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Biomedical subjects

T Thompson

Publications and source records attributed to T Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Self-injurious behavior: gene-brain-behavior relationships.

This paper summarizes a conference held at the National Institute of Child Health and Human Development on December 6-7, 1999, on self-injurious behavior [SIB] in developmental disabilities. Twenty-six of the top researchers in the U.S. from this field representing 13 different disciplines discussed environmental mechanisms, epidemiology, behavioral and pharmacological intervention strategies, neurochemical substrates, genetic syndromes in which SIB is a prominent behavioral phenotype, neurobiological and neurodevelopmental factors affecting SIB in humans as well as a variety of animal models of SIB. Findings over the last decade, especially new discoveries since 1995, were emphasized. SIB is a rapidly growing area of scientific interest to both basic and applied researchers. In many respects it is a model for the study of gene-brain-behavior relationships in developmental disabilities.

Animals↗
PubMed2001

Non-invasive antidromic neurostimulation: a simple effective method for improving bladder storage.

Patients with intractably diminished bladder storage function are encountered frequently by neurourologists, occasionally requiring reconstructive surgery for appropriate resolution. Although sacral neuromodulation is a recognized effective therapeutic modality, present techniques are technically demanding, invasive, and expensive. This study investigated the effect of non-invasive third sacral nerve (S3) stimulation on bladder activity during filling cystometry. One hundred forty-six patients underwent standard urodynamic filling cystometry that was then immediately repeated. Patients in the study group (n = 74) received antidromic transcutaneous sacral neurostimulation during the second fill and the control group (n = 72) underwent a second fill without neurostimulation. A statistically significant increase in bladder storage capacity without a corresponding rise in detrusor pressure was observed in the neurostimulated patients. This improvement in functional capacity is an encouraging finding that further supports the use of this non-invasive treatment modality in clinical practice.

Adolescent↗
PubMed2001

Wheat starch, gliadin, and the gluten-free diet.

Individuals with celiac disease generally are advised to follow a lifelong gluten-free diet and avoid consumption of the prolamins gliadin (wheat), secalin (rye), and hordein (barley). Although the designation of the diet as glutenfree may imply that the diet contains zero gluten, this is not necessarily true. In some countries (eg, United States, Canada), the gluten-free diet is completely devoid of gluten and is based on foods such as rice and corn that are naturally gluten free. In others (eg, Scandinavia, United Kingdom), the gluten-free diet may include foods such as wheat starch that have been rendered gluten free but nonetheless contain small amounts of toxic prolamins. The discrepancy in the use of foods rendered gluten free exists because the amount of toxic prolamins that individuals with celiac disease may consume without damaging the mucosa of the small intestine is unknown. Minimal research has been conducted on the toxicity of foods rendered gluten free, and there are no definitive data about whether the small amount of prolamin found in these products is safe to consume. Nonetheless, the Codex Alimentarius Standard for gluten-free foods allows a certain amount of prolamin in foods designated gluten free, and these products have been used in many countries for several decades. Well-designed, scientifically sound studies are needed to help determine the amount of toxic prolamins, if any, that may be safely consumed by individuals with celiac disease. Until this research is conducted, dietitians in the United States should continue to advise their patients against the use of wheat starch and other foods rendered gluten free.

Celiac Disease↗
PubMed2001

Sensitive method for nontransferrin-bound iron quantification by graphite furnace atomic absorption spectrometry.

