bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal Antibodies Specific to the Acute Lymphoblastic Leukemia t(1; 19)-Associated E2A/pbx1 Chimeric Protein: Characterization and Diagnostic Utility
Authors: Sang Bi-Ching , Shi Liangru , Dias Peter , Liu Li , Wei Jia , Wang Zhi-Xue , Monell Craig R. , Behm Fred , Gruenwald Stefan 
Published: October 2019

Abstract
Nonrandom chromosomal abnormalities are found in most human malignancies, particularly leukemias and lymphomas. A characteristic t(1; 19) (q23; p13.3) chromosomal translocation is detected in 5% of childhood acute lymphoblastic leukemia (ALL) cases. This translocation results in the formation of a fusion gene, which leads to the expression of an oncogenic E2A/pbx1 protein. Breakpoints in the E2A gene almost invariably occur within a single intron, and the identical portion of PBX1 is joined consistently to exon 13 of E2A in fusion mRNA. In this article, we report the development of monoclonal antibodies against E2A/pbx1 fusion protein using a specific peptide that corresponds to the junction region of the protein. The obtained antibodies recognize specifically the chimeric E2A/pbx1 fusion protein and lack cross-reactivities with E2A and pbx1. Immunohistochemical staining and flow cytometric studies show that these antibodies can distinguish t(1; 19)-positive from t(1; 19)-negative leukemic cells. These results indicate that the obtained E2A/pbx1-specific monoclonal antibodies might prove to be valuable diagnostic reagents and important tools for elucidating the mechanisms involved in oncogenesis and progression of t(1; 19)-positive childhood ALL.
In Vitro Drug Sensitivity Testing Can Predict Induction Failure and Early Relapse of Childhood Acute Lymphoblastic Leukemia
Authors: Hongo Teruaki , Yajima Shuhei , Sakurai Minoru , Horikoshi Yasuo , Hanada Ryoji 
Published: October 2019

Abstract
It is vital to develop effective therapy for children with acute lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer relapse with current protocols. Cellular drug resistance is thought to be an important cause of induction failure and relapse. We performed in vitro tests of bone marrow samples in 196 children with newly diagnosed ALL with a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic cell survival (LCS) rate for dexamethasone and prednisolone. For each single drug, patients were classified into two groups, sensitive or resistant, by median concentration of LD70 or LCS. When patients were classified into three groups by sensitivity to four drugs of DPAV (dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year event-free survival (EFS; 95% confidence intervals) of the super sensitive group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735 (0.609 to 0.863), and that of the relatively resistant group (RR; sensitive to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then investigated the relationship between the above four-drug sensitivity and the time of relapse. The SS and IS patients tended to maintain continuous complete remission, and RR patients tended to undergo induction failure and early and late relapse (P = .004). Initial white blood cell count, immunologic classification, and age were also predictive factors, but the patient numbers showed no statistical correlation between these factors and the four-drug sensitivity groups (SS, IS, and RR). When we took three groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In vitro drug sensitivity testing provides additional prognostic information about childhood ALL, and early detection of drug resistance at the time chemotherapy commences may provide a successful strategy for individualizing treatment, as the results indicate de novo resistance to front-line drugs and suggest alternative, second-line drugs.
CD3−CD56+ Non-Hodgkin's Lymphomas With an Aggressive Behavior Related to Multidrug Resistance
Authors: Drénou Bernard , Lamy Thierry , Amiot Laurence , Fardel Olivier , Caulet-Maugendre Sylvie , Sasportes Maryline , Diebold Jacques , Le Prisé Pierre-Yves , Fauchet Renée 
Published: October 2019

