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Biomedical subjects

B Cox

Publications and source records attributed to B Cox.

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

Guidelines for the management of women with abnormal cervical smears 1998.

Four important changes have been introduced in the revised guidelines for the management of women with abnormal cervical smears, 1998. 1. For the purposes of management, atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS) have been included with low grade squamous intraepithelial lesions (LSIL/CIN1/HPV) except where the smear raises the possibility of a high grade squamous intraepthelial lesion (HSIL) or favours glandular dysplasia. 2. Women with low grade cytological and histological intraepithelial abnormalities will, after initial follow-up, revert to three yearly screening. 3. Requirements for those practising colposcopy have been defined. 4. A formal review of all cases of invasive cervical cancer is advocated.

Adenocarcinoma↗
PubMed2000

Search for the weak decay of a lightly bound H0 dibaryon

We present results of a search for a new form of hadronic matter, a six-quark, dibaryon state called the H0, a state predicted to exist in several theoretical models. Analyzing data collected by experiment E799-II at Fermilab, we searched for the decay H0-->Lambdappi(-) and found no candidate events. We place an upper limit on [B(H0-->Lambdappi(-))dsigma(H)/dOmega]/(dsigma(Xi)/dOmega) and, in the context of published models, exclude the region of lightly bound mass states just below the LambdaLambda mass threshold, 2.194<M(H)<2.231 GeV/c(2), with lifetimes from approximately 5x10(-10) sec to approximately 1x10(-3) sec.

Journal Article↗
PubMed2000

An evaluation of the National Cervical Screening Programme Otago site.

AIM: To evaluate progress of the Otago Cervical Screening Programme towards achieving its goal of reducing cervical cancer incidence and mortality using data routinely collected by the National Cervical Screening Register (NCSR), and to investigate whether all data required for this task are available from the NCSR. METHOD: Non-identifying data for Otago women aged 20-69 years were obtained from the New Zealand National Cervical Screening Register for the period 1 July 1993 to 30 June 1996. For each five-year age group, proportion screened in three years, short interval re-screening estimates and age-specific reporting rates for squamous atypia of uncertain significance (ASCUS), low-grade intraepithelial lesions (LGIL) and high-grade intraepithelial lesions (HGIL) were calculated. Age-specific reporting rates were also calculated for 20-69 year-old New Zealand women for the same period and compared to the Otago rates. RESULTS: The proportion of eligible women screened was 82.5%, slightly less than the target 85%. Women aged 55 years or more were underscreened, short interval rescreening was more common among younger women, age-specific reporting rates for ASCUS, LGIL and HGIL had increased since 1991/92, and the rate of HGIL was higher than expected in the 20-34 year age group. CONCLUSIONS: In order to maximise the effectiveness and efficiency of the Otago Cervical Screening Programme, it is recommended that participation amongst older women be increased and frequent screening be reduced in the younger age groups. Unexpected elevated rates of HGIL amongst 20-34 year-old women were not adequately explained and require further investigation. Not all data required for an outcome evaluation were available through the NCSR.

Adult↗
PubMed2000

Observation of CP violation in K(L)-->pi(+)pi(-)e(+)e(-) decays

We report the first observation of a manifestly CP violating effect in the K(L)-->pi(+)pi(-)e(+)e(-) decay mode. A large asymmetry was observed in the distribution of these decays in the CP-odd and T-odd angle straight phi between the decay planes of the e(+)e(-) and pi(+)pi(-) pairs in the K(L) center of mass system. After acceptance corrections, the overall asymmetry is found to be [13.6+/-2. 5(stat)+/-1.2(syst)]%. This is the largest CP-violating effect yet observed when integrating over the entire phase space of a mode and the first such effect observed in an angular variable.

Journal Article↗
PubMed2000

Cloning and expression throughout mouse development of mfat1, a homologue of the Drosophila tumour suppressor gene fat.

