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J V O'Connor

Publications and source records attributed to J V O'Connor.

At least 19 recordsLinked to original sources
PubMed1998

Thoracic splenosis.

Thoracic splenosis is a rare pathologic entity resulting from seeding of splenic tissue in the pleural cavity after thoracoabdominal trauma. A 45-year-old man with a history of splenectomy secondary to abdominal trauma presented with a left lung mass and an inconclusive tissue diagnosis after needle biopsy. Thoracic splenosis was not suspected preoperatively, considered on an intraoperative frozen section, and established on permanent pathologic biopsy specimens obtained during thoracotomy. A history of thoracoabdominal trauma, combined with radiologic and radionuclide imaging studies, may establish the diagnosis without thoracotomy.

Abdominal Injuries↗
PubMed1998

Popliteal pseudoaneurysm following total knee arthroplasty.

Arterial injuries complicating total knee arthroplasty are rare but may result in significant morbidity. There are three reports of popliteal artery pseudoaneurysm resulting from arterial trauma during total knee replacement. We report a case of a popliteal pseudoaneurysm with rupture into the surrounding muscle, its evaluation, and successful repair 5 months after arthroplasty.

Aged↗
PubMed1997

The structure of the exopolysaccharide of Pseudomonas fluorescens strain H13.

An acidic exopolysaccharide was isolated from P. fluorescens strain H13. The structure of the polysaccharide repeating unit was determined using chemical methods and 1D and 2D NMR techniques. The repeating unit was characterized as a trisaccharide composed of D-glucose, 2-acetamido-2-deoxy-D-glucose and 4-O-acetyl-2-acetamido-2-deoxy-D-mannuronic acid.

Acetylglucosamine↗
PubMed1992

Proper response.

Explore the source record for details and available documents.

AIDS-Related Complex↗
PubMed1989

Carbohydrate structures of human tissue plasminogen activator expressed in Chinese hamster ovary cells.

Recombinant human tissue plasminogen activator (rt-PA), produced by expression in Chinese hamster ovary cells, is a fibrin-specific plasminogen activator which has been approved for clinical use in the treatment of myocardial infarction. In this study, the structures of the Asn-linked oligosaccharides of Chinese hamster ovary-expressed rt-PA have been elucidated. High mannose and hybrid oligosaccharides were released from the protein by endoglycosidase H digestion, whereas N-acetyllactosamine-type ("complex") oligosaccharides were released by peptide:N-glycosidase F digestion. The oligosaccharides were fractionated by gel permeation chromatography and anion exchange high performance liquid chromatography (HPLC), and their structures were analyzed by composition and methylation analysis, high pH anion exchange chromatography, fast atom bombardment-mass spectrometry (FAB-MS), and 500-MHz 1H NMR spectroscopy. High mannose oligosaccharides were found to account for 38% of the total carbohydrate content of rt-PA and consisted of Man5GlcNAc2, Man6GlcNAc2, and Man7GlcNAc2 in the ratio 1.8:1.7:1. Two hybrid oligosaccharides were identified and accounted for 3% of the carbohydrate of rt-PA. The N-acetyllactosamine-type oligosaccharides were found to comprise diantennary (34% of total carbohydrate), 2,4-branched triantennary (11%), 2,6-branched triantennary (9%), and tetraantennary (5%) structures. Sialylation of these oligosaccharides was by alpha (2----3) linkages to galactose. Most (greater than 90%) of the N-acetyllactosamine-type structures contained fucose alpha (1----6) linked to the Asn-linked N-acetylglucosamine residue. The distribution of oligosaccharide structures at individual glycosylation sites (Asn residues 117, 184, and 448) was also determined. rt-PA exists as two variants that differ by the presence (type I) or absence (type II) of carbohydrate at Asn-184. Tryptic glycopeptides were isolated by reversed phase high performance liquid chromatography and treated with peptide:N-glycosidase F. The oligosaccharides released from each glycosylation site were analyzed by high pH anion exchange chromatography. By this analysis, Asn-117 was demonstrated to carry exclusively high mannose oligosaccharides. When glycosylated, Asn-184 carried diantennary, 2,4-branched triantennary, 2,6-branched triantennary, and tetraantennary N- acetyllactosamine oligosaccharides in the ratio 9.0:4.5:1.4:1. Asn- 448 carried the same types of oligosaccharides, but in the ratio 7.5:1.6:2.1:1. The distributions of Asn-linked oligosaccharides at positions 117 and 448 were found not to be affected by the presence or absence of carbohydrate at position 184. The relevance of the

Animals↗
PubMed1988

The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator.

