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Biomedical subjects

J Ryan

Publications and source records attributed to J Ryan.

At least 19 recordsLinked to original sources
PubMed1992

Endothelial monocyte-activating polypeptide II. A novel tumor-derived polypeptide that activates host-response mechanisms.

An important means by which tumor cells influence the vasculature is through the production of soluble mediators altering vascular properties. A approximately 22-kDa polypeptide was purified to homogeneity from conditioned medium of murine methylcholanthrene A (meth A) fibrosarcoma cells by ion-exchange chromatography and preparative sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE), based on its ability to induce tissue factor procoagulant activity in endothelial cells (ECs). The final product migrated as a broad band on reduced and nonreduced SDS-PAGE and had an unique amino-terminal sequence. This meth A-derived polypeptide modulated EC coagulant properties through the induction of tissue factor, induced monocyte migration and tissue factor expression, and was also chemotactic for granulocytes. Injection of the polypeptide into mouse footpads resulted in an inflammatory response with tissue swelling and polymorphonuclear leukocyte infiltration. The ability of this mediator to activate ECs and monocytes has led us to name it EMAP II (endothelial monocyte-activating polypeptide). EMAP II is distinct from a previously described approximately 40-kDa meth A-derived polypeptide termed EMAP I. Through its potential to activate host effector mechanisms, EMAP II could contribute to the biology of immunogenic tumors, such as the meth A fibrosarcoma.

Amino Acid Sequence↗
PubMed1992

Conservative management of fourth tarsal bone fracture in a draft horse.

A fourth tarsal bone fracture was treated conservatively in an adult draft horse. Seven months after the injury, the horse had no evidence of lameness and was able to compete in athletic events. It has been suggested that conservative management of these fractures be considered for brood animals or animals used for less strenuous activities. The outcome of this case suggests that fourth tarsal bone fractures can be successfully treated in athletic animals with conservative management.

Animals↗
PubMed1992

Tumor necrosis factor-induced endothelial tissue factor is associated with subendothelial matrix vesicles but is not expressed on the apical surface.

Cultured endothelial cells can be induced by tumor necrosis factor/cachectin (TNF) and other cytokines to synthesize the procoagulant cofactor tissue factor (TF). Intact monolayers of TNF-treated endothelial cells showed only minimal TF activity. In contrast, after permeabilization of these monolayers with detergent (saponin, 0.02%), there was approximately 10- to 20-fold increase in TF-mediated, factor VIIa-dependent factor Xa formation. Extracellular matrix derived from TNF-treated endothelium, prepared after removing the cells by hypotonic lysis or ammonium hydroxide (0.1 N), also had similarly enhanced TF activity. Incubation with a blocking monoclonal antibody to TF inhibited the procoagulant activity of both TNF-stimulated endothelial cells, whether they were intact or permeabilized, and of their matrices. However, when the apical cell surface was pretreated with anti-TF antibody, washed, and then cells were lysed with water or permeabilized with saponin, similar augmentation of TF activity was still observed, suggesting the presence of a pool of TF to which the antibody did not initially gain access. Consistent with this concept, the presence of TF in the matrix of TNF-treated endothelial cells was shown by immunoblotting and morphologic studies; cultured endothelial monolayers and the native endothelium of aortic segments after exposure to TNF showed TF in extracellular matrix, associated with vesicles. In contrast, TF was virtually undetectable on the apical endothelial surface. Taken together, these findings suggest that endothelial TF can be present in a cryptic pool that only gains access to the blood after alteration in the integrity of the endothelial monolayer.

Antibodies↗
PubMed1992

Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface.

Nonenzymatic glycosylation of proteins, as occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation end products of proteins (AGEs), which can bind to endothelial cells, thereby altering cellular function in a manner which could contribute to the pathogenesis of diabetic angiopathy. In this report, we describe the isolation of two endothelial cell surface-associated proteins which mediate, at least in part, the interaction of AGEs with endothelium. Based on pilot studies demonstrating AGE binding activity with comparable characteristics in bovine endothelial cell and lung extracts, the material from lung was sequentially subjected to chromatography on hydroxylapatite, fast protein liquid chromatography Mono S, and gel filtration. Two distinct polypeptides, approximately 35 and approximately 80 kDa, were purified to homogeneity, each of which bound AGEs as demonstrated by competitive binding assays using cellular binding proteins immobilized on a plastic surface. NH2-terminal sequence analysis indicated that the approximately 35-kDa protein was novel, whereas the NH2-terminal sequence of the approximately 80-kDa protein was identical to that of lactoferrin. Immunocytologic studies using polyclonal antibody prepared to each of the purified polypeptides demonstrated the presence of immunoreactive material on the surface of bovine endothelial cells maintained under serum-free conditions. Furthermore, immunoelectron microscopic studies with antibodies to the approximately 35- and approximately 80-kDa AGE-binding proteins conjugated to different size colloidal gold particles confirmed the presence of the target antigens on the cell surface and suggested that they were closely associated. IgG purified from polyclonal antisera to either the 35- or 80-kDa AGE-binding proteins blocked the binding of 125I-AGE-albumin to the cell surface. These results indicate that endothelial cells express specific cell surface molecules which mediate AGE-endothelial interaction. These polypeptides represent a novel class of cell surface acceptor molecules for glucose-modified proteins which may promote degradation and/or transcytosis of the ligand, and modulation of cellular function.

