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PubMed2003

Nuclear and microtubule dynamics of G2/M somatic nuclei during haploidization in germinal vesicle-stage mouse oocytes.

During the haploidization process, it is expected that diploid chromosomes of somatic cells will be reduced to haploid for the generation of artificial gametes. In the present study, we aimed to use enucleated mouse oocytes at the germinal vesicle-stage (G2/M) as recipients for somatic cells that are also synchronized to the G2/M stage for haploidization. The reconstructed oocytes were then induced to undergo meiosis in vitro and observed for their nuclear morphology and microtubule network formation at various expected stages of the meiotic division. Following in vitro maturation, more than half (62/119, 52.1%) of the reconstructed oocytes completed the first round of meiosis-like division, as evidenced by the extrusion of pseudopolar bodies (PBs). However, accelerated PB extrusion, approximately 3-4 h earlier than that by control oocytes occurred. Furthermore, abnormally large pseudo-PBs, as large as four times the normal PB sizes, were observed. During the process of in vitro maturation at both the expected stages of metaphase I (MI) and metaphase II (MII), condensed chromosomes were observed in 38.7% and 55.2% of oocytes, respectively. However, two other types of nuclear configurations were also observed: 1) uneven distribution of chromatin and 2) an interphase-like nucleus, indicating deficiencies in chromosome condensation. Following oocyte activation, more than half (21/33, 63.6%) of the reconstructed oocytes with pseudo-PBs formed separated pseudopronuclei (PN), suggesting formation of functional spindles. The formation of bipolar spindle-like microtubule network at both the expected MI and MII stages during in vitro maturation was confirmed by immunohistochemistry. In summary, this study demonstrated that a high proportion of G2/M somatic nuclei appear to undergo meiosis-like division, in two successive steps, forming a pseudo-PB and two separate pseudo-PN upon in vitro maturation and activation treatment. Moreover, the enucleated geminal vesicle cytoplast retained its capacity for meiotic division following the introduction of a somatic G2/M nucleus.

Animals↗
PubMed1991

DNA packaging and organization in mammalian spermatozoa: comparison with somatic cells.

Mammalian sperm DNA is the most tightly compacted eukaryotic DNA, being at least sixfold more highly condensed than the DNA in mitotic chromosomes. To achieve this high degree of packaging, sperm DNA interacts with protamines to form linear, side-by-side arrays of chromatin. This differs markedly from the bulkier DNA packaging of somatic cell nuclei and mitotic chromosomes, in which the DNA is coiled around histone octamers to form nucleosomes. The overall organization of mammalian sperm DNA, however, resembles that of somatic cells in that both the linear arrays of sperm chromatin and the 30-nm solenoid filaments of somatic cell chromatin are organized into loop domains attached at their bases to a nuclear matrix. In addition to the sperm nuclear matrix, sperm nuclei contain a unique structure termed the sperm nuclear annulus to which the entire complement of DNA appears to be anchored when the nuclear matrix is disrupted during decondensation. In somatic cells, proper function of DNA is dependent upon the structural organization of the DNA by the nuclear matrix, and the structural organization of sperm DNA is likely to be just as vital to the proper functioning of the spermatozoa.

Animals↗
PubMed1999

Developmentally regulated loss and reappearance of immunoreactive somatic histone H1 on chromatin of bovine morula-stage nuclei following transplantation into oocytes.

One difference between chromatin of bovine oocytes and blastomeres is that somatic subtypes of histone H1 are undetectable in oocytes and are assembled onto embryonic chromatin during the fourth cell cycle. We investigated whether this chromatin modification is reversed when nuclei containing somatic H1 are transplanted into ooplasts. Donor nuclei obtained from morula-stage bovine embryos were fused to ooplasts at different times before and after parthenogenetic activation of the ooplasts. After fusion, immunoreactive H1 became undetectable, and the loss occurred more rapidly when fusion was performed near the time of ooplast activation compared with several hours after activation, when the host oocytes were at a stage corresponding to interphase. Although the loss of immunoreactive H1 occurred independently of DNA replication and transcription, exposure of reconstructed oocytes to cycloheximide or 6-dymethylaminopurine (6-DMAP) delayed the loss of immunoreactive H1 from transplanted nuclei. During further development of nuclear-transplant embryos, somatic H1 remained undetectable at the 2- and 4-cell stages, and it reappeared on the chromatin at the 8- to 16-cell stage, as previously observed in unmanipulated embryos. We conclude that factors in oocyte cytoplasm are able to modify morula chromatin so that somatic H1 becomes undetectable, and that the amount or activity of these factors declines over time in activated ooplasts.

