensitivity (tail flick latency), plasma corticosterone level, adrenal and thymus weight were investigated under conditions of the formation and the healing of gastric ulcers. The application of the acid resulted in the formation of kissing gastric ulcers, the increase of somatic pain sensitivity (the decrease of tail flick latency) as well as the appearance of typical signs of chronic stress: long-lasting increase of plasma corticosterone level, adrenal gland hypertrophy and thymus gland involution. Natural healing of gastric ulcers was accompanied by restoration of pain sensitivity as well as attenuation of the signs of chronic stress. Delay of ulcer healing by the daily indomethacin administration (2 mg/kg, s.c.) prevented the restoration of somatic pain sensitivity. The results suggest that chronic gastric ulcers may trigger somatic hypersensitivity.

Acetic Acid↗

Prediction of major depression in Japanese adults: somatic manifestation of depression in annual health examinations.

BACKGROUND: The present study examined whether somatic symptoms found in annual health examinations, could be predictive of major depression in the ensuing year. METHOD: Subjects analyzed were 1027 non-major-depressive workers (706 men, mean age 35) attending annual health examinations at a research institute. All were Japanese and found not to be suffering from major depression when interviewed, according to the semi-structured interviews of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). A self-administered questionnaire containing items relating to twelve major somatic symptoms was completed by all the subjects. The same DSM-IV interviews for the diagnosis of major depression were conducted to calculate the odds ratio of baseline variables for depressive and somatic symptoms, physical examination items, and health-related life-styles for the prediction of major depression in the ensuing year. RESULTS: The prevalence of major depression in the ensuing year was 2.5%. For four somatic symptoms (fatigue, lower back pain, dizziness, and nausea), the prevalence was higher (all p < 0.05) in those who complained of each somatic symptom at baseline than in those who did not. Furthermore, the multiple logistic regression analysis indicated that lower back pain and dizziness at baseline were independent risk factors of major depression in the ensuing year [odds ratio (95% confidence intervals), 3.2 (1.1, 8.9) and 6.0 (1.8, 20.1), respectively]. LIMITATIONS: It is possible that somatic manifestations of depression are culturally bound phenomena and results might be generalizable only to Japanese workers. CONCLUSION: Somatic symptoms reported at annual health examinations may be useful indicators for predicting major depression.

Adult↗

Is there an independent somatic symptom dimension in older people?

OBJECTIVE: In explaining the dimensions underlying nonpsychotic symptom reporting, traditional psychiatric paradigm has advocated a hierarchical model in which somatic symptoms are subsumed within two correlated psychological dimensions. A more recent alternate view is that somatic symptoms may be clearly separated from typical anxiety and depression symptoms if somatic symptoms are adequately recorded. The main aim of this study is to determine whether discrete somatic dimension(s) could be derived in older people. METHOD: Exploratory factor analysis was used to determine the factor structure underlying the responses of 10662 ambulatory primary care patients, aged 60 years and over, who completed the 34-item SPHERE (Somatic and Psychological HEalth REport) questionnaire of somatic and psychological symptoms. In addition, weighted factor scores were compared according to whether there was a physical or psychological reason for presentation to a doctor. RESULTS: A clinically interpretable four-factor solution, consisting of mood, cognitive, musculoskeletal, and fatigue symptoms, was derived. When factor analysis was repeated by gender, the only difference was that mood, cognitive, and pain-fatigue factors were derived in males. In the overall sample, all factor scores were higher in patients with a purely psychological reason for presentation. CONCLUSION: Somatic symptoms could be measured independently of psychological symptoms in the current sample of older primary care patients.

Adult↗

Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion.

