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[Somatization--problems in the borderland between somatic medicine and psychiatry].

The repeated presentation of multiple bodily symptoms which cannot be accounted for by detectable somatic illness is called somatization. It is frequently based on psychosocial stress, mainly one leading to adjustment problems, which in particular may initiate psycho-physiological dysbalance. Somatization, which does not include classical psychosomatic disorders is a common problem in primary care and inpatient settings. The concept of somatization has a firm empirical basis and offers fair therapeutic possibilities when the syndrome is recognized early and correctly.

Adaptation, Psychological↗

The somatic white-ivory eye spot test does not detect the same spectrum of genotoxic events as the wing somatic mutation and recombination test in Drosophila melanogaster.

A groups of six chemical compounds was tested in parallel in two different somatic genotoxicity assays in Drosophila melanogaster, the wing somatic mutation and recombination test (SMART) and the white-ivory eye spot test. The wing spot test makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. The white-ivory eye spot test makes use of the white-ivory (wi) quadruplication and detects the somatic reversion of the recessive eye color mutation wi to the wild-type (w+). Three- or two-day-old larvae were fed chronically with the compounds ethylnitrosourea (ENU), N-nitrosopyrrolidine (NNP), caffeine (CAF), chromium (VI) oxide (CRO), potassium chromate (POC), and 2,4-dichlorophenoxyacetic acid (2,4-D). All six compounds are genotoxic to various degrees in the wing spot test. The percentage of the genotoxic activity that is due to mitotic recombination was between 84% and 91% for the hexavalent chromium compounds CRO and POC and about 68% for 2,4-D. In contrast, ENU and NNP showed only 46% and 25% recombinagenic activity, respectively. In the white-ivory eye spot test, the three compounds (CRO, POC, and 2,4-D) with high recombinagenic activity and CAF were clearly nongenotoxic, whereas only ENU and NNP gave a positive response. From these results, it is concluded that the spectrum of genotoxic events detected by the two assays is different. In particular, the white-ivory eye spot test appears not to detect mitotic recombination the way the wing spot test does.

2,4-Dichlorophenoxyacetic Acid↗

Loss of information concerning hair displacement and other somatic stimuli in the first somatic sensory cortex of unanesthetized Macaca mulatta monkeys following dorsal funiculus transections.

Metal microelectrodes were used to record extracellular potentials from single cells in the four cytoarchitectural areas 3a, 3b, 1 and 2 of the representation of the lower body of the postcentral gyrus of Macaca mulatta monkeys. The animals were paralyzed and artificially respirated while remaining awake. Non-noxious natural stimuli were employed to determine response characteristics, like the submodality, of cells. After recording from a series of normal animals, spinal cord lesions of the dorsal funiculus, were surgically performed at cervical or high thoracic spinal levels. The animals were allowed to recover, and the above-mentioned cell characterization procedures were performed. After the recording, animals were humanely sacrificed and histological reconstructions of the penetrations and the spinal lesions were made. In the postcentral gyrus of normal animals, cells in cytoarchitectural areas 3b and 1 responded predominantly to cutaneous stimuli while cells in areas 3a and 2 responded predominantly to deep stimuli. Responses to displacement of hairs were only recorded in the predominantly cutaneous areas. In these areas in animals with dorsal funiculus transections at cervical or high thoracic spinal cord levels, many fewer cells responded to somatosensory stimulation than in the same areas in normal animals. There were no longer any responses to hair displacement stimuli. In this lower body region, responses to cutaneous stimuli and responses to some deep stimuli were reduced. Cortical areas 3b and 1, that normally showed responses predominantly to cutaneous stimuli, had an increased percentage of responses to deep stimuli. Cells that did not respond to our somatic stimuli but that had a spontaneous firing pattern were found in the first somatic sensory cortex (SI). We conclude that at rostral spinal levels, the dorsal funiculus contains all of the information about hair displacement stimuli of the lower body that projects to the first somatic sensory cortex as well as much information from cutaneous receptors and some from deep receptors on the body surface. Temporal information as well as precise receptive field demarkation is also supplied to SI cells by the dorsal funiculus.

