Objective Rats with nonalcoholic fatty liver disease (NAFLD) were used to investigate the secretory state of pancreas and the expression of insulin receptor (IR). Methods NAFLD rat model was reproduced, and then the structure of pancreatic tissue, secretory states of ? and ? cells (serum, tissue) and the expression of IR were examined and determined by means of HE staining, ELISA, and immunohistochemistry. Results In all experimental groups, the structure of pancreatic tissue showed no obvious change; the blood sugar level tended to rise. The insulin level in serum began to elevate obviously at 4th week (P≤0.01), while the insulin content in tissue began to increase at 6th week (P≤0.01), and distributed mainly in the middle part of the pancreas with a tendency of elevation along with the time. The content of glucagon in pancreatic tissue began to increase at 8th week (P≤0.01), and reached the peak at 12th week. The expression of IR in tissue began to decrease at 6th week (P≤0.01), and then tended to be stable after 8th week. Conclusions In NAFLD, there was changes in secretory state of pancreas with the accompaniment of insulin resistance. There was a tendency of elevation of levels of insulin both in serum and pancreatic tissue, but the time of expression was different. The expression of glucagen shows an increase tendency, while the decrease of IR might be the crucial cause of insulin resistance in NAFLD.

Objective To study the changes in serum endotoxin level of the patients with primary biliary cirrhosis (PBC) and the relationship between endotoxin and serum biochemical parameters. Methods Clinical data of 63 cases PBC patients confirmed by liver puncture biopsy were retrospectively studied. The clinical features, results of laboratory tests, pathological findings of all the 63 patients were analyzed. Endotoxin level was determined by limulus amebocyte lysate test in the serum obtained from the 63 cases of patients with primary biliary cirrhosis, and then compared with that of 30 healthy individuals. Results The sex ratio (male to female) of PBC patients was 1 to 8, and the mean age was 43.8 years. The prevalent complaints were jaundice and fatigue. 70.3% patients showed AMA positive. The levels of ?-glutamyltransferase (r-GGT), alkaline phosphatase (ALP) and bilirubin in the serum were markedly elevated in the majority of the patients. Compared with the early stage, the levels of ALT and AST declined slightly during the advanced stage (P

In order to develop ELISA method for measuring the degradation fragment of fibronectin (MAD2),hybridoma technique was used to obtain the monoclonal antibody (McAb)IgG 1 against MAD2 without cross reaction with fibronectin.The sera from 277 patients with hepatocellular carcinoma (HCC),76 with metastatic hepatic carcinoma (HMC),98 with alimentary canal carcinoma (ACC) and 156 with chronic liver disease(CLD) and 48 healthy subjects were assayed with ELISA method using this antibody.The examination showed that the mean value of MAD2 from the patients with HCC showed obviously significant difference compared with those of CLD,HMC,ACC and normal control groups ( p

To investigate MT 1 MMP mRNA expression in the development of liver fibrosis and during the reversal of liver fibrosis ,we undertook a dynamic observation by situ hybridization. Liver fibrosis model was established by intraperitoneal injection with CCl 4 in Wistar rats, then allowed them fo recover spontaneously to observe the reversal of liver fibrosis .The results showed that MT 1 MMP mRNA was expressed mainly in mesenchymal cells(such as hepatic stellate cell), also in a part of hepatocytes.The levels of MT 1 MMP mRNA expression were increased gradually in the development of liver fibrosis and decreased gradually during reversal of liver fibrosis. These results suggest that the expression of MT 1 MMP may have an important role in the development of liver fibrosis and its reversal.

To study the mechanism of matrix degradation in alcoholic liver disease (ALD), the liver tissues from 28 patients with ALD were divided into three groups according to their fibrosis degree. The mRNA expression of matrix metalloproteinase 1 (MMP 1), matrix metalloproteinase 2 (MMP 2), membrane type metalloproteinase (MT1 MMP), and tissue inhibitors of metalloproteinase (TIMP) was detected using in situ hybridization method. The results showed that the cells with positive MMP 1, MMP 2, MT1 MMP, and TIMP mRNA staining were mainly located around the fibrotic central veins, walls of sinusoids, and portal triads. These positive cells were the cells of hepatic sinusoidal walls and a few hepatocytes, meanwhile, some cells expressed both the MMP 2 and the MT 1MMP mRNA. The positive cells of the MMP 2, MT1 MMP, and TIMP mRNA increased in parallel with the severity of fibrosis, whereas the expression of MMP 1 mRNA decreased. These changes were observed predominantly in moderate fibrosis group. There findings demonstrated that down regulation of MMP 1 expression and up regulation of TIMP expression might be involved in excessive accumulation of extracellular matrix (ECM) in ALD. MMP 2 might collaborate with MT1 MMP in degradation of ECM. thereby contributing to fibrosis of central veins.Hepatic stellate cells might be the main cellular source of MMP 1, MMP 2, MT1 MMP and TIMP in ALD.

micro), hepatocyte ballooning degeneration, mild diffuse lobular inflammation and perisinusoidal collagen deposition. Zone 3 accentuation could be detected. Mallory hyaline, vacuolated nuclei in periportal hepatocytes were common. NASH has some clinical and pathological characteristics. The authors hold that combinative consideration of clinics, pathology and laboratory can ensure the diagnosis of NASH, and liver biopsy interpretation continues to be the "gold standard " for diagnosis.

