Fatal reactivation of precore mutant hepatitis B virus associated with fibrosing cholestatic hepatitis after bone marrow transplantation.
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Bone Marrow Transplantation↗
Biomedical subjects
A Bryant
Publications and source records attributed to A Bryant.
Passive exposure to tobacco smoke in children aged 5-7 years: individual, family, and community factors.
OBJECTIVE: To examine the importance of parental smoking on passive exposure to tobacco smoke in children and the social and geographical patterns of exposure. DESIGN: Cross sectional study. SETTING: Schools in 10 towns in England and Wales; five towns with high adult cardiovascular mortality and five with low rates. SUBJECTS: 4043 children aged 5-7 years of European origin. MAIN OUTCOME MEASURES: Salivary cotinine concentration and parents self reported smoking habits. RESULTS: 1061 (53.0%) children were exposed to cigarette smoke at home or by an outside carer. Geometric mean cotinine rose from 0.29 (95% confidence interval 0.28 to 0.31) ng/ml in children with no identified exposure to 4.05 (3.71 to 4.42) ng/ml in households where both parents smoked and 9.03 (6.73 to 12.10) ng/ml if both parents smoked more than 20 cigarettes a day. The effect of mothers' smoking was greater than that of fathers', especially at high levels of consumption. After adjustment for known exposures geometric mean cotinine concentrations rose from 0.52 ng/ml in social class I to 1.36 ng/ml in social class V (P < 0.0001); and were doubled in high mortality towns compared with the low mortality towns (P = 0.002). In children with no identified exposure similar trends by social class and town were observed and the cotinine concentrations correlated with the prevalence of parental smoking, both between towns (r = 0.69, P = 0.02) and between schools within towns (r = 0.50, P < 0.001). CONCLUSIONS: Mothers' smoking is more important that fathers' despite the lower levels of smoking by mothers. Children not exposed at home had low cotinine concentration, the level depending on the prevalence of smoking in the community.
Age Factors↗
Failure in IgA secretion by surface IgA-positive B cells in common variable immunodeficiency (CVID).
CVID is an acquired disease with low serum immunoglobulins. Patients are classified into three groups on the ability of their B cells to secrete IgM and IgG in vitro in response to IL-2. We have now extended this patient classification to include IgA secretion and to assess whether the patients have IgA+ B cells in the circulation. B cells from almost all of the CVID patients studied were unable to secrete any IgA in vitro, with or without IL-2, although all B cells tested from normal donors showed some spontaneous IgA secretion. Thus, the defect with IgA secretion is more profound than with the secretion of IgM or IgG. Despite this failure to secrete IgA, using flow cytometry techniques all CVID patients tested were found to have IgA+ cells (expressed as a percentage of B cells) within the normal range. This suggests that CVID may involve a defect in the secretion of immunoglobulin isotypes rather than a defect in isotype switching.
B-Lymphocytes↗
The stability of cotinine in unfrozen saliva mailed to the laboratory.
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Adult↗
Foot types and lower limb injuries in elite netball players.
In assessing the foot types and lower limb injuries of elite netball players, the following summary seems warranted. Ninety percent of elite female netball players had symmetrical foot types for both feet and these players had experienced at least one lower limb injury. Only 7.6% players (N = 16) of the 204 players surveyed had never sustained a lower limb injury during their netball careers. Regardless of foot type, the injury history of these elite netball players presented with a total number of 449 injuries that occurred to both ankle joints (36%), one ankle joint (16%), both knee joints (6%), one knee joint (13%), shin soreness (18%), and retropatellar pain problems (11%). On further inspection, 55% of players experienced one to two lower limb injuries throughout their netball careers. Injured players showed that players with the pronating foot types with rearfoot abnormalities (57%) were the most commonly injured and that compensated rearfoot varus foot type presented the most lower limb injuries for all body sites.
Adolescent↗
Staphylococcal enterotoxin B up-regulates interleukin-2 receptor beta chain expression on tonsillar B cells.
