Acta pathologica japonica最新文献

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.

Oral administration of N-methyl-N'-nitro-N-nitrosoguanidine induced gastrointestinal tumors in 15 out of 19 rats: six adenomas, seven adenocarcinomas, one fibrosarcoma and one malignant schwannoma that was homotransplantable. Both the original and transplantable tumor exhibited characteristic morphological features and immunoreactivity identical to that of a human malignant schwannoma: positive reaction for S-100 protein, neuron specific enolase, glial fibrillary acidic protein, myelin basic protein and vimentin. In addition, alpha-smooth muscle actin was expressed in both tumors. Cultured tumor cells derived from the transplantable tumor at passage 3 produced 18 clones which showed anchorage independent growth in soft agar. From these clones, two cell lines showing characteristic immunoreactivity, designated as RMS-1 and 2, were established. In general, the immunoreactivities of the two cell lines were similar to those of the original tumor; however, the RMS-1 cell line demonstrated positive immunoreaction for neurofilaments and RMS-2 was negative for alpha-smooth muscle actin. Subcutaneous, injection of cultured cells from both cell lines into athymic BALB/c nude mice induced tumors identical to the original tumor. In the present study, transplantable malignant schwannoma was established in the rat and two phenotypes were isolated and established as cell lines.

A new human cell line, LC-2/ad was established from pleural effusion of pulmonary adenocarcinoma of a 51 year old Japanese female. The LC-2/ad cells exhibit an epithelial appearance and a tendency to form small domes as observed with phase-contrast microscopy. The modal chromosome number was 53-56. Plating efficiency and doubling time were 6.8% and 58 h, respectively (32th passage). Immunocytochemically, the cells were strongly positive for CEA and cytokeratins including cytokeratin no. 18 which is present in simple epithelia. Ultrastructurally, the cultured cells were characterized by well-formed junctional complexes and microvilli. Subcutaneous injection of 5 x 10(6) cells into a nude mouse resulted in tumor formation classified histologically as a moderately differentiated adenocarcinoma. This cell line produced at least two functionally active trypsin inhibitors together with several proteinases in vitro. The main inhibitor was purified partially from the serum-free conditioned medium and confirmed immunologically as human alpha 1-antitrypsin (AAT). Immunohistochemically, the xenografted tumor was also positive for AAT. The cell line LC-2/ad is useful for the study of tumor-derived serine proteinase inhibitors, in particular AAT.

Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma of the human thyroid. Immunohistochemically, it was found that the reactivity for bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary carcinomas. However the extract of the papillary carcinomas contained the mitogenic activity for endothelial cells. This bioactive molecule was determined as bFGF by using the heparin-Sepharose affinity chromatography and western blot analysis. The bFGF derived from human thyroid papillary carcinoma and the recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the cultured human thyroid papillary carcinoma cells. These cells also showed positive staining for thyroglobulin and cytokeratin. These results indicate that bFGF, probably produced by the neoplastic cells, plays an important role in the development of papillary carcinoma of the thyroid with stimulation of angiogenesis as well as proliferation of the parenchymal cells.

The influence of sex hormones on induction of intestinal metaplasia was examined in 5 week old Crj: CD (SD) rats of both sexes. At the age of 4 weeks, the animals were gonadectomized and given testosterone or dimethyl estradiol (DES). One week after operation, they were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3 day interval for a total of 20 Gy. At the termination of the experiment, 6 months after the alkaline phosphatase (ALP) positive foci in males was significantly higher than in females, in orchidectomized males or orchidectomized plus DES treated rats (P < 0.01). On the other hand, the incidence of intestinal metaplasia with ALP-positive foci in normal females appeared lower than in ovariectomized females (P < 0.01), and was increased in rats by treatment with testosterone or decreased by DES. Numbers of foci of intestinal metaplasias with Paneth cells and total numbers appeared to increase in males treated with DES. The results suggested a promoting role for testosterone in the development of ALP positive lesions and indicated considerable heterogeneity between intestinal metaplasia subtypes.

