Biomedical subjects

S He

Publications and source records attributed to S He.

At least 163 records · Page 9Linked to original sources

PubMed1998

Identification of the active site nucleophile in jack bean alpha-mannosidase using 5-fluoro-beta-L-gulosyl fluoride.

Mannosidases play a key role in the processing of glycoproteins and thus are of considerable pharmaceutical interest and indeed have emerged as targets for the development of anti-cancer therapies. Access to useful quantities of the mammalian enzymes has not yet been achieved; therefore, jack bean mannosidase, a readily available enzyme, has become the model system. However, the relevance of this enzyme has not been demonstrated, nor is anything known about the active site structure of this, or any other, mannosidase. Hydrolysis by this enzyme occurs with net retention of sugar anomeric configuration; thus, a double displacement mechanism involving a mannosyl-enzyme intermediate is presumably involved. Two new mechanism-based inhibitors, 5-fluoro-alpha-D-mannosyl fluoride and 5-fluoro-beta-L-gulosyl fluoride, which function by the steady state trapping of such an intermediate, have been synthesized and tested. Both show high affinity for jack bean alpha-mannosidase (Ki' = 71 and 86 microM, respectively), and the latter has been used to label the active site nucleophile. The labeled peptide present in a peptic digest of this trapped glycosyl-enzyme intermediate was identified by neutral loss scans on an electrospray ionization triple quadrupole mass spectrometer. Comparative liquid chromatographic/mass spectrometric analysis of peptic digests of labeled and unlabeled enzyme samples confirmed the unique presence of this peptide of m/z 1180.5 in the labeled sample. The label was cleaved from the peptide by treatment with ammonia, and the resultant unlabeled peptide was purified and sequenced by Edman degradation. The peptide identified contained only one candidate for the catalytic nucleophile, an aspartic acid. This residue was contained within the sequence Gly-Trp-Gln-Ile-Asp-Pro-Phe-Gly-His-Ser, which showed excellent sequence similarity with regions in mammalian lysosomal and Golgi alpha-mannosidase sequences. These mammalian alpha-mannosidases belong to family 38 (or class II alpha-mannosidases) in which the Asp in the above sequence is totally conserved. This finding therefore assigns jack bean alpha-mannosidase to family 38, validating it as a model for other pharmaceutically interesting enzymes and thereby identifying the catalytic nucleophile within this family.

Amino Acid Sequence↗

PubMed1998

Apoptosis in surgically excised choroidal neovascular membranes in age-related macular degeneration.

BACKGROUND: Choroidal neovascular membranes (CNVMs) in age-related macular degeneration show progressive histologic changes from active, cellular, highly vascularized membranes to inactive paucicellular scars. The purpose of this study was to determine whether apoptosis was involved in the evolution of these changes, what cell types are involved, and whether there was an association with the Fas antigen (Fas or CD95) and Fas ligand (FasL). METHODS: Serial frozen sections from 10 surgically excised CNVMs were stained by the TUNEL (terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine 5-triphosphate nick-end labeling) method for detection of DNA strand breaks and by propidium iodide staining for morphologic detection of apoptosis. Immunoperoxidase staining was used for detection of Fas, FasL, and cell-type specific antigens. RESULTS: Highly vascularized membranes contained cells with TUNEL-positive nuclei, particularly in the regions of neovascularization, while fibrotic membranes showed few, if any, TUNEL-positive cells. Many of the TUNEL-positive cells were stromal retinal pigment epithelial cells, although smaller numbers were identified as endothelial cells and macrophages. Confocal microscopy of propidium idoide-stained sections confirmed the presence of apoptotic nuclei. The extent of Fas antigen expression correlated with extent of apoptosis. FasL expression was found in all specimens but was most intense in the highly vascularized membranes. CONCLUSIONS: Highly vascularized CNVMs related to age-related macular degeneration show apoptosis in stromal retinal pigment epithelial cells, endothelial cells, and occasional macrophages. Apoptosis is associated with prominent Fas and FasL expression.

Aged↗

PubMed1998

Contrast-modulation flicker: dynamics and spatial resolution of the light adaptation process.

