bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Measurement of the Survival of Human Erythrocytes by In Vivo Tagging with Cr51
Authors: SUTHERLAND DONALD A. , MCCALL MARY SUE 
Published: October 2019

Abstract
1. The deviation from a rectilinear form of the complex curvilinear curves of erythrocyte decay produced by the in vitro tagging of the cells with Na2Cr51O4 is not a result of the in vitro tagging procedure per se.
2. Human erythrocytes can be tagged its vivo with Na2Cr51O4. One can determine the in vivo survival of such cells if the gamma detecting unit is sufficiently sensitive and the amount of radiochromium used is sufficient. Such decay curves are similar to those produced by the in vitro Cr51 tagging method.
3. The in vivo method permits a study of the life span of erythrocytes in patients who have a very active cold agglutinin or in whom the cells are easily hemolyzed by mechanical trauma.
The Mechanics of the "L.E." Cell Phenomenon, Studied with a Simplified Test
Authors: SNAPPER I. , NATHAN DANIEL J. 
Published: October 2019

Abstract
1. A simple method is described for the formation of large numbers of lupus cells by positioning one drop of finger or ear blood of a lupus patient upon an accumulation of dried, normal polynuclear leukocytes. Thick leukemic smears and perhaps even imprints of various carcinomas or Hodgkin’s tissue can also be used as substrates.
2. No false positive results were obtained in a group of control patients.
3. Striking results were obtained with this method itt 20 of 21 known cases of disseminated lupus erythematosus. The remaining case in whom a single "L.E." cell was found by a conventional method, to date has yielded no lupus cells by our method.
4. The difference in appearance of the inclusion body of some of these cells from the characteristic Hargraves cell is highlighted.
5. Theoretic considerations of the mechanism of lupus cell formation are discussed and reassessed in the light of our experience with this method. For the formation of "L.E." cells it seems necessary that living polynuclear leukocytes, dead cells and lupus serum be brought together. The lupus serum can depolymerize the desoxyribose nucleic acid of the nuclei of the dead cells, but not of living cells. The depolymerized material is then phagocytized by living polynuclear cells and formation of lupus cells results.
Megaloblastic Anemia Associated with Anatomic Lesions in the Small Intestine
Authors: THOMPSON R. B. , UNGLEY C. C. 
Published: October 2019

Abstract
This paper describes the development of anemia in six patients with strictures and anastomoses in the small intestine. The marrow proved to be megaloblastic in three instances, and megaloblastic change is presumed in the other three because of the clinical and laboratory findings, and the characteristic hemopoietic response to liver therapy. Responses to crude and refined liver extracts and vitamin B12 compared unfavorably with those to be expected in Addisonian pernicious anemia; they were similar to the poorer responses often observed in megaloblastic anemia associated with idiopathic steatorrhea. The relationship of the intestinal lesion to the development of megaloblastic anemia is briefly discussed.
Case Report: Infectious Mononucleosis and Acute Hemolytic Anemia; Report of Two Cases and Review of the Literature
Authors: THURM RICHARD H. , BASSEN FRANK 
Published: October 2019

Abstract
1. Two cases of infectious mononucleosis complicated by acute hemolytic anemia are presented. One of these patients had, in addition, an underlying Mediterranean anemia.
2. Hemolytic anemia is a rare complication of infectious mononucleosis.
3. Thirteen similar cases have been collected from the literature, and the cumulative data summarized.
4. Recovery occurred in all cases. Splenectomy was considered necessary in only two.
5. The etiology of hemolytic anemia in infectious mononucleosis is obscure but there is good evidence to indicate it may be different in different cases. Hypersplenism initiated by infectious mononucleosis could best explain the authors’ cases whereas the elaboration of hemolytic antibodies would best explain some of the reported cases.
Effect of Repetitive Exposures to Gamma Rays on the Hematopoietic System of the Rat
Authors: BAUM SIEGMUND J. , KIMELDORF DONALD J. , JACOBSEN ELLY M. 
Published: October 2019