Adenine↗
PubMed2000

Development of mouse and rat oocytes in chimeric reaggregated ovaries after interspecific exchange of somatic and germ cell components.

The germ cell and somatic cell compartments of newborn rat and mouse ovaries, which contain only primordial stage follicles, were completely exchanged and reaggregated to produce xenogeneic chimeric ovaries. The reaggregated ovaries were grafted beneath the renal capsules of ovariectomized SCID mice to develop for periods up to 21 days. Xenogeneic follicles developed with essentially normal morphological characteristics. Both rat and mouse oocytes with species-specific characteristics grew within follicles that were composed of somatic cells exclusively of the alternative species. Rat oocytes grown in mouse follicles became competent to resume meiosis, and progressed to metaphase II when they were removed from follicles and cultured. In addition, mouse oocytes grown in rat follicles underwent fertilization and preimplantation development in vitro, and developed to term after embryos were transferred to pseudopregnant mouse foster mothers. Therefore, despite an estimated 11 million years of divergent evolution, oocytes and somatic cells of rat and mouse ovaries can be exchanged and can produce functional oocytes. It is concluded that factors involved in oocyte-somatic cell interactions necessary to support oocyte development and appropriate differentiation of the oocyte-associated granulosa cells are conserved between rats and mice. Moreover, although granulosa cells play important roles in oocyte development, the development of species-specific characteristics of oocytes occurs without apparent modification by a xenogeneic follicular environment.

Animals↗
PubMed1998

Antinociceptive effects of intrathecal L-type calcium channel blockers on visceral and somatic stimuli in the rat.

UNLABELLED: L-type calcium channels can modulate neuronal transduction in the spinal cord. However, their role in noxious information processing in animals that are physiologically intact has not been elucidated. We evaluated the effects of L-type calcium channel blockers diltiazem and verapamil on somatic and visceral nociception at the level of the spinal cord. Intrathecal catheters were inserted at the L4-5 level in Sprague-Dawley rats. The tail flick (TF) test and colorectal distension (CD) test were used to assess somatic and visceral antinociceptive effects, respectively. Motor function was assessed by posture and muscle tone in the limbs. TF latency and CD threshold were measured before and for 180 min after the intrathecal administration of verapamil (50, 100, 300, and 500 microg), diltiazem (100, 300, 500, and 1000 microg), or isotonic sodium chloride solution. The percent maximal possible effect (%MPE) was calculated by transforming response threshold in TF and CD tests. Intrathecally administered diltiazem or verapamil increased both TF latency and CD threshold in a dose-dependent fashion. Isotonic sodium chloride solution, diltiazem 100 microg, and verapamil 50 microg did not increase %MPE in either test. Diltiazem 300 or 500 microg or verapamil 300 or 500 microg significantly (P < 0.05) increased %MPE, with the peak effects 5 min after administration and short-duration antinociception. %MPE was 100% until 15 min after the administration of diltiazem 1000 microg, and significant antinociception continued until 180 min in the TF test. Motor paralysis was observed after the administration of the larger dose of each drug. We demonstrated that intrathecally administered L-type calcium channel blockers diltiazem or verapamil produced both somatic and visceral antinociception and motor block dose-dependently. IMPLICATIONS: We examined the effects of intrathecally administered L-type calcium channel blockers diltiazem and verapamil on somatic and visceral nociception in rats. L-type calcium channel blockers produced antinociceptive effects, suggesting a possible clinical application to control pain.

Analgesics↗
PubMed2000

Spinal coadministration of ketamine reduces the development of tolerance to visceral as well as somatic antinociception during spinal morphine infusion.

