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53. Abstracts of papers presented at the 63rd annual PAA meeting

Author

Rueda, Jose L., Berrios, Donald, Amoros W. R., Mendoza, H. A., Archuleta Jose Gil, Easton, Gene D., Brown C. R., Bruce Doug, Camadro Elsa, Peloquin, S. J., Davis J. R., Jones, W. B., Dearborn Curtis H., Deboer S. H., Dwelle Robert B., Kleinkopf, Gale E., Steinhorst, R. K., Pavek, J. J., Easton Gene D., Estrada Nelson, Ewing Elmer E., Hedges, Anne, Sieczka, Joseph B., Freeman Jack A., Goth R. W., Webb, R. E., Graham D. C., Hammond David F., Zozimo, Hauman, Henninger M. R., Patterson, J. W., Hiller L. K., Koller, D. C., VanDenburgh, R. W., Huang Don Y., Ryan, Clarence A., Swanson, Barry G., Hyde Gary M., Thornton, R. E., Kunkel, Robert, Iwanaga Masaru, Jackson Michael T., Gonzalez, L. C., Jaworski C. A., Goth, R. W., Phatak, S. C., Arthur, Kelman, Kintner Judy, Kloepper J. W., Schroth, M. N., Weinhold, A. R., Bowman, T., Kuenemann Ray, Kunkel R., Holstad, N. M., Mitchell, D. C., Russell, T. S., Landeo J. A., Hanneman, R. E., Lazin M. B., Mendoza, Humberto A., Sung, I. J., Ewing, E. E., Sieczka, J. B., Levy David, Martin Mark W., McLaughlin Richard, Munoz F. J., Plaisted, R. L., Ng K. C., Weaver, M. L., Nielsen, L. W., O’keefe R. B., Osman S. F., Zacharius, R. M., Otazu V., Zink, R. T., Secor, Gary A., Rasco Eufemio T., Plaisted, Robert L., Reeves A. F., Hunter, J. H., Ross Craig, Kunkel, R., Gardner, W., Rowe R. C., Sacher R. F., Iritani, W. M., Sand Paul, Aphis, F., Sanford L. L., Ladd, T. L., Sinden S. L., Sanford, L. L., Osman, S. F., Steven, Slack, Slack S. A., Sanford, H. A., Manzer, F. E., Sparks Walter C., Stiles Dwight G., Tai G. C. C., Tarn, T. R., Tarhan A. F., Cash, J. N., Markakis, P., Thornton Robert E., Vandenburgh R. W., Hiller, L. K., Vitosh M. L., Bird, G. W., Chase, R. W., Noling, J. W., Vruggink H., Geesteranus, Maas, H. P., Weaver M. L., Ng, K. C., Weis G. G., Wade, E. K., Baldock, J. O., Wells Arthur L., Workman Milton, Cameron, Arthur, Twomey, James, Yu Wen-Wei, Swanson, B. G., and Zink R. T.

Published
1979
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55. Hepatitis C virus prevalence and clearance among US blood donors, 2006-2007: Associations with birth cohort, multiple pregnancies, and body mass index

Author

Murphy, EL, Fang, J, Tu, Y, Cable, R, Hillyer, CD, Sacher, R, Triulzi, D, Gottschall, JL, and Busch, MP

Subjects
virus diseases, digestive system diseases
Abstract

Background. During the period 1992-1993, the prevalence of hepatitis C virus (HCV) antibodies (anti-HCV) among US blood donors was 0.36%, but contemporary data on the prevalence of antibody to HCV and the prevalence of HCV RNA are lacking. Methods. We performed a large, cross-sectional study of blood donors at 6 US blood centers during 2006-2007. Anti-HCV was measured with enzyme-linked immunosorbent assay followed by immunoblot, and HCV RNA was measured with nucleic acid testing. Adjusted odds ratios (aORs) were derived using multivariable logistic regression. Results. Of 959,281 donors, 695 had anti-HCV detected (prevalence, 0.072%). Of those with anti-HCV, 516 (74%) had test results positive for HCV RNA, and 179 (26%) had test results that were negative for HCV RNA. Compared with the prevalence during the period 1992-1993, prevalence during 2006-2007 was lower and peaked in older age groups. Anti-HCV was associated with a body mass index (BMI) >30 (aOR, 0.6; 95% confidence interval [CI], 0.5-0.8), and among women, it was associated with higher gravidity (aOR for ≥5 vs 0 pregnancies, 3.2; 95% CI, 1.9-5.4). HCV RNA negative status was associated with black race (aOR, 0.4; 95% CI, 0.2-0.7), having more than a high school education (aOR, 1.6; 95% CI, 1.1-2.4), and BMI >30 (aOR, 2.4; 95% CI, 1.4-3.9). Conclusions. Decreasing HCV prevalence is most likely attributable to culling of seropositive donors and a birth cohort effect. We found new associations between anti-HCV prevalence and gravidity and obesity. Recently discovered genetic factors may underlie differences in HCV RNA clearance in black donors. © 2010 by the Infectious Diseases Society of America.

