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Biomedical subjects

J Gray

Publications and source records attributed to J Gray.

At least 109 records · Page 6Linked to original sources
PubMed2000

Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

BACKGROUND: While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. METHODS: EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. RESULTS: There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. CONCLUSIONS: These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

Adult↗
PubMed2000

Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin.

PURPOSE: To evaluate the toxicity, response rate and short-term survival associated with the chemotherapy combinations of docetaxel plus cisplatin or carboplatin when used for the treatment of patients with metastatic carcinoma of unknown primary site. PATIENTS AND METHODS: Twenty-six patients were treated with docetaxel 75 mg/m2 i.v. and cisplatin 75 mg/m2 i.v. given every three weeks (study A) and subsequently, 47 patients were treated with docetaxel 65 mg/m2 and carboplatin (AUC dose = 6) every three weeks (study B). Stable or responding patients received a maximum of eight courses of therapy. Patients who were known to be in treatable subset groups were excluded from these trials. The majority of patients had two or more sites of metastasis; about 45% had adenocarcinoma and 50% poorly differentiated carcinoma. RESULTS: In study A, 6 of 23 (26%) assessable patients had a major response to therapy. The median survival was eight months and one-year survival 42%. Seven patients were removed from the study early for grade 3 or 4 nausea and vomiting. In study B, 9 of 40 assessable patients (22%) had a major response to therapy. Median survival was eight months and one-year survival 29%. Toxicity associated with this regimen was predominantly myelosuppression. Comparisons of the two sequential trials showed no differences in response rates or survivals (P = 0.75). CONCLUSIONS: Docetaxel and cisplatin (study A) is an active combination in carcinoma of unknown primary site, but associated with substantial gastrointestinal toxicity. A combination of docetaxel plus carboplatin (study B) is better tolerated and produced a similar response rate, median survival and one-year survival. Comparative phase III trials will be necessary to unequivically prove a survival advantage for any form of therapy in these patients. However, the survival for patients with carcinoma of unknown primary site receiving docetaxel-based chemotherapy is comparable to the survivals for several other groups of advanced cancer patients, such as non-small cell lung cancer, receiving various types of chemotherapy.

Adult↗
PubMed2000

A comparison of methods currently used in clinical practice to estimate familial breast cancer risks.

BACKGROUND: With the identification of genes predisposing to hereditary breast cancer, the accurate and consistent estimation of a woman's risk of developing breast cancer based on her family history is of paramount importance if national service guidelines are to be developed. PATIENTS AND METHODS: The residual lifetime risk of developing breast cancer was estimated for 200 women attending a breast cancer genetic assessment clinic by three different methods currently in use in the UK. Risks were computed on the basis of the Cancer and Steroid Hormone (CASH) study data and were classified as 'low/moderate' (<20%) or 'high' (>20%). These risk categories are representative of those currently used to allocate surveillance and genetic testing. Risks were then compared to estimates derived by other methods used in current clinical practice, including those of Houlston and Murday. RESULTS: The CASH data-based method ascribed 27% to the high risk category, as compared to 53% for the combined Houlston and Murday methods. A method based on the number of affected relatives alone ascribed only 14% to the high risk category. Overall, 108 (54%) women were placed in the same risk category by all three methods. CONCLUSIONS: This study demonstrates that there is a significant degree of variability between methods currently used to estimate breast cancer risk which has serious implications for individual patient management, service provision and multicentre studies evaluating the benefits of genetic testing for breast cancer susceptibility.

Adult↗
PubMed2000

Linkage analysis in an autosomal dominant 'zonular nuclear pulverulent' congenital cataract, mapped to chromosome 13q11-13.

PURPOSE: To determine by linkage analysis the chromosomal locus responsible for autosomal dominant congenital cataract (ADCC) in a four-generation Welsh pedigree. METHODS: The family pedigree was traced through two members of the family attending the hospital for treatment of their cataracts. Twenty-five members of the family were examined ophthalmologically and blood was collected with consent for genetic linkage analysis. RESULTS: Fifteen members of this family were known to have bilateral congenital cataracts, of whom 11 had a cataract extraction prior to examination. The youngest member of the pedigree was 5 years old and the oldest was 78 years old. Four children, unoperated at the time of this study, had a phenotypically identical morphology of their zonular pulverulent congenital cataracts. The known loci for congenital cataract were excluded. Significant lod scores for markers in the 13q11-13 region were detected with a Zmax of 3.59 D13S1236 (theta = 0.00). CONCLUSIONS: We report linkage of an ADCC of the zonular pulverulent type to chromosome 13q11-13 in a four-generation family.