Amino Acid Sequence↗
PubMed1992

Cyclic AMP-independent effects of cholera toxin on B cell activation. II. Binding of ganglioside GM1 induces B cell activation.

Although the physiologic function of gangliosides is unknown, evidence suggests they play a role in the regulation of cell growth. The binding of ganglioside GM1 by recombinant B subunit of cholera toxin (rCT-B) inhibited mitogen-stimulated B cell proliferation without elevating intracellular cAMP. CT-B paradoxically enhanced the expression of MHC class II (Ia) molecules and minor lymphocyte-stimulating determinants without altering the expression of some other immunologically relevant B cell surface Ag. Increased expression of Ia was not detected until 4 h after stimulation, kinetics similar to those seen when B cells are stimulated with anti-Ig antibody or IL-4, suggesting that the enhancement was not the result of redistribution of existing cell surface markers but rather the result of a new metabolic event. Both the inhibitory and stimulatory effects of CT-B could be blocked by incubation of CT-B with ganglioside GM1. Furthermore, enhancement of the CT-B-mediated effect was seen when additional ganglioside GM1 was incorporated into the B cell membrane. rCT-B with a mutation that interfered with its binding to ganglioside GM1 did not enhance Ia expression. Taken together, these results indicate that the observed effects of CT-B were most likely mediated through the binding of cell surface ganglioside GM1. CT-B-mediated stimulation of Ia expression provides a potential explanation for the previously described ability of CT-B to act as an immunoadjuvant. These results suggest that the binding of ganglioside GM1 has multiple B cell growth-regulating effects.

Animals↗
PubMed1992

Choroid plexus carcinoma of childhood.

The presentation, growth patterns, and response to therapy of 11 consecutive children with choroid plexus carcinomas were analyzed, and the results were compared with the outcome reported in other series. Patients were a median of 26 months of age at diagnosis. Two patients had thalamic tumors, one had a posterior fossa primary, and the rest had ventricular lesions. Five of 11 (45%) children remain in continuous progression-free remission a median of 48 months from diagnosis. Four of the five in continuous remission had a "gross total" surgical resection, and only one received radiation therapy. Five of six patients with subtotal resections relapsed despite postoperative treatment with radiation therapy (three) and chemotherapy (one). The response to treatment with radiation therapy or chemotherapy at relapse was disappointing, with only one child (treated with etoposide) responding. In combination with other series, 11 of 14 children had prolonged progression-free survival after gross total resection (only two of whom received adjuvant therapy) compared with two of 20 after less than total resections, independent of the type of adjuvant therapy given. Adjuvant therapy for children with choroid plexus carcinomas is of unproven benefit, and this must be considered when analyzing innovative treatment trials for such children, especially for those with totally resected tumors. Patients with partially resected lesions fare poorly with present forms of treatment.

Child↗
PubMed1992

Costs and benefits of preemployment drug screening.

OBJECTIVE: This study provides a cost-benefit analysis of preemployment drug screening and evaluates the sensitivity of this analysis to variation in its underlying assumptions. DESIGN: Cost-benefit analysis, based on a cohort analytic study previously reported. SETTING: Employees of the US Postal Service in Boston, Mass. PARTICIPANTS: Estimates of costs and benefit are based on a cohort of 2533 postal workers in Boston and on average costs for the Postal Service in Boston and nationwide. RESULTS: Drug screening would have saved the Postal Service $162 per applicant hired. However, these results were sensitive to the assumptions in the model. If the prevalence of drug use in the population screened were 1% rather than 12%, the program would lose money. Similarly, if the cost per urine sample screened were $95 rather than the $49 assumed, then the program would lose money, even if the prevalence of drug positives was as high as 9%. CONCLUSIONS: Because of the sensitivity of this analysis to changes in its underlying assumptions, any company considering preemployment drug screening should carefully weigh the costs and benefits in its own industry.

Adult↗
PubMed1992

Cefoperazone versus ceftriaxone monotherapy of nosocomial pneumonia.

Ceftriaxone and cefoperazone monotherapy was compared in a multicentered, randomized, nonblinded, prospective study of patients with nosocomial pneumonia. These antibiotics were equally effective, with an overall successful treatment rate of 48 (80%) of 60 for the cefoperazone-treated patients and 35 (70%) of 50 for the ceftriaxone-treated patients. Patients with nursing-home-acquired pneumonia had similar bacterial pathogens and an almost identical cure rate to those patients with hospital-acquired infection. There was no statistical difference in the incidence of side effects of superinfections. The development of secondary pneumonia with resistant bacteria was low, 3% with cefoperazone and 4% with ceftriaxone. When antibiotic, administrative, and laboratory costs were calculated, cefoperazone was slightly less expensive than ceftriaxone. Both cefoperazone and ceftriaxone are effective therapy for the treatment of nosocomial pneumonia.

