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Biomedical subjects

P Naylor

Publications and source records attributed to P Naylor.

18 recordsLinked to original sources

Hepatitis C screening and prevalence among urban public safety workers.

This study examines the prevalence of anti-hepatitis C virus by using an enzyme-linked immunoassay test (EIA-2) in 2447 volunteers (including 1560 police, 678 fire, and 209 emergency medical service personnel) and a self-reported questionnaire on potential occupational and non-occupational risk factors. Subjects consisted of 76% men, 54.8% blacks, and 40.3% whites. Twenty-eight individuals (1.1%) tested positive, with prevalence rates of 1.1% and 1.3%, respectively, among blacks and whites. Although firefighters and emergency medical service workers had a higher prevalence (2.3% and 2.8%) than police (0.6%), the overall prevalence was lower than that typical of urban populations. In a multivariate analysis, the most important risk factors were behavioral, with no significant occupational exposure risk observed. Previously reported racial differences were not detected in this study, most likely because the subjects were of similar socioeconomic status.

Adult↗

Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: implications for vaccination strategy.

OBJECTIVES: Administration of vaccine for hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic hepatitis C (CHC) because of the potential for increased severity of acute hepatitis superimposed on existing liver disease. The aim of this study is to determine the prevalence of antibodies directed against HAV and HBV in patients with CHC, analyze demographic and risk factors associated with this prevalence, and develop a cost-effective vaccination strategy. METHODS: We reviewed records from 1092 CHC patients. Demographics and information regarding risk factors were obtained by history and questionnaire administered to all patients. The costs of vaccination and antibody testing were determined, based on standard laboratory and clinic charges at our institution. HAV and HBV markers were correlated to race, age, and risk factors. RESULTS: Of the total population studied (n = 1092), 72% were African-Americans, 27% white, and 1% others. Of 671 CHC patients tested for anti-HAV IgG, 252 (38%) were positive. Of 743 CHC patients tested for HBV antibodies (anti-hepatitis B core IgG or anti-hepatitis B surface), 494 (67%) were positive. African-Americans are more likely to have antibodies to HAV and HBV (67% and 75%, respectively) compared to whites (27% and 20%). The prevalence of anti-HAV was 76% in patients >60 yr, 34% in the 40- to 60-yr-old age group, and 21% in patients <40 yr. The highest prevalence of HBV antibodies was found in patients between the ages of 40-60 yr. No HCV risk factors were associated with increased HAV risk. In CHC patients with HBV antibodies, however, illicit injection drug use was the predominant risk factor. CONCLUSIONS: The prevalence of anti-HAV in patients with CHC was found to be similar to that of the general population in the United States (33% according to recent Centers for Disease Control data), consistent with the hypothesis that the two infections do not share risk factors. Because the prevalence of HAV immunity is low in CHC patients <40 yr, empiric HAV vaccination is cost effective. If two doses of vaccine are to be given, however, antibody testing of all HCV patients is indicated. In the subset of patients >60 yr of age or who are African-American, where the prevalence of HAV exposure is considerably higher, it would be cost effective to check the antibody ($36.00), before vaccination ($97.00). The prevalence of HBV antibodies, however, is significantly increased in patients with CHC compared with the general population (5.3% per the Centers for Disease Control), likely as a result of exposure to similar parenteral risk factors. HBV antibody testing ($26.00 per test) should, therefore, be undertaken in all CHC patients who are hepatitis B surface antigen negative, as this approach is cost-effective compared to empiric HBV vaccination ($438.00 for a three injection course).

Adult↗

The effectiveness of peer support systems in challenging school bullying: the perspectives and experiences of teachers and pupils.

This large-scale questionnaire survey (n=2313) has sought teachers' and pupils' perceptions and experiences of peer support systems in challenging bullying in U.K. (mainly English) secondary schools and colleges (n=51). In general, these systems have been found to be effective in reducing the negative effects of bullying for victims. Collectively, the respondents also perceive many important benefits to users of these systems, to peer supporters and to the school as a whole, including helping to create a socio-emotional climate of "care". The respondents also perceive problems with these systems and, importantly, how they have been overcome and might be further improved.

Adolescent↗

Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus.

