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Biomedical subjects

E Adams

Publications and source records attributed to E Adams.

At least 91 records · Page 5Linked to original sources
PubMed1991

Breakdown of self-tolerance in anergic B lymphocytes.

Production of autoantibodies, which characterizes most autoimmune diseases, is normally avoided by active elimination or functional inactivation (anergy) of B and T lymphocytes bearing receptors for self antigens. The mechanisms leading to the escape of self-reactive clones from these normal tolerance mechanisms in autoimmune diseases nevertheless remain obscure. Here, we demonstrate that clonal anergy in B lymphocytes is a reversible process, and that silenced self-reactive B cells can be reactivated under particular conditions to give rise to vigorous antibody responses. Reactivation of anergic lymphocytes may explain many examples of transient autoimmune reactions in normal individuals, and may under pathological conditions be important in the development of chronic autoimmune disease.

Animals↗
PubMed1991

Sequence and immunogenicity of the 70-kDa heat shock protein of Mycobacterium leprae.

The gene encoding the Mycobacterium leprae 70-kDa heat shock protein has been isolated from a cosmid library using a fragment of the clone JKL2. Southern blot analysis of a positive clone identified a 4.4-kb fragment containing the entire coding region of the gene plus 2.4 kb upstream. Sequencing revealed the gene to encode a 621-amino acid protein, bearing 56% identity with the Escherichia coli dnaK gene product and 47% and 46% identity with the human and Caenorhabditis elegans hsp70, respectively. Comparison with the C-terminal 203 amino acids of the Mycobacterium tuberculosis 71-kDa Ag yielded 70% identity. Recombinant M. leprae p70 was produced in E. coli as a fusion protein (rp70f) with a portion of the schistosomal glutathione-S-transferase, using the expression vector, pGEX-2T. Cleavage with thrombin resulted in the release of a 70.0-kDa protein (rp70c) from the glutathione-S-transferase. Examination of the proteins by immunoblotting demonstrated that anti-M. leprae mAb, L7, and sera from lepromatous leprosy patients bound to both the cleaved and fusion proteins. We compared the T cell reactivity of the M. leprae recombinant proteins with that of mAb affinity-purified bacille Calmette-Guerin (BCG) 70-kDa Ag using proliferation assays. PBMC of BCG vaccinees responded to both M. leprae cleaved and fusion p70, though more subjects responded to the rp70c (18 of 20) than to rp70f (13 of 20). Responses were generally higher to rp70c than to rp70f, however all responses to the M. leprae recombinant proteins were lower than to mAb affinity-purified BCG p70. Thus, the M. leprae 70-kDa heat shock protein elicits T and B cell responses in subjects exposed to mycobacteria, despite its homology with the human hsp70.

Amino Acid Sequence↗
PubMed1991

Normal sequence of the gonadotropin-releasing hormone gene in patients with idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) results from absent or greatly diminished secretion of GnRH. Defects in the GnRH gene have been identified in an animal model of IHH and have been hypothesized as a possible basis for GnRH deficiency in humans. In this study, we used the polymerase chain reaction to clone and sequence the coding regions, promoter, and 3' untranslated tract of the GnRH genes from both alleles of four unrelated patients with IHH. One of the patients studied is a member of a kindred in which X-linked inheritance has been excluded by father-to-son transmission of the disease. No DNA sequence mutations were found. We conclude that most cases of IHH in humans do not involve mutations in the GnRH gene and are presumably caused by mutations at one or more other genetic loci that are required for normal function of GnRH-producing neurons.

Adolescent↗
PubMed1991

The prediction of dentists' work behaviour; factors affecting choice or intention in the treatment of special need patients.

The present study was undertaken as part of an overall strategy to develop a co-ordinated dental health care programme for special need patients between general dental practitioners and the community dental service. The beliefs, attitudes and work behaviours of the practitioners were examined, using the theory of reasoned action, in order to highlight perceived difficulties associated with treating this particular patient group as well as to find those dentists willing to treat and carry out domiciliary dental care for them. The results demonstrated that those dentists who had previous experience of treating special need patients and carrying out a variety of domiciliary dental treatments intended to provide dental care for this group. Furthermore, the dentists differed in their evaluations with regard to beliefs and attitude. Those dentists who intended to provide dental care appeared to have more positive attitudes and were able to assess and perceive the relevance as well as the reality of their own beliefs in the light of their previous working behaviours.

