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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 235 records · Page 13Linked to original sources

Role of microtubules in LPS-induced macrophage inflammatory protein-2 production from rat pneumocytes.

We have recently demonstrated that primary cultured rat pneumocytes produce macrophage inflammatory protein-2 (MIP-2) in response to lipopolysaccharide (LPS) stimulation. In this study, we found that brefeldin A, by blocking anterograde transport from the endoplasmic reticulum (ER) to the Golgi apparatus, decreased LPS-induced MIP-2 in the culture medium and increased its storage in cells. This suggests that MIP-2 is secreted via a pathway from the ER to the Golgi apparatus, a process commonly regulated by microtubules. We further found that LPS induced depolymerization of microtubules as early as 1 min after LPS stimulation, and it lasted at least for 4 h. Preventing depolymerization of microtubules with paclitaxel (Taxol; 10 nM to 10 microM) partially inhibited LPS-induced MIP-2 production, whereas the microtubule-depolymerizing agents colchicine (1-10 microM) and nocodazole (1-100 microM) increased LPS-induced MIP-2 protein production without affecting MIP-2 mRNA expression. These results suggest that in pneumocytes, LPS-induced microtubule depolymerization is involved in LPS-induced MIP-2 production and that secretion of MIP-2 from pneumocytes is via the ER-Golgi pathway.

Animals↗

A novel cell culture model for studying ischemia-reperfusion injury in lung transplantation.

Many cell culture models have been developed to study ischemia-reperfusion injury; however, none is specific to the conditions of lung preservation and transplantation. The objective of this study was to design a cell culture model that mimics clinical lung transplantation, in which preservation is aerobic and hypothermic. A549 cells, a human pulmonary epithelial cell line, were preserved in 100% O(2) at 4 degrees C for varying periods in low-potassium dextran glucose solution, simulating ischemia, followed by the introduction of warm (37 degrees C) DMEM plus 10% fetal bovine serum to simulate reperfusion. Cultures were assayed for cell attachment and viability. Sequential extension of ischemic times to 24 h showed a time-dependent loss of cells. There was a further decrease in cell number after simulated reperfusion. Cell detachment was due mainly to cell death, as determined by cell viability. The effects of chemical components such as dextran 40 and calcium in the preservation solution and various preservation gas mixtures were examined by use of this model system. With its design and validation, this model could be used to study mechanisms related to ischemia-reperfusion injury at the cellular and molecular level.

Cell Adhesion↗

Invited review: mechanochemical signal transduction in the fetal lung.

Growth and maturation of fetal lungs are regulated by both humoral and physical factors. Mechanical stretch stimulates fetal lung cell proliferation and affects fetal lung maturation by influencing the production of extracellular matrix molecules and the expression of specific genes of fetal lung cells. These effects are mediated through special signal transduction pathways in fetal lung cells. Various in vivo and in vitro model systems have been developed to investigate the mechanotransduction process. The diversity and discrepancy of these studies have raised many questions. We will briefly summarize mechanical force-induced signals in fetal lung cell proliferation and differentiation and then discuss several important issues related to these studies.

Animals↗

Analysis of related factors in complications of stereotactic radiosurgery in intracranial tumors.

OBJECT: To investigate the related factors in complications of stereotactic radiosurgery for intracranial tumors. METHODS: A retrospective review of 146 patients with intracranial tumors treated with stereotactic radiosurgery was conducted. Sixty-five patients received single-dose treatment and the rest received fractionated stereotactic radiosurgery. Ninety-five patients received conventional radiotherapy in the meantime. RESULTS: Follow-up period was 18-54 months. Follow-up rate was 92.5% and 39 patients (26.7%) had different complications. The Cox statistics showed that target volume, target peripheral dose, target maximal dose, and ratio of maximal dose to peripheral dose are related to the complications. Conversely, neither type of tumor disease, gender, radiation schedule with or without conventional radiotherapy, target minimal dose, nor ratio of target peripheral isodose volume to target volume were found to be related to complications. CONCLUSION: Target volume and dose are the major factors causing complications, and the optimization of the therapeutic planning can play a significant role in reducing them.

Brain Edema↗

Cyclic GMP-dependent protein kinase expression in coronary arterial smooth muscle in response to balloon catheter injury.

