Incarcerated obturator hernia: early diagnostic using helical computed tomography.

Obturator hernia is a rare event with poor clinical signs. Delayed diagnosis is a cause of increased mortality due to ruptured gangrenous bowel. We report a case of incarcerated obturator hernia which highlights the usefulness of computed tomography (CT) scanning in diagnosing this condition.

Pyothorax-associated lymphoma: relationship with Epstein-Barr virus, human herpes virus-8 and body cavity-based high grade lymphomas.

Pyothorax-associated lymphoma (PAL) is a newly-described entity developing several decades after artificial pneumothorax treatment for pulmonary or pleural tuberculosis. It is known to be associated with Epstein-Barr virus (EBV) with constant expression of the two latent membrane proteins: latent membrane protein (LMP)-1 and EBV-associated nuclear antigen (EBNA)-2. We are reporting three new cases of PAL. All of the tumours were of B-cell lineage and classified as large-cell diffuse lymphomas according to the International Working Formulation for the Classification of Lymphomas. The EBV genome was detected in two of the cases with LMP-1 and EBNA-2 expression. No EBV could be detected in the third case suggesting that different mechanisms may be involved in the pathogenesis of the disease. Body cavity-based high grade lymphomas (BCBL) represent a new disease, developing mainly in human immunodeficiency virus (HIV) infected patients: the tumoural cells often contain both human herpes virus (HHV)-8 (or Kaposi's sarcoma herpes virus) and EBV genomes, suggesting that these viruses might co-operate in the pathogenesis of the disease. The pleural location and the association of EBV have led to speculation that PAL could also be related to HHV-8 infection. However, no HHV-8 genome could be detected in any of the 14 tested cases already reported in the literature nor in the two cases we studied (one EBV-positive and one EBV-negative), suggesting that PAL and BCBL are two different entities.

Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers.

One hundred and thirty-seven lung cancer patients (123 non-small-cell lung cancers (NSCLC), 10 small-cell lung cancers (SCLC) and four carcinoid tumours) who underwent surgery in an attempt at complete resection were prospectively entered in a study whose aim was to determine the prognostic significance of a hypodiploidy or a multiploidy pattern of tumour cell DNA content and a high immunohistochemical reactivity of Ki-67, a nuclear antigen related to the cell cycle. Indirect immunoperoxidase reactivity of Ki-67 on frozen tumour tissue sections was evaluated both visually, using a classical semiquantitative scale, and by means of a computer-assisted image processor. Cell DNA content analysis was done using static computer-assisted cytometry on tumour cytological prints stained by the pararosaline Feulgen-Schiff technique. The ploidy was characterised for each tumour by DNA index (DI), percentage of hypodiploid cells and type of DNA content histogram (near diploid, hyperdiploid, hypodiploid and multiploid). Ki-67 immunostaining was negative in 64 tumours (48%) and positive in 69 (52%). DNA histogram classification disclosed 57 (42%) near diploid tumours. Among the 80 (58%) aneuploid tumours, 16 were hypodiploid, 44 hyperdiploid and 20 multiploid. The prevalence of both a positive Ki-67 immunostaining and an aneuploid DNA histogram differed according to histology as SCLC demonstrated a higher frequency of both features when compared with NSCLC and carcinoid tumours. On the other hand, Ki-67 immunostaining and ploidy did not significantly differ according to degree of differentiation, nodal status and Mountain's stage grouping. The percentage of cells in the hypodiploid modal DNA was significantly higher for tumours which demonstrated a high Ki-67 immunostaining, suggesting a link between growth fraction and DNA content abnormalities. In univariate analysis, survival did not differ significantly according to either the Ki-67 immunohistochemical reactivity or the DNA index. Patients with a hypodiploid tumour had a shorter survival than patients with other DNA histogram patterns but, owing to the low frequency of hypodiploidy, this difference did not reach statistical significance. In Cox's proportional hazard model, an SCLC histology, an advanced tumour status, a positive nodal status and a hypodiploid tumour (hazard ratio: 2.070; 95% confidence interval 1.041-4.116) were significant determinants of survival. We conclude that hypodiploidy in lung cancer is a distinct DNA content abnormality as it contributes significantly to prognosis. Neither visually assessed nor computer-generated Ki-67 immunostaining measurements significantly determine prognosis.

Neural cell adhesion molecule and prognosis of surgically resected lung cancer.

