137 results on '"Bollinger RR"'
Search Results
2. Ileoanal pull-through improves health related quality of life (HRQL) in patients with a history of ulcerative colitis (UC)
- Author
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Muir, A, primary, Phillips-Bute, B, additional, Eloubeidi, M, additional, Sears, C, additional, Bollinger, RR, additional, Koruda, M, additional, Hurd, L, additional, Bachwich, D, additional, Drossman, D, additional, and Provenzale, D, additional
- Published
- 1998
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3. Health-related quality of life after ileoanal pull-through evaluation and assessment of new health status measures
- Author
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Provenzale, D, primary, Shearin, M, additional, Phillips-Bute, BG, additional, Drossman, DA, additional, Li, Z, additional, Tillinger, W, additional, Schmitt, CM, additional, Bollinger, RR, additional, and Koruda, MJ, additional
- Published
- 1997
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4. Evolution of the hygiene hypothesis into biota alteration theory: what are the paradigms and where are the clinical applications?
- Author
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Villeneuve C, Kou HH, Eckermann H, Palkar A, Anderson LG, McKenney EA, Bollinger RR, and Parker W
- Subjects
- Culture, Host-Pathogen Interactions, Humans, Inflammation immunology, Inflammation microbiology, Microbiota physiology, Public Health, Biodiversity, Biota physiology, Hygiene Hypothesis, Models, Biological
- Abstract
For thousands of years, changes in human cultures have altered the biota associated with the human body, and those alterations have strongly influenced human health. The hygiene hypothesis has evolved over the past 30 years into a nuanced biota alteration theory, but modern medical priorities and regulatory policies have resulted in tragic underutilization of the acquired knowledge., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
- Full Text
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5. Appendectomy and Clostridium difficile colitis: relationships revealed by clinical observations and immunology.
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Sanders NL, Bollinger RR, Lee R, Thomas S, and Parker W
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- Appendix microbiology, Humans, Microbiota, Anti-Bacterial Agents adverse effects, Appendectomy adverse effects, Appendix immunology, Clostridioides difficile, Enterocolitis, Pseudomembranous etiology
- Abstract
Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon. These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure. However, more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile (C. difficile)-associated colitis, and probably other diseases associated with an altered microbiome. At the same time, appendectomy does not apparently put patients at risk for an initial onset of C. difficile-associated colitis. These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics, the use of which precedes the initial onset of C. difficile-associated colitis. Further, these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats, particularly the use of broad spectrum antibiotics.
- Published
- 2013
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6. Incorporation of secretory immunoglobulin A into biofilms can decrease their resistance to ciprofloxacin.
- Author
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Lee YH, Su KY, Wyse A, Barbas A, Palestrandt D, Shieh K, Everett ML, Devalapalli A, Orndorff PE, Bollinger RR, and Parker W
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- Animals, Culture Media chemistry, Escherichia coli drug effects, Escherichia coli physiology, Humans, Mice, Milk immunology, Anti-Bacterial Agents pharmacology, Biofilms drug effects, Ciprofloxacin pharmacology, Drug Resistance, Bacterial drug effects, Drug Resistance, Bacterial immunology, Immunoglobulin A, Secretory pharmacology
- Abstract
Extracellular matrices utilized by biofilms growing on inert surfaces are generally produced entirely by the bacteria growing within those biofilms, whereas symbiotic (mutualistic) biofilms growing in or on a wide range of plants and animals utilize host-derived macromolecules, such as mucoid substances, as components of their extracellular matrix. Incorporation of host-derived molecules may have a profound effect on the resistance to antibiotics of symbiotic biofilms, which may have important implications for medicine and biology. As an initial probe of the potential effects of host-derived molecules in the extracellular matrix on the sensitivity of biofilms to antibiotics, an in vitro model was used to evaluate the effects of ciprofloxacin on biofilms grown in the presence and absence of SIgA, a host-derived glycoprotein associated with biofilms in the mammalian gut. In five out of six strains of Escherichia coli tested, the incorporation of SIgA into the biofilms apparently reduced the resistance of the bacteria to ciprofloxacin. On the other hand, SIgA generally increased the resistance of planktonic bacteria to ciprofloxacin, perhaps due in part to the SIgA-mediated aggregation of the bacteria. These findings suggest that incorporation of host-derived molecules into the extracellular matrix of symbiotic biofilms might profoundly alter the properties of those biofilms, including the resistance of those biofilms to antibiotics., (© 2011 The Societies and Blackwell Publishing Asia Pty Ltd.)
- Published
- 2011
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7. Adaptation in a mouse colony monoassociated with Escherichia coli K-12 for more than 1,000 days.
- Author
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Lee SM, Wyse A, Lesher A, Everett ML, Lou L, Holzknecht ZE, Whitesides JF, Spears PA, Bowles DE, Lin SS, Tonkonogy SL, Orndorff PE, Bollinger RR, and Parker W
- Subjects
- Animals, Escherichia coli K12 genetics, Longitudinal Studies, Mice, Restriction Mapping, Escherichia coli K12 growth & development, Gastrointestinal Tract microbiology
- Abstract
Although mice associated with a single bacterial species have been used to provide a simple model for analysis of host-bacteria relationships, bacteria have been shown to display adaptability when grown in a variety of novel environments. In this study, changes associated with the host-bacterium relationship in mice monoassociated with Escherichia coli K-12 over a period of 1,031 days were evaluated. After 80 days, phenotypic diversification of E. coli was observed, with the colonizing bacteria having a broader distribution of growth rates in the laboratory than the parent E. coli. After 1,031 days, which included three generations of mice and an estimated 20,000 generations of E. coli, the initially homogeneous bacteria colonizing the mice had evolved to have widely different growth rates on agar, a potential decrease in tendency for spontaneous lysis in vivo, and an increased tendency for spontaneous lysis in vitro. Importantly, mice at the end of the experiment were colonized at an average density of bacteria that was more than 3-fold greater than mice colonized on day 80. Evaluation of selected isolates on day 1,031 revealed unique restriction endonuclease patterns and differences between isolates in expression of more than 10% of the proteins identified by two-dimensional electrophoresis, suggesting complex changes underlying the evolution of diversity during the experiment. These results suggest that monoassociated mice might be used as a tool for characterizing niches occupied by the intestinal flora and potentially as a method of targeting the evolution of bacteria for applications in biotechnology.
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- 2010
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8. Comparative anatomy and phylogenetic distribution of the mammalian cecal appendix.
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Smith HF, Fisher RE, Everett ML, Thomas AD, Bollinger RR, and Parker W
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- Animals, Cecum microbiology, Cecum anatomy & histology, Mammals anatomy & histology, Mammals classification, Phylogeny
- Abstract
A recently improved understanding of gut immunity has merged with current thinking in biological and medical science, pointing to an apparent function of the mammalian cecal appendix as a safe-house for symbiotic gut microbes, preserving the flora during times of gastrointestinal infection in societies without modern medicine. This function is potentially a selective force for the evolution and maintenance of the appendix, and provides an impetus for reassessment of the evolution of the appendix. A comparative anatomical approach reveals three apparent morphotypes of the cecal appendix, as well as appendix-like structures in some species that lack a true cecal appendix. Cladistic analyses indicate that the appendix has evolved independently at least twice (at least once in diprotodont marsupials and at least once in Euarchontoglires), shows a highly significant (P < 0.0001) phylogenetic signal in its distribution, and has been maintained in mammalian evolution for 80 million years or longer.
- Published
- 2009
- Full Text
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9. Altering and assessing persistence of genetically modified E. coli MG1655 in the large bowel.
