PROLIFERATIVE MYOSITIS AND FASCIITIS: Report of Five Cases with an Ultrastructural and Immunohistochemical Study

Cases of proliferative myositis and fasciitis were studied immunohisto-chemically and ultra structurally for further understanding of the nature of ganglion cell-like giant cells. Blood coagulation factor XIIIa, fibronectin, myoglobin, myosin, CPK MM, and alpha-1-antichymotrypsin were detected in three cases of proliferative myositis and two cases of proliferative fasciitis by the avid in-biotin-peroxidase complex method. Factor XIIIa (a fibrin-stabilizing factor) and flbronectin were strongly positive in the giant cells, but not in striated muscle fibers. A small quantity of myosin was demonstrated in the giant cells, but myoglobin and CPK MM were never demonstrated in these cells. No alpha-1-antichymotrypsin was demonstrated in the giant cells. One case of proliferative myositis showed ultrastructural features suggestive of fibroblast rather than muscle cell or histiocytic origin. Strongly positive factor XIIIa in the giant cells is suggestive of the fact that they are active fibroblasts.     

PERINEURIAL CELL TUMOR AND THE SIGNIFICANCE OF THE PERINEURIAL CELLS IN NEUROFIBROMA

The authors attempted to clarify the exact cell components of neurofibroma by immunohistochemical and ultrastructural studies. Materials were randomly selected, 40 cases of neurilemoma and neurofibroma (-tosis) in addition to 2 cases of tumors composed exclusively of perineurial cells and three cases of normal peripheral nerve. The applied markers included antisera of S-100 protein for Schwann cells, blood coagulation factor XIIIa for endoneurial fibroblasts or perineurial cells, and laminin and collagen type IV for the basement membrane. S-100 protein was demonstrated only in normal or neoplastic Schwann cells, but not in perineurial cells. On the other hand, factor XIIIa was often recognized in endoneurial fibroblasts and perineurial cells, but not in Schwann cells. Neurofibroma was basically composed of a mixture of Schwann cells, perineurial cells, and endoneurial fibroblasts, the population of each type of cell differing according to the case and area within a given tumor. Perineurial cell tumor exclusively composed of perineurial cells, though rare, appears to be a definite entity, and its characteristic histological and ultrastructural features were described.     

The assessment of cell proliferation during 9,10-dimethyl-1,2-benzanthracene-induced hamster tongue carcinogenesis by means of histone H3 mRNA in situ hybridization

The aim of this study was to investigate cell kinetics and ultrastructural changes during carcinogenesis using a hamster 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced tongue cancer model. Five squamous cell carcinomas, five dysplastic epithelia, seven hyperplastic epithelia, and four normal epithelia were obtained from 21 hamster tongues by applying 1.0% acetone solution of DMBA on the left lingual mucosa after scratching with a root canal broach. Ultrastructural examination revealed that the number of microvilli increased, whereas that of desmosomes decreased during carcinogenesis. Cell proliferation was analyzed by means of 5-bromodeoxyuridine (BrdU) immunohistochemistry and in situ hybridization (ISH) for histone H3 mRNA. The BrdU and histone H3 mRNA labeling indices (LIs) were lowest for normal epithelium, higher for hyperplastic and dysplastic epithelia, and highest for squamous cell carcinoma. Cytoplasmic histone H3 mRNA and nuclear BrdU were localized in virtually identical areas of serial sections. The correlation coefficient for the relationship between these two LIs was 0.97 (P 0.001). These results suggest that the assessment of cell proliferation using H3 mRNA ISH will be a useful technique for investigating biological behavior during carcinogenesis.     

Modifying effects of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids Re-80, Am-580 and Am-55P in a two-stage carcinogenesis model in female rats

Effects of dietary administration of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all-trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.     

Overexpression of the Del1 gene causes dendritic branching in the mouse mesentery

In the present study, we established transgenic mice overexpressing Del1, a ligand of integrins, to examine the effect of overexpression of Del1 on vascular morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes consisting of a long stalk and short branches at the periphery. In contrast, those in transgenic mice showed typical dendritic architecture consisting of a few large primary branches with smaller spreading branches. The phenotype of mice overexpressing Del1 suggests the existence of a tissue-specific mechanism for branching morphogenesis in the mesentery.     

