T Kajiume, Y Kawano, Y Takaue, T Abe, Y Okamoto, A Makimoto, T Watanabe, J Sato, A Yokobayashi, Y Kuroda
{"title":"Continuous monitoring of hematocrit values during apheresis for allogeneic peripheral blood stem cell collection.","authors":"T Kajiume, Y Kawano, Y Takaue, T Abe, Y Okamoto, A Makimoto, T Watanabe, J Sato, A Yokobayashi, Y Kuroda","doi":"10.1089/scd.1.1998.7.493","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.493","url":null,"abstract":"<p><p>Rapid changes in the circulating blood volume or hemoglobin level during apheresis may pose a risk for healthy individuals donating allogeneic PBSC. In this study, a real-time noninvasive monitor CRIT-LINE was used for continuous monitoring of hematocrit values in a total of 16 aphereses performed in 4 adult (median age 30 years) and 4 pediatric donors (4 years). Donors received recombinant G-CSF (10 microg/kg s.c. for 5 days) for mobilization of PBSC. A CS3000 plus blood cell separator (Baxter) was used in two different procedures. Adults donors were subjected to modified program 1-120 using a combination of the granulocyte chamber and the small volume collection chamber (SVCC), and pediatric donors were subjected to specialized program 4 with a combination of the newly developed small volume separation chamber holder (SVSCH) and SVCC. In all of the procedures for children, the extracorporeal line was primed with 400 ml leukocyte-depleted allogeneic RBC or 200 ml autologous RBC after regular priming with normal saline, whereas none of the adult donors received this treatment. We found a marked contrast in the hematocrit kinetics during apheresis in the two cohorts/procedures. In adults, the initiation of apheresis was followed by an immediate decline in the hematocrit value over the initial 10 min until a stable plateau level was reached (7% decrease). In children, the values decreased slowly but progressively throughout the entire procedure to finally reach a 9% decrease at the completion of apheresis. These data may suggest that the use of SVSCH plus SVCC or priming with RBC can eliminate the abrupt decline in blood hemoglobin levels that occurs during apheresis.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 6","pages":"493-7"},"PeriodicalIF":0.0,"publicationDate":"1998-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20825760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M W Sugrue, C E Hutcheson, D D Fisk, C G Roberts, A Mageed, J R Wingard, J S Moreb
{"title":"The effect of overnight storage of leukapheresis stem cell products on cell viability, recovery, and cost.","authors":"M W Sugrue, C E Hutcheson, D D Fisk, C G Roberts, A Mageed, J R Wingard, J S Moreb","doi":"10.1089/scd.1.1998.7.431","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.431","url":null,"abstract":"<p><p>The cost of harvesting, processing, and freezing multiple peripheral blood stem cell (PBSC) products could easily exceed that of bone marrow harvest. To reduce costs while maintaining product viability, we examined the effect of overnight storage on PBSC products. Sixteen consecutive leukapheresis samples from 12 patients were examined prospectively. Each initial leukapheresis product was stored overnight on ice (median temperature 15 degrees C) after adding an equal amount of M199 culture medium containing heparin. After overnight storage, the product was combined with the next day PBSC harvest if required and processed/frozen per protocols. Parameters measured before and after storage include cell count and differential, viability, bacterial cultures, and colony-forming unit (CFU) assays. The results show that the median cell concentration during storage was 7.12 x 10(7)/ml and the median length of storage was 20 h. After storage, the median viability and nucleated cell recovery were 100% and 99.5%, respectively. In addition, 98% recovery of CFU-GM was achieved. No clotting or bacterial contamination was detected. All 12 patients studied engrafted promptly. In addition, 124 similarly treated patients were retrospectively analyzed. Of these, 48% required > or = 2 large-volume leukaphereses to achieve the target cell dose. As a result of overnight storage, 150 final products, instead of 224, were processed and cryopreserved. This difference is equivalent to 33% cost savings. Again, all patients were transplanted and engrafted successfully. In conclusion, overnight storage and pooling of two consecutive PBSC products are safe, reduce cost, and allow for optimum laboratory staffing.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"431-6"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M R Koller, R J Maher, I Manchel, M Oxender, A K Smith