- Author
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Barbas AS, Lesher AP, Thomas AD, Wyse A, Devalapalli AP, Lee YH, Tan HE, Orndorff PE, Bollinger RR, and Parker W
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- Adhesins, Bacterial genetics, Adhesins, Bacterial metabolism, Animals, Bacterial Adhesion, Cecum immunology, Cecum metabolism, Escherichia coli K12 genetics, Feces microbiology, Female, Fimbriae, Bacterial metabolism, Immunoglobulin A, Secretory immunology, Immunoglobulin A, Secretory metabolism, Intestinal Mucosa immunology, Intestinal Mucosa metabolism, Intestine, Large immunology, Mice, Mice, Inbred Strains, Probiotics metabolism, Time Factors, Escherichia coli K12 metabolism, Intestine, Large metabolism
- Abstract
One of the primary factors limiting the efficacy of probiotic therapies is short persistence time. Utilizing a novel method for assessment of persistence in the large bowel independent of survival of the organisms in the upper GI tract, we tested whether overexpression of the type 1 pilus, a colonization factor, or the presence of secretory immunoglobulin A (sIgA) might increase the persistence time of a laboratory strain of E. coli in the gut. For this purpose, cecal ostomies were created in mice and bacteria were placed in the ostomies, with or without sIgA. The persistence of the bacteria was assessed by evaluating the length of time after placement in which the bacteria were found in fecal samples. E. coli MG1655 expressing pili with the mannose-specific adhesin persisted in vivo significantly longer [mean (hours) +/- SEM: 91.50 +/- 15.98, n = 12] than bacteria expressing pili without adhesin [43.67 +/- 8.22, n = 12] (P = 0.01) and significantly longer than bacteria expressing neither pili nor adhesin [22.00 +/- 4.22, n = 12] (P = 0.0004). Although the persistence time of bacteria was not significantly affected by the presence of sIgA, the sIgA did cause a relative increase in retention of inert particles. These results, combined with an acute increase in stool production and stool water content in those animals not receiving sIgA following introduction of bacteria, suggest that sIgA might have anti-inflammatory properties in the gut when administered with enteric bacteria. Modifying expression of probiotic colonization factors may provide substantial benefit to patients with digestive tract diseases by virtue of increased persistence of the probiotic and, in the case of sIgA, an anti-inflammatory effect. This novel in vivo model may be useful in evaluating persistence time in a variety of current and future probiotic regimens.
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- 2009
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10. Pulmonary histopathology in an experimental model of chronic aspiration is independent of acidity.
- Author
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Downing TE, Sporn TA, Bollinger RR, Davis RD, Parker W, and Lin SS
- Subjects
- Animals, Bronchoalveolar Lavage Fluid chemistry, Chronic Disease, Cytokines analysis, Disease Models, Animal, Gastric Juice physiology, Gastroesophageal Reflux complications, Gastrointestinal Contents, Hydrogen-Ion Concentration, Male, Pneumonia, Aspiration etiology, Pneumonia, Aspiration physiopathology, Rats, Rats, Inbred F344, Respiratory Aspiration complications, Respiratory Aspiration physiopathology, Gastric Acid physiology, Lung pathology, Pneumonia, Aspiration pathology, Respiratory Aspiration pathology
- Abstract
Gastroesophageal reflux has become a major health concern in industrialized countries, with drugs aimed at blocking acid production being more frequently prescribed than any other drug. Damage to lung tissue as a result of chronic aspiration of gastric fluid is a primary health risk associated with gastro-esophageal reflux, with such aspiration being suspected in the induction or exacerbation of asthma and other lung diseases. In this study, a rodent model of chronic aspiration was used to characterize the pulmonary histopathology produced by repetitive aspiration events and to investigate the pathologic roles of individual gastric fluid components such as acid and particulate food matter. Rats exposed to chronic aspiration of whole gastric fluid developed a pathology distinct from that of acute lung injury, characterized by granulomatous interstitial pneumonitis with prominent formation of multinucleated giant cells. This pattern of injury could be reproduced with chronic aspiration of particulate food matter and with chronic aspiration of pH-neutralized gastric fluid, but not with chronic aspiration of hydrochloric acid. Thus, since acid-neutralizing therapy is currently the mainstay of treatment for patients with reflux-associated respiratory symptoms, these results strongly suggest that alternative therapeutic approaches aimed at preventing chronic-aspiration induced lung injury may be warranted.
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- 2008
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11. Biofilms in the normal human large bowel: fact rather than fiction.
- Author
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Bollinger RR, Barbas AS, Bush EL, Lin SS, and Parker W
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- Humans, Intestinal Mucosa microbiology, Symbiosis, Biofilms, Intestine, Large microbiology
- Published
- 2007
12. Secretory IgA and mucin-mediated biofilm formation by environmental strains of Escherichia coli: role of type 1 pili.
- Author
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Bollinger RR, Everett ML, Wahl SD, Lee YH, Orndorff PE, and Parker W
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- Adenocarcinoma pathology, Animals, Cell Line, Tumor microbiology, Colonic Neoplasms pathology, Escherichia coli isolation & purification, Feces microbiology, Female, Humans, Immunoglobulin A, Secretory isolation & purification, Mannose-Binding Lectins physiology, Membranes, Artificial, Mice microbiology, Milk, Human immunology, Polystyrenes, Species Specificity, Bacterial Adhesion physiology, Biofilms, Escherichia coli K12 physiology, Fimbriae, Bacterial physiology, Immunoglobulin A, Secretory physiology, Mucins physiology
- Abstract
Recent studies suggest the importance of secretory IgA (SIgA) and mucin in the mediation of biofilm formation by commensal bacteria within the mammalian gut. Studies using a variety of strains of Escherichia coli have indicated that the interaction between E. coli and SIgA is dependent on the type 1 pilus. In this study, the importance of the pilus in SIgA-mediated biofilm formation by a laboratory strain (MG1655) and environmental (fecal) strains of E. coli was evaluated. Transient expression of the type 1 pilus by the laboratory strain of E. coli failed to facilitate SIgA-mediated biofilm formation, whereas constitutive expression of the type 1 pilus by the laboratory strain was sufficient. In contrast, transient expression of the type 1 pilus was sufficient to facilitate SIgA-mediated biofilm formation by environmental isolates. The "threshold" for mucin-mediated biofilm formation appeared to be lower than that for SIgA-mediated biofilm formation, perhaps reflecting disparate roles of mucin and SIgA in mediating biofilm formation in the gut. These studies also provide the first procedures for the growth of bacterial biofilms on live epithelial cells in vitro, an important development that may facilitate future studies on the effects of bacterial biofilms on epithelial cells.
- Published
- 2006
- Full Text
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13. Organ allocation for transplantation in the USA and Korea: the changing roles of equity and utility.
- Author
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Bollinger RR and Cho WH
- Subjects
- Humans, Kidney Transplantation, Korea, Liver Transplantation, United States, Health Care Rationing, Organ Transplantation, Tissue and Organ Procurement
- Abstract
Realizing the promise and managing the success of organ transplantation requires the creation of unique institutions. An Organ Procurement and Transplant Network (OPTN) must be capable of increasing the supply of cadaver donor organs, of allocating those organs properly to recipients with due consideration for equity and utility, and of using scientific data to improve the system for the good of society. The OPTN should answer to the public and should expect public support. Both in the United States and in Korea major changes in deceased donor organ procurement and allocation are in progress. In the United States change takes the form of a renewed emphasis on achieving equity in kidney allocation without significantly sacrificing transplant graft or patient survival and the first ever use of purely objective, statistically evaluated criteria for liver allocation. In Korea where the OPTN is only four years old, change takes the form of a new brain death law and the creation of that country's first organ procurement organizations. In both countries, success in meeting the transplant needs of their populations will ultimately depend on the support of society and the cooperation of the entire medical community.
