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Biomedical subjects

W Gao

Publications and source records attributed to W Gao.

At least 199 records · Page 11Linked to original sources
PubMed1995

Role of Kupffer cells in failure of fatty livers following liver transplantation and alcoholic liver injury.

Kupffer cells have been implicated in mechanisms of pathophysiology following liver transplantation. Recently, postoperative injury in ethanol-induced fatty liver has been evaluated because fatty livers often fail following transplantation. The low-flow, reflow liver perfusion model was used to study the role of Kupffer cells (KC) in reperfusion injury to fatty livers from rats fed a diet containing ethanol for 4-5 weeks. Treatment with GdCl3, which selectively destroys KC, decreased cell death significantly. Thus, destruction of KC minimized hepatic reperfusion injury, most likely by inhibiting free radical formation and improving microcirculation. Since it was demonstrated recently that destruction of KC prevented the hypermetabolic state observed with acute alcohol exposure, their involvement in events leading to alcohol-induced liver disease was investigated. In rats exposed to ethanol continuously via intragastric feeding for up to 4 weeks, GdCl3 treatment prevented elevation of aspartate aminotransferase (AST) and dramatically reduced the average hepatic pathological score. These results indicate that KC participate in the early phases of alcohol-induced liver injury. Endotoxaemia occurs in alcoholics and activates KC; therefore, we evaluated the effect of minimizing bacterial endotoxin by intestinal sterilization with the antibiotics polymyxin B and neomycin. Antibiotics diminished plasma endotoxin levels significantly and prevented ethanol-induced increases in AST values. These results indicate that endotoxin is involved in the mechanism of ethanol-induced liver injury. A six-line radical spectrum was detected with electron paramagnetic resonance spectroscopy in bile from alcohol-treated rats which was blocked by GdCl3. The free radical adducts had hyperfine coupling constants characteristic of lipid-derived free radical products. In conclusion, these studies demonstrate that KC are involved in reperfusion injury to ethanol-induced fatty livers and hepatic injury due to long-term treatment with ethanol.

Animals↗
PubMed1995

Dual role of Kupffer cell activation and endothelial cell damage in reperfusion injury to livers stored for transplantation surgery.

In rat models of liver preservation, the primary event leading to liver graft failure after cold storage is a reperfusion injury causing damage to sinusoidal endothelial cells and activation of Kupffer cells (KC). After storage for longer than 16 h in University of Wisconsin solution, reperfusion induces rapid endothelial cell killing. Kupffer cell activation also occurs as indicated by cell surface ruffling, degranulation, release of hydrolytic enzymes, generation of oxygen radicals, and increased phagocytosis. Down-regulation of KC activity with nisoldipine or pentoxifylline improves graft survival. Moreover, pretreatment of donors with small amounts of endotoxin to activate KC causes a drastic reduction of graft survival. Together, KC activation and endothelial damage cause marked microcirculatory disturbances after transplantation characterized by reduced and uneven blood flow and increased leucocyte and platelet adhesion. Such events culminate in inflammation, necrosis and fulminant graft failure. Modification of reperfusion conditions can reduce the extent of injury. In particular, flushing livers with Carolina rinse solution (CRS) at the end of storage reduces endothelial cell killing, suppresses KC activation, improves the microcirculation, and increases graft survival. Active ingredients in CRS include antioxidants (allopurinol, desferrioxamine and glutathione), adenosine and slightly acidic pH (6.5). Other potentially important ingredients are nicardipine, a calcium channel blocker, and fructose, glucose and insulin to promote glycolysis. The cytoprotective amino acid, glycine, further improves the performance of Carolina rinse solution. Reperfusion-induced changes to nonparenchymal cells play an essential role in damage to livers preserved for transplantation surgery. Understanding the role of sinusoidal endothelial cells and KC in this injury has led to promising new strategies to prolong organ storage and reduce graft failure.

Animals↗
PubMed1995

[Percutanous transluminal coronary angioplasty for unstable angina].

