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Discrimination between painful and painless diabetic neuropathy based on testing of large somatic nerve and sympathetic nerve function.

The syndromes of painful diabetic neuropathy and painless foot ulceration are distinct clinical entities. To investigate whether there is a pattern of nerve fibre involvement that could clearly discriminate between them, we have studied three groups of diabetic patients, 19 with painful neuropathy, 14 with painless foot ulceration, and 19 with no clinical neuropathy. Large somatic nerve fibre function was assessed by nerve conduction studies and vibration thresholds, small somatic nerve function by cooling and warming thresholds, the parasympathetic system by heart-rate dependent cardiac autonomic reflexes, and the sympathetic system by postural drop in blood pressure and plasma noradrenaline (supine and erect). Normal ranges were obtained from 25 age-matched healthy subjects. Painful neuropathy was characterized by uniform dysfunction of small somatic fibres and preserved sympathetic nerve activity (plasma noradrenaline) with a wide range of large somatic fibre and autonomic reflex abnormalities. By contrast, in painless foot ulceration there was universal severe dysfunction of all nerve fibre populations. Discriminant analysis identified peroneal motor conduction velocity as the best single variable for distinguishing between painful and painless neuropathy (81% of cases). A combination of peroneal motor conduction velocity with vibration threshold and plasma noradrenaline discriminated completely between the two clinical syndromes. These findings suggest that the key differences between painful and painless diabetic neuropathy are in large somatic and sympathetic fibre function.

Diabetic Neuropathies↗

Acetylcholine and somatically evoked inhibition on perigeniculate neurones in the cat.

1 Perigeniculate neurones in cats were found to be inhibited by iontophoretically applied acetylcholine (ACh) and some of them by somatic sensory stimulation under certain experimental conditions. 2 Under chloralose anaesthesia, perigeniculate neurones could be divided into two groups with regard to their spontaneous activity, sensitivity to glutamate and reaction to sensory inputs. Somatic sensory stimulation clearly inhibited the glutamate discharges of those perigeniculate neurones which were characterized by a high sensitivity to glutamate and the absence of spontaneous activity. ACh had no clear inhibitory effect. 3 Under fluothane and urethane anaesthesia, no somatic sensory influence was noticed but ACh depressed almost all perigeniculate neurones. 4 In an unanaesthetized midpontine pretrigeminal preparation, the inhibitory effect of ACh was confirmed. 5 No conditions were found which the inhibitory influences of ACh and those of somatic sensory stimulation could be observed simultaneously on the same neurone. Therefore, it could not be established whether ACh mediates the somatic sensory influences on perigeniculate cells.

Acetylcholine↗

Somatization, depression and medical illness in psychiatric inpatients.

In a study to determine the relationship between somatic symptoms and psychiatric diagnosis, 206 consecutively admitted inpatients at the University of Iowa Psychiatric hospital were given a structured medical history (MH) and physical examination (PE). Depressed patients were significantly older, had an increase in number of medical diagnoses (NDX), and were found to have a significant increase in somatic symptoms in which there was no confirmatory evidence on the PE and in which there was confirmation on the PE. When age, sex, and NDX were controlled for, depressed patients did not have an increase in either of the types of somatic symptoms noted above but did have a slight increase in the vague somatic symptoms in which PE findings would be unlikely. Our results suggest that the majority of the increases in somatic symptoms in depressed patients may not be due to depressive psychopathology but rather to their increased number of medical problems and increased age.

Adult↗

Somatization and conversion disorders: comorbidity and demographics at presentation.

Although somatization disorder and conversion disorder are linked in DSM-III and DSM-III-R, they have very different histories. To directly compare these disorders, we reviewed the records accrued for 2 years at a large medical center and identified 65 somatization disorder patients and 51 conversion disorder patients. They differed substantially. The large majority (78%) of conversion disorder patients and nearly all (95%) of the somatization disorder patients were women. Ages at onset occurred throughout the life span among conversion disorder patients but mostly before the age of 21 among the somatization disorder patients. Somatization disorder patients were more likely to have had a history of depression, attempted suicide, panic disorder and divorce.

