Confocal observation of senile plaques in Alzheimer's disease: Senile plaque morphology and relationship between senile plaques and astrocytes

Senile plaques In the brains of Alzheimer's disease (AD) were examined by confocal laser scanning microscopy (CLSM) with the following three findings. First, in sections stained with Congo red, the serial CLSM images of optical sections clearly revealed that a classic plaque is composed of a plaque core and a corona. Radially arranged process-like structures, corresponding to bundles of amyloid fibrils, formed amyloid cores and stronger signals were detected in the center of some cores. Second, in sections stained with Congo red and anti-gllal fibrillary acidic protein (GFAP), reactive astrocytes were found around the senile plaques and many astrocytlc processes surrounded the plaque cores and some processes had penetrated into them. Third, three-dimensional reconstruction on classic plaque revealed that the surface of classic plaque showed a 'coral-like' appearance.     

Immunolocalization of extracellular matrix proteins and integrins in sarcoid lymph nodes

 To improve our understanding of the role of extracellular matrix (ECM) proteins and integrins during the processes of granuloma formation in sarcoidosis, we examined the distribution of ECM proteins and the expression of integrins in sarcoid lymph nodes by immunohistochemical methods. We also examined the expression of transforming growth factor-β1 (TGF-β1), which is one of major regulators for synthesis of ECM proteins. Most ECM proteins were detected in the periphery of the granulomas in a concentric pattern, and fibronectin was diffusely detected from an early to a regressive stage. Compared with normal lymph nodes, most β1-integrin subfamilies (α1, α4, α5 and α6) were more strongly expressed on lymphocytes around the granulomas. Epithelioid cells exhibited strong expression of the α5 molecule. Fibroblasts exhibited the expression of the α2 and α5 molecules surrounding ECM proteins. The α5β1 molecule had a distribution similar to that of fibronectin. TGF-β1 was detected in epithelioid cells throughout the various evolutional stages and its expression was especially marked in mature granulomas. Interaction of fibronectin and the α5β1 molecule may have an important role in the process of formation of sarcoid granuloma. The expression of TGF-β1 may be involved in the regression of sarcoid granuloma by initiating fibrosis and atrophy of epithelioid cells. Received: 2 December 1997 / Accepted: 19 February 1998     

Ultrastructural,immunohistochemical and biochemical studies on amylase and ACTH producing lung cancer

Summary Tumour tissue from a lung cancer patient who showed elevated serum amylase and adrenocorticotropin (ACTH) was studied ultrastructurally, immunohistochemically and biochemically. Histologically the tumour was a small cell carcinoma. On electron microscopic examination the tumour cells contained large zymogen-like granules within the cytoplasm. Furthermore, cells which possessed many small dense core granules of the endocrine type were also observed. It was of interest that the large zymogen-like granule-containing tumour cells had microvilli at the apical border, connected by desmosomes and forming lumina showing adenocarcinomatous differentiation. Electrophoretic analysis of the serum revealed that the major elevated amylase was of the salivary type with minor components. Immunostaining clearly demonstrated that most of the tumour cells possessed immunoreactive ACTH, whereas salivary amylase was only found in occasional clusters of the tumour cells. The results seem to indicate that the tumour showed both endocrine and exocrine characteristics - an amphicrine carcinoma, expressing amylase and ACTH simultaneously.     

LYMPHOMATOID GRANULOMATOSIS: Light Microscopic, Electron Microscopic and Immunohistochemical Study

A case of lymphomatoid granulomatosis (LYG) involving the lungs, skin, stomach, and possibly the left kidney in a 60-year-old man is presented. The infiltrates in the lungs, stomach, and skin showed a polymorphic appearance, and consisted predominantly of lymphocytes of mature and blastic form and of a few neutrophils, plasma cells, and histiocytes. Most lymphoid cells showed irregularly shaped nuclei and clustered dense bodies, characteristics indicative of T lymphocytes. An immunohistochemical study confirmed the T cell origin of the lymphocytes; i.e. they were positive for Leu-1, Leu-3a and la-like antigens but negative for Leu-2a antigen and the antibodies against light chains. The homogeniety of the major population of infiltrates in LYG indicates that at least some forms of LYG may be neoplastic or pre-neoplastic lymphocytic disorders which may ultimately progress to malignant lymphoma. ACTA PATHOL. JPN. 35 : 711–721, 1985.     

