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Somatic symptoms in Gulf War mortuary workers.

OBJECTIVE: The objective of this article is to examine the relationship between exposures to the dead and the development of somatic symptoms. METHODS: We studied the pre-post responses of 352 military men and women who worked in the mortuary that received the dead from the Persian Gulf War (Operation Desert Storm) in 1990 to 1991. Symptoms of somatization were measured before and after exposure to the dead. The respondents were volunteers and nonvolunteers for assignment to the mortuary; some had prior experience in handling the dead and some did not. Four groups of participants were examined based on the degree of exposure to remains. Age, sex, volunteer status, prior experience handling remains, and preexposure measures of depression and mutilation fear were statistically controlled. RESULTS: Postexposure somatic symptoms increased significantly over preexposure levels for the two groups with the most exposure to the dead. CONCLUSIONS: These results provide additional evidence that exposure to the dead is related to somatic distress.

Adult↗

Health-related quality of life and somatization in patients with long-term low back pain: a prospective study with 109 patients.

STUDY DESIGN: For this study, a prospective cohort of 109 patients was recruited consecutively at an orthopedic inpatient unit of a university hospital. Three self-report instruments were administered to patients with sciatica believed to be caused by a herniated lumbar disc to examine their quality of life and psychic stress at baseline and at the 1-year follow-up visit. OBJECTIVES: To investigate whether patients who have undergone a previous discectomy experience greater psychic stress than patients with no surgery, and to determine whether the groups differed regarding their health-related quality of life at the follow-up visit. SUMMARY OF BACKGROUND DATA: Previous studies have described psychic abnormalities in patients with long-term back pain, particularly patients with severe chronicity (i.e., history of surgeries and persistent problems) or those who underwent a previous discectomy. Additionally, a series of studies has shown that psychic and psychosocial parameters exert a significantly greater influence on the success of treatment than do clinical and imaging findings or the extent of disc abnormality. METHODS: The Short Form Health Survey 36, the Symptom Checklist 90, and Screening for Somatoform Disorders were administered to 109 patients consecutively treated in the authors' orthopedic university clinic, at baseline and at the 1-year follow-up visit. RESULTS: In all the patients examined, the physical and mental quality of life improved regardless of their group classification. The psychological distress, according to the Symptom Checklist 90, was clearly reduced in both groups at the follow-up visit, with the exception of somatization, as indicated by Symptom Checklist 90 and Screening for Somatoform Disorders. Whereas the patients who had undergone surgery remained nearly unchanged with regard to their somatization, the patients with no previous surgery improved significantly, as indicated by Screening for Somatoform Disorders and Symptom Checklist 90. Somatization, particularly that surveyed by the comprehensive Screening for Somatoform Disorders, proved to be quite a stabile factor over time in both groups. The extent of the physical impairment before treatment was nearly the same in both groups, as indicated by Short Form Health Survey 36. Despite a markedly higher chronicity of reported problems, patients who had undergone surgery were hardly more greatly impaired in terms of their mental quality of life and psychological distress, as indicated by Symptom Checklist 90, than those without a history of surgery. At the follow-up visit, the differences tended to be minimal as well. As compared with those who had no previous surgeries, the patients who had undergone surgery were significantly more heavily impaired in their physical quality of life despite significant improvements. CONCLUSIONS: Patients with sciatica demonstrated less abnormality in terms of the psychopathologic markers investigated than described in previous studies. Nevertheless, the predisposition to somatize influences health-related quality of life to a high degree.

Adult↗

Cardiac arrest in pregnancy and somatic support after brain death.