The neural basis underlying the cognitive side effects of ECT is unknown. Recent studies suggest that the memory dysfunction may be caused by alterations in hippocampal synaptic efficacy [20]. In situ hybridisation was used to examine the possible receptor mechanisms responsible for this effect. Repeated ECS markedly increased mRNA expression for the GluR1 subunit of the AMPA receptor, but not the NMDAR1A-G subtypes of the NMDA receptor, relative to control treatments. This effect was present 24 h after the last seizure and may be responsible for the expression of the ECS-induced increase in synaptic efficacy.

Animals↗

IL-1, ICAM-1, LFA-3, and hydrocortisone differentially regulate cytokine secretion by human fetal thymic epithelial cells.

Human fetal thymic epithelial cells (TEC) were cultured under serum-free conditions. The TEC were analyzed for the secretion of 14C-labelled peptides and of IL-3, IL-6 IL-7, IL-8, GM-CSF, LIF, fibronectin and thymosin alpha 1 by ELISA tests. IL-3 and IL-7 were not detected from these TEC. Lack of IL-7 and presence of thymosin alpha 1 and of the surface molecule TE-4 depicts these cells as subcapsular/medullary TEC. TEC secreted constitutively IL-6, IL-8, fibronectin and thymosin alpha 1 but not GM-CSF of LIF. Stimulants included recombinant IL-1 and monoclonal antibodies to the surface adhesion molecules ICAM-1 and LAF-3. In addition, hydrocortisone (2.7 x 10(-7) M) was used to dissect secretion patterns. Recombinant IL-1, anti ICAM-1, and anti LFA-3 alone and collectively induced modest but significant increases in the secretions of 14C-labelled peptides and of IL-6 and IL-8 which were not inhibited by HC. Recombinant IL-1 but not anti ICAM-1 and anti LFA-3 induced GM-CSF and LIF. HC inhibited the secretion of GM-CSF and LIF induced by IL-1. None of the stimulants augmented the constitutive secretion of fibronectin or thymosin alpha 1 and HC inhibited thymosin alpha 1 secretion. TEC secretion of cytokines but not thymosin alpha 1 and fibronectin appear to be regulated in a more complex manner than heretofore recognized.

CD58 Antigens↗

Digital imaging of umbelliferone clearance: a method for repeated measurements of cerebral cortical blood flow with high temporal and spatial resolution.

We have developed a procedure for digital imaging of the exposed cerebral cortex during elution of a fluorescent dye. This avoids disturbing the cortex and has provided a method for the repeated estimation of regional CBF (rCBF) with a high topographical resolution. Under varying conditions of MABP and arterial blood gases, grey-level images of the exposed cortex irradiated with ultraviolet light (340 or 370 nm) were digitised (8 bits) at 15-s intervals after the injection of 1-2 ml of saturated umbelliferone solution into the lingual or external carotid artery of anaesthetised cats and rabbits. Specifically designed software allowed (a) regions of interest (ROIs) in the exposed cortex to be defined that were automatically applied to the sequence of images in a selected clearance and (b) solution of the initial slope equation for rCBF from the decay in grey-level fluorescence by exponential regression. Separate software that solved the equation at the level of a single pixel allowed a pseudocolour map of cortical rCBF to be generated. The factors affecting the resolution of this technique have been identified and quantified. Thus consistent and reproducible results were obtained provided that the fluorescence enhancement exceeded 20 grey levels and the r2 coefficient for regression was 90% or above. Mean rCBF values of 99.5 [95% confidence interval (CI), 89.4-110] ml 100 g-1 min-1 were obtained for rabbits (N = 12; mean MABP = 75.2; mean PaCO2 = 32.9; PaO2 = 111.8; pH 7.38) and 65.1 (95% CI, 55.1-75.1) ml 100 g-1 min-1 for cats (N = 8; mean MABP = 92.8; PaCO2 = 31.5; PaO2 = 114.6, pH 7.40).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Malignant thymoma associated with T-cell lymphocytosis. A case report with immunophenotypic and gene rearrangement analysis.