Adult↗
PubMed1990

Intrinsic B-cell hyporesponsiveness accounts for self-tolerance in lysozyme/anti-lysozyme double-transgenic mice.

In double-transgenic mice expressing a gene construct encoding hen egg lysozyme as well as rearranged anti-lysozyme antibody genes, large numbers of anti-lysozyme B cells are present in peripheral lymphoid tissues but are profoundly tolerant. The cellular basis for this form of non-deletional self-tolerance was explored. The tolerant anti-lysozyme B cells from double-transgenic mice were found to produce much less antibody than nontransgenic controls in T-cell-dependent antigen-specific responses, in adoptive transfer in vivo, and in hanging-drop cultures in vitro, as well as in response to stimulation with the nonspecific mitogen lipopolysaccharide. The diminished responsiveness of the tolerant B cells was not due to a reduction in the number of responding B-cell precursors per se nor were suppressor cells detected in titration, depletion, or mixing experiments. Nondeletional tolerance in this model, therefore, appears to result from an intrinsic functional change in the self-reactive B cells themselves.

Animals↗
PubMed1990

T cell reactivity to the purified mycobacterial antigens p65 and p70 in leprosy patients and their household contacts.

T cell reactivity to the 70 and 65 kD (p70 and p65) protein antigens derived from Mycobacterium bovis BCG strain was studied by measuring the proliferative responses of peripheral blood mononuclear cells from members of an isolated Aboriginal community resident in the Torres Straits islands. In the nine index leprosy cases the pattern of responsiveness to the purified antigens paralleled that to whole sonicates from M. leprae and BCG. In the 40 contacts of the index cases, a high correlation was observed between the responses to p70 and p65 as well as to the crude sonicates. Significant T cell responses to the purified antigens, as well as the crude sonicates, were obtained with cells from the majority of contacts. Limiting dilution analysis of precursor frequencies in the contacts confirmed the immunogenicity of the purified antigens and excluded both a mitogenic component and the presence of suppressor cells in those moderate or low responders whose blood contained sufficient precursors to be tested. p70 appeared to be more potent in stimulating a proliferative response than p65 at equivalent protein concentrations. No correlation between responder status to either antigen and disease type was detected in families. These findings provide confirmation of the importance of p70 and p65 as major T cell immunogens in man and indicate that they are both potential candidates for inclusion in a bivalent vaccine for leprosy and tuberculosis.

Antigens, Bacterial↗
PubMed1989

Human papillomavirus associated with adenocarcinoma and adenosquamous carcinoma of the cervix: analysis by in situ hybridization.

The incidence of adenocarcinoma of the cervix appears to be increasing. Recent reports have demonstrated an association between adenocarcinoma of the cervix and human papillomavirus (HPV) by Southern blot hybridizations. In situ deoxyribonucleic acid (DNA) hybridization was performed on paraffin-embedded specimens to localize the source of HPV DNA. In pure adenocarcinoma five of six specimens were positive for HPV DNA. Four specimens contained HPV type 18 and one HPV type 16. Only one of three adenosquamous lesions was positive and it contained both HPV types 16 and 31. These findings suggest an association between HPV and adenocarcinoma of the cervix.

Adenocarcinoma↗
PubMed1989

Inhibition of human lymphoproliferative responses by mycobacterial phenolic glycolipids.

The effect of mycobacterial phenolic glycolipids from Mycobacterium leprae, M. bovis BCG, and M. kansasii on in vitro proliferative responses by human blood mononuclear cells from healthy BCG vaccinees was investigated. All three phenolic glycolipids inhibited proliferation in a concentration-dependent manner. Inhibition was independent of the stimulus used and involved neither antigen-presenting cells nor antigen-specific CD8+ suppressor T cells. It was concluded that the phenomenon may be a general property of mycobacterial phenolic glycolipids, perhaps analogous to the growth-modulating properties of gangliosides. Despite the lack of specificity of inhibition in vitro, de facto specificity may occur in vivo by virtue of the localization of glycolipid in the leprosy lesions.