We present the entire sequence of the mouse Fat orthologue (mFat1), a protein of 4,588 amino acids with 34 cadherin repeats, 27 potential N-glycosylation sites, five EGF repeats and a laminin A G-motif in its extracellular domain. A single transmembrane region is followed by a cytoplasmic domain containing putative catenin-binding sequences. mFat1 shows high homology to human FAT and lesser homology to Drosophila Fat. The sequence of this giant cadherin suggests that it is unlikely to have a homophilic adhesive function, but may mediate heterophilic adhesion or play a signalling role. Expression analysis shows that the mfat1 gene is expressed early in pre-implantation mouse development, at the compact eight cell stage. Whole-mount and section in situ analyses show that transcripts are widely expressed throughout post-implantation development, most notably in the limb buds, branchial arches, forming somites, and in particular in the proliferating ventricular zones in the brain, being down-regulated as cells cease dividing. RT-PCR detects widespread expression in the adult suggesting a role in proliferation and differentiation of many tissues and cell types.

Amino Acid Sequence↗
PubMed2000

MHC class II associations with autoantibody and T cell immune responses to the scleroderma autoantigen topoisomerase I.

Topoisomerase I (topo I) is a major autoantigen recognized by autoantibodies in about 30% of sera from patients with systemic sclerosis (SSc). Certain HLA-DRB1 and HLA-DQB1 alleles have been reported to be associated with autoantibody and T-cell responses to topo I suggesting a T-cell dependent process. We have examined the MHC class II allele associations with anti-topo I antibodies in 16 patients with SSc compared to 250 healthy controls. Furthermore, we have studied the T cell responses to a recombinant full-length topo I molecule purified from a baculovirus expression system in eight patients with SSc and eight controls (five healthy and three with autoimmune disease). HLA-DR5 was significantly increased in patients with anti-topo I antibodies (P< 0.02). Proliferative peripheral blood mononuclear cell (PBMC) responses to soluble topo I were present in nine of 16 individuals (four of eight with SSc and five of eight controls), including the three SSc patients with anti-topo I antibodies. Homozygosity for HLA DQB1:30:Y alleles was present in five of nine responders (P< 0.03) compared to none of the non-responders. Our findings support the notion that the MHC class II background influences the ability to generate an autoimmune response to intracellular autoantigens to which the immune system may not have been tolerized. Additional factors associated with the generation of autoantibodies appear to be more intimately associated with the development of SSc.

Alleles↗
PubMed2000

Calcium channel blockers and pain therapy.

This review focuses on the advances in the development of N-type calcium channel blockers as analgesic agents over the last 2 years. Firstly, it highlights the clinical progress with SNX-111 (Ziconotide; Elan Pharmaceuticals, Smithfield, RI) and then secondly, it outlines the various approaches being taken by researchers to design orally active, selective, small molecule modulators without the perceived disadvantages associated with SNX-111.

Animals↗
PubMed2000

Assessment of anxiety in older adults: a community-based survey and comparison with younger adults.

The reliability and validity of existing anxiety self-report scales in elderly adults has not been adequately established, and the phenomenology of anxiety in older adults is largely unknown. In the present study, three anxiety scales and measures of depression and somatization were used to compare symptoms between older (n = 84, mean age = 75.3) and younger (n = 48, mean age = 40.3) community-dwelling adults. Results showed that the anxiety scales demonstrated good internal consistency in both age groups, although the reliabilities of the Fear Questionnaire subscales ranged from poor to good. Convergent and divergent validity were found to be variable in the older group, but this may reflect differences in anxiety as it occurs in older persons rather than psychometric problems. Anxiety symptoms did not vary with age, and levels of anxiety also remained constant. However, gender differences were found only within the older age group, with women reporting more anxiety than men. Findings are discussed with respect to current conceptualizations of anxiety in older people, as well as implications for future research.

Adult↗
PubMed2000

Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies.