OBJECTIVES: Stage 1 palliation of hypoplastic left heart syndrome requires the interruption of whole-body perfusion. Delayed reflow in the cerebral circulation secondary to prolonged elevation in vascular resistance occurs in neonates after deep hypothermic circulatory arrest. We examined relative changes in cerebral and somatic oxygenation with near-infrared spectroscopy while using a modified perfusion strategy that allowed continuous cerebral perfusion. METHODS: Nine neonates undergoing stage 1 palliation for hypoplastic left heart syndrome had regional tissue oxygenation continuously measured by frontal cerebral and thoraco-lumbar (T10-L2) somatic (renal) reflectance oximetry probes (rSO(2), INVOS; Somanetics, Troy, Mich). Surgery was accomplished using cardiopulmonary bypass with whole-body cooling (18 degrees C-20 degrees C) and regional cerebral perfusion through the innominate artery at flow rates guided by estimated minimum flow requirements and measured rSO(2) during reconstruction of the aortic arch. Data were logged at 1-minute intervals and analyzed using repeated measures analysis of variance. RESULTS: A total of 3176 minutes of data were analyzed. Prebypass cerebral rSO(2) was 65.4 +/- 8.9, and somatic rSO(2) was 58.9 +/- 12.4 (P <.001, cerebral vs somatic). During regional cerebral perfusion, cerebral rSO(2) was 80.7 +/- 8.6, and somatic rSO(2) was 41.4 +/- 7.1 (P <.001). Postbypass cerebral rSO(2) was 53.2 +/- 14.9, and somatic rSO(2) was 76.4 +/- 7.7 (P <.001). The risk of cerebral desaturation was significantly increased after cardiopulmonary bypass. CONCLUSIONS: Cerebral oxygenation was maintained during regional cerebral perfusion at prebypass levels with deep hypothermia. However, after rewarming and separation from cardiopulmonary bypass, cerebral oxygenation was lower compared with prebypass or somatic values. These results indicate that cerebrovascular resistance is increased after deep hypothermic cardiopulmonary bypass, even with continuous perfusion techniques, placing the cerebral circulation at risk postoperatively.

Analysis of Variance↗

Comparative Analysis of Somatic and Germline Polymerase Proofreading Deficiencies in Cancer: Molecular and Clinical Implications.

Polymerases &#x3b5; and &#x3b4; maintain genome integrity through exonuclease proofreading. Germline and somatic pathogenic variants (PVs) in the exonuclease domain (ED) of POLE and POLD1 impair proofreading, causing hypermutated tumors. Despite shared mutational features that make these tumors highly immunogenic, molecular and clinical distinctions between POLE and POLD1 mutations and between somatic and germline variants remain incompletely understood. We compared the molecular and clinical characteristics of POLE and POLD1 ED PVs (n = 31), assessing their location, pathogenicity, clinical phenotypes, mismatch repair (MMR) status, tumor mutational burden, and signatures. We analyzed 360 proofreading-deficient tumors (source: The Cancer Genome Atlas [TCGA] and Catalogue Of Somatic Mutations In Cancer [COSMIC]) and 70 families (249 individuals) with polymerase proofreading-associated polyposis. All germline and somatic PVs had high AlphaMissense scores (0.87-1) and clustered within or near Exo motifs. Recurrent, nonfounder germline PVs, POLE L424V and POLD1 S478N, showed low/modest REVEL scores. Somatic variants occurred mainly in endometrial cancers (75% of proofreading-deficient TCGA cancers), whereas colorectal cancer predominated in polymerase proofreading-associated polyposis (56% of carriers). Cancer risks and tumor spectra differed between POLE and POLD1 PV carriers. Aggressive hereditary phenotypes were linked to either specific POLE PVs (eg, S297F, V411L, P436R, M444K, A456P, and S461T) or the co-occurrence of germline ED PVs with germline MMR gene PVs. Distinct hypermutator profiles were confirmed for polymerase &#x3b5; and polymerase &#x3b4; proofreading deficiencies via unique mutational signatures (Polymerase &#x3b5;: SBS10a/b, SBS28; Polymerase &#x3b4;: SBS10c/d). Tumors with combined proofreading and MMR deficiencies had significantly higher tumor mutational burden and a shift in the associated mutational spectra. Unlike POLE, POLD1 ED PVs exhibited haplosufficiency, typically requiring a somatic second hit (eg, loss of heterozygosity) or MMR deficiency to drive hypermutation. In conclusion, differences between POLE and POLD1 and between somatic and germline mutations influence clinical presentation, mutagenic potential, and reliance on cooperating defects in tumorigenesis. These insights advance the understanding of proofreading-deficient cancers, with implications for diagnostics, genetic counseling, and precision oncology.

