Virchows Archiv. B, Cell pathology including molecular pathology最新文献

Desmin is an intermediate filament protein that in striated muscle is normally located at Z-bands, beneath the sarcolemma, and prominently at neuromuscular junctions. It is abundant during myogenesis and in regenerating fibers, but decreases in amount with maturation; in regenerating and denervated muscle fibers it is co-expressed with vimentin. Aggregates of desmin occur as nonspecific cytoplasmic bodies or cytoplasmic spheroid complexes, similar to the aggregates of keratin filaments in Mallory bodies or the neurofilament aggregates in Lewy bodies. In all three instances, alpha-B crystallin may be associated with desmin. There are now increasing numbers of neuromuscular disorders in which abnormal amounts of desmin, some abnormally phosphorylated, feature prominently in muscle fibres. Several of these diseases, including spheroid body myopathy, granulo-filamentous body myopathy and the dystrophinopathies, are familial. Ultrastructural and immunohistochemical studies of desmin have considerably broadened our understanding of the pathology of the cytoskeleton in muscle fibers and in certain hereditary neuromuscular diseases.

The new cell line PaTu 8902 was established from a human pancreatic grade II adenocarcinoma of ductal origin. In early passages, cultured cells showed a high degree of heterogeneity in terms of their morphology and the number of chromosomes per cell. When transplanted subcutaneously into nude mice, these cells grew as tumors with a similar morphology and differentiation (grade II) to the primary tumor. In contrast, after prolonged cultivation, cells were more homogenous in terms of their morphology and number of chromosomes per cell, and the corresponding nude mouse xenografts were less differentiated (grade III). When cells from late passages were injected intravenously into nude mice, lung metastases occurred after 3-4 weeks. In addition, tumor cells were found in the wall of the esophagus and in the pleural cavity, indicating a high metastatic potential for PaTu 8902 cells in nude mice.

Expression of tissue factor (TF), the cellular receptor of clotting factor VII/VIIa, is a feature of certain malignant tumours. The TF gene has been classified as an immediate early gene responsive to serum and cytokines. Thus, the regulation of TF gene expression seems to play a role in cell growth. Recently, we have shown that constitutive TF expression in MCF-7 breast cancer cells is modulated by such growth factors as EGF, TGF alpha, and IL-1. The present study deals with the immunocytochemically detectable cellular distribution of TF in human breast cancer cell lines MCF-7 and MaTu stimulated by EGF and TGF alpha. In MCF-7 cells growing logarithmically, stimulation led to a significant increase of TF mRNA after 2 h (in situ hybridization, Northern blot) and to maximum TF expression after 6 h (immunohistochemistry). When decorated by monoclonal antibodies, TF protein showed a pronounced localization at ruffled membrane areas, cell edges, and processes of spreading cells after 6 and 20 h. In more flattened cells TF was concentrated in peripheric lamellae and microspikes communicating with neighbouring cells. After epithelial colony pattern had established, TF was predominantly accumulated at the intercellular boundaries. The vary same distribution patterns as seen in MCF-7 cells were true for the stimulated MaTu cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

In an experimental series of preneoplastic lesions and neoplasms induced in the rat kidney by dimethylnitrosamine, four of the 54 tumors showed particular morphological features that allowed them to be grouped separately. The leading characteristic of these lesions was an abundant PAS-positive matrix in which the tumor cells were embedded. The demonstration of variable amounts of laminin, heparan sulfate proteoglycan, collagen types IV and V in the tumor matrix provided circumstantial evidence that it consisted of basement membrane material. Since the tumor cells were in intimate contact with the matrix and no fibroblasts were present, it was assumed that the matrix was a product of the tumor cells. Until now, no similar renal tumors have been described in laboratory animals and no human equivalent is known.

This report describes a new method using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to visualize live viable tissue at the microscopic level. The visualization of the MTT stained tissue provides a metabolic assessment of tissue damage, and can be utilized as an extension of conventional hematoxylin-eosin (H & E) staining. In this report, several tissues were studied with MTT and H & E staining after incisions had been made by a variety of surgical dissecting instruments. A marked improvement in the detection of tissue damage was seen using MTT, regardless of how the damage was caused, i.e., physical, heat, or photon energy. In addition, a distinct zone of damage not noted on conventionally prepared and stained tissues is readily apparent. Thus MTT staining will have utility in both clinical and research studies, concerned with assessing the viability of tissues.

Cytomegalovirus (CMV) is a member of the herpes virus group. Infection results in a variety of disorders which depend largely on the immune status of the host. A well known property of CMV is that after primary infection the virus persists in the body of the host resulting in latency. Severe immunodepression or immunodeficiency can cause reactivation of the virus from its latent state, leading to endogenous reinfection. In contrast to other herpes viruses, such as herpes simplex virus which persists in neurons, and Epstein Barr virus which persists in B lymphocytes, little is known about the localization of latent CMV. In order to obtain more insight in the organ or cell type serving as a reservoir for latent CMV, it is important to know more about the course of natural infection and the cells and organs involved. When more information is available about the localization of latent virus, studies concerning the physical state of viral DNA or the extent of viral transcription and/or translation will follow in the near future. In this review some properties of the epidemiology and transmission of human CMV, as well as data about acute infection will be given. In addition, some characteristics of the localization of latent CMV and the physical state of the virus will be discussed. Where necessary, particularly regarding insight into CMV-host interactions, knowledge of animal, particularly murine, rat and guinea pig CMV infections, will be discussed.