Arterial smooth muscle cells undergo phenotypic and proliferative changes in response to balloon catheter injury. Nitric oxide (NO) and cGMP have been implicated in the inhibition of vascular smooth muscle cell proliferation and phenotypic modulation in cultured-cell studies. We have examined the expression of the major cGMP receptor protein in smooth muscle, cGMP-dependent protein kinase I (PKG), in response to balloon catheter injury in the swine coronary artery. On injury, there was a transient decrease in the expression of PKG in neointimal smooth muscle cells when compared with medial smooth muscle cells. The decrease in PKG expression was observed in the population of proliferating cells expressing the extracellular matrix protein osteopontin but not in cells present in the uninjured portion of the media. Coincident with the suppression of PKG expression in neointimal cells after injury, there was a marked increase in the expression of type II NO synthase (inducible NOS [iNOS], NOS-II) in the neointimal cells. These results suggest that PKG expression is transiently reduced in response to injury in the population of coronary arterial smooth muscle cells that are actively proliferating and producing extracellular matrix proteins. The reduction in PKG expression is also correlated temporally with increases in inflammatory activity in the injured vessels as assessed by iNOS expression. Coupled with our current knowledge regarding the role of PKG in the regulation of cultured cell phenotypes, these results imply that PKG may also regulate phenotypic modulation of vascular smooth muscle cells in vivo as well.

Angioplasty, Balloon↗

Cochrane report: A systematic review of mannitol therapy for acute ischemic stroke and cerebral parenchymal hemorrhage.

BACKGROUND: Mannitol was reported to decrease cerebral edema associated with tissue damage and is used to treat acute stroke in many countries. SUMMARY OF REVIEW: We tested whether there is any evidence from unconfounded randomized clinical trials that treatment with mannitol reduces short- and long-term case fatality and dependency if administered after ischemic stroke or cerebral parenchymal hemorrhage. Trials were identified by the standard search strategy of the Cochrane Collaboration Stroke Review Group. A supplementary MEDLINE search was performed, and the Chinese Stroke Trials Register and the Latin-American databank LILACS were checked. A search was performed of master's and PhD degree theses in the databank of Sao Paulo University and in abstracts of medical congresses on neurology and neurosurgery during 1965-1997 in Brazil. Investigators were contacted for unpublished information. Only truly randomized unconfounded clinical trials were eligible for inclusion. Two of the reviewers independently extracted data from the trials. Data synthesis and analysis was performed with the use of the Cochrane Review Manager software (RevMan version 4.0.4). CONCLUSIONS: Only 1 trial fulfilled the inclusion criteria. The number of included patients was small, and the follow-up was short. Case fatality, the proportion of dependent patients, and side effects were not reported and were not available from the investigators. As a result of lack of appropriate randomized trials, currently no conclusion can be drawn on the effects of mannitol in acute stroke. The routine use of mannitol in all patients with acute stroke is not supported by evidence from randomized controlled clinical trials.

Acute Disease↗

Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury.

Prevention of ischemia-reperfusion (IR) injury is crucial for successful lung transplantation. We investigated whether a nitric oxide donor, nitroglycerin (NTG), could suppress the oxidative stress of IR injury and improve pulmonary function after reperfusion in an ex vivo rat lung perfusion model. In Fresh group of animals, the lungs were flushed with perfusate, followed immediately by reperfusion, and no lung injury was observed. In NTG- and NTG+ groups of animals, the lungs were flushed with perfusate alone or perfusate containing NTG, respectively. Harvested lung and heart blocks from these latter two groups were immersed in the corresponding perfusate at 4 degrees C for 15 h, and were then reperfused for 60 min. Reperfusion induced pulmonary edema in the NTG- group, but not in the NTG+ group. Shunt fractions in NTG+ group were significantly lower than in the NTG- group throughout reperfusion. NTG had no effect on pulmonary arterial pressure or myeloperoxidase activity. In contrast, oxidative DNA damage assessed immunohistochemically with a monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly increased in the NTG- group, in the order alveolar epithelium > pulmonary endothelium > bronchial epithelium. NTG treatment significantly decreased staining with the anti-8-OHdG antibody in all three areas of tissue. Therefore, administration of NTG attenuates the oxidative stress of IR injury, and may improve pulmonary function after reperfusion.

