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Biomedical subjects

B Jordan

Publications and source records attributed to B Jordan.

At least 55 records · Page 3Linked to original sources

Views of what's wrong: diagnosis and patients' concepts of illness.

A group of women were interviewed about their construction of their illness experiences before they saw a physician and subsequently over a period of several months following consultation. It was found that the physician's input was one of many components of their post-consultation understanding of their illnesses. The women built up their understandings in an interactive process, drawing significantly on their prior histories, ongoing experiences and social worlds. They continually tried out, adjusted and reworked the construction of their illnesses to adapt them to the exigencies of everyday life. We conclude that illness explanations are dynamic entities whose adequacy is determined by their usefulness within the extra-medical social environment.

Adult↗

A study of functionally active amino acids involved in the interaction of HLA-A2 or HLA-A3 molecules with cytolytic T lymphocytes.

A large series of HLA-A2/HLA-A3 recombinant genes were generated by using the in vivo recombination technique. These genes have each been modified in the last two-thirds of the third exon such that one or several HLA-A2-specific substitutions have been made in the HLA-A3 gene and vice versa. The recombinant genes were transfected into the murine cell line P815 and the transfectants were used as targets for a series of 20 human CTL lines or clones specific for HLA-A2 or HLA-A3, or restricted by HLA-A2 and specific for influenza A. Several patterns of anti-HLA-A2, anti-HLA-A3, and HLA-A2-restricted anti-influenza CTL activity were observed and when uncloned cell lines were studied, a progressive selection of some clones with a similar pattern of activity was regularly found. From the comparison of these different patterns the following conclusions can be drawn: 1) In most but not all cases both domains of the class I molecule were essential for CTL recognition, but residue 152 was critically important for the majority of CTL tested; 2) amino acids 114/116 were also critical in most cases, and their position close to amino acid 152 in the tertiary structure of the molecule may have some functional significance; and 3) amino acid 161, although highly conserved, plays an unexpected but very important role in CTL function.

Amino Acids↗

Hybrid genes between HLA-A2 and HLA-A3 constructed by in vivo recombination allow mapping of HLA-A2 and HLA-A3 polymorphic antigenic determinants.

HLA-A2 and -A3 genes have been modified in their third exon (second domain) by using in vivo recombination. In this method Escherichia coli are transfected with a plasmid which contains two highly homologous sequences (e.g., the third exons of HLA-A2 and -A3) and has been linearized by cleavage between these two sequences. Circularization takes place in the bacteria by homologous recombination leading to hybrid A2-A3 sequences. The analysis by DNA sequencing of a number of such recombinants shows that they indeed occur by homologous recombination (no insertions or deletions) and that the probability of crossing over decreases as the distance from the free end of DNA in the homologous region increases. No double recombinants were observed. These hybrid exons were reinserted into either HLA-A2 or HLA-A3 genes, thus generating a panel of functional hybrid genes containing one or several HLA-A2 specific substitutions in an HLA-A3 background or vice versa. These genes were expressed by transfection into murine P815-high transfection efficiency recipient cells. Serologic analysis leads to the conclusion that expression of polymorphic antigenic determinants specific for HLA-A2 (detected with M58, A2A28M1, and CR11.351 mAb) is linked to the presence of threonine residue (amino acid (AA) 142) and/or histidine residue (AA 145) and valine residue (AA 152). The expression of specific HLA-A3 polymorphic determinants (recognized by GAP-A3 mAb) is correlated with the existence of a asparagine residue (AA 127) and a aspartic residue (AA 161). But aspartic residue 161 contributes with glutamic acid residue 152 in the formation of the A3 epitope recognized by the anti-A3 mAb X1.23.2.

Antibodies, Monoclonal↗

H2-restricted recognition of cloned HLA class I gene products expressed in mouse cells.

