慢性活动性肝炎中单核性细胞超微形态研究

经电镜观察,慢活肝中主要为淋巴细胞及单核巨噬细胞浸润。淋巴细胞分3型,通过4种方式与肝细胞接触,可能代表杀伤肝细胞的动态过程。与肝细胞接触的主要为起细胞毒作用的T_8~+Ⅱ型淋巴细胞及单核巨噬细胞。多数T_4~+淋巴细胞为Ⅰ型淋巴细胞,可能为T辅助细胞。在肝细胞损伤中,淋巴细胞及单核巨噬细胞均起重要作用。     

Tamoxifen induces ultrastructural alterations in membranes of Bacillus Stearothermophilus

Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for chemotherapy and chemoprevention of breast cancer. However, the mechanisms by which TAM inhibits cell proliferation in breast cancer are not fully understood. TAM strongly incorporates in biomembranes and a variety of effects have been assigned to biophysical and biochemical interactions with membranes. Therefore, a better understanding of the physicochemical basis of interaction of TAM with biomembranes is essential to elucidate the molecular mechanisms of action. A strain of Bacillus stearothermophilus has been used as a model to clarify the interaction of TAM with the cell membrane. TAM effects on the ultrastructure of membranes of this bacterium were evaluated by electron microscopy. Important ultrastructural alterations were observed in B. stearothermophilus treated with TAM, namely change in the geometry of the membrane profile from asymmetric to symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix, occurrence of mesossomes, appearance of fractures in membranes and the alteration of the ultrastructure of cell wall. These ultrastructural alterations confirm that TAM is a membrane-active drug and that membrane damage may be involved in molecular mechanisms of cell death induced by this drug.     

Tamoxifen induces ultrastructural alterations in membranes of Bacillus Stearothermophilus.

Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for chemotherapy and chemoprevention of breast cancer. However, the mechanisms by which TAM inhibits cell proliferation in breast cancer are not fully understood. TAM strongly incorporates in biomembranes and a variety of effects have been assigned to biophysical and biochemical interactions with membranes. Therefore, a better understanding of the physicochemical basis of interaction of TAM with biomembranes is essential to elucidate the molecular mechanisms of action. A strain of Bacillus stearothermophilus has been used as a model to clarify the interaction of TAM with the cell membrane. TAM effects on the ultrastructure of membranes of this bacterium were evaluated by electron microscopy. Important ultrastructural alterations were observed in B. stearothermophilus treated with TAM, namely change in the geometry of the membrane profile from asymmetric to symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix, occurrence of mesossomes, appearance of fractures in membranes and the alteration of the ultrastructure of cell wall. These ultrastructural alterations confirm that TAM is a membrane-active drug and that membrane damage may be involved in molecular mechanisms of cell death induced by this drug.     

Solid and Cystic Tumor of the Pancreas in an Adult Male

A solid and cystic tumor (SCT) was located at the head of the pancreas in a 43-year-old Japanese male, and pancreatoduodenectomy was performed on the suspicion of papillary carcinoma or cystadenocarcinoma of the pancreas. The lesion, which measured 4.5 X 4.5 X 4.0 cm, was clearly demarcated by connective tissue. The cut surface showed solid grayish-white areas with central cystic degenerative changes. The solid areas consisted of small round cells proliferating in a small solid or a pseudopapillary pattern. The tumor cells partially invaded the surrounding normal pancreatic parenchyma. Immunohistochemical studies revealed positive staining for alpha-1-antitrypsin and neuron-specific enolase, but no staining for known pancreatic hormones. Moreover, ultrastructural studies showed the absence of zymogen granules and the presence of anullate lamellae and neurosecretory granules. On the basis of these findings, a diagnosis of SCT of the pancreas was established. In order to clarify the histogenesis and biological behavior of the tumor, it is necessary to accumulate and analyze similar cases, an endeavor which in turn will contribute to the successful management of this disease. Acta Pathol Jpn 41: 763-770, 1991.     

Sinonasal teratocarcinosarcoma: ultrastructural and immunohistochemical evidence of neuroectodermal origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Ultrastructural myeloperoxidase activity and expression of myeloid-associated antigens in acute lymphoblastic leukemia

Ultrastructural myeloperoxidase (MPO) activity and myeloid-associated antigen (MyAg) expression were investigated in 12 adult patients with acute lymphoblastic leukemia (ALL). Ultrastructural MPO was detected by 3 different methods. Immunophenotyping was performed by flow cytometry, using a series of monoclonal antibodies. Ultrastructural MPO-positive blast cells were detected in 6 patients (50%). In 5 of these 6 patients, the methods detecting both MPO and platelet peroxidase (PPO) activities found MPO-positive blast cells more frequently than those detecting MPO activity alone. In 2 patients (17%), at least one kind of MyAg was positive. Ultrastructural MPO activity was detected more frequently than MyAg expression in ALL patients. This method of detecting PPO and MPO is recommended for detection of ultrastructural MPO-positive ALL.     

