Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

Specificity of autoantibodies in autoimmune thrombocytopenia

In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients.     

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.     

Biallelic neutrophil Na-antigen system is associated with a polymorphism on the phospho-inositol-linked Fc gamma receptor III (CD16)

Neutrophils express two distinct types of receptor for the Fc region of IgG, FcRII and FcRIII, in amounts of 10,000 to 20,000 FcRII (40 Kd) and 100,000 to 200,000 FcRIII (50 to 80 Kd) per neutrophil. We showed that the FcRIII exhibits genetically determined heterogeneity, detectable by differences in electrophoretic mobility with sodium dodecyl sulfate (SDS) as well as by reaction with antibodies against the biallelic neutrophil-specific antigen system NA. FcRIII was precipitated with an FcRIII-specific monoclonal antibody (MoAb) from the neutrophils of 35 donors. NA1NA1 donors expressed an FcRIII with a molecular weight (mol wt) of 50 to 65 Kd, NA1NA2 donors expressed an FcRIII with a mol wt of 50 to 80 Kd, and NA2NA2 donors expressed an FcRIII with a mol wt of 65 to 80 Kd. Statistical analysis showed that the electrophoretic heterogeneity corresponds with the NA polymorphism (k = 1). Sequential immunoprecipitation with a MoAb against NA1 and a MoAb against anti- FcRIII, followed by SDS-polyacrylamide gel electrophoresis (PAGE), showed that NA1-FcRIII is distinct from NA2-FcRIII. Moreover, immunoprecipitation with a MoAb against NA1 yielded a protein of 50 to 65 Kd, and immunoprecipitation with human anti-NA2 sera or an MoAb against NA2 yielded a protein of 65 to 80 Kd. Preincubation of NA1NA2 neutrophils with F(ab')2 fragments of an MoAb against anti-NA1 reduced binding of IgG dimers to these cells with about 50%, whereas it completely prevented binding of the dimers to NA1NA1 neutrophils. Inhibition experiments with the MoAb against NA2 yielded the same results for NA1NA2 cells, whereas binding of IgG dimers to NA2NA2 cells was completely prevented. Thus, the products of both NA alleles bind IgG. Immunoprecipitation from the medium of neutrophils either stimulated with formyl- methionyl-leucyl-phenylalanine (FMLP) or treated with glycosyl-phosphatidyl-inositol-specific phospholipase C (GPI- PLC) showed that both the NA1-FcRIII and the NA2-FcRIII are released from the cell surface, indicating that both forms of FcRIII have some structural features in common. Deglycosylation of FcRIII from homozygous donors yielded material that showed several bands on SDS- PAGE. GPI-PLC treatment of neutrophils indicated that all of this material is phosphatidyl-inositol linked.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.