Antigen-Presenting Cells↗
PubMed1989

Faculty practice: nurse educators' views and proposed models.

Faculty practice is an issue that has been extensively debated, yet no consensus about its definition, purposes, or implementation has yet been achieved among nurse educators. This nationwide survey of a random sample of 909 AD and BSN educators was designed to elicit concepts of faculty practice and to find how and why faculty are implementing practice. Sixty percent of the sample are practicing nursing; the reason most frequently given was to maintain clinical skills. The 40% not practicing stated lack of time as the primary reason. Responses demonstrated no differences between AD and BSN educators regarding definition, implementation, and motivation for faculty practice. As a result of the survey, a definition of faculty practice has been formulated and conceptual models of faculty practice delineated. The models that have been developed are the Nurse-Researcher Model, Nurse-Clinician Model, and Nurse-Consultant Model.

Humans↗
PubMed1989

Indicators of impact of services on persons with developmental disabilities: issues concerning data-collection mandates in P.L. 100-146.

Public Law 100-146 requires the Administration on Developmental Disabilities to report to the Congress in 1990 on the status of services to persons with developmental disabilities. Considerable effort has been devoted by the National Association of Developmental Disabilities Councils to providing a national methodology for characterizing state services and for surveying consumer satisfaction with these services; but these data alone will not be sufficient to adequately characterize all variables required by the 1990 report. Definitional, conceptual, and methodological issues related to measurement of scope and extent of services, documenting eligibility and accessibility, and estimating the effectiveness of services was reviewed. A framework was suggested for integrating data-collection with consumer satisfaction survey efforts already underway.

Consumer Behavior↗
PubMed1987

Intraindividual variability in theophylline pharmacokinetics in subjects with mild/moderate asthma.

Intrasubject variability in theophylline pharmacokinetics was assessed in six subjects with mild/moderate asthma. On four occasions, each separated by a minimum of 3 weeks, a 6 mg/kg intravenous aminophylline dose was infused during 30 minutes, and multiple blood samples were obtained thereafter. The pharmacokinetic parameters of clearance (Cl), volume of distribution, and half-life were determined by noncompartmental analysis. There was evidence for within-subject variability in these parameters. In comparison to the first study day, Cl changed by greater than 15% in all but one subject and by greater than 25% in two of six subjects. Changes in half-life exceeding 25% of the value observed on the first study day occurred in three of six subjects. Within-subject coefficient of variation for Cl was 14.9% (range 3.9% to 33.3%) and 14.4% (range 5.8% to 24.3%) for half-life. Volume of distribution, however, was a more stable parameter with a within-subject coefficient of variation of 7.2% (range 2.3% to 11.1%). Thus, within-subject changes in the pharmacokinetics of theophylline do exist over time. These data suggest that close monitoring of patients receiving theophylline is warranted, particularly when theophylline concentrations are maintained at either extreme of the therapeutic range.

Adult↗
PubMed1987

High dose suppression of human anti-influenza A virus responses using T cell clones.

Human T cells exposed to high concentrations of influenza A virus cause specific suppression of the in vitro antibody response to the virus, but the phenomenon does not require viable T cells. In order to investigate the mechanism of this form of suppression, IL-2-dependent T cell clones of helper phenotype (CD4+, HLA-DR+, IL-2R+) were prepared with specificity for influenza A (Mem/Bel) and B (B HK) viruses and the non-crossreacting antigen purified protein derivative (PPD). When pulsed with high dose Mem/Bel virus, all three clones transferred suppression equally well to effector cultures of syngeneic or allogeneic E+ and E- cells stimulated with an immunogenic dose of the same virus. Thus, although suppression was specific at the level of expression, the induction phase was non-specific and non-major histocompatibility complex (MHC) restricted and did not involve interaction of antigen with the T cell receptor. HLA-DR, CD3 and CD8 determinants were excluded as the binding site for the virus by two-colour immunofluorescent staining and flow cytometric analysis. The concentrations of antigen required for high dose suppression inhibited antigen-specific proliferation by the clones; on the other hand, they remained partially sensitive to IL-2 and could still release gamma-interferon. These findings suggest that this phenomenon is distinct from conventional antigen-specific suppression mediated by CD8 T cells, but may play a biologically important role in regulating immune responses at least to viral antigens.