We report a perceptual phenomenon that originates from a nonlinear operation during the visual process, and we use these observations to study the functional organization of the responsible nonlinearity; the regulation of visual sensitivity to light. When the contrast of a high frequency grating was modulated while its spatial and temporal average luminance was kept constant, observers saw brightness changes or desaturation in the field. If the contrast was modulated periodically between zero and a peak value, observers saw vivid flicker (contrast-modulation flicker), and this flicker could be seen even when the grating was too fine to be visually resolved as a pattern. This uniform-field flicker can be nulled by a modulation of space-average luminance at the contrast-modulation frequency, with appropriate phase and modulation depth. Contrast-modulation flicker is still measurable with gratings at 100 cycles/deg. The dynamics of contrast-modulation flicker suggest that it results from an early sensitivity-controlling mechanism, acting very rapidly (within about 20 msec). Its dependence on stimulus spatial frequency implies a strictly local luminance nonlinearity, one that either resides within individual photoreceptors or operates on signals from individual receptors.

Adaptation, Ocular↗

PubMed1998

Local nonlinearity in S-cones and their estimated light-collecting apertures.

When an high frequency grating of high retinal contrast is presented intermittently by modulating its contrast at constant average luminance, observers experience uniform field flicker, even if the grating is too fine to be resolved. For long and middle wavelength cones, this contrast-modulation flicker can be seen for fringe periods as small as the diameter of a cone [MacLeod & He (1993). Nature, 361, 256-258], implying no substantial neural spatial integration prior to the nonlinear site. We now report that the short-wavelength cone system, despite its greater spatial integration than the other cone systems, can generate contrast-modulation flicker at spatial frequencies as high as 50 cycles/deg, a value comparable with that of the other cone systems in the same retinal area. Spatial resolution at the nonlinear site is in all cases apparently limited by the size of the cones. Likewise, little temporal filtering (in the range up to 18 Hz) precedes the S-cone nonlinearity. This suggests that the reduced S-cone system sensitivity for rapid flicker is due to postreceptoral limitations.

Adaptation, Ocular↗

PubMed1998

Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering.

OBJECTIVES: We tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering. BACKGROUND: Competing hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow. METHODS: Diastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpson's method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation. RESULTS: The diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r2 = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm2, p = NS). CONCLUSIONS: Patients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients with IMLC that can restrict both diastolic opening and systolic closure.

Adult↗

PubMed1998

Estimation of mitral regurgitation with a hemielliptic curve-fitting algorithm: in vitro experiments with native mitral valves.

To date, studies on the mitral flow convergence method have used rigid, circular, or slit orifices to represent the regurgitant orifice. In this study, explanted porcine mitral valves, with the entire mitral apparatus preserved, were mounted in an in vitro model to reproduce the three-dimensional regurgitant orifice geometry while permitting close control and measurement of the experimental conditions. This experimental setup permitted the evaluation of the hemispheric and hemielliptic formulas under realistic physiologic conditions. In this study, a heart rate of 70 beats/min was used with cardiac outputs between 1.5 and 6 L/min. Peak regurgitant flow rates ranged from 7 to 16 L/min (regurgitant jet velocities ranged from 2 to 5.5 m/sec); peak aortic flow rates ranged from 9 to 30 L/min. Four native mitral valves were used for these studies for a total of 28 stages. Although the hemielliptic modification has previously shown success in vitro and computationally, it has not been used clinically because of difficulty imaging the flow convergence region in three orthogonal planes. A curve-fitting algorithm was developed to extract the hemielliptic dimensions from two standard ultrasound views by rotating the transducer 90 degrees. Improved agreement was obtained between true and calculated flow rates by the hemielliptic formula (y = 1.02 x + 0.29; r = 0.91) compared with the hemispheric formula (y = 1.18 x - 2.2; r = 0.66). This method provides accurate results with a realistic three-dimensional regurgitant orifice geometry and has the capability of being incorporated as a function key on an ultrasound machine for clinical application.

Algorithms↗

PubMed1998

Development of novel 19F NMR pH indicators: synthesis and evaluation of a series of fluorinated vitamin B6 analogues.

