Experimental studies suggest that captopril plays an important preventive role in radiation induced renal injury (RRI). To elucidate the pathogenesis of RRI and effect of captopril, one subgroup was irradiated with a single dose of 9 gray (Gy) total body irradiation and another subgroup with 17 Gy local irradiation in the right kidney. Twenty-four healthy looking Sprague-Dawley rats, weighing 200~250 g, were divided into one control and three experimental group (EG)s for this study. The control group, composed of 2 rats, was maintained on stock diet and drinking tap water. EG was divided into three. EG 1 composed of two subgroups, the first subgroup, 3 rats each, was sacrificed within 12 hours after 9 Gy and 17 Gy single dose irradiation only and the second subgroup, 2 and 1 rats each, was sacrificed 8 weeks after the same doses irradiation. EG 2 composed of subgroups of 2 and 3 rats was given 500 mg/L of captopril in the drinking water after irradiating them with 9 Gy and 17 Gy and sacrificed in the 8th week. EG 3 was subdivided into four subgroups by captopril doses given, 62.5 mg/L, 125 mg/L and 250 mg/L and sacrificed 20 weeks after 9 Gy and 17 Gy irradiation. On light microscopy proximal convoluted tubules showed cytoplasmic vacuolization and focal necrosis in the subcapsular region in EG 1 sacrificed within 12 hours after 9 Gy and 17 Gy irradiation only (sham) and very mild fibrosis in juxtamedullary regions in rats sacrificed 8 weeks after irradiation. In EG 3 these changes were severely increased with additional increased fibrosis in the juxtamedullary region in the group given captopril 62.5 mg/L. On transmission electron microscopy, there were various degenerative changes of organelle. Among the captopril administered EG 2 and EG 3, rats given a high dosage revealed milder degree of damage compared to that of rats given a low dosage, and thickening of basement membrane was remarkable in rats given a low dosage. There was a reduction in tubular damage related to the captopril dosage. According to the above findings, administration of a high dose of captopril might preserve the ultrastructure in RRI and the possible mechanism of captopril was discussed.
Animals ; Basement Membrane ; Captopril ; Cytoplasm ; Diet ; Drinking ; Drinking Water ; Fibrosis ; Kidney ; Microscopy ; Microscopy, Electron, Transmission ; Necrosis ; Organelles ; Rats* ; Rats, Sprague-Dawley ; Water ; Whole-Body Irradiation

Both fibronectin and vitronectin bind to Pneumocystis carinii (P. carinii) and mediate the attachment of the organisms to respiratory epithelial cells. Surfactant A and D play a role in the interaction between P. carinii and host cells. In this study we examined the expression of fibronectin, vitronectin, surfactant-A and D in the interaction between P. carinii and alveolar epithelial cells by immunohistochemistry and pre-embedding immunoelectron microscopy. The experimental rat model of P. carinii pneumonia was induced by administration of low protein diet (8%) and drinking water containing dexamethasone (2 mg/liter) for 6 to 8 weeks. The primary antibodies for light and electron microscopic immunohistochemistries were monoclonal antibodies including fibronectin (1:100) and vitronectin (1:100), and polyclonal antibodies including surfactant A (1:50) and D (1:50), respectively. Light microscopic immunohistochemistry for the fibronectin, vitronectin, surfactant-A and D showed strong expressions on the P. carinii and surface linings of type I alveolar epithelial cells. The electron microscopic immunohistochemistry of the fibronectin and vitronectin showed a strong immunoexpression along the surface pellicles and tubular extensions of P. carinii trophozoites, and surface membranes of the type I epithelial cells. The surfactant-A and D proteins showed a strong expression on the pellicles of P. carinii and surface membranes of the type I epithelial cells, but a weak expression on the free-floating surfactant materials. In conclusions, the trophozoites of P. carinii were mostly attached to type I epithelial cells. The fibronectin, vitronectin, surfactant-A and D were strongly expressed, and played an enhancing role in the binding between the P. carinii organisms and the type I alveolar epithelial cells.
Antibodies ; Antibodies, Monoclonal ; Dexamethasone ; Diet, Protein-Restricted ; Drinking Water ; Epithelial Cells* ; Fibronectins* ; Immunohistochemistry ; Membranes ; Microscopy, Immunoelectron ; Models, Animal ; Pneumocystis carinii* ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis* ; Trophozoites ; Vitronectin*

