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

The histogenesis of the myofibroblast continues to be a controversial issue. The most popular view is that the myofibroblast is derived directly from the fibroblast. The important role of myofibroblasts in the synthesis of collagen and in wound contraction was demonstrated initially in granulation tissue in experimental animals. Four settings are recognized in which myofibroblasts are the principal proliferative cells: reparative responses, pseudoneoplastic disorders, stromal response to neoplasia, and true neoplasms, both benign and malignant. To identify of fibroblastic cells with smooth muscle differentiation features in the nonneoplastic and neoplastic lesions, we examined a variety of histological, immunohistochemical and ultrastructural features of 7 cases of granulation tissue, 7 of hypertrophic scar, 10 of chronic persistent hepatitis, 10 of chronic active hepatitis, 7 of liver cirrhosis, 7 of fibromatosis, 42 of cervical intraepithelial neoplasia, 14 of microinvasive carcinoma, 14 of invasive carcinoma, 7 of fibroma, 20 of fibrosarcoma and 72 of malignant fibrous histiocytoma. Antibodies against alpha-smooth muscle actin and desmin were used in a biotin-streptavidin procedures. The results of immunohistochemical and electron microscopical examinations yielded virtually identical findings. The identification of fibroblastic cells with smooth muscle cell differentiation features in the desmoplastic reactions of carcinomas, fibroma, fibrosarcoma and malignant fibrous histiocytoma offers also novel diagnostic and prognostic perspectives, that might help in evaluating preneoplastic lesions and malignant lesions. So degree of proliferative myofibroblasts was helpful diagnostic aid in differentiation of chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis.
Animals

The purpose of this study is to evaluate histologic result of bone substituting material on defects followed tooth extraction. We compare the histologic findings control, DFDBA, Bio-Oss(R), and Regenafil(TM), Briefly, mandibular premolar teeth were extracted available for bone filling. All alveolar sites were checked after extraction and thoroughly debrided with a dental curet to remove the periodontal ligament. Extraction sites were prepared dehiscence on buccal side 7mm height from alveolar crest. The graft materials were filled into the extraction socket and dehiscenc defects. The animals were sacrificed 12 weeks after implantation. Both treated and control mandibular sites were histologically evaluated with light microscopy. Histologic observation at 12 weeks revealed that control and experimental sites were healed uneventfully and directly apposed to new bone without any adverse tissue reaction. DFDBA and Bio-Oss(R) sites maintain width of alveolar crest but were not fully resorbed. Regenafil(TM) sites also maintain width and particles were resorbed more than other graft materials. From this results, it was suggested that Regenafil(TM) is promising boen substituting materials maintaining the width of alveolar crest and height follewed tooth extraction.
Animals

PURPOSE: We assessed the impact of using a porcine model on the training of laparoscopic partial nephrectomy(LPN) and compared the training effectiveness between surgeons with and without previous laparoscopic experience. MATERIALS AND METHODS: Surgeon A had previous laparoscopic experience, with the exception of LPN, while surgeon B had no prior laparoscopic experience. A tumor model was created by subcapsular injection of liquid plastic(Smooth-Cast 320) in the kidney. We recorded the total operation time, the bowel dissection time, the renal pedicle dissection time, the warm ischemic time, the mass resection time, the suture time, and the presence of major complications for each surgeon. RESULTS: The mean operation time was significantly shorter for surgeon A compared to surgeon B(49.1+/-4.5 and 63.6+/-8.4 minutes, respectively, p<0.001). Although the mass resection time was significantly shorter for surgeon A as well, there were no significant differences between the two surgeons in terms of warm ischemia time and suture time. As the training progressed, surgeon B improved in all surgical steps and surgeon A showed improvement in time for warm ischemia and suturing the defect. Five complications occurred(two cases by surgeon A and three cases by surgeon B). CONCLUSIONS: A porcine model improved the skills needed for LPN, including shortening the warm ischemia and suture times. LPN is a procedure requiring technically-demanding skills that can be improved by training using a animal model, regardless of the previous laparoscopic experiences.
Animals

