Major histocompatibility complex class II antigen expression is suppressed by estradiol in cardiac allografts.
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Animals↗
Biomedical subjects
Y N Wang
Publications and source records attributed to Y N Wang.
Inhibition of transplant coronary arteriosclerosis in rabbits by chronic estradiol treatment is associated with abolition of MHC class II antigen expression.
BACKGROUND: Accelerated coronary arteriosclerosis is a major complication in long-term survivors of cardiac transplantation. Estrogen prevents transplant arteriosclerosis in experimental cardiac and aortic allografts and may act by an immune mechanism. METHODS AND RESULTS: New Zealand White rabbits immunosuppressed with cyclosporine were recipients of cardiac allografts from Dutch Belted rabbits. The recipients received either estradiol or placebo daily until they were killed 6 weeks later. Histological cross sections of the cardiac allograft were used for quantification of major histocompatibility complex (MHC) class II antigen expression, T lymphocytes, and macrophages by immunohistochemistry using monoclonal antibodies. MHC class II antigen expression was not detectable in allograft coronary arteries from any of the estradiol-treated recipients, whereas this antigen expression was present in the allograft coronary arteries from all the placebo-treated recipients. Macrophage and lymphocyte infiltration of the allograft coronary artery myointima was significantly less frequent in the estradiol-treated group. Rejection was moderate but slightly less in the estradiol-treated group. These findings were associated with a 60% decrease in allograft coronary artery myointimal thickening (determined by morphometry) in the estradiol-treated compared with the placebo-treated group. CONCLUSIONS: Estradiol treatment of cardiac allograft recipients abolishes MHC class II antigen expression in the coronary arteries and decreases macrophage infiltration in all three layers of the vessel wall, whereas T-lymphocyte infiltration is decreased only in the myointima. These findings are associated with estradiol inhibition of myointimal proliferation. Thus, estradiol treatment may have a beneficial effect on graft arteriosclerosis through immune mechanisms.
Animals↗
[Population pharmacokinetics/pharmacodynamics of magnesium sulfate in pregnancy induced hypertensive gravidas treated with the drug].
NONMEM program was applied for analyzing population pharmacokinetics/pharmacodynamics of magnesium sulfate in pregnancy induced hypertensive patients treated with the drug. A 2-compartment open model with fast and slow consecutive intravenous infusion was used to estimate population pharmacokinetics from 60 patients. A 3-compartment model comprised an effect compartment linked to the central compartment, sigmoid Emax effect model and parametric method were used to estimate population pharmacodynamic parameters from 26 patients. Serum magnesium concentration was determined by spectrophotometric method ant it was adjusted with basic value determined before dosage. The diastolic blood pressure lowering effect was chosen as index of effect of cardiovascular response. The population pharmacokinetic parameters of magnesium sulfate were: the standard value of K10(h-1), K12(h-1), K21(h-1), and Vc(L.kg-1) were estimated to be 1.62, 20.8, 2.70, and 27.0, respectively. Their interindividual varibilities were estimated to be 25.70%, 14.13%, 24.33%, and 34.04%, respectively. The residual error of concentrations was 15.03%. The population pharmacodynamic parameters of magnesium sulfate were: the standard value of Emax (%), Ce(50) (microgram.ml-1), upsilon, and Keo (h-1) were estimated to be 28.73, 28.39, 4.22, and 0.43. Their interindividual variability were estimated to be 56.32%, 62.24%, 33.47% and 42.76%. The residual error of effect was 28.54%.
Adult↗
L-arginine prevents heart transplant arteriosclerosis by modulating the vascular cell proliferative response to insulin-like growth factor-I and interleukin-6.