Humans↗

Somatic complaints and health care use in children: Mood, emotion awareness and sense of coherence.

In this study, we compared several aspects of the emotional functioning of schoolchildren reporting very few somatic complaints (n=59), schoolchildren reporting many somatic complaints (n=61), and a clinical group of children with functional abdominal complaints who visited the outpatient clinical of the VU University Medical Centre in Amsterdam (n=33). The children had an average age of 10.6 years. We studied whether general moods (happiness, anger, fear, and sadness), symptoms of depressiveness, emotion awareness, and sense of coherence contributed to group classification. Eighty-three percent of the schoolchildren reporting very few somatic complaints were identified correctly on the basis of better emotional functioning. However, there was little difference in the emotional functioning of schoolchildren with many somatic complaints and that of the clinical group. We concluded that the variables studied are valuable for differentiating children who are troubled by somatic complaints from children experiencing few somatic complaints. The results stress the existence of emotional problems in children reporting many somatic complaints.

Adolescent↗

Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: evidence for a uniform developmental program in mice.

H1 linker histones (H1s) are key regulators of chromatin structure and function. The functions of different H1s during early embryogenesis, and mechanisms regulating their associations with chromatin are largely unknown. The developmental transitions of H1s during oocyte growth and maturation, fertilization and early embryogenesis, and in cloned embryos were examined. Oocyte-specific H1FOO, but not somatic H1s, associated with chromatin in oocytes (growing, GV-stage, and MII-arrested), pronuclei, and polar bodies. H1FOO associated with sperm or somatic cell chromatin within 5 min of intracytoplasmic sperm injection (ICSI) or somatic cell nuclear transfer (SCNT), and completely replaced somatic H1s by 60 min. The switching from somatic H1s to H1FOO following SCNT was developmentally regulated. H1FOO was replaced by somatic H1s during the late two- and four-cell stages. H1FOO association with chromatin can occur in the presence of a nuclear envelope and independently of pronucleus formation, is regulated by factors associated with the spindle, and is likely an active process. All SCNT constructs recapitulated the normal sequence of H1 transitions, indicating that this alone does not signify a high developmental potential. A paucity of all known H1s in two-cell embryos may contribute to precocious gene transcription in fertilized embryos, and the elaboration of somatic cell characteristics in cloned embryos.

Animals↗

Exaggerated perception of normal physiological responses to stress and hypercapnia in young women with numerous functional somatic symptoms.

OBJECTIVE: This study tested whether functional somatic symptoms are associated with exaggerated increases in self-reported anxiety and somatic complaints in response to stress and CO(2)-enriched air breathing, and whether this association exists in parallel to or in the absence of exaggerated physiological responses. METHODS: Out of 499 young somatically healthy undergraduate women, 18 participants high in functional somatic symptoms (HSS group) and 18 participants low in symptoms (LSS) were selected. They were submitted to mental stress, mild physical exercise and relaxation during conditions of normal breathing, breathing compressed normal air, and breathing compressed 5% CO(2)-enriched air. In all conditions, self-reported anxiety and somatic symptoms and respiratory and autonomic responses were assessed. RESULTS: HSS participants reported, as compared to LSS, more tenseness, anxiety, and somatic symptoms at baseline and increased responses to mental stress and during 5% CO(2) breathing, but not in response to exercise. However, no evidence was found for a corresponding exaggerated respiratory or autonomic response. CONCLUSIONS: A young, female, and nonclinical population with numerous functional somatic symptoms and high levels of anxiety is characterized by an exaggerated perception of a normal physiological response.