Adolescent↗

Somatization in primary care: pattern and correlates in a clinic in Nigeria.

During a study of mental disorder in a primary care clinic in Nigeria, 214 patients, selected on the basis of their scores on the General Health Questionnaire, were interviewed with the Composite International Diagnostic Interview, a structured clinical interview that allows for a systematic assessment of somatization symptoms. Only 1.1% of this clinical sample fulfilled the DSM-III-R criteria for somatization disorder, but 4.7% and 10.8% met the criteria for somatoform pain disorder and undifferentiated somatoform disorder, respectively. Age, gender and the presence of a DSM-III-R diagnosis of depression or dysthymia accounted for significant variability in the number of reported somatization symptoms. On factor analysis, a factor with close similarity to DSM-III-R somatization disorder was obtained. This factor is associated with the demographic features commonly found among patients with DSM-III-R somatization disorder.

Adult↗

The impact of somatic morbidity on the Hamilton Depression Rating Scale in the very old.

The Hamilton Depression Rating Scale (HDRS) is world-wide the most important observer rating scale for depression. Many items of this scale refer to somatic symptoms of depression which cast doubt on the validity of HDRS scores in the presence of somatic comorbidity as, for example, in elderly patients. The present study, therefore, was planned to investigate the validity of the HDRS in cases in which the patient is suffering from a depressive illness together with somatic illnesses. The study population (n = 516) is a representative sample of citizens aged 70 years and older in West Berlin. They were assessed independently by internists and psychiatrists. Each positive item of the HDRS scale was then rated by the internists as to what degree it reflects somatic morbidity. Results show that multimorbidity interferes with the validity of the HDRS. There were 8 items for which more than half of all positive scores as rated by psychiatrists were seen by the internists as being possibly related to somatic disorders. Patients with corrections in the HDRS score showed a somewhat increased rate of medicines and cardiovascular diagnoses. There was less ambiguity for items with greater severity.

Aged↗

Timing, genetic requirements and functional consequences of somatic hypermutation during B-cell development.

While somatic antibody mutants are rare in the preimmune repertoire and in primary immune responses, they dominate secondary and hyperimmune responses. We present evidence that somatic hypermutation is restricted to a particular pathway of B-cell differentiation in which distinct sets of B-cell clones are driven into the memory compartment. In accord with earlier results of McKean et al. (1984) and Rudikoff et al. (1984), somatic mutation occurs stepwise in the course of clonal expansion, before and after isotype switch, presumably at a rate close to 1 X 10(-3) per base pair per generation. At this rate, both selectable and unselectable mutations accumulate in the rearranged V region genes. The distribution of replacement mutations in the V regions shows that a fraction of the mutations in CDRs is positively selected whereas replacement mutations are counterselected in the FRs. By constructing an antibody mutant through site-specific mutagenesis we show that a point mutation in CDR1 of the heavy chain, found in most secondary anti-NP antibodies, is sufficient to increase NP binding affinity to the level typical for the secondary response. Somatic mutation may contribute to the immune repertoire in a more general sense than merely the diversification of a specific response. We have evidence that clones producing antibodies which no longer bind the immunizing antigen can be kept in the system and remain available for stimulation by a different antigen. Somatic mutations are 10 times less frequent in DJH loci than in either expressed or non-expressed rearranged VDJH or VJ loci. We therefore conclude that a V gene has to be brought into the proximity of the DJH segment in order to fully activate the hypermutational mechanism in these loci.

Animals↗

Ionic differences between somatic and axonal action potentials in snail giant neurones.

