Advances in Brachiocephalic Angioplasty.
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Biomedical subjects
Publications and source records attributed to S Iyer.
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Human endothelium obtained from both the aorta and the pulmonary artery has been evaluated for the presence of the messenger RNA coding for the expression of sterol 27-hydroxylase. Unique oligomers were designed to detect the mRNA by reverse transcription followed by the polymerase chain reaction. The amplified product was sequenced and was found to be identical to the published sequence for nucleotides 491 to 802 of the human sterol 27-hydroxylase cDNA. Northern blot analysis confirmed the presence of 27-hydroxylase mRNA in pulmonary artery and aortic endothelium. As part of these studies, enzymatic activity was assayed in cultured arterial endothelium using cholesterol as a substrate and isotope ratio gas-liquid chromatography-mass spectrometry to identify the metabolites, 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, in the medium. Localization of sterol 27-hydroxylase to vascular endothelium indicates intracellular production of the biologically active metabolite 27-hydroxycholesterol.
Po (M(r) 30 kDa), the major protein component of peripheral nervous system (PNS) myelin, is known to be phosphorylated by protein kinase C on serine residues at multiple sites. This study was conducted to assess whether other amino acids might be phosphorylated in the protein. Segments of rat sciatic nerve were incubated with 32P in either the presence or absence of phorbol ester. Labeled Po was isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subjected to partial acid hydrolysis. Upon separation of the hydrolysis products by either thin-layer electrophoresis or thin-layer chromatography, a radioactive spot was detected which comigrated with authentic phosphotyrosine. In other experiments, nerves were incubated with the tyrosine phosphatase inhibitors vanadate or vanadyl hydroperoxide (pervanadate). When the nerve homogenate proteins were separated on gels and probed with a monoclonal antibody to phosphotyrosine on Western blots, a positive immune reaction was obtained for a protein species which migrated with the same mobility as PO on Coomassie Blue-stained gels. In the absence of 2-mercaptoethanol, this immunoreactive band displayed increased mobility on gels which is characteristic of the migration pattern of Po. The same immunostaining results were obtained using a purified peripheral myelin fraction prepared from nerve homogenates. Furthermore, the positions of immunoreactive bands produced by anti-Po and antiphosphotyrosine antibodies coincided on the same immunoblot of myelin proteins and purified Po. These data indicate that one or more tyrosyl residues in Po can be phosphorylated in intact sciatic nerve.
Phagocytosis of the virulent Erdman and H37Rv strains of Mycobacterium tuberculosis, but not that of the attenuated H37Ra strain, by human macrophages is mediated by the mannose receptor (MR) in addition to complement receptors. We have recently determined that a major capsular lipoglycan, lipoarabinomannan (LAM), from the Erdman strain serves as a ligand for the MR during phagocytosis of bacteria. In this study we directly compare uptake of Erdman, H37Rv, and H37Ra LAM by human macrophages and assess the relative contribution of the MR in this process. Microspheres coated with LAM served as model phagocytic particles for studies of LAM as a capsular ligand. Uptake (37 degrees C) of LAM microspheres by monocyte-derived macrophages was greatest for Erdman LAM and intermediate for H37Rv and H37Ra LAM compared with that of buffer microspheres or microspheres coated with LAM from a nontuberculosis strain of mycobacterium (AraLAM). Inhibition of microsphere uptake in the presence of mannan or mannose-BSA was highest for Erdman LAM (75 +/- 8 and 50 +/- 7%, respectively) and H37Rv LAM (57 +/- 13 and 21 +/- 5%, respectively) relative to H37Ra LAM (36 +/- 16 and 22 +/- 11 %, respectively). Inhibition of microsphere uptake in the presence of anti-MR Ab followed a similar pattern: Erdman LAM (80 +/- 9%) > H37Rv LAM (53 +/- 1%) > H37Ra LAM (26 +/- 12%). Attachment (4 degrees C) of microspheres coated with Erdman LAM, H37Rv LAM, and H37Ra LAM was enhanced 12-, 5-, and 4-fold, respectively, compared with that of microspheres coated with AraLAM, and mannose-BSA inhibited attachment of these microspheres by 82 +/- 7, 69 +/- 8, and 12 +/- 17%. Galactose-BSA did not inhibit attachment of any LAM microsphere groups. Chromatographic analyses of mild acid hydrolysates of LAM from Erdman, H37Rv, and H37Ra all revealed the major terminal dimannosyl units. These studies demonstrate differences in the ability of LAM from different M. tuberculosis strains to mediate adherence to macrophages and to serve as ligands for the macrophage MR despite the presence of terminal dimannosyl units. Thus, these studies point toward other subtle structural alterations in LAM among strains that influence initial interactions with human phagocytes.