Published
2010

59. RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42

Author

Misselwitz, B, Dilling, S, Vonaesch, P, Sacher, R, Snijder, B, Schlumberger, M, Rout, S, Stark, M, von Mering, C; https://orcid.org/0000-0001-7734-9102, Pelkmans, L, Hardt, W D, Misselwitz, B, Dilling, S, Vonaesch, P, Sacher, R, Snijder, B, Schlumberger, M, Rout, S, Stark, M, von Mering, C; https://orcid.org/0000-0001-7734-9102, Pelkmans, L, and Hardt, W D

Abstract

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G-nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome-scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE-mediated entry. Follow-up assays assigned these 'hits' to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella-containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI-facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs.

Published
2011

60. Laboratory test differences associated with HTLV-I and HTLV-II infection

Author

Murphy, EL, Glynn, S, Watanabe, K, Fridey, J, Sacher, R, Schreiber, G, Luban, N, and University of Groningen

Subjects
EXPRESSION, lactic dehydrogenase, calcium, mean corpuscular volume, RECEPTOR, eosinophil count, creatine kinase, viruses, virus diseases, platelet count, HTLV-I, CARRIERS, HTLV-II, immune system diseases, hemic and lymphatic diseases, BLOOD-DONORS, JAMAICA, RISK-FACTORS, SPONTANEOUS LYMPHOCYTE-PROLIFERATION, lymphocyte count, MYELOPATHY, CELL LEUKEMIA-VIRUS
Abstract

Reports of laboratory abnormalities associated with HTLV-I and HTLV-II infection are inconsistent. We assessed complete blood counts and selected serum chemistry measures at enrollment in a cohort of 153 HTLV-I-seropositive, 386 HTLV-II-seropositive, and 795 HTLV-seronegative blood donors. Linear and logistic regression were used to adjust for potential confounding variables including age, gender, race/ethnicity, education level, blood center, and injection drug use. Compared with seronegative donors, absolute lymphocyte counts were 6% and 10% higher, on average, in HTLV-I-infected (p = .03) and HTLV-II-infected (p = .0001) donors, respectively. HTLV-I- and HTLV-II-seropostive donors had, on average, 17,630 (p = .003) and 15,160 (p = .0005) more platelets, respectively. HTLV-I-infected donors also had an average of 30 fewer eosinophils/mu l (p = .003) and a slightly higher level of lactic dehydrogenase (p = .05). HTLV-II-infected subjects had on average, an 11% decrease in creatine kinase (p = .006), a minor increase in mean corpuscular volume (p = .01), and a slightly lower serum calcium level (p = .0005). These results indicate that both HTLV-I and HTLV-II may raise levels of lymphocytes and platelets by unknown mechanisms. Lower eosinophil counts may be related to the increased susceptibility of HTLV-I-infected subjects to parasitic diseases.

Published
1998

79. Approach to Management of Thrombotic Thrombocytopenic Purpura at University of Cincinnati.

Author

Karim, N. Abdel, Haider, S., Siegrist, C., Ahmad, N., Zarzour, A., J. Ying, Yasin, Z., and Sacher, R.

Subjects
THROMBOTIC thrombocytopenic purpura treatment, RARE diseases, BLOOD platelet aggregation, THROMBOTIC thrombocytopenic purpura, THROMBOCYTOPENIA, KIDNEY abnormalities, IMMUNOSUPPRESSIVE agents, PATIENTS
Abstract

Thrombotic Thrombocytopenic Purpura (TTP) is a rare hematologic emergency, congenital or acquired, characterized by ischemic damage of various organs because of platelet aggregation. It is the common name for adults with microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic or renal abnormalities, and without another etiology; children without renal failure are also described as TTP. Plasma exchange (PE) is the main stay of treatment in combination with steroids and immunosuppressive therapies. The monoclonal antibody against CD20 Rituximab decreases the production of antibodies from B lymphocytes and it is used for antibodies-mediated diseases including TTP. We present our data on retrospective analysis of rituximab in treatment of TTP at University of Cincinnati in a series of 22 patients from 1997 to 2009. Our results showed that PE with immunosuppressive therapy resulted in decreased duration of PE, relapse rate, and increased duration of remission in patients with TTP. [ABSTRACT FROM AUTHOR]

Published
2013
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80. BMI and obesity in US blood donors: a potential public health role for the blood centre.