Animals↗

Possible involvement of abscisic acid in the induction of secondary somatic embryogenesis on seed-coat-derived carrot somatic embryos.

When seed coats (pericarps) were picked from 14-day-old carrot (Daucus carota) seedlings and cultured on agar plates, embryogenic cell clusters were produced very rapidly at a high frequency on the open side edge. Embryo induction progressed without auxin treatment; indeed treatment caused the formation of non-embryogenic callus. The embryogenic tissues (primary embryos) developed normally until the torpedo stage; however, after this a number of secondary somatic embryos were produced in the hypocotyl and root regions. "Tertiary" embryos were formed on some of the secondary embryos, but many developed into normal plantlets. The primary embryos contained significantly higher levels of abscisic acid (ABA) than the hypocotyl-derived normal and seed-coat-derived secondary embryos. Fluridone inhibited the induction of secondary embryogenesis, while exogenously supplied ABA induced not only "tertiary" embryogenesis on the seed-coat-derived secondary embryos, but also secondary embryos on the hypocotyl-derived normal somatic embryos. These results indicate that ABA is one of the important endogenous factors for the induction of secondary embryogenesis on carrot somatic embryos. Higher levels of indole-3-acetic acid (IAA) in primary embryos also suggest the presence of some concerted effect of ABA and IAA on the induction of secondary embryogenesis in primary embryos.

Abscisic Acid↗

Somatic diversification of immunoglobulin heavy chain VDJ genes: evidence for somatic gene conversion in rabbits.

Rabbits preferentially utilize only one of their multiple functional germline immunoglobulin VH genes. This preferential usage of one gene, VH1, raises the question of how rabbits generate antibody diversity. VDJ diversification was analyzed by cloning and sequencing VH1 gene rearrangements. Comparison of these sequences with that of germline VH1 identified clusters of nucleotide changes, including codon insertions and deletions. To investigate whether gene conversion was involved in this somatic diversification, we searched a data base of rabbit germline VH gene sequences for donor VH genes; potential donors were identified for five diversified regions. We conclude that somatic gene conversion has a major role in generating antibody diversity in rabbits. These studies provide clear evidence for somatic gene conversion of mammalian VDJ genes.

Animals↗

On distinguishing cause and consequence: do high somatic cell counts lead to lower milk yield or does high milk yield lead to lower somatic cell count?

Researchers have reported that as milk yield increases composite milk somatic cell count (SCC) is diluted in cattle with no intramammary infection (IMI) and as a consequence, estimates of SCC from high yields are lower than estimates of SCC from low yields in dairy cows without an IMI. To date, estimates of reduced milk yield associated with high SCC because of intramammary infection have not been adjusted for any dilution of SCC. Ignoring dilution is therefore likely to lead to an overestimate of reduction in yield with increasing SCC. This paper investigates scenarios of the possible impact of dilution and inflammation on the association between somatic cell count and yield. The data used to investigate this relationship come from 8373 monthly records of milk yield and composite somatic cell count, together with incidence of clinical mastitis, which were recorded on 850 cows from five dairy cattle farms in Gloucestershire, UK. Two sets of models were used to investigate dilution and inflammation using two-level hierarchical models. The first set of models was used to estimate the linear (dilution) and log10-linear (inflammation) impact of SCC on the outcome variable milk yield. Five general linear models with increasing inclusion of higher test day SCC values were run. The cumulative categories were test day SCC values of up to and inclusive of 30, 50, 100, 200 and 400x10(3)cells/ml. Linear and log linear SCC influences on milk yield were estimated. At low SCC values the linear SCC predictor was dominant, while at higher values the log linear predictor was dominant. Up to 100x10(3)cells/ml there was mostly a slightly negative linear relationship between SCC and yield, potentially indicating a dilution effect. In the second set of models, three approaches to adjust milk loss for dilution were compared with an unadjusted model. In general, dilution-adjusted SCC values fitted the data better and resulted in a slightly lower milk loss per SCC category compared with unadjusted SCC. In all models with a dilution term there was a significant reduction in yield with SCC>200x10(3)cells/ml.