Patients with malignant thymoma rarely may also have a peripheral T-cell lymphocytosis. "Lymphocyte spillover" from the thymus into the peripheral blood as well as a second, associated neoplasm (ie, T-cell chronic lymphocytic leukemia) are two hypotheses that have been proposed to explain this clinical phenomenon. We describe another patient with a lymphocyte-rich malignant thymoma associated with peripheral T-cell lymphocytosis. At the time of initial diagnosis, the patient's complete blood cell count was unremarkable. However, subsequent to the development of pulmonary metastases, the patient developed persistent lymphocytosis. The total leukocyte count ranged from 20 to 30 x 10(9)/L, 80% of these cells being lymphocytes. Immunophenotypic analysis of peripheral blood specimens from this patient proved that the circulating cells were mature, polyclonal T cells. The cells expressed the alpha/beta T-cell receptor and the pan-T-cell antigens CD2, CD3, CD5, and CD7, and were negative for both terminal deoxynucleotidyl transferase (TdT) and the CD1 antigen. A mixture of T-helper (CD4+) and T-suppressor (CD8+) cells were present in a ratio of 1:1.6. Gene rearrangement studies revealed that the T-cell receptor beta chain and the immunoglobulin heavy-chain genes were in the germline configuration. Serum samples from this patient were also analyzed for thymic hormones; the level of thymosin alpha 1 was markedly elevated, while that of thymosin beta 4 was decreased. These results effectively exclude the hypothesis that the lymphocytosis represents a second, associated neoplasm. The lymphocyte spillover hypothesis also seems unlikely (although not excluded), since the lymphocytes in lymphocyte-rich thymomas usually have an immature thymic cortical immunophenotype. Furthermore, one might expect nonspecific elevation of all thymic hormone levels with lymphocyte spillover. Thus, we suggest that the lymphocytosis results from a poorly defined immunoregulatory disorder, related to the presence of thymoma, and perhaps secondary thymic hormone imbalance.

Aged↗

Interleukin-2-dependent control of disease development in spontaneously diabetic BB rats.

Long-term treatment with recombinant interleukin-2 (IL-2) of diabetes-prone BB rats had contrasting effects in two different BB rat sublines. Diabetes development was enhanced in the subline with a low intrinsic diabetes risk and suppressed in the subline with a high diabetes risk. IL-2 treatment started between 35 and 42 days of age and lasted for 3 months. In subline 1, diabetes incidence increased from 23% to 53% (P less than 0.01), in subline 2 it decreased from 73% to 32% (P less than 0.01). The two sublines differed in serum levels of factors controlling IL-2 synthesis and activity. Mean IL-2 inhibitory activity was higher in subline 2 (between 140% and 290% of levels in subline 1, P less than 0.01). Conversely, mean concentrations of thymosin alpha 1 and beta 4 were higher in subline 1 (between 140% and 200% of levels in subline 2, P less than 0.01). Thus the two sublines differ in their response to exogenous IL-2 and also in serum levels of mediators affecting availability of IL-2. We conclude that an internal network of hormonal factors, including IL-2, contributes to the control of diabetes development in the BB rat.

Animals↗

Signal transduction pathway for IL-1. Involvement of a pertussis toxin-sensitive GTP-binding protein in the activation of adenylate cyclase.

Human Il-1 alpha induces the synthesis of kappa Ig L chains by the pre-B cell line 7OZ/3, IL-2R alpha by the human NK cell line YT, and PGE2 by human rheumatoid synovial cells. Pertussis toxin (PT) markedly inhibited all three IL-1-induced activation events. The inhibition by PT was associated with a decrease in IL-1-mediated cAMP production. PT also inhibited IL-1-stimulated cAMP production in crude membrane fractions from 7OZ/3, YT, and 3T3 fibroblasts. In addition, IL-1 stimulated GTPase activity present in the membranes IL-1-responsive cells. Furthermore, the IL-1-induced GTPase activity was sensitive to PT. PT induced the ADP-ribosylation of a 46-kDa substrate in membrane preparations from IL-1-responsive cells. Cholera toxin also induced the ADP-ribosylation of a 46-kDa substrate in the same membrane preparations. The present findings indicate that the IL-1R is linked to a PT-sensitive G protein that stimulates the activity of adenylate cyclase.

