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Biomedical subjects

F Xiao

Publications and source records attributed to F Xiao.

At least 55 records · Page 3Linked to original sources
PubMed1998

Histological characterization and pharmacological control of chronic rejection in xenogeneic and allogeneic heart transplantation.

BACKGROUND: Chronic allograft rejection remains a major barrier to successful long-term allograft transplantation in humans. Chronic allograft rejection is characterized by the appearance of arterial lesions with concentric intimal thickening. This study investigates the development and control of chronic rejection in hamster cardiac xenografts transplanted into Lewis rats. METHODS: Chronic rejection in the xenograft model involves transplantation of hamster hearts into Lewis rats treated with leflunomide (Lef) continuously at 15 mg/kg/day. The allograft model involves transplantation of Lewis hearts into Fisher-334 rats treated with cyclosporine (CsA) at 2.5 mg/kg for 5 days. RESULTS: The average scores of arterial intimal thickening on day 45 after transplantation were 1.89+/-0.43 in the xenograft and 2.50+/-0.72 in the allograft. The basic pathology of both xenografts and allografts undergoing chronic rejection was arterial intimal thickening comprising smooth muscle cell proliferation, mononuclear cell infiltration, and fibrosis. The majority of cells infiltrating the arterial intima and myocardium were T cells and macrophages. Compared with the allograft, intimal edema, matrix deposition and fibrinoid necrosis were specifically presented in the xenografts and generally involved the larger arteries. The predominant isotype of antibody deposited was IgM in xenografts and IgG in allografts. When combined Lef and CsA therapy was initiated on day 45 after transplantation, the changes of chronic rejection were reversed in both xenografts and allografts by day 90. The scores of intimal thickening were significantly reduced to 0.97+/-0.45 and 1.48+/-0.56, respectively. CONCLUSIONS: We conclude that chronic rejection can be induced in xenografts under conditions of inadequate immunosuppression. Chronic rejection in xenografts involves arterial lesions that bear some histological similarities to, as well as differences from, those observed in chronically rejected allografts. Finally, combination therapy with CsA and Lef reduced the incidence and severity of the intimal lesions in both chronically rejecting xenografts and allografts.

Animals↗
PubMed1998

[Molecular cytogenetic study on four human esophageal cancer cell lines].

OBJECTIVE: To investigate the possible involvement of chromosome abnormalities in pathogenesis of human esophageal cancer. METHODS: Four cell lines of human esophageal cancer (EC) established in our laboratory were analysed using interphase fluorescence in situ hybridization (FISH), chromosome painting technique and comparative genomic hybridization (CGH). RESULTS: Chromosome gain of 1,2,3,8,16, 17, and 20 was found in the four cell lines, and loss of chromosome Y in cell line EC8712, EC8733 and EC8501 was noted. Other frequent changes were partial deletion of 1p, translocation of 2q and amplification of 5p in all 4 cell lines, and amplification of 8q and 13q in EC8733 and deletion of 17p in EC8712. CONCLUSION: The data suggest that nonrandom chromosome aberrations may play an important role in the pathogenesis of human esophageal cancer.

Adult↗
PubMed1998

Mild protective and resuscitative hypothermia for asphyxial cardiac arrest in rats.

It has been shown in dogs that mild hypothermia (34 degrees C) during or immediately after ventricular fibrillation cardiac arrest can improve cerebral outcome. The effect of mild hypothermia on outcome after 8 minutes of asphyxiation (5 minutes' cardiac arrest) was studied for the first time in rats. Restoration of spontaneous circulation was with external cardiopulmonary resuscitation and observation to 72 hours. Three groups of 10 rats each were studied. At 72 hours postarrest, compared with the normothermic control group 1, final overall performance categories (OPC) and neurological deficit scores (NDS) were numerically better in the resuscitative (post-arrest) hypothermia group 2 and significantly better in the protective (pre-intra-arrest) hypothermia group 3 (P < .05). Total brain histopathological damage scores (HDS) were 17 +/- 5 in group 1, 14 +/- 6 in group 2 (NS), and 6 +/- 2 in group 3 (P < .001 versus group 1). HDS correlated with OPC (r = .6, P < .05) and NDS (r = .7, P < .05). Mild hypothermia improved cerebral outcome after asphyxial cardiac arrest in rats, more when induced before than after arrest. The model's insult is within the therapeutic window, which makes it also suitable for screening other cerebral resuscitation potentials.