Animals↗

Screening for somatization and hypochondriasis in primary care and neurological in-patients: a seven-item scale for hypochondriasis and somatization.

The aim of this study was to investigate the internal and external validity of the Whiteley Index as a screening instrument for somatization illness. A 14-item version of the Whiteley Index for hypochondriacal traits was given to 99 of 191 consecutive primary care patients, aged 18-65 years, and to 100 consecutive patients, aged 18-60 years, admitted for the first time to a neurological ward. The primary care sample was, in addition, interviewed by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) psychiatric interview. The GPs and the neurologists were asked to rate various characteristics of the patients that might indicate somatization. The internal validity of the Whiteley Index was tested by means of latent structure analysis. On this basis, a reduced seven-item scale (Whiteley-7 scale) and two subscales (i.e., an Illness Conviction and Illness Worrying scale, each with three items) were constructed. All three had a high internal validity fitting into the very restricted Rasch statistical model (p>0.05) and an acceptable transferability between most of the subpopulations investigated. In the primary care population, the Whiteley-7 and the Illness Conviction scales at cut-point 0/1 showed 1.00 and 0.87 sensitivity and 0.65 and 0.87 specificity, respectively, using as "gold standard" the fulfillment of criteria for at least one ICD-10 somatoform disorder, and 0.71 and 0.63 sensitivity and 0.62 and 0.87 specificity, respectively, as gold standard for the fulfillment of criteria for at least one DSM-IV somatoform disorder, excluding the NOS diagnostic group. The Illness Worrying subscale showed less impressive performance in this respect. The agreement between the Whiteley-7 scale including the two subscales and neurologists' rating and the GPs' rating and the somatization subscale on the SCL-90 was modest or worse. It may be concluded that the Whiteley-7 scale and the Illness Conviction subscale had acceptable psychometric profiles, and both seem to be promising screening tools for not only hypochondriasis but also for somatoform disorders in general.

Adolescent↗

Parallel evolution of antibody variable regions by somatic processes: consecutive shared somatic alterations in VH genes expressed by independently generated hybridomas apparently acquired by point mutation and selection rather than by gene conversion.

We identified, in independently generated hybridoma antibodies, blocks of shared somatic alterations comprising four consecutive amino acid replacements in the CDR2s of their heavy chain variable regions. We found that the nucleotide sequences encoding the shared replacements differed slightly. In addition, we performed genomic cloning and sequencing analyses that indicate that no genomic sequence could encode the block of shared replacements in any one of the antibodies and thus directly serve as a donor by a recombinational process. Finally, in a survey of other somatically mutated versions of the same heavy chain variable gene, we found several examples containing one, two, or three of the shared CDR2 mutations in various combinations. We conclude that the shared somatic alterations were acquired by several independent events. This result, and the fact that the antibodies containing the four shared mutations were elicited in response to the same antigen and are encoded by the same VH and VK gene segments, suggests that an intense selection pressure has fixed the shared replacements by favoring the clonal expansion of B cells producing antibodies that contain them. The basis of this selection pressure is addressed elsewhere (Parhami-Seren, B., L. J. Wysocki, M. N. Margolies, and J. Sharon, manuscript submitted for publication).

Amino Acid Sequence↗

Somatic cell counts and infection rates for cows of varying somatic cell count in initial test of first lactation.