BACKGROUND: L-arginine, a nitric oxide precursor, inhibits myointimal hyperplasia induced by balloon injury in native vessels. No studies are published on L-arginine effects on transplant arteriosclerosis. Insulin-like growth factor-I and interleukin-6 are mitogenic for smooth muscle cells and are involved in the cell-mediated and humoral immune response. METHODS: New Zealand White rabbits received cardiac allografts from Dutch Belted rabbits. All animals were fed a 0.5% cholesterol diet and received drinking water with (eight pairs) or without (eight pairs) L-arginine (2.5%) from day 7 to until they were killed at day 42. The recipients received cyclosporine A 10 mg/kg/day from transplantation until the time they were killed. RESULTS: Dietary L-arginine reduces myointimal hyperplasia in allograft coronary arteries from 44% +/- 4% in the non-L-arginine group to 16% +/- 2% (p < 0.002). The L-arginine significantly inhibits graft vascular cell proliferation induced by (1) insulin-like growth factor-I, from 328% +/- 66% to 154% +/- 28% (p < 0.05), (2) interleukin-6, from 376% +/- 97% to 138% +/- 30% (p < 0.05) and (3) the combination of insulin-like growth factor-I and interleukin-6 from 710% +/- 201% to 226% +/- 72% (p < 0.05). In recipient native aorta explants L-arginine also abolishes vascular cell proliferation stimulated by insulin-like growth factor-I and interleukin-6. The rejection grading is similar in the L-arginine (2.9 +/- 0.1) and control groups (2.7 +/- 0.1). Class II major histocompatibility antigen expression, T-lymphocyte, and macrophage infiltration in the cardiac allograft are unaffected by L-arginine. However, the diet significantly increased plasma nitric oxide from 15.4 +/- 2.3 to 45.1 +/- 11 mumol (p < 0.05). CONCLUSIONS: Dietary L-arginine attenuates transplant arteriosclerosis in vivo without affecting rejection. The protective effect seen in these experiments may relate to the generation of sufficient nitric oxide to prevent smooth muscle cell response to mitogens like insulin-like growth factor-I and interleukin-6.
Animals↗
Treatment of locally recurrent soft tissue sarcomas of the retroperitoneum: report of 30 cases.
To assess the results in treating locally recurrent soft tissue sarcomas of the retroperitoneum, we reviewed the clinical, therapeutic, and pathologic characteristics of 30 patients who underwent surgical exploration. Complete resection was achieved in 18 patients (60%), 6 with en bloc resection of adjacent organs involved by the tumors. Following the first operation for recurrent lesions, the median survival was 33 months for those undergoing complete resection and 14 months for those undergoing partial resection or biopsy (P = 0.04). Patients with a disease-free interval (DFI) of > 24 months were associated with better prognosis than those with DFI of < or = 24 months (median survival: 40 months vs. 17 months, P = 0.03). Patients with tumor size of < or = 20 cm had longer survival than those with tumor size of > 20 cm (median survival: 39 months vs. 23 months, P = 0.04). Among 14 patients who received adjuvant radiation therapy, four patients whose tumors had been considered unresectable at first exploration for recurrence underwent complete resection after preoperative radiation therapy. An aggressive surgery aimed at complete resection in treating recurrent retroperitoneal sarcomas is strongly recommended. We suggest that in large tumors preoperative radiation therapy should be used to reduce the tumor volume and therefore a higher rate of complete resection may be achieved.
Adult↗
Total pelvic exenteration for locally advanced rectal carcinoma.
Total pelvic exenteration was performed in 31 patients (30 males and 1 female) who had rectal cancers involving adjoining pelvic structures. Twenty-nine patients had primary tumors and two had recurrent diseases after previous abdominoperineal resection. Preoperative irradiation was used in nine patients with fixed tumors. When performing the surgical procedure, we also actively employed lateral node dissection to make the operation more radical. Three patients (one with primary tumor and two with recurrent) underwent the exenteration with partial sacrectomy because of the sacral involvement and they all died of local failure within 15 months. The overall 5-year survival rate was 52 percent for all patients and 56 percent for those who had primary tumors. The results suggest that total pelvic exenteration with lateral node dissection should be performed for locally advanced rectal cancer if the tumor is not completely fixed to the pelvic wall and preoperative irradiation should be used to convert a fixed tumor to a resectable one.
Adult↗
Effects of isoflurane on regional coronary blood flow and myocardial tissue pressure in chronically instrumented dogs.
