Epithelial hyperplasia in human polycystic kidney diseases. Its role in pathogenesis and risk of neoplasia.

The importance of tubular epithelial hyperplasia in polycystic kidney diseases has become apparent during the last decade. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease. Neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease. A histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In each of these conditions, epithelial hyperplasia may be related to cyst formation and may also impose an increased risk of malignancy--a risk that seems to be highest in patients under treatment with long-term hemodialysis for end-stage kidney disease. Although hyperplasia in some of these diseases may share a common pathway of development, it is more probable that the histopathologic differences reflect different pathogenetic pathways that converge on a common endpoint.     

Evaluation of phagocytic function in Mycobacterium lepraemurium infection

Infection of mice with Mycobacterium lepraemurium caused significant functional alterations of the mononuclear phagocyte system. Accelerated clearance of sheep red blood cells was consistently demonstrated throughout the infection and the infected mice showed progressive anaemia. Infected mice showed an enhanced ability to limit growth of phagocytosed Listeria monocytogenes in spleens during the early stages of infection, whereas moribund leprous mice lost this ability. Autoradiography showed that uninfected Kupffer cells and splenic macrophages of moribund mice could still phagocytose Listeria, suggesting that MLM infection did not affect the capacity of Listeria to localize to macrophages but interfered in some way with subsequent killing of such bacteria. The possible mechanisms underlying these observations are discussed.     

Identification of CD56 and CD57 by flow cytometry in Ewing’s sarcoma or primitive neuroectodermal tumor

 CD56 and CD57 are commonly considered as natural killer and neuroectodermal markers, but their expression has been identified in a wide spectrum of neoplasms including some cases of Ewing’s sarcoma (ES) and primitive neuroectodermal tumor (PNET). We report two cases of small, round blue cell tumor (SRBCT), in which flow cytometry immunophenotyping (FCI) detected strong expression of CD56 and CD57 (one case). Immunohistochemical staining with Leu-19 and Leu-7 confirmed the FI results. Although CD56 and CD57 expression is consistent with ES/PNET, it can be potentially misleading if results of FCI are interpreted in the absence of other findings. These cases suggest the utility of FCI in undifferentiated SRBCT. The literature on CD56 and CD57 expression in ES/PNET is reviewed and discussed. Received: 5 January 1998 / Accepted: 19 February 1998     

Morphogenetic clonal growth of kidney epithelial cell line MDCK

MDCK (Madin-Darby canine kidney) cells were cultured either dispersed within hydrated collagen gel (HCG) or seeded atop a collagen substrate and then immediately overlaid with HCG. Individual cells exhibited clonal growth in three dimensions to form spherical cysts made up of a simple epithelium enclosing a fluid-filled lumen. The cells of MDCK cysts were polarized with the basolateral surface in contact with the collagen gel and the apical surface bordering the lumen. The ultrastructure of MDCK cysts showed similarities to distal nephron. The cells bore apical microvilli and solitary cilia and had occluding junctions and a simple basolateral surface. MDCK cysts increased in size (greater than 800 microns diameter) with continued culture. MDCK cysts grown between layers of HCG were stripped free of the overlying collagen to give direct access to basolateral surface membrane. Unlike monolayer culture, morphogenetic clonal growth of cell line MDCK produces a polarized cell population with a true lumenal and basolateral surface. Collagen-gel-cultured MDCK cysts provide an easily manipulable in vitro cell system that may offer unique advantages for the study of renal cell structure and function.     

Evaluation of chromosomal diagnosis for hereditary adenomatosis of the colorectum

Hereditary adenomatosis, particularly familial polyposis coli (FPC) and Gardner's syndrome (GS), has been investigated from family pedigrees and chromosomal markers for precancer and cancer. FPC and GS are much alike in phenotypes. Studies are in progress to determine if the two adenomatous diseases are controlled by the same DNA sequence. Chromosome numerical and structural instability is a good diagnostic criterion for hereditary adenomatous diseases where risk factors are already determined to the level of 0.5 probability from pedigree analysis. This has been applied successfully at the pediatric age level to identify family members who carry the gene but have no adenomas in the colorectum. Sister chromatid exchange (SCE) did not distinguish plasma samples from FPC, GS, or solitary adenoma patients form each other or from controls with no adenomas. SCE did distinguish invasive from recurrent and noninvasive cancer. The chromosome #2 polymorphism observed at 2q-21.3 has not been confirmed as a deletion, but is under investigation with more refined methods.     

Human papillomavirus types in anogenital warts of children

Tissue from anogenital warts of 25 children, 10 of whom were suspected of being victims of sexual abuse, was investigated by dot blot and Southern blot techniques for human papillomavirus (HPV) types. HPV DNA was detected in 22 children, two of whom had double infections. The genital HPV types 6 and/or 11 were detected in 20 children, and in three children other HPV types were found. One had HPV 18 (as well as 11); in a second child a possible skin type, HPV 2, was detected; and the third child was infected with an unidentified type. In three cases genital wart material was available from one of the parents, and in all three the HPV type was the same as that of the child. For nine other children one or both parents were reported to have genital warts. The source of infection appeared to be the adult genital tract, but sexual contact might not be the only means of transmission.