AbstractCD56 expression has been reported previously in some non-Hodgkin's lymphoma (NHL) characterization. They principally involve the nasopharynx, are related to Epstein-Barr virus (EBV), and may be classified as either T- or non–T-natural killer (NK) cells according to CD3/T-cell receptor (TCR) status at the genomic or protein level. The present study reports three cases of non-nasal NK-NHL with the following characteristics: an agressive clinical behavior, heterogenous morphological data evoking pleomorphic T-cell malignant lymphoma, a non–T-NK phenotype using flow cytometry, and immunochemistry. The three cases were CD56+ without membrane expression of specific T markers (CD3, CD5, and TCR). Heterogenous results were observed concerning different antigens: CD2, CD4, CD8, CD16, CD94, CD122, TiA1, perforin, and granzyme B. There was no evidence of detectable clonal TCR gene rearrangement with polymerase chain reaction. No NK activity was detected in the two tested cases, and no relation was found with EBV. Multidrug resistance investigations suggest that agressive clinical findings could be related to MDR1 gene expression as confirmed by MDR1 mRNA detection, MDR1 gene product (Pgp) expression, and a functional multidrug resistance study using rhodamine efflux by flow-cytometry.
Expression and Regulation of Bcl-2, Bcl-xl, and Bax Correlate With p53 Status and Sensitivity to Apoptosis in Childhood Acute Lymphoblastic Leukemia
Authors: Findley Harry W. , Gu Lubing , Yeager Andrew M. , Zhou Muxiang 
Published: October 2019

AbstractBcl-2 and its homologue, Bcl-xl, encode membrane-associated proteins that protect neoplastic cells from DNA damage-induced apoptosis, whereas Bax is a Bcl-2 antagonist that promotes cell death. In the present study, we examined the expression and regulation of these genes at both the mRNA and protein level in 22 pediatric acute lymphoblastic leukemia (ALL) cell lines, as well as their sensitivity to apoptosis after exposure to ionizing radiation (IR). Eleven of 22 lines expressed wild-type (wt) p53, 4 expressed mutant p53, and 7 did not express p53 (p53-null). Nine of 22 (41%) lines expressed Bcl-2; of these, 8 were wt-p53+ and 1 expressed mutant p53. Bcl-2 was not expressed in any p53-null lines. In contrast, all 22 lines were positive for Bcl-xl and Bax, although expression level varied. Treatment with IR (10 Gy) induced both downregulation of Bcl-2 and upregulation of Bax at 2 to 5 hours post-IR in 5 of 8 (63%) wt-p53+ lines, leading to apoptosis. Conversely, lines that failed to both downregulate Bcl-2 and upregulate Bax after IR were resistant to apoptosis. Although levels of Bcl-xl expression varied among the 22 lines, high levels of Bcl-xl were observed in 5 of 7 (71%) p53− lines. There were no obvious changes in the expression of Bcl-xl in these lines after IR. However, among the p53-null lines, resistance to IR was observed only in those expressing high levels of Bcl-xl. These results suggest that expression of Bcl-2 but not Bcl-xl is p53-dependent and that IR-induced downregulation of Bcl-2 and upregulation of Bax occur in most wt-p53+ lines and are associated with radiosensitivity. Furthermore, high-level expression of Bcl-xl occurs predominantly in p53-null lines and is associated with resistance to IR-induced apoptosis in these lines, indicating differential expression and regulation of Bcl-2 and Bcl-xl in pediatric ALL.
Microphthalmia (mi) in Murine Mast Cells: Regulation of Its Stimuli-Mediated Expression on the Translational Level
Authors: Nechushtan Hovav , Zhang Zhaocheng , Razin Ehud 
Published: October 2019

AbstractMice harboring a mutation in the microphthalmia (mi ) gene display a variety of abnormalities, including microphthalmia, depletion of skin melanocytes, deafness, a defect in osteoclasts, and a major decrease in mast cell number and function. However, despite the possible critical role played by this protein in mast cell development and function, characterization of its mRNA and protein synthesis in these cells has not yet been performed. In this study, we investigated the regulation of the synthesis of mi in murine mast cells activated by various physiologic stimuli. Using a specific rabbit polyclonal anti-mi antibody, we found that interleukin-3, interleukin-4, or aggregation of the mast cell high-affinity receptor for IgE (FcεRI) induced the synthesis of mi protein in these cells. None of these stimuli significantly affected the level of mi mRNA in the mast cells at any of the time points tested. Also, using this specific anti-mi antibody, an increase in mi protein synthesis was shown during differentiation of mast cells from their bone marrow cell precursors. Moreover, a complex containing mi bound to upstream stimulating factor 2 was detected only in activated mast cells. We conclude that the regulation of mi expression is on the translational level. Thus, stimulation of mast cells by a variety of stimuli elicits a signaling pathway that regulates mi expression.
Marrow Transplantation for Chronic Myeloid Leukemia: The Influence of Plasma Busulfan Levels on the Outcome of Transplantation
Authors: Slattery J.T. , Clift R.A. , Buckner C.D. , Radich J. , Storer B. , Bensinger W.I. , Soll E. , Anasetti C. , Bowden R. , Bryant E. , Chauncey T. , Deeg H.J. , Doney K.C. , Flowers M. , Gooley T. , Hansen J.A. , Martin P.J. , McDonald G.B. , Nash R. , Petersdorf E.W. , Sanders J.E. , Schoch G. , Stewart P. , Storb R. , Sullivan K.M. , Thomas E.D. , Witherspoon R.P. , Appelbaum F.R. 
Published: October 2019