Animals↗

Targeting the angiotensin system in posttransplant airway obliteration: the antifibrotic effect of angiotensin converting enzyme inhibition.

The angiotensin system plays a role in the pathogenesis of fibrotic diseases. We used a rat heterotopic tracheal transplant model of bronchiolitis obliterans (BO) to examine the role of angiotensin converting enzyme (ACE) in development of the fibroproliferative lesion of BO. Isograft and allograft tracheal transplants were performed. Allograft rats received either no treatment (control) or captopril (100 mg/kg/d) in their drinking water. The drug treatment given to the recipient rats was begun 5 days before transplantation, on postoperative Day 1, or on postoperative Day 5. The treatment was continued until postoperative Day 21, when tracheal specimens were harvested and subjected to histologic, immunohistologic, and morphometric analyses. We noted heavy staining for ACE in the obliterated portion of the tracheas of allograft control animals. This area was not present in nontransplanted or isograft tracheas. Captopril administration begun 5 d before transplantation and on postoperative Day 1 resulted in a significant attenuation in the percent airway obliteration (45% and 26%, respectively) as compared with that in control allografts (83%; p < 0.05). This study demonstrates the presence of ACE in the fibroproliferative lesion in a rat model of BO, and shows that inhibition of ACE can limit development of airway obliteration.

Angiotensin-Converting Enzyme Inhibitors↗

Dynamic changes in apoptotic and necrotic cell death correlate with severity of ischemia-reperfusion injury in lung transplantation.

Ischemia-reperfusion (IR) injury is a major cause of organ dysfunction following lung transplantation. We have recently described increased apoptosis in transplanted human lungs after graft reperfusion. However, a direct correlation between ischemic time, cell death, and posttransplant lung function has not yet been demonstrated. We hypothesized that an increased ischemic period would lead to an increase in cell death, and that the degree and type of cell death would correlate with lung function. To investigate this, we preserved rat lungs at 4 degrees C for 20 min and 6, 12, 18, and 24 h, and then transplanted the lungs and reperfused them for 2 h. Cell viability was determined with a triple staining technique combining trypan blue, terminal deoxynucleotidyl transferase-uridine nucleotide end-labeling, and propidium iodide nuclear staining. Percentages of apoptotic and necrotic cells were calculated from total cell numbers. Following 20 min and 6 and 12 h of cold preservation, less than 2% of graft cells were dead, whereas after 18 and 24 h of cold preservation, 11% and 27% of cells were dead (p < 0.05), the majority of which were necrotic. After transplantation and reperfusion, the mode of cell death changed significantly. In the 6- and 12-h groups, approximately 30% of cells were apoptotic and < 2% were necrotic, whereas in the 18- and 24-h groups, 21% and 29% of cells, respectively, were necrotic and less than 1% were apoptotic. Lung function (Pa(O(2))) decreased significantly (p < 0.05) with increasing preservation time. The percentage of necrotic cells was inversely correlated with posttransplant graft function (p < 0.0001). The study demonstrates a significant association among cold preservation time, extent and mode of cell death, and posttransplant lung function, and suggests new potential strategies to prevent and treat IR injury.

Animals↗

RANTES plays an important role in the evolution of allograft transplant-induced fibrous airway obliteration.

Although lung transplantation is a widely applied therapeutic modality for end-stage pulmonary disease, the long-term survival following this procedure is limited by the development of bronchiolitis obliterans (BO). We investigated the role of RANTES, a C-C chemokine, in the evolution of fibrous airway obliteration (FAO) using a rat heterotopic tracheal transplant model. RANTES was highly expressed in infiltrating mononuclear cells in both allogeneic and isogeneic grafts as revealed by immunohistochemistry. Using a miniosmotic pump, neutralizing anti-RANTES antibody was locally and continuously infused to allografts, whereas recombinant rat RANTES was administered to isografts. Anti-RANTES antibody treatment decreased the number of CD4(+) infiltrating cells in allotracheas and preserved luminal patency compared with those of allocontrols. However, RANTES infusion in isografts did not induce FAO, even though CD4(+) cell migration was increased by this treatment. It appears that RANTES is relevant to the recruitment of CD4(+) cells and the development of FAO in the process of allorejection. Local administration of anti-RANTES might be a therapeutic option for BO following lung transplantation.