Percutanous transluminal coronary angioplasty (PTCA) was performed in 190 patients with 250 diseased vessels and 278 lesions from Dec. 1987 to Feb. 1994. All the patients had unstable angina (UA). There were 52 (18.7%) type A lesions, 175 (62.9%) type B lesions and 51 (18.3%) type C lesions. Of the 190 patients undergoing PTCA, 134 (70.5%) patients had dilatation of a single vessel, 46 (24.2%) of two vessels and 10 (5.3%) of three or more vessels. In 121 patients with multivessel disease, 98 (81.0%) had incomplete revascularization of the ischemia-related vessel (the culprit vessel) and only 23 (19.0%) had complete vessel revascularization. Kissing balloon technique was used in six patients and autoperfusion balloon in five. There were four patients undergoing directional coronary atherectomy (DCA) and four intracoronary stent. The clinical (patient) success rate was 94.7% (180/190) and technical (vessel) success rate 95.2% (238/250). The average degree of vessel stenosis was 88.7% +/- 8.3% before PTCA and the residual tenosis was 17.9% +/- 9.2% after PTCA. Acute vascular complications occurred in 18 (6.5%) lesions. 15 were managed successfully, two developed Q wave myocardial infarct and one died. None needed emergency coronary bypass operation. PTCA was not successful in 10 patients. In 180 patients with successful PTCA, 165 (91.7%) were free from UA, 15 (8.3%) patients had symptoms improved and oxygen need reduced. During a six-month follow-up, 26 patients had chest pain again with confirmed restenosis, repeated PTCA was performed successfully.

Adult↗
PubMed1995

[The result of re-resection of lung cancer].

In 38 cases of primary lung cancer with post-operative recurrence and metastasis or second primary lung cancer, re-resection was performed. The time interval between the first operation and re-resection was 2 months-9 years. The resectibility rate was 89.5%. Postoperative complication rate was 23.7% and the operative mortality rate within 1 months was 5.3%. With radical re-resection the one, three and five year-survival rate were 80%, 45.8% and 35% respectively. The survival time depends more on the thoroughness of resection than on the histologic type of the tumor and the time interval. It is of the opinion that wherever recurrence and/or metastasis occur. Radical reresection is the treatment of choice.

Adenocarcinoma↗
PubMed1995

Extensive wound excision in shock stage in patients with major burns.

To stop excessive plasma loss, alleviate noxious effects of devitalized tissues on the body and shorten the hospitalization time, we performed extensive escharectomy during the shock period in extensively burned patients. Group A consisted of 21 patients aged 9-45 years (26.1 +/- 7.9 years), with a mean total burn area of 63.2% +/- 18.1% TBSA, and full-thickness injury involving 35.9% +/- 19.6% TBSA. The first escharectomy was done at 24.1 +/- 13.9 hours postburn, and excision area averaged 32.3% +/- 6.7% TBSA (24%-46%). In 15 of them, Swan-Ganz catheter was introduced to monitor the hemodynamic changes. It was found that RAP, PAP, PAWP, ABP, HR, CO and CI were all stable during and after the operation. Group B consisted of 29 patients aged 11-50 years (30.4 +/- 11.7 years), in whom escharectomy was begun 4-5 days postburn. The mean healing time of the patients in group A was 33.1 days, shorter than that of group B patients (40.1 days). The duration of hemoconcentration was shorter in group A. The amount of blood transfusion was almost 700 ml less in group A during the first two weeks. Less antibiotics were used with fewer visceral complications in group A. We believe that escharectomy during the burn shock stage is feasible.

Adolescent↗
PubMed1995

Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats.

Reperfusion injury was studied in blood-free perfused livers from fat-loaded, ethanol-treated rats. Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 36% calories as ethanol or isocaloric maltose-dextrin for 4 to 5 weeks. Reperfusion injury to the liver, which occurs in previously hypoxic regions upon reintroduction of oxygen, was studied in a low-flow, reflow perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol treatment elevated values to 37 IU/g/h. Pretreatment of rats with gadolinium chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers from both groups. Rates of malondialdehyde production were 144 and 166 nmol/g/h during reperfusion in control and alcohol-treated rats, respectively, but values reached only 54 and 79 nmol/g/h after GdCl3 treatment. Interestingly, a typical PBN/carbon-centered free radical adduct signal was detected in bile of livers from ethanol-treated rats, but not in controls or ethanol-treated rats given GdCl3. Portal pressure increased during the reperfusion period in livers from alcohol-treated rats, although not in controls, and GdCl3 reduced it significantly. Taken together, these data indicate that reperfusion injury is greater in fatty livers from alcohol-treated rats in a blood-free model. Inactivation of Kupffer cells minimized reperfusion injury in both control and alcohol-treated rats, most likely by diminishing lipid peroxidation thereby improving hepatic microcirculation.

Animals↗
PubMed1995

[Escharectomy during burn shock stage contributed to controlling or alleviating infectious complication].

Among 29 patients with extensive burn, 14 received escharectomy during the shock period, and the other 15 after 96 hrs. LPS and TNF were determined before and after escharectomy 3, 7, 14 and 21 PBD. Incidence of sepsis and subeschar bacterial count were analyzed. Clinical conditions were compared. The results showed that escharectomy during burn shock stage significantly reduced infectious complications in extensively burned patients. We believe that as long as general condition of the patient allowed, early removal of eschar was beneficial in reducing the threat of sepsis.