The prognostic significance of the expression of neural cell adhesion molecule (NCAM), a neuroendocrine antigen in lung cancer, was analyzed by an indirect immunoperoxidase method in 97 surgically treated patients. Reactivity of MOC-1 and S-L 11.14, both cluster-1 monoclonal antibodies directed against NCAM, was positive in all nine small-cell lung cancers and in 16 of 88 (18%) non-small-cell lung cancers. For the latter group, this expression demonstrated a phenotypic heterogeneity that was mainly observed in poorly differentiated squamous cell carcinomas and in stage N2 non-small-cell lung cancers. Patients with NCAM-positive non-small-cell lung cancer proved to have a shorter survival than those with NCAM-negative disease. In Cox's model for multivariate analysis, nodal status and histology were the main independent determinants of prognosis. We therefore concluded that NCAM expression in non-small-cell lung cancer is correlated to nodal status and that it indicates a poor prognosis. These findings confirm that the diversification of lung cancer phenotype leads to tumor progression and brings a negative prognosis to surgically resected non-small-cell lung cancer. However, nodal status remains the most important prognostic variable, suggesting that NCAM expression is only one of numerous biological events that promote tumor progression.

Dysdifferentiative nature of aging: passage number dependency of globin gene expression in normal human diploid cells grown in tissue culture.

Aging may be a result of cells drifting away from their proper state of differentiation. This process has been called dysdifferentiation. Normal diploid cells grown in tissue culture conditions undergo numerous biochemical and morphological changes and have a finite division potential. These changes could be a result of such a dysdifferentiation process. Changes in the differentiated state of a cell are frequently manifested by the expression of genes that are normally repressed. Previous studies have shown about a two-fold age-dependent increase of alpha and beta globin-like RNA in mouse brain and liver tissues. Therefore, the possible presence and increase of globin RNA was investigated in the nonerythroid human diploid strain WI-38 grown in tissue culture as a function of population doublings. A DNA X RNA hybridization technique using specific complementary DNA (cDNA) to alpha and beta human globin was used to detect possible complementary RNA sequences in total cellular RNA preparations extracted from cells at population doublings of 26.4 and 46. No globin-like RNA sequences could be detected above background noise levels for either of these two passage numbers. Thus, the globin RNA genes appear to be highly repressed and this degree of repression maintained as the culture approaches its characteristic population doubling limit.

Characterization of a new human diploid cell line--IMR-91.

A human diploid fibroblast cell line has been established from the lung tissue of a male fetus. This has been characterized and frozen away in large quantity. A smaller quantity of fibroblastlike cells from skin has also been established, partially characterized, and placed in frozen storage from the same fetus. This project is in support of the National Institute on Aging research in general cell biology. The present lines designated IMR-91 lung and IMR-91 skin complement the previous human diploid fibroblast culture (IMR-90) established from a female fetus. The lack of random inactivation of one of the two X chromosomes in the present male line reduces the genetic heterogeneity inherent in the female line.

Normal and neoplastic human cells have different histone H1 compositions.

The H1 histone is the least conserved of the five major groups of histone proteins. There are as many as five subtypes of H1 histone (1-3). These H1 subtypes occur in different amounts in different animal species and also show tissue specificity (1-3). Normal and neoplastic tissues from the same animal, e.g. rat or calf, contain the same H1 subtypes but in different relative amounts (4, 5). Because H1 subtypes exhibit tissue specificity, it is therefore difficult to identify the changes in their composition that are associated with neoplasia reported in studies utilizing tissues of different origins (4, 5). Tissue culture cells and their in vitro transformed neoplastic counterparts, on the other hand, offer an excellent system in which to study these changes because the cells are derived from the same origin. We have examined normal and neoplastic human cells and found a relationship between the H1 composition and the ability of the cells to form tumors in nude mice. The ratio of H1A to H1B in normal human cells is considerably lower than that in neoplastic cells and this ratio increases with the increased ability of the cells to form tumors in nude mice.

Effect of cell density and senescence of WI-38 cells on cytochemically demonstrable phosphatases.

Exponentially growing and stationary phase young and old cultures of the human cell line WI-38 were studied using cytochemistry at the ultrastructural level. 5'-Nucleotidase activity was present in the plasma membrane of all cells examined; in exponentially growing cultures the reaction was more intense in mitotic cells than in interphase cells. An increase in the amount of the reaction product was observed at confluencey, especially in older cells. The reaction of Mg2+-activated adenosine 5'-triphosphatase was absent or very weak in exponentially growing cells and increased at confluency, especially in older cells. Alkaline phosphatase was detectable only in the cell membranes and in intercellular spaces of young cells at confluency. Acid phosphatase activity was increased in old cells, especially at confluency. In these old cells, positive reactions appeared in numerous small lysosomes, autophagic vacuoles and in some flattened sacs of the Golgi apparatus. The obtained results confirm and extend previous biochemical observations and indicate that changes in phosphatase activity are associated with proliferative activity and senescence of cells growing in vitro.