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Biomedical subjects

S S Zheng

Publications and source records attributed to S S Zheng.

17 recordsLinked to original sources

p38 Mitogen-activated protein kinases is required for counteraction of 2-methoxyestradiol to estradiol-stimulated cell proliferation and induction of apoptosis in ovarian carcinoma cells via phosphorylation Bcl-2.

INTRODUCTION: 2-Methoxyestradiol (2ME2), a natural endogenous product of estradiol (E2) metabolism, has been shown to be a selective apoptotic agent for cancer cells but not for normal cells. In this study, we determined that 2ME2 counteracts E2-stimulated cell growth and induces apoptosis in ovarian carcinoma cells. In addition, we demonstrate that 2ME2 induces apoptosis via p38 and phospho-Bcl2 pathway. METHODS: 2ME2 and/or E2 were administered to the OVCAR-3 (human ovarian cancer) cell line. Cell growth inhibition was analyzed by [3H] Thymidine incorporation assay and DNA fluorometric assay. Cell apoptosis was tested by DNA fragmentation analysis and FACS. The signaling pathway was determined by a series of biochemical assays. RESULTS: 2ME2 inhibited estradiol-stimulated cell growth and induced apoptosis in an ovarian carcinoma cell line. MAPK and p38, but not JNK, were found to be critical mediators in this process. Expression of a dominant negative mutant of p38 kinase or p38 specific inhibitor, SB 203580, almost completely blocked the process. Furthermore, Bcl-2 phosphorylation was required for 2ME2-induced effects. CONCLUSION: Our data suggest that 2ME2 inhibits E2-stimulated proliferation and induces apoptosis in ovarian carcinoma cells. Furthermore, activation of p38 and phosphorylation of Bcl-2 plays a critical role in the mechanism. 2ME2 therefore, may have a clinical application for the treatment of ovarian cancer.

2-Methoxyestradiol↗

Prevalence of human cytomegalovirus UL97 D605E mutation in transplant recipients in China.

Human cytomegalovirus (CMV) resistance to gancyclovir (GCV) occurs via mutation in the UL97 gene, ethylene diamine tetraacetic acid blood samples were obtained from 23 transplant recipients who received a GCV implant. A nested polymerase chain reaction amplifying UL97 codons 450 to 672 was performed. Nested amplifications were sequenced directly. No known UL97 GCV resistance mutations were found. Eighteen of 23 patients (78%) had revealed mutations at codon 605 (D to E). Mutant D605E may reverse to wild-type during the follow-up treatment. We conclude that human CMV UL97 D605E mutation occurred in Chinese transplant recipients. This mutation may be regarded as a natural sequence variant.

Bone Marrow Transplantation↗

A rat model of chronic allograft liver rejection.

INTRODUCTION: The aim of this study was to develop a rat model of chronic irreversible rejection, which is a major causes of late graft loss and retransplantation after orthotopic liver allotransplantation. METHODS: Allogeneic liver transplantation was performed in a rat combination of Dark Agouti (DA) to Brown Norway (BN). Group A was left without treatment, group B received cyclosporine' (CsA; 1 mg/kg/d) and group C, CsA (4 mg/kg/d). Animals were followed for 6 months. Liver tissue was harvested to construct a time course of histological changes after liver transplantation using histopathological and morphometric techniques. We compared the total histological score of rejection activity index and survival rates. RESULTS: In untreated animals, irreversible acute rejection developed, all animals died within 15 days. In the low-dose CsA group, all animals that survived more than 30 days developed moderate to severe manifestations of chronic liver rejection, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy, and liver fibrosis. No apparent histological alterations were observed in group C. Survival analysis showed significant differences between the three groups. CONCLUSIONS: In the rat strain combination of DA --> BN with low-dose immunosuppression, early mild inflammation was followed by the development of chronic rejection.

Animals↗

[The tissue culture of medicinal plant Trichosanthes kirilowii and its protein analysis].

