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Biomedical subjects

G Goodwin

Publications and source records attributed to G Goodwin.

At least 37 records · Page 2Linked to original sources
PubMed2000

A population-based study of personality in 34,000 sib-pairs.

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be efficiently used to ascertain phenotypically extreme individuals and increase power to detect genetic linkage. Phenotypes that can be reliably measured by questionnaire are of obvious utility for such selection strategies, as large numbers of individuals can be contacted without laborious individual interview. As the first step in developing a large randomly-ascertained family cohort in southwest England, a sample of 88,000 individuals, including more than 34,000 sibling pairs in 20,000 sibships, was administered the Eysenck Personality Questionnaire (EPQ) by commercial mailing. The sample age ranges were 20-67 years and comprised 59% males and 41% females. Descriptive properties of the EPQ scales are similar to those reported from other large family cohorts. Test-retest correlations on 1681 probands in the sample are substantial for the N-scale (r = 0.93), but somewhat more modest for the other scales (range r = 0.70-0.88). Phenotypic and sibling correlations correspond quite closely to those of twin studies.

Adult↗
PubMed1999

Expression of Drosophila trithorax-group homologues in chick embryos.

Mll, Brg1 and Brm are vertebrate homologues of Drosophila trithorax group (trxG) genes. We isolated chicken Mll cDNA clones, and examined patterns of Mll, Brg1 and Brm expression in chick embryos. All three genes were expressed from embryonic stage 2 onwards. Mll transcripts were just detectable in all tissues by in situ hybridization, with highest level in dorsal neural tube and notochord. Brg1 transcripts were readily detectable in all tissues, with highest levels in dorsal neural tube, dorsal trunk epithelium and limb bud epithelium and mesenchyme. Brm transcripts were more restricted, being found in dermomyotome, notochord, dorsal limb bud epithelium, eye and the roof and floor plates of the neural tube.

Animals↗
PubMed1999

Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus.

The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences. Deletion of the SNH domain results in a more active transcriptional activator, suggesting that this domain acts as an inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX translocation protein contributes a transcriptional repressor domain to the protein. Thus, the fusion protein has transcriptional activating and repressing domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of how the SYT protein activates gene transcription.

Amino Acid Sequence↗
PubMed1998

The high mobility group protein, HMGI-C.

HMGI-C is a nuclear phosphoprotein that contains three short DNA-binding domains (AT-hooks) and a highly acidic C-terminus. Interest in the protein has recently been stimulated by three observations: the expression of the gene is cell-cycle regulated, the gene is rearranged in a number of tumours of mesenchymal origin and mice that have both HMGI-C alleles disrupted exhibit the pygmy phenotype. These observations suggest a role for HMGI-C in cell growth, more specifically, during foetal growth since the protein is normally only expressed in embryonic tissues. It is likely that the HMGI-C protein acts as an architectural transcription factor, regulating the expression of one or more genes that control embryonic cell growth. Since HMGI-C binds to the minor groove of AT-rich DNA this interaction could be a target for minor groove chemotherapeutic agents in the treatment of sarcomas expressing the rearranged gene.

Amino Acid Sequence↗
PubMed1997

The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies.

The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the fusion of the SYT gene on chromosome 18 to either of two closely related genes SSX1 and SSX2 on chromosome X. The resulting chimaeric genes express SYT-SSX1 or SYT-SSX2 fusion proteins in which the C-terminal amino acids of SYT are replaced by amino acids from the C-terminus of the SSX proteins. Using green fluorescent protein fusions we demonstrate that the SYT, SSX and the SYT-SSX proteins are nuclear proteins. We demonstrate that whilst the SSX1 protein has a uniform nuclear distribution the SYT protein has a speckled distribution in the cell nucleus, and this distribution is retained with the SYT-SSX2 fusion protein. Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or spliceosomes it is possible that they represent a novel nuclear structure. Transfection of constructs expressing GAL4 fusion proteins demonstrate that the SYT domains present in the SYT-SSX fusion proteins can activate transcription of a luciferase reporter. It is proposed that the t(X;18) translocation results in the generation of an SYT-SSX transcriptional co-activator in which the addition of the C-terminal SSX domain to SYT provides a new interacting domain that redirects the SYT activation domain to different target promoters.

Cell Nucleus↗
PubMed1996

Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.

The specific chromosomal translocation t(9;22)(q22-31;q11-12) has been observed in the myxoid variant of human chondrosarcoma. In agreement with this observation we report that the EWS gene located at chromosome band 22q12 becomes fused to CHN, a member of the steroid/thyroid receptor gene superfamily located at 9q22-31, in a skeletal myxoid chondrosarcoma. CHN appears to be the human homologue of the rat gene NOR1, which was recently identified as a sequence overexpressed in rat brain cells undergoing apoptosis. Our results also indicate that the chimaeric EWS-CHN gene encodes a EWS-CHN fusion protein in which the C-terminal RNA-binding domain of EWS is replaced by the entire CHN protein, comprising a long N-terminal domain, a central DNA binding domain and a C-terminal ligand-binding/dimerisation domain.

