A B S T R A C T The neutrophils and monocytes of a patient with disseminated candidiasis were found to lack detectable levels of the lysosomal enzyme myeloperoxidase (MPO), although they had normal levels of other granule-associated enzymes. Leukocytes from one of the patient's sisters also lacked detectable MPO; leukocytes from his four sons contained approximately one-third of mean normal peroxidase levels. Neither the patient nor his affected relatives had experienced frequent or unusual bacterial infections.The phagocytic activity of the patient's MPO-deficient neutrophils was intact, and the cells displayed normal morphologic and metabolic responses to phagocytosis. In contrast to normal leukocytes which killed 30.5 ±7.3% of ingested Candida albicans in 1 hr, however, the patient's neutrophils killed virtually none. His leukocytes also failed to kill the strain of C. albicans recovered from his lesions, as well as other Candida. species. These MPO-deficient neutrophils killed Serratia marcescens and Staphylococcus aureus 502A at an abnormally slow rate, requiring 3-4 hr to achieve the bactericidal effect attained by normal leukocytes after 45 min. No other abnormalities in his cellular or humoral immune responses were demonstrated.These findings suggest that hereditary MPO deficiency is transmitted as an autosomal recessive characteristic, that the homozygous state conveys enhanced susceptibility to disseminated candidiasis, and that MPO is necessary for candidacidal activity in human neutrophils.This work was presented in part at the National Meeting of the American Federation for Clinical Research, Atlantic City, N. J., and published in abstract form (1).

Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.

p53 is a 53-kDa nuclear protein that is associated with malignant transformation in several tumor model systems. In a survey of 134 human carcinomas, sarcomas, leukemias, and lymphomas obtained at surgery or from peripheral blood, we found rearrangements of the p53 gene only in osteogenic sarcomas (3 of 6 osteogenic sarcomas examined). Normal tissue from one of these patients had an unrearranged gene, indicating that the genetic abnormality in the tumor was acquired. Two of the sarcomas with rearranged genes expressed levels of p53 protein that were elevated relative to other tumors. Rearranged p53 genes were also found in human osteogenic sarcoma cell lines.

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