Dimeric S100A8 in human neutrophils is diminished after phagocytosis.

S100A8 is a major cytoplasmic protein of neutrophils and monocytes/macrophages and has been associated with myeloid cell differentiation and activation. Little is known about its functions or mechanisms of release from neutrophils. We have developed a monoclonal antibody to murine S100A8, which cross-reacts with human S100A8. This antibody, which recognizes the homodimeric form of the protein, detects its expression specifically in human neutrophils and is reactive in formalin-fixed, paraffin-embedded tissues. Using this antibody as well as a commercially available antibody to human S100A8, we show that phagocytic activation of neutrophils, in vivo in acute appendicitis and in vitro following phagocytosis of opsonized zymosan, is characterized by loss of cytoplasmic immunoreactivity for S100A8. In vitro, phagocytosis is associated with rapid diminution of immunostaining without loss of viability. Loss of immunoreactivity for S100A8 may serve as a marker of localized neutrophil activation in tissues.

Keratoacanthomas have an immunosuppressive cytokine environment of increased IL-10 and decreased GM-CSF compared to squamous cell carcinomas.

To investigate the relationship between keratoacanthoma (KA) and squamous cell carcinoma (SCC), cytokine mRNA in 12 KA and eight SCC were compared. Normal skin was also studied. Reverse transcription polymerase chain reaction (RT-PCR) was used to quantitate mRNA in each sample utilizing DNA standards. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control, and CD3delta as an indication of the T-cell infiltrate. KAs showed a significant increase in interleukin (IL)-10, and a decrease in granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA compared to SCCs. CD3delta mRNA was also increased in the KAs. There was no difference between KAs and SCCs in expression of lymphotoxin-alpha, IL-2, interferon-gamma (IFN-gamma), IL-13, transforming growth factor-beta (TGF-beta), or the pro-inflammatory cytokines IL-8 or tumour necrosis factor-alpha (TNF-alpha). These results indicate that KAs spontaneously resolve in an immunosuppressive environment. KAs grow rapidly over a period of weeks and then involute. It is possible that a suppressed immune response enables unimpeded growth and that the KA cells rapidly undergo the finite number of cell divisions of which they are capable, and then die without reaching immortality.

Health promotion, health protection, and preventive services.

Health promotion, health protection, and preventive services reflect the 21 priority areas of Healthy People 2000. This article focuses on the cost-effectiveness of health promotion and the role that primary care physicians can play in this initiative.

Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma.

Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The T lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin-2 receptor (IL-2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM-1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL-2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response.

Regression in basal cell carcinoma: an immunohistochemical analysis.

Spontaneous regression of some cutaneous tumours is well recognized, and is thought to result from an immunological response to the tumour. Regression has previously been noted in basal cell carcinomas, but no studies defining the role of the immune response in the regression of this malignancy have been performed. We have examined 45 primary basal cell carcinomas (BCCs) (20 nodular, 25 superficial) and identified the cellular phenotypes and activation states of the cells infiltrating primary regressing and non-regressing BCCs, by immunocytochemistry. We have found a significantly increased number of CD3+ and CD4+ T cells infiltrating regressing compared with non-regressing tumours, and the expression of interleukin-2 receptor (an early activation marker for T cells) was also increased. There were no significant differences in class II major histocompatibility complex (MHC), CD1, or macrophage antigen expression in these groups. These findings suggest that activated CD4+ cytokine-secreting cells are important in the regression of BCCs.

11 beta-Hydroxysteroid dehydrogenase in the rat ovary: high expression in the oocyte.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the conversion of physiological glucocorticoids to inactive products, thus modifying the access of glucocorticoids to glucocorticoid and mineralocorticoid receptors. Glucocorticoids may affect ovarian function both indirectly and via binding to ovarian receptors. We have demonstrated 11 beta-HSD bioactivity and mRNA expression in rat ovary in vitro. The enzyme was localized to oocytes and luteal bodies immunohistochemically using two antibodies raised against purified rat liver 11 beta-HSD. These data are supported by in-situ hybridization studies, which also localized 11 beta-HSD mRNA expression to oocytes and luteal bodies. The results suggest that 11 beta-HSD may modulate the effects of glucocorticoid on ovarian function.

The coexistence of lymphangiosarcoma and Kaposi's sarcoma in a renal transplant recipient.

A case of coexisting lymphangiosarcoma and Kaposi's sarcoma that occurred in a female renal transplant recipient is presented. Both sarcomas were localized to the skin and were slowly progressive over several years. The coexistence of these two sarcomas may indicate that they arose from a common precursor endothelial cell and that systemic immune suppression may be important in the pathogenesis of both these malignancies.

Paget's disease of bone with involvement of the dental pulp.

A case of Paget's disease of bone in a 65-yr-old woman is described with partial obliteration of the pulps of teeth in the affected mandible. This hard tissue had the typical mosaic pattern of bone or cementum seen in that condition.

A phantom to assess quantitative recovery of positron tomographs.

A simple phantom has been employed to investigate the image linearity for a wide range of activity distributions and count rates. The phantom is composed of two activity regions, one contains a short-lived isotope and the other a long-lived isotope. Specifically, the phantom consists of a 20 cm flood phantom containing 68Ga (half-life 1.14 h) into which a 6 cm diameter cylinder containing 64Cu (half-life 12.7 h) is placed in an off-centre position. The copper region is initially a cold spot but, after many gallium half-lives, becomes a hot spot. Successive data sets from the phantom are taken over a long period and the reconstructed images analysed to establish the linearity within each region and hence the stability against "cross-talk" from neighbouring regions.

Fate of mismatched base-pair regions in polyoma heteroduplex DNA during infection of mouse cells.

Heteroduplex DNA has been constructed from two variants of polyoma virus that differ genotypically at four distinct sites. The genotypes of the progeny virus derived from infections of mouse cells with single heteroduplexes have been analyzed to determine how the genotypic markers of the parental heteroduplex segregate. Markers that are separated by a length of DNA greater than 600 nucleotides segregate independently. Segregation was not detected between two markers separated by only approximately 90 nucleotides. We interpret these results on the basis of the correction of mismatched base-pair regions in the heteroduplex before the completion of DNA replication. We suggest that this technique provides valuable information concerning gene conversion in mamalian cells and permits the transfer of genotypic markers from one virus strain to another.

Median rhomboid glossitis. Candidiasis and not a developmental anomaly.

Infection by Candida Albicans was found in all biopsies taken from ten patients presenting with midline lesions of the tongue which clinically presented as median rhomboid glossitis.