OBJECTIVE: To review the important causes of cardiopulmonary arrest during pregnancy and the recommended modifications to resuscitation protocols when applied to pregnant patients, including the indications for perimortem cesarean section and the expected fetal outcomes, and to review the literature regarding extended somatic support after brain death during pregnancy. DATA SOURCES: MEDLINE review of publications relating to cardiac arrest and resuscitation in pregnancy, physiologic changes after brain death, and attempted somatic support of brain-dead pregnant women. CONCLUSIONS: Cardiac arrest during pregnancy is rare, but it is important to recognize the causes, which may be either unrelated to pregnancy or unique to the pregnant woman. For the most part, the resuscitation protocol is the same as for nonpregnant victims of cardiac arrest, with a few important modifications, including especially the need for relieving aortocaval compression by the gravid uterus, the need for rapid intubation, and the importance of rapid perimortem cesarean delivery when indicated. In those rare cases of brain death occurring in a pregnant patient, continued somatic support of the mother may be possible, even for prolonged periods, to extend the pregnancy and further fetal maturation. The expected physiologic changes after brain death, challenges to successful somatic support, and specific recommendations regarding organ support of the brain-dead pregnant woman are reviewed.

Brain Death↗

The relationship between somatic growth and in vivo esophageal segmental and sphincteric growth in human neonates.

BACKGROUND: Measurement of aerodigestive tract length is an important determinant for accurate placement of esophageal probes and gavage tubes at the desired location. The relationship of esophageal body, upper esophageal sphincter (UES) and lower esophageal sphincter (LES) lengths with somatic growth in neonates is not well understood. OBJECTIVES: Our objectives were to (1) evaluate a relationship between segmental esophageal lengths and somatic growth parameters and (2) ascertain the relationship between segmental esophageal lengths and gestational age (GA) and postmenstrual age (PMA) in preterm and full-term born human neonates. DESIGN/METHODS: One hundred esophageal manometry studies were performed in 75 infants (30-60 weeks PMA) and the high-pressure zones of LES and UES identified. The distance from nares to LES and from nares to UES, esophageal body length, length of UES and LES derived from the manometry studies were correlated with somatic growth parameters. Growth rate of different esophageal segments was also determined in 26 subjects that underwent longitudinal studies. Analysis of variance and linear regression analysis were performed. RESULTS: Seventy-five neonates of 23.0-40.6 weeks gestational age (0.6-4.4 kg) were studied at 29.1-58.6 weeks PMA (1.0-6.4 kg). Significant correlation (P < 0.001) of PMA and physical growth parameters with the growth of nares-LES (R = 0.8), esophageal body length (R = 0.6) and nares-UES (R = 0.4) were noted. Nares-to-LES length increased at a rate of 0.25 cm/wk PMA during 33.0-36.0 weeks of age. CONCLUSIONS: In vivo esophageal segmental lengths correlated strongly with somatic growth parameters and PMA in neonates. We speculate that this approach has many practical applications with the use of esophageal probes and catheters.

Age Factors↗

The course of PTSD, major depression, substance abuse, and somatization after a natural disaster.

Flood research has used a variety of methods, yielding inconsistent findings. Universal definitions of illness are paramount to the science of psychiatric epidemiology of disasters. St. Louis area survivors (N = 162) of the Great Midwestern Floods of 1993 received a structured diagnostic assessment at 4 and 16 months postdisaster, with 88% follow-up. The purpose of the assessment was to examine predisaster and postdisaster rates of disorders and symptoms. Flood-related posttraumatic stress disorder was diagnosed in 22% and 16% at index and follow-up, respectively. Comorbidity with major depression determined whether the posttraumatic stress disorder would have remitted by 1 year later. Nearly one half of the men in the sample had a pre-existing alcohol use disorder. Virtually no new substance abuse followed the floods, and hence, substance abuse did not develop in response to the disaster or as part of coping with its aftermath. Somatization disorder was not observed; new somatoform symptoms represented a fraction of postflood somatic complaints. Findings are inconsistent with causal attribution of floods in the etiology of alcohol abuse and somatization. Methodological differences may account for much of the apparent discrepancy of these findings, with recent reports of increased alcohol use and somatic symptoms observed after other disasters.

Adolescent↗

The naturalistic course of unipolar major depression in the absence of somatic therapy.