Abstract
Rats were subjected to a series of one or more doses of 75 r gamma irradiation, at seven day intervals between exposures. Hematologic examinations were made following the last exposure in each series of irradiations. The maximum changes observed were, to a great extent, independent of the number of previous exposures, and appeared to reflect principally the effects of the last irradiation. These results were ascribed to the regenerative capacity of the hematopoietic system to recover during the seven day interval between radiation exposures.
A Second Example of Anti-Fyb
Authors: LEVINE PHILIP , SNEATH JOAN S. , ROBINSON ELIZABETH A. , HUNTINGTON P. W. 
Published: October 2019

Abstract
A second example of anti-Fyb was found in the serum of a patient immunized by transfusions and pregnancies. In addition to anti-Fyb, anti-c and anti-E were also present. The identification of the antibody as anti-Fyb was made in part with the aid of a 2 x 3 table in parallel tests with anti-Fya.
Phase I Study Using Alternate Week Administration of the Farnesyl Transferase Inhibitor R115777 (Zarnestra™) in Patients with Myelodysplastic Syndrome.
Authors: Kurzrock Razelle , Verstovsek Srdan , Wright John J. , Pilat Susan R. , Cortes Jorge E. , Estey Elihu H. , Giles Francis J. , Beran Miloslav , Kantarjian Hagop M. 
Published: October 2019

Abstract
R115777 is an oral selective inhibitor of farnesyltransferase with potent antiangiogenic, antiproliferative, and apoptotic effects. The current study assesses the tolerance and response rate in patients (pts) with myelodysplastic syndrome (MDS) receiving R115777 on a one-week on/one-week off schedule. Starting dose was 100 mg bid with a standard 3+3 design for a total initial treatment period of eight weeks. Escalation was 100 mg po bid until grade 2 non-hematologic toxicity was observed, then 100 mg total dose per day escalation until MTD. Fifty-three pts were treated (median age 68.5 yrs; range 35–83) with RA (n=12), RARS (n=4), RAEB (n=22), RAEBt (n=7), and CMMoL (n=8). Three pts (5%) had IPSS score low; 24 (45%), INT-1; 19 (36%), INT-2; and 7 (13%) high score. Three patients had an N-RAS mutation and one had a K-RAS mutation. Fifty-three patients are evaluable for toxicity and 51 are evaluable for response (1 non-compliant, 1 ineligible). This regimen was well tolerated. The most common toxicity was myelosuppression (60% of the patients). Twenty percent reported no side effects. Non-hematologic toxicities included mild skin rash (15%), diarrhea (13%), increase in SGPT (13%), increase in bilirubin (10%), and nausea (8%). DLTs of ataxia (n=1) and fatigue (n=1) occurred at doses of 1300 mg/day. The MTD appears to be 1200 mg/day. Fifteen of 51 evaluable patients responded (3 CRs and 12 hematologic improvements). Interestingly, 3 of 6 pts at the lowest dose level (100 mg bid) responded, including a CR. Major platelet responses were most common; 11 of the 15 responders had a platelet response. Only one patient among the responders (hematologic improvement) had a RAS (N-RAS) mutation. Median time to response is eight weeks (range: 4–32 weeks). In conclusion, alternate week therapy with R115777 is well tolerated and a response rate of 29% is achieved in the Phase I setting. This intermittent schedule would lend itself well to combination or maintenance regimens.
Global Gene Expression in Leukemic Blasts as a Function of Germline Genetic Variation.
Authors: French Deborah , Wilkinson Mark R. , Yang Wenjian , de Chaisemartin Luc , Cook Edwin H. , Das Soma , Ratain Mark J. , Evans William E. , Downing James R. , Pui Ching-Hon , Relling Mary V. 
Published: October 2019