Animals↗
PubMed1998

Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins.

Intestinal ischemia-reperfusion (I-R) is associated with lung injury and the acute respiratory distress syndrome. The hypothesis of this study was that intestinal I-R activates circulating neutrophils to promote elastase-mediated lung injury. Isolated rat lungs were perfused with blood or plasma obtained after intestinal I-R, and lung neutrophil retention and injury and bronchoalveolar lavage (BAL) elastase were measured. Perfusion with I-R blood caused lung neutrophil accumulation and injury and increased BAL elastase. These effects were attenuated by the elastase inhibitor L-658758. Interference with neutrophil adherence before gut reperfusion blocked BAL elastase accumulation. The role of endothelial junction proteins (cadherins) in I-R-elicited lung damage was also evaluated. Activated human neutrophils proteolyzed cadherins in human umbilical vein endothelial cells. Furthermore, plasma of patients with acute respiratory distress syndrome contained soluble cadherin fragments. The results of this study suggest that the elastase released by systemically activated neutrophils contributes to lung neutrophil accumulation and pulmonary microvascular injury. Elastase-mediated proteolysis of endothelial cell cadherins may represent the mechanism through which lung microvascular integrity is disrupted after intestinal I-R.

Animals↗
PubMed1998

[Establishment of two human esophageal carcinoma cell lines and their cytogenetic analysis].

OBJECTIVE: To explore the relation between chromosomal aberration and carcinogenesis of the esophagus by molecular cytogenetic analysis of two esophageal carcinoma cell lines. METHODS: Small tissue blocks taken from resected specimens of patients with esophageal cancer (EC) were cultured in medium 199 added with 1.5% fetal bovine serun, and two esophageal carcinoma cell lines, EC8712 and EC8733, were established in 1987. They grew in monolayers. Molecular cytogenetic studies were performed on the two cell lines using chromosome G-banding, fluorescence in situ hybridization (FISH) and comparative gene hybridization (CGH) techniques. RESULTS: Both cell lines were aneuploid. Loss of chromosome Y, partial deletion of 1p, translocation of 2q and amplification of 5p, were observed in the 2 cell lines. Amplification of 8q and 13q in EC8733 and deletion of 17p in EC8712 were detected. CONCLUSION: The presene of the reported chromosomal aberrations may be related to the carcinogenesis and cancer development of the esophagus.

Aneuploidy↗
PubMed1997

Complement-mediated lung injury and neutrophil retention after intestinal ischemia-reperfusion.

Complement-mediated neutrophil activation appears to play an important role in ischemia-reperfusion (I/R) injury in a variety of tissues, including the heart, lung, and small bowel. The objective of this study was to determine whether inhibition of the alternative and classic complement cascades by administration of soluble complement receptor 1 (sCR1) prevents the increased neutrophil stiffness, lung neutrophil retention, and pulmonary microvascular injury elicited by a systemic inflammatory insult. Isolated lungs were perfused with blood obtained from animals subjected to 2 h of intestinal ischemia and 20 min of reperfusion (I/R) or control (nonischemic) surgery. Intestinal I/R resulted in a significant increase in neutrophil stiffness, lung neutrophil retention, and increased pulmonary microvascular permeability, effects that were prevented by administration of sCR1 before intestinal reperfusion. The results of this study suggest that I/R injury in the gut is a potent systemic inflammatory stimulus that induces complement-mediated neutrophil stiffness, lung neutrophil entrapment, and pulmonary microvascular dysfunction.

Animals↗
PubMed1997

Lung neutrophil retention and injury after intestinal ischemia/reperfusion.