To study the significance of immunocytes in pathogenesis of autoimmune hepatitis (AIH), 36 cases of patients with AIH were analyzed. Dendritic cell (DC) and lymphocytes (LC) in the liver tissues were observed with a panel of DC markers and monoclonal antibodies of lymphocyte by the method of immunohistochemistry, and DC was isolated and incubated from peripheral blood from 8 patients who were selected from these 36 patients. The expression of surface markers on DC and lymphocytes and their numbers were detected by using the flow cytometric analysis. The results showed that the expression levels of HLA DR were much higher than those in control groups ( P

G 1, P

Objective To explore the pathological features and the causative particles of severe acute respiratory syndrome (SARS) for providing evidences of SARS prevention and clinical treatment. Methods A dead case of SARS of China was studied by light microscopy, electron microscopy, histochemical and immunohistochemical stain. Results The major pathological changes of lung in the SARS case were acute pulmonary interstitial exudative and leakage inflammation, with predominant lymphocyte infiltration. The hyaloid membranes were formed in 20%～30% pulmonary alveoli. The diffuse pulmonary epithelial injury was observed, and virus like inclusions were found in about 30% of total alveolar epithelia by histochemical stain, but chlamydia like inclusions were found occasionally. Meanwhile, the extra pulmonary organs, such as lymph nodes and spleen, showed extensive haemorrhagic necrosis inflammation, accompanied macrophage/histocyte reactive proliferation with erythrocytophage. The double adrenal glands also presented focal haemorrhagic necrosis inflammation. Under the electron microscopy observation, virus like particles with 100 ～150 nm diameter and halo or garland envelopes were found in more than 30 % alveolar epithelial cells, endothelial cells in lung tissues, and also in a part of cardiomyocytes, lymphocytes and macrophages in lymph nodes. The virus like particles were mainly located in cytoplasm and dilated reticular endoplasm. In contrast, chlamydia like particles were commonly visualized in multiple extra lung organs such as liver, but very few in the lung. Immunohistochemistry showed the positive reactions in the lung tissues with the serum IgG and/or IgM from the dead case himself and other SARS convalescent stage cases from Guangdong province of China. Conclusion In the severe SARS case, predominant acute interstitial exudative and leakage inflammation, often with the formation of hyaloid membranes in pulmonaryalveoli, and the haemorrhagic necrosis inflammation of immune organs might be pathological features of SARS. According to the structures, diameter and location of the virus like particles found in this case, combined with the pathological changes, we should consider that those virus like particles might be a new kind of coronavirus, and this kind of virus might be the main causative agent of SARS. However, the chlamydia like particles frequently observed in extra lung organs also suggested the potential new kind of coronavirus might be coexist and synergicallly cause SARS. Our findings in this study provide several evidences for SARS clinical therapy such as application of corticosteroid and enhancement of immune ability and combination of anti virus and anti chlamydium drugs.

Objective To study the pathological changes in organs remote from the lung in SARS patient. Methods The pathological changes in extra lung organs and potential coronavirus infection were studied by using light and electron microscopic examinations as well as special virus inclusion stains in the tissues obtained from an autopsy of a patient who died of SARS. Results Besides the lesions in the lung, pathological changes were found also in the central nervous system (CNS), including the cerebrum, cerebellum, thalamus, pons, and medulla oblongata, such as widening of the Virchow Robin′s space, infiltration of a few lymphocytes and macrophages in the parenchyma, vasodilatation and congestion. However, no significant neuron degeneration or necrosis was identified. Vasodilatation in the lamina propria of mucosa and submucosa of the digestive tract with some lymphocytes infiltration, and epithelial nuclear vacuolation, and occasional apoptosis were observed in the mucosal epithelial and glandular cells, as well as focal hemorrhage in segments of the small intestine. Mesenchymal edema and infiltration of a few lymphocytes in the pancreas were noted. Very mild lymphocyte infiltration, but no viral inclusions, was found in the convoluted seminiferous tubules of the testis. The patient who died of SARS was proved to have arteriosclerosis of the coronary arteries, and coronavirul particles were identified in the blood vessels under electron microscopic examination, however no coronavirul particles were found in the brain or the testis of the patient. Conclusion There were mild hypoxic changes in the tissue of CNS in the patient with severe SARS without invasion of the virus. It was confirmed that there were coronavirul particles in the blood of the patient at the acute stage of SARS. Since the patient who succumbed to the disease had a history of coronary arteriosclerosis, it was inferred that cardiovascular disease might be a contributory factor of mortality in this patient with severe SARS.