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Biomedical subjects

S J Thompson

Publications and source records attributed to S J Thompson.

At least 73 records · Page 4Linked to original sources

The impact of prenatal diagnosis on NTD surveillance.

Active and passive surveillance methods were utilized in an attempt to identify all neural tube defect (NTD)-affected pregnancies in South Carolina, a state previously identified to have a high prevalence of these defects (Greenberg et al., 1983). Sources of case ascertainment included maternal serum alpha-fetoprotein (MSAFP) programmes, prenatal diagnosis (amniocentesis) programmes, physician offices, perinatal centres, hospital medical record departments, and vital records. One hundred and nine NTD cases were identified over 24 months, indicating a prevalence of 1.60 cases per 1000 recorded births and fetal deaths (surveillance 1 October 1992-30 September 1994). Fifty-three (49 per cent) of the 109 NTD-affected pregnancies were either spontaneously or electively aborted prior to 26 weeks' gestation. Only three (6 per cent) of these early termination NTD cases were recorded in vital records, while medical records recorded 40 cases (75 per cent). By monitoring MSAFP programmes and maintaining frequent contact with physician offices and perinatal centres, 85 per cent of these early termination NTD-affected pregnancies were identified. However, for complete ascertainment of NTD-affected pregnancies, the utilization of all of these ascertainment methods was necessary, as each ascertainment method identified NTD cases missed by the other methods. Consideration of the significant impact of prenatal diagnosis on NTD surveillance and the use of multiple ascertainment methods in an attempt at complete ascertainment is particularly important now because of the recent recommendation for the periconceptional use of folic acid to prevent neural tube defects and the need for epidemiological studies to monitor the effectiveness of this prevention.

Abortion, Induced↗

Gastrointestinal symptoms and psychiatric disorders in the general population. Findings from NIMH Epidemiologic Catchment Area Project.

High rates of psychiatric disorder have been documented in patients with functional bowel syndromes sampled from physicians' offices. Lifetime psychiatric disorder and/or current psychiatric symptoms are thought to be much more highly associated with current gastrointestinal bowel symptoms in clinical settings than in the community. The relationship of lifetime functional gastrointestinal symptoms to lifetime psychiatric disorders has not been examined systematically in randomly selected samples of general community populations. The current study reports findings from existing data on a large, randomly selected population sample that may help to clarify these associations. Epidemiologic Catchment Area (ECA) project data were analyzed to examine relationships of functional gastrointestinal symptoms and psychiatric diagnoses in the community. Individuals with two or more medically unexplained gastrointestinal symptoms had high rates of psychiatric disorders. This was also true for the subgroup in which abdominal pain was one of the two symptoms. The overwhelming majority of subjects reporting medically unexplained gastrointestinal symptoms said they had consulted physicians for those symptoms. General population ECA data indicate that women in the community report more functional gastrointestinal complaints than men, that individuals with lifetime gastrointestinal complaints have high rates of lifetime psychiatric disorders (not necessarily currently symptomatic), and most have contacted a physician regarding their gastrointestinal symptoms. These data complement studies showing that patients with current gastrointestinal symptoms often do not consult a physician, or when they do, such behavior is associated with active psychiatric symptoms. These present data are consistent with the hypothesis that patients with recurrent symptoms are those who routinely seek medical help and who have high rates of psychiatric disorders, whereas those with symptoms that resolve or are improved by a medical intervention do not maintain treatment-seeking behavior.

Catchment Area, Health↗

B- and T-cell autoantigens in pristane-induced arthritis.

Pristane-induced arthritis (PIA) is a murine disease resembling rheumatoid arthritis (RA) which is characterized by autoimmune responses to joint tissues. To identify the range of potential antigens targeted in PIA, proteins from arthritic or normal joint extracts were fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and systematically screened for the ability to react with either serum IgG, or cultured splenic T cells, obtained from healthy or arthritic mice. Extracts from both normal and arthritic animals contained multiple proteins that were capable of reacting with murine serum IgG in immunoblotting experiments. In healthy controls, more bands were identified in extracts prepared from 30-week-old mice than from 8-week-old animals, but the widest range of proteins bound were derived from arthritic joints. Furthermore, the sera from PIA-positive mice reacted with more bands from each of the extracts than did normal sera. Fractionated extracts prepared from healthy joints failed to stimulate the in vitro proliferation of splenic T cells from either normal or arthritic animals. When arthritic joint components were screened, T cells from healthy mice responded weakly to some fractions, but multiple fractions elicited strong proliferation by T cells from mice with PIA. A band of apparent molecular mass 60000 was the protein most commonly bound by serum IgG from arthritic mice, and the corresponding fraction stimulated the highest responses by T cells from PIA-positive animals. These results are consistent with the notion that the 60,000 MW mammalian heat-shock protein is an important antigen in PIA, but that the autoimmune response diversifies with the development of arthritis to target multiple joint components.