BACKGROUND: The effects of isoflurane on distribution of transmural blood flow and transmural intramyocardial tissue pressure (IMP) were studied in chronically instrumented dogs, to address following aims: (1) to evaluate the direct effects of isoflurane on transmural blood flow distribution in the absence of compounding effects of baseline anesthetics, acute surgery, and indirect effects caused by changes in systemic blood pressures and heart rate--factors that were not well controlled in the past studies; (2) to examine the relation between transmural myocardial perfusion pressure and concurrent changes in transmural blood flow distribution during isoflurane anesthesia; and (3) to evaluate the effects of isoflurane on transmural myocardial oxygen supply-demand relation. METHODS: Dogs were allowed to recover at least 1 week after surgery for instrumentation. Blood flow of the left anterior descending coronary artery and subendocardial and subepicardial blood flows, regional IMPs, regional segmental dimension, heart rate, aortic pressure and left ventricular pressure were measured while dogs were awake and during 1.3% isoflurane anesthesia, with and without correction of heart rate and aortic pressure. Concurrently regional myocardial perfusion pressure, regional myocardial stroke work, and systolic pressure time index were calculated, based on direct measurements of IMP in subendocardium and subepicardium. RESULTS: Without correction of aortic pressure, neither left anterior descending coronary artery flow nor transmural blood flow distribution was altered with isoflurane. When aortic pressure and heart rate were corrected to the awake values, left anterior descending coronary artery flow increased (37 +/- 2%) and the increase was preferentially distributed to subendocardium, resulting in a shift in transmural blood flow. The subendocardial/subepicardial blood flow ratio increased from 1.2 +/- 0.3 to 1.4 +/- 0.4 (p, 0.05). The transmural blood flow changes were closely related to changes in regional myocardial perfusion pressure ratio between subendocardium and subepicardium (r = 0.76, P < 0.001). Concurrent with marked increases in blood flow (55 +/- 4% increase), regional myocardial stroke work and systolic pressure time index of subendocardium were decreased more than 50% with isoflurane, resulting in a favorable subendocardial oxygen supply-demand balance. CONCLUSIONS: Isoflurane is a coronary vasodilator and redistributes blood flow in favor of subendocardium and depresses subendocardial work when heart rate and aortic pressure are controlled. These changes in regional myocardial blood flow, regional myocardial stroke work, and systolic pressure time index appear to be a result of changes in regional IMP.
Animals↗
[Results of surgical treatment of recurrent retroperitoneal soft tissue sarcomas].
Thirty patients with locally recurrent retroperitoneal soft tissue sarcomas, whose primary tumors had been previously resected, were surgically treated. Complete resection was achieved in 18 patients (60%), of which 6 underwent en bloc resection of adjacent organs involved by the tumor. The overall 3- and 5-year survival rate for all patients was 39% and 14%, respectively. Survival at 3 and 5 years was 49% and 24% respectively for those undergoing complete resection, compared to 25% and 0% respectively for those undergoing partial resection or biopsy only (P < 0.005). An aggressive surgery aimed at complete resection. in treating recurrent retroperitoneal soft tissue sarcomas is strongly recommended. Prognostic value and clinical significance of factors such as disease-free interval, tumor size, and histologic type were discussed.
Adult↗
[The treatment of retroperitoneal soft tissue sarcomas an analysis or 110 cases].
We analyzed the treatment results of 110 patients with retroperitoneal soft tissue sarcomas. Liposarcoma (31.8%) was most common followed by leiomyosarcoma and malignant peripheral nerve sheath tumors (11.8% and 11.8%, respectively). Complete resection was performed in 56 patients (50.9%), of which 18 underwent reoperation for 2-4 times. Adjacent organs were included in 13 patients in the en bloc rejection. Overall 5-year survival rate was 55.6% for those undergoing complete resection, compared to 11.1% and 6.6% respectively for those undergoing partial resection and biopsy only (P < 0.001). 37.5% of patients survived 5 years after their recurrent tumors were completely resected. Adjuvant radiation therapy or chemotherapy failed to have significant impact on survival.
Adolescent↗
Effects of warm ischemia following harvesting of allograft cardiac valves.
The clinical use of cryopreserved allograft valves is rapidly increasing. Viability of valve leaflet fibroblasts has been proposed to be critical to durability. Harvesting of allograft valves involves variable warm ischemia times, defined as the time from cessation of donor heart beat to initial cooling for transport. This ischemic period has been implicated as one of the more critical periods of injury to leaflet cell, even though adequate characterization of this potentially injurious phase has never been accomplished. The present study was undertaken to characterize the metabolic response to warm ischemia in a porcine valve leaflet model. Valve handling was similar to clinical valve harvest and transport protocols. Injury was assessed by protein (1H) and phosphorus (31P) magnetic resonance spectroscopy of 224 porcine semilunar valves. Leaflets were analyzed over time for lactate accumulation and ATP degradation. A radiolabelled incubation assay (48 valves) was used to measure proline accumulation by fibroblasts. Electron microscopy was performed on 36 valves with varying warm ischemia times. ATP stores were entirely depleted after 2 h hypoxia (p less than 0.05). However, lactate continued to accumulate over 24 h. Although aerobic metabolism ceased after 2 h warm ischemia, anaerobic metabolism continued for up to 24 h, which may represent an extended window for harvesting fresh tissue for allograft valve implantation.
Adenosine Triphosphate↗
Big endothelin in plasma and amniotic fluid.
