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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

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

Spontaneously regressing oral papillomas induce systemic antibodies that neutralize canine oral papillomavirus.

Canine oral papillomavirus (COPV) infection of naive beagle dogs causes oral papillomas, most of which spontaneously regress. Regressor beagles do not develop new oral papillomas because of COPV type-specific, cell-mediated immunity, COPV neutralizing antibodies, or both. Formalin-fixed native and recombinant COPV vaccines that target the systemic immune system induce neutralizing antibodies that prevent development of oral papillomas. This study was designed to determine whether spontaneously regressing mucosal papillomas also targeted the systemic immune system to induce circulating, neutralizing IgG antibodies that protect against infection by COPV. To accomplish this goal, IgG was fractionated from sera collected from weanling beagles and regressor beagles and tested for conferring protection by passive immunization. Serum was tested by ELISA for antibodies against intact virions and then pooled for passive transfer to naive beagles. Preimmune sera were neither reactive by ELISA nor protective by passive transfer. On the other hand, IgG antibodies from regressor beagles were reactive by ELISA and passive transfer conferred protection against COPV challenge. Circulating IgG antibodies induced by spontaneous regression of canine oral papillomas protect beagles against intraoral infection by COPV, a model for mucosotropic HPV.

Animals↗
PubMed2000

A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study.

BACKGROUND: Some endometrial cancers are hormonally dependent. A principal source of circulating estrogen is conversion of adrenal androstenedione by aromatase. Anastrozole (Arimidex) is an oral nonsteroidal aromatase inhibitor which is active in recurrent breast cancer. This Phase II study was undertaken to evaluate anastrozole in recurrent endometrial carcinoma. METHODS: Patients with advanced or recurrent endometrial cancer not curable with either surgery or radiation therapy and with measurable disease, a GOG (Zubrod) performance status of < or = 2, no more than one prior hormonal therapy regimen, and no prior chemotherapy were eligible. Anastrozole was administered at a dose of 1 mg/day orally for at least 28 days. RESULTS: Twenty-three patients were entered on this trial. On central pathology review, 9 of them had grade 2 and 14 had grade 3 tumors. One to 24 courses (median: 1) of therapy were administered. Two partial responses were noted (9%; 90% confidence interval 3 to 23%). Two additional patients had short-term stable disease. With the exception of 1 case of venous thrombosis, the toxicity profile was mild. Median durations of progression-free survival and overall survival are 1 and 6 months, respectively. CONCLUSIONS: Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer.

Administration, Oral↗
PubMed2000

A dendritic cable model for the amplification of synaptic potentials by an ensemble average of persistent sodium channels.

The persistent sodium current density (I(NaP)) at the soma measured with the 'whole-cell' patch-clamp recording method is linearized about the resting state and used as a current source along the dendritic cable (depicting the spatial distribution of voltage-dependent persistent sodium ionic channels). This procedure allows time-dependent analytical solutions to be obtained for the membrane depolarization. Computer simulated response to a dendritic current injection in the form of synaptically-induced voltage change located at a distance from the recording site in a cable with unequally distributed persistent sodium ion channel densities per unit length of cable (the so-called 'hot-spots') is used to obtain conclusions on the density and distribution of persistent sodium ion channels. It is shown that the excitatory postsynaptic potentials (EPSPs) are amplified if hot-spots of persistent sodium ion channels are spatially distributed along the dendritic cable, with the local density of I(NaP) with respect to the recording site shown to specifically increase the peak amplitude of the EPSP for a proximally placed synaptic input, while the spatial distribution of I(NaP) serves to broaden the time course of the amplified EPSP. However, in the case of a distally positioned synaptic input, both local and nonlocal densities yield an approximately identical enhancement of EPSPs in contradiction to the computer simulations performed by Lipowsky et al. [J. Neurophysiol. 76 (1996) 2181]. The results indicate that persistent sodium channels produce EPSP amplification even when their distribution is relatively sparse (i.e. , approximately 1-2% of the transient sodium channels are found in dendrites of CA1 hippocampal pyramidal neurons). This gives a strong impetus for the use of the theory as a novel approach in the investigation of synaptic integration of signals in active dendrites represented as ionic cables.