Clinicopathological and cytofluorometric studies were performed on nine encapsulated (EPC) and 23 non-encapsulated (non-EPC) carcinomas of the thyroid gland. The average age of the patients with EPC was 33 years, which was significantly younger than that of those with non-EPC. The average tumor size of EPC was twice as large as that of intraglandular non-encapsulated carcinoma. All patients with EPC were alive without disease, but three out of 23 patients with non-EPC had a recurrence of the disease or died. Cytofluorometric studies showed that the mean nuclear DNA content and percentage of tumor cells in the S-G2M phase of EPC were lower than that of non-EPC. According to the DNA histogram pattern, all EPC showed distinct modal DNA values in the diploid or near diploid region of normal cells. However non-EPC, especially extra-glandular non-encapsulated papillary carcinoma, showed a wide variety of DNA histogram patterns. The present study suggested that EPC is a distinct subtype of papillary carcinoma of the thyroid gland clinicopathologically and that cytofluorometrically it is different from non-EPC.

A cell line derived from medial smooth muscle cells (SMC) was established from the porcine coronary artery by transfection with ori-defective simian virus 40 plasmid DNA (SV40 DNA). The characteristics of transfected cells (SV40-SMC) such as cell growth, collagen and non-collagen syntheses were investigated. SV40-SMC expressed SV40 large T antigen, c-myc and c-myb encoded proteins in the nuclei. SV40-SMC demonstrated a 'hills and valleys'-like arrangement in overconfluence and actin filaments upon immunofluorescent staining. Under electron microscopic observation, SV40-SMC had larger amounts of synthetic organelles and smaller amounts of filament bundles than those of SMC. SV40-SMC demonstrated three times higher growth activity and 4.4 times greater cellular density than SMC. Smooth muscle cells did not grow in media containing 5% plasma derived serum (PDS) instead of normal serum, whereas SV40-SMC proliferated in this medium. SV40-SMC did not grow in soft agar gel, while HeLa S3 cells, a cell line of human cervical carcinoma, formed colonies in this gel. By immunofluorescent (IF) staining, collagen phenotypes I, III, IV and V were detected in both SV40-SMC and SMC. However, protein synthesis including collagen and non-collagen was higher in SV40-SMC than in the control sample. It was concluded that SV40-SMC were a continuous cell line for vascular SMC regarding morphological characteristics, and demonstrated a higher growth activity, with increased collagen and non-collagen syntheses. This cell line is useful for the investigation of atherogenesis in relation to a proliferation of SMC and an accumulation of extracellular matrices in vascular intima.

Morphological alterations of the glomerulus were induced by infusion of cationized ferritin. After a direct injection of highly cationized ferritin (CF) into the left kidney of rats, endothelial injuries were followed by activation of platelets and the coagulation system after 1-2 h, which occluded capillary loops. In most glomeruli, resolving processes occurred from 2 h onward, leaving a mild thickening of the mesangial region at 7 days. On the other hand, in severely involved glomeruli, capillary loops were still obstructed even at 24 h by hypertrophic and proliferated endothelial cells as well as mesangial cells, instead of platelets and fibrin strands. After this period, exfoliation of podocytes and endothelial cells occurred over a wide area, which resulted in glomerular obsolescence at 7 days. These progressive glomerular injuries were assumed to be closely related to the persistence of CF in glomeruli, which might be caused by disturbances of glomerular clearing systems. Mild proteinuria was only noticed in severely involved cases. It is concluded that an assault on glomerular endothelial cells by cationic macro-molecules can cause thrombotic complications leading to glomerular obsolescence.

A human hepatocellular carcinoma (HCC) cell line, KIM-1, was cultured in three different concentrations (0.1, 0.2 and 0.3%) of type-I collagen gel matrix and its morphologic features, growth kinetics and alpha-fetoprotein and albumin productions were compared with each other or with those of cells growing on a plastic dish. KIM-1 cells in any concentration of collagen gel matrix formed various sized three-dimensional colonies with compact to trabecular cell arrangement. Larger colonies with a more definitive trabecular cell arrangement, resembling the in vivo structure of HCC, tended to form in the collagen gel matrix of a low concentration. The prolongation of doubling time was identified as the collagen concentration in the gel became higher. The cells on a plastic dish proliferated in a monolayered sheet with a shorter doubling time than others. Ultrastructurally, the cells in collagen gel matrix have more distinct cell membranes, junctional complexes and bile canaliculus-like structures, and less cytoskeletons than those on plastic dishes, similar to those in vivo. The productions of alpha-fetoprotein per 10(4) cells and albumin per 10(5) cells were much higher in the collagen gel matrix culture than on a plastic dish in a stationary phase. These data suggest that collagen gel matrix culture is suitable to monitor the morphologic features and protein production of the tumor cells in similar conditions to those in vivo, and tht the three-dimensional presence of an extracellular matrix is important in cellular proliferation and differentiation.