Glucocorticoid receptors in alveolar macrophages: methodological aspects of the determination of the number of glucocorticoid receptors per cell

Among patients with asthma or chronic obstructive pulmonary diseases the response to glucocorticoids varies considerably. To investigate the possible relationship between clinical response and number of glucocorticoid receptors in alveolar macrophages or their KD value a micro receptor assay was developed. Assay conditions were adjusted because of receptor occupancy by endogenous or therapeutically used glucocorticoids and high aspecific binding.     

PSYCHOLOGICAL EFFECTS OF AN EPIDEMIOLOGICAL STUDY OF BENIGN PROSTATIC HYPERTROPHY

SUMMARY The psychological impact of an epidemiological study of benign prostatic hypertrophy (BPH) was assessed in a representative sample of practice list patients. Of the 889 men completing a general health self-report questionnaire previously validated in a screening programme, 75% knew nothing of problems of the prostate, and 84.5% were not at all worried about prostate problems prior to commencement of the study. Receiving the letter of invitation and the procedures neither increased nor reduced anxiety levels for 69% and 70% respectively. In the 227 men referred to hospital for further investigation the procedure increased anxiety in 28%, decreased anxiety in 20%, and had no effect on the remainder. The sample of 137 (16%) men who, prior to interview, were in some way worried about problems of the prostate had significantly more urinary tract symptoms than those who were not at all worried about prostatic problems. Despite being worried about prostatic problems and having significant urinary symptoms, this group was no more likely to have attended a GP for investigation and/or treatment. Results are discussed in relation to the possible psychological effects of general health screening and the reluctance of men to attend for consultation despite awareness and concern regarding urinary symptomatology.     

Detection of Undiagnosed Coeliac Disease with Atypical Features Using Antireticulin and Antigliadin Antibodies

Eighteen patients with a variety of non-gastrointestinal symptomswere incidentally found to have circulating antireticulin antibodyand on subsequent testing were also positive for antigliadinantibody. They prospectively underwent jejunal biopsy to determinewhether or not they had coeliac disease. Their age range was21–79 years (mean 42 years). Enteropathy was present in13 (72 per cent) and was always associated with circulatingIgA antigliadin antibody. Enteropathy was not present in thefive cases who had only IgG antibody. Clinical improvement occurredin eight of 11 patients who complied with a gluten-free dietand was paralleled by an improvement in the mucosal histologyin seven of eight who were re-biopsied. The most remarkablecases were two patients who presented with severe debility andno apparent haematological or biochemical abnormalities, andwho subsequently made a dramatic recovery on a gluten-free diet.It is concluded that antireticulin antibody detected by routineautoantibody screening and confirmed to have IgA antigliadinantibody specificity is a useful indicator of an otherwise undiagnosedenteropathy. This serves to emphasize that the condition cansometimes be associated with atypical features and significantmorbidity.     

Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones

PPAR gamma is required for fat cell development and is the molecular target of antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that inactivation of PPAR gamma in macrophages results in the development of significant glucose intolerance plus skeletal muscle and hepatic insulin resistance in lean mice fed a normal diet. This phenotype was associated with increased expression of inflammatory markers and impaired insulin signaling in adipose tissue, muscle, and liver. PPAR gamma-deficient macrophages secreted elevated levels of factors that impair insulin responsiveness in muscle cells in a manner that was enhanced by exposure to FFAs. Consistent with this, the relative degree of insulin resistance became more severe in mice lacking macrophage PPAR gamma following high-fat feeding, and these mice were only partially responsive to TZD treatment. These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs.     

Graft-vs.-host reactions: mechanisms and contemporary theories

A graft-vs.-host (GvH) reaction can be initiated by injection of immunocompetent lymphocytes into a histoincompatible host that is unable to reject these cells. The reaction is characterized by splenomegaly, hepatomegaly, lymph node atrophy, body weight loss, dermatitis, and diarrhea, often leading to mortality. The onset and severity of the GvH reaction are determined by differences in histocompatibility antigens between the donor and the acceptor, and by the number and nature of the transplanted allogeneic cells. Many different in vivo and in vitro systems have been devised for experimental studies of the GvH reaction. In several of these models, however, different parameters are measured. Furthermore, the conclusions drawn from these investigations sometimes contradict each other. This paper reviews the experimental data, and discusses the mechanisms underlying the GvH reaction.