Animals↗
PubMed2000

Theoretical analysis of the amplification of synaptic potentials by small clusters of persistent sodium channels in dendrites.

We extend on the work developed by R.R. Poznanski and J. Bell from a linearized somatic persistent sodium current source to a non-linear representation of the dendritic Na(+)P current source associated with a small number of persistent sodium channels. The main objective is to investigate the modulation in the amplification of excitatory postsynaptic potentials (EPSPs) in dendrites studded with persistent sodium channels. The relation between membrane potential (V) and persistent sodium current density (I(NaP)) is approximated heuristically with a sigmoidal function and the resultant cable equation is solved analytically using a regular perturbation expansion and Green's function techniques. The transient simulated (non-evoked) response is found as a result of current injection in the form of synaptically induced voltage change located at a distance from the recording site in a cable with a uniform distribution of ion channel densities per unit length of cable (the so-called 'hot-spots') and with the conductance of each hot-spot (i.e., number of channels per hot-spot) assumed to be a constant. The results show an amplification in the observed EPSPs to be compatible with the experimentally derived estimates, and in addition a saturation in the amplification is observed indicating an optimum number of ionic channels.

Animals↗
PubMed2000

Fear-potentiated startle response in mice: genetic analysis of the C57BL/6J and DBA/2J intercross.

The role of genetic factors in the fear-potentiated startle (FPS) response was examined in the inbred C57BL/6J (B6) and DBA/2J (D2) mouse strains. Mice in the D2 strain displayed a significant potentiation in the acoustic startle response (ASR) when presented with a visual condition stimulus (CS) previously paired with an aversive unconditioned stimulus (US). The maximal FPS response was observed following 20 conditioning trials but a near maximal response was noted following as few as five trials. Forty conditioning trials produced a significant reduction in the FPS response that may be related to overtraining. The FPS response in the B6 strain was significantly lower than the D2 strain, regardless of the number of conditioning trials. The contrasting FPS responses were not related to differences in auditory sensitivity known to exist between these strains. Analysis of a full Mendelian cross formed from the B6 and D2 strains found that the FPS response was a highly heritable trait, best described by a simple additive model of inheritance and with a broad-sense heritability of 0.46. The distribution of the FPS response in F2 hybrids formed from the intercross of the D2 and B6 strains was continuous which suggests a multigenic substrate. The light + noise and noise-alone trial types were highly correlated, but no association was detected between the baseline ASR amplitude and the FPS response. Mice from the phenotypic extremes of the F2 distribution displayed FPS responses that were more extreme than either of the progenitor strains. However, both baseline startle amplitude and the salience of auditory stimuli did not differ in these groups. The results of this study confirm an early report by Falls et al. (1997), and provide additional quantitative genetics information necessary for the eventual mapping of the chromosomal regions or genes associated with the FPS response in mice.

Acoustic Stimulation↗
PubMed2000

Epidemiology of erectile dysfunction: a community-based study in rural New York State.

PURPOSE: Few published population-based studies that deal with the prevalence of erectile dysfunction (ED) involve rural populations. This study determined the prevalence and determinants of ED among a rural population. It also evaluated the relevance of some major predictors of help-seeking decisions. METHODS: A self-administered survey was conducted by mail among 5198 randomly selected men 50-76 years old, living in four rural counties in Central New York State. RESULTS: The response rate was 44.7% and the participation rate among respondents was 71.0%. Mean ages of men reporting and those not reporting ED were 64.5 7.2 and 59.8 7.2 years respectively. The mean duration of self-reported ED was 4.9 4.6 years. The overall prevalence of ED was 46.3% while the minimum prevalence was estimated as 21.3%. Age-specific prevalence was 26.0%, 34.9%, 46.9%, 57.8% and 69.4% among men 50-54, 55-59, 60-64, 65-69, and 70-76 years old respectively. There was a statistically significant relationship between age, socio-economic status, perceived state of health and erectile function status (p < 0.001). However, socio-economic status, marital status, perceived state of health and age were not significant predictors of help-seeking decisions. CONCLUSIONS: The prevalence of ED among men 50-76 years old in rural Central New York State is at least 21.3% and may be as high as 46.3%. Age, perceived state of health and socio-economic status were found to be important determinants of erectile dysfunction among this population. For purposes of comparative analyses, future epidemiological studies should report both the overall and minimum rates among men with clinically relevant erectile dysfunction.