Modification of the carbohydrate structures of recombinant tissue-type plasminogen activator (rt-PA) can increase or decrease its rate of clearance in rabbits. When rt-PA was treated with sodium periodate to oxidize carbohydrate residues, the rate of clearance was decreased from 9.6 +/- 1.9 ml min-1 kg-1 to 3.5 +/- 0.6 ml min-1 kg-1 (mean +/- SD, n = 5). A similar change in the clearance of rt-PA was introduced by the use of endo-beta-N-acetyl-glucosaminidase H (Endo-H), which selectively removes high mannose asparagine-linked oligosaccharides; the clearance of Endo-H-treated rt-PA was 5.0 +/- 0.5 ml min-1 kg-1. A mutant of rt-PA was produced with an amino acid substitution at position 117 (Asn replaced with Gln) to remove a potential glycosylation site that normally contains a high mannose structure. The clearance of this material was also decreased, similar to the periodate and Endo-H-treated rt-PA. Conversely, when rt-PA was produced in the CHO 15B cell line, which can produce only high mannose oligosaccharide structures on glycoproteins, the clearance was increased by a factor of 1.8. These results demonstrate that the removal of rt-PA from the blood depends significantly upon the nature of its oligosaccharide structures.

Animals↗
PubMed1986

Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1.

Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the fever produced by rIL-1. On a weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce the same amount of fever and induce comparable levels of PGE2 in rabbit hypothalamic cells in vitro; like IL-1, TNF fever is blocked by drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) rTNF alpha produces biphasic fevers. The first fever reaches peak elevation 45-55 min after bolus injection and likely represents a direct action on the thermoregulatory center. During the second fever peak (3 h later), a circulating endogenous pyrogen can be shown present using passive transfer of plasma into fresh rabbits. This likely represents the in vivo induction of IL-1. In vitro, rTNF alpha induces the release of IL-1 activity from human mononuclear cells with maximal production observed at 50-100 ng/ml of rTNF alpha. In addition, rTNF alpha and rIFN-gamma have a synergistic effect on IL-1 production. The biological activity of rTNF alpha could be distinguished from IL-1 in three ways: the monophasic pyrogenic activity of rIL-1 was destroyed at 70 degrees C, whereas rTNF alpha remained active; anti-IL-1 neutralized IL-1 but did recognize rTNF alpha or natural cachectin nor neutralize its cytotoxic effect; and unlike IL-1, rTNF alpha was not active in the mitogen-stimulated T cell proliferation assay. The possibility that endotoxin was responsible for rTNF alpha fever and/or the induction of IL-1 was ruled-out in several studies: rTNF alpha produced fever in the endotoxin-resistant C3H/HeJ mice; the IL-1-inducing property of rTNF alpha was destroyed either by heat (70 degrees C) or trypsinization, and was unaffected by polymyxin B; pyrogenic tolerance to daily injections of rTNF alpha did not occur; levels of endotoxin, as determined in the Limulus amebocyte lysate, were below the minimum rabbit pyrogen dose; and these levels of endotoxin were confirmed by gas chromatography/mass spectrometry analysis for the presence of beta-hydroxymyristic acid. Although rTNF alpha is not active in T cell proliferation assays, it may mimic IL-1 in a T cell assay, since high concentrations of rTNF alpha induced IL-1 from epithelial or macrophagic cells in the thymocyte preparations. These studies show that TNF (cachectin) is another endogenous pyrogen which, like IL-1 and IFN-alpha, directly stimulate hypothalamic PGE2 synthesis. In addition, rTNF alpha is an endogenous inducer of IL-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The protective effect of profound hypothermia on the canine central nervous system during one hour of circulatory arrest.

Circulatory arrest during profound hypothermia is a safe technique of cardiac surgery when used in selected instances. Despite its proven safety, the degree of cerebral protection offered by this technique is still poorly defined. Ten dogs anesthetized with Pentothal (thiopental sodium) were surface cooled to 32 degrees C. They were placed on cardiopulmonary bypass, cooled to 13 degrees C (cerebral temperature), and then underwent one hour of circulatory arrest. At the end of the arrest period, the dogs were rewarmed, resuscitated, and successfully weaned from bypass. A control group of 6 dogs were subjected to the same protocol but without the one-hour period of circulatory arrest. There were no group differences in animal weight, duration of surface cooling, cardiopulmonary bypass, or rewarming, mean flow, or mean arterial pressure. After a 7-day observation period, the dogs were killed with rapid tissue fixation using formalin. No neurological deficits were noted in any of the dogs during the observation period. The fixed brains were examined by a neuropathologist. No gross or microscopic evidence of cerebral hypoxia was seen in any of the animals. We conclude that one hour of circulatory arrest under profoundly hypothermic temperatures produces no detectable neurological changes or histological evidence of cerebral hypoxia.

Animals↗
PubMed1985

Cricothyroidotomy for prolonged ventilatory support after cardiac operations.