Animals↗

Treatment of in-stent coronary restenosis with excimer laser angioplasty.

OBJECTIVE: To evaluate the efficacy and safety of excimer laser coronary angioplasty (ELCA) with adjunctive balloon angioplasty in patient with in-stent restenosis. METHODS: ELCA was performed in 20 patients of instent restenosis. All patients were symptomatic and had class III-IV angina. ELCA was performed with the Spectranetics CVX-300 System. The laser catheter of Vittesse C (concentric) and E (eccentric) with diameter of 1.4-2.0 mm was used. RESULTS: Laser catheter crossed all stenotic stents without difficulty. The lesion length was 4.6-51.2 mm, mean 20.7 +/- 13.7 mm, including 14 lesions > 10 mm. Laser treatment alone increased minimal lumen diameter (MLD) from 0.3 +/- 0.3 mm to 1.4 +/- 0.3 mm (P < 0.0001) and improved the diameter stenosis from 88.8% +/- 10.0% to 46.0% +/- 8.0% (P < 0.0001). Adjunctive balloon angioplasty further increased minimal lumen diameter to 2.3 +/- 0.7 mm and reduced diameter stenosis to 14.2% +/- 8.2% (P < 0.0001). At follow-up (1-17 months, mean 8.9 +/- 5.7 months), 17 (85%) patients had remained asymptomatic, 3 (15%) patients had mild to moderate exertional angina, 1 (5%) patient received CABG. CONCLUSION: ELCA with adjunctive percutaneous transluminal coronary angioplasty (PTCA) is an efficient and safe technique to debulk tissue in the patient with in-stent restenosis. The incidence of procedural related complication was low and ELCA may be used as a good method for in-stent restenosis treatment.

Aged↗

A pilot study with simvastatin and folic acid/vitamin B12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH).

BACKGROUND AND AIM: This study was conducted in preparation for the Study Evaluating Additional Reduction in Cholesterol and Homocysteine (SEARCH). SEARCH is a 12,000 patient 2X2 factorial study in post-myocardial infarction patients that will compare simvastatin 20 mg with simvastatin 80 mg to evaluate whether greater LDL-C reductions with simvastatin provide greater coronary event reductions. SEARCH will also test the hypothesis that lowering plasma homocysteine with folic acid and vitamin B12 will reduce coronary events. This pilot study was performed to determine whether any clinically meaningful interaction between simvastatin and folic acid/vitamin B12 exists. METHODS AND RESULTS: Following a 2-week diet/placebo run-in period, 141 patients with primary hypercholesterolaemia were randomised to one of three treatments for 6 weeks: 80 mg/day simvastatin and 2 mg folic acid/0.8 mg vitamin B12 daily (combination group); or 80 mg/day simvastatin and placebo vitamins (simvastatin alone group); or 2 mg folic acid/0.8 mg vitamin B12 daily and placebo simvastatin (vitamins alone group). The combination group and simvastatin alone group experienced similar serum lipid changes with reductions in LDL-cholesterol of 55.2% and 51.5% respectively. The combination group and vitamins alone group experienced similar homocysteine lowering with reductions in homocysteine of 25.3% and 23.1% respectively. All therapies were well tolerated. CONCLUSIONS: There was no detectable antagonistic effect when simvastatin and folic acid/vitamin B12 were administered concomitantly.

Cholesterol↗

[Yeast (Saccharomyces cerevisiae) secretory expression vector maintained stably in Pro3+ transformants in rich medium].

A yeast (Saccharomyces cerevisiae) secretory expression vector containing PRO3 gene was constructed (pCBy310). beta HCG(Human choriogonadotropin beta subunit)-cDNA was inserted into pCBy310 to form a recombinant plasmid pCBy314. Since yeast proline auxotroph will not survive in rich medium (YPD), YPD could be used as a selection pressure, and pCBy314 could be maintained mitotically stable in transformants of yeast Pro3- auxotroph (MB299-7A) in rich medium. At an improved, yet not optimized cultural condition, the expression of beta HCG in culture medium was 650 micrograms/L. Our results showed not only that YPD could be used as a selection medium, but also that yeast grew better in YPD so as to increase the gene expression product, and that the component of YPD was simple and cheap. Our data suggested that PRO genes might be used widely in constructing vectors to clone and express foreign genes in yeast so that rich medium can be used as a selection pressure for direct selection.

