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Biomedical subjects

S Simpson

Publications and source records attributed to S Simpson.

At least 19 recordsLinked to original sources
PubMed1998

Monoallelic expression of the interleukin-2 locus.

The lymphokine interleukin-2 (IL-2) is responsible for autocrine cell cycle progression and regulation of immune responses. Uncontrolled secretion of IL-2 results in adverse reactions ranging from anergy, to aberrant T cell activation, to autoimmunity. With the use of fluorescent in situ hybridization and single-cell polymerase chain reaction in cells with different IL-2 alleles, IL-2 expression in mature thymocytes and T cells was found to be tightly controlled by monoallelic expression. Because IL-2 is encoded at a nonimprinted autosomal locus, this result represents an unusual regulatory mode for controlling the precise expression of a single gene.

Alleles↗
PubMed1998

Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression.

BACKGROUND: Late-life depression is associated with increased subcortical white matter hyperintensities. There is some evidence that they are associated with a poorer response to acute treatment. Neurological signs and neuropsychological dysfunction are further evidence of abnormalities in the brain, but they have not been studied in relation to therapy resistance. METHODS: A prospective study of 24 normal controls and 75 consecutive elderly (aged 65 to 85) patients with DSM-III-R major depression entered a naturalistic study of treatment. Assessment of response to monotherapy and then lithium augmentation or ECT created three outcome groups. Investigations included magnetic resonance brain imaging, neuropsychological and neurological examination. RESULTS: Response to monotherapy within 12 weeks was shown by 42.7%, a further 37.3% responded to lithium augmentation or ECT within 24 weeks and 20% had responded poorly to all treatments at 24 weeks. Subcortical hyperintensities were significantly increased in the more resistant patients. These included confluent deep white matter, multiple (> 5) basal ganglia lesions and pontine reticular formation lesions. Most of the neuropsychological impairment was restricted to the resistant groups and was of a subcortico-frontal type. Extrapyramidal, frontal and pyramidal neurological signs characterized the resistant groups. The combination of extrapyramidal signs, pyramidal tract signs and impairment of motor hand sequencing strongly predicted resistance to 12 weeks of antidepressant monotherapy with 89% sensitivity and 95% specificity. CONCLUSION: In late-life depression a poor response to antidepressant monotherapy can be expected in those patients with a frontal lobe syndrome, extrapyramidal signs or if MRI T2-weighted lesions are present in both the basal ganglia and the pontine reticular formation.

Aged↗
PubMed1998

pANCA represents a cross-reactivity to enteric bacterial antigens.

pANCA (perinuclear antineutrophil cytoplasmic antibodies) occur at a high frequency in patients with ulcerative colitis. The purpose of this study was to investigate the frequency of pANCA in different mouse models of colitis and to determine whether there is any cross-reactivity of pANCA with bacterial antigens. Sera from 146 colitic mice and controls and from 30 patients with ulcerative colitis were tested for the presence of pANCA by indirect immunofluorescence with or without prior absorption with homogenized murine cecal bacteria. pANCA was found in 24 of 36 IL10(-/-) mice. In contrast to the human pANCA, both nuclear and perinuclear staining was found. Absorption of either human or mouse pANCA-positive sera with enteric bacterial antigens greatly reduced or abolished the specific perinuclear staining of pANCA. We conclude that pANCA occurs not only in humans but also in IL19(-/-) mice with colitis and likely represents a cross-reactivity with enteric bacterial antigens.

Animals↗
PubMed1998

Longitudinal estimates of pulmonary function in refractory ceramic fiber manufacturing workers.

