Proliferation, atrophy and lipoprotein catabolism are nodal points in an intricate network of pathogenetic factors which influence the complex morphogenesis of atherosclerosis with its ambiguous phenotypes. The compiled findings of our group show that leiomuscular atrophy of the arterial media represents a hitherto widely ignored pathogenetic hinge in atherogenesis which is expected to impede intramural transport of low density lipoproteins (LDL), contributes to the formation of atheromatous plaques due to chemical modification of stagnant LDL, and influences the topographic distribution of plaques. Contrary to the age-dependent atrophy seen in the smooth muscle cells of the tunica media, myointimal cells of the intima, the so-called Langhans cells, are prone to proliferation. In part, cellular growth in atherosclerotic lesions seems to be triggered by biosynthesis of endothelin-1 by lipid-storing macrophages. Similar to self-limited tumour growth, proliferation of atherosclerotic lesions in their cellular phase are controlled by p53, P21 and the gene products of MDM2, Bcl-2 and Bax. Apoptotic cell loss eventually leads to fibrotic end stage lesions.

Arteriosclerosis↗

PubMedDate not supplied

Age-dependent leiomuscular atrophy in vertebral arteries of individuals under low fat diet.

The volumetric density of vascular smooth muscle cells (VSMC) in the proximal vertebral artery was investigated. In order to identify VSMC, paraffin-embedded sections of the proximal vertebral artery, obtained from autopsy specimens, were immunostained for smooth muscle alpha-actin by a modified ABC-technique. The 63 autopsy specimens, including 35 males and 28 females, covered the entire range from 2 months to 85 years. The volumetric density of alpha-actin positive VSMC in the tunica media was morphometrically assayed by the point-counting method. It is important to note that the morphometrical evaluation was performed on arteries obtained from autopsy specimens of the years 1953/54, a post-war time characterized in Germany by low fat diet as compared to the present-day nutrition of most industrial nations. Probably due to their origin, the vertebral arteries showed almost no atheroma. As the main purpose of this study was to find out about the atherosclerosis-independent process of aging, these arteries seemed particularly suitable. The evaluation showed a strictly age-dependent leiomuscular atrophy which became morphometrically evident in early adulthood. The average degree of regression was measured at 0.62% per year. These results may justify the conclusion that the leiomuscular atrophy of the media represents a primary age-related process and does not in any way result as a secondary event from an atheromatous transformation of the intima.

Actins↗

PubMedDate not supplied

Preleukemic myelodysplastic syndromes (MDS): pathogenetical considerations based on retrospective clinicomorphological sequential studies.

Analysis of myelodysplastic syndromes (MDS) in 77 patients terminating in "overt" leukemia revealed sequential changes of marrow morphology with respect to cellularity and involvement of lineages, indicating that different "forms" of MDS represent in reality different phases. Three main phases were observed, which occurred in the following non-reversible sequence: (a) hypocellular dysplasia (H), (b) hypercellular dysplasia with predominance of erythropoiesis (E), and (c) with predominance of myelo(mono)poiesis (MM). Published studies suggest that these phases represent different manifestation stages of the stem cell lesion leading to MDS. Manifestation may probably be promoted by factors causing marrow aplasia. Transition to "overt" leukemia in several cases occurred locally, not throughout the whole marrow. In some patients a mature myelo(mono)-cytic cell population showed the capacity for widespread tissue infiltration, characteristic of leukemic cells. This argues against the theory that "overt" leukemia is the result of continuous dedifferentiation in MDS, but favours the concept of multiple initiating "events" leading to evolution of a leukemic subclone within a myelodysplastic clone. A connection between leukemia differentiation and MDS phase, from which leukemia developed, was also observed indicating that the risk of different stem cell subpopulations to become the target of the leukemia initiating "event" varies during the course of myelodysplasia.

Adult↗

PubMedDate not supplied

The value of the immunoperoxidase slide assay in the diagnosis of malignant pleural effusions in breast cancer.

Whether immunocytochemical studies of malignant pleural effusions due to breast cancer would increase the diagnostic yield as compared with conventional effusion cytology was examined in 30 cases with biopsy-proven metastatic spread to the pleura. Conventional cytology was performed on air-dried smears as well as on cytocentrifuge preparations stained with the May-Grünwald-Giemsa stain. Immunocytochemistry was performed with monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and human leukocyte antigen (HLA) and the peroxidase-antiperoxidase technique on glass slides after Ficoll-Hypaque centrifugation. By conventional cytology, 13 cases (43%) were positive for malignant cells, 6 cases (20%) were suspicious, and 11 cases (37%) were negative. In marked contrast, all 30 cases were immunocytologically positive for malignancy. Tumor cells in all cases demonstrated a positive reaction for EMA. Some mesothelial cells were also positive for EMA, but their reaction pattern was clearly distinguishable from that of the tumor cells. Twenty-one cases (70%) also showed CEA-positive tumor cells; mesothelial cells never reacted with CEA. Some tumor cells showed a loss of HLA expression. In conclusion, this immunocytologic method can be recommended as a routine procedure for greatly increasing the diagnostic yield of cytology in pleural effusions due to breast cancer.

Breast Neoplasms↗

PubMedDate not supplied

Oncogene and HSP-70 expression in primary tumor cell cultures of renal cell carcinoma compared to their corresponding cell line.

BACKGROUND: Tumor progression in renal cell carcinoma (RCC) can be explained by a multistep model, in which the activation of certain oncogenes such as c-neu and c-fos appear to be early events in tumorigenesis, while the expression of p53 and pan-ras are found in advanced stages. MATERIAL AND METHODS: The expression of oncogenes and growth factors was examined in 29 primary tumor cell cultures (PTCC) of RCC using immunocytochemistry. RESULTS: In PTCC high expression of c-neu and c-fos was present in all tumors, whereas mdr, TGF-alpha, EGF, c-myc, pan-ras, p53 and HSP-70 was detected at low expression levels. In 27% (8/29) of PTCC, cell lines (CL) were established. Oncogene expression was increased in CL compared to PTCC. CONCLUSION: The pattern of oncogene expressions found in CL is similar to findings described in highly malignant tumors in vivo. Therefore, the establishment of CL seems to depend on a selective recruitment of tumor cells with an upregulated oncogene expression.

Adenocarcinoma, Clear Cell↗