Adult↗
PubMed1995

[The effect of different topical agents on pseudomonas infection of burn wound].

48 Wistar rats were scalded resulting in 15% TBSA full-thickness burn. Pseudomonas aeruginosa (10(9)/ml was inoculated to the wounds. The rats were divided into 6 groups. 5 different topical agents were separately applied to the wounds constituting 5 groups, and no drug was used in control group. Through observing the appearance of wound, the quantity of bacteria in the subeschar tissue and histo-pathological changes, we confirmed that AgSD-ZnSD-A cream was a satisfactory topical agent.

Animals↗
PubMed1994

Role of carboxy-terminal region in proofreading function of methionyl-tRNA synthetase in Escherichia coli.

The synthetic and editing functions of three forms of Escherichia coli methionyl-tRNA synthetase with different C-terminal sequences have been compared in vivo and in vitro. These forms include a full-length wild-type dimer (MRS676), a truncated monomer (MRS547) believed to be equivalent to the biologically active large tryptic fragment, and a third form denoted MRS581*. DNA sequencing revealed that MRS581* is predicted to contain 18 additional amino acids from the wild-type full-length sequence at the carboxy terminus of truncated form MRS547, and this is then fused to an additional 16 amino acids encoded by vector pBR322. Both MRS676 and MRS581* were found to edit endogenous homocysteine about 20-fold more efficiently than MRS547 in vivo. However, the three methionyl-tRNA synthetases edited exogenously supplied homocysteine in bacterial cultures to similar extents. Purified proteins exhibited no significant differences in editing function in vitro. Synthetic activity of purified MRS676 in vitro was found to be about 2.5-fold higher per subunit compared to the shorter forms of the enzyme. The C-terminal region in E. coli methionyl-tRNA synthetase is thus suggested to play an important role in editing in vivo, most likely by allowing interaction of the enzyme with the methionine biosynthetic pathway. These data support a model of channeling of at least some metabolites in bacterial protein synthesis.

Escherichia coli↗
PubMed1994

Luffin-S--a small novel ribosome-inactivating protein from Luffa cylindrica. Characterization and mechanism studies.

We purified and characterized a novel RIP (ribosome inactivating protein), Luffin-S from the seeds of Luffa cylindrica. Different from Luffin-A and B, which are RNA N-glycosidases with molecular weights of 27 and 28 kDa, respectively, Luffin-S has an M.W. of only approx. 10 kDa, much smaller than any other RIPs so far investigated. Its abundant resources, toxicity similar to TCS in a cell-free protein synthesis system and unique mechanism as phosphodiesterase, like alpha-sarcin, promisingly make it a potential toxic moiety of immunotoxin.

Amino Acids↗
PubMed1994

New reactive oxidizing species causes formation of carbon-centered radical adducts in organic extracts of blood following liver transplantation.

alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN) radical adducts from Folch (chloroform:methanol) extraction of blood of transplanted livers exhibited a large 6-line electron paramagnetic resonance (EPR) spectrum. Slow EPR sample preparation involving freezing and thawing prior to extraction over 15 min yielded a spectrum assigned as a lipid-derived free radical species, whereas rapid (< 1 min) extraction without a freeze-thaw cycle yielded a mixture of radicals, one with coupling constants similar to the alpha-hydroxymethyl-4-POBN adduct (4-POBN/.CH2OH). Extraction with purified chloroform, however, yielded a much weaker, probably lipid-derived signal. Use of 13C-methanol in the Folch extracting solution yielded a 12-line EPR spectrum, indicating that a new, highly reactive oxidant species from blood following liver transplantation can convert organic solvents used in tissue extractions to free radicals. This hypothesis was supported by simulation of EPR spectra of free radicals extracted rapidly with Folch, which indicated that the spectrum contained two carbon-centered species, one with hyperfine coupling constants similar to the alpha-methylhydroxyl-4-POBN adduct, the other probably lipid-derived. Because the former originates from methanol in the Folch, extraction of samples with alcohol-free organic solvent is most likely superior when the potential for formation of stable oxidant species exists, such as after liver transplantation.

Animals↗
PubMed1994

SPC-100270, a protein kinase C inhibitor, reduced hypoxic injury due to reperfusion following orthotopic liver transplantation in the rat.