Animals↗

T-helper 1 dominated responses to erythrocyte Band 3 in NZB mice.

Band 3, the red blood cell (RBC) anion channel protein, is the target autoantigen for the pathogenic RBC autoantibodies and T-helper (Th) cells in New Zealand Black (NZB) mice with autoimmune haemolytic anaemia (AIHA). To determine the subpopulation of these Th cells, they were stimulated with Band 3 and the profile of the cytokines elaborated by the responding cells was measured. NZB T cells stimulated with Band 3 produced high levels of the Th1 cytokine, interferon-gamma (IFN-gamma), but little or no interleukin-4 (IL-4), IL-5 or IL-10. Similar patterns were produced by NZB T cells responding to a spectrin preparation from the RBC membrane skeleton, or to mycobacterial heat-shock protein (hsp) 65 following immunization of mice with hsp 65 in incomplete adjuvant. By contrast, T cells from CBA mice similarly immunized with hsp 65 produced high levels of IL-4 and IL-5 in response to hsp 65. Examination of the isotype of the RBC-bound immunoglobulins in NZB mice revealed that immunoglobulin G2a (IgG2a) autoantibodies were the first to be detected in most mice and that later in the disease, IgG3 autoantibodies were often prominent. It is concluded that, contrary to expectation, the development of RBC autoantibodies in NZB mice is associated with Th1 cytokine-dominated responses.

Anemia, Hemolytic, Autoimmune↗

Expression of mammalian 60-kD heat shock protein in the joints of mice with pristane-induced arthritis.

Previous work has indicated that autoimmunity to the mammalian 60-kD heat shock protein (hsp60) may be necessary for the development of pristane-induced arthritis (PIA), a murine model of rheumatoid arthritis. To characterize the expression of hsp60 in murine joints, immunoblots of joint extracts and frozen histological sections prepared from normal or arthritic mice were probed with the hsp60-specific MoAb 4B989. Hsp60 could be detected in the joints of mice with PIA by both techniques, and was seen to be localized within the inflamed pannus using immunhistochemistry. Immunoblotting revealed that lower concentrations of hsp60 are also present in normal mouse joints, and that the level of expression increases with age, in parallel with greater susceptibility to PIA. In other studies, it was demonstrated that the titres of serum IgG antibodies reactive with the related mycobacterial hsp65, and the in vitro responsiveness of splenic T cells to hsp65, are both elevated in older mice. It is considered that the results are consistent with the hypothesis that PIA develops following environmental priming with mycobacterial hsp65, and the targeting of cross-reactive T cells to self-hsp60 in the joints.

Age Factors↗

Major histocompatibility proteins, anti-Hu antibodies, and paraneoplastic encephalomyelitis in neuroblastoma and small cell lung cancer.