UNLABELLED: This study was designed to investigate the effects of ketamine, an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to morphine and morphine antinociception during intrathecal infusion. Two intrathecal catheters were implanted in the subarachnoid space in male rats under pentobarbital anesthesia. One catheter was used for the intrathecal infusion with the following solutions: morphine 1 microg x kg(-1) x hr(-1)(M1) and 5 microg x kg(-1) x hr(-1) (M5);ketamine 250 microg x kg(-1) x hr(-1) (K250); morphine plus ketamine, 1 microg x kg(-1) x hr(-1) plus 250 microg x kg(-1) x hr(-1) (M1 + K250) and 5 microg x kg(-1) x hr(-1) + 250 microg x kg(-1) x hr(-1) (M5 + K250); or saline. The other catheter was used for morphine challenge tests. The responses to noxious somatic and visceral stimuli were measured by tail flick (TF) and colorectal distension (CD) tests, respectively. Measurements were performed once a day for 7 days. Challenge tests with intrathecal morphine were performed to assess the magnitude of tolerance on Day 5 and Day 7. The antinociceptive effect was evaluated by using the percent of maximal possible effect (%MPE). Morphine infusion produced significant increases in %MPEs in TF and CD tests, while the saline and K250 infusions did not show any changes. The M1 + K250 infusion significantly increased the %MPEs in TF and CD tests, although the M1 and K250 infusions alone showed no changes. M5 + K250 enhanced the increases of %MPEs in TF and CD tests compared with the M5 infusion alone. In the challenge tests, the M1 + K250 infusion showed no significant decrease in %MPEs and TF and CD tests. The M5 + K250 infusion significantly inhibited those decreases in %MPEs, although the M5 infusion showed significant decreases in TF and CD tests. We concluded that ketamine attenuated the development of morphine tolerance to antinociceptive effects and increased the somatic and visceral antinociception of morphine. IMPLICATIONS: Intrathecally coinfused ketamine attenuated morphine tolerance to somatic and visceral antinociception and increased morphine antinociception at the spinal level. These results suggest that a combination of morphine with ketamine may have an advantage in long-term use of opioids for controlling visceral as well as somatic pain.

Analgesics, Opioid↗
PubMed1992

Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat.

Clinical investigations have suggested a synergistic interaction between the analgesic effects of intrathecal opioids and local anesthetics; however, basic pharmacologic evidence for this observation has not been reported. Therefore, the authors have used models of visceral and somatic nociception to quantify the interaction between intrathecal morphine and lidocaine in a crossover study of 24 rats in four equal groups. Combinations of morphine and lidocaine were administered separately, corresponding to time of peak effect for each drug. Colorectal distention, as a noxious visceral stimulus, was applied to two groups while cardiovascular and visceromotor responses, respectively, were recorded. A third group received hot plate testing as a somatic nociceptive stimulus. Intrathecal morphine and lidocaine both attenuated the cardiovascular and visceromotor responses to colorectal distention and increased hot plate latencies in a dose- and time-dependent manner. With the use of isobolographic analysis, the coadministration of morphine and lidocaine demonstrated a synergistic, supraadditive interaction during visceral nociception (P less than 0.001) and somatic nociception (P less than 0.005). In a fourth group, motor function was evaluated by an inclined screen method. Intrathecal lidocaine in the dosage range tested during isobolographic analysis revealed no motor deficits. These data clearly demonstrate antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception at dosages that do not impair motor function.

Analgesia, Epidural↗
PubMed2002

Remifentanil requirements during sevoflurane administration to block somatic and cardiovascular responses to skin incision in children and adults.

BACKGROUND: The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults. METHODS: Forty-one adults (aged 20-60 yr) and 24 children (aged 2-10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 microg x kg(-1) x min(-1) for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant. RESULTS: The IR50 +/- SD was 0.10 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.22 +/- 0.03 microg x kg(-1) x min(-1) in children (P < 0.001). The IRBAR50 +/- SD was 0.11 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.27 +/- 0.06 microg x kg(-1) x min(-1) in children (P < 0.001). CONCLUSIONS: To block somatic and autonomic responses to surgery, children require a remifentanil infusion rate at least twofold higher than adults.

Abdomen↗
PubMed2002

Defective somatic markers in sub-clinical psychopathy.

Damasio's somatic marker hypothesis is argued to be specifically applicable to psychopathy, though evidence has been meager until now. The principal evidence for the somatic marker hypothesis is based on findings in patients with orbitofrontal lesions, showing absent punishment learning on the Iowa gambling task. Interestingly, neuroimaging studies indicate orbitofrontal dysfunction in psychopathy also. Here we investigated the somatic marker hypothesis in subjects selected on low and high psychopathic behavioral characteristics from the outer extreme ranges of a large subject pool (n = 525). The low psychopathic subject group (n = 16) showed intact punishment learning, suggesting somatic markers came to guide their decisions in the course of the game. In contrast, such punishment learning was not observed in the high psychopathic subject group (n = 16), who mimicked the gambling behavior of orbitofrontal patients. These findings provide further evidence for the hypothesized link between psychopathy and orbitofrontal dysfunction.

Adult↗
PubMed1991

The role of somatic complaints in the diagnosis of depression in children and adolescents.

The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety.

Adolescent↗
PubMed1999

Somatic complaints and psychopathology in children and adolescents: stomach aches, musculoskeletal pains, and headaches.