Mixed lymphohematopoietic chimerism can be induced in mice with bone marrow transplantation (BMT) after a nonmyeloablative preparative regimen that includes cyclophosphamide, anti-T-cell antibody therapy, and thymic irradiation. These mixed chimeras are resistant to the induction of graft-versus-host disease (GVHD) after delayed donor leukocyte infusions (DLIs), despite a potent lymphohematopoietic graft-versus-host reaction that converts the mixed chimeric state to a full donor one. Based on this animal model, we initiated a trial of nonmyeloablative therapy with HLA-matched or -mismatched donor BMT and DLI for refractory hematologic malignancies. Twenty-one of 36 patients enrolled in this trial received a genotypically (n = 20) or phenotypically (n = 1) HLA-matched donor transplant; results reported here are for those patients only. Preparative therapy consisted of cyclophosphamide in doses of 150 to 200 mg/kg; peritransplant antithymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal radiation therapy); and cyclosporine. Eighteen of 20 evaluable patients developed persistent mixed lymphohematopoietic chimerism as defined by >1% donor peripheral white blood cells until at least day 35 posttransplantation. Ten patients received prophylactic DLI beginning 5 to 6 weeks after BMT for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-leukemia effect. Fourteen of 20 evaluable patients (70%) achieved an antitumor response; 8 of these responses were complete, and 6 were partial. Of the 8 evaluable patients who received prophylactic DLI, 6 showed conversion to full donor chimerism. Five of the 9 evaluable patients (56%) who received prophylactic DLI achieved a complete response, compared with 3 of 11 patients (27%) who did not receive prophylactic DLI. Currently 11 patients are alive, and 7 of these are free of disease progression at a median follow-up time of 445 days (range, 105-548 days) posttransplantation. Transplantation-related complications included cyclophosphamide-induced cardiac toxicity in 3 of 21 patients (14%) and grade II or greater GVHD in 6 patients (29%). One patient (5%) died from a complication of BMT, and 1 patient (5%) died from GVHD after 2 prophylactic DLIs were given for conversion of chimerism. In summary, mixed lymphohematopoietic chimerism was reproducibly induced after a novel nonmyeloablative preparative regimen incorporating chemotherapy, peritransplant antithymocyte globulin, and thymic irradiation, allowing for early administration of DLI in 10 of 21 patients. After treatment, striking antitumor responses were observed in the majority of patients with chemotherapy-refractory hematologic malignancies.

Adult↗
PubMed2000

Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.

Retigabine is a novel anticonvulsant with an unknown mechanism of action. It has recently been reported that retigabine modulates a potassium channel current in nerve growth factor-differentiated PC12 cells (), however, to date the molecular correlate of this current has not been identified. In the present study we have examined the effects of retigabine on recombinant human KCNQ2 and KCNQ3 potassium channels, expressed either alone or in combination in Xenopus oocytes. Application of 10 microM retigabine to oocytes expressing the KCNQ2/3 heteromeric channel shifted both the activation threshold and voltage for half-activation by approximately 20 mV in the hyperpolarizing direction, leading to an increase in current amplitude at test potentials between -80 mV and +20 mV. Retigabine also had a marked effect on KCNQ current kinetics, increasing the rate of channel activation but slowing deactivation at a given test potential. Similar effects of retigabine were observed in oocytes expressing KCNQ2 alone, suggesting that KCNQ2 may be the molecular target of retigabine. Membrane potential recordings in oocytes expressing the KCNQ2/3 heteromeric channel showed that application of retigabine leads to a concentration-dependent hyperpolarization of the oocyte, from a resting potential of -63 mV under control conditions to -85 mV in the presence of 100 microM retigabine (IC(50) = 5.2 microM). In control experiments retigabine had no effect on either resting membrane potential or endogenous oocyte membrane currents. In conclusion, we have shown that retigabine acts as a KCNQ potassium channel opener. Because the heteromeric KCNQ2/3 channel has recently been reported to underlie the M-current, it is likely that M-current modulation can explain the anticonvulsant actions of retigabine in animal models of epilepsy.

Animals↗
PubMed2000

Cutaneous malignant melanoma in New Zealand: trends by anatomical site, 1969-1993.