OBJECTIVE: To establish a sensitive method for measuring nontransferrin-bound iron (NTBI) in serum samples using graphite furnace atomic absorption spectrometry (GFAAS). DESIGN AND METHODS: Nontransferrin-bound iron (NTBI) was chelated using nitrilotriacetic acid (NTA) and then ultrafiltered according to the method employed by Singh et al. [1]. Serum ultrafiltrates were diluted eightfold with distilled water. NTBI from the Fe-NTA complex present in the serum ultrafiltrate was measured using GFAAS. RESULTS: Nontransferrin-bound iron (NTBI) and other parameters were measured in seven patients diagnosed with hereditary hemochromatosis by liver biopsy. Total serum iron, NTBI and transferrin saturation values (ranging from 87% to 90%) were elevated for three of the seven hemochromatosis patients tested before therapeutic phlebotomy. Six of the seven hemochromatosis patients had undergone phlebotomy and revealed normal total serum iron, NTBI and transferrin saturation values. Nine test subjects (not diagnosed with hemochromatosis) with abnormally high total serum iron and/or ferritin concentrations exhibited normal NTBI values (< or =0.14 micromol/L to 0.29 micromol/L). The detection limit was 0.1 micromol/L for a 25 microL injection volume. CONCLUSIONS: The GFAAS method presented here provides a sensitive assay to quantitate NTBI in serum samples. The method developed is 4 to 5 times more sensitive than the only other GFAAS method [2] and more than an order of magnitude more sensitive than other colorimetric methods [1,3]. Improvement in sensitivity over the other GFAAS method [2] may be accounted for by differences in sample preparation between this method and that of Nielsen et al. [2]. Serum ultrafiltrates in this study were diluted eightfold with distilled water and mixed with a magnesium nitrate matrix modifier before GFAAS analysis. NTBI results obtained from this study indicate that the plasma iron pool in hemochromatosis patients awaiting phlebotomy increases to a level at which transferrin's ability to bind iron becomes exhausted and elevated NTBI levels appear in the serum. NTBI can mediate the production of reactive oxygen species and may cause organ damage associated with iron overload.

Adult↗
PubMed2001

Kinetic form discrimination in Prader-Willi syndrome.

Discrimination of the shape of motion-produced forms generated by random elements (i.e. second-order stimuli varying in element density and temporal correlation) was tested in four groups: (1) subjects with Prader-Willi syndrome (PWS), chromosome 15q deletion subtype; (2) subjects with PWS, uniparental maternal disomy (UPD) subtype; (3) equivalent non-PWS controls; and (4) normal controls. The performance of the normal controls exceeded that of all other groups (78% correct, P < 0.009). The PWS deletion (66%) and the equivalent control groups (59%) did not differ (P < 0.95). The UPD group performed significantly less well (38%, P < 0.04) than all the other groups. The performance of the PWS deletion and equivalent control groups is consistent with other data indicating that these populations encounter difficulty meeting the processing demands posed by second-order stimuli. The inferior performance of the UPD group may be attributed to receiving two active alleles of a maternally expressed gene influencing neural development. One candidate is the ubiquitin protein ligase gene (UBE3A), which is maternally expressed only and localized to the 15q region. Other possibilities include the requirement of a paternally expressed gene, residual mosaic trisomy 15 in the brain tissue or complex interactions including specific ratios of differentially spliced gene products.

Adult↗
PubMed2001

Self-handicapping status, claimed self-handicaps and reduced practice effort following success and failure feedback.

BACKGROUND: Self-handicapping involves the strategic establishment of an impediment or obstacle to success prior to a performance situation which thereby provides a convenient excuse for poor performance. AIMS: The study sought to establish that relative to low trait self-handicappers, high trait self-handicappers exposed to failure in an intellectually evaluative situation will (a) pre-emptively claim more handicaps, and (b) behaviourally self-handicap through reduced practice effort, and (c) report greater anxiety and negative affect relative to low trait self-handicappers. SAMPLE: Participants were 72 undergraduate students, divided equally between high and low self-handicapping groups. METHOD: This study utilised a 2 (self-handicapping status: high, low) x 3 (performance feedback: fail, low task importance; fail, high task importance; success) between-subjects factorial design to investigate claimed and behavioural self-handicapping through reduced practice effort. This was done by manipulating performance outcome and perceived task importance. RESULTS: Relative to low trait self-handicappers, high trait high self-handicappers claimed more handicaps and engaged in greater behavioural self-handicapping following failure when working on tasks that were described as potentially diagnostic of low ability. While low self-handicappers internalised their success more than their failure in the high task importance condition, high self-handicappers were undifferentiated in their attributions across performance conditions. Greater anxiety and greater negative affect were also characteristic of high self-handicappers. CONCLUSIONS: The study highlights the self-protective benefit of self-handicapping in sparing the individual from conclusions of low ability, and the failure of high self-handicappers to fully internalise their success. These elements and the role of uncertain estimates of ability are discussed in considering implications for intervention.