BACKGROUND: Patients with neuroendocrine-related tumors and paraneoplastic encephalomyelitis (PEM) or paraneoplastic sensory neuronopathy (PSN) develop high titers of antibodies, called anti-Hu, against neuronal proteins expressed in their tumors, usually small cell lung cancer (SCLC). These tumors appear to be more indolent than those not associated with anti-Hu antibodies. The aims of this study were to determine 1) if patients with neuroblastoma (NB) also have anti-Hu antibodies, 2) the correlation between antibody titer and survival, and 3) if coexpression of Hu antigens and major histocompatibility proteins (MHC) by the tumor correlates with the development of anti-Hu associated PEM/PSN: METHODS: Using immunohistochemistry and Western blot analysis, the sera of 109 patients with NB whose neurologic condition was concealed at the time of the study were examined for the presence of anti-Hu antibodies. The expression of Hu antigens and MHC proteins in 50 nonselected NB and 26 SCLC (16 known to be from seropositive and 10 from seronegative patients) was examined using immunohistochemistry. RESULTS: Four Stage 4 NB patients were seropositive and had longer survival (median 86 months) than 71 seronegative patients in the same age group and with the same tumor stage (median survival, 28.5 months). Seventy-eight percent of NB and all SCLC expressed Hu antigens. Overall, 17 of 20 tumors from seropositive patients expressed both Hu and MHC Class I proteins, but only 4 of 30 tumors from seronegative patients expressed both proteins (P < 0.0001). CONCLUSIONS: 1) Some patients with NB develop anti-Hu antibodies; a search for that type of tumor is indicated in seropositive children, 2) most NBs and SCLCs express Hu antigens but only a few are associated with anti-Hu antibodies, and 3) Class I MHC expressed by some Hu antigen-bearing tumors may play a role in the development of anti-Hu associated PEM/PSN:

Adult↗

Maternal serum placental alkaline phosphatase level and risk for preterm delivery.

OBJECTIVE: The purpose of this study was to determine whether elevated midtrimester serum placental alkaline phosphatase levels are predictive of preterm delivery. STUDY DESIGN: By use of banked serum specimens from a sample of women who had received maternal serum alpha-fetoprotein screening, placental alkaline phosphatase values for multiples of the median were obtained from 270 mothers who had experienced a preterm delivery and from 1598 mothers of term, appropriate-for-gestational-age infants. Specimens were analyzed for placental alkaline phosphatase by means of a monoclonal antibody enzyme-linked immunosorbent assay. Logistic regression was used to determine whether placental alkaline phosphatase was associated with preterm birth, while potential confounders were controlled for. RESULTS: Women with placental alkaline phosphatase levels > or = 2.0 multiples of the median were significantly more likely to be delivered of a preterm infant in the current pregnancy compared with women with levels < 2.0 multiples of the median (odds ratio 2.9, 95% confidence interval 2.1 to 3.9). The likelihood of preterm birth increased significantly with higher multiples of the median (p < 0.001). CONCLUSION: Women with elevated placental alkaline phosphatase levels are at increased risk for preterm delivery. Additional studies are needed to evaluate the clinical utility of placental alkaline phosphatase testing as a means of identifying mothers at risk for preterm birth.

Adolescent↗

Immunologically ignorant autoreactive T cells, epitope spreading and repertoire limitation.

The factors that may cause antigen-presenting cells to alter the pattern of protein processing and presentation to autoreactive T cells, and thereby stimulate autoimmune disease, are currently under debate. In this article, Chris Elson and colleagues suggest that cytokines associated with T helper 1 (Th1) cells alter the processing of proteins and that this effect can be counteracted by Th2-associated cytokines.

Animals↗

Adenocarcinomatous transformation of intracranial germ cell tumors.

Germ cell tumors arising in the gonads, retroperitoneum, and mediastinum are occasionally overgrown by cancers of somatic type that are widely assumed to derive from the "malignant transformation" of included teratomatous tissues. These malignant, nongerminal neoplasms are typically chemoresistant, and their emergence is often associated with fatal treatment failure. Only rare, well-documented reports of sarcomatous transformation complicating intracranial germ cell neoplasia are on record. We describe two nongerminomatous germ cell tumors of the pineal region that underwent transformation into enteric-type adenocarcinoma. Both recurred in a locally aggressive fashion, one proving rapidly fatal owing to the development of multiple cerebral and cerebellar metastases and spinal leptomeningeal adenocarcinomatosis.

Adenocarcinoma↗

Primary infertility and oral contraceptive steroid use.

OBJECTIVE: To determine the association between combined monophasic oral contraceptive (OC) use and primary infertility. DESIGN: Case-control. SETTING: Women serving as controls of the Cancer and Steroid Hormone Study. PARTICIPANTS: Women were 19 to 40 years of age at first conception or infertility diagnosis. Based on 24 consecutive months of unprotected intercourse without a recognized conception, 419 nulligravid women had primary infertility; controls were 2,120 fertile women. A calendar of each women's reproductive history was used to determine fertility status and contraceptive use before infertility diagnosis or first conception. MAIN OUTCOME MEASURE: Primary infertility. RESULTS: Combined monophasic OC use was associated with a lower frequency of primary infertility, particularly among younger (age 20 years) compared with older women (age 30 years) after adjusting for barrier method use and education. A similar association was found for duration of OC use. When adjusted for age at first conception or infertility and barrier method, both higher (> 50 micrograms) and lower (< or = 50 micrograms) estrogen dose use were associated with decreased risk of primary infertility. CONCLUSION: Combined monophasic OC use was associated with a lower frequency of primary infertility.