Adult↗
PubMed1992

Methodological concerns in evaluating psychiatric nursing care modalities and a proposed standard group protocol format for nurse-led groups.

The importance of detailing therapeutic effort and its outcome cannot be underestimated. The need to document outcomes has been re-emphasized in recent psychiatric mental health literature; however, the methodology for addressing threats to validity is well established. This article identifies the problems and issues related to a systematic evaluation of a therapeutic group intervention in an inpatient setting, specifically threats to validity, and describes the processes used in planning and implementing a standard group protocol format. The findings of this project depicting problems in the clarity and precision of documenting nursing practice are believed to be typical and generalizable. However, problems related to clarity and precision have not been addressed in the nursing literature. For a number of reasons, nursing staff members have not been sensitized to the importance of describing their practices in sufficient detail to allow others to replicate these practices. And yet, adequate evaluations of nursing efforts, particularly programmatic initiatives, require systematic testing with repeated trials. Although no description can describe in absolute terms what occurred, clear and precise descriptions of an intervention provide the foundation for valid conclusions about the effort. A detailed standard group protocol format provides a basis for establishing internal validity in subsequent quasi-experimental research designs as well as program evaluation studies.

Hospitalization↗
PubMed1992

The effectiveness of preemployment drug screening in the prediction of employment outcome.

Studies of adverse employment outcomes associated with positive preemployment drug screens have tracked employees for only about 1 year. Changes in drug use after hire may invalidate the predictions of employment outcome in later years which are essential for cost-benefit analyses. This blinded, prospective cohort study tracks absence, industrial accidents, occupational injuries, discipline, and turnover in 2537 screened employees through an average of 2 years. Marijuana-positive urines predicted increased turnover, accidents, injuries, discipline, and absence, but these risks appeared lower in the second year than the first. Cocaine-positive urines predicted increased turnover, accidents, injuries, discipline, and absence at levels not consistently different than the first year. Cost-benefit analyses of drug screening project employment risks throughout employees' careers. This study raises the possibility that elevated risks may decrease after the first year.

Boston↗
PubMed1992

Rabbit trachealis tension responses to receptor-mediated agonists are diminished by elastase.

The present study examined the effects of elastase, in concentrations present in respiratory secretions, on airway smooth muscle contractile responses in vitro and the magnitude of the airway epithelial inhibition of smooth muscle tension. Experiments were performed on 126 full-thickness tracheal strips from 25 rabbits. Isometric tension responses to acetylcholine (10(-8) to 10(-4) M) and potassium chloride (10 to 110 mM) were examined before and after a 5-min exposure to either porcine pancreatic elastase (PPE) or human neutrophil elastase (HNE). PPE (5 to 40 micrograms/100 microliters) reduced the tension response to acetylcholine but had no effect on the tension response to potassium chloride. PPE and HNE (20 micrograms/100 microliters) produced similar effects. Mechanical removal of the epithelium per se significantly (P less than 0.005) decreased the ED50 response to acetylcholine but did not affect maximal tension. However, the airway epithelial inhibitory effect on the acetylcholine tension response was similar in the presence and absence of PPE (20 micrograms/100 microliters). These data suggest that the diminution of tracheal smooth muscle tension responses to receptor-mediated agonists induced by elastase is a direct effect on the muscle and is not mediated by an effect of elastase on the respiratory epithelium.

Acetylcholine↗
PubMed1992

Synthesis and release of interleukin 1 by reoxygenated human mononuclear phagocytes.

To examine the possible involvement of cytokines in reperfusion injury, we have studied production of IL-1 by human vascular cells, including smooth muscle and mononuclear phagocytes. Exposure of cells to hypoxia (pO2 approximately 14 torr) followed by reoxygenation led to significant release of IL-1 only from the mononuclear phagocytes. Elaboration of IL-1 was dependent on the oxygen tension and duration of hypoxia (optimal at lower pO2s, approximately 14-20 torr, and after 9 h), as well as the time in reoxygenation (maximal IL-1 release at 6-9 h). Although a period of hypoxia was necessary for subsequent IL-1 production during reoxygenation of either peripheral blood monocytes or cultured monocyte-derived macrophages, no IL-1 release occurred during the hypoxic exposure. IL-1 released during reoxygenation was newly synthesized, and its production was triggered by the generation of oxygen free radicals, as it could be blocked by the addition of either allopurinol or free radical scavengers to cultures and could be stimulated in part by low concentrations of hydrogen peroxide or xanthine/xanthine oxidase. The potential pathophysiological effects of IL-1-containing supernatants from reoxygenated macrophages was shown by their induction of endothelial tissue factor and enhancement of endothelial adhesiveness for neutrophils, both of which could be blocked by anti-IL-1 antibody. The relevance of IL-1 to hypoxia/reoxygenation in vivo was suggested by the presence of circulating nanogram amounts of this cytokine in the plasma of mice during the reoxygenation period following a hypoxia.

Animals↗