BACKGROUND: Site-specific trend analysis is probably the most effective method available for assessing how the long-term trend in melanoma rates relates to changes in sun exposure and behaviour. New Zealand has very high incidence of and mortality from melanoma and the fraction of melanoma cases and deaths with a site specified has been comparatively high. METHODS: Trends in incidence and mortality from melanoma in New Zealand were analysed between 1969 and 1993, by sex and body site. A graphical representation of the trend by birth-cohort and age-period-cohort modelling were used. RESULTS: For all sites combined, the annual increase in incidence was 6.7% (95% CI : 6.3-7.1%) in men and 3.1% (95% CI : 2.3-3.7%) in women. The increase was significantly greater at each site for males. The largest increases occurred for the upper limbs in males (7.3% a year) and the trunk in females (3.8% a year). Incidence rates slowed appreciably in the later years (currently about 26/100 000 for each sex) and no further increase in lifetime risk of melanoma was observed among post World War II generations. Mortality trends paralleled those for incidence with a 25-year gap, with a more modest rate of increase (2-3% per annum for each sex), essentially due to the increased risk among generations born up to 1919 or 1924. Age-standardized death rates have now stabilized in New Zealand at about 5.5/100 000 (men) and 3.2/100 000 (women). Trends between cohorts were the most marked for sites with a likely intermittent pattern of exposure, and were consistent overall for the trunk and the limbs. CONCLUSIONS: Results support the hypothesis that changes in lifestyle factors resulted in a pattern of carcinogenic exposures that explains both the upsurge in melanoma in the last few decades and the current levelling off in incidence.

Adult↗
PubMed1999

Determination of glutamic acid decarboxylase 65 peptides presented by the type I diabetes-associated HLA-DQ8 class II molecule identifies an immunogenic peptide motif.

Particular HLA class II allelic sequences are associated with susceptibility to type I diabetes. To understand the mechanism, knowledge of the molecular nature of the specific TCR/peptide/class II interactions involved in the disease process is required. To this end, we have introduced the diabetes-associated human class II HLA-DQ8 allele (DQA1*0301/DQB1*0302) as a transgene into mice and analyzed T cell responses restricted by this molecule to an important Ag in human diabetes, human glutamic acid decarboxylase 65. Hybridomas were used to determine the particular peptides from this Ag presented by HLA-DQ8 to T cells and to map the core minimal epitopes required for T cell stimulation. Analysis of these core epitopes reveals a motif and relevant features for peptides that are immunogenic to T cells when presented by HLA-DQ8. The major immunogenic epitopes of glutamic acid decarboxylase 65 do not contain a negatively charged residue that binds in the P9 pocket of the HLA-DQ8 molecule. PBMC from HLA-DQ8+ diabetic and nondiabetic individuals respond to these peptides, confirming that the mouse model is a useful tool to define epitopes of autoantigens that are processed by human APC and recognized by human T cells.

Animals↗
PubMed1999

Confirmatory factor analysis of the Fear Questionnaire in injured workers with chronic pain.

In an effort to extend the validity of the Fear Questionnaire (FQ) in a sample of patients with high levels of blood/injury phobia, the FQ responses of 255 injured workers with chronic pain were subjected to confirmatory factor analysis. Results indicated that an intercorrelated three-factor model of the FQ provided a better fit to the data than unidimensional, two-factor, hierarchical three-factor, or categorical three-factor models. These findings provide further support for the factorial validity of the FQ and the corresponding multidimensional theory of fear.

Accidents, Occupational↗
PubMed1999

Treatment preference in hypochondriasis.

Promising cognitive-behavioral and medication treatments for hypochondriasis are in the early stages of evaluation. Little is known about the treatment preferences and opinions of individuals seeking help for this problem. In this exploratory study, 23 volunteers from the community with a DSM-IV diagnosis of hypochondriasis were recruited through a newspaper advertisement. Participants were presented with a survey which included balanced descriptions of both a medication and a cognitive-behavioral treatment for intense illness concerns (hypochondriasis). The brief descriptions of the treatments discussed the time commitment required as well as the major advantages and disadvantages of each. Results showed that, relative to medication treatment, cognitive-behavioral treatment was predicted to be more effective in both the short and long terms and was rated as more acceptable. Psychological treatment was indicated as the first choice by 74% of respondents, medication by 4%, and 22% indicated an equal preference. Forty-eight percent of respondents would only accept the psychological treatment.

Adult↗