Adolescent↗

Somatic mutation of the glucose-6-phosphate dehydrogenase (g6pd) gene in colonic stem cells and crypt restricted loss of G6PD activity.

The study of somatic mutation frequency, particularly stem cell somatic mutation, is important to the understanding of mechanisms of carcinogenesis. The models currently in use for studies in stem cell tissues such as the colon infer the presence of stem cell somatic mutation from alteration in enzyme function, when this has shown to be mutagen dose dependent, restricted to the unit of clonal architecture, and persistent. The present study identifies and characterises somatic mutations in the g6pd gene in individual mouse colonic crypts showing histochemically demonstrable loss of G6PD activity. Microdissection of single crypts, showing either normal or low G6PD activity by histochemistry was performed in mice treated with ethylnitrosourea (ENU), and the presence of point mutations sought by PCR and direct sequencing. Because of the limitation of the small amount of partially degraded (due to fixation) DNA available from each crypt, only about 20% of the coding region of the g6pd gene could be sequenced. Despite this, somatic mutations were identified in 3 of the 9 crypts analysed which showed loss of G6PD activity, but in none of the crypts with normal activity. Each of the mutations identified would be predicted to lead to a decrease in enzyme activity. We conclude that we have confirmed that the crypt restricted loss of G6PD activity is indeed due to stem cell somatic mutation in the g6pd gene, and suggest that the G6PD model can be used as a paradigm for other models where somatic mutation is inferred from a change in histochemically identifiable gene expression.

Animals↗

Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies.

A survey of glycophorin A (gpa) in vivo somatic cell mutation in a population of 394 healthy people from 8 to 77 years of age (mean age +/- SD 41 +/- 15 years) revealed a subset of 37 individuals with stably elevated allele-loss and/or allele-loss with duplication variant erythrocyte frequencies (Vf) exceeding 30 x 10(-6). These 37 individuals with gpa outlier Vf are significantly older (P < 0.001) than the remainder of the larger study population from which they were drawn reflecting a highly significant increase in the prevalence of these individuals in the population beyond age 40 years. A study of hpt mutant frequencies (Mf) in the peripheral blood T-lymphocytes of 27 of these individuals, together with 15 matched control individuals with unremarkable gpa Vf, was undertaken to determine if these subjects also displayed elevated mutation frequencies at this independent locus indicative of globally elevated somatic mutation. The hprt Mf in these 27 subjects (geometric mean 11.5 x 10(-6)(dispersion interval 5.8 x 10(-6) to 22.8 x 10(-6)) was not significantly different from that observed in the 15 controls (geometric mean 12.1 x 10(-6)(dispersion interval 5.7 x 10(-6) to 25.5 x 10(-6)). These Mf are higher than typically reported values reflecting the older age distribution of these individuals (arithmetic mean age +/- SD 53 +/- 12 and 50 +/- 16 years for the subjects and controls, respectively). Taken together, these data suggest that several genetic mechanisms may be responsible for producing the gpa outlier Vf observed in these subjects. The observation that hprt Mf were not increased indicates that the majority did not arise by a genome-wide increased rate of somatic mutation detectable at both loci. The fixation and subsequent expansion of 'jackpot' mutations at the gpa locus occurring early in embryonic/fetal development also does not appear to be a predominant mechanism. Some cases may result from a stable over-representation of gpa variant cells, perhaps associated with a marked age-dependent decrease in the number of contributing erythroid stem cells in the bone marrow. The subset that displays elevated allele-loss with duplication Vf involving both gpa alleles may represent individuals with increased rates of somatic recombination. Elevations arising by this mechanism are not detected in the hprt assay, but could be confirmed using a autosomal locus in vivo somatic cell mutation endpoint such as the hla-a assay. Of primary biological significance, these results demonstrate that genetics/stochastic processes leading to the loss of heterozygosity of somatic cells occur ubiquitously in humans and in some individuals this level of somatic mosaicism can approach a frequency of 10(-3) at the gpa locus in erythroid lineage cells.