Adolescent↗
PubMed2000

The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1).

The endogenous cannabinoid anandamide was identified as an agonist for the recombinant human VR1 (hVR1) by screening a large array of bioactive substances using a FLIPR-based calcium assay. Further electrophysiological studies showed that anandamide (10 or 100 microM) and capsaicin (1 microM) produced similar inward currents in hVR1 transfected, but not in parental, HEK293 cells. These currents were abolished by capsazepine (1 microM). In the FLIPR anandamide and capsaicin were full agonists at hVR1, with pEC(50) values of 5. 94+/-0.06 (n=5) and 7.13+/-0.11 (n=8) respectively. The response to anandamide was inhibited by capsazepine (pK(B) of 7.40+/-0.02, n=6), but not by the cannabinoid receptor antagonists AM630 or AM281. Furthermore, pretreatment with capsaicin desensitized the anandamide-induced calcium response and vice versa. In conclusion, this study has demonstrated for the first time that anandamide acts as a full agonist at the human VR1.

Amides↗
PubMed2000

An exploratory population-based case-control study of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a disease of unknown etiology, with unexplained geographical variation. Various exposures have been suggested as triggers for disease development-possibly in susceptible individuals, but the evidence was not always well founded. We therefore conducted a population-based case-control study in Northeast England to investigate these and other exposures. All cases incident during 1993 to 1995 in a defined area of Northeast England were identified, and age- and sex-matched population controls were identified from primary care population registers. Cases and controls were sent postal self-completion questionnaires covering medical history and lifestyle. Information was received from 100 cases and 223 controls. The familial tendency of PBC was found to be less marked than has been claimed: Only weak associations were found with other autoimmune diseases. Among factors considered previously, no significant associations were found with surgical procedures, events in pregnancy, past infections, vaccinations, and medications. No significant associations were found for previously unconsidered lifestyle factors (drinking alcohol, previous pets, or stressful events), but there was an unexpected association with past smoking (ever smoked: 76% in cases vs. 57% in controls, odds ratio 2.4; smoked for 20 years or more: 64% vs. 35%, odds ratio 3.5). There were also unexpected significant associations with psoriasis (13% in cases vs. 3% in controls, odds ratio 4.6) and eczema (3% in cases vs. 11% in controls, odds ratio 0. 13). These findings merit further investigation.

Adult↗
PubMed2000

Male cancer: a qualitative study of male breast cancer.

Breast cancer is a rare condition in males. There is a dearth of information about the psychological and social impact of this condition. Data from six in-depth interviews with men who had breast cancer identified seven major issues. These were associated with delay in diagnosis, shock, stigma, body image, causal factors, the provision of information and emotional support. The findings from this small study suggest that there are psychological and social factors for men diagnosed with breast cancer which have implications for their care and management. The recommendations arising from this study are the development of a structured education programme aimed at all primary health-care professionals; with availability of pre and postoperative gender-specific information to alleviate the potential psychological problems associated with the diagnosis; and provision of appropriate support/counselling services for partners of patients.

Journal Article↗
PubMed2000

Radiation doses to members of the public near to Sellafield, Cumbria, from liquid discharges 1952-98.

Liquid wastes containing low levels of radioactivity have been discharged to the Irish Sea from the nuclear fuel reprocessing site at Sellafield since operations began in the early 1950s, and monitoring of radioactivity in foodstuffs has been undertaken over many years. Based on the best available monitoring data, supplemented by modelled values where necessary, doses to local critical groups have been reassessed using the most recent dosimetry. Contemporary habits data have been used where available, again supplemented by assumed habits where necessary. During the 1950s and 1960s the highest doses were received by individuals consuming Cumbrian Porphyra as laverbread, and peak doses around 0.8 to 1.0 mSv year(-1) have been estimated. During the 1970s and 1980s the critical exposure group switched to consumers of local fish and shellfish, with peak doses possibly reaching 2.5 to 3.0 mSv year(-1). Latterly, doses to all marine-related groups have declined to less than 150 to 200 microSv year(-1). At all times, doses have been within the appropriate limits set for members of the public.