OBJECTIVE: To examine the associations of somatic complaints with DSM-III-R-defined depression, anxiety disorders, conduct disorder, oppositional defiant disorder, and attention-deficit hyperactivity disorder in a population-based sample of children and adolescents. METHODS: Data from 4 annual waves of interviews with 9- to 16-year-olds from the Great Smoky Mountains Study were analyzed. RESULTS: Overall, somatic complaints were strongly associated with emotional disorders in girls and with disruptive behavior disorders in boys. For girls, stomach aches and headaches together and musculoskeletal pains alone were associated with anxiety disorders. For boys, stomach aches were associated with oppositional defiant disorder and attention-deficit hyperactivity disorder. Musculoskeletal pains were associated with depression in both girls and boys. CONCLUSIONS: There were gender-, illness- and complaint-specific associations between somatic complaints and psychopathology. It appears likely that there are differences in the psychobiological processes underlying these associations in boys and girls. Clinical recommendations include screening children and adolescents with persistent complaints of headaches, stomach aches, or musculoskeletal pains for psychiatric disorders with an awareness that gender may affect the type of psychopathology associated with the somatic complaints.

Abdominal Pain↗
PubMed1999

Somatization in pediatric primary care: association with psychopathology, functional impairment, and use of services.

OBJECTIVE: To determine whether classification as pediatric "somatizers" identifies a group of children and adolescents at high risk for psychopathology, functional impairment, and frequent use of health services in a large, multisite study of pediatric primary care. METHOD: Parental reports of frequent aches and pains and visits to the doctor for medically unexplained symptoms in children aged 4 to 15 years were used to construct a classification of somatization in pediatric primary care. Affected and unaffected children and adolescents were compared on measures of demographics, family functioning, psychopathology, functional status, and service use. RESULTS: Classification as a somatizer was more common in adolescents, females, minority subjects, urban practices, nonintact families, and families with lower levels of parental education and was associated with heightened risk of clinician- and parent-identified psychopathology, family dysfunction, poor school performance and attendance, perceived health impairment, and more frequent use of health and mental health services. CONCLUSIONS: Children classified as pediatric somatizers are at heightened risk for psychiatric disorder, family dysfunction, functional impairment, and frequent use of health services. Additional research is warranted, and clinicians should recognize the need for careful assessment and potential behavioral health referral in this population.

Adolescent↗
PubMed2005

Somatic complaints in children and community violence exposure.

Somatic complaints of children in primary care settings often go unexplained despite attempts to determine a cause. Recent research has linked violence exposure to stress symptomatology and associated somatic problems. Unknown, however, is whether specific physical symptom complaints can be attributed, at least in part, to violence exposure. Urban African-American 6- and 7-year-old children (N = 268), residing with their biological mothers, recruited before birth, and without prenatal exposure to hard illicit drugs participated. Children and mothers were evaluated in our hospital-based research laboratory, with teacher data collected by mail. Community violence exposure (Things I Have Seen and Heard), stress symptomatology (Levonn), and somatic complaints (teacher-and self-report items) were assessed. Additional data collected included prenatal alcohol exposure, socioeconomic status, domestic violence, maternal age, stress, somatic complaints and psychopathology, and child depression, abuse, and gender. Community violence witnessing and victimization were associated with stress symptoms (r = .26 and .25, respectively, p < .001); violence victimization was related to decreased appetite (r = .16, p < .01), difficulty sleeping (r = .21, p < .001), and stomachache complaints (r = .13, p < .05); witnessed violence was associated with difficulty sleeping (r = .13, p < .05) and headaches (r = .12, p < .05). All associations remained significant after control for confounding. Community violence exposure accounted for 10% of the variance in child stress symptoms, and children who had experienced community violence victimization had a 28% increased risk of appetite problems, a 94% increased risk of sleeping problems, a 57% increased risk of headaches, and a 174% increased risk of stomachaches. Results provide yet another possibility for clinicians to explore when treating these physical symptoms in children.

Black or African American↗
PubMed1985

Hostility, somatic symptoms, and hypochondriacal fears and beliefs.

The authors administered self-rating scales of anger-hostility, somatic symptoms, and hypochondriacal fears and beliefs to seven groups of patients and nonpatients. Somatic symptoms were positively correlated with anger-hostility and were negatively correlated with feelings of friendliness; the correlation coefficients ranged from low to moderately high and were significant in most groups. Somatic symptoms tended to be associated more strongly with symptoms of anxiety and depression than with those of hostility. The associations of hypochondriacal fears and beliefs with hostility were inconsistent, varied between groups and with the concern measured. The findings do not support the view that anger or hostility are main or specific etiological factors either in somatization or in hypochondriacal fears or beliefs.

Adult↗
PubMedDate not supplied

Mood and somatic symptoms during pregnancy.