Adolescent↗

Screening for somatizing patients in the pulmonary subspecialty clinic.

Somatizing patients present a history of vague, unexplained medical symptoms. This study compared somatizing patients with pulmonary control subjects by using the Diagnostic Interview Schedule (DIS-III-R), the Illness Attitude Scales (IAS), and the Minnesota Multiphasic Personality Inventory (MMPI-2). The groups differed in the number of somatization symptoms reported and in the frequency of somatization disorder diagnoses when the screening criteria were used. The somatizing group obtained higher scores on the bodily preoccupation and hypochondriacal beliefs subscales of the IAS; no differences were found on the MMPI-2. These findings indicate that the DSM-III-R somatization screening items can be useful for detecting somatization when patients present with unexplained respiratory complaints.

Adult↗

Somatic complaints among pregnant women cared for in obstetrics: normal pregnancy or depressive and anxiety symptom amplification revisited?

Despite the extensive research documenting the significance of medically unexplained somatic symptoms in primary care patients, few studies have examined somatic symptoms as a predictor of depressive and anxiety disorders among pregnant women cared for in Obstetrics. We utilized the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PHQ) to assess current depressive and anxiety disorders and self-reported somatic symptoms among 186 women receiving prenatal care. We examined the bivariate relationships between depressive and anxiety disorders and mean number of somatic symptoms. Linear regression analyses assessed the unique association between maternal depression, anxiety and somatic symptoms, while controlling for selected demographics and maternal medical risk. Twenty three percent (N=43) of women met screening criteria for depressive and/or anxiety disorders. Women with depression and/or anxiety were significantly more likely to report somatic symptoms (mean=7.1, SD=2.6) compared to women without depression or anxiety (mean=5.0, SD=2.6) [t(df)=4.54(184), P<.001]. This association persisted in multivariate models. Our findings suggest that antenatal depressive and anxiety disorders are associated with an amplification of physical symptoms of pregnancy. Eliciting and tracking somatic symptoms during prenatal visits could potentially improve detection of depressive and anxiety disorders in the obstetrical sector.

Adult↗

The somatization in primary care study: a tale of three diagnoses.

Somatization is a common phenomenon that has been defined in many ways. The two most widely used diagnoses, Somatization Disorder (SD) and Abridged Somatization Disorder (ASD), are based on lifetime unexplained symptoms. However, reports indicate instability in lifetime symptom recall among somatizing patients. Multisomatoform disorder (MSD) is a new diagnosis based on current unexplained symptoms. To understand how knowledge about SD and ASD translates to MSD, we examined the diagnostic concordance, impairment and health care utilization of these groups in a sample from the Somatization in Primary Care Study. The diagnostic concordance was high between MSD and SD, but lower between MSD and ASD. All three groups reported considerable physical impairment (measured using the PCS subscale of the SF-36). The mental health (MCS) scores for the three groups were only slightly lower than those of the general population. Over the course of one year, physical functioning fell significantly for all three groups. Mental functioning did not change significantly for any of the three groups over this period. Utilization patterns were very similar for the three groups. The high prevalence, serious impairment, and worsening physical functioning over the course of one year suggest the importance of developing interventions in primary care to alleviate the impaired physical functioning and reduce utilization in somatizing patients. MSD should be a useful diagnosis for targeting these interventions because it identifies a sizable cohort of somatizing patients reporting impairment of comparable severity to full SD, using a more efficient diagnostic algorithm based on current symptoms.

Female↗

Somatic symptoms in treatment-resistant depression.