Measurement of plasma von Willebrand factor cleaving protease in patients with varied thrombotic microangiopathy

Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma of patients with TTP has been shown to contain unusually large von Willebrand factor(vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP. We examined the activity of the vWF-cleaving protease(vWF-CP), by modified Furlan's method, in plasma from patients with a familial TTP, 3 acquired TTP, 4 thrombotic microangiopathy(TMA) and 2 veno-occlusive disease(VOD) associated after allo-BMT. Diluted plasma samples of patients were incubated with protease-free vWF purified from normal human plasma, in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in SDS-agarose gels and immunoblotting. Activity of vWF-CP from 12 normal plasma have been shown as 77-180%(average 115%), whereas, no vWF-CP(below 5%) was observed in plasma from familial TTP, before and after plasma exchange, although FFP infusion therapy has been effective for this patient to recover thrombocytopenia. In 3 acquired TTP, 2 patients showed lack of vWF-CP activity in plasma, and inhibitors against vWF-CP have been elucidated by plasma cross-mixing test. After extensive plasma exchange and FFP infusion followed by corticosteroid therapy, normal vWF-CP was recovered in plasma from 2 acquired TTP patients. Among BMT patients, plasma from 4 BMT-TMA showed normal vWF-CP activities as 55-111%, whereas plasma from 2 BMT-VOD revealed low vWF-CP activity, as 24% and 37%, respectively. Thus, measurement of vWF-CP is crucial to predict differentiation of primary forms of TMA to establish the pathogenesis in varied endothelial dysfunction.     

Prototype heel effect compensation filter for cone-beam CT

The prototype cone-beam CT (CBCT) has a larger beam width than the conventional multi-detector row CT (MDCT). This causes a non-uniform angular distribution of the x-ray beam intensity known as the heel effect. Scan conditions for CBCT tube current are adjusted on the anode side to obtain an acceptable clinical image quality. However, as the dose is greater on the cathode side than on the anode side, the signal-to-noise ratio on the cathode side is excessively high, resulting in an unnecessary dose amount. To compensate for the heel effect, we developed a heel effect compensation (HEC) filter. The HEC filter rendered the dose distribution uniform and reduced the dose by an average of 25% for free air and by 20% for CTDI phantoms compared to doses with the conventional filter. In addition, its effect in rendering the effective energy uniform resulted in an improvement in image quality. This new HEC filter may be useful in cone-beam CT studies.     

Incidence of latent infection of Epstein–Barr virus in lung cancers—an analysis of EBER1 expression in lung cancers by in situ hybridization

To evaluate the presence of Epstein–Barr virus (EBV) in lung cancers of Japanese patients, 81 lung cancers were examined using a highly sensitive in situ hybridization (ISH) method, employing an antisense oligonucleotide probe for EBV-encoded small nuclear RNA-1 (EBER). EBER1 expression was demonstrated in one poorly differentiated squamous cell carcinoma associated with marked lymphoid stroma (PDSCC-LS), two well differentiated adenocarcinomas, and two moderately differentiated squamous cell carcinomas, but was not detectable in other lung cancers, including small cell carcinomas. Unlike lymphoepithelioma-like undifferentiated carcinoma (LELC) of the lung, the PDSCC-LS consisted of poorly differentiated cells with distinct cell borders and nuclei with a coarse chromatin pattern and some prominent nucleoli. Most of the cancer cells expressed intense EBER1 signals. Although small to moderate numbers of cells positive for EBER1 were present in two adenocarcinomas and two squamous cell carcinomas, EBER1 signals varied in intensity and number in these four cases. Although polymerase chain reaction (PCR) and Southern blot hybridization with a ³²P-labelled probe internal to the primers were conducted to detect the EBV genome in 24 lung cancers, including five EBER1-positive cases, the genome was found to be positive in the five cases with EBER1-positive staining, including the PDSCC-LS, two adenocarcinomas and two squamous cell carcinomas, but not in the other cases. This study indicates that the morphological features of EBV-associated lung cancers are not restricted to the typical LELC type.     

Absence of either gastric or intestinal phenotype in microscopic differentiated gastric carcinomas

Differentiated gastric carcinoma (DGC) corresponds roughly to the intestinal type of gastric carcinoma described by Laurén. It has been suggested that DGCs arise from intestinalized gastric mucosa, but recent findings regarding their mucin expression do not support this hypothesis. To evaluate the histogenetic relationship between DGCs and intestinal metaplasia, lesions that are as small as possible should be examined. Twenty-five DGCs, ranging in their greatest dimension from 0.4 to 2.7 mm, were collected and divided into two groups by size. Group A consisted of 13 lesions less than 1.4 mm across, and group B of 12 lesions 1.4 mm or more. The presence of mucin and a brush border was assessed by immunostaining with antibodies against human gastric mucin, pyloric-gland-type mucin, Muc-2 glycoprotein, and CD10 antigen, and the lesions were classified as having the gastric phenotype (G-type), intestinal phenotype (I-type), mixed gastric and intestinal phenotype (M-type), or null phenotype (N-type). Thirteen (52%) of the 25 lesions were N-type, 5 (20%) lesions were G-type, 5 (20%) were I-type, and 2 (8%) were M-type. Group A had a larger proportion of N-type lesions than B (10/13, or 77%, vs. 3/12, or 25%; p = 0.027, chi-square test for proportions). Group B had a larger proportion of G-type lesions than A (5/12, or 42%, vs. 0/13, or 0%; p = 0.033). The phenotypes of the carcinomas and their surrounding mucosa were unrelated. Therefore, DGCs may arise from gastric mucosa affected by intestinal metaplasia or not, without having either the gastric or intestinal phenotype.