Aged↗
PubMed2000

The biology of Meteorus gyrator (Hymenoptera: Braconidae), a solitary endoparasitoid of the tomato moth, Lacanobia oleracea (Lepidoptera: Noctuidae).

There is a need to identify potential biological control agents for use against lepidopterous pests in greenhouses. The solitary endoparasitoid Meteorus gyrator (Thunberg) attacks a range of macrolepidopterous larvae, including those of some important horticultural pest species. Laboratory trials designed to investigate the biology of M. gyrator on larvae of the tomato moth, Lacanobia oleracea Linnaeus, reveal that this parasitoid is capable of parasitizing all larval stages of its host, third instars being parasitized most frequently. Each female parasitoid lives for up to 40 days (at 25 degrees C), ovipositing into an average of 78 hosts. Preadult development is rapid ( approximately 2 weeks), and the sex ratio of offspring is 1:1. Parasitism by M. gyrator suppresses the growth of both early and late host instars, and there is a concomitant reduction in the amount of food consumed (overall feeding reduction over a 12 day period is 68%). Our results indicate that inoculative releases of M. gyrator could provide effective biological control of L. oleracea and other noctuid pests of greenhouses.

Animals↗
PubMed2000

Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus.

Numbers of neurones, synapses and axon terminals were quantified in a murine scrapie model with severe hippocampal pyramidal cell loss, in which definite clinical scrapie is evident from 226 days post-infection (dpi) and death occurs around 250 dpi. Disease-specific PrP accumulations were first seen at 70 dpi (28% of the incubation period (IP)) in thalamus and as sparse foci within the stratum pyramidale of CA1. By 98 dpi (39% IP), PrP was seen in the stratum radiatum and was found at later stages throughout all levels of the hippocampus. At the ultrastructural level in the stratum radiatum of CA1, a decrease in the numbers of simple synapses from 84 dpi (34% IP) and in perforated synapses from 98 dpi (42% IP) was found using an unbiased stereological method, the disector analysis. Degeneration of axon terminals was found from 98 dpi (39% IP) onwards. Neuronal loss was detected in CA1 from 180 dpi (72% IP). The results suggest that the fundamental lesion in the hippocampus of ME7-infected mice is associated with PrP release from CA1 pyramidal neurones, which perturbs synaptic function and leads to degeneration of preterminal axons, and that subsequent pathological changes including neurone loss are sequelae to this initial insult.

Animals↗
PubMed2000

Completeness of cancer registration: a new method for routine use.

We report a new method of estimating the completeness of cancer registration, in which the proportions of unregistered patients are derived from the time distributions of three probabilities, each of which can be directly estimated from the registry's own data--the probabilities of survival, of registration of the cancer during the patient's life, and of the mention of cancer on the death certificate of a cancer patient who dies. This method allows completeness to be assessed routinely by factors such as age, sex, geographical area and tumour type.

Death Certificates↗
PubMed2000

Genetic relatedness of multidrug-resistant, methicillin (oxacillin)-resistant Staphylococcus aureus bloodstream isolates from SENTRY Antimicrobial Resistance Surveillance Centers worldwide, 1998.