The goal of the study was to describe the naturalistic course of unipolar major depression in subjects not receiving somatic therapy for their depressive illness. Affectively ill individuals were recruited into the Collaborative Depression Study and followed prospectively for up to 15 years. One hundred thirty subjects who recovered from their intake episode of major depression subsequently experienced a recurrence that went untreated for at least 4 weeks following onset of the recurrence. The duration of the recurrent episode was examined using survival analytic techniques. Of the 130 subjects, 46 obtained somatic therapy at some time during the course of their depressive illness, while 84 subjects received no somatic therapy throughout their entire depressive episode. Survival analysis, which accounts for these 46 individuals by censoring their episodes at the time treatment was obtained, yielded a median time to recovery of 23 weeks. In the subsample of 84 subjects whose depressive illness went untreated from its inception through its resolution, the median time to recovery was 13 weeks. These results suggest that there is a high rate of recovery in individuals not receiving somatic treatment of their depressive illness, particularly in the first 3 months of an episode. Because treatment-seeking behavior is known to be associated with a worse prognosis, 23 weeks probably represents a lower-limit approximation of the median duration of an untreated depressive episode.

Adolescent↗

Cross-cultural differences in somatic presentation in patients with generalized anxiety disorder.

Little is known about cultural differences in the expression of distress in anxiety disorders. Previous cross-cultural studies of depression have found a greater somatic focus in Asian populations. We examined anxiety symptoms in patients with generalized anxiety disorder (GAD) in urban mental health settings in Nepal (N = 30) and in the United States (N = 23). Participants completed the Beck Anxiety Inventory (BAI). The overall BAI score and somatic and psychological subscales were compared. While there was no difference in total BAI scores, the Nepali group scored higher on the somatic subscale (i.e. "dizziness" and "indigestion," t[df] = -2.63[50], p < 0.05), while the American group scored higher on the psychological subscale (i.e. "scared" and "nervous," t[df] = 3.27[50], p < 0.01). Nepali patients with GAD had higher levels of somatic symptoms and lower levels of psychological symptoms than American patients with GAD. Possible explanations include differences in cultural traditions of describing distress and the mind-body dichotomy.

Adolescent↗

Somatic activity of the mariner transposable element in natural populations of Drosophila simulans.

The characteristics of the mariner transposable element in natural populations of Drosophila simulans from different parts of the world were analysed. The somatic excision rate (estimated from a test-cross with a reference strain), the average number of copies (determined by Southern blots), and the presence of deleted copies (detected by polymerase chain reaction amplification) were estimated for each population. There was a great variability in the somatic excision rate, measured as the percentage of mosaic males, both within and between populations. The population effect was highly significant. The average copy number also varied widely and was correlated with the excision rate. Rare deleted elements were detected by polymerase chain reaction and Southern blots. Percentage of mosaic males increased in strains kept for a long time at low temperature, and the somatic excision rate increased with the latitude of origin of populations. Therefore, these results strongly suggest that temperature could be involved in the regulation of mariner somatic excision in D. simulans.

Animals↗

Comprehensive benchmarking of somatic structural variant detection at ultra-low allele fractions.

Postzygotic mosaicism gives rise to somatic structural variants (SVs) at ultra-low variant allele fractions (VAFs), which pose challenges for detection due to the high-coverage sequencing required and noise introduced by sequencing artifacts. Although somatic SV detection has been extensively studied in cancer, these studies are not directly applicable to the study of tissue mosaicism, as they rely on matched normals, target higher VAF ranges, and are enriched for different types of SVs. We present comprehensive benchmark data and best practices for non-cancer somatic SV detection. We created a synthetic mosaic sample by combining six HapMap individuals at varying proportions, generating allele fractions as low as 0.25%. This sample was sequenced to ~2,300x total coverage using Illumina, PacBio, and Nanopore technologies across multiple sequencing centers. A high-confidence benchmark SV set containing over 21,000 pseudo-somatic insertions and deletions &#x2265;50bp was derived from haplotype-resolved assemblies. We evaluated 12 SV discovery pipelines and identified caller-specific strengths and sequencing platform-specific shortcomings. We find that short read-based approaches show reduced recall for insertions and repeat-associated SVs, whereas long-read sequencing achieves high accuracy throughout the genome, increasing linearly with coverage. The best algorithm's sensitivity exceeded 80% for VAFs &#x2265;4% and 15% for VAFs of 0.5-1% with 60x coverage. The publicly available benchmarking data and comparative analysis of current methods provide a foundation for robust discovery of SV mosaicism in non-cancer tissues..