Somatic cell counts (log, base 2) and rates of infection in first and subsequent lactations were examined by classes of somatic cell count in initial test day of first lactation to determine if cows with initially low counts were more at risk to subsequent mastitis infection. Classes of initial somatic cell counts were less than 100,000, 100,000 to 400,000 and greater than 400,000. Differences among initial classes in subsequent cell counts were small, but the initial rank of classes was maintained throughout the remainder of first lactations and in subsequent lactations. Differences among initial classes for rates of infection in first and subsequent lactations consistently favored low initial cell counts. Results gave no indication that cows initially low in cell count are at greater risk of subsequent mastitis infection.

Animals↗

[Somatic hypermutagenesis in immunoglobulin genes. I. Connection of somatic mutations with repeats. A statistical weighting method].

Based on the analysis of a number of immunoglobulin genes' nucleotide sequences, it has been suggested, that somatic mutations emerge by means of imperfect duplexes correction, formed by mispairing of complementary regions of direct and inverted repeats. In the present work provides new data, confirming this mechanism of somatic hypermutagenesis. It has been shown that the presented sample of V- and J-segments of immunoglobulin genes is abundant in nonrandom imperfect direct repeats and complementary palindromes. To prove the connection of somatic mutations with the correction of imperfect duplexes, made up by the regions of these repeats, we have developed the method of statistical weights, permitting us to analyse the samples of mutations and repeats and to reveal the reliability of the connection between them. Using this method we have investigated the collection of 203 nucleotide substitutions in V- and J-segments and have shown a statistically reliable (P less than 10(-4) connection of these mutation positions with imperfect repeats.

Animals↗

Differentiation between antibodies to protamines and somatic nuclear antigens by means of a comparative fluorescence study on swollen nuclei of spermatozoa and somatic cells.

The indirect immunofluorescence test on swollen nuclei of rat thymocytes, chicken red blood cells and human and salmon spermatozoa was found to be an easy and satisfactory method for the discrimination between antibodies to sperm-specific nuclear antigens and somatic nuclear antigens. This study shows that nuclear antibodies present in the sera of vasectomized men and in rabbit antisera to human protamines are directed against the human sperm-specific nuclear antigens (protamines), and that they may cross-react with salmon protamine. These sera do not react with somatic nuclear antigens. This comparative fluorescence study and a complement fixation study, performed with sera from diabetic patients, proved that the administration of insulin retard (protamine-zinc-insulin) may lead to the formation of antibodies to the fish protamine. These antibodies may reveal a weak cross reaction with human protamines. The results obtained in this study also prove that the nuclei of chicken red blood cells and human sperm do not contain, or contain very small amounts of, histone fraction H1, and that salmon sperm nuclei do not contain any of the histone fractions, and suggest that the nuclei of mature human spermatozoa contain smaller amounts of histones in comparison to somatic cell nuclei.

Animals↗

[Missed somatic diagnoses--inexcusable, missed psychogenic somatic disorders--a gentleman's offense].

Overlooking somatic diagnoses is judged a serious failing, overlooking psychogenic somatization a minor mistake. This situation derives from the medical theory on which the physician bases his opinions, decisions and treatments. In this case, the mechanistic model deriving from the introduction of physics and chemistry into medicine in the 18th century. A 19 minute verbatim first interview illustrates how the biopsychosocial interview method serves to pinpoint psychogenic somatization in a woman who had been unsuccessfully examined and treated for four years, bringing the underlying blocked process of grief to light and making it the focus of therapy. Savings in time, cost and suffering are obvious.

Aged↗

Spatial relationships between the terminations of somatic sensory motor pathways in the rostral brainstem of cats and monkeys. II. Cerebellar projections compared with those of the ascending somatic sensory pathways in lateral diencephalon.