Long-term syngeneic mouse cytolytic T lymphocyte (CTL) clones were obtained from DBA/2 (H2d) mice immunized with P815 (H2d) cells transfected with cloned human class I histocompatibility genes, HLA-CW3 or HLA-A24. Three distinct patterns of specificity were defined on P815 HLA transfectant target cells. One clone lysed HLA-CW3 but not -A24 transfectants, and a second lysed HLA-A24 but not -CW3 transfectant target cells. The third clone lysed P815 targets transfected with either HLA gene. None of the CTL clones lysed L cells (H2k) transfected with the same HLA genes or human targets that expressed these HLA specificities. Several lines of evidence indicated that recognition of HLA transfectants by these CTL clones was H2 restricted. First, lysis of P815 HLA transfectants could be inhibited by anti-H2Kd monoclonal antibody. In addition, the anti-P815-HLA CTL clones could lyse a (human X mouse) hybrid target that expressed both HLA class I and H2Kd antigens, but not a clonal derivative that no longer expressed H2Kd. The most direct evidence for H2-restricted recognition of P815-HLA transfectants by the syngeneic CTL clones was obtained by double transfection of mouse L cells (H2k) with both HLA and H2 class I genes. L cells transfected with HLA and H2Kd genes were susceptible to lysis by the same CTL clones that lysed the corresponding P815-HLA transfectant targets. Thus under certain conditions, CTL recognition of xenogeneic class I histocompatibility gene products can be restricted by other class I gene products.

Animals↗

Naltrexone and Alzheimer's disease.

Naltrexone, an oral opiate antagonist, was administered to nine patients with a diagnosis of Alzheimer's-type dementia (ATD) in a two-phase design: an open dose-ranging phase and a double-blind placebo-controlled trial for patients who showed improvement during the open phase. After a three day placebo (baseline) period, patients received increasing doses of naltrexone over two weeks up to a maximum daily dose of 100 mg. Assessments were made at baseline and at daily dose of 5 mg, 50 mg and 100 mg. Testing was done 2 to 4 hours after medication was administered. Any patient who showed cognitive/behavioral improvement on a given dose of naltrexone was then treated with this dosage in a double-blind crossover comparison to placebo. Criteria for inclusion in the double-blind phase consisted of improvement on three behavioral scales and at least one cognitive test on a given dose of naltrexone. Each double-blind phase followed a one-week washout and was two weeks long. Two of the nine patients demonstrated apparent cognitive enhancement on 100 mg daily of naltrexone and were then tested in the double-blind crossover period. Only one of these patients improved during active naltrexone administration. We conclude that the opiate antagonist naltrexone in a dosage range of 5-100 mg daily is not efficacious in ATD.

Alzheimer Disease↗

Essential fatty acid supplementation in tardive dyskinesia.

Preclinical and clinical observations suggest that enhancement of prostaglandin activity inhibits catecholamine release and may have antidyskinetic effects. A double-blind therapeutic trial with prostaglandin precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia. No beneficial effects were seen.

Clinical Trials as Topic↗

Human T cell recognition of cloned HLA class I gene products expressed on DNA transfectants of mouse mastocytoma P815.

Cloned genes for human major histocompatibility complex (MHC) class I antigens were introduced by DNA-mediated gene transfer into a high-efficiency transfection recipient (HTR) cell line previously derived from mouse mastocytoma P815. Cell surface expression of HLA-A3, AW24 and CW3 gene products on P815 transfectants was demonstrated by radioimmune assay and by flow cytometry. The human MHC class I gene products were apparently expressed on P815 transfectants in a form recognized by human cytolytic T lymphocytes (CTL). Human CTL generated in unidirectional mixed lymphocyte culture against AW24+ donor lymphocytes clearly lysed P815-HLA-AW24+ transfectant target cells, but not untransfected P815(HTR) controls. Moreover, P815-HLA transfectants could stimulate in vitro a significant alloreactive human CTL response. Lysis of P815-HLA transfectant target cells by human CTL was inhibited by a monoclonal antibody directed against human MHC class I gene products. These mouse cell transfectants may be useful for the study of human T cell responses.