In an attempt ultrastructural study of alcohol-induced gastric mucosal change, we selected sixty Sprague-Dawley rats. The rats were administrated with 4 ml of 10% and 40% ethanol enterically and examined by light and electron microscopy. Light microscopically, the thickness of the mucus layer of both 10% and 40% ethanol groups was decreased. The antral mucosa revealed focal inflammatory infiltrates, disturbed glandular arrangements, and significant decrease of mucosal thichness and proper glands. On scanning electron microscopy, flattened or swollen mucosal epithelium and irregularly distributed gastric pits were seen in both experimental groups, and these changes were more severe in the groups of higher concentration and longer duration. On transmission electron microscopy, mitochondrial abnormalities with myelin-like materials and dilatation of endoplasmic reticulum and cytoplasmic blebs were observed. Also the mucus cells show significantly decreased mucus globules, increased fat vacuoles, and large autophagic vacuoles. These alterations were similar to those produced by ethanol in the liver and small intestine. This study indicates that, prolonged administration of ethanol induced chronic gastritis, especially chronic atrophic gastritis.
Rats ; Animals

The apoptosis, a distinctive type of individual cell necrosis, has been considered to play a complementary but opposite role to mitosis in the regulation of animal cell populations. It can be initiated or inhibited by a variety of environmental stimuli, physiologically and pathologically. Apoptosis seems to appear in either non-neoplastic or neoplastic tissues, even malignant tumors in the state of untreatment or irradiation. This study was carried out to investigate the spontaneous occurrence of apoptosis in squamous carcinomas of the uterine cervix and its mechanisms. Light microscopically, noted were the condensation and fragmentation of individual tumor cells with formation of apoptotic bodies that were frequently phagocytosed by nearby intact tumor cells. They were commonly seen in the neighbourhood of coagulative necrosis. Electron microscopically (TEM and SEM), noted were nuclear condensation, margination toward the nuclear membrane and fragmentation of membrane-bounded apoptotic bodies that were well preserved. The intracellular apoptotic bodies were phagosomes and reduced to electron-dense lysosomal residual bodies. The conclusion obtained was as follow: Apoptosis was found in all cases of squamous carcinoma of the uterine cervix, of which the frequency was higher in tumors of poor differentiation than those of well to moderate differentiation. The process of the apoptosis is considered to pass through the step of formation of the apoptotic bodies, phagocytosis by adjoining tumor cells or histiocytes, and then degradation as lysosmal residual bodies.
Animals