1. The ionic requirements of the somatic and axonal action potentials of ;H' neurones of the snail Cryptomphallus aspersa were studied using intracellular micro-electrodes.2. The overshoot of the somatic action potential increased by 10 mV for a tenfold increase in [Ca(2+)](o). In calcium-free media the action potential decreased gradually to values of 50 to 90% of the control and they could be completely eliminated with 2 mM-EGTA. The maximum rate of rise also varied with [Ca(2+)](o).3. After 2 hr in sodium-free solution the somatic action potential decreased 6% in overshoot and 24% in rate of rise.4. The somatic action potential was not affected by TTX, 5 x 10(-6) g/ml. Procaine, 18 mM, reduced its rate of rise but did not eliminate it whereas 30 mM-CoCl(2) did.5. The size of the axonal action potential increased with increased [Na(+)](o), but decreased with an increase in [Ca(2+)](o).6. Procaine, 18 mM, abolished the axonal action potential whereas it was not affected by TTX, 5 x 10(-6) g/ml., nor, usually, by 30 mM-CoCl(2).7. The results obtained by studying the compound action potential of the nerves were similar to those from axonal action potentials.8. The possibility that the somatic action potential is mainly calcium dependent while the axonal action potential is mainly produced by sodium is discussed.

Action Potentials↗

Development of a purified cholera toxoid. III. Refinements in purification of toxin and methods for the determination of residual somatic antigen.

The addition of an ultrafiltration step to the purification procedures previously described for cholera toxin (Rappaport et al., (1974) permitted the preparation of highly purified antigenic toxoids essentially free of somatic antigen(s). The purity of such toxoids is established: (i) by the absence of more than about one part limulus amebocyte lysate (LAL)-positive endotoxin per 10(5) parts toxoid and (ii) by the inability of the toxoids to elicit a significant rise in rabbit vibriocidal antibody. The antigenicity of the toxoids is demonstrated by their ability to produce the same high levels of rabbit serum antitoxin as are produced by comparable toxoids containing small amounts of somatic antigen. The results also indicate that amounts of somatic antigen of the order of less than or equal to 1 mug/100 mug of toxoid do not exert an adjuvant effect on the toxoid, at least with respect to circulating antitoxin. Other data show that, where present, the ability of somatic antigen to elicit vibriocidal antibody is influenced by the immunization schedule employed and that a correlation exists between the LAL-determined endotoxin content of the toxoids and their ability to stimulate vibriocidal antibody. Somatic antigen-free toxoids, purified and tested by the refinements herein described, were prepared for use in the National Institutes of Health sponsored field trials, and data pertaining to their purity and antigenic properties are presented.

Animals↗

Antigenically related iron-regulated outer membrane proteins produced by different somatic serotypes of Pasteurella multocida.

An 84-kilodalton outer membrane protein was expressed when Pasteurella multocida, somatic serotype 3, was grown in brain-heart infusion broth containing the iron chelator dipyridyl but not in brain-heart infusion broth alone. Antigenically related outer membrane proteins of various molecular masses were also expressed by P. multocida strains belonging to all of the other 15 somatic serotypes (somatic serotype 12 being the possible exception) as well as by isolates expressing somatic antigens representative of multiple somatic serotypes when grown under the same conditions of iron deprivation.

Animals↗

Demethylation of somatic and testis-specific histone H2A and H2B genes in F9 embryonal carcinoma cells.

In contrast to many other genes containing a CpG island, the testis-specific H2B (TH2B) histone gene exhibits tissue-specific methylation patterns in correlation with gene activity. Characterization of the methylation patterns within a 20-kb segment containing the TH2A and TH2B genes in comparison with that in a somatic histone cluster revealed that: (i) the germ cell-specific unmethylated domain of the TH2A and TH2B genes is defined as a small region surrounding the CpG islands of the TH2A and TH2B genes and (ii) somatic histone genes are unmethylated in both liver and germ cells, like other genes containing CpG islands, whereas flanking sequences are methylated. Transfection of in vitro-methylated TH2B, somatic H2B, and mouse metallothionein I constructs into F9 embryonal carcinoma cells revealed that the CpG islands of the TH2A and TH2B genes were demethylated like those of the somatic H2A and H2B genes and the metallothionein I gene. The demethylation of those CpG islands became significantly inefficient at a high number of integrated copies and a high density of methylated CpG dinucleotides. In contrast, three sites in the somatic histone cluster, of which two sites are located in the long terminal repeat of an endogenous retrovirus-like sequence, were efficiently demethylated even at a high copy number and a high density of methylated CpG dinucleotides. These results suggest two possible mechanisms for demethylation in F9 cells and methylation of CpG islands of the TH2A and TH2B genes at the postblastula stage during embryogenesis.