UNLABELLED: We previously demonstrated that endothelin-1 (ET-1) exists both in the peripheral circulation and the amniotic fluid (AF). The objects of the present study were (a) to measure the concentrations of ET-1 and big endothelin (big ET) in plasma and AF by radioimmunoassay (RIA) and (b) to characterize the molecular forms of endothelin in human AF by high-performance liquid chromatography (HPLC) coupled with RIAs. Plasma samples from healthy male and female volunteers, and AF samples from full-term and mid-trimester pregnant women were extracted by C18 cartridges. Big ET, like ET-1, exists both in plasma and in AF. Significant increases (p less than 0.01) of big ET and ET-1 in AF from mid-trimester to full-term pregnancy were observed. The reverse-phase HPLC elution profile of immunoreactive (ir-) ET-1 presented a single major peak at a position corresponding to that of the standard ET-1 in the extracted AF. Two major components of ir-big ET were revealed: one corresponded to the elution position of standard big ET; the other one to that of the standard endothelin fragment [22-38] (EF). IN CONCLUSION: (a) Three molecular forms of ET exist in AF: ET-1 as a major form, big ET, and EF. (b) ET-1 and big ET are both present in higher concentrations in AF at full-term pregnancy than during mid-trimester.
Adult↗
Hexaheme nitrite reductase from Desulfovibrio desulfuricans. Mössbauer and EPR characterization of the heme groups.
Mössbauer and EPR spectroscopy were used to characterize the heme prosthetic groups of the nitrite reductase isolated from Desulfovibrio desulfuricans (ATCC 27774), which is a membrane-bound multiheme cytochrome capable of catalyzing the 6-electron reduction of nitrite to ammonia. At pH 7.6, the as-isolated enzyme exhibited a complex EPR spectrum consisting of a low-spin ferric heme signal at g = 2.96, 2.28, and 1.50 plus several broad resonances indicative of spin-spin interactions among the heme groups. EPR redox titration studies revealed yet another low-spin ferric heme signal at g = 3.2 and 2.14 (the third g value was undetected) and the presence of a high-spin ferric heme. Mössbauer measurements demonstrated further that this enzyme contained six distinct heme groups: one high-spin (S = 5/2) and five low-spin (S = 1/2) ferric hemes. Characteristic hyperfine parameters for all six hemes were obtained through a detailed analysis of the Mössbauer spectra. D. desulfuricans nitrite reductase can be reduced by chemical reductants, such as dithionite or reduced methyl viologen, or by hydrogenase under hydrogen atmosphere. Addition of nitrite to the fully reduced enzyme reoxidized all five low-spin hemes to their ferric states. The high-spin heme, however, was found to complex NO, suggesting that the high-spin heme could be the substrate binding site and that NO could be an intermediate present in an enzyme-bound form.
Desulfovibrio↗
Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans.
Recent interest has focused on the potential role of amylin in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). This 37-amino acid peptide is found in extracellular amyloid deposits in approximately 50% of pancreatic islets of patients with NIDDM and has been shown to inhibit skeletal muscle glycogen synthesis in vitro. Immunocytochemical studies have colocalized amylin and insulin within beta-cell secretory granules in nondiabetic humans, provoking the following questions. Is amylin cosecreted with insulin? Are circulating amylin concentrations higher in patients with NIDDM either before or after food ingestion? To answer these questions, we developed a sensitive and specific immunoassay to measure plasma concentrations of amylin in humans. Use of this assay indicated that, in lean nondiabetic subjects, glucose ingestion resulted in an increase (P less than 0.001) in the plasma concentration of amylin (from 2.03 +/- 0.22 to 3.78 +/- 0.39 pM) and insulin (from 48.3 +/- 3.1 to 265 +/- 44 pM). There was a significant correlation between the concentrations of insulin and amylin (r = 0.74, P less than 0.001) and the increase in insulin and amylin concentration (r = 0.65, P less than 0.005). Fasting concentrations of amylin did not differ in diabetic and weight-matched nondiabetic subjects and showed a similar pattern of change after ingestion of a mixed meal. We conclude that amylin is secreted in response to ingestion of either glucose or a mixed meal and circulates at concentrations that do not differ in patients with NIDDM and nondiabetic subjects. It remains to be determined whether amylin at physiological concentrations influences carbohydrate metabolism and if so whether its effects differ in diabetic and nondiabetic humans.
Adult↗
[Hydroxyapatite ceramic (HAC) used as transmucosal endosseous implant material in dogs].