OBJECTIVE: To define the mechanisms responsible for the lung leukosequestration and injury elicited by intestinal ischemia/reperfusion (I/R). METHODS: The effect of 120 minutes of superior mesenteric artery occlusion and 90 minutes of reperfusion on neutrophil deformability, lung neutrophil retention, and pulmonary microvascular permeability was determined. RESULTS: Compared with control surgery, intestinal I/R resulted in a significant increase in neutrophil stiffness (mean yield pressure [Pyield], 1.533 +/- 0.075 and 2.302 +/- 0.288 cm H2O, respectively) and lung neutrophil content (6.3 +/- 1.4 and 31.5 +/- 6.4 U/g wet weight, respectively). These changes were not affected by inhibition of neutrophil adherence before gut reperfusion. However, the increased lung microvascular permeability elicited by gut I/R (0.111 +/- 0.020 [control surgery] and 0.255 +/- 0.041 [I/R] mL/min/cm H2O/100 g lung tissue) was significantly attenuated by administration of antibodies directed against neutrophil or endothelial determinants of leukocyte adhesion. CONCLUSIONS: The results of this study suggest that intestinal I/R is a potent inflammatory stimulus that elicits an increase in neutrophil stiffness and lung neutrophil retention independent of neutrophil-endothelial cell adhesion. In contrast, the increased lung microvascular permeability elicited by gut I/R is attenuated by strategies that interfere with neutrophil-endothelial cell adhesion.

Animals↗
PubMed1997

[Employing deconvolution method for correcting scatter in radiography].

It is well known that the scattered-radiation (SR) results in degradation of the images contrast in digital X-ray radiograph. The main reason affecting radiographic image quality is the SR arising from interaction of the photons with object being radiographed and veiling glare from detector system in the II-TV chai imaging system. With the aim of improving the image quality, we employed the Gaussian function to approximate the scattered point spread function (PSF) and determined the fraction of SR, rho and the parameter, sigma experimentally on an individual system; then we built an inverse filter to process the digital chest X-ray images, which were acquired with the same system and transformed in 2-D Fourier tansform operation. The images processed were corrected by using a variable weihting factor and the resulting images are shown in this paper. The method provides a useful way for solving the problem of correction of the SR in digital X-ray images.

Algorithms↗
PubMed1996

Delayed xenograft rejection in the concordant hamster heart into Lewis rat model.

The inability to provide an adequate supply of human organs for clinical transplantation has created a strong interest in the use of nonhuman, especially nonprimate, organs. The first biological obstacle confronting such discordant transplantations is a series of violent reactions that result in hyperacute rejection of the xenograft. Significant advances in controlling hyperacute rejection have been achieved recently through the generation of transgenic pig donors bearing human complement regulatory proteins. However, when hyperacute rejection is averted, the xenografts are rejected in 2-70 days in spite of high-dose immunosuppression, by a process collectively termed delayed xenograft rejection. Delayed xenograft rejection is characterized by a refractoriness to conventional immunosuppression, extensive xenoreactive antibody deposition, and cellular infiltration that is dominated by macrophages. We have examined the features of extended host and graft response in the concordant hamster-to-rat xenotransplant model, where such features have historically been obscured by early graft destruction. Hamster hearts transplanted into rats do not encounter hyperacute rejection but are rejected within 3-4 days when xenoreactive antibody titers rise exponentially to levels that elicit a classical antibody- and complement-mediated acute xenograft rejection. We have successfully blocked acute xenograft rejection by a combination of immunosuppressive agents, leflunomide, and cyclosporine. Stopping the immunosuppression resulted in graft rejection that is histologically characterized by extensive xenoreactive antibody deposition and cellular infiltration that is predominantly composed of macrophages. We have noted the similarities between the histopathology of rejection of long-surviving concordant xenografts and that described for discordant xenografts and refer to the process of rejection of concordant grafts that have escaped acute xenograft rejection, delayed xenograft rejection.

Acute Disease↗
PubMed1996

Granulocyte colony-stimulating factor immunomodulation in the rat cardiac transplantation model.

