What are health authorities doing about the health problems caused by unemployment?

Unemployment is over three million in Britain, and unemployment is known to be associated with poor health. It has been suggested that health authorities should produce a comprehensive response to the health problems caused by unemployment, and a survey was undertaken to find how many had done so. All the regional and district health authorities in England, the health boards of Wales, Scotland, and Northern Ireland, and the family practitioner committees of England and Wales were asked by letter what they were doing to respond to the health problems of unemployment. A list of suggestions of what they might be doing was enclosed. The overall response rate was 77% (255/331), and 50% (127/255) of the respondents were doing something--33.3% (3/9) of the regional health authorities, 64% (101/158) of the district health authorities and health boards, and 26% (23/88) of the family practitioner committees. The paper describes what they were doing. A relation was sought between the level of unemployment in an area and the extent of the response, and a significant association was found. Half of Britain's health authorities are now responding in some way to the health problems associated with unemployment.     

Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2

Monoclonal antibodies against human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.     

Glucocorticoid effects on phenylethanolamine N-methyltransferase (PNMT) in explants of embryonic rat medulla oblongata

Although glucocorticoid hormones have important roles in the development of neurotransmitter systems in cells derived from the neural crest, it is not known whether they have parallel effects on neuronal development in the brain. To address this issue, we have established an in vitro system of fetal medulla oblongata (MO) to follow development of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT). Embryonic MO was explanted from E13 or E18 embryos and maintained for up to 3 weeks. Successful culture of adrenergic neurons was possible only in explants taken from young embryos, since E18 explants failed to develop. In E13 explants, immunoreactivity to both PNMT and tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, was observed. PNMT catalytic activity which was barely detectable at the time of explanation increased markedly during the first week in vitro. To study the effects of glucocorticoids on PNMT development in central neurons, MO explants were grown in glucocorticoid deficient medium in which rat serum from adrenalectomized rats was substituted for human placental serum. Addition of natural glucocorticoids, cortisol or corticosterone, or the mineralcorticoid, deoxycorticosterone, during the third culture week had no effect on PNMT activity. Dexamethasone (DEX), a synthetic glucocorticoid, also had no effect on PNMT during the first or second weeks in culture. However, addition of DEX during the third culture week resulted in a doubling of PNMT activity. However, attempts to block the DEX effect during the third week or to block the increase in PNMT activity during the first week in control cultures with the glucocorticoid receptor antagonist, dexamethasone 21-mesylate, were unsuccessful. These results suggest that PNMT in central neurons does not require glucocorticoids for ontogeny during the embryonic period. This is in contrast to PNMT in adrenal medulla which requires glucocorticoids for normal development during both the embryonic and postnatal periods. More generally, these studies suggest that development of the same neurotransmitter phenotype in brain and periphery may be differentially regulated.     

Effect of dithranol therapy on membrane, basement membrane and nuclear markers in psoriasis lesions

We investigated the effects of anti-psoriatic therapy with dithranol (1/20-1%) in salicylic acid (0.5%) in white petrolatum on lesional skin. FITC-labeled lectins and pemphigus vulgaris antibodies (PV) served as analytical means to study the glycocalyx. Antibodies of bullous pemphigoid (BP) were used as basal membrane markers. Nuclear antigens were recorded according to the binding of speckled, anti-nuclear antibodies (ANA) as well as antibodies to dsDNA. With some lectins, dithranol therapy resulted in pronounced fluorescence of the lower parts of the basal cells. ConA was fixed by the basal cell layer. To a lesser degree, ANA were fixed by nuclei of keratinocytes. PV antibodies were not fixed at all.     

Improved estimates of discordance ratios in twin studies

In the study of monozygotic twins relative to disease and risk factors, particular interest focuses on the subset who are discordant for some suspected risk factor (for example, smoking), since such twins constitute a natural case-control pair. In such studies, questionnaires designed to identify the status of all twin pairs are sometimes error prone and can yield misleading estimates of the concordance-discordance ratios. Greater efforts to verify the characteristics of apparently discordant pairs than to verify those of apparently concordant pairs can result in the 'unequal ascertainment' fallacy. Using the results of a questionnaire with known error rates and the 'apparent' frequencies yielded, we present unbiased, maximum likelihood estimates of the 'true' proportions of concordant and discordant pairs. concordant and discordant pairs. We also present approximate covariances among these estimates.     

Cardiac involvement in Lyme disease: manifestations and management

Cardiac involvement in Lyme disease may manifest as atrioventricular block, myopericarditis, and left ventricular dysfunction. Diagnosis depends on recognition of the systemic nature of Lyme disease, including cardiac involvement, and its natural history. Serologic tests that are both sensitive and specific may aid in diagnosis. Although current recommendations for the treatment of Lyme disease with carditis include antibiotics and salicylates or corticosteroids, these types of therapy have not been unequivocally demonstrated to alter the natural history of cardiac involvement. Supportive therapy may necessitate temporary transvenous cardiac pacing in symptomatic patients.     

Advances in understanding cell interactions in tissue resorption. Relevance to the pathogenesis of periodontal diseases and a new hypothesis

Much of the connective tissue degradation that takes place in periodontal diseases is mediated by proteolytic enzymes. Previous studies have focused on the action of proteinases released by invading polymorphonuclear neutrophils and macrophages, and bacterial enzymes. In view of recent work establishing that resident connective tissue cells can be induced by cytokines to bring about the destruction of their own matrix, we propose a new hypothesis. In this we envisage that a critical step is the interaction of bacterial antigens with inflammatory cells, resulting in the production of a cytokine, interleukin-1. Our interpretation of in vitro evidence is that the loss of connective tissue attachment and bone matrix resorption in periodontal diseases is mediated by metalloproteinases such as collagenase and stromelysin released by cells of the periodontium. Such proteolytic destruction can be induced by interleukin-1, whose production may not be dependent on a specific microbial flora but may be triggered by a number of organisms. It is now clear that interleukin-1 has multiple actions on both immune and non-immune cells; these include the induction of lymphocyte differentiation and proliferation and the stimulation of bone and cartilage resorption, and prostaglandin and metalloproteinase synthesis by connective tissues. It seems likely that further knowledge about the production and function of this cytokine will have an increasing impact in many diseases that involve resorption, particularly since interleukin-1-like molecules can be produced by cell types other than monocytes/macrophages, including keratinocytes and fibroblasts.