Refractory ceramic fibers (RCF) are man-made vitreous fibers (MMVF) used in high-temperature industrial applications. Between 1987 and 1994, a prospective study evaluated pulmonary function of 361 male workers currently employed in RCF manufacturing and related operations for plausibility of a causal relationship between RCF exposure and pulmonary function changes. Workers included in the analysis provided at least five pulmonary function tests. The exposure-response relationship was modeled with two exposure variables: years in a production job, and cumulative fiber exposure (fiber-mo/cc). Comparison groups were nonproduction workers and workers with up to 15 fiber-mo/cc cumulative exposure. A statistically significant decrease in FVC was demonstrated among workers employed in production jobs more than 7 yr prior to initial test. A similar but nonstatistically significant result was demonstrated for FVC in workers with greater than 60 fiber-mo/cc cumulative exposure prior to initial pulmonary function test. Similar but nonstatistically significant results were obtained for FEV1. These findings, which primarily reflect workers employed before 1980, did not persist with analysis of follow-up production years and accumulated RCF exposure from initial pulmonary function test. Since longitudinal analyses are sensitive to influences that continue to affect annual decline during the study period, lower RCF exposure levels since the 1980s may be responsible for eliminating any further effect on pulmonary function.

Adult↗
PubMed1998

A gregarizing factor present in the egg pod foam of the desert locust Schistocerca gregaria.

The behavioural phase state and coloration of hatchling Schistocerca gregaria were examined in a series of experiments to determine the means by which phase characteristics are passed between generations. Both crowding of solitary-reared females at the time of oviposition and high egg pod densities promoted behavioural gregarization, although the former appeared to be a rather more potent factor. In contrast, egg pod density alone appeared to promote the development of hatchlings with dark patterns characteristic of the gregarious phase. The phase characteristics of hatchlings were unaffected when sand previously used for oviposition was used to collect further egg pods. Early separation of presumptive gregarious eggs from egg pods laid by crowd-reared females led to solitarization of the hatchlings, indicating that a factor, either in or around the eggs, removed by early separation promoted gregarization. Both the eggs and foam plugs of egg pods from crowd-reared, gregarious females appeared to be a source of this gregarizing factor. In contrast, there was no evidence for a solitarization factor in egg pods from solitary-reared S. gregaria. Saline extracts of egg pod foam plugs produced an active factor which promoted gregarization both in eggs from solitary-reared females and in eggs from gregarious females which were separated and washed to removed the factor. Solitary eggs were influenced by the gregarizing factor in foam plug extracts for up to 1 day after oviposition. Saline extracts of foam plug retained their activity for up to 1 day. Initial studies on the properties of this factor were made. We conclude that the foam plugs of egg pods from crowd-reared, gregarious locusts contain a small (<3 kDa), hydrophilic gregarizing factor which is produced at the time of oviposition and which predisposes hatchlings to attain characteristics of the gregarious phase.

Journal Article↗
PubMed1998

Idiopathic localized dilatation of the ileum. A rare cause of gastrointestinal haemorrhage in an adult.

A case of idiopathic localized dilatation of the ileum presenting in adulthood and associated with small bowel malrotation, ulceration and bleeding is described. To our knowledge, this is the first such report of this combination of features. The diagnosis was made using a small bowel barium study and intra-operative enteroscopy. Idiopathic localized dilatation of the ileum with ulceration should be considered as a rare small intestinal cause of occult or frank gastrointestinal blood loss in children or young adults.

Adult↗
PubMed1997

Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 1, 6, 8, 10, and 12.

A report on an initial genome screen on 540 individuals in 97 families was collected as part of the NIMH Genetics Initiative on Bipolar Disorder. Families were ascertained to be informative for genetic linkage and underwent a common ascertainment and assessment protocol at four clinical sites. The sample was genotyped for 65 highly polymorphic markers from chromosomes 1, 6, 8, 10, and 12. The average intermarker interval was 16 cM. Genotypic data was analyzed using affected sib pair, multipoint affected sib pair, and pedigree analysis methods. Multipoint methods gave lod scores of approximately two on chromosomes 1, 6, and 10. The peak lod score on chromosome 6 occurred at the end of the q-arm, at some distance from the 6p24-22 area previously implicated for schizophrenia. We are currently genotyping additional markers to reduce the intermarker interval around the signals. The interpretation of results from a genome screen of a complex disorder and the problem of achieving a balance between detecting false positive results and the ability to detect genes of modest effect are discussed.

Bipolar Disorder↗
PubMed1997

Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 4, 7, 9, 18, 19, 20, and 21q.