Amino Acid Sequence↗
PubMed1996

Cortisol blockade of progesterone: a possible molecular mechanism involved in the initiation of human labor.

In most mammals, labor is heralded by progesterone withdrawal, which is believed to be related to the activation of multiple pathways leading to parturition. In humans, despite no decrease in placental progesterone production, activation of similar pathways preceding labor suggests the presence of an endogenous antiprogestin, which we reasoned might be cortisol, whose secretion from the fetal adrenal rises markedly at the end of human gestation. We report that in primary cultures of human placenta, cortisol is able to compete with the action of progesterone in the regulation of the corticotropin-releasing hormone (CRH) gene. CRH is a peptide highly expressed in human placenta at the end of gestation, which has been suggested to be involved in regulating the timing of parturition. These findings provide a model for functional progesterone withdrawal at the end of human pregnancy, which may be involved in the initiation of labor.

Cells, Cultured↗
PubMed1996

An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes.

We have isolated and analyzed human CTCF cDNA clones and show here that the ubiquitously expressed 11-zinc-finger factor CTCF is an exceptionally highly conserved protein displaying 93% identity between avian and human amino acid sequences. It binds specifically to regulatory sequences in the promoter-proximal regions of chicken, mouse, and human c-myc oncogenes. CTCF contains two transcription repressor domains transferable to a heterologous DNA binding domain. One CTCF binding site, conserved in mouse and human c-myc genes, is found immediately downstream of the major P2 promoter at a sequence which maps precisely within the region of RNA polymerase II pausing and release. Gel shift assays of nuclear extracts from mouse and human cells show that CTCF is the predominant factor binding to this sequence. Mutational analysis of the P2-proximal CTCF binding site and transient-cotransfection experiments demonstrate that CTCF is a transcriptional repressor of the human c-myc gene. Although there is 100% sequence identity in the DNA binding domains of the avian and human CTCF proteins, the regulatory sequences recognized by CTCF in chicken and human c-myc promoters are clearly diverged. Mutating the contact nucleotides confirms that CTCF binding to the human c-myc P2 promoter requires a number of unique contact DNA bases that are absent in the chicken c-myc CTCF binding site. Moreover, proteolytic-protection assays indicate that several more CTCF Zn fingers are involved in contacting the human CTCF binding site than the chicken site. Gel shift assays utilizing successively deleted Zn finger domains indicate that CTCF Zn fingers 2 to 7 are involved in binding to the chicken c-myc promoter, while fingers 3 to 11 mediate CTCF binding to the human promoter. This flexibility in Zn finger usage reveals CTCF to be a unique "multivalent" transcriptional factor and provides the first feasible explanation of how certain homologous genes (i.e., c-myc) of different vertebrate species are regulated by the same factor and maintain similar expression patterns despite significant promoter sequence divergence.

Amino Acid Sequence↗
PubMed1993

Munchausen's syndrome and organic brain disorder.

A case of Munchausen's syndrome was probably caused by brain damage sustained during a necessary cholecystectomy. Doctors should not be discouraged from seeking treatable disorder because of such patients' behaviour.

Abdominal Pain↗
PubMed1992

Intoxication and injury.

The relationship between alcohol use and injury severity was investigated in trauma patients admitted to a tertiary referral hospital during a 23-month period. Admission blood alcohol levels (BALs) were obtained on 427 trauma patients, who were stratified into three groups: those with no measurable blood alcohol, those within the legal limit of 100 mg/dL, and those over the legal limit or intoxicated. The no-alcohol group had significantly lower injury severity than the other two groups (p less than 0.001). Even when the BAL was well within the legal limit, injuries suffered by those in the alcohol-positive groups were more severe than those in the no-alcohol group. Confirmatory evidence of the effect of alcohol on injury severity was reflected by a 2.3% mortality in alcohol-negative patients compared with a 13.3% death rate in alcohol-positive patients (p less than 0.0001). To assess the potentially confounding effect of alcohol on injury scoring accuracy, we examined the change in Glasgow Coma Scale (GCS) scores following admission. No significant differences were found when admission GCS values were compared with GCS determinations made 24 hours following admission by separate observers. To correct for any potential bias as a tertiary referral center, repeat analysis with exclusion of transferred patients was done with essentially no change in results. Our data revealed a highly significant relationship between alcohol use, degree of injury, and resource consumption.

Adult↗
PubMed1992

Physician and consumer attitudes and behaviors regarding self-help health support groups as an adjunct to traditional medical care.

This study assessed the creditability of self-help health support groups as an adjunct to traditional medical care among a sampling of physicians (N = 120) and group members (N = 73) located in the Dallas/Ft. Worth Metropolitan area. Findings suggest a general lack of awareness of local groups among physicians, referral to only a few select groups, as well as little communication between health care professionals and their patients. Physicians in group practice, surgical specialties, and having never referred patients to support groups responded less favorably. Several benefits were reported by the group members, although for a majority their patient-physician relationship remained relatively unchanged.

Adult↗
PubMed1991

Low doses of the 5-HT1A receptor agonist 8-OH-DPAT increase ingestive behavior in late preweanling and postweanling, but not neonatal rat pups.

