In 129 of 140 attempts, human skin cells were successfully cultured on the dermal collagen bed of sterile, dead pigskin. Diploid epithelial cells grew selectively on the collagen bed; fibroblasts grew on the glass surfaces of the culture dishes. The cultures could be subdivided physically up to six times at a 1:2 split ratio, but at least 24 to 48 cell generations were produced over the months the cells could be carried. Much of the cell multiplication resulted in maturation into distinct basal, squamous, granular, and keratinized cell layers. The cultured cells were considered epithelial because of their shape, possession of intercellular bridges, desmosomes and tonofibrils, and because they formed maturating epithelium in vitro and upon transplantation back to the original human donor. As the cells grew they digested the pigskin collagen, thus producing clear zones that could be used to monitor and quantitate cell growth. Multiplication of epilthelial cells, rather than migration, was indicated by mitotic figures in colchicine-treated cultures and by DNA synthesis.
The induction of lymphomas in C57BL mice by methylcholanthrene, urethan, or diethylnitrosamine was accompanied by the development of murine leukemia viral antigen in most of the lymphoid tumors. The cell-free transmission of lymphomas induced by methylcholanthrene and the development of antibody to murine leukemia virus prior to the detection of overt lymphoma in these mice suggest that unmasking of a latent leukemia virus is an indigenous actuating cause of the lymphomas.
The pathogenesis of lymphocytic choriomeningitis virus infection in fetal, newborn, and young adult hamsters was studied. Infected newborn hamsters initially developed a persistent viremia and viruria with titers often in excess of 10(4.0) mean infectious doses/0.03 ml of blood or urine. After week 12 two different patterns of infection became evident. Approximately one-half of the hamsters eventually cleared the infection, whereas the others developed a chronic progressive and ultimalely fatal disease characterized by continuous high-titered viremia and viruria and high titers of virus in their tissues. Complement-fixing antibody and, to a lesser degree, virus-neutralizing antibody coexisted with the viremia. Hamsters with persistently high levels of viremia and viruria developed chronic glomerulonephritis and widespread vasculitis, whereas hamsters that cleared their infections did not develop these lesions. Litters of hamsters born to viremic mothers were invariably infected. Litter sizes were small and breeding effectiveness was reduce; however, vertical, congenital infection was successfully passed through three generations. The course of infection in the congenitally infected hamsters was similar to that in newborn infected hamsters, with all animals producing complement-fixing antibody, some animals being capable of clearing the viremia and remaining healthy, and other animals having persistent viremia and fatal disease. Inoculated young adult hamsters did not become diseased, developed viremia and viruria which persisted up to 3 and 6 months, respectively, and developed complement-fixing antibody by 10 days after infection. The prolonged urinary excretion of large amounts of lymphocytic choriomeningitis virus by asymptomatic, chronically infected hamsters is an important public health consideration when dealing with potential human infection.
The value of histologic evaluation in the analysis of material from first trimester abortions is not completely defined. We prospectively analyzed placenta and decidua from 75 first trimester, spontaneous abortions to ascertain if morphologic features were predictive of karyotype. The histologic features analyzed included hydropic villus change, villus fibrosis, villus scalloping with trophoblastic invaginations, atypical stromal cells, aggregates of lymphocytes in placenta or decidua, and acute inflammation of placenta or decidua. Normal karyotypes were observed in 44 cases and abnormal karyotypes were demonstrated in 31. The presence of villus scalloping with trophoblastic invagination was significantly associated with abnormal karyotypes, particularly triploidy, and the demonstration of acute inflammation was seen significantly more often in cases with normal karyotypes. We conclude that histology can provide only a suggestion as to the likelihood of an abnormal karyotype; the findings are not specific enough to obviate the need for karyotyping in the individual case.
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