Achievement↗
PubMed2001

Emergence of compulsive behavior and tantrums in children with Prader-Willi syndrome.

Many adults with Prader-Willi syndrome are affected by behaviors such as tantrums, skin-picking, and compulsions. The nature and extent of these problems suggest more attention be directed to their emergence in childhood. Our purpose was to investigate behavior problems in children with this syndrome and identify the age at which these behaviors emerge. Parents of children with Prader-Willi syndrome, Down syndrome, and those developing typically completed questionnaires. Children with Prader-Willi syndrome exhibited more compulsions, skin-picking, and tantrums than did the other groups. A discriminant analysis of behavior variables derived two statistically significant functions that were interpreted as developmental milestones and problematic behavior. These functions correctly predicted membership for 79% of grouped cases.

Child↗
PubMed2001

Experimental analyses of gene-brain-behavior relations: some notes on their application.

The fields of genetics and neuroscience are yielding findings useful in understanding complex behavior-environment relations. We believe that these developments in interdisciplinary basic research are of interest to applied behavior analysts because of the long history of basic findings being used by the readership of the Journal of Applied Behavior Analysis to improve everyday human activities. An awareness of contemporary developments in a range of basic research disciplines may facilitate the systematic replication of those functional relations in applied settings. In this context, we selectively review papers published in the Journal of the Experimental Analysis of Behavior and other basic research journals that relate to gene-brain-behavior relations.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects.

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.

Adolescent↗
PubMed2000

Phase I clinical trials of aroA aroD and aroA aroD htrA attenuated S. typhi vaccines; effect of formulation on safety and immunogenicity.

PBCC211, an aroA aroD derivative of S. typhi strain CDC10-80, was tested in phase I trials as a single dose typhoid fever vaccine. Three different vaccine preparations, reconstituted lyophilized bacteria, freshly grown bacteria or lyophilized bacteria reconstituted from sachets, were orally administered to a total of 86 adult volunteers. An aroA aroD htrA strain, PBCC222, was also tested in 38 volunteers. Formulation impacted on the determination of a safe and immunogenic dose; reconstituted lyophilized cultures required higher doses than the broth cultures to stimulate seroconversion. In general, doses which seroconverted the majority of group members produced undesirable symptoms regardless of attenuation or formulation. The inability to separate the presence of symptoms from achieving significant immunogenicity in these aroA aroD or aroA aroD htrA strains precludes their use as single dose typhoid vaccines in the formulations tested. Multiple doses of these strains at a lower, safe level may be effective as vectors for foreign antigens.

Adolescent↗
PubMed2000

Appetitive behavior, compulsivity, and neurochemistry in Prader-Willi syndrome.

Advances in genetic research have led to an increased understanding of genotype-phenotype relationships. Excessive eating and weight gain characteristic of Prader-Willi syndrome (PWS) have been the understandable focus of much of the research. The intense preoccupation with food, lack of satiation, and incessant food seeking are among the most striking features of PWS. It has become increasingly clear that the behavioral phenotype of PWS also includes symptoms similar to obsessive compulsive disorder, which in all probability interact with the incessant hunger and lack of satiation to engender the intense preoccupation and food seeking behavior that is characteristic of this disorder. Several lines of evidence suggest that genetic material on chromosome 15 may alter synthesis, release, metabolism, binding, intrinsic activity, or reuptake of specific neurotransmitters, or alter the receptor numbers and/or distribution involved in modulating feeding. Among the likely candidates are GABAnergic, serotonergic, and neuropeptidergic mechanisms. This review summarizes what is known about the appetitive behavior and compulsivity in PWS and discusses the possible mechanisms underlying these behaviors. MRDD Research Reviews 2000;6:125-130.