Journal Article↗

The mechanism of somatic inhibition of Drosophila P-element pre-mRNA splicing: multiprotein complexes at an exon pseudo-5' splice site control U1 snRNP binding.

Somatic inhibition restricts splicing of the Drosophila P-element third intron (IVS3) to the germ line. We have exploited this simple system to provide a model for a mechanism of alternative pre-mRNA splicing. Biochemical complementation experiments revealed that Drosophila somatic extracts inhibited U1 snRNP binding to the 5' splice site. Using sensitive RNase protection and modification-interference assays, we found that U1 snRNP bound to a pseudo-5' splice site in the 5' exon and that multiprotein complexes bound to an adjacent site. Binding of these factors appeared to mediate the inhibitory effect, because mutations in the pseudo-5' splice sites blocked binding and activated splicing in vitro. Likewise, wild-type, but not mutant, 5' exon RNA titrated inhibitory factors away from the pre-mRNA and activated splicing. Thus, we have defined the pseudo-5' splice sites as crucial components of the regulatory element, correlated the inhibitory activity with specific RNA binding factors from Drosophila somatic cells, and provided a mechanistic description of somatic inhibition. Because the inhibitory activity involves general splicing functions such as protein recognition of 5' splice site sequences and changes in the distribution of bound U1 snRNP, our data may also provide insights into how splice sites are selected.

Animals↗

Genetic plasticity of V genes under somatic hypermutation: statistical analyses using a new resampling-based methodology.

Evidence for somatic hypermutation of immunoglobulin genes has been observed in all of the species in which immunoglobulins have been found. Previous studies have suggested that codon usage in immunoglobulin variable (V) region genes is such that the sequence-specificity of somatic hypermutation results in greater mutability in complementarity-determining regions of the gene than in the framework regions. We have developed a new resampling-based methodology to explore genetic plasticity in individual V genes and in V gene families in a statistically meaningful way. We determine what factors contribute to this mutability difference and characterize the strength of selection for this effect. We find that although the codon usage in immunoglobulin V genes renders them distinct among translationally equivalent sequences with random codon usage, they are nevertheless not optimal in this regard. We find that the mutability patterns in a number of species are similar to those we find for human sequences. Interestingly, sheep sequences show extremely strong mutability differences, consistent with the role of somatic hypermutation in the diversification of primary antibody repertoire in these animals. Human TCR V(beta) sequences resemble immunoglobulin in mutability pattern, suggesting one of several alternatives, that hypermutation is functionally operating in TCR, that it was once operating in TCR or in the common precursor of TCR and immunoglobulin, or that the hypermutation mechanism has evolved to exploit the codon usage in immunoglobulin (and fortuitously, TCR) rather than vice-versa. Our findings provide support to the hypothesis that somatic hypermutation appeared very early in the phylogeny of immune systems, that it is, to a large extent, shared between species, and that it makes an essential contribution to the generation of the antibody repertoire.

Base Sequence↗

Clustering of microarray data reveals transcript patterns associated with somatic embryogenesis in soybean.