We reviewed Staphylococcus aureus bloodstream infection isolates from SENTRY centers worldwide during 1998 to evaluate the molecular epidemiology of multiply drug-resistant methicillin (oxacillin)-resistant S. aureus (MDR-MRSA). MDR-MRSA was defined as a S. aureus isolate with a MIC for oxacillin at >2 microg/ml and with four or more additional resistances. A total of 325 unique patient isolates of MDR-MRSA from five continents were analyzed using ribotyping and pulsed-field gel electrophoresis (PFGE). The frequency of MDR-MRSA among all S. aureus BSI isolates ranged from only 2.2% in Canada to 35.6% in the Asia-Pacific region. Forty-eight ribotypes (RT) were distinguished, but over 80% of the isolates were contained within the 10 most prevalent RTs. The most common RT, RT 184.5, which included 30% of all MDR-MRSA, was found on four of five continents. PFGE provided superior discrimination and identified numerous clusters of possible clonal dissemination of MDR-MRSA within individual medical centers and between institutions that are in geographic proximity. In four instances, strains with indistinguishable PFGE patterns were found on more than one continent. The predominant PFGE subtype in South America (RT 893.5/Ia) was isolated from patients at centers in Brazil, Argentina, and Portugal, and closely related subtypes were isolated in Chile and Italy. There is great geographic variation in rates of methicillin- and multidrug-resistance among S. aureus bloodstream isolates worldwide. Although many MDR-MRSA strains group geographically, a few closely related epidemic strains have wide regional and even global range.

Anti-Bacterial Agents↗
PubMed2000

Cancer registries--future development and uses in Britain.

Cancer registries are a vital source of information on cancer epidemiology and cancer services. Their role has changed dramatically over the past 15 years. A number of factors will affect their future role, including health service changes, information technology, development of clinical datasets and greater demand for both health service and public information. The potential of cancer registration needs to be realized by clinicians and health authorities: how they can use the data, its limitations, and how they can support and influence it through this period of change. A strategic direction is needed so that cancer registries develop into a dynamic, interactive source of knowledge for the twenty-first century.

Confidentiality↗
PubMed2000

Mycosis fungoides: review of epidemiological observations.

BACKGROUND: Mycosis fungoides (MF) is a chronic cutaneous T-cell lymphoma characterized by small cells with cerebriform nuclei that usually express a mature peripheral T-helper cell (CD4+) immunophenotype. Its evolution is typically quite slow, with years between the first manifestations and development of advanced stages of disease. OBJECTIVE: The purpose of the present paper is to contribute to the material about MF already present in the literature. The review articles that have appeared to date fundamentally address the morphological characteristics, diagnostic criteria and treatment of the disease; in contrast, the present study centers on the evolution of the incidence of MF and on the knowledge of the possible risk factors implicated in its development. METHODS: Review of published papers about MF epidemiology. RESULTS: The evidence suggests that the incidence is increasing, but this may be artifactual due to improved diagnostic techniques. The risk of MF is limited to gender and race, being higher in males and in blacks. Survival is highly stage dependent, but 90% of patients survive 15 years with only 10% of cutaneous involvement. Few risk factors have been identified, but several studies have found an association with industrial exposure, particularly to oils. CONCLUSION: MF is a rare disease and its risk factors have not been studied in any great detail. A European case-control study in progress will substantially increase the evidence available and progress towards identifying a prevention strategy.

Adult↗
PubMed2000

Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia.

Infection with the human immunodeficiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.

AIDS Dementia Complex↗
PubMed2000

Influence of gelatin and bovine serum lubricants on ultra-high molecular weight polyethylene wear debris generated in in vitro simulations.

