Leukocytic Inclusions--Dohle Bodies--Associated with Platelet Abnormality (The May-Hegglin Anomaly): Report of a Fami1y and Review of the Literature

A six-year-old girl with thrombocytopenia was found to have the May-Hegglin anomaly, consisting of Döhle bodies in the leukocytes in associationwith giant platelets. This was also observed in the patient’s mother and brotherwho had normal platelet counts. The familial nature of this anomaly is againconfirmed, and the world literature reviewed. Its morphologic and clinicalfeatures are contrasted with those seen in the leukocytes of the Chediák-Higashi anomaly.

Submitted on July 8, 1962 Accepted on July 30, 1962     

POTENTIAL FALSE-POSITIVE RESULTS WITH ANTIGEN ENHANCEMENT FOR IMMUNOHISTOCHEMISTRY OF THE p53 GENE PRODUCT IN COLORECTAL NEOPLASMS

Aberrant crypt foci (ACF) are putative precursor lesions of colon cancer, recently identified on the methylene blue-stained mucosal surface of human colon. No mutations in K- ras or p53 genes were found by non-radioactive single-strand conformation polymorphism analysis in 14 ACF collected from five patients. Using the more sensitive method of allele-specific polymerase chain reaction (PCR) for K- ras , 8 of 14 ACF were found to contain K- ras mutations, suggesting that mutated cells are present in minute clones in ACF. No dysplasia was observed in any of the ACF containing a mutated clone. The presence of K- ras mutations in ACF suggests that these lesions occur at a very early stage in human colorectal carcinogenesis.     

AMINOPEPTIDASE A IS A CONSTITUENT OF ACTIVATED PERICYTES IN ANGIOGENESIS

Monoclonal antibody (MAb) RC38 recognizes a human renal antigen of 160 kD recently identified as human aminopeptidase A (APA; EC 3.4.11.7). This ectoenzyme is able to hydrolyse selectively N-terminal glutamyl and aspartyl residues from oligopeptides. By enzyme histochemistry, APA activity has also been localized in the microvessels of all organs in animals and man. The purpose of this study was to investigate the distribution of human APA as recognized by MAb RC38 in the microvasculature of normal human tissues and pathological conditions associated with neovascularization. Unexpectedly, in normal tissues vascular staining with MAb RC38 was generally weak and often absent, while in tumours, granulation tissue, and chronic synovitis, marked microvascular staining was demonstrated. By immuno-electron microscopy, the antigen was found on the cell membrane of activated pericytes and their processes in the tumour vasculature. RC38 expression could not be detected on cultured human endothelial cells or pericytes. These observations suggest that pericyte expression of a subtype of APA (as recognized by MAb RC38) is markedly enhanced in the vasculature of tumours and wound healing tissue as compared with normal resting tissues. This provides further evidence of the altered state of pericytes in these conditions. Pericyte APA may be involved in the metabolism of biologically active oligopeptides during neovascularization, supporting a regulatory role of pericytes in this process. In addition, MAb RC38 may be useful as a marker of pericyte activation in tissue sections.     

Idiopathic Intrahepatic Cholestasis of Pregnancy

An atypical case of idiopathic cholestasis of pregnancy occurring in the 16th week of gestation in a 24-year old Pakistani female is presented. The case is unusual both in the duration of the jaundice as well as in the high levels of bilirubin found in the presence of normal renal function. A review of the recent literature emphasizes that this disorder is not entirely benign for the mother and the fetus. It also discusses some of the alterations in estrogen and lipid metabolism that are seen, as well as the possible mechanisms responsible for the increased incidence of gallstone formation found in these patients.     

Mast cell degranulation and parenchymal cell injury in the rat mesentery.

OBJECTIVE: The objective of this study was to explore the degree of parenchymal cell injury after mast cell degranulation by application of compound 48/80 (CMP 48/80) in the absence of adherent leukocytes in the rat mesentery. METHODS: Rats were rendered leukopenic by injection of an antibody against leukocytes, and the mesentery was superfused with CMP 48/80 during intravital microscopy. The extent of cell injury was determined using a fluorescent cell-viability indicator, propidium iodide (PI). In an additional group, mast cell degranulation with CMP 48/80 was prevented by using the mast cell stabilizer Ketotifen. RESULTS: After a reduction in the number of circulating leukocytes, mast cell degranulation produced a mild increase in parenchymal cell injury. The injury levels significantly increased when individual regions of the mesentery were compared. Stabilization of the mast cells with Ketotifen reduced the injury to below baseline values. CONCLUSIONS: In the absence of leukocyte adhesion to the endothelium, mast cell degranulation contributes to parenchymal cell injury in the mesentery.