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Biomedical subjects

B Bradley

Publications and source records attributed to B Bradley.

At least 19 recordsLinked to original sources

Classical conditioning and cognitive determinants of subjective craving for opiates: an investigation of their relative contributions.

Subjective craving for drugs is frequently reported by detoxified addicts. Explanatory models emphasizing classical conditioning (CC) and cognitive mechanisms have been proposed, and the mechanisms postulated by the two approaches are discussed here. There are three major variants of the CC model, arguing that craving is associated with conditioned changes which are respectively drug-agonistic, opponent-process, or withdrawal reactions. The cognitive model highlights the role of 'outcome expectancies' as determinants of both appetitive and avoidant motivations. The present investigation has identified correlates of craving predicted by the above models, and tested them empirically. Detoxified opiate addicts participated in in a Craving Test requiring them to rate their craving, physical state, and emotions during exposures to both neutral and drug-related material. Other measures, including personality and outcome expectancies for drug use, were also taken, and interrelationships among the variables were explored statistically. Whilst some of the predictions of the CC formulations were borne out, the cognitive model received more consistent support. The theoretical and treatment implications of these data are considered.

Adult

Nucleotide sequencing of HLA-DQ gene second exons in Chinese homozygous cells.

Six HLA class I and class II-homozygous Chinese cell lines with unique HLA-Dw types were studied. Since the majority of HLA class II nucleotide sequence polymorphism is localized within the second exons of the genes, we used the polymerase chain reaction (PCR) to amplify these regions in HLA-DQA and DQB genes and subsequently determined the nucleotide sequences. No unique DQA1 or DQB1 alleles were found. However, a new haplotype of DQA1*0601-DQB1*0301-DRB1*1202 was found in two cells; and DQA1*03011 was found in association with DR9 in another two cells. This indicates that new DR-DQ associations may explain the observed new HLA-Dw types. The DQB2 sequences were identical in all six cells and were identical to a sequence previously reported in a DR6 haplotype. The DQA2 sequences from two clones obtained from two cells differed from each other and from previously reported sequences. The results show that the DQA1 and DQB1 alleles in the Chinese individuals studied are as previously reported in Caucasian populations and as such may be typed by restriction fragment-length polymorphism (RFLP) or PCR-sequence-specific oligonucleotide typing (PCR-SSO) or PCR-RFLP using conventional probe or restriction enzyme sets.

Base Sequence

Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness.

Using immunohistochemistry and a panel of monoclonal antibodies, we have compared T-lymphocyte, eosinophil, macrophage, and neutrophil infiltration in bronchial biopsies from 10 intrinsic (nonallergic) asthmatics (IA) and seven extrinsic (allergic) asthmatic (EA), with similar degrees of disease severity. The results were compared with 12 normal healthy nonatopic controls (NC). All subjects were nonsmokers and were not taking oral or inhaled corticosteroids. An intense mononuclear cell infiltrate was identified in IA with an increase in the number of CD45+ cells (total leukocytes), CD3+ and CD4+ lymphocytes, and CD68+ macrophages (p < 0.03, p < 0.01, p < 0.03, and p < 0.03, respectively), compared with NC. Increases were also found in CD4+ (p < 0.05) and CD68+ (p < 0.05) cell numbers between IA and EA. IL-2 receptor-bearing cells (CD25+) and the number of total (MBP+) and actively secreting (EG2+) eosinophils, were also increased in IA compared with NC (p < 0.01, p < 0.01, and p < 0.01, respectively). Similar increases in EG2+ eosinophils and CD25+ (IL-2 receptor-positive) cells were observed in EA (p < 0.01 and p < 0.02, respectively). No differences were detected in the three groups for the number of elastase-positive cells (neutrophils). EG2+ numbers in IA correlated with the Aas asthma symptoms score (r = 0.65, p < 0.05), whereas EG2+ cell numbers in all asthmatics (IA + EA) correlated with airway methacholine responsiveness (r = -0.55, p < 0.03) and with the Aas asthma symptom score (r = 0.54, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Interleukin-5 mRNA in mucosal bronchial biopsies from asthmatic subjects.

Using in situ hybridization, we have investigated the expression of interleukin-5 (IL-5) mRNA in bronchial biopsies from asthmatics (n = 10) and controls (n = 9). The number of IL-5-nRNA-positive cells were compared with the number of CD25+ and EG2+ cells and total eosinophil counts. Specific hybridization signals for IL-5 mRNA were demonstrated in 6 out of the 10 asthmatic subjects but in none of the controls. The 6 IL-5-mRNA-positive asthmatics tended to have more severe disease and showed a significant increase in the degree of infiltration of the bronchial mucosa by activated T lymphocytes and eosinophils.

Asthma

Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma.