Antibodies, Viral↗
PubMed1985

Co-expression of an epitope on human free kappa-light chains and on a cytoplasmic component in activated T cells.

K-1-21 is a murine monoclonal antibody that reacts with human kappa-light chains in free form but not when they are associated with immunoglobulin heavy chains. K-1-21 was unexpectedly shown to bind to a determinant, STA (Sezary T cell antigen), detected by immunofluorescence in the cytoplasm but not on the surface of Sezary T cells isolated from peripheral blood (4/4 cases) and in Sezary T cells from lymph node and bone marrow (one patient). STA was detected in F2/F7, CCRF-CEM, Molt-4, and CCRF-HSB (four human T ALL cell lines), in JURKAT (a human T cell leukemia line), and in MLA144 (a Gibbon T cell lymphoma line). It also occurred in Leu-3a+ antigen-specific T cell clones (6/6 tested). Moreover, although STA was absent from freshly isolated normal T cells, its expression could be evoked in E+ cells from peripheral blood by in vitro culture with phytohemagglutinin. Thus, STA appears to be a cytoplasmic marker for activated T cells. Cytoplasmic inhibition immunofluorescence studies indicated that K-1-21 binding to STA in Sezary cells or T cell lines was inhibited by preincubation of the K-1-21 antibody with purified kappa-Bence Jones protein. STA from radiolabeled MLA144 cell lysates was immunoprecipitated by K-1-21 and was identified on polyacrylamide gel electrophoresis under reducing conditions as a protein of m.w. 57,000. Additional experiments are underway to define the molecular basis of the interesting cross-reactivity between a determinant in T cells and the K-1-21 reactive epitope on free kappa-light chains.

Antigen-Antibody Reactions↗
PubMed1984

Efficacy of mexiletine in chronic ventricular arrhythmias compared with quinidine: a single-blind, randomized trial.

This single-blind, randomized study was designed to evaluate the efficacy and safety of oral mexiletine compared with oral quinidine in suppressing premature ventricular contractions (PVCs). Fifty-one patients were studied for less than or equal to 12 weeks; 26 patients were randomized to the mexiletine group and 25 to the quinidine group. The drugs were administered in an increasing dose regimen to suppress the PVCs by 70% from the baseline value in both groups. Mexiletine reduced the average number of PVCs by 70% of the baseline number in a comparable fashion to quinidine; 69% in the mexiletine group vs 70% in the quinidine group (p greater than 0.05). There was a comparable reduction (greater than or equal to 50%) of ventricular couplets from the baseline value in the 2 groups, 78% in the mexiletine group vs 86% in the quinidine group (p greater than 0.05). The effect of mexiletine on suppression of ventricular tachycardia was also similar, 72% in the mexiletine group vs 71% in the quinidine group (p greater than 0.05). There was no significant difference in the 2 groups in side effects. This study shows the comparable efficacy and tolerance of mexiletine and quinidine for the control of ventricular arrhythmias in a large number of patients with diverse forms of heart diseases.

Adult↗
PubMed1984

Mitral valve prolapse and spasm of normal coronary arteries: report of four cases and review of the literature.

The association between mitral valve prolapse (MVP) and atypical chest pain has been well-described. Numerous theories have been proposed to explain this association. A number of lines of evidence suggest that underlying ischemia may cause chest pain in some patients with MVP. We have recently evaluated 4 patients with chest pain syndromes who had angiographic evidence of MVP and spasm of angiographically normal coronary arteries. The possibility that coronary spasm is the underlying etiology of chest pain in some patients with mitral valve prolapse raises a theoretical argument against beta-blockade in these patients. Three of our patients were successfully treated with calcium channel blockers.

Adult↗