A predominantly white, middle class sample of pregnant women (N = 93) completed the AACL (Anxiety), the DACL (Depressive Mood), the SCL (Somatic Symptoms) and the IPAT Anxiety Questionnaire at the second, fifth and eighth months of pregnancy. A menstrual history questionnaire was administered on the first testing occasion. Analyses revealed that anxiety varied significantly as a function of trimester and that previous pregnancy history interacted significantly with trimester. Depressive mood was not significantly affected by any of the sources of variation. Correlational analysis (average correlations over trimesters) indicated significant relationships between somatic symptoms and anxiety, but not between somatic symptoms and depressive mood; a small but significant relationship between history of menstrual complaint and somatic symptoms; and a significant negative correlation between education and overt anxiety.

Abortion, Spontaneous↗
PubMedDate not supplied

Assessment of alexithymia in posttraumatic stress disorder and somatic illness: introduction of a reliable measure.

The authors examined ratings on four scales of alexithymia in 45 patients in four groups: Vietnam veterans in inpatient (Inpt-PTSD) or outpatient (Outpt-PTSD) treatment for posttraumatic stress disorder (PTSD), patients on a medical service with somatic illnesses that have been the subject of psychosomatic research (Somatic), and a comparison group of psychiatric inpatients with a diagnosis of affective disorder (Affective). The data suggest a greater degree of alexithymia in the Inpt-PTSD and Somatic samples than in the Affective patients. In addition, the Inpt-PTSD and Somatic groups exhibited a similar degree of alexithymia. This study also introduces a novel measure of alexithymia, the Alexithymia Provoked Response Questionnaire (APRQ), which showed a high degree of interrater reliability and a greater degree of correlation with the Beth Israel Psychosomatic Questionnaire (BIPQ) than a MMPI subscale or the Schalling-Sifneos scale.

Affective Symptoms↗
PubMedDate not supplied

Globus hystericus--a somatic symptom of depression? The role of electroconvulsive therapy and antidepressants.

OBJECTIVE: An association of "globus hystericus" with depressive illness has already been established. Successful treatment with antidepressants has been previously reported but this is the first report of globus symptom responding to electroconvulsive therapy (ECT) followed by long-term remission on maintenance dose with tricyclic antidepressant. METHOD: A detailed retrospective study of an elderly patient's General Practice medical notes revealed 45-year history of recurrent globus symptom, interspersed with other somatic complaints. Patient's frequency of consultations with her family physician was noted before treatment and during the 5-year follow-up period. Using DSM-III diagnostic categories, the patient was diagnosed as suffering from major depressive disorder with globus symptom. The notes were insufficient to ascertain whether past episodes of globus occurred in a setting of depressive disorder. RESULTS: A prompt response of globus symptom to ECT was observed with 5-year symptom-free follow-up period as long as the patient remained on a maintenance dose of antidepressant. A marked reduction in frequency of medical consultations for other somatic complaints was noted. CONCLUSIONS: The case illustrates a strong association of globus symptom with depressive disorder and other somatic concerns. Patients with recurrent globus symptom and family history of depressive illness should be screened for a possibility of depressive disorder. ECT and antidepressants may be successfully used in treatment of globus in a setting of depressive illness. Long-term maintenance with antidepressive medication may keep at least some of these patients symptom-free. It is suggested that globus hystericus could be more appropriately viewed as a somatic symptom of depression rather than a conversion disorder.

Aged↗
PubMedDate not supplied

Somatization symptoms and hypochondriacal features in the general population.

OBJECTIVE: The principal goal of this study is to examine the base rates of somatoform symptoms and of hypochondriacal features in the general population. METHODS: A representative sample of 2050 persons in Germany was examined by use of screening for somatoform symptoms and the Whiteley Index. RESULTS: The most frequent somatoform symptoms were back pain, joint pain, pain in extremities, and headache, as well as abdominal symptoms (bloating or intolerance of several foods) and cardiovascular symptoms (palpitation). People reported a mean of two somatization symptoms of DSM-IV somatization disorder (SD) during the prior 2 years. Strong age and medium gender effects were found for most somatoform symptoms, as well as for composite indices. However, the sex ratio suggested in DSM-IV for SD seems to be an overestimation. Hypochondriacal features showed only small sex differences but, again, pronounced age effects. In contrast to low rates for SD, the base rates for somatization and hypochondriacal features were high and represented the health care relevance of subthreshold syndromes. CONCLUSION: We present base rates of hypochondriacal and somatization features that may be important facets in the development of classification criteria and in the interpretation of health care expenditure.

Adolescent↗