Chorionic Gonadotropin, beta Subunit, Human↗

[Study on the inhibitory effect of antisense phosphorothioate oligodeoxynucleotide on coxsackie virus B replication in vitro].

OBJECTIVE: To investigate the antiviral effect of antisense phosphorothioate oligodeoxynucleotide (AODN) on CVB3 replication in vitro. METHODS: In this study, 21 mer antisense phosphorothioate oligodeoxynucleotide which complemented to nt 581-601 in 5' NCR of Coxsackie Virus B3 (CVB3) RNA was used to investigate antiviral activity in Vero cells as a specific inhibitor of CVB3 replication. Specific AODN of CVB3 RNA, sense oligodeoxynucleotide (SODN) and randomized nonsense-sequence RODN were synthesized for effect comparison among them. Vero cells infected by CVB3 were transfected with different concentrations of AODN mediated by lipofectamine reagent, so that the cells could take in more AODN. Cell control and viral control were set up. The inhibitory effect of AODN on CVB3 replication was evaluated with a number of variables, including inhibitory rates of cytopathic effect (CPE), cell survival rates by MTT assay, inhibitory rates of CVB3 antigen by ELISA, inhibitory rates of RNA by dot blotting and 50% tissue culture infective dose (TCID50). RESULTS: The specific AODN could significantly inhibit CPE of CVB3-infected Vero cells, decrease the production of antigen and RNA of CVB3 and viral titers, and increase cell survival rates, in a dose-dependent manner. The strongest inhibitory effect appeared at 48 hours after transfection, the most effective concentration of AODN was 10 micromol/L. On the other hand, 10 micromol/L SODN also showed weaker inhibitory effect on CPE of CVB3-infected cells, but no antiviral effect of 10 micromol/L RODN was shown. AODN showed no-inhibition on HSV-1 replication, but inhibited some enteroviruses such as CVB3, Polio-1 and Echo-6 to some extent. CONCLUSIONS: These results indicate that nt 581-601 in 5' NCR of CVB3 RNA may play an important role in regulating CVB3 replication and AODN may have inhibitory effect on CVB3 replication.

Animals↗

[Effects of space conditions on mutation and inheritance of tomato].

OBJECTIVE: To study the effects of space conditions on mutation and inheritance of tomato. METHOD: Air-dried seeds of tomato were carried by a satellite for 7-15 d. These seeds were planted after returning. The mutagenic effects of space conditions on some of their variations of the botanical characteristics were studied. RESULT: Tomato dry seeds were carried to the outer space by satellite. After returned to the earth it was found that SP1 generation was of their germination percentage lower than the control. This physiological damage returned to normal in SP2 generation. Seeding isoenzyme, plant growth, resistance, and output, showed variation, and profitable variation had been expressed in later generations. The characters were expressed in the progenies. By observation and screen, promising line of tomato TF873, was obtained. CONCLUSION: It was suggested that space conditions induce profitable mutation of crop and it a possible way for plant mutation breeding.

Germination↗

Modified sternal elevation for children with pectus excavatum.

OBJECTIVE: To describe our experience in the treatment of pectus excavatum (PE) using a modified sternal elevation procedure. METHODS: From Oct. 1986 to Dec. 1997, 171 patients with PE were admitted to the Department of Pediatric Surgery of the First Hospital of West China University of Medical Sciences. All patients were diagnosed through a history and physical examination. Cardiopulmonary function was assessed by M-mode echocardiography and instrument of pulmonary function in 40 patients before and 4.2 years after surgery which was performed between 1989 and 1994. We performed the following three procedures in the sternal elevation: (1) forming the metal strut in a "arch" shape, (2) suturing the perichondrium into a "pipe" shape, and (3) encouraging patients to do chest expansion exercise after operation. All patients were followed up for 1 to 12 years. RESULTS: The normal contour of the costal cage was enlarged in all but one patient. Exercise tolerance was improved, and cardiac function recovered to the same level as in healthy children, while pulmonary function recovered very slowly after surgery. CONCLUSION: The normal appearance of chest wall can be recovered and normal cardiopulmonary function can be restored by the modified sternal elevation procedure in children with PE.

Adolescent↗