Animals↗

A case-control study of somatic and behavioural symptoms in sexually abused boys.

OBJECTIVES: To ascertain how often sexually abused boys present with somatic and behavioural symptoms. DESIGN: A case-control study. SETTING: A primary school in South Wales where a male teacher had been convicted of sexually abusing boys since 1981. The police investigation started in 1993 and he was convicted in 1994. A similar large primary school where abuse had not taken place. SUBJECTS: All 107 boys who had been identified by a police inquiry to have been subject to sexual abuse by a single teacher in a single primary school; 107 age matched controls. MAIN OUTCOME MEASURES: Symptoms that might have had a somatic or behavioural basis reported in general practice, hospital, and school health records. RESULTS: Somatic and behavioural complaints were uncommon in both cases and controls. There was no significant difference between the numbers of cases and controls who had presented with somatic and behavioural complaints (18 cases v 25 controls). However the difference between the cases and controls with symptoms lasting over a year was significant (p < 0.05). There were no differences in the nature of reported symptoms between the control and abused groups. CONCLUSIONS: This suggests that extensive investigation for possible abuse is not indicated where are short lived somatic symptoms but it should be considered as a possible diagnosis where symptoms are long standing.

Behavior↗

Axo-somatic and apical dendritic Kv7/M channels differentially regulate the intrinsic excitability of adult rat CA1 pyramidal cells.

Kv7/KCNQ/M channel subunits are widely expressed in peripheral and central neurons, where they give rise to a muscarinic-sensitive, subthreshold, and noninactivating K+ current (M current). Immunohistochemical data suggest that Kv7/M channels are expressed in both axons, somata and dendrites, but their distinctive roles in these compartments are not known. Here we used intracellular microelectrode recordings to monitor the effects of selective Kv7/M channel modulators focally applied to the axo-somatic region and to the apical dendrites of adult rat CA1 pyramidal cells. We show that both compartments express functional Kv7/M channels that synergistically control intrinsic neuronal excitability, albeit in different ways. Axo-somatic Kv7/M channels activate during the spike afterdepolarization (ADP) and counteract the depolarizing drive furnished by conjointly activated persistent Na+ channels. Thereby they limit the size and duration of the spike ADP and prevent its escalation into a somatic spike burst. Apical dendritic Kv7/M channels do not ordinarily regulate the somatic spike ADP and spike output. In hyperexcitable conditions that promote Ca2+ electrogenesis in these dendrites, they elevate the threshold for initiating Ca2+ spikes and associated downstream spike bursts. Thus the concerted activity of Kv7/M channels in both compartments serves to reduce the propensity to generate self-sustained burst responses and fosters a regular, stimulus-graded spike output of the neuron. Given that the activity of Kv7/M channels is regulated by multiple neurotransmitters, they may provide a substrate for neuromodulation of neuronal input/output relations at both the axo-somatic and apical dendritic regions.

Action Potentials↗

Serum neopterin and somatization in women with chemical intolerance, depressives, and normals.

The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation. Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11). Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of 'unexplained' multiple somatic symptoms in subtypes of apparent somatizing disorders.

Adult↗

Histone H3 lysine 4 dimethylation is enriched on the inactive sex chromosomes in male meiosis but absent on the inactive X in female somatic cells.