Brain↗
PubMed2000

Evaluation of the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent human adenovirus following intraprostatic administration in the mouse.

Adenovirus-mediated gene transfer may hold much promise in the treatment of human cancer. However, concerns regarding vector dissemination beyond the target tissue, particularly with replication-competent viruses, require an evaluation of the persistence of viral infection in collateral tissue and vector-associated toxicities. In addition, for indications such as prostate cancer, the proximity of the point of viral administration to organs of the male reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus. To address these concerns, the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent adenovirus (Ad5-CD/TKrep) following intraprostatic administration in the mouse was examined. Ad5-CD/TKrep (10(10) vp, 5 x 10(11) vp/kg) was injected intraprostatically on Day 1 of the study and its presence in the major organs of the male urogenital tract (prostate, testes, seminal vesicles, and urinary bladder) and liver was determined on Days 8 and 29. For comparison, a parallel group of animals was injected with the same dose of a related replication-defective Ad5-FGNR virus. To evaluate germ-line transmission, Ad5-CD/TKrep-injected males were mated to females on Days 8 and 29 and resulting embryos were examined for AdS-CD/TKrep viral DNA. Ad5-CD/TKrep viral DNA was detected in all major organs of the adult male urogenital tract and liver 7 and 28 Days postinjection. Interestingly, relative to the replication-defective Ad5-FGNR adenovirus, the replication-competent Ad5-CD/TKrep virus accumulated to a much greater level (approximately 300-fold) and persisted for a longer period of time in prostate, testes, and liver. This difference could not be explained on the basis of differences in viral infectivity, suggesting that the AdS-CD/TKrep virus may be capable of replicating in mouse tissues in vivo. In vitro infection of six mouse cell lines representing prostate, testes, and liver demonstrated that the Ad5-CD/TKrep virus was indeed capable of replicating in these mouse cell types, albeit with reduced efficiencies relative to human cells. Despite the fact that the Ad5-CD/TKrep vector persisted in the adult male gonads and may have replicated in vivo, we observed no evidence of germ-line transmission in 149 offspring examined. To evaluate the toxicity of combining Ad5-CD/TKrep viral therapy with CD/5-FC and HSV-1 TK/GCV suicide gene therapies as a prerequisite for a human trial, an escalating dose (10(8), 10(9), 10(10) vp) of Ad5-CD/TKrep was administered intraprostatically followed by 7 days of 5-FC and GCV double prodrug therapy. Although the virus persisted in the mouse urogenital tract and liver for up to 28 days postinjection, most of the toxicities observed were expected, minimal, and self-limiting. These results lead us to believe that intraprostatic administration of the Ad5-CD/TKrep virus to humans concomitant with double suicide gene therapy will be associated with acceptable toxicities and will not result in vertical transmission of viral-encoded genes through the germ line.

Adenoviridae↗
PubMed2000

Transcription of the transfer genes traY and traM of the antibiotic resistance plasmid R100-1 is linked.

Three separate traY deletion mutants of R100-1 were prepared by allele replacement. These mutants retained the ability to transfer at a level 100 times greater than R100 and 1/50 that of the parental R100-1. The mutants were complemented to normal R100-1 transfer levels by pDSP06, a multicopy traY clone. Comparison of transcripts initiated at the traY promoter, P(Y), by primer extension experiments showed that there was no detectable P(Y) activity in R100 and that the level of P(Y) activity in the traY deletion mutants was lower than that in R100-1. Similar measurements performed on RNA from a set of previously described traM deletion mutants showed that those traM deletion mutants that produced more traM and finM (M) transcripts than the parental R100-1 also produced more traY transcripts than R100-1 and that those traM mutants that produced fewer M transcripts than R100-1 also produced fewer traY transcripts than R100-1. We conclude that in R100, TraY regulates P(Y) activity and that transcripts originating in traM affect P(Y) activity.

Amino Acid Sequence↗