IL-1 increases the ability of human endothelial cells to transform linoleic acid into monohydroxy-isomers and their incorporation into cell lipids.
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Carbon Radioisotopes↗
Biomedical subjects
M Camacho
Publications and source records attributed to M Camacho.
Phase II clinical trial with 5-fluorouracil, recombinant interferon-alpha-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus.
BACKGROUND: Recombinant interferon-alpha (IFN) augments the cytotoxicity of both 5-fluorouracil (5-FU) and cisplatin in vitro. A phase II study of 5-FU and IFN resulted in response rates of 25-27% in patients with metastatic esophageal carcinoma. METHODS: A Phase II trial was initiated to determine the clinical utility of a three-drug combination (FIP) in patients with regionally advanced or metastatic esophageal carcinoma. Eligibility included biopsy-proven Stage III or IV squamous cell carcinoma or adenocarcinoma of the esophagus with no prior chemotherapy, adequate performance status, nutritional status, bone marrow, hepatic and renal function, and signed informed consent. Patients were treated in the exact sequence of IFN==>cisplatin==>5-FU. Patients received 5-FU, 750 mg/m2/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/m2 on Day 1, followed by weekly therapy, 25 mg/m2 over the course of 1 hour; and IFN, 10 MU subcutaneously 3 times/week beginning on Day 1. All patients received sargramostim (granulocyte-macrophage colony-stimulating factor, Escherichia coli-derived), 5 micrograms/kg subcutaneously 5 times/week. No patients received radiotherapy. RESULTS: Twenty-four patients were enrolled; 23 were eligible, and 1 was excluded on pathology review (patient was found to have a leiomyoblastoma). The demographics of the population were: median age, 63 years (range, 43-73 years); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 22:1, and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institute Common Toxicity Criteria toxicities included: leukopenia (13), thrombocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respectively. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65%; 95% confidence interval, 43%, 85%) (1 complete response, 14 partial responses). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31%. CONCLUSIONS: This regimen, although moderately toxic, has substantial activity in metastatic and regionally advanced squamous cell carcinoma of the esophagus. Further investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma.
Adenocarcinoma↗
Routine use of unilateral and bilateral radial arteries for coronary artery bypass graft surgery.
OBJECTIVES: This study sought to evaluate the routine use of radial artery (RA) grafts in patients undergoing coronary artery revascularization. BACKGROUND: Previous long-term studies have documented poor patency of saphenous vein grafts compared with internal thoracic artery (ITA) grafts. METHODS: We performed a prospective review of 175 of 249 consecutive patients. RESULTS: Fifty-four patients had bilateral RAs harvested. Mean number (+/- SD) of grafts/patient was 3.27 +/- 0.93, with 2.76 +/- 0.97 arterial grafts; a mean of 1.53 +/- 0.68 grafts were performed with the RA. The operative mortality rate was 1.6%. No deaths were related to RA grafts, and there were no RA harvest site hematomas or infections. Transient dysesthesia 1 day to 4 weeks in duration occurred in the distribution of the lateral antebrachial cutaneous nerve in six extremities (2.6%). Elective cardiac catheterization in 60 patients at 12 weeks postoperatively demonstrated a 95.7% patency rate. CONCLUSIONS: Because of potential benefit of long-term patency associated with arterial grafts, minimal morbidity and mortality associated with use of the RA and excellent short-term patency rates, we cautiously recommend use of one or both RAs as additional conduits to be used concomitantly with the ITA for arterial revascularization of the coronary arteries.
Adolescent↗
Molecular forms of tegumental and muscle acetylcholinesterases of Schistosoma.
Acetylcholinesterase (AChE) is present in the muscle and on the tegument of schistosomes. Molecular forms of schistosome AChE were examined because particular AChEs are found in tissues of distinct function elsewhere. The dimeric globular form (G2) is the only form evident in adult Schistosoma haematobium: 32% of the muscle AChE is hydrophilic and 61% is membrane associated. A substantial amount of this enzyme is phosphatidylinositol (PI) anchored since it could be released by PI-specific phospholipase C from both muscle and tegumental membranes.
Acetylcholinesterase↗
Prostaglandin H-synthase-2 is the main enzyme involved in the biosynthesis of octadecanoids from linoleic acid in human dermal fibroblasts stimulated with interleukin-1beta.