Globular somatic embryos can be induced from immature cotyledons of soybean (Glycine max L. Merr. cv Jack) placed on high levels of the auxin 2,4-dichlorophenoxyacetic acid (2,4-D). Somatic embryos develop from the adaxial side of the cotyledon, whereas the abaxial side evolves into a callus. Using a 9,280-cDNA clone array, we have compared steady-state RNA from the adaxial side from which embryos develop and from the abaxial callus at five time points over the course of the 4 weeks necessary for the development of globular embryos. In a second set of experiments, we have profiled the expression of each clone in the adaxial side during the same period. A total of 495 genes differentially expressed in at least one of these experiments were grouped according to the similarity of their expression profiles using a nonhierarchical clustering algorithm. Our results indicate that the appearance of somatic embryos is preceded by dedifferentiation of the cotyledon during the first 2 weeks on auxin. Changes in mRNA abundance of genes characteristic of oxidative stress and genes indicative of cell division in the adaxial side of the cotyledons suggest that the arrangement of the new cells into organized structures might depend on a genetically controlled balance between cell proliferation and cell death. Our data also suggest that the formation of somatic globular embryos is accompanied by the transcription of storage proteins and the synthesis of gibberellic acid.

2,4-Dichlorophenoxyacetic Acid↗

Analysis of the rolC promoter region involved in somatic embryogenesis-related activation in carrot cell cultures.

In cell cultures of carrot (Daucus carota L.), somatic embryogenesis can be induced by transferring cells from a medium containing 2,4-dichlorophenoxyacetic acid (2,4-D) to one devoid of 2,4-D. Previous analysis of transgenic carrot cells containing the 5' non-coding sequence of the Ri plasmid rolC and a structural gene for bacterial beta-glucuronidase (uidA) has shown that the chimeric gene is actively expressed after induction of somatic embryogenesis. In this study, we demonstrate that activation of the rolC promoter is dependent on the process of embryo development but not on the duration of the cell culture in 2,4-D-free medium. We also analyzed the cis region of the rolC promoter that is responsible for somatic embryogenesis-related activation (SERA), namely relatively low beta-glucuronidase (GUS) activity in calli and proembryogenic masses (PEM) and high GUS activity in heart- and torpedo-stage embryos. When the -255-bp region of the rolC gene was used, SERA was retained. Internal deletions within this -255-bp region did not alter SERA by the rolC promoter. Furthermore, when a rolC promoter fragment (-848 to -94 bp) was fused to the cauliflower mosaic virus (CaMV) 35S core region (-90 to +6 bp), it conferred relatively low GUS activity in calli and PEM but high GUS activity in heart and torpedo embryos. When -848 to -255-bp or -255- to -94-bp fragments of the rolC promoter were fused to the same CaMV 35S core region, GUS activity patterns were not related to somatic embryogenesis. These results suggest that the combination of several regulatory regions in the rolC promoter may be required for SERA in carrot cell cultures.

Base Sequence↗

N-acetylglucosamine and glucosamine-containing arabinogalactan proteins control somatic embryogenesis.

In plants, complete embryos can develop not only from the zygote, but also from somatic cells in tissue culture. How somatic cells undergo the change in fate to become embryogenic is largely unknown. Proteins, secreted into the culture medium such as endochitinases and arabinogalactan proteins (AGPs) are required for somatic embryogenesis. Here we show that carrot (Daucus carota) AGPs can contain glucosamine and N-acetyl-D-glucosaminyl and are sensitive to endochitinase cleavage. To determine the relevance of this observation for embryogenesis, an assay was developed based on the enzymatic removal of the cell wall from cultured cells. The resulting protoplasts had a reduced capacity for somatic embryogenesis, which could be partially restored by adding endochitinases to the protoplasts. AGPs from culture medium or from immature seeds could fully restore or even increase embryogenesis. AGPs pretreated with chitinases were more active than untreated molecules and required an intact carbohydrate constituent for activity. AGPs were only capable of promoting embryogenesis from protoplasts in a short period preceding cell wall reformation. Apart from the increase in embryogenesis, AGPs can reinitiate cell division in a subpopulation of otherwise non-dividing protoplasts. These results show that chitinase-modified AGPs are extracellular matrix molecules able to control or maintain plant cell fate.

Acetylglucosamine↗

Substrate Utilization by Suspension Cultures and Somatic Embryos of Daucus carota L. Measured by C NMR.