We have synthesized a series of novel fluorinated vitamin B6 analogues (6-fluoropyridoxol derivatives) as potential 19F NMR pH indicators for use in vivo. Modifications included addition of aldehyde, carboxyl or aminomethyl groups at the 4- or 5-ring position, and examination of a trifluoromethyl moiety as an internal chemical shift standard. The variation in chemical shift with respect to acid-base titration showed pKa values in the range 7.05-9.5 with a chemical shift sensitivity in the range 7.4-12 ppm. Several of the molecules readily cross cell membranes providing estimates of both intra- and extra-cellular pH in whole blood. 6-Fluoropyridoxamine (6-FPAM) exhibits a pKa = 7.05, which is closer to normal physiological pH than the parent molecule 6-fluoropyridoxol (6-FPOL) (pKa = 8.2), and should thus, be useful for precise and accurate measurements of pH in vivo. Enhanced spectral resolution for 6-FPAM over 6-FPOL is demonstrated in whole blood and the perfused rat heart.

Animals↗

PubMed1998

Electron-beam CT angiography with three-dimensional reconstruction in the evaluation of coronary artery bypass grafts.

RATIONALE AND OBJECTIVES: The authors evaluated the use of electron-beam computed tomographic (CT) angiography and three-dimensional (3D) reconstruction for evaluation of coronary artery bypass grafts (CABGs). MATERIALS AND METHODS: Sixty patients (53 men and seven women; mean age, 56 years +/- 8) with 152 CABGs (29 internal mammary artery and 123 saphenous vein grafts) underwent electron-beam CT with 3D reconstruction. The time from bypass surgery to CT scanning was 7 days to 120 months (mean, 17 months +/- 28). Enhanced single-section and flow mode studies were performed in all cases. The results were correlated with CABG operation records, and patency was determined with time-attenuation curves. RESULTS: All patients were successfully examined. On the basis of time-attenuation curve criteria, 124 (81.6%) of 152 grafts were patent. The patency rate for the internal mammary artery subgroup was 93% (27 of 29 grafts); for the saphenous vein graft subgroup, 78.9% (97 of 123 grafts). CONCLUSION: Used in contrast-enhanced, single-section mode and flow studies with time-attenuation curves, electron-beam CT angiography with 3D reconstruction can provide quantitative data for evaluation of CABG patency.

Adult↗

PubMed1998

Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo.

The roles of chymase in acute allergic responses are not clear, despite the relative abundance of this serine proteinase in the secretory granules of human mast cells. We have isolated chymase to high purity from human skin tissue by heparin-agarose affinity chromatography and Sephacryl S-200 gel filtration procedures, and have investigated the ability of human mast cell chymase to stimulate cell accumulation following injection into laboratory animals. Injection of chymase provoked marked neutrophilia and eosinophilia in the skin of Dunkin Hartley guinea-pigs. Compared with saline injected control animals, there were some 60 fold more neutrophils and 12 fold more eosinophils present at the injection site. Following injection of chymase into the peritoneum of BALB/c mice, there were up to 700 fold more neutrophils. 21 fold more eosinophils, 19 fold more lymphocytes and 7 fold more macrophages recovered than from saline injected controls at 16 h. Doses of chymase as low as 5 ng (1.7 x 10(-13) mole) stimulated an inflammatory infiltrate, and significant neutrophilia was elicited within 3 h. The chymase induced cell accumulation in both the guinea-pig and mouse models was dependent on an intact catalytic site, being reduced by co-injection of proteinase inhibitors or heat inactivation of the enzyme. Co-injection of histamine or heparin significantly reduced the chymase induced neutrophil accumulation, whereas neither histamine nor heparin by themselves had any effect on the accumulation of nucleated cells. No synergistic or antagonist interactions between chymase and tryptase were observed when these two major mast cell proteinases were co-injected into the mouse peritoneum. Our findings suggest that chymase may provide an potent stimulus for inflammatory cell recruitment following mast cell activation.

Animals↗

PubMed1998

Long-term cryopreservation: successful trilineage engraftment after autologous bone marrow transplantation with bone marrow cryopreserved for seven years.