An initial genome scan was performed on 540 individuals from 97 families segregating bipolar disorder, collected through the National Institutes of Mental Health Genetics Initiative. We report here affected-sib-pair (ASP) data on 126 marker loci (approximately 68,000 genotypes) mapping to chromosomes 4, 7, 9, 18, 19, 20, and 21q, under three affection status models. Modest increases in identical-by-descent (IBD) allele sharing were found at the following loci: D4S2397 and D4S391 (P < 0.05) on 4p, D4S1647 (P < 0.05) on 4q, D7S1802 and D7S1869 (low P = 0.01) on 7p, D9S302 (P = 0.004) on 9q, and D20S604 on 20p and D20S173 on 20q (P < 0.05). In addition, five markers on 7q displayed increased IBD sharing (P = 0.046-0.002). Additional ASP analyses on chromosomes 18 and 21q marker data were performed using disease phenotype models defined previously. On chromosome 18, only D18S40 on 18p and D18S70 on 18q yielded a slight elevation in allele sharing (P = 0.02), implying that the reported linkages in these regions were not confirmed. On chromosome 21q, a cluster of markers within an approximately 9 cM interval: D21S1254, D21S65, D21S1440, and D21S1255 exhibited excess allele sharing (P = 0.041-0.008). Multilocus data on overlapping marker quartets, from D21S1265 to D21S1255, which were consistent with increased IBD sharing (P < 0.01, with a low of 0.0009), overlapped a broad interval of excess allele sharing reported previously, increasing support for a susceptibility locus for bipolar disorder on 21q.

Alleles↗
PubMed1997

Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X.

We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder-recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk lambda(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring lambda(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with lambda(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the markers in Xp22 would have lambda(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have lambda(i) > 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies.

Bipolar Disorder↗
PubMed1997

Altered expression of Erg and Ets-2 transcription factors is associated with genetic changes at 21q22.2-22.3 in immortal and cervical carcinoma cell lines.

Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved. Altered expression of the ets family transcription factors erg and ets-2 was found associated with the development of cervical carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell line, CX16-2, which has HPV integrated at a translocation breakpoint t(19;21) involving 21q22.2-22.3, where these genes have been mapped. Six of 10 cervical carcinoma cell lines overexpressed ets-2 RNA suggesting an association of overexpression with cervical cell neoplasia. A clonally related pair of cervical carcinoma cell lines, C-4I and C-4II, showed differential expression of erg and ets-2. C-4I overexpressed ets-2 RNA compared to normal cervical cells and C-4II. C-4II expressed a 5.3 kb erg transcript not seen in C-4I, ectocervical cells or other cervical carcinoma cell lines examined. Pulsed field gel electrophoresis was used to analyse changes in DNA fragments related to structural changes and to construct a physical map encompassing erg and ets-2. Alterations in erg and ets-2 RNA expression in each of three different cell lines examined were associated with translocations. Association between altered expression of erg and ets-2 and altered regional structural suggests that these genes are important targets in cervical carcinogenesis.

Blotting, Northern↗
PubMed1997

Sleep disruption and mood changes associated with menopause.

This study examined the sleep and mood differences between premenopausal and perimenopausal women matched for age and sociodemographic variables. Wrist actigraphy, Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), a sleep questionnaire, and responses to a sleep diary were recorded for a period of 1 week. It was found that the sleep disruption of perimenopausal subjects was significantly greater than that of the premenopausal group (p < 0.05). Overall, the perimenopausal group demonstrated a significant increase in sleep disruption and mood alterations when compared with the premenopausal group. Actigraphic data showed that perimenopausal subjects experienced longer and more numerous arousals resulting in significantly less sleep (p < 0.05). In addition, perimenopausal subjects scored significantly higher (p < 0.05) on the STAI and significantly lower on the Vigor subscale of the POMS (p < 0.01) than premenopausal subjects. Correlational analyses indicated that sleep and mood changes were significantly related in the perimenopausal group, but not in the premenopausal group. Taken together, these results suggest that the mood changes experienced by the perimenopausal group may be mediated by sleep disruption.