Inactivation of the X chromosome occurs in female somatic cells and in male meiosis. In both cases, the inactive X chromosome undergoes changes in histone modifications including deacetylation of core histone proteins and enrichment with histone H3 lysine 9 (H3-K9) dimethylation. In this study we show that while the inactive X in female somatic cells is largely devoid of H3-K4 dimethylation, the inactive X in male meiosis is enriched with this modification. However, the inactive X chromosome in female somatic cells and the inactive X and Y in male meiosis are devoid of H3-K4 trimethylation. Further, trimethylation of H3-K4 is present at discrete regions along most of the autosomes, while H3-K4 dimethylation shows a more homogenous staining. Also, the Y chromosome is largely devoid of H3-K4 di- and trimethylation in somatic cells of both humans and mice, however, the Y chromosome is enriched with H3-K4 di- but not trimethylation throughout spermatogenesis. Our results provide insights into the differences between female somatic cells and male germ cells in inactivating the X chromosome, and suggest that trimethylation, and not dimethylation, of H3-K4 is a more robust indicator of the active regions of the genome.

Animals↗

Somatic pairings of the Y heterochromatin in human XYY and XYqi cells.

In human interphase nuclei containing Yq isochromosomes or two Y chromosomes, there are conspicuous somatic pairings between the brightly fluorescing Y-heterochromatin regions. These somatic pairings cannot be demonstrated in metaphases from conventional cell cultures because they are disrupted at the mitotic prophase. However, in lymphocytes cultivated in a medium containing distamycin A, the somatic pairing between Y-heterochromatin is preserved to metaphase. The present findings are compared with earlier observations of somatically paired heterochromatin. An explanation for the highly disparate frequency of somatic pairing between the Y-heterochromatin regions in Yq isochromosomes and YY chromosomes is proposed.

Chromosome Aberrations↗

Do social and demographic factors influence the nature and localisation of somatic complaints?

Demographic characteristics of specific somatic complaints were studied systematically in 60 consecutive patients whose main complaints were bodily symptoms without organic pathology, to determine if the social and demographic factors in any way influenced the nature or localisation of specific common somatic complaints. The Scale for Assessment of Somatic Symptoms was used to systematically acquire details of individual complaints. The commonest somatic complaints identified were weakness of body or mind (72%), headache (67%), fatiguability (37%) and burning sensations (35%). Subjects with less education reported weakness of body and mind, and multiple sites of pain more often, but lethargy and fatiguability less often than those with higher education. Rural subjects reported burning sensations and pain in their extremities more frequently. A sensation of 'gas' was more often reported by younger subjects, and pain in the extremities by male subjects. The factors which determine the choice of somatic complaints remain elusive and the exact reasons for these demographic relationships are unclear at present.

Adolescent↗

Somatic mutations reveal hyperactive Notch signaling in prurigo nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by pruritic skin nodules of unknown etiology. Little is known about genetic changes in PN pathogenesis, particularly somatic events, which are often implicated in inflammatory conditions. We thus performed whole-exome sequencing on 54 lesional and nonlesional skin biopsies from 17 patients with PN and 10 patients with atopic dermatitis (AD) for comparison. Somatic mutational analysis revealed that PN lesional skin harbors recurrent somatic mutations in fibrotic, neurotropic, and cancer-associated genes that are absent in adjacent PN nonlesional skin. Nonsynonymous mutations were most frequently present in NOTCH1 and the Notch signaling pathway, a key regulator of cellular proliferation and tissue fibrosis. In contrast, NOTCH1 mutations were absent in AD. Somatic copy-number analysis, combined with expression data, identified recurrently deleted and downregulated genes in PN lesional skin, which are associated with axonal guidance and extension. Follow-up immunofluorescence validation demonstrated increased NOTCH1 expression in PN lesional skin fibroblasts and increased Notch signaling in PN lesional dermis. Finally, a multicenter analysis revealed increased risk of NOTCH1-associated diseases in patients with PN. In characterizing the somatic landscape of PN, this study highlights the potential role of Notch pathway dysregulation in PN pathogenesis and fibrosis.

Humans↗