bluuebunny/crossref_metadata_2025_split huggingface dataset:
A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins
Authors: Lee Douglas C. , Stenland Christopher J. , Miller Jeanette L.C. , Cai Kang , Ford Elizabeth K. , Gilligan Kevin J. , Hartwell Randal C. , Terry Jarrett C. , Rubenstein Richard , Fournel Michael , Petteway Stephen R. 
Published: March 2003

BACKGROUND: Experimental evidence from rodent models indicates that blood can contain transmissible spongiform encephalopathy (TSE) infectivity, which suggests a potential risk for TSE transmission via proteins isolated from human plasma. Because methods that can reduce TSE infectivity typically are detrimental to protein function, infectivity must be removed to ensure the safety of these therapeutic proteins. Animal bioassays are conventionally used to detect infectivity, but the pathogenic form of the prion protein (PrPSc) can serve as a marker for TSE infectivity.STUDY DESIGN AND METHODS: Seven plasma protein‐purification steps were performed after the plasma intermediates were spiked with TSE‐infected material. Resulting fractions were analyzed for PrPSc by using a Western blot assay and for TSE infectivity by using an animal bioassay. Western blots were quantitated by an endpoint dilution analysis, and infectivity titers were calculated by the Spearman‐Kärber method.RESULTS: PrPSc partitioning paralleled TSE infectivity partitioning, regardless of the nature of the protein‐purification step. The detection ranges for PrPSc and infectivity were 0 to 5.3 log and 1.1 to 8.9 log median infectious dose per unit, respectively. Clearance of PrPSc and infectivity ranged from 1.0 to 6.0 log.CONCLUSION: Purification steps for isolating therapeutic proteins from human plasma showed the removal of both PrPSc and TSE infectivity. PrPSc partitioning coincided with infectivity partitioning, which showed a close relationship between PrPSc and TSE infectivity. By exploiting this association, the in vitro Western blot assay for PrPSc was valuable for estimating the partitioning of TSE infectivity during plasma protein purification.
Optimizing pretransfusion antibody detection and identification:a parallel, blinded comparison of tube PEG,solid‐phase, and automated methods
Authors: Bunker Mark L. , Thomas Christine L. , Geyer Stanley J. 
Published: March 2003

BACKGROUND: The ideal pretransfusion testing strategy identifies maximal significant antibodies at minimal cost. Objectives of this study were to compare the characteristics of three testing methods and determine their optimal incorporation into the following generic testing sequence: 1) screen, for antibodies 2) if results are positive, use primary identification method, 3) if results are inconclusive, use secondary identification method.STUDY DESIGN AND METHODS: A total of 2000 consecutive, unselected, coded specimens were tested with three screening methods—PEG IAT, manual and automated solid phase red cell adherence assay (SPRCA). Of 202 positive results, 187 were of sufficient volume and were tested with both PEG and manual SPRCA identification panels, yielding 82 with significant antibodies, plus one that was negative by both methods found on retrospective review of nonstudy results. Calculations were made on the 1985 volume‐sufficient specimens, simulating the possible testing permutations.RESULTS: Manual SPRCA was the most sensitive antibody screen (67/83 = 81%) and the least specific (1840/1902 = 97%); automated SPRCA was the least sensitive (54/83 = 65%) and most specific (1883/1902 = 99%); and PEG was intermediate in both sensitivity (64/83 = 77%) and specificity (1860/1902 = 98%). Of the identification panels, manual SPRCA identified more antibodies than PEG (67 versus 66) but had more inconclusive results (41 versus 20). Of overall strategies, manual SPRCA screening with either sequence of identification methods identified the most antibodies (66). The combination of PEG screen, PEG identification, and manual SPRCA identification identified slightly fewer antibodies (63) but had the lowest reagent cost, total (reagent plus labor) cost, and cost per antibody identified. The sequence of automated SPRCA screening with manual SPRCA identification, and PEG identification had the lowest hands‐on time.CONCLUSIONS: The most cost‐effective pretransfusion strategy is PEG screen with PEG identification, plus manual SPRCA identification when PEG identification is inconclusive.
A multicenter study of in vitro and in vivo values in human RBCs frozen with 40‐percent (wt/vol) glycerol and stored after deglycerolization for 15 days at 4°C in AS‐3: assessment of RBC processing in the ACP 215
Authors: Valeri C. Robert , Ragno Gina , Pivacek Linda E. , Srey Rithy , Hess John R. , Lippert Lloyd E. , Mettille Frank , Fahie Roland , O'Neill E. Mary , Szymanski Irma O. 
Published: March 2003