This study was focused on the characterization of the metabolism of linoleic acid by human dermal fibroblasts and the effect of interleukin-1 on the biosynthesis of octadecanoids. Dermal fibroblasts untreated and treated with recombinant IL-1beta were incubated with exogenous labeled linoleic acid. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry was used as the analytic technique. We found that dermal fibroblasts convert linoleic acid mainly into 13-hydroxy-9-cis,11-trans-octadecadienoic acid (13-HODE) and 9-hydroxy-10-trans,12-cis-octadecadienoic acid (9-HODE), 13(S)-HODE and 9(R)-HODE being the predominant enantiomers. IL-1beta increased the formation of both 13-HODE and 9-HODE in a concentration-dependent manner with similar EC50 values as for prostanoid formation. This effect of IL-1beta on HODEs formation was concomitant with the expression of prostaglandin H-synthase-2. Formation of octadecanoids was inhibited in a concentration-dependent manner by acetylsalicylic acid and indomethacin. Dexamethasone, actinomycin D, and cycloheximide abolished the effect of IL-1beta on HODEs biosynthesis. Octadecanoid biosynthetic activity was associated with the microsomal fraction. Dermal fibroblasts incorporated [14C]-9-HODE and [14C]-13-HODE into phospholipids, mainly into phosphatidylcholine. IL-1beta increased significantly the esterification of 13-HODE in all glycerophospholipids, the major increase being observed in phosphatidylinositol. These results indicate that prostaglandin H-synthase-2 is the enzyme responsible for the increase in the ability to form HODEs of dermal fibroblasts stimulated with IL-1beta.
Cells, Cultured↗
An assay for the determination of reduced methotrexate accumulation in cells displaying limited viability in vitro.
Amongst the mechanisms known to mediate resistance to methotrexate (MTX), a major component in the treatment of childhood leukemia, reduced drug accumulation appears to have direct clinical relevance. However, due to the poor viability of patient-derived acute lymphoblastic leukemia cells in vitro, determination of this parameter in clinical samples is associated with a number of difficulties. We have therefore developed an assay for reduced MTX accumulation, which controls for the metabolic state of the cell population under study by utilizing accumulation of the nucleoside thymidine as an independent indicator of this parameter. To establish this assay, we have utilized pediatric leukemic cell populations maintained as xenografts in nude mice, which, despite displaying sensitivity to MTX, demonstrated reduced accumulation of MTX when assayed using standard methodology. When accumulation of MTX by such cell populations was expressed, however, relative to their accumulation of thymidine, MTX accumulation was shown to be equal to that of drug-sensitive CCRF-CEM cells maintained in long-term culture. In contrast, significantly less MTX was accumulated, in this assay, by xenografted cell populations with demonstrated resistance to MTX. Identical results were obtained using either fresh or cryopreserved cells. The data thus indicate that by controlling for variable metabolic status of leukemic cells, it is possible to accurately assess MTX accumulation in leukemic samples displaying limited viability in culture.
Animals↗
Interleukin-1 enhances the ability of cultured human umbilical vein endothelial cells to oxidize linoleic acid.
Human umbilical vein endothelial cells (HUVEC) were treated with recombinant interleukin (IL)-1 beta, and the metabolism of exogenous linoleic acid was studied. High performance liquid chromatography, gas chromatography-mass spectrometry, and chiral analysis revealed that HUVEC enzymatically convert linoleic acid mainly into 13-(S)hydroxy-9(Z),11(E)-octadecadienoic (13-HODE) and 9-(R)hydroxy-10(E),12(Z)-octadecadienoic acids, which may isomerize toward all-trans compounds. IL-1 beta increased the formation of all octadecanoids in a time- and dose-dependent manner with similar EC50 (approximately 1 unit/ml). The apparent Km values of linoleic acid were 15.59 +/- 8.39 and 152.9 +/- 84 microM (p < 0.05) in IL-1 beta-treated cells and controls, respectively, indicating a higher substrate affinity in cells stimulated with IL-1 beta. Ratios of S/R enantiomers for the hydroxyoctadecanoids produced by untreated and IL-1 beta-treated cells were similar to those from isolated cyclooxygenases (COXs), whereas isolated 15-lipoxygenase yielded 13-HODE with a strict S configuration. The formation of octadecanoids was inhibited in a dose-dependent manner by several COX inhibitors in both controls and IL-1 beta-treated cells, COX2 selective inhibitors being more effective on IL-1 beta-treated cells than on controls. COX1 and COX2 protein levels increased less than 2-fold and 8-fold, respectively, after IL-1 beta treatment. The specificity of COX inhibitors was proven since they did not inhibit 13-HODE formation by human polymorphonuclear leukocytes. Overall, these results indicate that COXs are responsible for the oxidative metabolism of linoleic acid in HUVEC, and IL-1 beta increases it by inducing the expression of new enzyme, mainly COX2.
Cells, Cultured↗
Schistosoma: rate of glucose import is altered by acetylcholine interaction with tegumental acetylcholine receptors and acetylcholinesterase.