We have attempted to identify mRNA for IL-5 in endobronchial mucosal biopsies from asthmatics and controls, using the technique of in situ hybridization. Bronchial biopsies were obtained from 10 asthmatics and 9 nonatopic normal controls. A radio-labeled cRNA probe was prepared from an IL-5 cDNA and hybridized to permeabilized sections. These were washed extensively before processing for autoradiography. An IL-5-producing T cell clone derived from a patient with the hyper-IgE syndrome was used as a positive control. As a negative control, sections were also treated with a "sense" IL-5 probe. Specific hybridization signals for IL-5 mRNA were demonstrated within the bronchial mucosa in 6 out of the 10 asthmatic subjects. Cells exhibiting hybridization signals were located beneath the epithelial basement membrane. In contrast, there was no hybridization in the control group. No hybridization was observed with the sense probe. The six IL-5 mRNA-positive asthmatics tended to have more severe disease than the negative asthmatics, as assessed by symptoms and lung function, and showed a significant increase in the degree of infiltration of the bronchial mucosa by secreting (EG2+) eosinophils and activated (CD25+) T lymphocytes. Within the subjects who showed positive IL-5 mRNA, there was a correlation between IL-5 mRNA expression and the number of CD25+ and EG2+ cells and total eosinophil count. This study provides evidence for the cellular localization of IL-5 mRNA in the bronchial mucosa of asthmatics and supports the concept that this cytokine regulates eosinophil function in bronchial asthma.

Adult

Postwithdrawal exposure treatment to prevent relapse in opiate addicts: a pilot study.

A major problem in treating opiate addiction is relapse within a few months after withdrawal. Learning models of relapse offer some promise toward understanding this problem. The present pilot study examines whether cue-exposure treatment to drug-related cues, in hospital and real life, might reduce relapse. Fourteen opiate addicts were withdrawn on clonidine over 6 days, and 10 of those were exposed to drug-related cues in hospital for 1 week and in real life for another. There were then followed as outpatients up to 6 months. Craving was elicited in half of the 10 patients exposed to drug cues who showed within- and between-session habituation. Four cases were opiate-free at 6 months follow up and 1 at 3 months. Half of the cases had relapsed to heroin at various times up to 6 months. Habituation to craving responses was not obviously related to outcome whereas vocational factors were. The operational use of craving in research is discussed.

Adult

Receptor expression and functional status of cultured human eosinophils derived from umbilical cord blood mononuclear cells.

Selective use of recombinant human cytokines has enabled the culture of large numbers of eosinophils from human cord blood mononuclear cells, raising the possibility of their use as a model of eosinophil function. Cultured eosinophils (CE) were compared with normal-density peripheral blood eosinophils (PBE) in terms of their membrane receptor expression and function. Fc gamma R and CR1 expression of CE and PBE was similar. In contrast, the specific mean fluorescence for LFA-1 alpha, p150,95 alpha, ICAM-1, and HLA-DR was significantly elevated for CE compared with PBE. CE responded in PAF-induced chemotaxis in a similar fashion to PBE. CE gave higher numbers of both resting and platelet activating factor (PAF)-stimulated immunoglobulin G (IgG)- and C3b-dependent rosettes than PBE. CE and PBE had comparable capacity to kill IgG- and C-opsonized schistosomula in terms of both baseline values and PAF-induced enhancement of cytotoxicity. Baseline adherence by CE and PBE to plasma-coated glass was essentially the same, but stimulated adhesion (PAF) of CE was lower. Compared with PBE, CE generated less than half the amounts of extracellular and cell-associated PAF induced by calcium ionophore A23187 stimulation. Unlike PBE, CE did not generate PAF after exposure to IgG-coated Sepharose particles. CE stimulated with IgG-coated beads generated small quantities of LTC4, while A23187 stimulation resulted in approximately half the LTC4 levels observed with PBE. The total cell content of eosinophil peroxidase (EPO) was similar for CE and PBE. These data suggest that although CE and PBE have many phenotypic and functional properties in common there are quantitative differences that may be a consequence of their immaturity and/or the influence of the cytokines used in their culture.

Animals

Detection of hepatic malignancies using Mn-DPDP (manganese dipyridoxal diphosphate) hepatobiliary MRI contrast agent.

A new hepatobiliary contrast agent (Mn-DPDP) was used in the detection of liver metastases in six rabbits with seven hepatic V2 carcinomas. This contrast agent is derived from pyridoxyl-5-phosphate which is biomimetically designed to be secreted by the hepatocyte. After Mn-DPDP administration, a 105% increase in liver signal to noise was obtained using a 200/20 (TR/TE) pulsing sequence, and a 62% decrease in intensity was observed using a 1200/60 pulsing sequence. Liver V2 carcinoma contrast enhancement increased 427% using the 200/20 pulsing sequence and 176% using the 1200/60 pulsing sequence. Four of seven V2 carcinomas were not detectable prior to the administration of Mn-DPDP (50 mumol/kg). Two neoplasms were only detectable in retrospect (after Mn-DPDP) on the 1200/60 sequence. The smallest neoplasms detected in this study were 1-4 mm. Mn-DPDP appears to be a promising MRI contrast agent.

Animals

Factors predicting outcome among opiate addicts after treatment.