BACKGROUND: The FDA has approved the storage of frozen RBCs at –80°C for 10 years. After deglycerolization, the RBCs can be stored at 4°C for no more than 24 hours, because open systems are currently being used. Five laboratoris have been evaluating an automated, functionally closed system (ACP 215, Haemonetics) for both the glycerolization and deglycerolization processes.STUDY DESIGN AND METHODS: Studies were performed at three military sites and two civilian sites. Each site performed in vitro testing of 20 units of RBCs. In addition, one military site and two civilian sites conducted autologous transfusion studies on ten units of previously frozen, deglycerolized RBCs that had been stored at 4°C in AS‐3 for 15 days. At one of the civilian sites, 10 volunteers received autologous transfusions on two occasions in a randomized manner, once with previously frozen RBCs that had been stored at 4°C in AS‐3 for 15 days after deglycerolization and once with liquid‐preserved RBCs that had been stored at 4°C in AS‐1 for 42 days.RESULTS: The mean ± SD in vitro freeze‐thaw‐wash recovery value was 87 ± 5 percent; the mean ± SD supernatant osmolality on the day of deglycerolization was 297 ± 5 mOsm per kg of H2O, and the mean ± SD percentage of hemolysis after storage at 4°C in AS‐3 for 15 days was 0.60 ± 0.2 percent. The paired data from the study of 10 persons at the civilian site showed a mean ± SD 24‐hour posttransfusion survival of 76 ± 6 percent for RBCs that had been stored at 4°C for 15 days after deglycerolization and 72 ± 5 percent for RBCs stored at 4°C in AS‐1 for 42 days. At the three sites at which 24‐hour posttransfusion survival values were measured by three double‐label procedures, a mean ± SD 24‐hour posttransfusion survival of 77 ± 9 percent was observed for 36 autologous transfusions to 12 females and 24 males of previously frozen RBCs that had been stored at 4°C in AS‐3 for 15 days after deglycerolization.CONCLUSION: The multicenter study showed the acceptable quality of RBCs that were glycerolized and deglycerolized in the automated ACP 215 instrument and stored in AS‐3 at 4°C for 15 days.
Quantitative and genotypic analysis of TT virusinfection in Chinese blood donors
Authors: Zhong Sheng , Yeo Winnie , Lin Che Kit , Lin Xiao‐Rong , Tang Mandy W. , Johnson Philip J. 
Published: March 2003