Since it was first described 25 years ago, phosphorylation has come to be recognized as a widespread and dynamic post-translation modification of myelin proteins. In this review, the phosphorylation characteristics of myelin basic protein, protein zero (P0), myelin-associated glycoprotein and 2'3' cyclic nucleotide 3'-phosphodiesterase are summarized. Emphasis is placed on recent advances in our knowledge concerning the protein kinases involved and the sites of phosphorylation in the amino acid sequences, where known. The possible roles of myelin protein phosphorylation in modulating myelin structure, the process of myelin assembly and mediation of signal transduction events are discussed.
We report a case of an 18-month-old female who presented with three supernumerary upper limbs of varying lengths on the right side. Each limb had a proximal, middle, and distal segment, and an intercalated elbow and wrist joint. A single digit was present in the superior limb, three digits in the middle limb, and two digits in the caudal-most limb. Right plagiocephaly, congenital torticollis, scoliosis involving the upper and mid thoracic region, and a hypoplastic right pectoralis major were the other abnormal features noted. Radiography showed two scapulae, humerus, a single forearm bone in each limb, and rudimentary metacarpals and phalanges. Limb duplication may rarely be encountered in parasitic conjoined twins. The role of mutagens, drugs, cellular contributions, and morphogens in the growth and differentiation of limbs has been studied in animals. It is rather difficult to deduce the time of action of the factors responsible for such a malformation.
BACKGROUND: The proposed mechanisms of restenosis after coronary angioplasty include neointima formation, vessel wall remodeling and mural thrombus. Poloxamer 188 does not inhibit coagulation factors, but was shown to reduce mural thrombus formation in pig coronary arteries after intracoronary stenting in an acute study. This study was performed to examine whether this agent may reduce neointima formation. METHODS: Thirty domestic juvenile pigs of weight 20-30 kg were anesthetized. A left angiogram was performed via a femoral artery. Proximal left anterior descending and circumflex arteries were dilated three times with a 20-30% oversized coronary angioplasty balloon catheter. Fifteen animals were allocated randomly to receive intravenous infusions of poloxamer 188, starting 30 min before angioplasty and continuing for 24 h. The remaining 15 received intravenous 0.45% saline and served as controls. The animals were killed 2 weeks after the angioplasty. Histologic studies of the arteries were performed. The severity of the injury and the amount of thrombus material incorporated in the neointima were assessed by semiquantitative methods. RESULTS: There was no significant difference between injury scores in the two groups. Thrombus material in the neointima in the treatment group was significantly less than that in those of the control group (thrombus areas 0.013 +/- 0.004 compared with 0.029 +/- 0.006 mm2, P < 0.02), but there were no significant differences between the neointimal (0.60 +/- 0.08 and 0.60 +/- 0.13 mm2) and luminal (2.51 +/- 0.21 and 2.44 +/- 0.26 mm2) areas in treatment and control groups. CONCLUSION: Continuous 24 h intravenous infusion of poloxamer 188 after balloon injury in pig coronary arteries may reduce mural thrombus formation significantly, but did not reduce neointima formation.
BACKGROUND AND PURPOSE: Endarterectomy for recurrent carotid stenosis after endarterectomy has a significantly higher complication rate than the original operation. Angioplasty and stenting may offer a useful alternative treatment for these patients. METHODS: Between September 1994 and April 1996, 22 patients had 25 carotid arteries treated with angioplasty and stenting for postendarterectomy restenosis. All patients had an independent neurological examination and National Institutes of Health Stroke Scale evaluation before and after the procedure. Patients were treated with aspirin and ticlopidine. All patients were requested to return at 6 months for follow-up angiography. The mean patient age was 69 +/- 7 years, and the mean elapsed time from endarterectomy was 73 +/- 69 months. Seventy-seven percent of the patients were symptomatic. RESULTS: Mean stenosis was reduced from 79 +/- 13% before the procedure to 1.8 +/- 3.6% after stenting. One patient had a minor stroke, for a complication rate of 4% per treated artery. In the eight patients who returned for 6-month angiography, mean stenosis was 19.4 +/- 4.4% and restenosis (> or = 50% stenosis) did not occur. CONCLUSIONS: In a small series, angioplasty and stenting appear to be safe and well tolerated for the treatment of postendarterectomy restenosis.
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Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.