Granulocyte colony-stimulating factor (G-CSF) administration decreases tumor necrosis factor(TNF) release, an important mechanism in allograft rejection. to study G-CSF's possible antirejection effects, 30 Lewis rats underwent heart transplantation using Brown-Norway donors and were assigned varying dosages of recombinant human G-CSF (0, 20, 100, 250 and 500 microgram/kg/day) for 14 days following the operation. Recipients receiving 250 microgram/kg/day experienced an improvement in graft survival (12.3+/-4 days vs. 7.0+/-0.6 days, P>0.05, Breslow). In a separate cohort, G-CSF-treated recipients (250 microgram/kg/day x 14) killed at 2,4,and 6 days after transplantation revealed improved serial allograft biopsy grading scores versus untreated controls (P<0.001 stratified Wilcoxon). Significant reduction in serum TNF levels was noted in the G-CSF-treated animals (P<0.025, analysis of variance). These data describe a moderate antirejection effect of G-CSF administration. Inhibition of circulating TNF in the G-CSF-treated recipients may describe a marker or possible mechanism of this antirejection effect.

Animals↗
PubMed1996

Protective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice.

Diallyl sulfone (DASO2) is a metabolite of diallyl sulfide, a compound derived from garlic. The present study investigated the effect of DASO2 as a protective agent against acetaminophen (APAP)-induced hepatotoxicity in mice. Oral administration of DASO2 protected mice against the APAP-induced hepatotoxicity in a dose- and time-dependent manner. When administered 1 hour prior to, immediately after, or 20 minutes after a toxic dose of APAP, DASO2 at a dose of 25 mg/kg completely protected mice from development of hepatotoxicity, as indicated by liver histopathology and serum lactate dehydrogenase levels. Protective effect was observed when DASO2 at a dose as low as 5 mg/kg was given to mice 1 hour prior to APAP administration. Oral administration of DASO2 to mice 1 hour prior to a toxic dose of APAP significantly inhibited the APAP-induced glutathione depletion in the liver. DASO2 treatment also decreased the levels of oxidative APAP metabolites in the plasma without affecting the concentrations of nonoxidative APAP metabolites. In liver microsomes, 0.1 mM of DASO2 caused a 60% decrease in the rate of APAP oxidation to N-acetyl-p-benzoquinone imine, which was determined as glutathione conjugate. This inhibitory effect is mainly due to its inhibition of cytochrome P450 2E1 activity; with an IC50 value equal to 0.11 mM. DASO2 also slightly inhibited the activities of P450s 3A and 1A, with IC50 values > 5 mM. Furthermore, a single oral dose of DASO2 inactivated P450 2E1- and P450 1A-dependent activities in liver microsomes. The results suggest that the protective effect of DASO2 against APAP-induced hepatotoxicity is due to its ability to block acetaminophen bioactivation mainly by the inactivation and inhibition of P450 2E1.

Acetaminophen↗
PubMed1996

Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion.

BACKGROUND AND PURPOSE: In past studies, cerebral outcome after normothermic cardiac arrest of 10 or 12.5 minutes in dogs was improved but not normalized by resuscitative (postarrest) treatment with either mild hypothermia or hypertension plus hemodilution. We hypothesized that a multifaceted combination treatment would achieve complete cerebral recovery. METHODS: With our established dog outcome model, normothermic ventricular fibrillation of 11 minutes (without blood flow) was followed by controlled reperfusion (with brief normothermic cardiopulmonary bypass simulating low flow and low PaO2 of external cardiopulmonary resuscitation) and defibrillation at < 2 minutes. Controlled ventilation was provided to 20 hours and intensive care to 96 hours. Control group 1 (n = 8) was kept normothermic (37.5 degrees C), normotensive, and hypocapnic throughout. Experimental group 2 (n = 8) received mild resuscitative hypothermia (34 degrees C) from about 10 minutes to 12 hours (by external and peritoneal cooling) plus cerebral blood flow promotion with induced moderate hypertension, mild hemodilution, and normocapnia. RESULTS: All 16 dogs in the protocol survived. At 96 hours, all 8 dogs in control group 1 achieved overall performance categories 3 (severe disability) or 4 (coma). In group 2, 6 of 8 dogs achieved overall performance category 1 (normal); 1 dog achieved category 2 (moderate disability), and 1 dog achieved category 3 (P < .001). Final neurological deficit scores (0% [normal] to 100% [brain death]) at 96 hours were 38 +/- 10% (22% to 45%) in group 1 versus 8 +/- 9% (0% to 27%) in group 2 (P < .001). Total brain histopathologic damage scores were 138 +/- 22 (110 to 176) in group 1 versus 43 +/- 9 (32 to 56) in group 2 (P < .001). Regional scores showed similar group differences. CONCLUSIONS: After normothermic cardiac arrest of 11 minutes in dogs, resuscitative mild hypothermia plus cerebral blood flow promotion can achieve functional recovery with the least histological brain damage yet observed with the same model and comparable insults.