BACKGROUND: The TT virus (TTV) is a member of a newly described family of human viruses related to the C ircoviridae viruses. Its association with specific diseases has not been established, and screening of blood donors has not been implemented. To date, 16 genotypes have been identified.STUDY DESIGN AND METHODS: Sera from 471 healthy blood donors (aged 11‐58 years) were randomly selected and tested for TTV by the use of two sets of primers: NG59d/NG61d/NG63d primers and T801/T935 primers. Quantitative competitive PCR (QC‐PCR) was developed to measure the TTV DNA concentration among the blood donors. Sequencing of a part of the genome was performed to identify the various genotypes. Several samples showed a mixed genotype infection.RESULTS: TTV was detected in 251 (53.3%) of 471 healthy Hong Kong blood donors by the use of NG59d/NG61d/NG63d primers. The prevalence of the virus increased steadily with age (p = 0.03). TTV DNA was detected in 90 percent (90 of a randomly selected 100) of samples by the use of T801/T935 primers. TTV DNA concentration was also measured by QC‐PCR in the blood donors who were positive for TTV DNA in the first round of the heminested PCR. TTV titers ranged from 4.8 × 102 copies per mL to 6 × 104 copies per mL, with a median value of 1.2 × 104 copies per mL. Sequencing and phylogenetic analysis of a 223‐bp fragment from open reading frame 1 showed three main genotypes (G1 [60.7%], G2 [24.3%], and G3 [14%]) and a new genotype 17 (G17), with the latter bearing 60‐percent nucleotide homology with other genotypes deposited at GenBank. In addition, a new TTV subtype, G2f, was found.CONCLUSION: The prevalence of TTV is high in healthy Chinese blood donors. Three main genotypes (G1, G2, and G3) were detected. In addition, a new TTV genotype, tentatively designated as G17, and a new subtype, G2f, were identified.
Partial expression of RHc on the RHD polypeptide
Authors: Faas Brigitte H.W. , Beuling Esther A. , Ligthart Peter C. , Van Rhenen Dick J. , Van Der Schoot C. Ellen 
Published: March 2003

BACKGROUND: In the human Rh blood group system, c is, after D, the most immunogenic antigen.STUDY DESIGN AND METHODS: The background of a new partial c phenotype (Dc), identified on the RBCs of two unrelated white persons, was studied. This was done by analyzing the reactivity of the RBCs from the donors with anti‐c reagents, by performing sequence analysis, and by carrying out transduction studies.RESULTS: Serologic results suggested the existence of a new partial c phenotype. Genomic DNA and cDNA analysis revealed a normal RHCe allele, a normal RHD allele, and an RHD allele that carried two point mutations: 307T>C and 329T>C (the latter known to be associated with the DVII, Tar‐positive phenotype). No normal RHc allele was found. Thus, it was most likely that c is encoded by the mutated RHD allele (phenotype DDcCCee). Indeed, subsequent transduction of K562 erythroleukemic cells with an RHD cDNA carrying the 307T>C point mutation (leading to S103P) resulted in the expression of c.CONCLUSION: In the human Rh system, P103 is involved in the expression of c. Moreover, c can be expressed in vivo on the D polypeptide.
A comparative study of the postoperative allogeneicblood‐sparing effects of tranexamic acid and of desmopressin after total knee replacement
Authors: Zohar Edna , Fredman Brian , Ellis Martin H. , Ifrach Nisim , Stern Avraham , Jedeikin Robert 
Published: March 2003

BACKGROUND: Tissue hypoxia and reperfusion induce abnormal hemostatic function. Therefore, bleeding after total knee replacement (TKR) may be a result of a tourniquet‐induced imbalance of the procoagulant and fibrinolytic systems. Because laboratory confirmation of tourniquet‐induced abnormal hemostasis is difficult to obtain, indirect evidence must be sought.STUDY DESIGN AND METHODS: A prospective, single‐blind study of 40 patients undergoing TKR was performed. In the tranexamic acid (TA) group, in the 30 minutes before the limb tourniquet was deflated, an IV bolus dose of TA (15 mg/kg) was administered. Thereafter, a constant IV infusion of 10 mg per kg per hour was administered until 12 hours after tourniquet deflation. In the desmopressin group, desmopressin (0.3 mg/kg) and saline were administered by a similar protocol. No blood was administered intraoperatively. A postoperative Hct <27 percent constituted the postoperative transfusion trigger. Patients were examined daily for signs of lower‐limb deep vein thrombosis, and they underwent lower‐limb Doppler ultrasound on postoperative Day 5. Three months after surgery, the incidence of delayed thromboembolic events was assessed.RESULTS: During the first 12 postoperative hours, blood accumulation in the surgical drain was significantly (p<0.05) lower in the TA group (162 mL ± 129) than in the desmopressin group (342 mL ± 169). From the sixth postoperative hour until 3 days postoperatively, Hct levels were significantly lower in the desmopressin group than in the TA group. Significantly more allogeneic blood was transfused in the desmopressin group (11 patients received 16 units) than in the TA group (3 patients each received 1 unit) (p<0.02). There were no clinical signs of deep vein thrombosis or abnormal Doppler ultrasound studies. Three months postoperatively, there were no thromboembolic events among the 37 patients interviewed.CONCLUSION: TA induces better blood sparing than desmopressin. Therefore, a tourniquet‐induced increase in fibrinolysis is the likely cause of delayed bleeding after TKR surgery. However, before routine administration, the effect of TA on the incidence of thromboembolic events requires further investigation.
Molecular basis of the Dombrock null phenotype
Authors: Rios Maria , Hue‐Roye Kim , Storry Jill R. , Lee Terry , Miller Jeffery L. , Reid Marion E. 
Published: March 2003