Twenty-six HAC implants were implanted in the mandible of 7 male mongrel dogs. Of the 26 HAC implants, 22 were supramergible implants penetrating the gingiva, and the other 4 were the submergible ones completely covered by the gingiva. Clinically and radiographically, all survival supramergible implants were in favorable status every one, three, and five months respectively after implantation. Histologically, the direct contact with the bone of supramergible implants was later than that of submergible ones at apical portion, because of mastication force. Transmission electron microscope showed that the epithelial cells were attached to HAC implants via hemidesmosomes and a basement lamina. The authors think that HAC is an excellent coating material for the composite implants.
Animals↗
[Hepatic proliferation factor of human fetus liver cells].
It was demonstrated in this study that after ultrasonification and centrifugation of human fetus liver cells the supernatant could increase the incorporation of 3H-TdR into DNA of mice liver cells approximately 2.57 times than that of control. This proliferation effect is not species-specific, but has a relationship with supernatant content. The maximal promotion of 3H-TdR into DNA of the guinea-pig liver cells took place when the supernatant protein content was about 0.55 mg/ml. The supernatant can be divided into four components by Ultrogel A6 chromatography and the fourth component is the dominant both in protein content and in proliferation activity. SDS-polyacrylamide gel electrophoresis showed that its molecular weight is about 15,000 dalton.
Animals↗
[Diagnostic value of ratio of serum hCG level to CSF in the brain metastasis of choriocarcinoma].
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Brain Neoplasms↗
Comparative immunohistochemical demonstration of peptide F- and other enkephalin-containing neurons in the enteric nervous system of the rat.
The immunohistochemical localization of peptide F and the related enkephalins met5-enkephalin (met-enk), leu5-enkephalin (leu-enk), met5-enkephalin-arg6-phe7 (met-enk-arg-phe), and met5-enkephalin-arg6-gly7-leu8 (met-enk-arg-gly-leu) was investigated by means of the indirect immunofluorescence technique in the enteric nervous system of the rat. Peptide F-like immunoreactivity was widely distributed within neuronal structures throughout the gastrointestinal (GI) tract of the rat. Peptide F-containing nerve cell bodies were mainly located in the myenteric plexus, and only rarely were seen in the submucosal plexus. Peptide F-immunoreactive nerve fibers were principally present in the myenteric plexus and circular muscle layer; few were found in the submucosal plexus, longitudinal muscle layer, muscularis mucosa, and mucosa. No peptide F-containing fibers were found associated with blood vessels in the gut. By comparing the distribution of immunoreactive peptide F with other related enkephalins met-enk, leu-enk, met-enk-arg-phe, and met-enk-arg-gly-leu, we observed that there was a remarkable similarity in the distribution of peptide F and other enkephalins in the GI tract. These data, combined with our previous studies, indicate that peptide F may coexist with other related enkephalins in the same neurons of the enteric nervous system. The results suggest that peptide F, a product of the proenkephalin A gene, may play a physiological role within the enteric nervous system.
Animals↗
Distribution and characterization of the opioid octapeptide met5-enkephalin-arg6-gly7-leu8 in the gastrointestinal tract of the rat.
The distribution and characterization of the opioid octapeptide met5-enkephalin-arg6-gly7-leu8 (met5-enk-arg6-gly7-leu8) within the gastrointestinal tract of the rat has been determined by immunohistochemistry and radioimmunoassay by use of a newly developed antibody to met5-enk-arg6-gly7-leu8. With both techniques, met5-enk-arg6-gly7-leu8-immunoreactivity (met5-enk-arg6-gly7-leu8-IR) was detected in all regions of the gastrointestinal (GI) tract except the esophagus. The highest concentration of immunoreactive met5-enk-arg6-gly7-leu8 was observed in the colon, while intermediate concentrations were found in the stomach, duodenum, jejunum, and ileum. Immunostained somata were observed chiefly in the myenteric plexus; immunostained processes were present primarily in the myenteric plexus and the circular muscle layer. This distribution pattern is similar to that previously observed with antiserum to met5-enkephalin-arg6-phe7 (met5-enk-arg6-phe7). Chromatographic analysis of met5-enk-arg6-gly7-leu8-immunoreactive peptides extracted from the GI tract revealed the presence of an immunoreactive peptide of high molecular weight which accounted for approximately three-quarters of met5-enk-arg6-gly7-leu8-IR in both stomach and colon. These findings suggest a role for peptides related to the octapeptide met5-enk-arg6-gly7-leu8 in the regulation of GI function.
Animals↗