- Published
- 2004
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14. Immunoglobulin-mediated agglutination of and biofilm formation by Escherichia coli K-12 require the type 1 pilus fiber.
- Author
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Orndorff PE, Devapali A, Palestrant S, Wyse A, Everett ML, Bollinger RR, and Parker W
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- Adhesins, Bacterial genetics, Adhesins, Bacterial metabolism, Bacterial Adhesion, Escherichia coli genetics, Escherichia coli growth & development, Escherichia coli physiology, Fimbriae Proteins genetics, Fimbriae Proteins metabolism, Fimbriae, Bacterial genetics, Fimbriae, Bacterial metabolism, Humans, Immunoglobulin A, Secretory immunology, Mannose, Agglutination, Biofilms growth & development, Escherichia coli metabolism, Immunoglobulin A, Secretory metabolism
- Abstract
The binding of human secretory immunoglobulin A (SIgA), the primary immunoglobulin in the gut, to Escherichia coli is thought to be dependent on type 1 pili. Type 1 pili are filamentous bacterial surface attachment organelles comprised principally of a single protein, the product of the fimA gene. A minor component of the pilus fiber (the product of the fimH gene, termed the adhesin) mediates attachment to a variety of host cell molecules in a mannose inhibitable interaction that has been extensively described. We found that the aggregation of E. coli K-12 by human secretory IgA (SIgA) was dependent on the presence of the pilus fiber, even in the absence of the mannose specific adhesin or in the presence of 25 mM alpha-CH(3)Man. The presence of pilus without adhesin also facilitated SIgA-mediated biofilm formation on polystyrene, although biofilm formation was stronger in the presence of the adhesin. IgM also mediated aggregation and biofilm formation in a manner dependent on pili with or without adhesin. These findings indicate that the pilus fiber, even in the absence of the adhesin, may play a role in biologically important processes. Under conditions in which E. coli was agglutinated by SIgA, the binding of SIgA to E. coli was not increased by the presence of the pili, with or without adhesin. This observation suggests that the pili, with or without adhesin, affect factors such as cell surface rigidity or electrostatic repulsion, which can affect agglutination but which do not necessarily determine the level of bound immunoglobulin.
- Published
- 2004
- Full Text
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15. Microbial biofilms in the gut: visualization by electron microscopy and by acridine orange staining.
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Palestrant D, Holzknecht ZE, Collins BH, Parker W, Miller SE, and Bollinger RR
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- Animals, Bacteria growth & development, Bacteria immunology, Bacteria ultrastructure, Fluorescent Dyes, Humans, Immunoglobulin A analysis, Immunohistochemistry, Intestine, Large immunology, Intestine, Large ultrastructure, Papio, Rats, Acridine Orange, Biofilms, Intestine, Large microbiology, Microscopy, Electron methods, Staining and Labeling methods
- Abstract
The expression of colonization factors by gut bacteria, the growth rate of gut bacteria, and the rate of plasmid exchange by gut bacteria indicate that biofilms are a normal component of bacterial growth in the large bowel. Further, in vitro experiments demonstrate that growth of normal enteric bacteria in biofilms can be facilitated by secretory IgA (SIgA) and by mucins, 2 major components of the gut milieu. However, biofilms have not been previously observed in the normal gut. In this study, bacterial colonies characteristic of biofilms were observed by electron microscopy in normal rat, baboon, and human gut by electron microscopy. Confirming these results, acridine orange staining of flash-frozen tissues revealed biofilms in the mucus lining along normal gut epithelium. Immunofluorescenct microscopy supported this finding and demonstrated an association between IgA and the biofilms. These findings provide direct evidence that biofilms are present and may play an important role in the commensal relationship between enteric bacteria and their hosts. Hematoxylin and eosin staining of formalin-fixed tissues resulted in dissociation of the luminal contents from the epithelium, suggesting that the association between biofilms and the gut epithelium is sensitive to some conditions used to preserve tissue for histologic evaluation.
- Published
- 2004
16. Optimization of operating room allocation using linear programming techniques.
- Author
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Kuo PC, Schroeder RA, Mahaffey S, and Bollinger RR
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- Financial Management, Hospital economics, Hospitals, University economics, Humans, Models, Organizational, Fees, Medical, Health Care Rationing methods, Operating Rooms economics, Operating Rooms supply & distribution, Programming, Linear, Time Management economics
- Abstract
Background: New and innovative approaches must be used to rationally allocate scarce resources such as operating room time while simultaneously optimizing the associated financial return. In this article we use the technique of linear programming to optimize allocation of OR time among a group of surgeons based on professional fee generation., Study Design: For the period of December 1, 2000, to July 31, 2002, the following individualized data were obtained for the Division of General Surgery at Duke University Medical Center: allocated OR time (hours), case mix as determined by CPT codes, total OR time used, and normalized professional charges and receipts. Inpatient, outpatient, and emergency cases were included. The Solver linear programming routine in Microsoft Excel (Microsoft Corp.) was used to determine the optimal mix of surgical OR time allocation to maximize professional receipts., Results: Our model of optimized OR allocation would maximize weekly professional revenues at 237,523 US dollars, a potential increase of 15% over the historical value of 207,700 US dollars or an annualized increase of approximately 1.5 million US dollars., Conclusions: Our results suggest that mathematical modeling techniques used in operations research, management science, or decision science may rationally optimize OR allocation to maximize revenue or to minimize costs. These techniques may optimize allocation of scarce resources in the context of the goals specific to individual academic departments of surgery.
- Published
- 2003
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17. Human secretory immunoglobulin A may contribute to biofilm formation in the gut.
- Author
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Bollinger RR, Everett ML, Palestrant D, Love SD, Lin SS, and Parker W
- Subjects
- Bacteria growth & development, Bacteria immunology, Bacterial Adhesion immunology, Caco-2 Cells, Digestive System immunology, Epithelium immunology, Epithelium microbiology, Escherichia coli immunology, Feces microbiology, Humans, Mucins immunology, Biofilms growth & development, Digestive System microbiology, Immunoglobulin A, Secretory immunology
- Abstract
It is critical, both for the host and for the long-term benefit of the bacteria that colonize the gut, that bacterial overgrowth with subsequent bacterial translocation, which may lead to sepsis and death of the host, be avoided. Secretory IgA (sIgA) is known to be a key factor in this process, agglutinating bacteria and preventing their translocation in a process termed 'immune exclusion'. To determine whether human sIgA might facilitate the growth of normal enteric bacteria under some conditions, the growth of human enteric bacteria on cultured, fixed human epithelial cells was evaluated in the presence of sIgA or various other proteins. Human sIgA was found to facilitate biofilm formation by normal human gut flora and by Escherichia coli on cultured human epithelial cell surfaces under conditions in which non-adherent bacteria were repeatedly washed away. In addition, the presence of sIgA resulted in a 64% increase in adherence of E. coli to live cultured epithelial cells over a 45-min period. Mucin, another defence factor thought to play a key role in immune exclusion, was found to facilitate biofilm formation by E. coli. Our findings suggest that sIgA may contribute to biofilm formation in the gut.
- Published
- 2003
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18. A prospective evaluation of health-related quality of life after ileal pouch anal anastomosis for ulcerative colitis.