BACKGROUND: The Dombrock blood group system consists of two antithetical antigens, Doa and Dob, and three high‐incidence antigens, Gregory (Gya), Holley (Hy), and Joseph (Joa). The null phenotype of the Dombrock blood group system (Donull) was identified when it was found that Gy(a–) RBCs also lack Doa, Dob, Hy, and Joa.STUDY DESIGN AND METHODS: DNA from three Gy(a–) persons was analyzed. PCR products for each of the three DO exons and their flanking intronic regions were sequenced in both directions. The cDNA from two of the people was subjected to PCR using primers in exon 1 and exon 3, and the products were sequenced.RESULTS: The Donull phenotype is associated with a single nucleotide mutation in the acceptor splice site of DO (IVS1–2a>g), which results in outsplicing of exon 2.CONCLUSION: Outsplicing of exon 2 is predicted to cause a –1 frameshift and a premature stop codon. Any product of such a transcript would lack the glycosyl‐phosphatidylinositol‐anchor motif, and RBCs would be devoid of the Do glycoprotein.
Transfusing methylene blue‐photoinactivated plasma instead of FFP is associated with an increased demand for plasma and cryoprecipitate
Authors: Atance Rosa , Pereira Arturo , Ramírez Begoña 
Published: March 2003

BACKGROUND: Photodynamic virus inactivation of plasma with methylene blue significantly decreases the recovery of fibrinogen and coagulation factors V and VIII. Because an adequate supply of fibrinogen is essential for the therapeutic efficacy of transfused plasma in many clinical settings, it was plausible that transfusing photoinactivated plasma (PIP) instead of FFP would result in an increased demand for plasma and cryoprecipitate.STUDY DESIGN AND METHODS: The study involved a retrospective analysis of the use of plasma at a university hospital (Barcelona, Spain) over three 1‐year periods: one before the implementation of PIP therapy and two after. Blood components transfused to plasma recipients were listed by broad diagnostic categories based on the Diagnosis‐Related Group classification.RESULTS: During the period under study, 2,967 patients were given plasma in this hospital. They received 27,434 units of plasma, 1,660 of cryoprecipitate, 10,079 of platelets, and 24,607 of packed RBCs. Patients undergoing surgical procedures accounted for 74 percent of all transfused plasma. In 71 percent of patient admissions, packed RBCs were transfused in addition to plasma. Diagnostic categories with the greatest requirement for plasma were cardiac valve surgery, liver transplant, wounds and traumatic injuries, and bowel surgery. The use of PIP was associated with a 56‐percent increase in the aggregated demand for plasma, whereas the transfusion of non‐virusinactivated cryoprecipitate increased twofold the first year and threefold the second year. The growth in the use of plasma took place in all the diagnostic categories. In those categories that include patients with liver disease, a partial substitution of PIP for cryoprecipitate was observed during the second year after PIP therapy implementation.CONCLUSION: The use of PIP was associated with a marked increase in the demand for plasma and cryoprecipitate, which probably was due to the low hemostatic quality of the new component. It is possible that such an increase overrode the potential health benefits derived from transfusing virus‐inactivated plasma.
The use of genotyping to predict the phenotypes of human platelet antigens 1 through 5 and of neutrophil antigens in Taiwan
Authors: Chu Chen‐Chung , Lee Hui‐Lin , Chu Thomas Weitao , Lin Marie 
Published: March 2003