We reported preliminary results of rapid propagation, callus induction and regeneration of Trichosanthes Kirilowii, and its protein analysis. Pre-existing meristerms regenerate shoots very rapidly when grown on MS medium containing 0.5 or 1.0 mg/L 6-BA; calli could be induced from leaf sections when put on MS medium containing 4.0 mg/L 6-BA + 0.2 mg/L IAA; shoots regenerated successfully 30 days after calli induction and the differentiation ratio was one shoot out of every four leaf sections; and all shoots gave rise to roots after removing onto MS medium containing 0.1 mg/L NAA and 100% survived when transplanted into soil. Very excitingly, these plants produced small tubers in one month, where satisfactory expression of TCS protein was detected by Western blot analysis.

Culture Media↗

Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide.

Glutathione peroxidases have been thought to function in cellular antioxidant defense. However, some recent studies on Gpx1 knockout (-/-) mice have failed to show a role for Gpx1 under conditions of oxidative stress such as hyperbaric oxygen and the exposure of eye lenses to high levels of H2O2. These findings have, unexpectedly, raised the issue of the role of Gpx1, especially under conditions of oxidative stress. Here we demonstrate a role for Gpx1 in protection against oxidative stress by showing that Gpx1 (-/-) mice are highly sensitive to the oxidant paraquat. Lethality was already detected within 24 h in mice exposed to paraquat at 10 mg.kg-1 (approximately (1)/(7) the LD50 of wild-type controls). The effects of paraquat were dose-related. In the 30 mg.kg-1-treated group, 100% of mice died within 5 h, whereas the controls showed no evidence of toxicity. We further demonstrate that paraquat transcriptionally up-regulates Gpx1 in normal cells, reinforcing a role for Gpx1 in protection against paraquat toxicity. Finally, we show that cortical neurons from Gpx1 (-/-) mice are more susceptible to H2O2; 30% of neurons from Gpx1 (-/-) mice were killed when exposed to 65 microM H2O2, whereas the wild-type controls were unaffected. These data establish a function for Gpx1 in protection against some oxidative stressors and in protection of neurons against H2O2. Further, they emphasize the need to elucidate the role of Gpx1 in protection against different oxidative stressors and in different disease states and suggest that Gpx1 (-/-) mice may be valuable for studying the role of H2O2 in neurodegenerative disorders.

Animals↗

Development and use of surgical procedures to bypass selected regions of the mammalian epididymis: effects on sperm maturation.

Microsurgical procedures have been used to examine the function of selected regions of the epididymis. Vasoepididymostomy in the rabbit and rat confirmed that spermatozoa require some exposure to the epididymal environment for normal development of motility and fertilizing ability. In both of these species surgical redirection of spermatozoa from a region just distal to the initial segment into the vas deferens resulted in a significant reduction in sperm viability, motility and fertility compared with untreated animals. Surgical bypass of the distal cauda epididymidis in the rabbit did not significantly reduce the number of spermatozoa in ejaculates or the total sperm output accumulated during exhaustive ejaculations. The capacity of these bypass animals to store spermatozoa may be explained by the post-surgical formation of convolutions in the normally straight segment of the rabbit vas deferens. Vas autografts in the rabbit and rat were used to bypass selected epididymal segments. In rabbits, vascularized grafts were used as bridges to bypass the distal caput and proximal corpus epididymidis. Despite high rates of graft survival and patency in this species, the motility and viability of ejaculated spermatozoa were similar to those observed following high level vasoepididymostomy. In rats, non-vascularized vas grafts also showed a high survival and patency rate. There was a transitory reduction in sperm viability and motility 2 weeks after surgery which was associated with structural changes, especially in the epithelium, in vas bridge autografts during revascularization. Longer term observations (3 and 6 months) showed recovery of epithelial morphology and by three months after surgery, no difference was observed in sperm motility, sperm viability or fertility between experimental groups and controls. Similar results were obtained when epididymoepididymostomy was used as the surgical procedure to bypass the same regions of the epididymis. The evidence considered in this review clearly shows that the proximity of vasoepididymal bypass to the testis is inversely related to the state of maturity of ejaculated spermatozoa. More surprisingly, perhaps, it reveals that exposure of spermatozoa to the distal caput and proximal corpus regions of the epididymis in the rat is not obligatory for spermatozoa to develop a level of maturation in the remaining regions of the epididymis sufficient to ascend the female tract and fertilize ova. This finding suggests that the epididymis is more flexible in its functions than had been considered previously and that sperm maturation may not be as dependent on specific regional functions of the epididymis as had been previously proposed.