- Author
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Muir AJ, Edwards LJ, Sanders LL, Bollinger RR, Koruda MJ, Bachwich DR, and Provenzale D
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- Adult, Female, Humans, Male, Middle Aged, Postoperative Period, Prospective Studies, Time Factors, Colitis, Ulcerative physiopathology, Colitis, Ulcerative surgery, Health Status, Proctocolectomy, Restorative, Quality of Life
- Abstract
Objectives: The ileal pouch anal anastomosis is a safe and effective procedure but is also associated with pouchitis, small bowel obstruction, and incontinence. We prospectively evaluated the health-related quality of life using generic and disease-specific measures in a cohort of patients with ulcerative colitis undergoing ileal pouch anal anastomosis., Methods: Health-related quality of life measures included the Time Trade-off, Rating Form of IBD Patient Concerns, and the Short-Form 36. Assessments occurred preoperatively and 1, 6, and 12 months postoperatively., Results: Time Trade-off scores had significantly improved at the 1-month postoperative assessment and approached perfect health at the 12-month postoperative assessment. The Rating Form of IBD Patient Concerns revealed a significant reduction in patient concerns at 1 month, and this difference persisted at 6 and 12 months. Seven of the eight subscales of the Short-Form 36 revealed improved health-related quality of life postoperatively., Conclusions: Health-related quality of life improved after ileal pouch anal anastomosis when assessed with both generic and disease-specific measures. Improvements were observed as early as 1 month postoperatively. These results may guide patients and physicians as they consider and prepare for the impact of ileal pouch anal anastomosis.
- Published
- 2001
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19. Unexpected anti-alpha GalNAc antibodies in alpha-galactosyl transferase-deficient mice: complex relationship between genotype and the natural antibody repertoire.
- Author
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Love SD, Lee W, Nakamura YC, Platt JL, Bollinger RR, and Parker W
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- Animals, Galactosyltransferases genetics, Genotype, Humans, Immunity, Innate, Immunoglobulin Isotypes biosynthesis, Mice, Mice, Inbred DBA, Mice, Knockout, Self Tolerance, Acetylgalactosamine immunology, Antibody Formation, Galactosyltransferases deficiency
- Abstract
Mice lacking the alpha-galactosyl transferase gene (GalT(-/-) mice) have been used extensively as a model for xenotransplantation. Unlike wild type (WT) mice, GalT(-/-) mice do not produce Gal alpha 1-3Gal and are known to produce natural IgM specific for Gal alpha 1-3Gal, as do humans and higher primates. In addition to natural anti-Gal alpha 1-3Gal IgM in GalT(-/-) mice, we identified natural IgM which bound alpha-N-acetylgalactosamine (alpha GalNAc) but not Gal alpha 1-3Gal or blood group A. Although unexpected, these antibodies were expressed at 10-fold greater concentrations in GalT(-/-) mice than in WT mice. One explanation for this unexpected observation is that the production of natural antibodies is affected by self-antigen(s) that are similar but not identical to targets recognized by the natural antibody. Thus, the natural humoral immune system may be unresponsive to "near-self" antigens even though the individual is not tolerant to those antigens. Another explanation for the unexpected results is that there may be unanticipated and uncharacterized differences between GalT(-/-) mice and WT mice. These studies underscore the need to extensively characterize phenotypes in KO mice and indicate that the relationship between genotype and the natural immune repertoire can be complex.
- Published
- 2001
- Full Text
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20. Organ procurement organization (OPO), best practices.
- Author
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Bollinger RR, Heinrichs DR, Seem DL, Rosendale JD, and Johnson KS
- Subjects
- Humans, Organ Transplantation, Regression Analysis, Tissue Donors, United States, Tissue and Organ Procurement standards
- Abstract
There are currently 59 organ procurement organizations (OPOs) in the United States which serve their assigned geographic areas with variable productivity. Knowledge of organizational characteristics, programs and practices of more successful OPOs may be useful to increase the productivity of less successful OPOs. A preliminary survey of all OPO executive directors in the United States ascertained the most important beneficial and detrimental factors affecting their success. Site visits were then conducted at OPOs based on a selection process utilizing population size, geographic location, minority population, donors per million population and donors per thousand deaths among potential donors. All OPOs were categorized and the highest ranking OPOs in each of seven categories, based on 4 years of national data, were selected for the site visits. Regression analysis and correlation analysis using Pearson's product-moment correlation were performed. The survey to identify the important factors was returned by 47 (77%) of 61 OPOs existent in 1999. The most important beneficial factors identified by responding OPOs were adequate staffing and experience, allocation of responsibilities, hospital development and leadership. The most important detrimental factors were inadequate staffing and experience, poor donor hospital/transplant center/ OPO relationships and failure in the consent process. Site visits of the highest-ranking OPOs demonstrated all had respected, experienced leadership focused on the donation process; efficient mechanisms for resolving allocation or transplant center conflicts; systems for monitoring activity and tracking outcomes; excellent communication between OPO and transplant centers; open internal communication at all levels of the OPO; immediate, on-site response to vascular donor referrals; and volunteer support of public and/or professional education. Regression and correlation analysis demonstrated that as minority population increases, OPO performance declines (P < 0.03). Moreover, independent OPOs were associated with poorer performance regardless of minority population (P < 0.05). All of the successful OPOs visited had strong leadership, excellent donor hospital and transplant center relationships, well-developed communication and innovative methods to deal with their minority populations. Application of these practices within all OPOs could significantly enhance organ donation.
- Published
- 2001
- Full Text
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21. Natural anti-carbohydrate IgM in mice: dependence on age and strain.
- Author
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Love SD, Lee W, Nakamura YC, Platt JL, Bollinger RR, and Parker W
- Subjects
- Animals, Enzyme-Linked Immunosorbent Assay, Immunoglobulin M blood, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Species Specificity, Acetylglucosamine immunology, Aging immunology, Immunoglobulin M immunology
- Abstract
Natural anti-carbohydrate antibodies in humans play a key role in natural immunity and in recognition of allogeneic and xenogeneic antigens. Presumably, natural anti-carbohydrate antibodies in mice have similar functions; but these antibodies have not been extensively characterized. An assay was developed and used to screen for anti-carbohydrate IgM in the serum of BDF-1 mice. Among the natural anti-carbohydrate IgM identified, anti-betaGlcNAc IgM were the most abundant. Anti-betaGlcNAc IgG was not detected. Levels of anti-betaGlcNAc IgM were very low in 3-week-old BDF-1 mice and increased until 5 to 7 months of age. Levels of serum anti-betaGlcNAc IgM similar to those in BDF-1 mice were found in the serum of some strains related to the BDF-1 strain (DBA and C57BL/6) and in BDF mice lacking the galactosyl transferase gene. However, in two strains unrelated to the BDF-1 strain (FVB and SJL), levels of anti-betaGlcNAc IgM were less than one-tenth of those found in BDF-1 mice. These results provide considerable insight into the effect of age on the production of natural anti-carbohydrate antibodies in mice and indicate that production of those antibodies is strongly dependent on the strain of mouse. These studies will help in future development of murine models for studying the biological and medical roles of natural anti-carbohydrate antibodies.
- Published
- 2000
- Full Text
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22. The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.
- Author
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Lin SS, Weidner BC, Byrne GW, Diamond LE, Lawson JH, Hoopes CW, Daniels LJ, Daggett CW, Parker W, Harland RC, Davis RD, Bollinger RR, Logan JS, and Platt JL
- Subjects
- Acute Disease, Animals, Animals, Genetically Modified, Antibodies, Anti-Idiotypic, Antibodies, Heterophile isolation & purification, CD55 Antigens genetics, CD59 Antigens genetics, Complement System Proteins metabolism, Graft Rejection prevention & control, Humans, Immunosorbent Techniques, Papio, Swine, Antibodies, Heterophile blood, Graft Rejection etiology, Graft Rejection immunology, Heart Transplantation adverse effects, Heart Transplantation immunology
- Abstract
Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens.