Eighty opiate addicts who had been successfully withdrawn from drugs were followed up for a period of six months after leaving treatment. Variables which might have been expected to relate to subsequent abstinence or drug taking were regressed against measures of outcome. Two variables consistently emerged as predictors of outcome. The number of protective factors identified by the subject and a measure of confidence about being able to remain drug free were both related to frequency of drug use during the first two months after leaving treatment, to drug status at six months and to improvement during the six-month period. In addition, the length of previous periods of abstinence related to outcome at six months, as did time spent in treatment, though caution is urged in the interpretation of this latter effect. Although risk factors have been found to relate to relapse there was no relation between perceived risks and outcome. Also, the number of coping strategies identified at admission was only related to outcome during the immediate post-discharge period. The implications of these findings are discussed in terms of a model of relapse.

Adaptation, Psychological

Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma.

We have used immunohistochemistry and monoclonal antibodies to analyze the phenotypic composition and activation status of the cellular infiltrate of bronchial biopsies obtained by fiber optic bronchoscopy of 11 atopic asthmatic subjects (FEV1% predicted range 78 to 114), 9 atopic nonasthmatic control subjects, and 10 normal healthy subjects. Examination of mucosal biopsies obtained from both central (level I) and subsegmental (level II) bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma. There was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells (a marker of lymphocyte activation) at airway level I in the asthmatic group compared with both nonasthmatic atopic (p less than 0.05) and normal control subjects (p less than 0.01). Eosinophil numbers were significantly increased in asthma at both airway levels and at airway level II in the nonasthmatic atopic group when compared with normal healthy control subjects (p less than 0.05). EG2-positive cells (an index of secretion of eosinophil cationic protein following activation) were found at both airway levels in the asthmatic group and at level I in the nonasthmatic atopic control group (p less than 0.05). When asthmatic subjects were compared with normal healthy subjects, there was a reduction in the number of neutrophil elastase-positive cells in the asthmatic subjects which, as a percentage of leukocytes, was significant (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Clonidine versus long- and short-term methadone-aided withdrawal from opiates. An uncontrolled comparison.

Twelve heroin addicts and one methadone addicts began withdrawal from street opiates, under clonidine cover, in a general psychiatric ward. Ten (80%) of them completed it within 6 days. Clonidine doses used were lower than in similar studies and all patients were alert and mobile throughout withdrawal. Two other groups of opiate addicts, of similar age and sex, were withdrawn on standard methadone regimens. Clonidine and methadone withdrawal had similar acceptability and attrition rates. Self-reports of subjective discomfort were higher in the clonidine group without affecting compliance with treatment. Withdrawal under clonidine cover deserves further study, in view of the need for postwithdrawal treatment to prevent relapse to opiate use.

Adult

Fc gamma and CD11/CD18 receptor expression on normal density and low density human eosinophils.

We have studied the expression of Fc gamma receptors and leucocyte integrins (CD11/CD18 family) on human eosinophils using specific monoclonal antibodies (mAb) and flow cytometric analysis. Peripheral blood eosinophils of normal density and low density were compared with neutrophils and monocytes. Several properties of the human eosinophil were established. These were (i) that the eosinophil expressed Fc gamma RII (CDw32) only (unlike monocytes which bear Fc gamma RI and Fc gamma RII and neutrophils which bear Fc gamma RII and Fc gamma RIII); (ii) that the absence of Fc gamma RIII (CD16) on eosinophils served as a basis for distinguishing eosinophil and neutrophil populations by immunofluorescence; (iii) that the leucocyte adhesion glycoproteins, LFA-1 alpha (CD11a), CR3-alpha (CD11b), p150, 95-alpha (CD11c) and the common beta-chain (CD18), were expressed on the eosinophil as well as the neutrophil; (iv) that CD18 expression was significantly reduced on low-density eosinophils from the hypereosinophilic syndrome. Thus, our findings emphasize the unique phenotype of the human eosinophil in terms of Fc gamma receptor expression, the similarity of the eosinophil and neutrophil with regard to the leucocyte integrins and that eosinophils of low density do not differ greatly from those of normal density in terms of receptor expression.

Antigens, Differentiation

Pancreatic islet-specific T-cell clones from nonobese diabetic mice.

We have produced a panel of islet-specific T-cell clones from nonobese diabetic (NOD) mice. These clones proliferate and make interleukin 2 in an antigen-specific manner in response to NOD antigen-presenting cells and islet cells. Most of the clones respond to islet-cell antigen from different mouse strains but only in the presence of antigen-presenting cells bearing the class II major histocompatibility complex of the NOD mouse. In vivo, the clones mediate the destruction of islet, but not pituitary, grafts. Furthermore, pancreatic sections from a disease transfer experiment with one of the clones showed a pronounced cellular infiltration and degranulation of islets in nondiabetic (CBA x NOD)F1 recipients.

Animals

Bismuth toxicity--a reassessment.

Bismuth compounds, in particular bismuth subsalicylate and colloidal bismuth subcitrate, are now being actively promoted for the treatment of diarrhoea and peptic ulcer disease. The past history of the therapeutic use of bismuth compounds has been marred by episodes of serious adverse reactions. Salicylism is a possible complication with bismuth subsalicylate. This article reviews the pertinent literature on the reported adverse reactions to bismuth compounds to provide the necessary background to assess the value of bismuth subcitrate and bismuth subsalicylate as therapeutic compounds.

Bismuth