Anastomosis, Surgical↗

Primary study of neovasculature correlating with metastatic nasopharyngeal carcinoma using computer image analysis.

The significance of neoangiogenesis in the metastasis of nasopharyngeal carcinoma (NPC) was investigated to clarify the role neovascularity in the prognosis of NPC and the probability of antiangiogenesis preventing NPC from distant metastasis. A group of 52 patients presenting with metastatic NPC were selected and strictly paired one-to-one, in sex, age, T stage, and N stage, with another 52 patients with non-metastatic NPC, who had survived for a long time after therapy. The tumor tissues of all 104 patients were retrieved for computer-assisted, immunohistochemical analysis of tumor vasculature. Counts of the microvessels and the relative area of all microvessels per image were significantly higher in metastatic NPC than they were in curable, non-metastatic NPC, while the average area of the microvessels and their average perimeter of in metastatic NPC were smaller than in non-metastatic disease. No significant difference in any microvessel parameter was found among the various types of metastasis. The alterations of microvessel parameters were significantly linked to the metastasis of NPC. Evaluation of neovascularity by computer image analysis may be helpful in estimating the prognosis of NPC and in determining the indicators for aggressive multimodal treatments.

Adult↗

Experimental study on pulmonary injury related to oxygen-derived free radicals in acute necrotizing pancreatitis in dogs.

It is postulated the pulmonary injury in acute necrotizing pancreatitis could be due to oxygen-derived free radicals released during the attack of acute pancreatitis. To elucidate the relationship between oxygen-derived free-radicals and the degree of pulmonary injury in acute necrotizing pancreatitis, lipid peroxide (LPO) in lung tissues, bronchoalveolar lavage fluid and serum were measured in 10 adult Mongrel dogs with acute necrotizing pancreatitis induced by injection of 5% sodium taurocholate into the pancreatic duct. Compared with the controls (n = 10), the weight of lung was increased (241.2 +/- 33.7 g vs 121.2 +/- 51.4 g, P < 0.05). LPO of bronchoalveolar lavage fluid (BALF) was higher (3.56 +/- 1.64 mumol/L vs 0.75 +/- 0.31 mumol/L, P < 0.05), LPO in peripheral and portal vein 10 hours after induction of acute pancreatitis was also significantly increased. The LPO content of lung tissue was not higher than that of the control group, but hemorrhage within alveolar space and infiltration by polymorphonuclear and phagocytic cells was seen on histological examination. In conclusion, lipid peroxidation could be an important cause of pulmonary injury in acute necrotising pancreatitis.

Acute Disease↗

Early treatment of acute biliary pancreatitis by endoscopic papillotomy.

BACKGROUND: Most patients with acute biliary pancreatitis have stones in the biliary tract or ampulla of Vater. Because these stones may be passed spontaneously soon after a patient is admitted to the hospital, the importance of early operative removal is not known. We tested the hypothesis that endoscopic papillotomy within 24 hours of admission decreased the incidence of complications in patients with acute biliary pancreatitis. METHODS: We studied 195 patients with acute pancreatitis who were randomly assigned to one of two groups: 97 patients underwent within 24 hours after admission emergency endoscopic retrograde cholangiopancreatography (ERCP) followed by endoscopic papillotomy for ampullary and common-bile-duct stones, and 98 patients received initial conservative treatment and selective ERCP with or without endoscopic papillotomy only if their condition deteriorated. RESULTS: One hundred twenty-seven patients ultimately proved to have biliary stones. Emergency ERCP with or without endoscopic papillotomy resulted in a reduction in biliary sepsis as compared with conservative treatment (0 of 97 patients vs. 12 of 98 patients, P = 0.001). The decrease in biliary sepsis occurred both in patients predicted to have mild pancreatitis (0 of 56 patients in the group that received emergency ERCP vs. 4 of 58 patients in the conservative-treatment group, P = 0.14) and in patients predicted to have severe pancreatitis (0 of 41 patients vs. 8 of 40 patients, P = 0.008). In all patients who had unrelenting biliary sepsis, persistent ampullary or common-bile-duct stones were identified. There were no major differences in the incidence of local complications (10 patients in the group that received emergency ERCP vs. 12 patients in the conservative-treatment group) or systemic complications (10 patients vs. 14 patients) of acute pancreatitis between the two groups, but the hospital mortality rate was slightly lower in the group undergoing emergency ERCP with or without endoscopic papillotomy (5 patients vs. 9 patients, P = 0.4). CONCLUSIONS: Emergency ERCP with or without endoscopic papillotomy is indicated in the treatment of patients with acute pancreatitis.