The blood dwelling stages of schistosomes have acetylcholinesterase (AChE) and nicotinic-like acetylcholine receptors (nAChR) on their teguments. Both AChE and nAChR are concentrated on the dorsal surface of the adult male, a major surface for nutrient uptake for the worm pair. Exposure of tegumental AChE and nAChR to acetylcholine (ACh), the natural ligand of these molecules, has a consequence for the transporting function of this membrane in some schistosome species. The rate of glucose uptake in vitro by Schistosoma haematobium and Schistosoma bovis adult worm pairs was enhanced by approximately 60% at blood concentrations of ACh. Schistosoma mansoni did not show a similar response. The specificity of the ACh interaction with nAChR and AChE was shown by ablation of the effect with specific antagonists of nAChR (d-tubocurarine and alpha-bungarotoxin) and an inhibitor of AChE (BW284C51). The primary effect occurs on the tegument since alpha-bungarotoxin and BW284C51 do not penetrate the schistosome tegument. The species differences in reliance on this mechanism are consistent with their relative sensitivities to the AChE inhibitory drug, metrifonate.
Acetylcholine↗
Nicotinic acetylcholine receptors on the surface of the blood fluke Schistosoma.
Blood dwelling stages of schistosomes have acetylcholinesterase (AChE) on their teguments. As an initial step towards understanding the function of tegumental AChE, we have used specific ligand-binding assays to identify nicotinic acetylcholine receptors (nAChR) on the schistosome surface. AChR could not be detected on migratory stages using fluoroscein isothiocyanate-alpha-bungarotoxin binding but the amount of specific labelling increased on sexual pairing and as the parasites matured into egg-producing adults. Both AChE and nAChR were concentrated on the dorsal surface of the adult male. These results indicate a role for AChE and AChR associated with the transporting function of this membrane.
Acetylcholinesterase↗
Glucose uptake rates by Schistosoma mansoni, S. haematobium, and S. bovis adults using a flow in vitro culture system.
A simple flow culture apparatus was designed for the short-term in vitro culture of adult schistosomes. The use of this system allowed sensitive estimation of relative rates of glucose uptake by different species of schistosome. These data suggest that in parasites maintained carefully in conditions within the physiological range of glucose concentration, uptake of glucose is entirely carrier mediated. The rates of glucose uptake by Schistosoma haematobium and its close relative Schistosoma bovis were more than twice that recorded for Schistosoma mansoni. The relationship between reproductive output, glucose requirements, and susceptibility to immune attrition as adults is considered.
Animals↗
The amount of acetylcholinesterase on the parasite surface reflects the differential sensitivity of schistosome species to metrifonate.
Acetylcholinesterase (AChE) is present in all stages of the life-cycle of schistosomes and is located in muscle and on the surface of the parasite. Metrifonate is a drug that inhibits AChE. We compared the AChEs from three schistosome species (Schistosoma mansoni, Schistosoma haematobium and Schistosoma bovis) that have different susceptibilities to metrifonate in vivo. Sensitivities to AChE inhibitors were similar. The subunits of AChE were 110 kDa and 76 kDa and the dominant molecular form of AChE was a G2 form in all three species. This was the major form on the tegument while additional molecular forms were associated with the internal tissues. Differences in relative amounts of AChE activity between these species were found in the adults but not in the schistosomula. At the adult stage the major difference between species lay in the relative amounts of AChE activity in their teguments. S. haematobium teguments carried 20 times and S. bovis 6.9 times the activity present on S. mansoni teguments. These quantitative differences associate with the relative sensitivities of these species to metrifonate.
Acetylcholinesterase↗
Effect of bovine respiratory syncytial virus infection on hypersensitivity to inhaled Micropolyspora faeni.
Respiratory syncytial virus causes mild-to-severe respiratory disease in human infants and young children; a closely related bovine respiratory syncytial virus causes a similar disease pattern in calves. Increased disease severity in atopic children suggests that allergic reactivity may enhance the severity of RSV-induced disease. To examine the association between bovine respiratory syncytial virus (BRSV) infection and allergic reactivity two groups of calves were exposed to aerosolized Micropolyspora faeni (Mf) during an experimental BRSV infection. One group exposed to Mf concurrent with BRSV was challenge-exposed to Mf while infected a second time with BRSV, while the other similarly sensitized and infected group was mock challenged. A control group was exposed only to Mf aerosol and another control group was infected with virus but not exposed to Mf aerosol. Parameters examined included: clinical signs, Mf-specific IgG and IgE, BRSV-specific antibody and IgE, leukotrienes C4 and B4 prostaglandins E2, F2 alpha and D2, and lung pathology. While the initial BRSV infection failed to enhance sensitization to inhaled Mf, a second BRSV infection exacerbated clinical signs resulting from Mf aerosol. Consideration of eicosanoid and antibody profiles together with clinical signs suggests that mechanisms of both type I and type III hypersensitivity were operative during Mf challenge of sensitized calves.