Lung cancer is one of the most common types of malignancy in western nations with serious health problem, and it has become the leading cause of cancer death of males, second only to stomach cancer, in Korea. A review of the histopathology of 1363 cases (1231 patients) of lung carcinoma, diagnosed at the Keimyung University Medical center from 1987 to 1996, was performed to reclassify the type of carcinomas and to investigate the change in the distribution of histologic types of lung carcinoma according to age, sex and year. Among the 1363 cases, 132 patients underwent a surgical operation after biopsy. The diagnosis of each case was proven by histopathologic analysis of surgical specimens (13.2%) and biopsy materials (86.8%). The histologic types in our study were basically based on modified WHO classification (1982) and on new WHO classification (1999). The classification of small cell carcinoma was based on International Association for the Small Cell Lung Cancer (IASLC, 1988). Of the 1231 patients with lung carcinoma, 1012 were male and 219 were female (male to female ratio was 3.6:1). According to the analysis of age distribution, the most prevalent age group was 60~69 years in both sex as (n=516, 42.0%). Changing trends in sex distribution of lung carcinoma patients showed that the proportion of men had decreased throughout the years, whereas the proportion of women had significantly increased. Histologically, squamous cell carcinoma was the most common (n=624, 50.7%), followed by small cell carcinoma (21.1%), adenocarcinoma (18.1%), large cell undifferentiated carcinoma (2.1%), adenosquamous carcinoma (0.4%), and large cell neuroendocrine carcinoma (0.4%), in order of frequency. In men, squamous cell carcinoma was the most frequent type (55.1%). In women, adenocarcinoma was the most frequent type (39.7%). In both sexes, adenocarcinoma was the most common type in patients under the age of 40 (n=12, 41.4%), while squamous cell carcinoma proved the most frequent type in patients over the age of 40 (n=617, 51.3%). Changing trends of histologic types of lung cancer showed that the incidences of squamous cell carcinoma had significantly decreased throughout the years, whereas those of adenocarcinoma and small cell carcinoma had increased. In conclusion, the results showing increases in the percentage of female patients and in the number of cases of adenocarcinoma were noteworthy, and well correlated with other related reports.
Academic Medical Centers ; Adenocarcinoma ; Age Distribution ; Biopsy ; Carcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Neuroendocrine ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Classification ; Diagnosis ; Female ; Humans ; Incidence ; Korea ; Lung Neoplasms ; Lung* ; Male ; Sex Distribution ; Small Cell Lung Carcinoma ; Stomach Neoplasms

Alveolar macrophages participate in the host defense against P. carinii, but the mechanisms in degradation and clearance of the organism from lung has not been well established. We observed the transmission and scanning electron microscopic features and evaluated the expression of TNF-alpha and Surfactant-D in the interaction of P. carinii with alveolar macrophages. Expression of TNF-alpha and Surfactant-D in the experimentally induced P. carinii pneumonia in rat was examined by immunohistochemistry and immunoelectron microscopy. Electron microscopically, the alveolar macrophages phagocytized trophozoites and cysts of P. carinii micro-organisms. Immunohistochemically TNF-alpha was strongly expressed in the cytoplasms of alveolar macrophages. Postembedding immunogold labeling for Surfactant-D protein was expressed on the pellicles of trophozoites and cysts, P. carinii micro-organisms in the cytoplasms of macrophages, free floating surfactant materials and multilamellar bodies of type II epithelial cells. We conclude that alveolar macrophages interacted with P. carinii micro-organisms respond with increased expression of TNF-alpha. TNF-alpha may bind to P. carinii and exert a direct toxic effect upon the micro-organisms. Surfactant-D protein may augment binding of P. carinii to the alveolar macrophages and enhance the clearance of the micro-organisms.
Animals ; Cytoplasm ; Epithelial Cells ; Immunohistochemistry ; Lung ; Macrophages ; Macrophages, Alveolar* ; Microscopy, Immunoelectron ; Pneumocystis carinii* ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis* ; Rats ; Trophozoites ; Tumor Necrosis Factor-alpha*

This study was carried out to investigate the mechanisms of interstitial pulmonary fibrosis of rats after the intratracheal administration of bleomycin. Both lungs after bleomycin injection were examined by light and electron microscopy. The results are as follows: Light microscopically, 1 or 2 weeks after bleomycin injection acute and chronic inflammatory infiltrates and edema in the interstitium and alveolar spaces were observed. Proliferation of alveolar type II pneumocytes was also found at 4 to 6 weeks after bleomycin injection, chronic inflammatory infiltrates with interstitial fibrous thickening were noted. Electron microscopically, the number of type II pneumocytes and irregular lamellar bodies were increased and blunted microvilli were noted at 2 weeks. 4 to 8 weeks, proliferation of fibroblasts with deposition of abundant collagen fibrils in the thickened interstitium revealing irregular or collapsed alveolar spaces were observed. Based on these findings, it can be concluded that bleomycin-induced interstitial pulmonary fibrosis is considered to pass from an early acute inflammation of the interstitium and alveolar spaces to an interstitial fibroblast proliferation and collagen deposition to the length of the period after injection.
Rats ; Animals