{"title":"Alternatives to animal sera for human bone marrow cell expansion: human serum and serum-free media.","authors":"M R Koller, R J Maher, I Manchel, M Oxender, A K Smith","doi":"10.1089/scd.1.1998.7.413","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.413","url":null,"abstract":"<p><p>The increasing use of cultured human cells in clinical trials is highlighting the need for alternatives to media containing animal sera that are typically used to support these cultures. Perfused cultures of BM mononuclear cells (MNC) were used to evaluate animal sera alternatives with respect to the output of primitive, progenitor, and stromal cells. A serum level of 20% was optimal, and this could be provided by FBS alone or by a mixture of horse serum (HoS) and FBS, but not by HoS alone. Allogeneic human plasma (20%) supported half the level of cell, CFU-GM, and LTC-IC output as compared with animal sera-containing control. Significant donor-to-donor variability in human plasma was observed, but this was mitigated by pooling of plasma samples. Autologous and allogeneic human plasma performed equivalently. The use of autologous or allogeneic human serum was found to be equivalent to the use of human plasma, but all were inferior to animal sera. Animal sera supported typical stroma and cobblestone formation, whereas stroma in human serum cultures was less dense. Eight commercial serum-free media were tested and found to support MNC expansion to varying degrees, but none approached the performance of the animal serum-containing control, particularly with respect to stromal (i.e., CFU-F) support. In fact, when MNC were cultured in parallel with CD34-enriched cells, output (from MNC) was higher only in control medium, apparently because serum-free media reduced accessory cell effects. Because of these results, a new serum-free medium was developed for MNC cultures. This formulation outperformed all commercial serum-free media, resulting in cell and LTC-IC output equivalent to that of control. However, CFU-GM and CFU-F output were 66% and 9% of control, respectively. Precoating the culture surface with collagen increased CFU-F (and Thy-1+ cell) output to control levels, although CFU-GM output was still lower than control. The addition of either fibronectin or PDGF had no measurable effect, nor did the use of 5-100-fold greater concentrations of growth factor supplementation. The serum-free medium also increased CD41+ and CD61+ cell output to 150%-220% of control levels. The development of this new serum-free medium has potential for use in the perfused BM MNC culture systems currently in clinical trials to test the efficacy of expanded cells after cytoablative chemotherapy.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"413-23"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B L Levine, J Cotte, C C Small, R G Carroll, J L Riley, W B Bernstein, D E Van Epps, R A Hardwick, C H June
{"title":"Large-scale production of CD4+ T cells from HIV-1-infected donors after CD3/CD28 costimulation.","authors":"B L Levine, J Cotte, C C Small, R G Carroll, J L Riley, W B Bernstein, D E Van Epps, R A Hardwick, C H June","doi":"10.1089/scd.1.1998.7.437","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.437","url":null,"abstract":"<p><p>We describe a procedure for large-scale enrichment, growth, and harvesting CD4+ T cells. This method may be effective for HIV-1 immunotherapy, as the mode of stimulation, with anti-CD3 plus anti-CD28 coated beads (CD3/CD28 beads) induces a potent antiviral effect. PBMC were obtained by density gradient centrifugation of an apheresis product. Monocytes/macrophages were removed by incubating PBMC with beads coated with IgG. The cells were then magnetically depleted of B cells and CD8+ cells with mouse anti-CD20 and anti-CD8 MAbs and sheep antimouse coated beads. The remaining cells were >80% CD4+ and were transferred to gas-permeable bags containing CD3/CD28 beads and cultured in a closed system. After 14 days, the cell number increased an average of 37-fold, and cells were nearly 100% CD4+. Viral load, assessed by DNA PCR for HIV-1 gag, decreased >10-fold during culture in the absence of antiretroviral agents. Removal of CD3/CD28 beads from the cell suspension was accomplished by passing cells plus beads (3-30 x 10(9) cells in 2-12 L) over a MaxSep magnetic separator using gravity-driven flow. The cells were then concentrated to 300 ml in an automated centrifuge. This process allows safe and efficient growth of large numbers of CD4+ T cells from HIV-1+ donors.