Successful autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation depend on safe hematopoietic stem cell (HSC) cryopreservation and storage. Several successful methods for cryopreservation and storage have been established and are commonly used all over the world. However, little is known about the effects of long-term cryopreservation on the capacity to sustain a complete immunohematopoietic engraftment. Several authors have investigated stem cell viability after cryopreservation and storage for more than 5 years and reported preclinical good viabilities in terms of dye-exclusion or colony-forming capability in vitro. Only two studies using BM cryopreserved for more than 5 years for transplantation are reported, but they did not provide proof of trilineage engraftment. In February 1997 at our institution, a patient with relapsed non-Hodgkin's lymphoma underwent ABMT with BM harvested in February 1990. He achieved a granulocyte count > 500 x 10(6)/L on day 21 and a self-supporting platelet count > 20 x 10(9)/L on day 30. After day 29, his hemoglobin level was satisfactory without need of transfusion support. This successful trilineage engraftment with cryopreserved BM that had been stored for 7 years suggests that HSC are able to maintain their capability to reconstitute hematopoiesis for a long time.

Bone Marrow↗

PubMed1998

Cloning and bacterial expression of sesquiterpene cyclase, a key branch point enzyme for the synthesis of sesquiterpenoid phytoalexin capsidiol in UV-challenged leaves of Capsicum annuum.

Sesquiterpene cyclase, a branch point enzyme in the general isoprenoid pathway for the synthesis of phytoalexin capsidiol, was induced in detached leaves of Capsicum annuum (pepper) by UV treatment. The inducibility of cyclase enzyme activities paralleled the absolute amount of cyclase protein(s) of pepper immunodetected by monoclonal antibodies raised against tobacco sesquiterpene cyclase. A cDNA library was constructed with poly(A)+ RNA isolated from 24 h UV-challenged leaves of pepper. A cDNA clone for sesquiterpene cyclase in pepper was isolated by using a tobacco 5-epi aristolochene synthase gene as a heterologous probe. The predicted protein encoded by this cDNA was comprised of 559 amino acids and had a relative molecular mass of 65,095. The primary structural information from the cDNA clone revealed that it shared 77%, 72% and 49% identity with 5-epi aristolochene, vetispiradiene, and cadinene synthase, respectively. The enzymatic product catalyzed by the cDNA clone in bacteria was identified as 5-epi aristolochene, as judged by argentation TLC. RNA blot hybridization demonstrated the induction of an mRNA consistent with the induction of cyclase enzyme activity in UV-treated pepper.

Amino Acid Sequence↗

PubMed1998

Frequency series expansion of an explicit solution for a dipole inside a conducting sphere at low frequency.

The electromagnetic field generated by a current dipole situated at an arbitrary position inside a conducting sphere is derived using the expansions of the spherical vector wave functions. The first few terms in a series expansion of this field with respect to the frequency are given for the normal magnetic field (used in magnetoencephalogram) and the tangential electric field (used in electroencephalogram) outside the conducting sphere at low frequency. It is shown that the first correction term to the static solution is linear in the frequency omega (the second correction term is proportional to omega 3/2) and, thus, the static solution can be used as a good approximation for the solution at a very low frequency.

Brain↗

PubMed1998

Stepwise recruitment of components of the preinitiation complex by upstream activators in vivo.

Recently, it was found that if either the TATA binding protein or RNA polymerase II holoenzyme is artificially tethered to a promoter, transcription is activated. This finding provided presumptive evidence that upstream activating proteins function by recruiting components of the preinitiation complex (PIC) to the promoter. To date, however, there have been no studies demonstrating that upstream factors actually recruit components of the PIC to the promoter in vivo. Therefore, we have studied the mechanism of action of two disparate transactivating domains. We present a series of in vivo functional assays that demonstrate that each of these proteins targets different components of the PIC for recruitment. We show that, by targeting different components of the PIC for recruitment, these activating domains can cooperate with each other to activate transcription synergistically and that, even within one protein, two different activating subdomains can activate transcription synergistically by cooperating to recruit different components of the PIC. Finally, considering our work together with previous studies, we propose that certain transcription factors both recruit components of the PIC and facilitate steps in transcriptional activation that occur subsequent to recruitment.