Adenosine Diphosphate Ribose↗

A cloned rat thymic epithelial cell line established from serum-free selective culture.

A serum-free system has been developed for selective growth and long-term culture of rat thymic epithelial cells. The growth media is a modification of McKeehan's WAJC 404, plus insulin, cholera toxin, dexamethasone, and epidermal growth factor. Cultures have been continuously passaged and maintained for over 6 mo., and a cloned cell line, TEA3A1, has been established. These cells are epithelial, judging by morphology and ultrastructure, and are positive for A2B5 and thymosin alpha 1 markers for thymic endocrine cells.

Animals↗

Intestinal lymphangiectasia and thymic hypoplasia.

We have evaluated the immunological abnormalities present in a 6 year old patient with primary intestinal and generalized lymphangiectasia confirmed by intestinal, lung and lymph node biopsies. Lymphocyte loss through the gut was confirmed by the detection of lymphocytes in her stool. An increased enteric protein loss was suggested by hypoproteinaemia, peripheral oedema, and a very short half-life for i.v. immune serum globulin (3 days). Lymphocyte subpopulation analysis revealed a selective loss of T lymphocytes, with a proportionally increased loss of the OKT4 positive helper/inducer subpopulation. Functionally, there was a decrease in proliferative responses to some mitogens and to allogeneic cells, and a lack of T cell help for in vitro B lymphocyte differentiation into immunoglobulin secreting cells. Natural killer function was normal. In this patient, a concomitant thymic deficiency was documented by failure to identify thymic tissue on a thymus biopsy and by an absence or decrease of the serum thymic factor (thymulin) and thymosin alpha 1. No compensatory lymphopoiesis was detected in the bone marrow. In an attempt to increase T lymphocyte development, the patient was treated with thymosin fraction 5. Daily treatment with this preparation resulted in a transient clinical improvement which could not be sustained on a weekly thymosin treatment schedule. However, lymphocyte numbers did not increase during this treatment. The findings in this patient support the notion that T lymphocytes are needed to stimulate thymic epithelium. In situations of excessive loss of long lived T lymphocytes a secondary thymic atrophy may occur and further contribute to the development of a deficiency in cell-mediated immunity.

Child↗

Specific antibody synthesis in vitro. II. Age-associated thymosin enhancement of antitetanus antibody synthesis.

A decline in T cell function accounts for many of the observed age-related deficient immune responses. Specific antibody response to many antigens requires T cell cooperation, and deficient antibody response to such antigens has been demonstrated with aging. In an effort to assess the potential reconstitutive capacity of Thymosin Fraction 5, in vitro antitetanus antibody production was measured in tetanus toxoid booster-immunized young and old volunteers. 22 young and 12 old volunteers were immunized with tetanus toxoid and plasma antitetanus antibody and in vitro lymphocyte production of antitetanus antibody was measured. Plasma antitetanus antibody response was significantly greater in the young. In vitro antitetanus antibody synthesis was negligible prior to immunization and peaked in cultures established 1 week after immunization from both young and old. When Thymosin Fraction 5 was added to the cultures, however, there was a dose-related enhancement of antibody synthesis in 7 of 10 from the group of elderly volunteers, but only 3 of 12 from the younger group. Our data indicate that specific antibody response is deficient in the elderly, but can be enhanced in vitro by thymosin. A future clinical trial of thymosin as an adjuvant to active immunization for the elderly is warranted.

Adjuvants, Immunologic↗

Infections from biomaterials and implants: a race for the surface.

Microorganisms in nature and disease are dependent on substratum attachment for optimal growth and development. Similarly, implanted biomaterials tend to potentiate bacteria on their surfaces so that normally friendly special or opportunistic organisms become virulent pathogens. Virulence is also enhanced because both bacteria and biomaterials interfere with host defense mechanisms. Infections centered on biomaterials are most difficult to eliminate and usually require removal of the device. The consequences of device failure are catastrophic and costly. It is the specific nature of the biomaterial surface, which is indirectly a reflection of bulk features, that causes and directs the changes in bacterial behavior which result in virulence. Features of organisms and materials and interactions responsible for these phenomena are reviewed.

Bacterial Adhesion↗