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"437-48"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"G-CSF-mobilized donor leukocyte infusions as immunotherapy in acute leukemia relapsing after allogeneic marrow transplantation.","authors":"R A Mandanas, R A Saez, G B Selby, D L Confer","doi":"10.1089/scd.1.1998.7.449","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.449","url":null,"abstract":"<p><p>Eight patients who relapsed with acute leukemia within a year after allogeneic BMT were treated with G-CSF-mobilized donor leukocyte infusions (mDLI) to induce GvHD as a form of immunotherapy. Prior to mDLI, 7 who had systemic relapse received one (2 AML, 1 ALL, 1 CML myeloid blast crisis) or two (2 AML, 1 ALL) rounds of conventional dose induction chemotherapy, and 1 patient with isolated central nervous system (CNS) lymphoid blast crisis CML received intrathecal chemotherapy followed by craniospinal irradiation. G-CSF (10 microg/kg/day) was given to original HLA-matched sibling donors for 4-5 days before leukapheresis of at least 6.0 x 10(8) mononuclear cells per kilogram of recipient weight. No GvHD prophylaxis was used when mDLI was given in 6 patients at the nadir of hematologic counts and in 2 who were in hematologic remission. There was no regimen-related mortality, as pancytopenic patients had rapid recovery of neutrophil counts (6-18 days after mDLI). All patients developed moderate to severe GvHD (5 grade III/IV, 3 grade II) at a median of 30 days (range 22-59) after mDLI. Two patients died of complications from refractory GvHD while in remission. The other 6 had short remissions lasting 2.2-9.4 months until leukemic relapse as their GvHD was reversed by corticosteroids with or without cyclosporine. Patients who relapse with acute leukemia within a year after BMT still have a poor prognosis. The success of GvHD as a form of immunotherapy in these patients may depend on the ability to control it to a state that is both safe and continually exerting an antileukemia effect.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"449-56"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD34+ cell selection from frozen cord blood products using the Isolex 300i and CliniMACS CD34 selection devices.","authors":"I K McNiece, G B Stoney, B P Kern, R A Briddell","doi":"10.1089/scd.1.1998.7.457","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.457","url":null,"abstract":"<p><p>Ex vivo expansion of cord blood (CB) cells requires CD34+ cell selection before expansion to obtain optimal numbers of progenitor cells. As a preliminary step to preclinical development of CB expansion, we have evaluated two clinical scale selection devices, the Isolex 300i (Baxter Healthcare, Immunotherapy Division) and the CliniMACS (Miltenyi Biotech Inc.), for CD34+ cell selection from frozen CB products. As expansion of CB results in differentiation of cells, there may be a depletion of stem cells. Therefore, only a fraction of the CB should be expanded while a portion of the CB is maintained unmanipulated for infusion. After thawing of 40% fractions of each CB product, we observed >95% viable cells, with a median total WBC count of 1.8 x 10(8) cells. Use of the Isolex 300i resulted in a median purity of 51% CD34+ cells (n=8) and a median recovery of 34% CD34+ cells. Use of the CliniMACS resulted in a median purity of 54% CD34+ cells (n=10) and a median recovery of 80% CD34+ cells. The absolute number of CD34+ cells recovered after selection varied with samples from 6.7 x 10(4) to 3.2 x 10(6) CD34+ cells. Expansion of CD34+ cells from both systems resulted in >20-fold expansion of CFU-GM, with a median of 44-fold expansion. These data demonstrate the feasibility of selecting small fractions of frozen CB products using clinical scale CD34+ cell selection devices.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"457-61"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J A Martinson, K Unverzagt, A Schaeffer, S L Smith, M Loudovaris, M J Schneidkraut, J G Bender, D E Van Epps
{"title":"Neutrophil precursor generation: effects of culture conditions.","authors":"J A Martinson, K Unverzagt, A Schaeffer, S L Smith, M Loudovaris, M J Schneidkraut, J G Bender, D E Van Epps","doi":"10.1089/scd.1.1998.7.463","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.463","url":null,"abstract":"<p><p>The influence of feeding schedules on the expansion and differentiation of enriched PB CD34+ cells (84.9+/-14.7% purity) was studied after 12-13 days of serum-free liquid culture. CD34+ cell cultures were initiated (n=6) on day 0 (2 x 10(5) cells) in X-VIVO 10 medium containing 1% human albumin (HA) and 100 ng/ml each of rIL-3, rIL-6, rSCF, and rG-CSF. The cultures were supplemented on days 3, 6, and 9 as follows: condition 1, unfed (static culture); condition 2, 100 ng/ml rG-CSF; condition 3, split 1:2 medium + 100 ng/ml each rIL-3, rIL-6, rSCF, and rG-CSF; condition 4, split 1:2 medium + 100 ng/ml rG-CSF. The proliferative capacities (fold increase) of condition 2 (49.1+/-21.3), condition 3 (75.6+/-33.4), and condition 4 (63.1+/-23.8) cultures were significantly higher (p < 0.05) than that of the condition 1 unfed (35.5+/-14.0) cultures. Flow cytometric analysis (CD15-FITC/CD11b-PE) showed that the highest CD15+ cell purity (neutrophil precursors) was found in the condition 3 (1.18 x 10(7)+/-4.29 x 10(6)) cultures, followed by condition 4 (9.84 x 10(6)+/-3.57 x 10(6)), condition 2 (7.54 x 10(6)+/-2.06 x 10(6)), and condition 1 (4.78 x 10(6)+/-9.80 x 10(5)), respectively. The average cloning efficiency of the day 0 enriched CD34+ cells, 15.1%+/-10.3%, decreased to less than 0.2% in all of the day 12-13 cultures. These data suggest that feeding CD34+ cell cultures with rG-CSF alone, medium + rG-CSF, or medium + rIL3, rIL-6, rSCF, and rG-CSF enhances CD15+ neutrophil precursor (promyelocytes, myelocytes, metamyelocytes) production in vitro.