Abstract
The influence of busulfan (BU) plasma concentration on outcome of transplantation from HLA identical family members for the treatment of chronic myelogenous leukemia (CML) was examined in 45 patients transplanted in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). All patients received the same regimen of BU, 16 mg/kg orally and cyclophosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (CSSBU) during the dosing interval were measured for each patient. The mean CSSBU was 917 ng/mL (range, 642 to 1,749; median, 917; standard deviation, 213). Of patients with CSSBU below the median, seven (five of 18 in CP and two of four in AP) developed persistent cytogenetic relapse and three of these patients died. There were no relapses in patients with CSSBU above the median. The difference in the cumulative incidence of relapse between the two groups was statistically significant (P = .0003). CSSBU was the only statistically significant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with CSSBU above and below the median (P = .33). There was no statistically significant association of CSSBU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 and 0.64 was only 0.24, similarly CSSBU above the median was not associated with an increased risk of severe regimen-related toxicity. We conclude that low BU plasma levels are associated with an increased risk of relapse.
Tumor-Specific Idiotype Vaccines in the Treatment of Patients With B-Cell Lymphoma — Long-Term Results of a Clinical Trial
Authors: Hsu Frank J. , Caspar Clemens B. , Czerwinski Debra , Kwak Larry W. , Liles Tina Marie , Syrengelas Athanasia , Taidi-Laskowski Behnaz , Levy Ronald 
Published: October 2019

AbstractThe surface Ig on each B-cell lymphoma has unique portions (idiotypes), which can be recognized by the immune system. In this study, we immunized patients against the Ig expressed by their tumor and observed their clinical outcomes. After standard chemotherapy, 41 patients with non-Hodgkin's B-cell lymphoma received a series of injections with a vaccine consisting of tumor Ig protein coupled to keyhole limpet hemocyanin and emulsified in an immunologic adjuvant. Subjects were observed for toxicity, immune responses, and tumor status. The median duration of follow-up of all patients is 7.3 years from diagnosis and 5.3 years from the last chemotherapy given before vaccine treatment. Twenty patients (49%) generated specific immune responses against the idiotypes of their tumor Ig. Two patients who had residual disease experienced complete tumor regression in association with the development of these immune responses. The median duration of freedom from disease progression and overall survival of all 20 patients mounting an anti-idiotype immune response are significantly prolonged compared to the patients who did not mount an immune response. Thirty-two patients were in their first remission and nine were in subsequent remissions before beginning vaccine treatments. Analysis of the 32 first remission patients also shows an improved clinical outcome for those patients who mounted a specific immune response compared to those who did not (freedom from progression, 7.9 years v 1.3 years P = .0001; median survival from time of last chemotherapy not yet reached v 7 years, P = .04). This study confirms an earlier report that patients with B-cell lymphoma can be induced to make a specific immune response against the Ig expressed by their own tumor. It further shows that the ability to make such an immune response is correlated with a more favorable clinical outcome. Prospective controlled trials will be needed to prove a causal relationship between anti-idiotype immunity and improved clinical outcome.
Strategies for Hematopoietic Stem Cell Gene Therapy: Insights From Computer Simulation Studies
Authors: Abkowitz Janis L. , Catlin Sandra N. , Guttorp Peter 
Published: October 2019

Abstract
We simulated gene therapy using parameters derived from the analysis of autologous transplantation studies in glucose-6-phosphate dehydrogenase heterozygous cats to determine how hematopoietic stem cell (HSC) biology might influence outcomes. Simulation illustrates that a successful experiment can result by chance and may not be the repeated outcome of a specific protocol design or technical approach. As importantly, in many simulated gene therapy experiments where 1, 2, or 6 of 30 transplanted HSC were labeled, there was significant variation in the contribution from marked clones over time. Variability was minimized in simulations in which large numbers of HSC were transplanted. Strategies that may permit consistent clinically successful results are presented. Taken together, these simulation studies demonstrate that the in vivo behavior of HSC must be considered when optimizing approaches to gene therapy in large animals, and perhaps by extension, in humans.
Mediterranean Anemia
Authors: MINNICH VIRGINIA , NA-NAKORN SUPA , CHONGCHAREONSUK SOODSARKON , KOCHASENI SU-ED 
Published: October 2019