Animals↗
PubMed1996

[Changes of brain potentials related to visual attention during simulated weightlessness].

To study the possible effect of simulated weightlessness on brain function state, the brain event-related potentials (ERPs) during a simple visual selective response task were compared between head down tilt (HDT) and head up tilt (HUT) in 9 normal subjects. The results were: both the target (T) and non-target (NT) flash signals induced significant slow positive potentials which were supposed to be related to the attention activity; the amplitude of the positive potentials in the frontal regions decreased significantly especially for NT-ERPs during HDT as compared with that during HUT. The data provide new evidence indicating that the ability of brain response declined during simulated weightlessness and more attention should be paid to the study of brain function during space flight.

Attention↗
PubMed1996

Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms.

Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no-flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical-triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free-radical reactions, DNA cleavage, and transient extracerebral organ malfunction? For future mechanism-oriented studies of the brain after cardiac arrest and innovative cardiopulmonary-cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points.

Altitude Sickness↗
PubMed1996

Cerebral resuscitation from cardiac arrest: treatment potentials.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

Animals↗
PubMed1996

Resuscitative hypothermia.

Resuscitative (postinsult) hypothermia is less well studied than protective-preservative (pre- and intra-arrest) hypothermia. The latter is in wide clinical use, particularly for protecting the brain during cardiac surgery. Resuscitative hypothermia was explored in the 1950s and then lay dormant until the 1980s when it was revived. This change occurred through the discoveries of brain damage mitigating effects after cardiac arrest in dogs, and after forebrain ischemia in rats, of mild (34 degrees C) hypothermia (which is safe), and of benefits derived from moderate hypothermia (30 degrees C) after traumatic brain injury or focal brain ischemia in various species. The idea that protection-preservation or resuscitation by hypothermia is mainly explained by its ability to reduce cerebral oxygen demand has been replaced by an increasingly documented synergism of many beneficial mechanisms. Deleterious chemical cascades during and after these insults are suppressed even by mild hypothermia. Prolonged moderate hypothermia carries some risks, e.g., arrhythmias, infection and coagulopathies. These side effects need further study. In global brain ischemia, protective-preservative mild hypothermia provides lasting mitigation of brain damage. Resuscitative mild hypothermia, however, may be beneficial in terms of long-term outcome or may merely delay the inevitable loss of selectively vulnerable neurons. Even if the latter is true, mild hypothermia may extend the therapeutic window for other interventions. This extension of the therapeutic window requires further documentation. After normothermic cardiac arrest of 11 mins in dogs, mild resuscitative hypothermia from 15 mins to 12 hours after reperfusion plus cerebral blood flow promotion normalized functional recovery with the least histologic damage seen thus far. Optimal duration of, and rewarming methods from, resuscitative hypothermia need clarification. The earliest possible induction of mild hypothermia after cardiac arrest seems desirable. Head-neck surface cooling alone is too slow. Among many clinically feasible rapid cooling methods, carotid cold flush and peritoneal cooling look promising. After traumatic brain injury or focal brain ischemia, which seem to still benefit from even later cooling, surface cooling methods may be adequate. Resuscitative hypothermia after cardiac arrest, traumatic brain injury, or focal brain ischemia should be considered for clinical trials.

Animals↗