Animals↗

Induction with a synthetic peptide of antibodies to HLA class I C-terminal intracytoplasmic region.

Site-specific antibodies to HLA class I molecules have been raised in rabbits immunized with a synthetic peptide with the same amino acid sequence as HLA residues 328-338, which corresponds to the highly conserved intracytoplasmic region. Antibodies were detected by radioimmunoassay and were able to recognize isolated HLA heavy chains blotted onto nitrocellulose as well as the biosynthetically labeled HLA-beta 2 microglobulin complexes solubilized by non-ionic detergents. The intracellular localization of the determinants recognized by the antibodies was shown by indirect immunofluorescence labeling and the specificity of the reaction confirmed by its inhibition with the synthetic peptide. No cross-reaction was seen with H-2 antigens on murine cells. These antibodies will be important for further characterization of HLA antigens and detection of their expression in mouse cells transfected with human genes.

Animals↗

External cephalic version as an alternative to breech delivery and cesarean section.

External cephalic version (ECV), the transabdominal manipulation of a breech-presenting fetus into a head-down position before birth, is common in traditional ethno -obstetric systems as well as in the modern scientific obstetrics of Europe. In the United States, this practice has fallen out of use and is no longer taught in medical schools or obstetric residencies. The currently standard American management options for breech are either breech delivery or, most frequently, cesarean section. This paper examines the historical and cross cultural distribution of ECV, describes the various methods for effecting version of the fetus, and assesses the risks of the procedure. It is concluded that the data available are inadequate to either condemn the practice or to advocate it without reservation. It is suggested that ECV may constitute an attractive conservative management strategy for breech presentation in scientific obstetric systems as well as in those developing countries where the skill to do versions is part of the traditional inventory of midwifery skills.

Breech Presentation↗

HLA class I genes integrated into murine cells are inducible by interferon.

In human cells treated with interferon, there is an increase in the amount of HLA-A, B, C mRNA and, to a lower extent, membrane-bound antigen. However, the mechanism of this mRNA enhancement is still unknown. Using mouse L cells transfected with a unique class I HLA gene, we were able to show that both the related HLA mRNA and protein are increased after murine but not human interferon treatment. Moreover, the discrepancy between interferon-directed HLA mRNA and protein enhancement is also observed. The mouse transfected cells allowed us to study more precisely the origin of this discrepancy.

Animals↗

Rat IgD myeloma protein: cell-free translation of the delta mRNA and biochemical analysis of intracellular and membrane delta chain.

The analysis of IgD molecules produced by the tumor-derived IR 731 cell line showed that these molecules are not secreted and are only present at the cell surface as covalent dimers of 48 000 dalton delta chains. The original IR 731 tumor secreted complete IgD; thus, the disppearance of secretion in the cell line was correlated with the absence of light chain synthesis. The mRNA coding for the cell line delta chain was isolated and translated. The analysis of the translated delta chain (mol. wt.: 40 000) confirmed the absence of a region having the size of a domain as previously shown by partial amino acid sequence. The observation that the absence in delta chain of this region, which comprises most of the CH2 domain, could be a general feature of murine species is discussed.

Animals↗

A double-blind comparison of trebenzomine and thioridazine in the treatment of schizophrenia.

Forty inpatient volunteers with diagnoses of schizophrenia were randomly assigned to treatment either with trebenzomine or thioridazine in a double-blind study of clinical antipsychotic efficacy following a 1-week placebo treatment. Psychopathology was rated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). There was a significant difference in therapeutic response to the two drugs in that psychopathology decreased significantly for the thioridazine group, but not for the trebenzomine group. Serum prolactin was elevated during treatment with thioridazine, but not with trebenzomine. Side effects were more frequently reported for the thioridazine group. These results fail to confirm previous reports of clinical antipsychotic efficacy for trebenzomine.

Adolescent↗