Reduced CD43 expression on the neutrophils of MDS patients correlates with an activated phenotype of these cells.

CD43 (also known as leukosialin and sialophorin) is a surface sialoglycoprotein expressed at high levels on most leukocytes implicated in adhesion, antiadhesion, and activation/proliferation mechanisms. We studied the expression of this molecule on the leukocytes of patients with myelodysplastic syndromes (MDSs) in an effort to detect acquired deficiencies of this molecule. We used immunofluorescence flow cytometry in analyzing whole blood and isolated neutrophils from 49 MDS patients, 33 men and 16 women aged 33 to 85 years (median, 75 years), and 18 healthy individuals aged 35 to 80 years (median, 72 years). According to French-American-British classification criteria, 13 patients had refractory anemia, 18 had refractory anemia with ringed sideroblasts, 9 had refractory anemia with excess of blasts, 4 had refractory anemia with excess of blasts in transformation to acute leukemia, and 5 had chronic myelomonocytic leukemia. We found decreased expression of CD43 on the neutrophils of these patients, and we correlated this finding with the activation status of these cells as it is defined by their phenotypes. We studied the expression of CD11b, CD18, CD35, CD67, CD69, CD44, and CD53 molecules known to be changed in the activated form of neutrophils. CD43 expression correlated positively with CD53 and CD44 expression and negatively with CD11b, CD18, CD35, CD67, and CD69 expression. Additionally, increased levels of soluble vascular cell adhesion molecules were detected in these patients, suggesting endothelial cell activation. In conclusion, we believe that the decreased expression of CD43 on the neutrophils of MDS patients is associated with activation of these cells and is probably due to cleavage of the molecule from the cell surface and that the same mechanism is possibly responsible for the parallel down-regulation of CD44 and CD53.

Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas.

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.

Aberrant expression of the major sialoglycoprotein (CD43) on the monocytes of patients with myelodysplastic syndromes.

CD43, a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling. The reduced expression of this antigen in patients with Wiscott-Aldrich syndrome, in which progressive immunodeficiency is a major problem, raised the question whether abnormal expression of this molecule could affect the susceptibility to infections in patients with myelodysplastic syndromes (MDS). We studied the expression of this antigen on the monocytes of ten patients with chronic myelomonocytic leukemia (CMML) and compared the results with 67 patients suffering from other MDS syndromes and with 18 healthy individuals. We chose this series as it plays an important role in MDS patients where in most cases the neutrophils are defective. We also examined the following antigens as indicative of activation and adhesion of the monocytes in these patients: CD11b, CD18, CD35, CD38, CD44, CD69. We found decreased expression of CD43 on the monocytes of the RA, RAS, RAEB, and RAEB-t patients compared with the CMML and controls. The other activation molecules studied were found to be upregulated, suggesting the existence of activated monocytes in these patients. The increased levels of soluble vascular cell adhesion molecule in these patients suggest vascular endothelial activation in the absence of infection. Further experiments are needed to investigate the significance of CD43 downregulation in these patients, its role in cell adherence and tissue migration, and the correlation of the phenomenon to the increased susceptibility to infections observed in these patients.

Bringing community involvement into a Cretan primary/hospital care center: an evaluation of population habits and attitudes toward health care.

In a small Cretan township hospital combining secondary and primary care, a questionnaire was distributed to a consecutive visitor sample. The questionnaire requested information on the participants' personal smoking and other life habits, perceptions and expectations of the delivery of the health care services, and attitudes toward their own doctors and others who provide various health services. Three hundred and one individuals of both sexes who were 15 years and older participated in the study (participation rate, more than 97%). An interesting and varied response was recorded, covering a wide range of perceptions, opinions, and attitudes not only toward the services, but also toward the staff. Although a high confidence in and appreciation of both the primary care and hospital sections appeared in the study results, these attitudes should not be allowed to deteriorate. Therefore, specific actions should be undertaken: constant upgrading of the existing organizational context, implementation of promotional and educational programs, and use of the questionnaire as an effective tool for periodically assessing the population's attitudes, experiences, and expectations.