The purpose of this work was to study the prevalence of somatic symptoms in patients with treatment-resistant depression (TRD) and their impact on the response to antidepressant treatment. Somatic symptoms were assessed during the screen visit with the Symptom Questionnaire (SQ) somatic symptom (SQ-SS) and somatic well-being sub-scales (SQ-SWB) in 40 patients with TRD enrolled in a 6-week open trial of nortriptyline. A logistic regression was used to test whether SQ-SS or SQ-SWB scores predicted clinical response to nortriptyline. Ninety-five percent of patients reported at least one somatic symptom. Higher SQ-SS scores during the screen visit predicted poorer response to nortriptyline. There was a trend for lower SQ-SWB scores to predict poor response to nortriptyline. None of the patients with SQ-SS scores above the mean for the sample responded to nortriptyline. The overwhelming majority of patients with TRD presented with somatic symptoms. In addition, a greater number of somatic symptoms during the screen visit placed patients at risk for further treatment resistance.

Adult↗

Post-traumatic stress disorder and somatization symptoms: a prospective study.

The objective of this study is to determine whether persons with a history of post-traumatic stress disorder (PTSD) are at increased risk for somatization symptoms. Using the NIMH Diagnostic Interview Schedule, 1007 21-30-year-old members of a large health maintenance organization in south-east Michigan were interviewed initially in 1989, with follow-up interviews conducted in 1992 and 1994. Prevalence of somatization syndrome and number of somatization symptoms in the 5-year follow-up period were compared in relation to PTSD status at baseline, using logistic regression. History of PTSD was associated with significantly more symptoms in each of the somatic symptom groups, except pain. In addition, persons with PTSD were more likely to report each of the symptoms of somatization, compared to those with other psychiatric disorders. Prospectively, baseline history of PTSD signaled an increased risk of pain (OR = 2.1) and conversion symptoms (OR = 2.3) in the follow-up interval, relative to those with no disorder. PTSD increased the risk of somatization symptoms beyond that expected by the presence of comorbid psychiatric disorders. The excess of somatization symptoms in persons with history of PTSD might be attributable to PTSD per se, or to the greater severity of the associated comorbidity, compared to persons with disorders other than PTSD.

Adult↗

Somatic fixation: the harm of healing.

The term somatic fixation describes a model in which the patient's problems are medicalized both by the patient and by the physician. This phenomenon was described by a group of researchers from the Netherlands, in 1983. This paper discusses somatic fixation and its implications. Somatic fixation should be distinguished from "somatization" or "somatoform disorder", which are psychiatric diagnoses, although there is probably a large degree of overlap. Predisposing factors to somatic fixation include social, cultural and medical circumstances, both related to the patient and to the physician. The medical care system may predispose to somatic fixation by offering prepaid medical care, and by incorporating the "rule out" model in fear of medical law-suits. Preventing somatic fixation is a major aim for every physician; being more aware of its possible occurrence may help, as well as exploring the patient's history and psychosocial background.

Attitude to Health↗

Characterization of expression at the human XIST locus in somatic, embryonal carcinoma, and transgenic cell lines.

X inactivation requires XIST, a functional RNA that is expressed exclusively from, and localizes to, the inactive X in female somatic cells. In mouse, low-level unstable transcription of Xist is observed prior to the time of inactivation, and an antisense transcript, Tsix, is a critical regulator of early Xist expression. To examine the presence and impact of an antisense transcript in humans we have characterized the extent of sense and antisense transcription in human somatic, transgenic, and embryonal carcinoma (EC) cell lines. Downstream antisense expression at the human XIST locus was not detected in somatic cells, but was detected in the EC line N-Tera2D1 and in somatic cells with an ectopic XIST locus. Presence of the antisense did not disrupt the stability or localization of the sense transcript. We have also identified additional sense transcripts in EC and female somatic cells and demonstrate that the 5' flanking JPX/ENOX gene is expressed from both the active and the inactive X chromosome in somatic cell hybrids, delimiting the extent of inactive X-specific transcriptional control in somatic cells. These analyses reveal similarities to and differences from the murine Xist and Tsix transcripts and generate a complex picture of developmentally regulated transcription through the region.

Animals↗