Forty-nine patients required prolonged ventilatory support after cardiac operations. Cricothyroidotomy was used routinely in these patients after approximately 7 days of endotracheal intubation. There were no infections of the median sternotomy wounds despite frequent colonization of the stoma. The only immediate complication was mild stomal bleeding in a patient taking anticoagulants. Nineteen patients (39%) died of underlying disease. The average duration of cricothyroidotomy was 59 days (range, 3 to 270 days). Cannulas were successfully removed in all survivors after an average of 38 days (range, 6 to 187 days). All of the patients were followed by personal interview, telephone contact, or contact with the referring physician. The average length of follow-up was 17 months (range, 2 to 50 months). All symptomatic patients were evaluated by laryngoscopy and bronchoscopy. One patient required endoscopic removal of granulation tissue from the stomal site; 2 others required tracheal resection for stenosis at the balloon site. There were no instances of subglottic stenosis. There were 4 late deaths, none of which was related to the cricothyroidotomy. Based on these findings, we suggest that cricothyroidotomy, with its low complication rate, is the procedure of choice for patients requiring prolonged mechanical ventilation after cardiac operations.

Cardiac Surgical Procedures↗
PubMed1985

Control of recombinant DNA produced pharmaceuticals by a combination of process validation and final product specifications.

Traditional methods of product release for human pharmaceutical use are designed and selected to ensure control of purity, potency, safety and identity. The selection of these tests depends upon the nature of the product. In addition to the control achieved by these methods, control of the efficiency of the manufacturing process in removing substances that cannot be tested for in the final product is achieved by "process validation". Process validation allows the use of sophisticated experimental techniques that do not lend themselves to final product testing or the use of others which, when applied to the final product, are insufficiently sensitive to be used for product release. The removal of such components as DNA and process materials can be demonstrated by these studies. Demonstrations that the manufacturing process reproducibly removes these components, eliminate the need for these tests on every batch. The essential elements of a process validation study are development of a sensitive assay technique for the component of interest and quantitation of the efficiency of individual process steps in removing that component. Even when that component is undetectable in normal process samples, the efficiency of any process step can still be determined by the addition of that component during the validation studies. The values of process validation in demonstrating the removal of DNA and in the determination of E. coli protein contamination levels during the manufacture of methionyl human growth hormone is illustrated.

Animals↗
PubMed1984

Human leukocytic pyrogen test for detection of pyrogenic material in growth hormone produced by recombinant Escherichia coli.

Human growth hormone is biosynthetically produced in recombinant strains of Escherichia coli as methionyl human growth hormone (met-hGH). When purified from the bacterial culture, met-hGH is biologically active in established assays for growth hormone. Therefore, a phase I trial of met-hGH was carried out in healthy human adults; during the first trial, however, signs, symptoms, and clinical laboratory tests characteristic of an acute-phase response to pyrogenic agents was observed. Prior testing of the met-hGH preparation used in the phase I trial did not reveal evidence of toxicity, and the U.S. Pharmacopeial Convention rabbit pyrogen test, as well as the Limulus amoebocyte lysate (LAL) test, had not detected significant levels of exogenous pyrogens or endotoxin. In addition, standard inhibition studies with added endotoxin showed no inhibition by the LAL test. When this preparation of met-hGH was incubated with human blood mononuclear cells, leukocytic pyrogen (LP) was released into the supernatant medium, suggesting that the preparation contained pyrogenic material. Various lots of met-hGH based on different purification and formulating methods were tested by the human LP assay for contaminating pyrogens. The results of these tests aided in the identification of procedures for met-hGH preparations which did not induce LP in vitro. Thus, subsequent lots of met-hGH which had passed the LP test were used in repeat clinical studies, and no inflammatory or pyrogenic reactions were observed. When the LP test was used, experiments revealed that the original lot of met-hGH was contaminated with endotoxin which had not been detected in the LAL or rabbit pyrogen tests. Lyophilization in glycine-phosphate buffer had resulted in a 10- to 20-fold reduction of endotoxin reactivity in the LAL test and the U.S. Pharmacopeial Convention rabbit pyrogen test. These data provide a probable explanation for the negative result from the LAL and rabbit pyrogen test in the initial lot of met-hGH which induced acute-phase reactions. In addition, these studies demonstrate that the release of LP from human cells is a reliable indicator of the presence of materials that are pyrogenic for humans.

DNA, Recombinant↗
PubMed1983

Use of stapling instruments in surgery for aneurysms of the aorta.

Since their inception, surgical stapling devices have been used almost exclusively in pulmonary and gastrointestinal procedures. We present our experience with surgical staplers in operations for aneurysms of the aorta. Three illustrative case reports are presented that demonstrate the applicability of surgical stapling devices in excluding aortic aneurysms. Seven patients have undergone operation using this technique, all with excellent technical results. We believe that surgical stapling devices represent a safe, easy, and rapid means of excluding aneurysms of the aorta.

Aorta, Thoracic↗