- Published
- 1998
- Full Text
- View/download PDF
23. Effect of continuous complement inhibition using soluble complement receptor type 1 on survival of pig-to-primate cardiac xenografts.
- Author
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Pruitt SK, Bollinger RR, Collins BH, Marsh HC Jr, Levin JL, Rudolph AR, Baldwin WM 3rd, and Sanfilippo F
- Subjects
- Animals, Heart Transplantation methods, Immunosuppression Therapy methods, Infusions, Intravenous, Macaca fascicularis, Myocardial Reperfusion, Swine, Time Factors, Transplantation, Heterologous methods, Complement Inactivator Proteins, Graft Rejection prevention & control, Graft Survival immunology, Heart Transplantation immunology, Receptors, Complement immunology, Transplantation, Heterologous immunology
- Abstract
A single bolus of soluble complement (C) receptor type 1 (sCR1, TP-10) has been shown to delay hyperacute rejection (HAR) of porcine cardiac xenografts (Xgs) by primate recipients. In these recipients, C activity slowly returned and C deposition was noted in the Xgs at rejection. To evaluate the effect of sustained C inhibition using sCR1 on HAR, two additional cynomolgus monkeys received porcine cardiac Xgs and a continuous infusion of sCR1. In the first recipient, Xgs survival was 5 days (120+ hr), whereas in the second, Xg survival was 7 days (168+ hr). Serial biopsies of the Xgs were remarkable for an increasing cellular infiltrate composed predominantly of neutrophils and macrophages, and the development of edema, hemorrhage, and myocyte necrosis. These findings suggest that once C-mediated HAR has been inhibited, infiltration of the Xg by these cells may lead to accelerated acute rejection, which is an additional barrier to successful longer term Xg survival.
- Published
- 1997
- Full Text
- View/download PDF
24. Identification of poorly performing transplant centers using the UNOS center-specific data.
- Author
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Burdick J, Norman DJ, Hunsicker L, Costanzo-Nordin M, Edwards E, and Bollinger RR
- Subjects
- Chi-Square Distribution, Heart Transplantation mortality, Humans, Kidney Transplantation mortality, Liver Transplantation mortality, Multivariate Analysis, Quality Assurance, Health Care, Quality Control, Regression Analysis, Risk Factors, Survival Rate, Heart Transplantation standards, Kidney Transplantation standards, Liver Transplantation standards
- Published
- 1997
- Full Text
- View/download PDF
25. Orthostatic acute renal failure in a renal transplant.
- Author
-
Winn MP, Bollinger RR, and Conlon PJ
- Subjects
- Abdominal Muscles physiology, Female, Humans, Middle Aged, Obesity complications, Posture, Risk Factors, Acute Kidney Injury etiology, Kidney Transplantation
- Abstract
Complications due to ureteric obstruction are an occasional cause for renal transplant dysfunction. Here we report an unusual case of orthostatic renal failure in a renal transplant recipient. Our patient had the previously reported predisposing risk factors including: female sex, obesity, and lax abdominal musculature. It is important to recognize this unusual complication of renal transplantation early in order to preserve long-term graft function.
- Published
- 1997
- Full Text
- View/download PDF
26. Renal transplantation in adults with thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome.
- Author
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Conlon PJ, Brennan DC, Pfaf WW, Finn WF, Gehr T, Bollinger RR, and Smith SR
- Subjects
- Adult, Data Collection, Female, Graft Survival, Hemolytic-Uremic Syndrome complications, Humans, Kidney Failure, Chronic etiology, Kidney Failure, Chronic surgery, Male, Prognosis, Purpura, Thrombotic Thrombocytopenic complications, Recurrence, Reoperation, Time Factors, United States, Hemolytic-Uremic Syndrome surgery, Kidney Transplantation, Purpura, Thrombotic Thrombocytopenic surgery
- Abstract
Background: Thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome (TTP/HUS) is a rare cause of renal failure in adults. There is little data concerning the outcome of adult patients who receive a renal transplant for TTP/HUS:, Methods: We have carried out a survey of 22 transplant centres in the USA to determine the outcome of patients who developed ESRD from TTP/HUS and latter received a renal transplant., Results: Twelve of the 22 centres responded to our inquiry. Seven centres had not transplanted any patients with TTP/HUS, and five centres had transplanted a total of 24 grafts in 17 patients with TTP/HUS: Thirty-three per cent of patients demonstrated definite clinical and pathological evidence of recurrence of TTP/HUS: An additional 16% of patients demonstrated pathological evidence of possible recurrence of TTP/HUS in the absence of clinical manifestations. The overall 1-year graft survival rate was 42% and the 2-year graft survival rate was 35%. In our experience recurrence TTP/HUS was associated with universal graft failure. Although cyclosporin A does occasionally cause a thrombotic angiopathy in patients with no history of TTP/HUS, we found no evidence that it should be avoided in patients with a previous history of ESRD from TTP/HUS who subsequently receive a renal transplant., Conclusions: TTP/HUS frequently recurres in adults who receive a renal transplant, with a 2-year graft survival rate of 35%.
- Published
- 1996
27. The potential of xenotransplants.
- Author
-
Bollinger RR
- Subjects
- Animals, Bone Marrow Transplantation, Carbohydrate Sequence, Chimera, Disaccharides immunology, Graft Survival, Heart Transplantation immunology, Humans, Immunoglobulins, Intravenous therapeutic use, Immunosuppression Therapy methods, Immunosuppression Therapy trends, Immunosuppressive Agents therapeutic use, Molecular Sequence Data, Primates, Swine, Transplantation, Heterologous immunology, Heart Transplantation trends, Transplantation, Heterologous trends
- Published
- 1996
28. Continuous complement (C) inhibition using soluble C receptor type 1 (sCR1): effect on hyperacute rejection (HAR) of pig-to-primate cardiac xenografts.
- Author
-
Pruitt Sk, Bollinger RR, Collins BH, Marsh HC, Levin JL, Rudolph AR, Baldwin WM 3rd, and Sanfilippo F
- Subjects
- Animals, Graft Rejection pathology, Heart Transplantation pathology, Macaca fascicularis, Swine, Transplantation, Heterologous pathology, Complement Inactivator Proteins pharmacology, Graft Rejection prevention & control, Graft Survival, Heart Transplantation physiology, Receptors, Complement physiology, Transplantation, Heterologous physiology
- Published
- 1996
29. Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.
- Author
-
Magee JC, Collins BH, Harland RC, Lindman BJ, Bollinger RR, Frank MM, and Platt JL
- Subjects
- Animals, Dose-Response Relationship, Immunologic, Endothelium, Vascular immunology, Humans, Immunoglobulin M immunology, Primates, Swine, Transplantation, Heterologous, Complement C3 immunology, Graft Rejection prevention & control, Heart Transplantation immunology, Immunoglobulin G immunology
- Abstract
Immunoglobulins regulate the complement system by activating complement on foreign surfaces and diverting reactive complement proteins away from autologous cell surfaces. Based on this model, we explored the ability of Ig to balance complement activation versus control in a pig-to-primate cardiac xenotransplantation model in which the binding of xenoreactive antibodies of the recipient to graft blood vessels and the activation of complement cause hyperacute rejection. Human IgG added to human serum caused a dose-dependent decrease in deposition of iC3b, cytotoxicity, and heparan sulfate release when the serum was incubated with porcine endothelial cells. This decrease was not caused by alteration in antibody binding or consumption of complement but presumably reflected decreased formation of C3 convertase on the endothelial cells. Infusion of purified human IgG into nonhuman primates prevented hyperacute rejection of porcine hearts transplanted into the primates. As expected, the transplants contained deposits of recipient Ig and C1q but not other complement components. The inhibition of complement on endothelial cell surfaces and in the xenotransplantation model supports the idea that IgG regulates the classical complement pathway and supports therapeutic use of that agent in humoral-mediated disease.