Author

Murphy EL, Schlumpf K, Wright DJ, Cable R, Roback J, Sacher R, Busch MP, Murphy, Edward L, Schlumpf, Karen, Wright, David J, Cable, Ritchard, Roback, John, Sacher, Ronald, Busch, Michael P, and NHLBI Retrovirus Epidemiology Donor Study II

Abstract

Objective: According to the 2007-2008 National Health and Nutrition Examination Survey, the prevalence of obesity in the US population was 33·8 %; 34·3 % and 38·2 %, respectively, in middle-aged men and women. We asked whether available blood donor data could be used for obesity surveillance.Design: Cross-sectional study of BMI and obesity, defined as BMI ≥ 30·0 kg/m2. Adjusted odds ratios (aOR) were calculated with logistic regression.Setting: A network of six US blood centres.Subjects: Existing data on self-reported height and weight from blood donors, excluding persons deferred for very low body weight.Results: Among 1 042 817 donors between January 2007 and December 2008, the prevalence of obesity was 25·1 %; 25·7 % in men and 24·4 % in women. Obesity was associated with middle age (age 50-59 years v. <20 years: aOR = 1·92 for men and 1·81 for women), black (aOR = 1·57 for men and 2·35 for women) and Hispanic (aOR = 1·47 for men and 1·49 for women) race/ethnicity compared with white race/ethnicity, and inversely associated with higher educational attainment (college degree v. high school or lower: aOR = 0·56 for men and 0·48 for women) and double red cell donation and platelet donation.Conclusions: Obesity is common among US blood donors, although of modestly lower prevalence than in the general population, and is associated with recognized demographic factors. Blood donors with higher BMI are specifically recruited for certain blood collection procedures. Blood centres can play a public health role in obesity surveillance and interventions. [ABSTRACT FROM AUTHOR]

Published
2012
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82. Hepatitis C virus prevalence and clearance among US blood donors, 2006-2007: associations with birth cohort, multiple pregnancies, and body mass index.

Author

Murphy EL, Fang J, Tu Y, Cable R, Hillyer CD, Sacher R, Triulzi D, Gottschall JL, Busch MP, Murphy, Edward L, Fang, Junyong, Tu, Yongling, Cable, Ritchard, Hillyer, Christopher D, Sacher, Ronald, Triulzi, Darrell, Gottschall, Jerome L, Busch, Michael P, and Retrovirus Epidemiology Donor Study

Abstract

Background: During the period 1992-1993, the prevalence of hepatitis C virus (HCV) antibodies (anti-HCV) among US blood donors was 0.36%, but contemporary data on the prevalence of antibody to HCV and the prevalence of HCV RNA are lacking.Methods: We performed a large, cross-sectional study of blood donors at 6 US blood centers during 2006-2007. Anti-HCV was measured with enzyme-linked immunosorbent assay followed by immunoblot, and HCV RNA was measured with nucleic acid testing. Adjusted odds ratios (aORs) were derived using multivariable logistic regression.Results: Of 959,281 donors, 695 had anti-HCV detected (prevalence, 0.072%). Of those with anti-HCV, 516 (74%) had test results positive for HCV RNA, and 179 (26%) had test results that were negative for HCV RNA. Compared with the prevalence during the period 1992-1993, prevalence during 2006-2007 was lower and peaked in older age groups. Anti-HCV was associated with a body mass index (BMI) >30 (aOR, 0.6; 95% confidence interval [CI], 0.5-0.8), and among women, it was associated with higher gravidity (aOR for 5 vs 0 pregnancies, 3.2; 95% CI, 1.9-5.4). HCV RNA negative status was associated with black race (aOR, 0.4; 95% CI, 0.2-0.7), having more than a high school education (aOR, 1.6; 95% CI, 1.1-2.4), and BMI >30 (aOR, 2.4; 95% CI, 1.4-3.9).Conclusions: Decreasing HCV prevalence is most likely attributable to culling of seropositive donors and a birth cohort effect. We found new associations between anti-HCV prevalence and gravidity and obesity. Recently discovered genetic factors may underlie differences in HCV RNA clearance in black donors. [ABSTRACT FROM AUTHOR]

Published
2010
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83. Recommendations for off-label use of intravenously administered immunoglobulin preparations. University Hospital Consortium Expert Panel for Off-Label Use of Polyvalent Intravenously Administered Immunoglobulin Preparations.