Acute Disease↗

Appraisal of hepaticocutaneous jejunostomy in the management of hepatolithiasis.

Hepaticocutaneous jejunostomy offers the advantage of permanent percutaneous access to the biliary tract in patients with complex biliary problems. The long-term value, however, has not been assessed. In 41 patients who underwent this procedure for intrahepatic stones, there was no hospital mortality, and the postoperative morbidity rate was 10%. The presence of the cutaneous stoma facilitated postoperative flexible choledochoscopy for dilatation of biliary strictures and extraction of residual stones. On follow-up, symptoms recurred in 12 patients (29%) at a median time of 27 months (range: 1 to 97 months). Reconstruction of the cutaneous stoma and flexible choledochoscopy via the jejunal loop helped to resolve the acute cholangitis (n = 4) and to eradicate recurrent stones in all cases. Hepaticocutaneous jejunostomy was also beneficial in the management of three patients who experienced further recurrence of symptoms. There was no major difficulty in reconstructing the cutaneous stoma and in performing choledochoscopy via the jejunal loop. The overall complication rate related to the cutaneous stoma was 15%. Repeat laparotomy for recurrent disease was required in only one patient who underwent a second bilio-enteric anastomosis for a nondilatable left duct stricture. We conclude that hepaticocutaneous jejunostomy is a valuable procedure in the management of hepatolithiasis.

Adult↗

Prediction of the severity of acute pancreatitis.

We conducted a prospective study to validate our previous finding that serum urea and plasma glucose levels on admission could predict the outcome of acute pancreatitis. Forty-two (24%) of 176 patients developed complications related to the attack of acute pancreatitis and were classified as having severe disease. By logistic regression analysis of 17 admission parameters, serum urea and plasma glucose levels were again the factors with independent significance in defining the outcome. By adopting the same cutoff levels as in our previous study (serum urea level greater than 7.4 mmol/L and plasma glucose level greater than 11.0 mmol/L), and the presence of either factor above the cutoff level as indicative of severe disease, the sensitivity of prediction was 79%, specificity 67%, and overall accuracy 70%. All the deaths were correctly predicted by this urea/glucose criteria. The overall accuracy was also found to be comparable with those of the APACHE II (cutoff level greater than 11) and Ranson's scoring systems. We conclude that the simple prognostic criteria for acute pancreatitis were validated; these criteria have the potential to stratify risk rapidly at the time of admission for patients who might benefit from an aggressive interventional protocol.

Acute Disease↗

[Skin tests in patients with history of anaphylactic reaction to penicillin].

Skin tests including immediate patch test (IPT), skin prick test (SPT), or intradermal test (IT) with penicillin G(PenG) and SPT with benzylpenicilloyl human serum albumin (BPO) were done in 54 patients with history of anaphylactic reaction to penicillin or shock of unknown cause. 26 patients with penicillin allergy were diagnosed. BPO specific IgE measured with ELISA gave a lower positive rate in detecting penicillin allergy as compared with the tests mentioned above. The results of skin tests in 26 patients showed that IPT with 500 IU/ml of PenG was not only accurate but also safe. Because no skin injury occurred and PenG residue could be washed out, the amount of PenG penetrated into skin is very small, thus, adverse reactions were very few. It is recommended that IPT with PenG in 500 IU/ml concentration is performed at the beginning of skin tests. If negative, SPT and then IT both with a solution of 500 IU/ml concentration are carried out, until a positive reaction occurs. This procedure is relatively accurate, simple and safe.