Environmental Exposure↗
PubMed2000

A European multicenter study of immunoblotting in serodiagnosis of lyme borreliosis.

A European multicenter study of immunoblotting for the serodiagnosis of Lyme borreliosis showed considerable variation in results obtained from tests with a panel of 227 serum samples. Six laboratories used different immunoblot methods, and a wide range of bands was detected in all the assays. Multivariable logistic regression analysis of data from individual laboratories was used to determine the most discriminatory bands for reliable detection of antibodies to Borrelia burgdorferi sensu lato. These bands were used to construct individual interpretation rules for the immunoblots used in the six laboratories. Further analysis identified a subset of eight bands, which were important in all the laboratories, although with variations in significance. Possible European rules, all closely related, were formulated from these bands, although there was no single rule that gave high levels of sensitivity and specificity for all the laboratories. This is a reflection of the wide range of methodologies used, especially the use of different species and strains of B. burgdorferi sensu lato. The panel of European rules provides a framework for immunoblot interpretation which may be adapted in relation to the characteristics of Lyme borreliosis in local areas.

Antibodies, Bacterial↗
PubMed2000

A model protocol evaluating the introduction of genetic assessment for women with a family history of breast cancer.

Randomised controlled trials allow comparisons to be made between different models of service delivery, but have not been used in the field of clinical genetics. With the advent of clinical governance, the evidence provided by such trials will be increasingly important in informing and shaping clinical genetics practice. The TRACE project (Trial of genetic assessment in breast cancer) is a randomised controlled trial of genetic assessment for women who are at increased risk of breast cancer because of their family history. The absence of cancer genetics service provision in Wales before this study gave a window of opportunity in which this important trial could be conducted. The present paper describes how TRACE will provide crucial evidence regarding the psychosocial as well as resource implications of adding individualised genetic assessment, genetic counselling, and (where appropriate) gene testing to typical advice and surveillance from a hospital breast clinic. In addition, it is anticipated that TRACE will represent a model for future trials of service delivery in the increasing number of complex genetic disorders where evidence on the economic implications of screening and management is currently limited.

Adult↗
PubMed2000

Why do women attend familial breast cancer clinics?

The increasing demand for genetic assessment for familial breast cancer has necessitated the development of cancer genetics services. However, little is known about the factors motivating the client population likely to approach these services. A cross sectional questionnaire survey of 1000 women with a family history of breast cancer was conducted to identify self-reported reasons for attending a familial breast cancer clinic and possible differences in the characteristics of women who were attending for diverse reasons. Before attendance at clinic, 833 women completed a baseline questionnaire (83% response rate). Women who gave personal risk (n=188), awareness of a family history (n=120), risk to family members (n=84), reassurance (n=69), genetic testing (n=65), breast screening (n=46), or prevention (n=39) as their main reason for attending were compared on demographic and medical variables, and on psychological variables including general anxiety, cancer worry, perceived risk, and attitudes towards prophylactic surgery and genetic testing. Important differences in the psychological characteristics of these groups were found, which were unrelated to reported family history. In particular, women who primarily wanted genetic testing felt extremely vulnerable to developing breast cancer, were more likely to be considering prophylactic surgery, and perceived fewer limitations of testing. Those who primarily wanted reassurance were highly anxious about the disease. We recommend that cancer genetics services take into consideration the informational and psychological needs and concerns of their client group.