The superantigen staphylococcal enterotoxin B (SEB) selectively up-regulates the interleukin-2 receptor (IL-2R) beta chain (p70) without up-regulating the IL-2R alpha chain (CD25) on a human tonsillar B cell population depleted of T cells. This action of SEB, probably mediated by binding to major histocompatibility complex class II, renders B cells sensitive to T cell-derived IL-2 and is sufficient for induction of vigorous DNA synthesis with low concentrations of IL-2. This explains one of the mechanisms by which bacterial superantigens activate large numbers of B cells and may reflect a similar mechanism operative in cognate helper T cell/B cell interactions.
Adolescent↗
Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5.
We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release. The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells. The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma). In the presence of IFN-gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h. pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC). The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h. Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma. The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB). SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production. Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma. In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation. These cytokines also play a major role in human T-cell responses to this super antigen.
Adult↗
Relation of passive smoking as assessed by salivary cotinine concentration and questionnaire to spirometric indices in children.
BACKGROUND: Previous studies of the effects of passive exposure to smoke on spirometric indices in children have largely relied on questionnaire measures of exposure. This may have resulted in underestimation of the true effect of passive smoking. Biochemical measures offer the opportunity to estimate recent exposure directly. METHODS: The relation between spirometric indices and passive exposure to tobacco smoke was examined in a large population sample of 5-7 year old children from 10 towns in England and Wales. The effects of passive exposure to smoke on lung function were assessed by means of both salivary cotinine concentration and questionnaire measurements of exposure. Analyses of the relation between spirometric values and cotinine concentrations were based on 2511 children and of the relation between spirometric values and questionnaire measures on 2000 children. RESULTS: Cotinine concentration was negatively associated with all spirometric indices after adjustment for confounding variables, which included age, sex, body size, and social class. The strongest association was with mid expiratory flow rate (FEF50), the fall between the bottom and top fifths of the cotinine distribution being 6%, equivalent to a reduction of 14.3 (95% confidence limits (CL) 8.6, 20.0) ml/s per ng/ml cotinine. Salivary cotinine concentrations were strongly related to exposure to cigarette smoke at home but 88% of children who were from non-smoking households and not looked after by a smoker had detectable cotinine concentrations, 5% being in the top two fifths of the cotinine distribution. A composite questionnaire score based on the number of regular sources of exposure was as strongly related to mid and end expiratory flow rates as the single cotinine measure. The fall in FEF50 per smoker to whom the child was exposed was 51.0 (26.5, 75.5) ml/s. The relationships between the questionnaire score and forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) were not statistically significant. CONCLUSIONS: These effects of passive smoking on respiratory function are consistent with the results of previous studies and, although small in absolute magnitude, may be important if the effects of exposure are cumulative. In children aged 5-7 years the use of a single salivary cotinine concentration as a marker of passive exposure to smoke resulted in clear relationships between exposure and FVC and FEV1, whereas the associations were much weaker and not significant when based on the questionnaire score. The associations between exposure and mid or end expiratory flow rates were of similar magnitude for cotinine concentration and the questionnaire score. The use of salivary cotinine concentration in longitudinal studies may help to determine the extent to which these effects are cumulative or reversible.
Biomarkers↗
Effect of 12,13-phorbol dibutyrate and ionomycin on defective B cells in common variable immunodeficiency.
Secretion of IgM and IgG in vitro by B cells from patients with common variable immunodeficiency (CVI) has been used to classify the disease into three groups. On stimulation with anti-IgM and IL-2, group A patients' cells fail to secrete IgM or IgG, group B patients' cells secrete no IgG and significantly lower levels of IgM than normal cells, and group C patients' cells produce normal levels of both isotypes. Direct activation of protein kinase C using 12,13-phorbol dibutyrate and ionomycin followed by IL-2 or IL-4 has been reported to induce immunoglobulin secretion by normal human B cells. We therefore attempted to induce B cells from group A and group B CVI patients to secrete IgM and IgG after direct activation of protein kinase C together with IL-2 or IL-4. The data show that the failure of secretion of immunoglobulin by B cells from CVI patients could not be reversed using this approach. This finding suggests that the activation channel involving protein kinase C in B cells from CVI patients is not involved in the defect in cell differentiation.
B-Lymphocytes↗
Purification and characterization of the lethal toxin (alpha-toxin) of Clostridium septicum.