- Published
- 1995
- Full Text
- View/download PDF
30. Differential expression of substance P receptors in patients with Crohn's disease and ulcerative colitis.
- Author
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Mantyh CR, Vigna SR, Bollinger RR, Mantyh PW, Maggio JE, and Pappas TN
- Subjects
- Adult, Anti-Inflammatory Agents therapeutic use, Blood Vessels metabolism, Colitis, Ulcerative drug therapy, Colitis, Ulcerative pathology, Colon blood supply, Colon innervation, Colon metabolism, Crohn Disease drug therapy, Crohn Disease pathology, Female, Humans, Ileum blood supply, Ileum innervation, Ileum metabolism, Lymphocytes metabolism, Male, Middle Aged, Muscle, Smooth metabolism, Neurons metabolism, Colitis, Ulcerative metabolism, Crohn Disease metabolism, Receptors, Neurokinin-1 metabolism
- Abstract
Background & Aims: Although clinical and pathological differences exist between Crohn's disease (CD) and ulcerative colitis (UC), distinguishing features are often absent, making diagnosis and treatment problematic. This study evaluated the differences in the expression of substance P (SP) receptors in patients with CD or UC., Methods: Tissue samples from patients with inflammatory bowel disease or control patients were obtained at surgery, processed for 125I-SP binding, and analyzed by quantitative autoradiography., Results: Patients with CD showed a massive increase in SP receptors in lymphoid aggregates, small blood vessels, and enteric neurons of the small and large bowel relative to controls. Six of 16 CD specimens had no pathological evidence of CD yet continued to express high concentrations of SP receptors. Pathologically positive patients with UC showed high concentrations of SP receptors on colonic lymphoid aggregates and small blood vessels but not enteric neurons. No increased SP binding was evident in clinically and pathologically quiescent UC colons and normal UC ileostomy samples., Conclusions: The increased expression of SP receptors on the enteric neurons of patients with CD distinguishes CD from UC. The persistent increased SP binding in pathologically normal CD tissue may indicate a subclinical disease state. SP receptor expression may have important diagnostic, etiologic, and therapeutic usefulness in inflammatory bowel disease.
- Published
- 1995
- Full Text
- View/download PDF
31. Rapid, comprehensive analysis of human cytokine mRNA and its application to the study of acute renal allograft rejection.
- Author
-
Kirk AD, Bollinger RR, and Finn OJ
- Subjects
- Base Sequence, Cytokines metabolism, DNA Primers, DNA, Complementary biosynthesis, Graft Rejection diagnosis, Graft Rejection genetics, Humans, Interferon-gamma metabolism, Interleukin-10 metabolism, Interleukin-2 metabolism, Interleukin-6 metabolism, Interleukin-8 metabolism, Molecular Sequence Data, Polymerase Chain Reaction, Cytokines genetics, Graft Rejection immunology, Kidney Transplantation adverse effects, RNA, Messenger analysis
- Abstract
Cytokine mRNA analysis was performed on human renal allograft needle core biopsies by a PCR-based assay. The assay was specifically developed to be capable of simultaneous analysis of multiple interleukin transcripts (IL-1-IL-12), as well as those of other relevant cytokines, by one person in less than 1 day from cultured cells or directly from tissue samples. It was initially used on preparations containing known amounts of plasmid DNA encoding individual cytokine cDNA sequences, confirming that the sensitivity of this technique was both well defined and comparable for all target sequences tested. Analysis of human PBLs prior to stimulation, after polyclonal stimulation with PHA and after simultaneous treatment with PHA and MP or CyA, was also performed to show a proportional relationship between mRNA levels measured by PCR and protein release measured by ELISA (R2 = 0.86). This correlation was not adversely altered by pharmacologic immunosuppression by MP or CyA. Thus, this method of PCR primer design and usage was appropriate for the clinical study of cytokine mRNA levels during allograft rejection. Direct study of cytokine mRNA in allograft biopsy tissue showed that IL-2 was specifically and significantly (p = 0.006) elevated during ACR when compared to other causes of graft dysfunction. Transcripts from the IFN-gamma and IL-6 genes were also increased in ACR (p = 0.001 and 0.017, respectively), whereas increased IL-8 mRNA was correlated with irreversible loss of graft function (p = 0.02). TNF-alpha, IL-1 beta, and IL-10 gene transcripts were also detected during ACR, but were not quantitatively increased compared to other forms of graft injury (p > 0.2). We conclude that acute cellular rejection is associated with intragraft mRNA from the IL-2 gene. Other transcripts, including those from the IFN-gamma, IL-6, and IL-8 genes, are detected in increased amounts during this process. Messenger RNA from the TNF-alpha, IL-1 beta and IL-10 genes is also detected during ACR, but the presence of these transcripts is not exclusive to this process.
- Published
- 1995
- Full Text
- View/download PDF
32. Recipient Kupffer cell influx into xenografted liver.
- Author
-
Yamaguchi Y, Halperin EC, Mori K, Bollinger RR, and Ogawa M
- Subjects
- Animals, Cell Count, Cricetinae, Cyclosporine therapeutic use, Graft Rejection pathology, Graft Survival immunology, Immunohistochemistry, Liver Transplantation pathology, Lymphatic Irradiation, Male, Rats, Rats, Inbred Lew, Time Factors, Transplantation, Heterologous pathology, Graft Rejection immunology, Kupffer Cells immunology, Liver Transplantation immunology, Transplantation, Heterologous immunology
- Abstract
Previously we reported that the combination of total lymphoid irradiation (TLI), cyclosporine A (CsA), and splenectomy have an immunosuppressive effect sufficient to significantly prolong liver xenograft survival in the LVG hamster to the LEW rat model. Using this model, we have investigated recipient Kupffer cell influx into the xenografted liver. In the rat liver, the Kupffer cells are heavily stained with Ki-M2R, a rat anti-macrophage monoclonal antibody, whereas sinus endothelial cells and liver parenchymal cells are invariably negative. Kupffer cells of the hamster liver are not stained with Ki-M2R. In the xenografted animals, we found cells in the sinusoidal wall of the xenograft stained, with progressively increased activity, in animals 45-60 days after transplant. The morphological pattern of these Ki-M2R-positive cells in the hepatic xenograft resembled the Kupffer cells of the normal rat liver. These findings indicate recipient macrophage influx into the xenografted liver.
- Published
- 1995
- Full Text
- View/download PDF
33. Prevention of hyperacute xenograft rejection by intravenous immunoglobulin.
- Author
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Magee JC, Collins BH, Harland RC, Bollinger RR, Frank MM, and Platt JL
- Subjects
- Acute Disease, Animals, Endothelium, Vascular immunology, Graft Rejection immunology, Humans, Immunoglobulin G pharmacology, Immunoglobulin M metabolism, Macaca fascicularis, Papio, Swine, Transplantation, Heterotopic, Graft Rejection prevention & control, Heart Transplantation immunology, Immunoglobulins, Intravenous therapeutic use, Transplantation, Heterologous immunology
- Published
- 1995
34. Immunopathology of porcine livers perfused with blood of humans with fulminant hepatic failure.
- Author
-
Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, Bollinger RR, Meyers WC, and Platt JL
- Subjects
- Animals, Antibodies, Heterophile analysis, Complement System Proteins analysis, Enzyme-Linked Immunosorbent Assay, Fluorescein-5-isothiocyanate, Humans, Perfusion, Swine, Transplantation, Heterologous immunology, Hepatic Encephalopathy blood, Liver immunology, Liver pathology
- Published
- 1995
35. A UNOS perspective on donor liver allocation. United Network for Organ Sharing.
- Author
-
Bollinger RR
- Subjects
- Dissent and Disputes, Federal Government, Group Processes, Humans, Patient Selection, Public Policy, Tissue and Organ Procurement legislation & jurisprudence, Tissue and Organ Procurement trends, Voluntary Programs, Waiting Lists, Health Care Rationing, Liver Transplantation, Resource Allocation, Tissue Donors supply & distribution, Tissue and Organ Procurement organization & administration
- Published
- 1995
- Full Text
- View/download PDF
36. Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure.