Abstract
The possible impact of common, functional, germline polymorphisms on clinical outcome in patients with leukemia is under active investigation. However, little attention has been paid to the possible consequences of germline genetic variation on genome-wide phenotypic variation in human tissues. We determined the germline status of 16 well-characterized functional genetic polymorphisms (using normal leukocyte cell DNA) in unrelated children with newly diagnosed acute lymphoblastic leukemia (ALL). We assessed whether global gene expression (using oligonucleotide arrays that interrogated approximately 10,000 genes) of diagnostic ALL blasts from the same patients differed by germline polymorphic genotypes. Gene expression values were adjusted for ALL-subtype-specific patterns. In a supervised analysis that divided patients based on their germline genotypes, we identified two polymorphisms that were significant predictors of global gene expression: the UGT1A1 promoter repeat polymorphism [A(TA)nTAA] (181 probe sets, p=0.01, false discovery rate [FDR] = 35.6%) and the GSTM1 deletion (112 probe sets, p=0.008, FDR = 42.5%). Genes whose expression differed significantly in ALL cells from patients with and without the UGT1A1 (TA) 7/7 genotype included ATM and ABL1; genes whose expression differed significantly between patients with the GSTM1 null genotype and the non-null genotype included PCNA, PRIM1, CDC6 and SKP1A. In an unsupervised analysis, patients were separated into two clusters; only the UGT1A1 promoter repeat polymorphism differed in frequency between the two clusters (p=0.001, Fisher’s exact test). These findings illustrate that polymorphisms in genes whose direct products are restricted to other tissues (e.g. UGT1A1 is primarily expressed hepatically) may affect gene expression elsewhere (e.g. ALL blasts). Because UGT1A1 is involved in the conjugation (and thus the transport and excretion) of numerous endogenous steroids and hormones, it is plausible that genotypic variation in its activity could have consequences for gene expression in distant tissues, such as ALL blasts.
Valuation of Cytogenetics and FISH in Evaluation of Myelodysplastic Syndromes: A Cancer Cytogenetics Reference Lab’s Experience.
Authors: Sun Guoxian , Lorenzo Michael , Tripodi Joseph , Chrysostomou Chrysostomos , Stephenson Christine F. , McGill John R. 
Published: October 2019

Abstract
Cytogenetics has proven an essential tool not only for confirming a diagnosis/classification, but for providing prognostic value as well in myelodysplastic syndromes (MDS). However, approximately 50% of primary MDS do not show discernible chromosome changes. In recent years, the fluorescence in situ hybridization (FISH) technique using gene or chromosome locus/region specific probes has emerged as a promising test in various hematopoietic and lymphoid neoplasms. To evaluate the application of FISH panels and cytogenetic studies in MDS, we retrospectively analyzed 1,885 consecutive bone marrow results from patients with suspected MDS due to cytopenia(s). In particular, we assessed the additional information a FISH reflex testing might have given in cytogenetically normal cases. The probes used in the panel included the EGR1 at 5q31, the D7S522 at 7q31, the D8Z2 for the centromere of chromosome 8, the MLL at 11q23 and the D20S108 at 20q12 (Vysis, Inc.). Among all patients, 190 (10%) had clonal chromosome abnormalities, mostly as reported in the literatures, eg, -5/5q- accounted for 34.7% of abnormalities, trisomy 8 29.5%, -7/7q- 14.2%, 20q- 13.7%. Of 345 cases with a FISH reflex test ordered and performed, only 3 (0.87%) showed positive results: a deletion of 7q31, a deletion of 20q12 and a deletion of 5q31 in 9.6%, 8.2% and 71.5% of interphase cells respectively. For the case with 5q- detected by FISH, only 12 metaphases were available for cytogenetic analysis. From our data and experience, at present, interphase FISH panel testing seems not to be an efficient and cost-effective method used as a screening test for cytopenia(s) in the diagnosis of MDS, different from its applications in B-cell chronic lymphoid leukemias, non-Hodgkin lymphomas and plasma cell neoplasms where neoplastic cells inherited not to divide easily in culture for metaphase analysis. Rather, it should be used for suspected MDS cases as a technique of choice for problematic specimens compromised for cytogenetic analysis such as cellular insufficiency, extended transit time and extremely low mitotic index or poor chromosome morphology. Until more genetic defect targeted probes become available with a better understanding of the stem cell biology and pathogenesis in MDS, cytogenetics is still the best and a “must” technique for detecting genomic aberrations in MDS and nearly all other myeloid hematopoietic neoplastic disorders.
Administration of an HE2100 Depot Preparation after 60Co Total Body Irradiation (400 cGy) Reduces the Duration of Severe Neutropenia, Thrombocytopenia and Anemia in Rhesus Macaques.
Authors: Dowding Charles , Frincke James , Garsd Armando , Stickney Dwight R. , Reading Christopher L. 
Published: October 2019