Adult↗
PubMed1997

Exposure to alcohol in utero blunts splenic sympathetic neural response to endotoxin and interleukin-1beta in the rat.

Systemic administration of endotoxin (LPS) or interleukin-1beta (IL-1) to prepubertal rats induced a marked increase in splenic but not cardiac norepinephrine (NE) turnover, an index of sympathetic neural activity. In contrast, the splenic neural response was blunted in their fetal alcohol-exposed (FAE) cohorts. Because the sympathetic outflow to lymphoid organs is considered an important immune modulator, the anomalous neural response to immune signals may partly account for the impaired cellular immunity and, thus, for the increased susceptibility to infections associated with FAE.

Adrenocorticotropic Hormone↗
PubMed1997

Experience-dependent changes in the number of chemosensory sensilla on the mouthparts and antennae of

The effect of diet on the number of gustatory and olfactory sensilla was investigated in locusts. Insects fed for the final two stadia on nutritionally adequate synthetic foods have fewer sensilla on the maxillary palps and antennae than insects fed on the usual rearing diet of seedling wheat. This effect was seen irrespective of the nutritional balance of the foods and was independent of the concentration of nutrients present or the size of the insect. Supplying wheat odour to locusts fed synthetic foods had no effect on the number of sensilla present on the palps, but completely reversed the decrease in the number of olfactory sensilla of the antennae and partially reversed the decrease in the number of antennal uniporous trichoid sensilla. Locusts that were allowed to select between two nutritionally unbalanced but complementary synthetic foods had a higher number of sensilla on the maxillary palps than those fed individual synthetic foods, providing the two foods differed substantially in their protein:carbohydrate ratios. Insects also developed more sensilla if they were fed on two foods of identical nutritional composition but with different added flavours (1% tannic acid or amygdalin). Exposing locusts to synthetic foods for a single stadium did not cause any significant decrease in sensilla number. The results suggest that the number of sensilla that develop in a given sensory field is influenced by the variety of chemical stimuli experienced and the chemical complexity of the environment as provided by the presence of distinct individual sources of stimulation.

Journal Article↗
PubMed1997

Nutritional homeostasis in locusts: is there a mechanism for increased energy expenditure during carbohydrate overfeeding?

Maintenance of carbohydrate balance via changes in CO2 output volume was investigated in locusts using a flow-through respirometer. The effect of an imbalance in the dietary protein to digestible carbohydrate ratio on expired CO2 levels was measured in locusts fed one of two synthetic diets [7% protein, 21% digestible carbohydrate (7:21) and 21% protein, 7% digestible carbohydrate (21:7)]. Additionally, the effect of dietary dilution was investigated by feeding locusts one of two diets with a close-to-optimal ratio of protein to carbohydrate, one containing 7% protein and 7% digestible carbohydrate (7:7) and the other containing 21% protein and 21% digestible carbohydrate (21:21). For insects fed unbalanced diets, a higher CO2 output volume was measured during feeding on diet 7:21 when compared with insects fed on diet 21:7. Locusts also expired a greater volume of CO2 during the entire 2h observation period. This response is consistent with specific metabolic control of carbohydrate balance via enhanced respiration. For insects fed balanced diets, the total volume of CO2 expired over the duration of a meal was greater for insects fed diet 7:7 than for those fed diet 21:21, although this was due entirely to meals lasting longer on the more dilute diet. However, the basal level of respiration rate was greater for insects fed diet 21:21 and, as a result, over the entire 2h period, CO2 output volume did not differ between locusts fed diet 7:7 or 21:21. A possible mechanism for enhanced CO2 output volume on the nutritionally unbalanced diet was investigated, namely triglyceride/fatty-acid substrate cycling. There was no evidence for the presence of the thermogenic effect of this particular cycle on locusts as a means for dealing with excess ingested carbohydrate.

Journal Article↗
PubMed1997

Prognosis and outcome studies in late-life depression.

This article reviews our current understanding of the outcome of depression in older people and factors predictive of outcome. Research into neurobiological factors that may be of relevance to outcome is touched on, with suggestions for improving outcome.

Aged↗