Previous studies have shown that ascending somatic sensory pathways arising from the dorsal column nuclei, lateral cervical nucleus and spinothalamic tract terminate in parts of the thalamus adjacent to those which receive cerebellar terminations. This termination pattern creates a border between the ventroposterolateral nucleus (VPL) and the ventrolateral nucleus (VL) in the cat and between the caudal and oral parts of VPL (VPLc and VPLo, respectively) in the monkey. Since it is not clear how sharp these borders are, a double orthograde labeling strategy was used in the present study to make direct comparisons of the projections to the thalamus from these sources of input. It was found that there was a change in the sources of afferent input to the different target areas that paralleled changes in cytoarchitecture. Moving caudally to rostrally, VPL in the cat and VPLc in the monkey received projections predominantly from the middle, dorsal (clusters) portion of the dorsal column nuclei. These projections were gradually replaced near the VPL-VL border in the cat and VPLc-VPLo border in the monkey first by input from the lateral cervical nucleus (cat only) and the rostral and ventral portions of the dorsal column nuclei and then by spinothalamic projections. Towards VL in the cat and the rostral parts of VPLo in the monkey (referred to as Vim by Hassler, '59 and Mehler, '71), these projections were in turn replaced by those from the cerebellum. This sequence resulted in a complex pattern (summarized in Fig. 10) where some thalamic territories received input predominantly from one source and others received converging input from several sources. The major region receiving converging ascending somatic sensory and cerebellar terminations was located at the border between VPL and VL in the cat and in the caudal parts of Olszewski's ('52) VPLo in the monkey (that is, between VPLc and Vim). In general, the results in the cat were similar to those in the monkey. One notable difference was that the domain containing terminals from the cerebellum and the rostral-ventral parts of the dorsal column nuclei was located medially between VPLc and Vim in the monkey, whereas it extended across the entire mediolateral border between VPL and VL in the cat. In both species, thalamic neurons received input predominantly from one afferent source and only minor input, if any, from other sources.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers.

DNA mismatch repair is of considerable scientific and medical importance because of its essential role in maintaining genomic integrity, and its association with hereditary non-polyposis colon cancer (HNPCC). Germline mutations in five mismatch repair genes (MLH1, MSH2, PMS1, PMS2, and MSH6) have been associated with HNPCC susceptibility. Our laboratory recently identified MLH3, a novel DNA mismatch repair gene. We screened the MLH3 coding sequence in 60 probands with increased genetic risk factors for colorectal cancer susceptibility and no mutations in the other candidate genes. No definite MLH3 germline mutations were found. We subsequently screened 36 colon tumors, and discovered an appreciable frequency of somatic MLH3 coding mutations in MSI-H tumors (25%). In four of six tumors, evidence of biallelic inactivation was noted. Furthermore, MLH3 nonsense mutations were identified in two of 12 microsatellite stable (MSS) tumors with 14q24 loss of heterozygosity. While our analyses do not exclude the existence of germline MLH3 mutations in patients with increased genetic risk factors for colorectal cancer susceptibility, they suggest such mutations are uncommon in this patient population. The finding of an appreciable frequency of somatic MLH3 mutations is consistent with a possible role for this gene in the progression of colorectal cancer tumorigenesis. Hum Mutat 17:389-396, 2001. Published 2001 Wiley-Liss, Inc.

Adaptor Proteins, Signal Transducing↗

A cross sectional study of somatic complaints of Nigerian females using the Enugu Somatization Scale.

Among Nigerian mentally ill a constant male-female ratio of 2:1, over-representation of single males and married females and the tendency for the females who seek psychiatric aid to be psychotic with schizoaffective disturbances have been observed. The question arose as to why this is so. To answer this, the Enugu Somatization Scale, developed in an effort to avoid the difficulty encountered in using Western diagnostic illness categories and scales for assessing mental illness in Nigeria was administered to 51 mentally ill females, 60 adolescent secondary school girls, 67 post secondary school females, 149 pregnant females, and 60 women who were once able to bear children but now no longer can. It was found that somatization is used by Nigerian females to contain their stress. The pregnant females scored lowest while those women who can no longer deliver scored highest. Pregnancy is seen as a state of rest from societal stress for the females, who otherwise are not allowed by the society to be so mentally ill as to seek a psychiatrist and who have to be psychotic to be able to do so. Various tentative, dynamic explanations of the items in the scale answered in the affirmative by a wide cross section of the women, based on the clinical experience of the author, are offered.