- Author
-
Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, Bollinger RR, Meyers WC, and Platt JL
- Subjects
- Adult, Animals, Antibody Formation, Blood Cell Count, Complement C3 analysis, Female, Humans, Immunity, Innate, Immunoglobulin G blood, Immunoglobulin M blood, Leukocyte Count, Liver immunology, Male, Middle Aged, Perfusion, Swine, Hepatic Encephalopathy blood, Liver pathology
- Abstract
Hyperacute rejection of renal and cardiac xenografts is initiated by the reaction of recipient natural antibodies and complement with endothelial cell antigens of the donor organ. The liver is thought to be less susceptible to this form of rejection; however, the mechanisms underlying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 human subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary metabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic examination of the xenoperfused livers revealed focal hepatocellular necrosis, prominent infiltration of neutrophils, and, in 7 of 9 cases, periportal and centrilobular hemorrhage and thrombosis. Immunopathology demonstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along the luminal surfaces of large blood vessels in most cases. Trace deposits of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdin, and the membrane attack complex were not detected. Human anti-porcine natural antibody titers decreased less than expected during the perfusions. Serum CH50, C3, and C4 levels were low before each procedure and decreased slightly with perfusion. One patient perfused 2 porcine livers and a human liver. The human liver had focal hepatocellular necrosis, trace deposits of IgM, no deposits of complement, and an infiltrate consisting of neutrophils; however, the neutrophil influx was less than that observed in the xenoperfused livers. To further evaluate the effects of alloperfusion, venovenous bypass was established in 2 pigs and the extracorporeal circuit was utilized to perfuse 2 porcine livers. The alloperfused porcine livers had focal hepatocellular necrosis and a minimal infiltrate of neutrophils. There were no deposits of porcine IgM, IgG, or complement components. In conclusion, although the porcine livers perfused by human blood sustained structural damage, the time course, the absence of immune deposits, and the findings of similar, albeit less severe, lesions in the alloperfused livers suggest that the pathogenesis of tissue injury in the xenoperfused livers differs from that of hyperacute rejection and may be related to the action of recipient neutrophils.
- Published
- 1994
37. Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors.
- Author
-
Mantyh CR, Vigna SR, Maggio JE, Mantyh PW, Bollinger RR, and Pappas TN
- Subjects
- Binding Sites, Biphenyl Compounds pharmacology, Blood Vessels metabolism, Humans, Indoles pharmacology, Isoindoles, Neurokinin-1 Receptor Antagonists, Quinuclidines pharmacology, Substance P antagonists & inhibitors, Inflammatory Bowel Diseases metabolism, Intestinal Mucosa metabolism, Intestines blood supply, Lymphoid Tissue metabolism, Receptors, Neurokinin-1 metabolism, Substance P metabolism
- Abstract
Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflammatory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606 abolished saturable 125I-Bolton-Hunter substance P binding to the ectopically expressed receptors in frozen sections of surgically resected bowel from five patients with either Crohn's disease or ulcerative colitis. The rank order of affinity was approximately substance P approximately CP-96,345 approximately L-703,606 > RP-67,580. These results suggest that: (i) the ectopically expressed substance P binding sites in inflammatory bowel disease are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have similar receptor affinities and specificities for substance P and the non-peptide antagonists, and (iii) non-peptide antagonists may be therapeutically beneficial in inflammatory bowel disease by inhibiting the pro-inflammatory effects of substance P acting via the NK-1 receptor.
- Published
- 1994
- Full Text
- View/download PDF
38. Ganciclovir/acyclovir prophylaxis reduces the incidence of cytomegalovirus infections in pancreas transplant recipients.
- Author
-
Harland RC, Vernon WB, Bunzendahl H, Thompson JK, Lawrence C, and Bollinger RR
- Subjects
- Cytomegalovirus Infections epidemiology, Drug Therapy, Combination, Graft Rejection, Hospitalization, Humans, Incidence, Acyclovir therapeutic use, Cytomegalovirus Infections prevention & control, Diabetes Mellitus, Type 1 surgery, Ganciclovir therapeutic use, Pancreas Transplantation
- Published
- 1994
39. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.
- Author
-
Pruitt SK, Kirk AD, Bollinger RR, Marsh HC Jr, Collins BH, Levin JL, Mault JR, Heinle JS, Ibrahim S, and Rudolph AR
- Subjects
- Animals, Antibodies, Heterophile blood, Biopsy, Graft Survival, Haplorhini, Heart Transplantation pathology, Heart Transplantation physiology, Humans, Male, Microscopy, Fluorescence, Models, Biological, Swine, Transplantation, Heterologous physiology, Graft Rejection immunology, Receptors, Complement physiology, Transplantation, Heterologous immunology
- Abstract
The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.
- Published
- 1994
- Full Text
- View/download PDF
40. Adenine nucleotides of ischemic intestine do not reflect injury.
- Author
-
Canada AT, Coleman LR Jr, Fabian MA, and Bollinger RR
- Subjects
- Adenosine Diphosphate metabolism, Adenosine Monophosphate metabolism, Adenosine Triphosphate metabolism, Animals, Hot Temperature, Hypoxanthine, Hypoxanthines metabolism, Intestinal Diseases etiology, Intestinal Mucosa metabolism, Ischemia complications, Kinetics, Male, NAD metabolism, NADP metabolism, Rats, Rats, Sprague-Dawley, Reperfusion, Time Factors, Xanthine, Xanthines metabolism, Adenine Nucleotides metabolism, Intestinal Diseases metabolism, Intestines blood supply, Ischemia metabolism
- Abstract
Warm ischemia of the intestine is a medical emergency which results from mesenteric vascular occlusion. In addition, intestinal transplantation techniques will also inevitably result in intestinal ischemia. The recovery of organ function following ischemia depends on the extent of irreversible damage produced by the ischemia and the extent of reflow upon reperfusion. In some organs energy homeostasis has been found to correlate with organ recovery and graft survival following ischemia-reperfusion. Investigating the usefulness of the determination of adenine and pyridine nucleotides as indicators of the extent of ischemic injury in intestinal segments, we found that after an initial 40% decrease in ATP following 30 min of ischemia there was no further decrease despite increasing the ischemia period to 120 min. Similarly, the decrease in NAD+ and NADP which occurred after 30 min of ischemia did not decrease further after 60, 90, or 120 min of ischemia. Xanthine was the only biochemical where an increase appeared to correlate with ischemia duration while energy charge was of no value in indicating injury extent. Additionally, after reperfusion there was at best a poor correlation between recovery of ATP content and the duration of ischemia. Microcirculation reflow after reperfusion indicated ischemia time-related endothelial cell injury. Thus, the measurement of high-energy phosphates in intestinal segments is not of value as an indicator of the extent of intestinal ischemic injury.