Abstract
1. Thirty-two patients with Mediterranean anemia were studied in Thailand. The diagnotic criteria are presented. All cases fulfilled these requirements.
2. In addition to the classical blood findings, the following observations are presented: (a) fetal hemoglobin, (b) erythrocytic inclusion bodies, (c) liver function tests.
3. Eighty-four per cent of the patients studied were found to have abnormally high amounts of fetal hemoglobin.
4. The inclusion bodies observed in four cases (case histories included) are presented and discussed.
5. Tests for liver function, plasma protein fractions, cephalin cholesterol flocculation, bromsulfalein retention, and bilirubin are reported for twenty patients.
6. A consideration of the effects of splenectomy on the clinical and hematologic status in Mediterranena anemia is presented.
Splenic Neutropenia in the Felty Syndrome
Authors: HUTCHISON H. E. , ALEXANDER W. D. 
Published: October 2019

Abstract
A 59 year old woman with chronic rheumatoid arthritis of twenty years' duration developed chronic granulocytopenia and excessive susceptibility to infection. Mild anemia and symptomless thrombocytopenia were also present. Eight marrow punctures over two and one half years all showed what appeared to be maturation arrest affecting the neutrophils so that segmented polymorphs alone were reduced in number. Throughout this period no form of therapy, including a five day course of ACTH, was effective in promoting normal granulopoiesis; only at the end of this period did the spleen become palpable. Splenectomy resulted in complete symptomatic cure which has been maintained for one year but hematologic cure was not fully obtained. It is believed that this case of splenic neutropenia is really an exaggerated form of Felty's syndrome for the literature shows that malignant neutropenia is not rare in this disease. Furthermore analysis of the literature on splenic neutropenia reveals other cases of an essentially similar nature and the suggestion is put forward that Felty's syndrome may be a fairly common cause of what has been regarded as primary splenic neutropenia. The possible integration of these findings with the immunologic leukopenic mechanism of Moeschlin is briefly discussed.
Separation of Individuals of Any Blood Group into Secretors and Non-Secretors by Use of a Plant Agglutinin (Lectin)
Authors: BOYD WILLIAM C. , SHAPLEIGH ELIZABETH 
Published: October 2019

Abstract
It has been found that an anti-H agglutinin, prepared by simple saline extraction of seeds of Ulex europeus, is suitable for the routine separation of individuals into secretors and non-secretors, merely by testing the ability of the undiluted saliva of the subjects to inhibit the agglutination of group O erythrocytes by the undiluted Ulex extract.
Case Report: The Successful Therapy with Streptokinase-Streptodornase of Ankle Ulcers Associated with Mediterranean Anemia
Authors: COOPER CHARLES D. , WACKER WARREN E. C. 
Published: October 2019

Abstract
1. A successful method of treatment of chronic leg ulcers associated with Mediterranean anemia, employing streptokinase-streptodornase in carboxymethylcellulose jelly, is presented.
The Occurrence of Leukemia
Authors: COOKE JEAN V. 
Published: October 2019

Abstract
Since leukemia is always fatal, the mortality rates are a reasonably accurate reflection of the occurrence of the disease at various ages. Certain features about the occurrence of leukemia were analyzed from the Vital Statistics of the United States over a twenty year period with special reference to age. A comparison of the occurrence (mortality) during this time has shown a considerable and progressive increase in incidence in persons over 50 years of age from 1930 to 1949. In ages under 50 years the increase was apparently slight but not remarkable.
In addition a comparison of the clinical occurrence of patients with the chronic forms of leukemia has shown that, in recent years, the proportion of patients over 50 years of age is twice as great as in similar groups of patients observed some twenty years previously.
The evidence strongly suggests that the occurrence of leukemia in persons over 50 years of age is actually increasing.
A Dynamic State in Stored Erythrocytes as Reflected by the Undulating Nature of in Vitro Measurements
Authors: THIELE ELIZABETH H. , PENNELL ROBERT B. 
Published: October 2019