Ultrastructural study of 4 cases of Ki-1 positive large anaplastic cell malignant lymphoma

Summary The ultrastructural morphology of 4 cases of large anaplastic cell malignant lymphoma (Ana ML) is reported. Three cases were primary Ana ML and one pleomorphic large T cell lymphoma with some Ki-1 positive cells. All were confirmed by immunohistochemistry on frozen and paraffin sections. The Ki-1 and EMA positive tumour cells had an abundant cytoplasm, with no differentiation and large pale nuclei with multiple compact or dispersed nucleoli. The morphology is that of an activated cell engaged in protein synthesis and/or in the mitotic cycle. These tumour cells resemble to the Hodgkin's and monolobated Reed-Sternberg cells described in Hodgkin's disease.     

Adenoid cystic carcinoma of minor salivary glands. Analysis of 86 cases

Summary 819 salivary gland tumors in surgical pathology files over a 25-year period were reviewed. Among 117 adenoid cystic carcinomas, 86 were located in minor salivary glands and were selected for a clinico-pathological analysis. Complementary histoenzymological investigations and electron microscopic study were performed on specimens from 7 and 13 patients respectively.Adenoid cystic carcinoma occured in older patients (mean age of 54 years) than the other salivary neoplasms. The sex ratio was 1/1. The tumor was located more often in the palate and, to a lesser degree in the buccal floor, tongue or gums.Histologically, epithelial nests contained characteristic cyst-like spaces (cylinders) and 3 varieties of such cylinders were described (mucoid, mucohyalin and hyalin). According to the predominant pattern, 3 types of tumors were shown: basaloïd, cribriform and trabecular. A comparison between histological results and clinical behaviour, available in 67 patients, demonstrated positive correlations. The basaloïd form had always a poor prognosis (numerous early recurrences and metastases, frequent lethal evolution). The cribriform type had an intermediate prognosis, better than basaloïd type and less good than trabecular group (100% of patients still alive at 8 years).Histoenzymological studies revealed high level of acid phosphatase, alkaline phosphatase and leucine aminopeptidase activities round cylindromatous cavities. On the other hand, high oxidative enzyme activities were evenly distributed in all cell types.Ultrastructural findings emphasized the immature characters of epithelial tumor cells. These cells contained numerous ribosomes, but few other organelles. Some more differentiated glandular or epidermoid cells were scattered in neoplastic islands. Rare myoepithelial cells lay in periphery of lobules. Cylinder-like spaces were filled with replicated basal lamellae, mucopolysaccharidic granules and fibrillar structures (microfibrils and periodic collagen fibrils).In the light of these results the histogenesis of this neoplasm was discussed. Like the pleomorphic adenoma, adenoid cystic carcinoma was thought to arise from intercalated ducts. Unable to acquire any high degree of differentiation, this blastomatous tumor had a cellular component almost similar to that shown in intermediate stage of salivary gland embryogenesis.The authors wish to thank M.A. Leost and M. Tacnet for their technical assistance     

Ultrastructural histochemistry of mesotheliomas and adenocarcinomas in malignant effusions

The results of electron microscopic examination of cytologic specimens from six cases of mesothelioma and 10 cases of metastatic carcinoma of different origins are presented. The formation of cell clusters in malignant effusions from the two neoplasms has been thoroughly investigated: in mesotheliomas, cells had longer, more slender microvilli than in carcinomas and more abundant bundles of intermediate filaments; the central cavity often seen in the clusters frequently contained collagen and showed basement membrane production. The application of periodic acid-silver methenamine (PASM) and phosphotungstic acid (PTA) demonstrated a peculiar ultrastructural difference in cell coat staining in the two tumor types: in mesotheliomas, PTA and PASM were consistently negative along the outer surface of the cell aggregates, while carcinomas displayed a positive reaction either on the outer surface or on both inner and outer surfaces of the clusters. The diagnostic significance of the above-mentioned difference between the two neoplasms will require further investigation in a larger number of cases.     

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

Summary The effects ofd-sotalol on intercellular electrical coupling and ultrastructure under hypoxic conditions were investigated in myocardial samples from eight young (1–2 months) and four older (10–12 months) guinea pigs. A right ventricular muscle strip was kept simultaneously in two divided chambers and superfused with normoxic and/or hypoxic (97% N₂+ 3% C_O2) Krebs solution. Hypoxia caused shortening of action potential duration (APD) and electrical cellto-cell uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30 min), administration of 3.10^–7M ofd-sotalol to the hypoxic perfusate led to a recovery of electrical coupling. Transmission electron microscopy revealed moderate reversible ultrastructural alterations of the cardiomyocytes. No apparent changes in intercellular junctions were observed. The recoupling effect of sotalol decreased with the time of hypoxia as the ultrastructural damage progressed. After prolonged hypoxia (more than 30min), cardiomyocytes were markedly injured, intercellular junctions were severely affected, and gap junctions occurred less frequently. In these cases, administration ofd-sotalol caused only transient recoupling. After 1h of hypoxia, no recoupling was observed. Pretreatment withd-sotalol prevented hypoxia-induced electrical uncoupling and markedly attenuated ultrastructural damage, although shortening of APD still persisted. Our results indicate that the cardioprotective effect ofd-sotalol on electrical intercellular coupling is closely associated with sotalol-induced prevention of the ultrastructural damage. Considering previous results, we suggest that this protective effect ofd-sotalol may be related to its ability to increase intracellular cyclic adenosine monophosphate and, thereby, to decrease cytosolic free Ca. These effects can explain the antiarrhythmic and defibrillating properties ofd-sotalol.