Clostridium septicum lethal (alpha-toxin) was purified and found to be a basic protein (pI 8.4) of approximately 48 kDa that is both lethal and hemolytic. The alpha-toxin had a hemolytic activity of approximately 2 x 10(7) hemolytic units per mg and a 50% lethal dose of approximately 10 micrograms/kg of body weight for mice. The alpha-toxin formed concentration-dependent, sodium dodecyl sulfate-resistant aggregates of approximately 230 kDa. Mice immunized with alpha-toxin showed a significant increase in survival time over mock-immunized mice when challenged with C. septicum. Rabbit polyclonal antibody was generated against the purified toxin and was used to confirm that toxin with the same molecular weight was present in seven different C. septicum isolates. No proteins in the supernatants from cultures of Clostridium perfringens, Clostridium histolyticum, Clostridium chauvoei, or Clostridium difficile were found to react with the C. septicum alpha-toxin-specific antibody.
Animals↗
Factors determining exposure to passive smoking in young adults living at home: quantitative analysis using saliva cotinine concentrations.
Saliva cotinine concentrations were used to examine determinants of exposure to environmental tobacco smoke in 393 non-smoking students (age range 16-19 years) attending a sixth form college and living at home. Average concentrations were low (median 0.60 ng/ml), reflecting partly the warm weather at the time of the survey and partly the predominantly middle class sample. Despite this, cotinine levels were strongly related to the extent of self-reported passive smoking in the past three days (medians 0.30, 0.60, 0.90 and 1.35 ng/ml in those reporting 'None at all', 'A little', 'Some' and 'A lot' respectively, p less than 0.0001). Individual sources of environmental tobacco smoke identified were smoking by mothers (p less than 0.0001), by fathers (p less than 0.01), and exposure at college (p less than 0.001) and when out in the evenings (p less than 0.001). The results indicate that exposure outside the home may become of equal or greater importance than family smoking in determining the overall passive smoking dose received by this age group.
Adolescent↗
Interleukin-2-induced DNA synthesis and immunoglobulin secretion by resting human tonsillar B cells: effects of protein kinase C activation.
Responses to interleukin-2 (IL-2) of high-density human tonsillar B lymphocytes were examined in 20 microliters hanging drop microcultures. DNA synthesis and secretion of IgM and IgG were induced by IL-2 alone. Activation of calcium-dependent protein kinase C (PKC) with phorbol 12,13-dibutyrate and ionomycin increased IL-2 driven DNA synthesis yet reduced IL-2 driven secretion of IgM and IgG. Forskolin, which increases cAMP, had no effect on the responses to IL-2. Intrinsic IL-6 played no role in IL-2-induced DNA synthesis but was partially responsible for the secretion of immunoglobulin. These data show that pre-activation of the high-density human tonsillar B lymphocyte is not a prerequisite for IL-2-driven responses. They also show an asymmetry between the growth and differentiation induced by IL-2. This is reflected by opposite modulation on activation of PKC and by the role of the autocrine factor, IL-6.
B-Lymphocytes↗
Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2.
We have classified patients with common variable immunodeficiency (CVI) on the basis of the ability of their B cells to respond to anti-IgM and interleukin (IL)-2 in vitro. Group A had cells unable to secrete IgM or IgG, Group B secreted IgM alone, and Group C secreted both IgM and IgG. A separate small group of patients lacked peripheral B cells. Where Ig secretion was present with anti-IgM and IL-2, EBV increased it, but where it was absent, EBV only induced IgM secretion in two out of eight Group A patients and IgG in one out of five Group B patients. These classifications are related to the sex of the patient and may represent different loci of the block in B-cell differentiation in CVI.
Antibodies, Anti-Idiotypic↗
An NADH-linked luciferase assay for glycogen: the preparation of glycogen-free, viable human eccrine sweat glands.
A glycogen assay based on bacterial NADH luciferase is described. It is free of tissue interference. The detection limit is 0.12 nmol glycogen, and the coefficient of variation is 5.5%. A method of depleting human eccrine sweat glands while retaining their viability is described. This depends on their incubation in 10(-5) M acetylcholine and 1 mM pyruvate. This method may be applicable to other tissues. The evidence for the viability of glycogen-depleted human eccrine sweat glands is reported and includes tissue contents of ATP and the rates of oxidation of glucose, pyruvate, beta-hydroxybutyrate, and palmitate.