Recently, we reported that SPC-100270, a sphingosine derivative and inhibitor of protein kinase C (50-90 microM) in mixed micelle assays, reduced reperfusion injury resulting from hypoxia in a low-flow, reflow model of liver perfusion. Here we report that SPC-100270 has similar beneficial effects following liver transplantation in vivo. Rat liver transplantation was performed using nonarterial and rearterial techniques. Livers from syngenic rats were harvested surgically, prepared with vascular cuffs and a splint, and stored for 24 or 48 h in University of Wisconsin (UW) cold storage solution. Just prior to completion of vascular reconstruction, the organ was rinsed with 3 or 10 ml of Ringer's solution, vehicle, or a solution containing SPC-100270 (up to 500 microM). Following implantation surgery, low doses of SPC-100270 were ineffective at reducing both parenchymal and nonparenchymal cell death, yet significant (P < 0.05) reductions were observed with 500 microM. Further, nonparechnymal cell viability was improved nearly four fold by the drug. SPC-100270 (500 microM) tended to increase survival following 48 h cold storage in UW solution, but the improvement was not statistically significant. SPC-100270 also did not diminish carbon-centered free radical formation in transplanted livers from alcohol-treated rats. Collectively, these data support the hypothesis that pretreatment of donor livers with an inhibitor of protein kinase C is effective in vivo at reducing reperfusion injury, particularly to nonparenchymal cells, following orthotopic liver transplantation in the rat.

Adenosine↗
PubMed1994

[The surface anatomic observation of cerebral porecentral and postcentral gyrus for scalp acupuncture].

10 heads of adult cadaver were used for investigation of the motor and sensory area of scalp acupuncture. The results are as follows: both the surface anatomy of precentral and postcentral gyrus were not exactly match with the motor and sensory area described in acupuncture textbook respectively. They were backward. Among them, the upper points were 0.5cm backward to motor area and 1.0cm to sensory area, the lower point of precentral gyrus was 1.0cm posterior to the intersecting point of the eyebrow--occiput line and the anterior border of the natural line of the hair at the temple, while the lower point of postcentral gyrus is 2.4cm posterior to the intersecting point above described. Therefore, the authors suggested that the motor and sensory area of the scalp acupuncture should be backward and recommended: take the point 1.0cm and 3.0cm posterior to the midpoint of anteroposterior midline as the upper point of motor and sensory area respectively, 1.0cm and 2.0cm posterior to the intersecting point above described as the lower point respectively. In this way, the motor and sensory areas are better matched with precentral and posrcentral gyrus than before (P < 0.05).

Acupuncture Points↗
PubMed1994

Percutaneous transluminal coronary angioplasty. Its success rate and affecting factors.

From December 1987 to October 1983, percutaneous transluminal coronary angioplasty (PTCA) was performed in 302 patients with 392 diseased vessels and 440 lesions. The success rate was 93.71% in 302 patients, 94.90% in 392 diseased vessels and 95.00% in 440 lesions. The success rate was 98.92% in Type A lesion, 95.71% in Type B lesion, and 86.57% in Type C lesion (A vs B P = NS, A vs C P < 0.01). There were 55 lesions with total or subtotal occlusion, the success rate was 89.09% (93.10% in Type B lesion and 84.62% in Type C lesion). As to the diseased vessels, the success rate was 95.65% in LAD, 94.38% in LCX and 93.75% in RCA. The results showed no significant difference. In this series, acute ischemic complications were found in 6.59% (29/440). Of these 29 lesions, 23 were treated successfully, 5 developed Q wave myocardial infarction and 1 died.

Aged↗
PubMed1994

Inactivation of Kupffer cells prevents early alcohol-induced liver injury.

It is well recognized that consumption of alcohol leads to liver disease in a dose-dependent manner; however, the exact mechanisms remain unclear. Hypoxia subsequent to a hypermetabolic state may be involved; therefore, when it was observed recently that inactivation of Kupffer cells prevented stimulation of hepatic oxygen uptake by alcohol, the idea that Kupffer cells participate in early events that ultimately lead to alcohol-induced liver disease became a real possibility. The purpose of this study was to test that hypothesis. Male Wistar rats were exposed to ethanol continuously by means of intragastric feeding for up to 4 weeks using the model developed by Tsukamoto and French. In this model, ethanol causes fatty liver, necrosis and inflammation--changes characteristic of alcohol-induced liver disease in human beings. Kupffer cells were inactivated by twice weekly treatment with gadolinium chloride (GdCl3), a selective Kupffer cell toxicant. AST levels were elevated to 192 +/- 13 and 244 +/- 56 IU/L in rats exposed to ethanol for 2 and 4 wk, respectively (control value, 88 +/- 7). This injury was prevented almost completely by GdCl3 treatment. Fatty changes, inflammation and necrosis were also all reduced dramatically by GdCl3 treatment. The average hepatic pathological score of rats treated with ethanol for 4 wk was 4.3 +/- 0.6, which was reduced significantly in ethanol- and GdCl3-treated rats to 1.8 +/- 0.5 (p < 0.05). Rates of ethanol elimination were elevated 2- to 3-fold in rats exposed to ethanol for 2 to 4 wk. This elevation was blocked by GdCl3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