Adaptation, Psychological↗

Quantitation of testicular and somatic cytochromes c in testis and somatic tissues from developing rats.

By combining chromatographic and spectral procedures, simple and quantitative assays for somatic cytochrome c (cyt cs) and testicular cytochrome c (cyt ct) in crude animal tissue extracts were developed. Using this assay procedure, limited developmental studies of cyt ct and cs were performed with tissue extracts of 27-, 58-, and 85-day-old rats. Specific contents of cyt cs in somatic tissues (i.e., micrograms of cyt c/g of tissue) of these three age groups did not show significant variations. However, the amounts of both cyt ct and cs in testis were markedly increased as the rats approached maturity. Increasing cyt ct/cyt cs ratios as the rat developed to maturity suggest that expression of cyt ct is preferentially required for specific function of testis. Application of both molecular biological techniques and this assay (for holo-cyt ct) should be useful to study the overall regulation of the expression of cyt ct in testis.

Aging↗

Somatic crossing-over in Glycine max (L.) merrill: activation of dimethyl nitrosoamine by plant seed and comparison with methyl nitrosourea in inducing somatic mosaicism.

The soybean system used for detecting environmental mutagens is analyzed for various types of spots on the leaves of heterozygous y11y11 plants and homozygous y11y11's induced by a nitrosoamine (dimethyl nitrosoamine, DMN) and a nitrosoamide (methyl nitrosourea, MNU). It is shown that the nitrosoamine can be "activated" by the seed (is converted to a true mutagen) without the addition of NADPH or S-9 fraction of the liver homogenate as is necessary in animal tissue culture or bacterial studies. Whereas somatic mosaicism in soybean can be induced with a dose as low as 1.25 ppm of DMN, the upper limit in spot production is reached at around 60 ppm concentration, applied for 0--24 h. Such saturation effect may be due to a limited amount of DMN being converted to true mutagen. MNU, on the other hand, does not show such limitations, perhaps because of its property of being a direct mutagen not necessitating an intermediate step required for converting the promutagen DMN. The frequency of twin spots on Y11y11 leaves increases only slightly by either DMN or MNU, suggesting only a small increase in somatic crossing-over induced by the two chemicals. The yellow spots increase the most, perhaps due to segmental losses carrying Y11 or non-complementary segregation of exchanges involving non-homologous chromosomes. Neither chemical is found capable of mutating y11 to Y11 as seen by the general lack of light green sectors on y11Y11 plants. Usefulness of the soybean system in studying mutagenesis is briefly discussed.

Crossing Over, Genetic↗

Noxious somatic inputs to hypothalamic-midbrain projection neurones: a comparison of the columnar organisation of somatic and visceral inputs to the periaqueductal grey in the rat.

The induction of Fos protein was used to localise hypothalamic neurones activated by noxious somatic stimulation. This was combined with retrograde transport of fluorescent latex microspheres from identified 'pressor' and 'depressor' sites in the dorsolateral/lateral or ventrolateral columns of the periaqueductal grey (PAG). Fos-positive neurones were found throughout the rostral hypothalamus. Of those neurones activated by noxious somatic stimuli that projected to the PAG all but one was retrogradely labelled from sites that included the lateral column. Only one neurone was double labelled following injection of tracer at a depressor site in the ventrolateral PAG. This is in marked contrast to visceroresponsive hypothalamic neurones, a larger proportion of which project to the PAG and which, as reported previously, preferentially target depressor sites in the ventrolateral sector. These results are discussed in relation to the roles of the anterior hypothalamus and the different functional columns of the PAG in co-ordinating autonomic and sensory functions in response to nociceptive inputs originating in different peripheral domains.

Animals↗