Late preweanling (postnatal day 17-18; P17-18) and postweanling (P28-29) Sprague-Dawley rat pups were tested in the presence of both mash and liquid diets following s.c. administration of 0, 0.03, 0.06, 0.1 or 0.5 mg/kg of the 5-HT1A receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Preweanling pups exhibited both a low dose stimulatory and high dose depressant effect of 8-OH-DPAT on mash-related ingestive behaviors, whereas postweanling rat pups were less sensitive to 8-OH-DPAT, exhibiting only an increase in mash ingestion within the dose range examined. In contrast, when neonatal (P3-4) rat pups were tested with milk across a dose range of 0.001-1.0 mg/kg 8-OH-DPAT, no increases in ingestion were seen, with lower doses in this range having no detectable effects and higher doses decreasing ingestion and mouthing. To the extent that low doses of 8-OH-DPAT increase feeding via preferential stimulation of 5-HT1A autoreceptors, these data suggest that neonates may lack functional 5-HT1A autoreceptors, with these receptors maturing by the late preweanling period.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Enhancer dependent expression of the chicken beta-hatching globin gene during erythroid differentiation.

The activity of the chicken beta H globin gene promoter has been analysed in functional assays in both chicken and murine erythroleukaemia cells. Sequences between -251 and -146 bp, in the presence or absence of the chicken beta globin locus enhancer, strongly repress transcription in erythroid cells before and after the induction of terminal differentiation. A 50 bp sequence (-98 to -146 bp), which contains adjacent cGATA-1 and NF1 protein binding sites in vitro, and which is bound by non-histone protein in vivo, is essential for full promoter activity. Mutagenesis studies indicate that both protein binding sites are required. During terminal differentiation, both the absence of repressor and the presence of the erythroid enhancer are required for maximal promoter activity, suggesting that the beta A, beta epsilon and beta H globin gene promoters compete for the enhancer during development.

Animals↗
PubMed1991

The epidemiologic features of nosocomial infections in patients with trauma.

Sepsis is a major cause of morbidity and mortality in patients with trauma. To elucidate factors that might lead to infection, we studied the epidemiologic characteristics of nosocomial infections in our patient population with trauma. During a 3.5-year period, 2496 patients were entered into our hospital trauma registry and cross-matched with hospital infection control surveillance information. Two hundred twenty-nine patients with trauma and nosocomial infections were identified (9.2%), a figure that was nearly twice the nosocomial infection rate for the general hospital population. The majority of those infected were either orthopedic (51%), general surgical (25%), or neurosurgical (13%) patients. The most common sites of first infection were urinary tract (61%) or respiratory system (14%). Patients developing nosocomial infections were significantly older and had a higher Injury Severity Score than those who did not. Injury site was related to risk of infection with injuries of the spine, chest, and extremity showing the most significant relationship. The length of stay as well as hospital charges were significantly related to the occurrence of infectious complications. By determining the patient with trauma at risk for infection, treatment strategies can be designed to minimize septic complications.

Accidents↗
PubMed1991

Blunting of neuroendocrine responses to infusion of L-tryptophan in women with perimenstrual mood change.

The neuroendocrine response to L-tryptophan infusion was measured at two stages of the menstrual cycle, premenstrually and postmenstrually, in 13 women with and 13 women without premenstrual depression (the MC and NMC groups respectively). Previous studies have shown that in non-depressed women, this challenge test results in an increase in circulating prolactin and growth hormone. In depressed women both responses are blunted. In this study the growth hormone and cortisol responses were smaller in the MC group than the NMC group on both occasions. The prolactin response was blunted premenstrually compared with postmenstrually in both groups. These findings suggest that women who experience premenstrual depression may have neuroendocrine abnormalities throughout the cycle. The neurotransmitter abnormalities reflected in these altered endocrine responses appear to interact with neuroendocrine changes that normally occur premenstrually resulting in a vulnerability to depression at that phase of the cycle.

Adolescent↗
PubMed1991

Human safety of lamotrigine.

The clinical safety of lamotrigine (LTG), assessed in four completed randomized, double-blind, placebo-controlled crossover trials and an interim analysis of 27 12-month open studies, is discussed. LTG was added to existing antiepileptic drugs (AEDs) of adult patients with refractory epilepsy, using a twice-daily regimen. In the pooled data from the four double-blind studies (n = 92), the incidence of adverse experiences with LTG and placebo did not differ significantly. Two patients were withdrawn on LTG due to adverse experiences (one rash, one nausea and vomiting). In the open studies (pooled data; n = 572) the most commonly reported adverse experiences were dizziness, diplopia, somnolence, headache, ataxia, and asthenia (10-14% incidence). Forty-nine patients (8.6%) were withdrawn with adverse events, most commonly for rash (2.3%). No patients were withdrawn from any of the studies with physical, neurological, or ECG abnormalities thought attributable to LTG treatment. Laboratory measures, vital signs, and weight did not show any consistent changes of clinical significance, and no significant changes in plasma concentrations of concomitant AEDs after the addition of LTG were observed.

Anticonvulsants↗