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"463-71"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Bornhäuser, B Mohr, U Ehrenlechner, A Neubauer, G Ehninger
{"title":"Fluorescence in situ hybridization for the BCR/ABL rearrangement is dependent on the percentage of nonlymphocytic cells in peripheral blood stem cell harvests.","authors":"M Bornhäuser, B Mohr, U Ehrenlechner, A Neubauer, G Ehninger","doi":"10.1089/scd.1.1998.7.425","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.425","url":null,"abstract":"<p><p>Interphase fluorescence in situ hybridization (FISH) for the translocation t(9;22) is widely used for quantifying minimal residual disease (MRD) in PBSC harvests from CML patients. We investigated the influence of cell composition on the percentage of positive FISH signals in 17 BCR/ABL-positive leukapheresis products from 12 CML patients. In these PBSC harvests, a significant correlation between the percentage of nonlymphocytic nucleated cells and BCR/ABL positivity was measured (k=0.81). This correlation was not seen in patients who became BCR/ABL negative after mini-ICE chemotherapy. CD34 enrichment was performed by immunomagnetic separation in 7 patients. There was a statistically significant increase in BCR/ABL positivity after CD34+ selection (p=0.018). This may have been caused by passive depletion of BCR/ABL-negative lymphocytes. Our findings suggest that quantitative results of t(9;22) FISH have to be corrected for cell composition when comparing different stem cell products. CD34+ selection before FISH analysis may be one way to enrich for nonlymphocytic cells and to concentrate on the progenitor compartment.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"425-30"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20739467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Buzz, hype...foundation.","authors":"N H Collins","doi":"10.1089/scd.1.1998.7.401","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.401","url":null,"abstract":"","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"401"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20740186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K L Kowalkowski, M T Alzona, F M Aono, D E Van Epps, M Vachula
{"title":"Ex vivo generation of dendritic cells from CD34+ cells in gas-permeable containers under serum-free conditions.","authors":"K L Kowalkowski, M T Alzona, F M Aono, D E Van Epps, M Vachula","doi":"10.1089/scd.1.1998.7.403","DOIUrl":"https://doi.org/10.1089/scd.1.1998.7.403","url":null,"abstract":"<p><p>Dendritic cells (DC) are efficient and potent APCs that can be generated ex vivo. For them to be used clinically, however, a closed culture system using serum-free medium should be used. Our goal was to differentiate DC from human blood CD34+ cells in serum-free media in a new gas-permeable culture container, PL2417. Apheresis products were collected from healthy G-CSF-mobilized donors, and CD34+ cells were selected using the Isolex immunomagnetic cell selection system. Cells were cultured in the presence of GM-CSF and tumor necrosis factor-alpha (TNF-alpha) in various serum-free media and compared with serum-containing medium in 4-well plates. One of the serum-free media was then selected and used in PL2417 containers and compared with serum-containing medium in standard flasks. The cells were evaluated at days 0, 7, and 14 for the presence of DC, which were identified morphologically after Wright-Giemsa staining by cytoplasmic processes extending from the surface of the cell. The cultures were evaluated phenotypically by flow cytometry and immunohistochemistry. The stimulatory capacity was examined in MLR. Overall, results from serum-free media and PL2417 containers were comparable results obtained under the other conditions. These data indicate that culture-deriving DC from CD34+ cells in PL2417 closed system containers using serum-free media is as effective as using standard flasks and serum-supplemented media.</p>","PeriodicalId":77208,"journal":{"name":"Journal of hematotherapy","volume":"7 5","pages":"403-11"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/scd.1.1998.7.403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20740187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}