The aim of the present investigation has been to evaluate the depletion pattern of the supercompensated glycogen of hindlimb muscles during strenous exercise in rats. The plan of the maximizing muscle glycogen stores is based on the fact that a glycogen-depleted muscle by exercise will have an increased avidity for glycogen when exposed to a high carbohydrate diet. The glycogen concentration of soleus, red gastrocnemius and plantaris muscle, and liver was measured at 0, 30 and 60 minutes during treadmill exercise. The experimental animals were divided into 5 group - Normal(N), Control(C), 1Hour(1HR:after 1hour of glucose ingestion), 2Hour(2HR:after 2hour of glucose ingestion) and Exercise-1Hour(EX-1HR:glucose ingestion after 1 hour of preloading treadmill exercise)group - for glycogen storage study. The glycogen concentration of soleus, red gastrocnemius and plantaris muscles in N group was 4.57+/-0.34, 5.11+/-0.24 and 6.55+/-0.20 mg/gm wet wt., respectively. The glycogen concentration of soleus and red gastrocnemius in EX-1HR group were about 1.9 and 1.8 times than that of N group, respectively, but the concentration of plantaris was not higher than that of N group. The glycogen concentration of liver in N group was 41.0+/-1.47mg/gm wet wt. and the concentration of the overnight fasted C group wad only 2.9% of the value of N group. The level of glycogen concentration of liver in the other glucose ingested groups(1HR, 2HR, including EX-1HR) was within 19 - 32% of that of N group. The blood glucose concentration of EX-1HR group was higher than that of N group, the plasma free fatty acid concentration of C and 2HR group was higher than that of N group, and the plasma insulin concentration of EX-1HR group was higher than that of N group. The concentration of supercompensated glycogen of soleus and red gastrocnemius were rapidly decreased during 30 minutes of exercise but there was almost no changes of the concentration during the other 30 minutes of continuing exercise. The concentration of N group during 30 minutes of exercise was decreased but more slowly than those of EX-1HR group. The remaining level of glycogen after 60 minutes of exercise in EX-1HR group was higher than that of N group. Taken together, the mobilization of endogenous muscle glycogen at the first stage of exercise was proportioned to the intial level of glycogen concentration, and later on, when exercise continued, the muscle glycogen level was stabilized. And the remaining level of supercompensated muscle glycogen after 60 minutes of exercise was higher than that of normally stored glycogen level. The mobilization of the glycogen stroed in slow and fast oxidative muscle fibers is faster than in the fast glycolytic muscle fibers during strenous exercise.
Animals

Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin (14+/-1.9 micronU/ml) and basal glucose (75+/-0.7 mg/dl), by normal saline infusion; group II, normal insulin (33+/-3.8 micronU/ml) and hyperglycemia (207+/-6.3 mg/dl), by somatostatin and glucose infusion; group III, hyperinsulinemia (134+/-34.8 micronU/ml) and hyperglycemia (204+/-4.6 mg/dl), by glucose infusion; IV, supramaximal insulin (100+/-2.2 mg/dl), by insulin and glucose infusion; group V, supramaximal insulin(4813+/-687.9 micronU/ml) and hyperglycemia (233+/-3.1 mg/dl), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were 1.88+/-0.151 in group II, 2.69+/-0.239 in group III, 3.54+/-0.198 in groupIV, and 4.32+/-0.621 in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were 16.9+/-3.88 in group I, 13.5+/-1.05 in group II, 11.2+/-1.17 in group III, 13.2+/-2.05 in group IV, and 10.4+/-1.01 in group V. A negative correlation was observed between amount of preloaded glucose and Rd )r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.
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