This study was carried out to investigate the mechanisms of acinar cell deletion, leading to the pancreatic atrophy of rat pancreas after experimental duct ligation. Fifty-seven male Sprague-Dawley rats, maintained on a stock diet, weighing 200 gm, in average, were divided into 2 experimental groups. Group 1. Control group. Six rats. Abdominal cavity was opened and closed without further treatment. Group 2. Fifty-one rats. Animals were treated with partial ligation of the pancratic ducts according to the procedure developed by Hultquist followed by sequential sacrifices at: 1 hour (3 rats), 3 hours (3 rats), 6 hours (6 rast), 12 hours (3 rats) and 24 hours (8 rats); 2 days (8 rats), 3 days (3 rats), 4 days (3 rats) and 5 days (5 rats); 1 week (3 rats), 2 weeks (3 rats) and 8 weeks (3 rats); after partial ligation was extirpated and examined by both light and electron microscopy. The results obtained were as follows: Light microscopically, noted were an interstitial edema and focal necrosis of the pancreatic tissue along with fine vacuolization and depletion of the zymogen granules in the acinar cell cytoplasms and condensation of the acinar cell nucleus. These changes were observed by 2 days after ligation. At about the same time, one can observe the dense body, identified to be apoptotic body, in the acinar cell which were found to be decreased in quantity. By 5 days after ligation, no recognizable acinar cells left in the collagenous stroma except intercalated ducts. Conspicuous stroma except intercalated ducts. Conspicuous stromal hyalinization, thereafter. Electron microscopically (TEM and SEM), nuclear condensation and margination toward the nuclear membrane was noted by 6 hours after duct ligation. By 24 hors sporadic membrane-bounded apoptotic bodies appeared in the acinar cells, the number of which reaching to the peak by 3 days after ligation. These apoptotic bodies were found to be phagocytosed by either intraepithelial mononuclear phagocytes or adjoining acinar cells. It can be concluded, therefore: That orderly remodeling of pancreatic exocrine tissue during atrophy is effected by rapid deletion of acinar cells by apoptosis.
Male ; Humans ; Rats ; Animals

This study was carried out to investigate the light and electron microscopic findings of the livers of rats after an intraperitoneal injection of cadmium chloride. The Sprague-Dawley rats were intraperitoneally injected with cadmium chloride dissolved in water, once a day for three days. These animals were sacrificed at 1, 3, 8, and 24 hr after the last injection. Control groups of the rats were also sacrificed in the same manner. The liver was extirpated and examined by both light and electron microscopy. The results obtained are as follows: The parenchyma of the liver shows focal neutrophilic infiltration and spotty necrosis. The hepatocytes show fatty change, ballooning degeneration, swelling of the endoplasmic reticulum and mitochondria, increase numbers of secondary lysosomes and residual bodies. Focal patic venules and sinusoids of the liver are congested. The Kupffer cells are increase in number. Therefore, it can be concluded that the cadmium is directly acted to hepatocytes resulting in cellular injuries and deposits in the fat droplets of the cytoplasm of the hepatocytes, not Ito cells as previously suggeted.
Rats ; Animals

The pulmonary microvasculatures of rats were studied by injection replicas prepared from Mercox. This medium enabled us to easily obtain consistent, stable, and complete injected replicas of the pulmonary vasculature. In order to investigate the three dimensional structures of the tributaries of the bronchial artery, such as the capillary plexus and vasa vasorum, we performed a scanning electron microscopic(SEM) study of the vascular casts, using Mercox CL-2B as a media. The alveolar capillaries revealed hexagonal or pentagonal rings of vascular networks. In some areas, the vascular rings composed a square network, The bronchial tree was supplied by the bronchial arteries which form a coarse capillary extending as far as the terminal bronchioles. Occasionally the capillary plexus was connected with adjacent capillary networks in and around the alveolar walls. The walls of the pulmonary artery revealed only a single layer of the vasa vasorum, but those of the pulmonary vein were surrounded by more complicated and well developed vasa vasorum than the pulmonary arterial side. The mean diameters of the venous vasa vasorum are greater than the arterial vasa vasorum.
Rats ; Animals