Adult↗

Kinetics of IgE antibody response to trichosanthin alpha-momorcharin and beta-momorcharin in mice.

Allergenicity of three plant abortifacient proteins, trichosanthin (TCS), alpha-momorcharin (alpha-MMC) and beta-momorcharin (beta-MMC) and the kinetics of IgE antibody response against these proteins were studied in C57BL/6N and BALB/cAn mice. These proteins were purified from Chinese medicinal herbs, characterized by biochemical and immunological procedures and found to be homogeneous by PAGE, SDS-PAGE and immunoelectrophoresis. The results obtained were summarized as follows: 1) different levels of IgE antibody responses against TCS, alpha-MMC and beta-MMC were induced when they were injected i.p. as antigen adsorbed onto AI(OH)3 gel into BALB/cAn or C57BL/6N mice on day 0 and day 28; 2) the allergenicity of the proteins was in the order of beta-MMC greater than alpha-MMC greater than TCS; 3) two injections of 10 micrograms or 50 micrograms of TCS or alpha-MMC given at 4 weeks interval without adjuvant elicited a low or undetectable PCA titer, while the same dose given weekly for 5 weeks resulted in high levels of IgE production; and 4) on the basis of PCA observations, no cross immunological reactivity among these three proteins was found, it seemed to support that TCS, alpha-MMC and beta-MMC may be alternately used for inducing abortion.

Abortifacient Agents, Nonsteroidal↗

[Protective effects of Salviae miltiorrhizae and anisodamine (654-2) against early lung injury in acute hemorrhagic necrotizing pancreatitis in the dog].

Experimental study had been conducted on 18 healthy adult mongral dogs of both sex, weighting from 7.5-11 kg, randomly divided into four groups. Experimental models of acute hemorrhagic necrotizing pancreatitis (AHNP) were established by retrograde injecting 1 ml/kg of sodium taurocholate directly into the pancreatic duct. The dogs were treated respectively with intravenous infusion of Salviae miltiorrhizae (5 g/kg), 654-2(5 mg/kg) or normal saline. The results showed that PaO2, PaCO2 and pH did not change in early stage of AHNP. The contents of lactic acid dehydrogenase (LDH), albumin and lipid peroxide (LPO) of bronchoalveolar lavage fluid in the AHNP group were significantly higher than that of Salviae miltiorrhizae group (P less than 0.05). The necrosis and disruption of conjunction of endothelial cells resulting from the defects of vascular wall were noted under transmission electron microscope. Both pulmonary vascular and type II pneumocyte were normal in the Salviae miltiorrhizae group. These results suggested that Salviae miltiorrhizae possess the effect of protecting endothelial cells of pulmonary vascular and type II pneumocyte, which could function as scavenger of oxygen-derived free radicals.

Animals↗

A study of the pathogenesis and prevention of central pontine myelinolysis in a rat model.

The development of central pontine myelinolysis was studied in rats. Severe hyponatraemia was induced using vasopressin tannate and 2.5% dextrose in water and then rapidly corrected with hypertonic saline alone, hypertonic saline and dexamethasone simultaneously, or hypertonic saline plus dexamethasone 24 h later. The permeability of the blood-brain barrier was evaluated using the extravasation of Evans blue dye and the expression of inducible nitric oxide synthase (iNOS) in the brain was examined using Western blot analysis. Histological sections were examined for demyelinating lesions. In rats receiving hypertonic saline alone, Evans blue dye content and expression of iNOS began to increase 6 and 3 h, respectively, after rapid correction of hyponatraemia and demyelinating lesions were seen. When dexamethasone was given simultaneously with hypertonic saline, these increases were inhibited and demyelinating lesions were absent. These effects were lost if dexamethasone injection was delayed. Disruption of the blood-brain barrier and increased iNOS expression may be involved in the pathogenesis of central pontine myelinolysis, and early treatment with dexamethasone may help prevent the development of central pontine myelinolysis.

Animals↗