BACKGROUND: The human platelet antigen (HPA) 1 through 5 and the human neutrophil antigen (HNA‐1) systems are relevant to immune‐related thrombocytopenia and neutropenia. The alloantigen distribution profiles in the population will aid in estimating the risk of alloimmunization.STUDY DESIGN AND METHODS: Genotyping of the genes that control the expression of the HPA‐1 through ‐5 and HNA‐1 systems in Taiwanese (n = 326) and Taiwan's indigenous peoples (n = 608) was performed by PCR with the sequence‐specific primer (PCR‐SSP) method.RESULTS: In the HPA system, HPA‐1b and HPA‐4b were absent among Taiwan's indigenous tribes and detected among other Taiwanese only with frequencies of <0.2 percent and <0.5 percent, respectively. The GP1BA*2 (HPA‐2b) and GP1A*2 (HPA‐5b) allele frequencies range from 1 percent to 7 percent and 0.4 percent to 3.5 percent among the two ethnic groups, respectively. GP2B*1 (HPA‐3a) and GP2B*2 (HPA‐3b) showed similar allele frequencies. In the HNA‐1 system, the FCGR3B*1 (HNA‐1a) allele frequency was about twice that of FCGR3B*2 (HNA‐1b) in Taiwanese and also in most of the indigenous tribes. Three FCGR3B (HNA‐1) null persons were found in one indigenous tribe (Ami tribe), for an FCGR3B null frequency of 19.8 percent. However, no FCGR3B*3 (HNA‐1c) allele was detected in Taiwan.CONCLUSION: The frequencies of HPA‐1b, ‐2b, and ‐5b in the Taiwanese population were much lower than those among whites. In Taiwan, all of the HNA‐1 null found was due to the deletion of the FCGR3B gene, and this deletion may be widely distributed in the Ami tribe.
Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure
Authors: Streiff Michael B. , Ness Paul M. 
Published: March 2003

BACKGROUND: FV inhibitors are a largely preventable iatrogenic coagulopathy in which the frequency is increasing in clinical practice. STUDY DESIGN AND METHODS: Three cases associated with our institution are reported. A systematic review of the MEDLINE database was performed, and reference lists were reviewed to identify relevant publications. RESULTS: One hundred twenty‐six cases of FV inhibitors have been reported in the world's literature. Eighty‐seven have been reported in the last decade, of which two thirds are due to exposure to bovine thrombin. Bovine thrombin‐associated FV antibodies develop in 40 to 66 percent of cardiac surgery patients and in 20 percent of neurosurgery patients. Thirty‐three percent of reported patients developed bleeding complications. Inhibitors persisted on average 2.3 months. Standard coagulation assays do not reliably predict clinical manifestations. Multimodality therapy, including immunosuppression, is useful for treatment of symptomatic patients. CONCLUSIONS: FV inhibitors are a common complication of bovine thrombin exposure that can have devastating clinical consequences. Transfusion medicine specialists and hematologists can play a critical role in reducing the incidence of FV inhibitors by educating the medical community about safer alternative fibrin sealants.
Molecular background of D(C)(e) haplotypes within the white population
Authors: Noizat‐Pirenne France , Le Pennec Pierre‐Yves , Mouro Isabelle , Rouzaud Anne‐Marie , Juszczak Geneviève , Roussel Michèle , Lauroua Pierre , Krause Claire , Rouger Philippe , Cartron Jean‐Pierre , Ansart‐Pirenne Hélène 
Published: March 2003