Cells, Cultured↗

PubMed1998

A quantitative competitive reverse transcription-polymerase chain reaction technique to measure porcine interferon-gamma.

In swine, as in other mammals, interferon-gamma (IFN-gamma) plays an important role in the regulation of the immune response. The objective of this work was to develop a sensitive, quantitative competitive reverse transcription-polymerase chain reaction (qcRT-PCR) assay, using an internal cRNA standard, to monitor the expression of porcine IFN-gamma gene. We applied this qcRT-PCR assay to quantify the expression of IFN-gamma transcripts in peripheral blood mononuclear cells (PBMC) incubated for different times with or without concanavalin A (ConA). Results showed that the expression of the IFN-gamma transcripts in PBMC occurred within the first 2 h after mitogenic stimulation and reached a peak after 24 h of incubation with ConA. The qcRT-PCR technique provides an efficient and sensitive tool for studying the expression of porcine IFN-gamma gene under a variety of experimental conditions. This will help to understand the regulation of T cell-mediated immune responses by IFN-gamma at the gene level.

Animals↗

PubMed1998

Preparation and characterization of monoclonal antibody against recombinant human tissue factor pathway inhibitor.

OBJECTIVE: To prepare and identify monoclonal antibody (McAb) against recombinant human tissue factor pathway inhibitor (rhTFPI) and to use it for measurement of TFPI by ELISA, and to evaluate the effects of the McAb on dilute prothrombin time (PT) and activated partial thromboplastin time (APTT). METHODS: After intrasplenic immunization of Balb/c mouse with TFPI, hybridoma technique was used to raise monoclonal antibody against rhTFPI. The McAb was well-characterized and labelled with horseradish peroxidase (HRP) by using assay of TFPI in ELISA. Furthermore, the McAb was added to normal and factor IX deficient plasma for observation of dilute PT and APTT. RESULTS: Two hybridomas (4F4, 4F8) secreting McAb against TFPI were established. The Ig class and subclass of the McAb purified from 4F8 was IgG1. Immunoblotting results indicated that the McAb4F8 only recognized a single band of TFPI with molecular weight of 34.8 KD. The results of Sandwich enzyme-linked immunosorbent assay (ELISA) by using the HRP labelled McAb4F8 showed that the mean of TFPI in normal human plasma is 103.2 +/- 11.5 micrograms/L. The McAb 4F8 was also proved to shorten markedly dilute prothrombin time of factor IX deficient plasma and normal plasma. CONCLUSIONS: We established two hybridomas cell lines (4F4, 4F8) and obtained the McAb4F8 against TFPI and reported the levels of TFPI in healthy adult human plasma by Sandwich ELISA with HRP labelled McAb4F8 in Chinese.

Animals↗

PubMed1998

Three-dimensional reconstruction of electron beam computed tomography angiography for evaluating coronary artery bypass grafts.

OBJECTIVES: To probe into electron beam computed tomography (EBCT) angiography and 3-D reconstruction of coronary artery bypass grafts (CABG) and to evaluate the clinical application of EBCT angiography and 3-D reconstruction of CABG. METHODS: EBCT angiography with 3-D reconstruction was achieved in 150 patients (142 men and 8 women, mean age, 57 +/- 8 years) with 399 grafts including 100 internal mammary artery grafts (IMG), 296 saphenous vein grafts(SVG) and 3 radial artery grafts (RAG) respectively. The time from bypass surgery to EBCT scanning ranged from 7 days to 120 months, averaging 15 +/- 28 months. Enhanced single slice mode (SSM) and flow studies were performed in all patients. The results of 3-D reconstruction of CABG were compared with bypass operation records and with coronary arteriograms (7 patients). RESULTS: 150 patients underwent successfully EBCT angiography and CABG 3-D reconstruction. According to 3-D reconstruction of the coronary bypass grafts with flow studies, 318 of 399 coronary bypass grafts were patent including IMG patency in 87/100 (87%), SVG in 228/296 (77%) and RAG in 3/3 (100/100). The overall patent rate was 79.7%. In 7 patients with 12 coronary bypass grafts, EBCT studies showed graft patency (7 grafts) and occlusion (5), which were confirmed by conventional graft angiography. CONCLUSIONS: EBCT angiography with 3-D reconstruction is effective in providing the entire anatomic structure of coronary bypass grafts and evaluating coronary bypass graft patency. EBCT flow study can provide quantitative data for evaluating coronary bypass graft patency and for supplemental diagnosis of CABG 3-D reconstruction. EBCT angiography is a noninvasive technique that could replace conventional coronary arteriography for follow-up survey of coronary bypass surgery in future.