The effects of hypercholesterolemia on both the initial and chronic phases of rat nephrotoxic serum (NTS) nephritis have been investigated. Injury during the initial phase of NTS nephritis in hypercholesterolemic rats maintained on a cholesterol-supplemented diet (Group 2) was characterized by segmentally accentuated accumulations of vacuolated cells with lipid droplets (foam cells) in the glomeruli, while the kidneys of rats fed a standard diet (Group 1) revealed only mild intracapillary cell proliferation. Immunoelectron microscopy showed that the foam cells observed in Group 2 rats were largely derived from macrophages. The glomerular macrophage number, defined by the number of ED1-positive cells per glomerulus, was significantly higher in Group 2 than in Group 1 animals at days 5-6 (3.4 +/- 1.4 in Group 1 against 6.3 +/- 1.0 in Group 2; p < 0.01) as well as at days 21-28 (5.5 +/- 2.6 in Group 1 against 10.9 +/- 2.8 in Group 2; p < 0.01). In contrast, the numbers of OX19-positive T-lymphocytes and OX33-positive B-lymphocytes were similar in both groups. In the chronic phase of NTS nephritis at week 20, semiquantitative evaluation of the glomerular lesions disclosed more severe focal segmental glomerulosclerosis (FSGS) in Group 2 compared with Group 1 animals (glomerular injury score: 14 +/- 10 in Group 1 against 73 +/- 17 in Group 2; p < 0.01). Accumulations of lipid and foam cells were invariably seen in the sclerotic foci of Group 2 animals. The results indicate that hypercholesterolemia played an important role in the accelerated development of FSGS in rat NTS nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin. In NC, alpha 2 staining was strongest in crypt cells; alpha 1,3 and alpha v, and beta 1,3 and beta 4, and Ck 20 and villin predominated in superficial enterocytes. In TA and VA, monolayered glands showed integrin, Ck 20 and villin patterns that differed slightly from both crypt and superficial enterocytes. Complex glands in VA showed decreased integrin staining and basal polarization; Ck 20 and villin were strong only in luminal cells. CA showed overall weaker integrin staining than adenomas. Regardless of invasion depth, well formed malignant glands mimicked TA; pleomorphic glands mimicked VA with focal basal integrin polarization and solid clusters displayed scanty integrins, uneven Ck 20, and villin in occasional cells. Diverse integrins in crypt compared with superficial enterocytes reflect changing adhesive requirements as cells migrate and terminally differentiate. Decreasing expression and altered distribution of integrins, Ck 20 and villin noted in TA, VA, and in CA of increasing grade indicate that certain adhesive and cytoskeletal features more closely relate to glandular architecture than to depth of invasion.

Platelet ultrastructural alterations are described in thrombocytopenic Saudi patients with acute falciparum malaria (AFM) and compared with the appearances of platelets from same patients after successful antimalarial treatment. Some altered platelets lost their discoid form and showed concentration of organelles in the cell centers. Other platelets were devoid of the alpha- and dense granules usually seen in normal cells. The lack of these granules is known to be associated with bleeding symptoms. The bundle of microtubules known to maintain the discoid form of platelets, and the contractile fibrillar elements responsible for "platelet propulsive movement" were either dispersed or absent. The open canalicular system known to be the main endocytic and secretory pathway was either absent, or distended and obstructed by cytoplasmic extensions. Most of platelets developed surface pseudopodia and endocytic vacuoles that are characteristic features of phagocytic cells. Different mechanisms have been suggested as the cause of these alterations. This study indicates that AFM is associated with platelet structural alterations which could be an important cause of thrombocytopenia; the frequency of these alterations correlated with the degree of parasitaemia. Older patients presented with less marked parasitaemia than younger patients, possibly due to the less mature immune system in the latter. It is also possible that AFM may have independent effects on the structure of human platelets.

A thyroid carcinoma cell line, BHT-101, has been established in vitro from a metastatic lymph node deposit in a female patient with a non-hormone producing anaplastic, partly thyroglobulin- and thyroxine (T4)-positive papillary thyroid cancer. The cell population is heterogeneous, containing epithelial-like and fibroblast-like cells, and has a doubling time of 24 h. The cell line is polyploid with hypertetraploid predominance and the karyotype showed trisomies, tetrasomies, pentasomies as well as many marker chromosomes. The majority of the cells are negative or weakly positive for thyroglobulin and thyroxine and estrogen and progesterone receptors are present in the cells. BHT-101 cells produce tumours when injected into immunosuppressed CBA/Ca mice. The cells are sensitive to adriamycin, methotrexate and tamoxifen but not to methimazole (Favistan). The epithelial-like clone 1 and the fibroblast-like clone 3, isolated from the parental line, differed in drug sensitivity. This new cell line is suitable for studying the biology of thyroid carcinoma and for parallel in vivo and in vitro studies of drug activity against thyroid cancer.