Influence of 1,25-(OH)2 vitamin D3 and gamma interferon on the phenotype of human peripheral blood monocyte-derived macrophages

The effects of 1,25-dihydroxy vitamin D3 and gamma interferon on the phenotypic changes associated with monocyte maturation in vitro were investigated. Human monocytes separated from peripheral blood mononuclear cell populations by adherence to plastic were cultured for 7 days on glass. Immunocytological analysis was performed on monolayers fixed at various times by using monoclonal antibodies specific for mature macrophages (RFD7), interdigitating (dendritic) cells (RFD1), and class II major histocompatibility complex antigen (RFDR1). Without any addition to the culture medium, proportions of these monocytes (normally RFD1 and RFD7 negative) developed either RFD1 positivity (23%) or RFD7 positivity (49%) over 7 days of culturing. The addition of gamma interferon to these cultures markedly reduced the proportion of RFD7-positive cells (less than 10%) but increased the proportion of RFD1-positive cells (40 to 60%). In contrast, 1,25-dihydroxy vitamin D3 reduced the expression of both RFD1 and RFD7. Both of these effects were dose dependent and required at least 3 days of contact with the cells. The possibility that RFD1- and RFD7-positive cells represent functionally distinct subsets makes these effects of significance in our understanding of the role of these mediators in controlling the immunocompetence of nonlymphoid accessory cell populations and in macrophage-associated antimicrobial activity.     

Iotrol versus metrizamide in lumbar myelography: a double-blind study

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Food and health at work–a review. The costs and benefits of a policy approach

The workplace is an important setting for health promotion and provides an ideal opportunity for shaping healthy eating patterns in occupational groups for whom inequalities have been identified (DHSS, 1980). Workplace food/health policies provide an intermediate and pragmatic step towards achieving the dietary targets set out in the Government's white paper Health of the Nation and the most recent COMA report (DoH, 1991,1992). Food/health policies have been widely adopted in the NHS (Gibson & Kallevik, 1990) and preliminary research suggests that they are an effective means of intervention (Wallis & Poulter, 1988; Frost et al., 1991). Industry has been slower to link food and health promotion to a policy making process. Surveys imply that action on healthy eating in companies often originates in the occupational health department and is based on individualistic approaches with little energy being put into preventive activities which would originate in the canteen (Mclnerney & Cooper, 1989; Poulter, 1990). Policies provide a means of balancing the environmental and educational paradigms of health promotion. If food/health policies are to grow in the private sector then industry has to be convinced that the benefits Justify the costs. Some philanthropic employers are motivated by interests other than financial gain, but others are commercially led. There is little hard evidence to demonstrate that any type of employer-sponsored healthy eating initiative provides a favourable return for investment. It has been ‘guesstimates’ and extrapolation from other situations which have provided the justification for UK companies to allocate any resources towards addressing food/health issues. In April 1990 the National Grid Company adopted a comprehensive food/health policy. This paper draws on the experiences in developing and implementing the policy document to discuss the issues around evaluative activity in a commercial setting. Views are expressed on the feasibility of measurement and the value of the informaton collected. One aim of the future should be to research this under-examined area to establish a solid body of information. This would raise the level of debate from one which is currently based on anecdotal evidence to a sounder scientific footing and, therefore, ensure the future growth of such policies in the corporate sector.     

Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage.

Bronchoalveolar lavage was used to obtain alveolar macrophages (AM) from the lower respiratory tract of healthy normal volunteers. Monoclonal antibody (MoAb) probes specific against macrophage determinants were then applied, in conjunction with density separation techniques, to identify and isolate three relatively homogeneous subpopulations from the AM pool. The MoAbs used, RFD1 and RFD7, have previously been shown to differentiate between "dendritic" cells and mature macrophages, respectively, in normal tissue. In addition to these two phenotypically distinct AM subsets (RFD1+D7- and RFD1-D7+ AM), a third AM subpopulation was isolated, which appeared to express both markers (RFD1+D7+). All three separated macrophage subsets were morphologically similar but exhibited distinct differences in surface receptor expression, enzyme content and physiology. Isolated RFD1+D7- AM (the phenotype of "dendritic" cells) did not adhere to the glass, had weak expression of C3b and FcR1 receptors, low fibronectin content and lysosomal activity; only a small proportion of these cells exhibited phagocytosis. The other two isolated AM subsets adhered to glass, expressed C3b and FcR1 receptors, had high fibronectin and acid phosphatase content, and a large majority exhibited phagocytic capacity; qualitative and quantitative differences in these features existed between the two AM subtypes. Furthermore, a diverse spectrum of hexose monophosphate shunt activity was observed throughout all three AM subpopulations, with the highest activity being recorded in the non-adherent AM. These data support the concept of a dynamic heterogeneity within the AM population. The variation in surface antigen expression and physiological capabilities observed amongst the three isolated AM subsets implies the presence of functionally distinct AM within the human lung, which, during steady-state conditions, may be critically balanced under the influence of stimuli in their local microenvironment. In support, proportional and functional shifts have been witnessed amongst these three AM subpopulations with the advent of disease.     

The involvement of interdigitating (antigen-presenting) cells in the pathogenesis of rheumatoid arthritis.

Macrophage like cells expressing high concentrations of HLA-DR antigen have been identified in situ within the synovium of patients with rheumatoid arthritis. The characteristics of these cells have been determined using immunohistological analysis and combined cytochemical techniques. It was found that the majority (greater than 80%) of these cells were interspersed within the perivascular lymphocytic infiltrates occurring in the synovium. These cells did not stain with antisera against surface immunoglobulin or any Mc Abs to T lymphocyte markers. Further combined staining demonstrated that the HLA-DR + ve cells did stain with an anti-monocyte monoclonal (FMC-17), but could not be stained with a Mc Ab against C3b receptors. The interfacing of cytochemical reactions for acid phosphatase (ACP) and adenosine triphosphatase (ATPase) with immunofluorescence staining for HLA-DR demonstrated that these cells were ACP - ve ATPase + ve. This analysis led to the conclusion that the HLA-DR + ve cells found in abundance in the rheumatoid synovium expressed identical characteristics to the interdigitating cells of the normal lymph node paracortex. The possible significance of the presence of large numbers of such antigen presenting cells in the rheumatoid synovium is discussed.