- Published
- 1993
- Full Text
- View/download PDF
41. Brequinar sodium potentiates the effects of cyclosporine in experimental small bowel transplantation.
- Author
-
Collins BH, Areford ML, Fabian MA, Jaffee BD, and Bollinger RR
- Subjects
- Animals, Drug Synergism, Drug Therapy, Combination, Graft Rejection, Graft Survival drug effects, Male, Rats, Rats, Inbred BN, Rats, Inbred Lew, Biphenyl Compounds pharmacology, Cyclosporine pharmacology, Immunosuppressive Agents pharmacology, Intestine, Small transplantation
- Published
- 1993
42. The human antiporcine cellular repertoire. In vitro studies of acquired and innate cellular responsiveness.
- Author
-
Kirk AD, Li RA, Kinch MS, Abernethy KA, Doyle C, and Bollinger RR
- Subjects
- Animals, CD4 Antigens metabolism, Chromium Radioisotopes metabolism, Cytotoxicity, Immunologic, Gene Expression, HLA-D Antigens immunology, Humans, Immunity, Cellular, Immunity, Innate, Lymphocyte Activation immunology, Lymphocyte Culture Test, Mixed, Protein Binding, Receptors, Antigen, T-Cell, alpha-beta genetics, Swine immunology, T-Lymphocytes physiology, Time Factors, Antibodies pharmacology, T-Lymphocytes immunology, Transplantation, Heterologous immunology
- Abstract
Discordant xenogeneic transplantation offers a potentially unlimited source of donor organs from easily bred, nonendangered, physiologically compatible animals, but has been limited by the inevitable occurrence of hyperacute rejection (HAR). The potential existence of cell-mediated discordant graft rejection has remained obscured by HAR, and hence is incompletely understood. To define the cellular elements capable of recognition of and subsequent response against discordant tissue in a clinically applicable species combination, we have studied the in vitro interaction of human peripheral blood lymphocytes against 3 porcine B lymphoblastoid cell lines and 6 primary porcine endothelial cell populations. PBL from all individuals tested (n = 10) proliferated in response to culture for 72 hr in xenogeneic mixed lymphocyte culture (XMLC) with cell lines expressing porcine MHC (SLA) class II antigens, while endothelial cultures lacking SLA class II generally failed to evoke a response. The proliferative response to class II-positive cells was attenuated by addition of anti-SLA class II antibody but not by anti-SLA class I antibody. Two endothelial populations expressing class II stimulated an inhibitable proliferative response. The magnitude of the short-term proliferative xenogeneic response was similar to that evoked by fully mismatched allogeneic human B lymphoblastoid stimulators. Additionally, extended XMLC was performed with PBL from 3 individuals. All populations responded with continued proliferation when repeatedly stimulated by porcine cells. This was characterized not only by T cell growth, but by prominent NK cell growth as well. Elucidation of the TCR V beta chain usage patterns by semiquantitative PCR documented selection of TCR transcripts from gene family V beta 2 in each group, complemented by a heterogeneous mixture of other transcripts including V beta 17.1, 20.1, and 6.1, suggesting that direct human TCR binding of porcine cells occurs, and that it is likely to be an individualistic response complemented by a more homogeneous NK response. A 51Cr release assay was utilized to demonstrate that unprimed PBL could also lyse porcine target cells. This cytotoxic response was maintained despite the complete removal of T cells, suggesting that porcine-directed NK cell activity is present prior to the maturation of any T cell response. Cytolysis was also demonstrated in serum-free medium and thus was not mediated solely by antibody-dependent cellular cytotoxicity. Chinese hamster ovary cells transfected with the human T cell receptor accessory molecule CD4 were used to study the ability of this molecule to stabilize the interaction between the human TCR and SLA class II.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1993
43. Human antiporcine mixed lymphocyte reaction.
- Author
-
Li RA, Kirk AD, Abernathy KA, and Bollinger RR
- Subjects
- Animals, Graft Rejection immunology, Humans, Immunity, Cellular, Lymphocyte Culture Test, Mixed, Swine, Transplantation, Heterologous immunology, T-Lymphocytes immunology
- Published
- 1993
44. Rapid translocation of bacteria in small bowel transplantation.
- Author
-
Fabian MA and Bollinger RR
- Subjects
- Animals, Rats, Rats, Inbred ACI, Rats, Inbred Lew, Reference Values, Transplantation, Homologous, Transplantation, Isogeneic, Escherichia coli isolation & purification, Intestinal Mucosa microbiology, Intestinal Mucosa transplantation, Intestine, Small microbiology, Intestine, Small transplantation, Liver microbiology, Spleen microbiology
- Published
- 1992
45. Rapamycin suppression of host-versus-graft and graft-versus-host disease in MHC-mismatched rats.
- Author
-
Fabian MA, Denning SM, and Bollinger RR
- Subjects
- Animals, Histocompatibility Testing, Mice, Mice, Inbred Strains, Rats, Rats, Inbred Lew, Sirolimus, Transplantation, Heterotopic, Transplantation, Homologous immunology, Transplantation, Isogeneic immunology, Graft Survival, Graft vs Host Disease prevention & control, Host vs Graft Reaction drug effects, Immunosuppressive Agents therapeutic use, Intestine, Small transplantation, Major Histocompatibility Complex, Polyenes therapeutic use
- Published
- 1992
46. Use of tissue blood flow and high energy phosphate content to predict small bowel graft survival.
- Author
-
Fabian MA, Canada AT, Coleman LR Jr, and Bollinger RR
- Subjects
- Animals, Intestine, Small blood supply, Intestine, Small physiology, Rats, Rats, Inbred Lew, Regional Blood Flow, Regression Analysis, Reperfusion, Transplantation, Heterotopic physiology, Energy Metabolism, Graft Survival, Intestine, Small transplantation, Phosphates metabolism
- Published
- 1992
47. Xenoantigens expressed on swine erythrocytes, lymphoblastoid cells, and endothelial cells.
- Author
-
Yang Q, Bollinger RR, and De Buysscher EV
- Subjects
- ABO Blood-Group System immunology, Animals, Models, Biological, Swine, Transplantation, Heterologous immunology, Antibodies, Heterophile immunology, Antigens, Heterophile analysis, Endothelium, Vascular immunology, Erythrocytes immunology, Lymphocytes immunology
- Published
- 1992
48. Species differences in natural xenoantibody to swine.
- Author
-
Fabian MA, Abernethy KA, and Bollinger RR
- Subjects
- Animals, Aorta, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Humans, Immunoglobulin G analysis, Immunoglobulin M analysis, Macaca fascicularis, Macaca mulatta, Species Specificity, Antibodies, Heterophile immunology, Endothelium, Vascular immunology, Swine immunology
- Published
- 1992
49. Effect of soluble complement receptor type 1 on natural antibody levels during xenograft rejection.
- Author
-
Pruitt SK, Baldwin WM 3rd, Marsh HC Jr, Lin SS, Yeh CG, and Bollinger RR
- Subjects
- Animals, Guinea Pigs, Immunoglobulin G metabolism, Immunoglobulin M metabolism, Rats, Rats, Inbred Lew, Antibody Formation, Graft Rejection, Heart Transplantation immunology, Receptors, Complement immunology, Transplantation, Heterologous immunology
- Published
- 1992
50. In vitro analysis of the human antiporcine T-cell repertoire.
- Author
-
Kirk AD, Hall BL, Finn OJ, and Bollinger RR
- Subjects
- Animals, Humans, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Macromolecular Substances, Polymerase Chain Reaction, RNA, Messenger genetics, RNA, Messenger metabolism, Swine, Transcription, Genetic, Lymphocytes immunology, Receptors, Antigen, T-Cell genetics, T-Lymphocytes immunology
- Published
- 1992
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