Abstract
The fluctuating capacity of stored erythrocytes to release gas when suspended in the presence of dextrose in Krebs-Ringer bicarbonate solution in an atmosphere of 5 per cent CO2-95 per cent N2 is demonstrated.
A not dissimilar fluctuation of the cholinesterase activity of the stored cells is reported.
Possible seasonal variation in the state of red cells is suggested.
Some implications of these observations for erythrocyte storage are suggested.
A Quantitative Comparison of the Nucleated Cells in the Right and Left Humeral Bone Marrow of the Guinea Pig
Authors: HARRIS H. S. , HERDAN G. , ANCILL R. J. , YOFFEY J. M. 
Published: October 2019

Abstract
In seventeen young male guinea pigs a quantitative study was made of the nucleated cells of the bone marrow in the right and left humerus. Analysis of the data shows a close correspondence between the two sides in regard to the main cell groups.
The Fecal Excretion of Urobilinogen of Normal and Lead Poisoned Guinea Pigs
Authors: BAIKIE A. G. 
Published: October 2019

Abstract
1. The method of Watson for the estimation of fecal urobilinogen has been modified for use in guinea pigs.
2. Estimations on three or four day fecal collections give less variable results than estimations on single day collections. Loss of urobilinogen consequent upon storage to the third or fourth day is small.
3. For normal guinea pigs a mean daily excretion of 0.23 mg. with a standard deviation of 0.10 was found.
4. Serial estimations were carried out of the urobilinogen excretion of guinea pigs before and during experimental poisoning with lead nitrate. During lead poisoning there developed a statistically significant increased excretion of urobilinogen. This increased excretion was shown, moreover, to be correlated with the fall in hemoglobin levels which occurred in the poisoned animals.
5. It is concluded that these results provide confirmatory evidence for the view that hemolysis plays an important part in the anemia of chronic lead poisoning.
Relationship of Erythrocyte Cholinesterase Activity to Cell Metabolism
Authors: THIELE ELIZABETH H. , PENNELL ROBERT B. 
Published: October 2019

Abstract
Production by normal human erythrocytes of a substrate for cholinesterase has been demonstrated.
At body temperature, the formation and hydrolysis of the cholinesterase substrate is delicately controlled.
At lowered temperatures, 0 to -1.5 C., production of cholinesterase substrate greatly exceeds its hydrolysis.
The quantity of cholinesterase substrate capable of exerting its influence governs the quantity of dextrose converted to lactic acid by the erythrocyte under anaerobic conditions.
The observations corroborate and extend the suggestion of Lindvig, Greig, and Peterson that cholinesterase is part of a cellular system governing erythrocyte permeability.
The balance between production and hydrolysis of cholinesterase substrate at low temperature exhibits the same undulating fluctuations during red cell storage that have been noted for other erythrocyte metabolic functions.
Serum Polysaccharide and Fever in Thrombocytopenic Bleeding of Leukemia
Authors: FREEMAN GUSTAVE , BUCKLEY EDWARD S. 
Published: October 2019

Abstract
Evidence indicates that bleeding is associated with fever in critically thrombocytopenic leukemic children. It appears that fever, generally the result of secondary infection, is associated with elevations of protein-bound serum polysaccharide. Polysaccharide and platelets are quantitatively independent but both excess polysaccharide and critical deficiency of platelets have direct relationships to the hemorrhagic diathesis in leukemic children. Implications are discussed.
Hematologic Findings in the Total Body X-irradiated Hamster
Authors: FULTON GEORGE P. , JOFTES DAVID L. , KAGAN ROMA , LUTZ BRENTON R. 
Published: October 2019

Abstract
Hematologic determinations were made on cardiac blood from normal hamsters and from four groups of hamsters at daily intervals after total body irradiation with 600 r, 1000 r, 1200 r and 1500 r. Pancytopenia, lowered hematocrit, and decreased hemoglobin occurred. The clotting times were extended in the 1200 r and 1500 r groups, and this defect was correlated temporally with thrombocytopenia and disrupted mast cells. The sedimentation rates were increased terminally in the lethally-irradiated hamsters. The significance of these findings and the relationships to visual observations on the peripheral circulation such as leukocytic pavements on capillary and venular endothelium, platelet thromboembolic phenomena, erythrocytic extravasations, and circulating red cell aggregates are discussed.