Adenosine Triphosphate↗
B cell function in acquired "common-variable" hypogammaglobulinemia: proliferative responses to lymphokines.
We have compared the proliferative responses of an enriched population of B lymphocytes from patients with acquired (common variable) hypogammaglobulinemia (CVH) with the responses of cells from normal individuals. The uptake of [3H]thymidine into DNA was measured on stimulation with a range of interleukins (IL-2, IL-4, and IL-6) and solid-phase anti-IgM. Flow cytometry using CD19 and surface IgM showed that the "non-T" preparations from the peripheral blood of CVH patients either contained B cells within the normal range (30-40% of the cells) or in a minority group no B cells (less than 3% of the cells). Overall, there were no significant differences between the proliferative responses of patients' cells (in the group where normal numbers of B cells were present) and normal cells with any combination of stimulus used. No IgG was produced by cells from any patient and in only one patient was IgM production observed. This suggests that the primary B lymphocyte defect in CVH is in the differentiation phase in B cell function rather than in the growth phase. However, the presence or absence of B cells suggests that different defects exist in subgroups of patients with this disease.
Agammaglobulinemia↗
Assessment of responses of normal human B lymphocytes to different isolates of human immunodeficiency virus: role of normal donor and of cell line used to prepare viral isolate.
The effect of different HIV-1 isolates on normal human B lymphocyte function has been studied in vitro. Production of IgM and IgG was measured by ELISA using a "standard" non-T preparation of B cells depleted of macrophages and T cells (but not of low-density accessory cells, LDC). Only one (H9/CBL-4) of five different isolates induced polyclonal production of immunoglobulin. Apart from intrinsic differences between isolates, important inherent variables were shown to affect the response. One was the mix of cell types in the responding preparation of B cells. This was tested by examining the effects of HIV-1 isolates independently on the accessory function of LDC and on B cell function when the LDC were removed. Isolate H9/HTLV-IIIRf was nonstimulatory on a B cell preparation containing LDC and suppressive on LDC accessory function yet could enhance function of B cells when the LDC were depleted. Another variable was the donor of the normal B cells. The B cell response was consistent with each donor but varied greatly with different donors. Thus, no single explanation emerges for the hypergammaglobulinemia in some adult AIDS patients and for the hypogammaglobulinemia in some pediatric cases. Additionally, the cell lines used to propagate the virus particularly affected the assay of B cells depleted of LDC. Uninfected supernatants had different effects on the B cell function, and these host cell effects (perhaps by release of cytokines or other mediators) may be exacerbated in infected cell lines. Our data show the complexity of the abnormal B cell function in AIDS.
Acquired Immunodeficiency Syndrome↗
Nicotine intake in young smokers: longitudinal study of saliva cotinine concentrations.
Smoking habits and smoke intake were studied over three consecutive years in 197 girls, initially aged 11 to 14 years. Saliva cotinine concentrations in girls who were smokers throughout the three years increased over each year of the study, the greatest increase occurring during movement from occasional to daily smoking. Cigarette consumption also increased over the two years. For a group of continuing daily smokers (n = 23), inhalation of smoke per cigarette as indexed by the ratio of cotinine concentration to average daily cigarette consumption did not change over time. Cotinine concentrations in 16 girls who were smoking on a daily basis within a year of starting to smoke suggested the early development of inhalation. Our findings suggest that young smokers learn to inhale cigarette smoke very early in their smoking careers, that further increases in smoke intake mainly reflect increased cigarette consumption, and that the pharmacological effects of nicotine are already important in reinforcing their smoking.
Adolescent↗
Accessory and T cell defects in acquired and inherited hypogammaglobulinaemia.
Cellular defects in patients with common variable hypogammaglobulinaemia (CVH) and X-linked agammaglobulinaemia (XLA) have been studied in vitro, using a mitogen-driven system of immunoglobulin production. We have confirmed our previous finding of impaired low-density (dendritic) accessory cell function in CVH and now show that accessory cell function is normal in XLA. We demonstrate that macrophage accessory function is normal in CVH. T cell help for IgM production is also deficient in CVH, and T cell help in XLA is also abnormal for both IgG and IgM. Some XLA patients have excessive T suppressor activity. The contribution of these defects to the clinical states is discussed.
Agammaglobulinemia↗