To investigate the microvascular changes in primary pulmonary hypertension, the lungs of 24 Sprague-Dawley rats were treated by an intraperitoneal injection of 2% monocrotaline(MCT) solution and then examined with scanning electron microscopy(SEM) after microvascular corrosion casting. Histologic examination revealed significant medial thickening in the small to medium-sized pulmonary arteries. Scanning electron microscopic findings of the normal lungs showed two kinds of microvascular structures. One showed a well-fortned three-dimensional basket structure of uniform flat-tubular alveolar capillaries, which were connected to each other in a T or Y shape or at right angles. The other revealed a two-dimensional reticular sheet of round tubular branches mainly in the bronchial artery-supplying regions. The MCT-treated groups(remodelling) showed apparent changes in both kinds of microvasculatures in comparison to the normal group but the more prominent change was found in Lbe bronchial artery microvasculature showing the dense thick encasement around large pulmonary arteries. Alveolar microvasculature of the pulmonary artery revealed individually enlarged angular appearance, with generally deformed alveolar architecture. Quantitatively, the significant enlargement of diameter and intercapillary distance appeared in both microvasculatures of MCT-induced rat lungs, but the density was increased only in the bronchial artery microvasculature. In conclusion, our three-dimensional microvascular study of the MCT-treated rat lungs demonstrates a new morphologic finding of vascular remodeling in primary puhnonary hypertension, which is thought to play an important vascular role in the pathogenesis in addition to interstitial fibrosis.
Rats ; Animals

To investigate the tubular major histocompatibility complex(MHC) expression and inflammatory phenotypes in tubulointerstitial nephritis, Lewis rats were inununized with azobenzen-earsonate-tyrosine in complete Freund adjuvant and challenged either foot pad or kidney, either by subcapsular injection or by ex vivo perfusion. The rats were sacrificed 2, 3, 5, 10 and 15 days after antigenic challenge. Foot pad swelling was significant at the antigenic challenge site (151.8 vs 6.8 x 10(-2) mm) at 24 hours. Tubulointerstitial nephritis was induced by both methods and the inflammatory infiltrate which first appeared on day 2, became prominent at day 5, then gradually subsided in ex vivo perfused rats, while inflannnation started on day 3 in subcapsular injected rats. The major site of inflammation was in the cortex and outer stripe of the outer medulla, with predominance of mononuclear cells throughout the course. The inflammatory cells showed mainly OX8 and ED1 positivity with OX19, W3/25 and CD5 positivity in minority. RT1B expression was diffuse in the cytoplasm of proximal tubules at day 2 and 5. These results suggest the involvement of cell mediated immunity in this experimental model, and the possibility that tubular epidielial cells process antigen and then become targets in immune injury.
Rats ; Animals

To understand the mechanism of cell injury when exposed to HgCl2, monitoring of cytosolic ionized free Ca2+([Ca2+]i), viability test, measurement of the amount of ATP, and Ca-ATPase activity were evaluated in cultured rabbit renal tubular cells(RTC) exposed to HgCl2. The results were as follows: 1) HgCl2 was cytotoxic to rabbit RTC at all doses except 10 uM and the rate of killing displayed a dose- and time-dependent relationship. 2) The absence of extracellular Ca provided partial protection from irreversible injury induced by HgCl2. 3) The increasing pattem of [Ca2+]i varied according to the concentrations of HgCl2. At the low concentrations of HgCl2 (2.5-10 microM), the level of [Ca2+]i increased slowly over the flat 2-3 min and then achieved plateau-state. In contrast, at the high concentrations of HgCl2 (25-100 microM) the level of [Ca2+]i achieved peak within 1 min and then decreased to a plateau state under normal concentrations. 4) The level of ATP was decreased to 27.5% of that of normal control cells within 3 min by using a treatment of 100 microM HgCl2. 5) HgCl2 did not affect the Ca2+ ATPase activity by enzyme histochemical observation. These findings suggest that the elevation of [Ca2+]i in response to the HgCl2-induced injury is an important event in accelerating injury that ultimately leads to cell death. But other possibilities such as HgCl2 might have direct deleterious effects on the also should be considered.
Rabbits ; Animals