Administration, Inhalation↗
[Pacemaker implantation in a patient with persistent left superior vena cava and atresia of the right superior vena cava].
Persistent left superior vena cava with absence or atresia of right superior vena cava is a congenital abnormality of systemic venous return to the heart which may complicate the insertion of a pacemaker electrode. We present a case report of a patient with conduction system disturbances in whom this abnormality was diagnosed during pacemaker implantation, with the possibility of using a transvenous electrode without active fixation system.
Aged↗
Development of a Babesia bovis live attenuated vaccine.
Babesia bovis is the blood parasite causing the highest morbidity and mortality of cattle in Cuba. Thus a control program based on immunization with a vaccine using an attenuated strain of the parasite was developed. For this purpose, a virulent B. bovis strain was isolated and then attenuated by the traditional method in which biological characteristics, proteolytic activity and vector transmissibility were studied. The protection conferred by the vaccine was measured by vaccinating cattle which then was challenged with a heterologous strain. In order to assess postvaccination accident risks, 2603 cattle were vaccinated and those showing clinical signs of babesiosis were treated. A study of cost-benefit was performed in a herd where frequent outbreaks of babesiosis occurred; prevalence and clinical case incidence in vaccinated and nonvaccinated animals were determined. Vaccinated animals survived to challenge whereas two control animals died. In 2% of the vaccinated animals less than 6 months of age, postvaccination accidents occurred, whereas in older animals this index was higher (p < 0.001). The cost-benefit study showed a rate of approximately $10 pesos (national currency) for each peso invested due to the high mortality caused by the parasite. Until an effective, killed vaccine is available, vaccination with live vaccines is advantageous to prevent bovine babesiosis.
Animals↗
Massive intraoperative pulmonary embolism.
Intraoperative massive pulmonary embolism is extremely rare. We describe such a case in a patient treated for a prolonged period preoperatively with intravenous heparin after an acute myocardial infarction and unsuccessful attempt at angioplasty, emphasizing that the problem should be borne in mind to facilitate expeditious and appropriate management. A clue to the diagnosis is interruption of venous return that is not due to a kink in the cannulae.
Aged↗
Limited proteolysis of tumor cells increases their plasmin-binding ability.
Mild proteolytic treatment of SW1116 tumor cells with trypsin or plasmin increases their plasmin-binding ability considerably by increasing the number of binding sites without altering their affinity. This mechanism may be operative for increasing the concentration of active plasmin at the surface of tumor cells. C-terminal lysine residues are involved in plasmin binding to cells, since treatment of cells with carboxypeptidase B decreases this binding by 50%.
Aprotinin↗
Corrosion cast studies of the bronchial arteries.
The bronchial a. are the nutrient vessels of the lung. Despite being high pressure (systemic) vessels they are of very small size compared to the pulmonary a. and their side branches are normally so minute that they are extremely difficult to visualize during in vivo studies--yet these branches also supply many important mediastinal structures including the esophagus, trachea, lymph nodes, pericardium, aorta, and mediastinal parietal pleura. The bronchial a. can react vigorously to pathological changes in the lung by hypertrophy and increased flow and their precise anatomy has become of increasing importance with the development of interventional techniques involving the systemic circulation of the lungs. In order to demonstrate the distribution and extent of these vessels we have adopted a casting technique using injections of various colors of latex to distinguish between pulmonary a. and veins, bronchial a. and veins and their connections with the pulmonary vascular bed in both normal and diseased lungs.
Adult↗
Aging and renal clearance of procainamide and acetylprocainamide.
Thirty-two patients had blood and urine collected simultaneously for measurement of procainamide, acetylprocainamide, and creatinine. The ratios of drug clearance to creatinine clearance were calculated for each. The procainamide:creatinine clearance ratio averaged 2.9 +/- 1.6 (SD) and fell as age of the patients rose (r = 0.5, p < 0.01). The acetylprocainamide:creatinine clearance ratio averaged 1.7 +/- 0.8 and also fell with age. The combination of decline in overall renal function with age with this decrease in the rate of renal tubular secretion of these drugs led to a progressive age-related rise in the steady-state serum level of procainamide (r = 0.56, p < 0.01) and acetylprocainamide (r = 0.36, p < 0.1) achieved by any dose of procainamide. Thus, the dosage of procainamide must be individualized for both overall renal function (GFR) and the age-related variations in renal tubular secretion that are of most note in children and the elderly.
Acecainide↗