The uptake and utilization of sucrose by embryogenic suspension cultures of carrot (Daucus carota L.) growing in the presence of 2,4-D and by somatic embryos derived from these cultures was monitored using (13)C nuclear magnetic resonance. The exogeneously supplied sucrose was completely hydrolyzed before cell entry; glucose was taken up preferentially when the cells were cultured in the presence of 2,4-D, while glucose and fructose were utilized at similar rates by somatic embryos in the absence of 2,4-D. Both suspension cells and somatic embryos accumulated high intracellular levels predominantly of glucose and sucrose, the latter being resynthesized intracellularly from the constitutive hexoses. Initially, fructose was converted mainly into glucose and sucrose rather than being catabolized directly through glycolysis or the pentose phosphate pathway. Carbohydrate supply that exceeded cellular demand resulted in intracellular accumulation of mono- or disaccharides. The capacity of cultured carrot cells to produce somatic embryos appeared to be positively correlated with high intracellular levels of glucose.

Journal Article↗

Somatic and germinal excision activities of the Arabidopsis transposon Tag1 are controlled by distinct regulatory sequences within Tag1.

Various sequences within Tag1, the endogenous transposon of Arabidopsis, were examined to determine how Tag1 excision and expression are regulated. The 5' intron for the major 2.3-kb Tag1 transcript was found to be critical for the accumulation of Tag1 transcripts and for high rates of somatic excision. This was true for the autonomous element in cauliflower mosaic virus 35S-Tag1-beta-glucuronidase constructs and for a two-component system using the 35S promoter to produce Tag1 transposase and a beta-glucuronidase::dTag1 marker construct to score for excision. The 3' introns of Tag1, although not needed for high transposase expression in primary transgenic plants, were important for maintaining high levels of somatic excision and accumulation of the major but not the minor Tag1 transcripts in subsequent generations. With both 5' and 3' introns present, exchanging the 5' promoter region of Tag1 with the 35S promoter did not affect the timing of Tag1 excision significantly, but it did disrupt germinal excision. Removal of the 5' intron did not abolish germinal excision activity, however. These results indicate that somatic and germinal excision of Tag1 are differentially controlled, with the 5' promoter region being critical for germinal excision activity and the 5' intron playing an important role for somatic excision, possibly via intron-mediated enhancement.

Arabidopsis↗

P53 gene deficiency does not enhance instability of mouse minisatellites in somatic cells of normal tissues.

The effect of p53-deficiency on somatic mutation of minisatellites in normal tissues was examined using p53-deficient (-/-) mice. In total, 248 mice consisting of three different genotypes, +/+, +/ -and -/-, were obtained and DNA from their embryos was probed with two minisatellites, Pc-1 and Pc-2. The somatic mutation was detected by Southern blot hybridization as the presence of a third nonparental band reflecting mosaicism in tissues. Mutation frequency of Pc-1 for (+/+) and (+/-) was 1.3% and 1.4%, respectively, which is consistent with previous studies. On the other hand, none of the mice lacking the p53 gene (-/-) exhibited mutation. The Pc-2 probe did not show any somatic mutation in the three groups. These results suggest that the p53 deficiency does not enhance the genomic instability of the minisatellite loci in normal somatic cells.

Animals↗

A novel somatic mutation in the RET proto-oncogene in familial medullary thyroid carcinoma with a germline codon 768 mutation.

In individuals who carry germline mutations in tumor suppressor genes predisposing them to inherited cancer syndromes, occurrence of somatic mutations in the same genes contributes to tumorigenesis. Germline mutations in the RET proto-oncogene predispose individuals to multiple endocrine neoplasia (MEN) type 2 syndromes. Since these mutations are oncogenic by themselves, somatic mutations in the same gene had been thought unnecessary. Recently, a somatic mutation at codon 918 of RET was reported in medullary thyroid carcinoma (MTC) and C-cell hyperplasia in patients with MEN 2A or familial MTC (FMTC), suggesting its possible contribution to tumorigenesis. We describe here a novel somatic mutation at codon 919 in a patient with FMTC carrying a germline mutation at codon 768 that may also be related to tumor progression.

Aged↗