Membrane Fusion In Mitochondria Ii. An Ultrastructural Interpretation Of Cristae-Enriched Megamitochondria Induced By Cuprizone

Ultrastructure of megamitochondria in mouse hepatocytes induced by cuprizone was analyzed in the light of the fusion of inner mitochondrial membranes. Hepatic parenchymal cells of mice fed with a 0.5% cuprizone-diet for 7–8 days were characterized by megamitochondria with numerous cristae including disoriented, shorter ones than those of the control and those in vesicular configuration. After feeding the animals with cuprizone for 15–16 days, megamitochondria increased their sizes further and the number of cristae decreased drastically. Numbers of cristae based on a unit-mitochondrial area were 41.3$pL10.8 for the former type of cristae-enriched megamitochondria and 3.8 $pL 1.8 for the latter type of megamitochondria with the value of 23.9 $pL 6.2 for the control. Considering the content of cytochromes in megamitochondria previously reported, these results might suggest that the fusion and defusion of inner mitochondrial membrane take place along with the fusion of outer membranes during the megamitochondrial formation. ACTA PATHOL. JPN. 34: 481–488, 1984.     

BRONCHIAL CARCINOID ACCOMPANIED BY THYROID ADENOMAS AND ADRENAL ADENOMAS

A large tumor massively occupying the left pleural cavity had the Andings of both typical carcinoid and oncocytoma which were thought to be of bronchogenic origin. The ultrastructural observation of the tumor revealed a mixture of rod-shaped granules in addition to usual round neurosecretory ones. In the nuclei of dark cells of the oncocytoma, a latticed or hatched structure was detected. Besides two adenomas and hyperplastic foci of large acidophilic cells in the thyroid, a black adenoma and cortical adenoma in the adrenal gland, were detected. Moreover, there was an ectopic adrenal gland in the retroperitoneum. Briefly it was suggested that the bronchial carcinoid presented may be related to multiple endocrine adenomatosis.     

AN IMMUNO-ELECTRON MICROSCOPIC STUDY ON INTRA and EXTRACELLULAR LOCALIZATION OF ALPHA-FETOPROTEIN IN HUMAN HEPATOCELLULAR CARCINOMA

Intra and extracellular localization of alpha-fetoprotein (AFP) has been studied by an indirect peroxidase labeled antibody method using 12 cases of human hepatocellular carcinoma (HCC). With light microscopic observation, positive immuno-staining for AFP was observed in 6 out of 12 cases and demonstrated as granular or diffuse deposits in the cytoplasm of neoplastic hepatocytes. In electron microscopic studies, 8 cases showed the positive immuno-staining for AFP in the neoplastic hepatocytes. Intracellular antigen was well circumscribed within certain cell organelles with the positive immuno-staining for AFP being observed in perinuclear space, cisternae of rough endoplasmic reticulum (RER), Golgi complexes, and secretory vesicles. In addition, the positive immuno-staining for AFP was observed in bile canaliculus-like space in most cases with increased levels of serum AFP and in some cases which showed normal levels of serum AFP. Furthermore, the positive immuno-staining for AFP was also observed in intercellular, Disse's-like and sinusoid-like spaces, and micropinocytotic and lysosome-like vesicles in the endothelial cells in a few cases which showed excessively high value of serum AFP. ACTA PATHOL. JPN. 37:915–928, 1987.     

Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease

To investigate the expression of human herpesvirus 8 (HHV8)-encoded proteins in the cells of primary effusion lymphoma (PEL), Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD), nine rabbit polyclonal antibodies to K2, ORF26, K8, K8.1, K10, K11, ORF59, ORF65, and ORF73 were developed. Western blot analysis in PEL cell lines (TY-1 and BCBL-1) revealed that the expression of these proteins, except ORF73 (LANA), was induced by tetradecanoylphorbol acetate (TPA) treatment, indicating that these proteins are lytic proteins. Immunofluorescence assay in primary PEL cells derived from pericardial effusion and PEL cell lines with and without TPA treatment revealed that primary PEL cells exhibited the same expression pattern as noninduced PEL cell lines, and the treatment changed localization of K8, ORF59, and ORF65 proteins. Immunohistochemistry revealed that 90% of KS spindle cells expressed the ORF73 protein, whereas a small population of KS cells expressed K8, K10, K11, ORF59, and ORF65 proteins. In MCD, ORF73, ORF59, K8, K2, and K10 proteins were expressed in the cells at mantle zone of the follicle. These data indicate that KS and PEL cells expressed predominantly latent proteins, whereas MCD expressed both latent and lytic proteins, suggesting that HHV8 plays a different role in the pathogenesis of HHV8-associated diseases.     

SS1 Helicobacter pylori disrupts the paracellular barrier of the gastric mucosa and leads to neutrophilic gastritis in mice

Helicobacter pylori induces severe neutrophilic infiltration in the lamina propria of the stomach, which leads to gastritis in humans. The possible involvement of a paracellular route for bacterial nutrients and etiologic agents that may play an important role in colonization of the bacteria and cause gastritis has been suggested. To study the functions of the paracellular barrier of gastric surface epithelium, SS1, a strain of H. pylori adapted to the murine stomach, was inoculated into the stomachs of C57BL/6 mice. At 4 months after inoculation, SS1 had achieved a high level of colonization (10(6)-10(7) colony-forming units/g tissue) associated with neutrophilic infiltration in the lamina propria of the junctional zone. Disruption of the paracellular barrier was observed in the SS1-infected stomachs, as revealed by the invasion of a lanthanum tracer into the paracellular space of the surface epithelium. Only 2% of junctions were permeable in control stomachs, whereas 72% of the paracellular barrier was disrupted in the SS1-infected gastric epithelia. Furthermore, distribution of tight junction-related molecules such as 7H6 antigen, occludin, and cortical actin was affected in the surface epithelium by SS1 infection. The linear expression pattern of occludin was disrupted and became irregular or punctuated. The 7H6 antigen accumulated as aggregates in the apical portion of the surface epithelium and cortical actin became irregular and punctuated. Taken together, these results indicate that infection by SS1 directly or indirectly caused an increase in paracellular permeability and altered the localization of tight junction-related molecules of the gastric surface epithelium. This observation suggests that the paracellular pathway may play a significant role in establishing H. pylori-induced gastritis in the clinical setting.     

Abnormal accumulation in lipopolysaccharide in biliary epithelial cells of rats with self-filling blind loop

Primary sclerosing cholangitis (PSC) is known to be frequently associated with inflammatory bowel diseases. In a rat with self-filling blind loop (SFBL), a proposed animal model for PSC, hepatobiliary inflammation has previously been demonstrated. In this study, we assessed the involvement of lipopolysaccharide (LPS), a bacterial endotoxin, in the pathogenesis of hepatobiliary inflammation of the SFBL model. The hepatic localization of LPS was examined by immunohistochemistry using an anti-lipid A antibody. The portal blood concentration of LPS was measured by an endotoxin-specific chromogenic Limulus test (Endospecy test). LPS was localized in the biliary epithelial cells (BECs) of rats with SFBL, and the portal blood concentration of LPS was significantly higher than that of sham-operated rats. Development of hepatobiliary inflammation, peribiliary fibrosis, and injury to the intestinal mucosa were histologically confirmed. Constriction in the biliary trees was radiologically demonstrated. These findings suggested that abnormal accumulation of LPS, which may be derived from portal blood, in BECs was involved in the pathogenesis of hepatobiliary inflammation with intestinal injury.