Eighty children with bronchial asthma and ten control cases underwent radionuclide gastroesophagography for the detection of gastroesophageal reflux. Thirty nine per cent asthmatic children demonstrated esophageal reflux on scintiscanning. The ten control subjects had no reflux. The presence of reflux correlated strongly with the presence of nocturnal exacerbation of symptoms. Bronchodilator therapy did not affect the prevalence of GER in asthmatic children.
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The balloon expandable, stainless steel, flexible coil stent is a useful device for the management of acute or threatened closure after percutaneous transluminal coronary angioplasty. Appropriate sizing is important to optimize immediate results and reduce the risk of acute thrombosis and restenosis. The in vivo size at deployment of this stent at nominal inflation pressures has not been evaluated. Forty patients who received a single flexible coil stent (10 patients each for stent sizes 4.0, 3.5, 3.0, and 2.5 mm) were studied. The stents were deployed at 3-5 atmospheres. The actual stent size achieved by the stent during deployment was found to be significantly less than the nominal size, being 3.7 +/- 0.3, 3.2 +/- 0.2, and 2.8 +/- 0.2 mm for nominal stent sizes of 4.0, 3.5, and 3.0 mm, respectively (P < 0.005, P < 0.001, and P < 0.01). For a 2.5 mm stent, it was 2.4 +/- 0.2 mm (P = ns). Thus, for optimal results with this device, we recommend that vessels 2.0-2.4 mm in diameter be supported by a 2.5 mm stent, vessels 2.5-2.9 mm in diameter by a 3.0 mm stent, vessels 3.0-3.4 mm in diameter by a 3.5 mm stent, and vessels 3.5-4.0 mm in diameter by a 4.0 mm stent.
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After placement of a Gianturco-Roubin metallic, coiled coronary stent(s) following balloon angioplasty (PTCA), a pre-discharge (7 day) angiogram determined the patency of the old coronary bypass vein graft(s) (SVG) (> or = 5 years remote from their last surgery, mean age: 8.5 +/- 1.8 years). Metallic, coiled stents were successfully deployed in 95/96 (99%) patients within 100/101 (99%) SVGs. The indications for deployment were threatened [81 patients (84%)] or acute [15 patients (16%)] vein graft closure following PTCA. Intragraft urokinase infusion was performed in 17 patients (17%) [6 patients with baseline occlusions; 11 with abrupt closure post PTCA]. Complications encountered included three (3%) in-hospital deaths (two procedure related) two (2%) Q wave myocardial infarctions, six (6%) non-Q wave myocardial infarctions, and 22 (22%) bleeding problems. These included, not mutually exclusively, 21 (22%) requiring transfusions, six (6%) cases of gastrointestinal bleeding, six (6%) pseudoaneurysms, five (5%) retroperitoneal haemorrhages and two (2%) cerebrovascular accidents. All patients received dipyridamole, aspirin, dextran, and anticoagulation (heparin 10-20,000 U intra-procedurally); a heparin infusion was continued for 5 +/- 1 days, despite warfarin administration which attained a therapeutic prothrombin time (PT) (1.5-2 times control) by 3 +/- 1 days. Out of the 95 successfully treated patients, six with eight stented grafts were ineligible for pre-discharge angiography. Of the six, three died in hospital (four SVGs), one had an intracerebral haemorrhage (one SVG), and two were asymptomatic patients with chronic renal failure (three SVGs).(ABSTRACT TRUNCATED AT 250 WORDS)
Specific receptors for lactoferrin (Lf) have been identified in the small intestine brush-border membrane and on lymphocytes. Little is known about the mechanism of Lf interaction with its receptor protein. Because of the pH dependence of this interaction, the possible involvement of surface exposed histidine residues was explored. His residues on purified human milk Lf were progressively modified by carboxyethylation with diethyl pyrocarbonate; the reaction was monitored by UV absorbance and by affinity chromatography on immobilized Cu(II) ions. Human infant brush-border membrane vesicles (BBMVs) were prepared by differential centrifugation and precipitation methods. Human peripheral lymphocytes were prepared by Ficoll centrifugation and stimulated by mitogen (PHA) exposure in culture. A competitive receptor binding assay was performed with 59Fe- and/or 125I-labelled native Lf and His-modified Lf. Binding assays with labelled native Lf were conducted in the presence of a 10-200 fold molar excess of DEPC-Lf, the DEPC-Lf was not competitive. A 100-fold molar excess of native Lf completely blocked the interaction of labelled Lf with the receptor. Similar results were obtained for receptor proteins on BBMVs and lymphocytes. Thus, Lf receptors on these two different cell types appear to require His residues for Lf binding.