Adult↗

Trace element concentrations in tissues of goats from Alabama.

Liver, kidney and muscle tissues of goats slaughtered in Alabama were analyzed for Cu, Fe, Mn and Zn. The Cu, Fe and Mn concentrations were significantly higher in livers than in kidneys and muscles. The Zn was significantly higher in livers and muscles than in kidneys. The concentrations of Cu, Fe, Mn and Zn in muscle were not significantly different between male and female goats. However, the Cu, Fe and Mn in livers and Fe in kidneys were significantly different between males and females. The concentrations of Fe, Mn and Zn in livers, Fe and Zn in muscles, and Fe in kidneys were significantly different between young and old goats. The Cu, Mn and Zn in kidneys were not significantly different between the young and old.

Alabama↗

The prognostic value of a risk score for necrotising enterocolitis.

Necrotising enterocolitis is the most common severe acquired gastrointestinal disorder in the neonate yet there remains disagreement on predictive and prognostic factors. A previously published risk score purports to predict infants at greater risk of the disease. Fifty-nine cases and 59 matched controls were evaluated using data from the first 24 h after birth to determine the predictive and prognostic value of the score for necrotising enterocolitis. In simple models the risk score was significantly, but inversely, associated with necrotising enterocolitis, primarily due to greater respiratory problems among controls. This finding contrary to the premise is clarified by a significant interaction of the risk score with feeding variables. Odds ratios for the risk score varied at different levels of daily feeding increments. However, the risk score was not statistically significant in any models which controlled for feeding increment and the interaction. The risk score was significantly associated with mortality among necrotising enterocolitis cases. Though the score was not statistically significant when the outcome was disease stage or surgery, trends were in the expected direction. The data suggest that the risk score itself may not be an independent predictor of necrotising enterocolitis, but may indicate infants more vulnerable to other potential risk factors and, in addition, may be related to prognosis for those who do develop necrotising enterocolitis.

Eating↗

Salivary theophylline concentrations in neonates.

Salivary theophylline concentrations in neonates were measured by a homogeneous enzyme immunoassay and compared with serum concentrations. Free serum theophylline concentrations were also compared with salivary concentrations and the values obtained were almost identical. Results using the immunoassay agreed well with those obtained using a high-performance liquid chromatographic procedure (HPLC).

Chromatography, High Pressure Liquid↗

Susceptibility to pristane-induced arthritis is altered with changes in bowel flora.

Pristane-induced arthritis (PIA) is unique among the animal arthritides in that a non-infectious, non-antigenic oil induces a chronic immune based arthritis with a prolonged delay between exposure to the inciting agent and development of the disease. Mice with pristane-induced arthritis have elevated T cell and humoral responses to the 65 kDa heat shock protein derived from Mycobacterium bovis (hsp65) and in common with several other models of autoimmune diseases the incidence of PIA is markedly suppressed by preimmunisation with hsp65 in Freund's incomplete adjuvant (Thompson et al. (1990) Eur. J. Immunol. 20, 2479). Recent studies have investigated how autoimmune reactions to heat shock proteins are involved in the development of arthritis. Arthritic CBA/Igb mice given pristane alone develop antibodies to both hsp65 and GroEl (bacterial 60 kDa heat shock proteins) and to hsp58 (the mammalian equivalent). Moreover, the splenic T cells of such mice proliferate vigorously in response to both bacterial and mammalian 60 kDa heat shock proteins. Remarkably, the anti-hsp65 antibody response in normal mice rises rapidly with age, directly correlating with the age related incidence of PIA. In addition, specific pathogen free mice (SPF) maintained in an isolator have negligible anti-hsp65 responses but these convert to positive responses if the animals are exposed to the open part of the animal facility (Thompson et al. (1992) Arthritis Rheum. 35, 139).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