Author

Ratko TA, Burnett DA, Foulke GE, Matuszewski KA, Sacher RA, Ratko, T A, Burnett, D A, Foulke, G E, Matuszewski, K A, and Sacher, R A

Abstract

Objective: To summarize consensus recommendations for off-label uses of standard intravenous immunoglobulin (IVIG), as developed by a University Hospital Consortium (UHC) Expert Panel. These findings are intended to help guide clinicians in the appropriate and efficient use of IVIG.Participants: The UHC-sponsored panel included eight physicians (board certified in critical care, hematology, immunology, neurology, oncology, pediatrics, or rheumatology) and two hospital pharmacists.Evidence: MEDLINE and EMBASE were searched to identify all English-language review articles (n = 201) and original reports (n = 1904) on IVIG (human use only, excluding editorials, letters, and comments) published between January 1982 and March 1994. Relevant original reports (250) and review articles (87) were evaluated by the first author (T.A.R.). Extracted data included laboratory and clinical findings, objective measures, or clinical impressions. The evidence quality was graded by study design according to the US Preventive Services Task Force.Consensus Process: Before the panel meeting, a draft literature review and recommendations were produced by one of the authors (T.A.R.). The recommendations herein represent consensus (100% agreement) based on the published evidence.Conclusions: The UHC Expert Panel made specific recommendations for 53 off-label indications and the following general recommendations: (1) Usually IVIG is indicated only if standard approaches have failed, become intolerable, or are contraindicated; (2) IVIG products should be considered therapeutically equivalent and interchangeable; (3) interproduct pharmaceutical differences should be considered with the patient's clinical and physiological status when selecting an IVIG product; and (4) currently, IVIG manufacturers cannot guarantee freedom from viral contamination in the finished product. [ABSTRACT FROM AUTHOR]

Published
1995
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90. Gibberellic Acid‐controlled Sex Expression of Corn Tassels1

Author

Hansen, D. J., Bellman, S. K., and Sacher, R. M.

Abstract

Foliage of corn (Zea maysL.) was sprayed with gibberellic acid (GA3) in an attempt to regulate sex expression of corn tassels. Complete suppression of staminate development would facilitate hybrid seed production. Tassels of inbred lines ‘A619’ and ‘Gaspd Flint’ became pistillate, male sterile, or remained male fertile depending on the time of GA3application. Maximum pistil development within the tassel occurred when 5 mg/plant of GA3was applied 8 or 9 days prior to the start of microspore meiosis. Complete male sterility without pistil development was observed when applications were made 1 to 3 days before the onset of meiosis. Sex expression of the tassel was not altered when GA3treatments were made after the start of meiosis. Ear sex expression was not modified by any of the treatments. Stem weakness accompanied pistillate expression within the tassel and the stem either broke or was incapable of holding the plant in a verticle position. GA3treatments altered stem and peduncle elongation but did not change total plant height. The precise timing needed to obtain male sterility without stem weakness reduces the utility of GA3for hybridizing large populations. Plants in a normal field population do not reach this time frame at an uniform rate.

Published
1976
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92. Effects of deletions in the N-terminal basic arm of brome mosaic virus coat protein on RNA packaging and systemic infection

Author

Sacher, R and Ahlquist, P

Abstract

The first 25 amino acids of brome mosaic virus (BMV) coat protein include 8 basic and no acidic residues and are implicated in binding the encapsidated RNA. Using infectious transcripts from BMV RNA3 cDNA clones, we modified this region of the coat gene. A coat protein mutant with the first 25 amino acids deleted failed to direct either packaging of viral RNA in protoplasts or systemic infection of whole barley plants. Neither symptoms, virions, nor viral RNA was detectable in plants inoculated with this mutant or a mutant with a frameshift mutation in the coat gene. Mutants with the normal start codon changed to AAG or with the first eight codons deleted allowed translation to start at a downstream AUG, resulting in a deletion of the first 7 amino acids of the mature wild-type coat protein. These mutants not only packaged viral RNA in protoplasts but directed symptomatic, systemic infections that developed with normal speed and degree of spread within the host. The AUG-to-AAG point substitution did not revert to the wild type after long-term culture in planta. Wild-type BMV virions were also found to contain small amounts of a protein that coelectrophoresed with the truncated coat protein produced by the viable AAG and eight-codon-deletion mutants. This minor coat protein species presumably arose by infrequent translation initiation at the second AUG in the wild-type coat protein gene. Absence of encapsidation-competent coat protein appeared to stimulate production of nonstructural proteins in protoplast infections.

Published
1989
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93. Infrared Spectroscopy Study of the SP-250 Epoxy Resin System.

Author

ARMY MATERIALS AND MECHANICS RESEARCH CENTER WATERTOWN MA, Sacher,R E, LaLiberte,B R, ARMY MATERIALS AND MECHANICS RESEARCH CENTER WATERTOWN MA, Sacher,R E, and LaLiberte,B R

Abstract

The various epoxides which are part of the SP-250 formulation (3M Company, St. Paul, Minnesota) were treated to three different curing procedures. In this study, the epoxides and the epoxy blends were individually cured with dicyandiamide (Dicy) and Monuron, respectively, and in combination (Dicy/Monuron). The acceleration of the Dicy-containing epoxy resin cure is linked to the formation of cyclic 2-0xazolidone. The characteristic nature of the carbonyl band of these cyclic derivatives prompted us to monitor the hardening process by infrared spectroscopy.

Published
1984

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