Adult↗

PubMed1998

Effects of proglumide, a gastrin receptor antagonist, on human large intestine carcinoma SW480 cell line.

OBJECTIVE: To explore the effects of proglumide, a gastrin receptor antagonist, on the amount of viable cells, synthesis of DNA and protein, and cell proliferation cycle in human large intestine carcinoma SW480 cell line in order to provide experimental basis for treatment of large intestine carcinoma using proglumide. METHODS: Large intestine carcinoma SW480 cells at logarithmic growth stage were cultivated with different concentrations of proglumide for different periods of time, then the amount of viable cells was determined by MTT colorimetric analysis. The SW480 cells were cultivated with proglumide, pentagastrin, proglumide + pentagastrin for the same period of time, then the contents of DNA and protein and the cell proliferation cycle were determined by flow-cytometry. RESULTS: The amount of viable cells, synthesis of DNA and protein, distribution of cell cycle, and proliferation index (PI) in the proglumide group did not differ significantly from those in the pentagastrin group (P > 0.05). The amount of viable cells in the pentagastrin group was significantly higher than that in the pentagastrin group (P < 0.01). In the proglumide + pentagastrin group the amount of viable cells, synthesis of DNA and protein, amount of S and G2M phase cells, and PI were all significantly lower than those in the pentagastrin group (all P < 0.01), and the amount of G0/G1 phase cells was significantly higher than that in the pentagastrin group (P < 0.01), but none of the above differed from those in the control group (all P > 0.05). CONCLUSIONS: Proglumide has no obvious effect on the growth of human large intestine carcinoma SW480 cell line, but can inhibit the growth-promoting effect of pentagastrin on large intestine carcinoma cells. The mechanism may be that proglumide inhibits the promoting effect of pentagastrin on the synthesis of DNA and protein of carcinoma cells, and then inhibits carcinoma cell growth from G0/G1 phase to S and G2M phase.

Antineoplastic Agents↗

PubMed1998

Experimental study on liver microcirculation disturbance following transplantation and the protective effect of prostaglandin E1 in the rat.

OBJECTIVE: To determine the effect of PGE1 on liver microcirculation disturbance following orthotopic liver transplantation in rats. METHODS: Forty male adult Wistar rats were divided randomly into 3 groups. Eight transplantations were established in both the experimental and control group, while in the sham group, the liver was dissected like in the experimental group, but no resection was performed. In the experimental group, PGE1(0.5 microgram/kg.min-1) was injected intravenously into the donor before the operation, and added (1 mg/L) to the flush and preservation fluid, while PGE1 was replaced by normal saline in the control group. Confocal laser scan microscopy, biochemical test, and optical and electronic microscopy were used. RESULTS: In the control group the reperfusion state was poor, leukocyte infiltration appeared in the center of lobule, and transaminase rose after transplantation. In the experimental group distinctive improvement was seen as compared with the control group (P < 0.05). Histological findings showed progressive degeneration and necrosis following transplantation in the control group, while in the experimental group the histological changes were improved to some degree by the use of PGE1. CONCLUSIONS: In liver transplantation, ischemic reperfusion damage may lead to hepatic microcirculation disturbance, which is the major cause of graft failure. Infusing PGE1 into the donor intravenously before ischemia and adding PGE1 to the cold storage fluid could improve hepatic microcirculation, and thus reducing ischemic reperfusion damage in liver transplantation.

Alprostadil↗