BACKGROUND: D(C)(e) and D(C)e haplotypes may be encountered in the white population. Few data are available on the molecular backgrounds responsible for depressed expression of C and e. STUDY DESIGN AND METHODS: Individuals of white origin carrying a D(C)(e) genotype resulting in depressed expression of C or both C and e were subdivided into two categories based on the RBC reactivity with the human sera Mol and Hor, which contain antibodies against low‐frequency antigens of the Rh (RH) system and other non‐Rh low‐frequency antigens. Neither Hor+, Mol+ nor Hor+, Mol– RBCs expressed the V (RH10), VS (RH20), and/or Rh32 (RH32) low‐frequency antigens. These results suggested that Hor+, Mol+ variants expressed Rh33 (RH33 or Har) and FPTT (RH50), whereas Hor+, Mol– variants might express an undefined low‐frequency antigen. Further serologic and molecular analyses were performed. RESULTS: Molecular analysis of Hor+, Mol+ variants revealed a hybrid gene structure RHCe‐D(5)‐Ce, in which exon 5 of RHCE (RHCe allele) was replaced by exon 5 of RHD (the so‐called RHCeVA allele). The presence of exon 5RHD resulted in several amino acid alterations predicted in the external loop 4 of the CeVA polypeptide. Molecular analysis of Hor+, Mol– variants revealed the presence of a new RHCe allele characterized by a single point mutation C340T within exon 3 (the so‐called RHCeMA allele), resulting in a R114W substitution predicted on the external loop 2 of the CeMA polypeptide. A serologic study showed a different pattern of reactivity with C and e MoAbs. CONCLUSION: Two types of mutations resulted in amino acid substitutions predicted in external loops 4 and 2, respectively, which altered both the C and e reactivity, and indicated conformation changes or defective interaction between nonadjacent loops of the Ce polypeptide. Serologic analysis showed that together with Hor and Mol sera testing, the use of different C and e MoAbs could help to identify these variants within the white population.
Acquired and transient RBC CD55 deficiency (Inab phenotype) and anti‐IFC
Authors: Matthes Thomas , Tullen Emanuelle , Poole Joyce , Banks Jackie , Nagy Monika , Stelling Marie‐Jose , Boehlen Françoise , Michel Martine , Beris Photis , Hustinx Hein , Crew Vanja , Daniels Geoff 
Published: March 2003

BACKGROUND: Antigens of the Cromer blood group system reside on the glycoprotein CD55 (decay‐accelerating factor). The Inab phenotype is the null phenotype of this system. So far, only five propositi have been described who exhibit this phenotype, and single‐nucleotide substitutions in the CD55 gene have been found in three of them. This report describes the first example of a patient with an acquired and transient form of the Inab phenotype. CASE REPORT: A 54‐year‐old black patient was admitted to the hospital because of abdominal pain. Multiple splenic infarctions were visualized in the abdominal computerized tomography scan, and a prophylactic splenectomy was performed. The patient's serum reacted by an IAT with all donor RBCs tested. RESULTS: Serologic analysis showed that the patient had the rare Inab phenotype and that his serum contained anti‐IFC. Flow cytometry demonstrated the absence of CD55 on his RBCs, whereas lymphocytes, monocytes, granulocytes, and platelets expressed CD55, albeit at a weaker level than cells of common phenotypes. cDNA revealed no differences from the published sequences. Flow cytometry performed 12 months after splenectomy showed reappearance of the CD55 antigen; serologic tests performed after 17 months revealed that the anti‐IFC had almost disappeared and that the RBCs were again agglutinated by various Cromer antibodies. CONCLUSION: A patient with an acquired and transient form of the Inab phenotype is described, in whom the CD55 deficiency is limited to the RBCs and is associated with splenic infarctions.