Ambulatory Care Facilities↗
PubMed2000

A biologically active single chain human chorionic gonadotropin analog with altered receptor binding properties.

hCG is a heterodimer consisting of an alpha-subunit common among all members of the glycoprotein hormone family, LH, FSH, and TSH, and a unique beta-subunit responsible for receptor specificity. Biologically active single chain analogs of these hormones have been engineered in which the C-terminus of the beta-subunit was fused to the N-terminus of the alpha-subunit (N-beta-alpha-C) either with or without a linker such as the hCGbeta C-terminal peptide (CTP). This tandem order of subunits was chosen based on studies suggesting that the N-terminal region of hCGbeta and particularly the C-terminal region of the alpha-subunit are important in receptor binding and activation. Single chain hCG (YhCG1) can, in turn, be fused to the LH receptor to yield a hormone-receptor complex that is biologically active in transfected cells. Herein, we report the construction of a new single chain hCG analog (YhCG3) in which the C-terminus of the alpha-subunit is fused to the N-terminus of hCGbeta via a CTP (N-alpha-CTP-beta-C). Compared with YhCG1, this analog binds receptor with a 25- to 30-fold lower affinity, but, surprisingly, is capable of stimulating intracellular cAMP levels to the same extent. Furthermore, YhCG3 can be covalently linked to its receptor to produce a biologically active complex that results in elevated levels of basal cAMP in transfected cells. These results suggest that free N- and C-termini of hCGbeta and the alpha-subunit, respectively, are not essential for receptor binding and activation and that YhCG3 is in a more efficacious conformation for receptor activation than YhCG1.

Blotting, Western↗
PubMed2000

GENESiS: creating a composite index of the vulnerability to anxiety and depression in a community-based sample of siblings.

There is considerable evidence for a unitary and dimensional view of the genetic vulnerability to symptoms of anxiety and depression. The GENESiS (Genetic Environmental-Nature of Emotional States in Siblings) Study aims to use a multivariate approach to detect genetic loci that contribute to individual differences in this vulnerability dimension. The study used the UK General Practice Research Framework to generate a community-based sample of siblings. Questionnaire measures of anxiety/depression included the short form of the neuroticism scale from the revised Eysenck Personality Questionnaire (EPQ-N), the General Health Questionnaire (GHQ-12), and the anxious arousal and high positive affect subscales from the Mood and Anxiety Symptoms Questionnaire (MASQ-AA and MASQ-HPA). Genetic model-fitting of 2658 unselected sibships provided evidence for a single common genetic (familial) factor that accounted for a substantial proportion of the genetic variances and covariances of these four measures. Using the parameter estimates of this model, we constructed a composite index of this common genetic factor. This index, which has a sib correlation of 0.22, will be used as a quantitative phenotype in the molecular genetic phase of GENESiS.

Adult↗
PubMed2000

In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002).

Phosphatidylinositol 3-kinase (PI3-K) induces mitogenesis, cell growth, and cell transformation. Amplification of the gene encoding the P110alpha subunit likely is an important event in ovarian cancer progression, and PI3-K inhibitors are possible therapeutic agents for this disease. We evaluated effects of LY294002, a potent inhibitor of PI3-K, on growth of ovarian carcinoma in vivo and in vitro, and on ascites formation in vivo. Athymic mice were inoculated i.p. with the ovarian cancer cell line OVCAR-3. Seven days after inoculation, mice were treated with or without LY294002 (100 mg/kg of body weight) for 3 weeks. Body weight and abdominal circumference were measured twice weekly. At the end of the experiment, mice were sacrificed, ascites volume was measured, and tumors were excised. Mean tumor burden in the LY294002-treated group was reduced by approximately 65% versus controls. Virtually no ascites developed in the treatment group; mean volume of ascites in controls was 3.3 +/- 0.38 ml. OVCAR-3 cells also were cultured in vitro without and with LY294002 (1, 5, and 10 microM) for 24 h. The number of cells in 1, 5, and 10 microM LY294002-treated wells was reduced by 27, 56, and 75%, respectively, versus controls. In vivo and in vitro morphological studies demonstrated that LY294002 induced marked nuclear pyknosis and diminished cytoplasmic volume in the tumor cells, confirmed as apoptosis. Thus, LY294002 significantly inhibits growth and ascites formation of ovarian carcinoma in vivo and markedly inhibits ovarian cancer cell proliferation in vitro, suggesting an important role of PI3-K inhibitors as a potentially useful treatment for women with ovarian carcinoma.

Animals↗