Ultra-high molecular weight polyethylene (UHMWPE) wear debris induced osteolysis has a major role in the late aseptic loosening and ultimate failure of total hip replacements (THR). Clinically relevant in vitro simulations of wear are essential to predict the osteolytic potential of bearing surfaces in artificial hip joints. Newborn calf or bovine serum has been accepted as a boundary lubricant for such in vitro tests, but its biological stability has been questioned. This study compared the wear factors, number of wear particles and levels of microbial contamination produced in bovine serum and a gelatin-based lubricant. The wear factors produced by the two lubricants were not significantly different, however the wear debris morphology produced was substantially different. The bovine serum became contaminated with micro-organisms within 28 h, whereas the protein-based lubricant remained uncontaminated. The results showed that bovine serum was not a stable boundary lubricant. They also showed that although the wear factors for the two solutions were not significantly different, the protein-based lubricant was not a suitable alternative to bovine serum because the wear debris produced was not clinically relevant.

Animals↗
PubMed2000

A risk-benefit analysis of methadone maintenance treatment.

Methadone maintenance treatment for heroin (diamorphine) addiction has been extensively researched. There is consistent evidence that while in treatment, heroin addicts are at a lower risk of death, are less involved in crime, and feel and function better than while using heroin. Despite the research evidence supporting methadone treatment, there remains widespread public scepticism about this form of treatment. This scepticism is frequently expressed in terms of the perceived risks of methadone treatment. The perceived risk that methadone treatment may maintain people in an addicted lifestyle is not supported by research literature. The risks of treatment include an increased risk of death during induction into treatment, and risks of diversion of drugs to the black market. For some patients, adverse effects of methadone pose a problem and the availability of new pharmacotherapies may provide useful options for these patients. Risks can be reduced and benefits increased by directing greater attention to the quality of treatment.

Analgesics, Opioid↗
PubMed2000

NFkappaB activation, TNF-alpha expression, and apoptosis in the AIDS-Dementia-Complex.

The role of NFkappaB activation and its relationship to inflammatory mediators and apoptosis in the HIV-infected brain have remained uncertain. The cellular and regional distribution of NFkappaB, TNF-alpha, and apoptosis was examined in the frontal cortex (FC), deep white matter (DWM) and the basal ganglia (BG) of 17 patients with ADC. Nuclear staining for NFkappaB was localized predominantly to perivascular microglia/macrophages in the BG and DWM and correlated with ADC severity. Correlations were further found with HLA-DR, iNOS, TNF-alpha, and gp41 expression in these regions. The number of TUNEL-positive cells, particularly in the BG, correlated with ADC stage. Logistic regression analysis further showed a significant relationship between the likelihood of TUNEL staining in the BG and worsening cognitive impairment.

AIDS Dementia Complex↗
PubMed2000

Melanoma and additional primary cancers.

The aim of this study was to examine the occurrence of additional, unrelated primary cancers in patients with melanoma. Data from the hospital-based, melanoma registry of a specialist unit (the Melanoma Unit at Charing Cross Hospital, London, UK) were compared with the incidence rates in a population-based cancer registry (the Thames Cancer Registry). In total, 2076 patients with the histological diagnosis of melanoma established between 1960 and 1997 who were registered with the Melanoma Unit at Charing Cross Hospital, were included in the study. Patterns in time and in the tumour type of the additional cancers were analysed in the cohort. The relative risk of subsequent cancers was evaluated, the number of expected cancers being calculated by applying incidence rates in the population of south-east England to the person-years of follow-up in the cohort. Sixty-six (3%) of the 2076 evaluable patients had a history of, or developed, 69 histologically verified additional cancers, the commonest being colorectal, breast and lymphoma. Twenty-six additional cancers preceded the diagnosis of melanoma by 1-42 years, 16 were diagnosed within 12 months and 27 followed the diagnosis of melanoma, 1-28 years later. Seven cancers occurred after chemotherapy for metastatic melanoma: two colorectal, one bladder, one renal, two myelodysplasias and one acute myeloid leukaemia. The relative risk of additional cancers developing after the diagnosis of melanoma during the 8537 evaluable years-at-risk was 0.64 (95% confidence interval 0.41-0.96; P = 0.0006). Thus, the risk of additional cancers following treatment for metastatic melanoma in this cohort is small. The potential influence of other factors on the occurrence of additional cancers observed overall in this study requires further investigation.

Adolescent↗