Abstract
HE2100 (androst-5-ene-3β,17β-diol) is a naturally occuring adrenal steroid hormone that exhibits a relatively weak interaction with the androgen receptor, estrogen receptor-α and estrogen receptor-β but not the glucocorticoid receptor. We previously reported (Blood [2003] 1002;20) that subcutaneous HE2100 administration (daily for 10 days) eliminated severe neutropenia in rhesus macaques exposed to 400 cGy 60Co total body irradiation (TBI). The current study utilized the same model of myelosuppression in rhesus macaques and evaluated the activity of HE2100 when administered as a depot-type preparation on duration of Grade 4 neutropenia (<500/μL, G4 Neut), at least Grade 3 thrombocytopenia (<50,000/μL, G3 Thromb) and Grade 4 anemia (<6.5 g/dL, G4 Anemia). Blood was analysed daily during the cytopenic phase and approximately every three days at other times through Day 35 (irradiation Day 1) to minimize the effect of phlebotomy. HE2100 (15 mg/kg) was administered by daily intramuscular injection for 5 days (Regimen 5d-IM), by four once-weekly intramuscular injections (Regimen 1w-IM) or by four once-weekly subcutaneous injections (Regimen 1w-SQ). The first dose for all regimens was administered 2 to 4 hours after TBI. All groups comprised of 2 male and 1 female young adult rhesus macaques with the exception of the vehicle group (2 males and 2 females). Vehicle-treated animals experienced on average G4 Neut, G3 Thromb and G4 Anemia for 11.8, 3.5 and 4.0 days, respectively. Animals treated by 5d-IM experienced on average 2.7 days of G4 Neut, 0 days of G3 Thromb and 0 days of G4 Anemia. The values for Regimens 1w-IM and 1w-SQ were 6.0 and 4.5 days (G4 Neut), 0.3 and 0.3 days (G3 Thromb) 0 and 0 days (G4 Anemia), respectively. These results indicate that HE2100 depot-type preparations delivered by either 4 or 5 SQ or IM injections substantially reduced the duration of severe neutropenia following 400 cGy TBI. Major morbidity or mortality associated with acute Hematopoietic Syndrome is believed to result from sepsis associated with severe neutropenia. Hence it is possible that HE2100 would protect against acute Hematopoietic Syndrome-related major morbidy or mortality. The contribution of thrombocytopenia or severe anemia to Hematopoietic Syndrome-related major morbidity or mortality is unknown but it is possible that HE2100-mediated protection of these blood elements might be beneficial by, for example, reducing tissue hypoxia. In conclusion, HE2100 affords significant protection as a countermeasure to TBI in rhesus macaques. There is an umet medical need for a cost-effective countermeasure for acute Hematopoietic Syndrome that may result from exposure to a nuclear event. It is possible that the protection seen in rhesus macaques may extend to man.
Cholinergic Stress Responses Facilitate the Molecular Mechanisms Underlying Granulocytosis.
Authors: Deutsch Varda R. , Pick Marjorie , Grisaru Dan , Perry Chava , Naparstek Elizabeth , Lapidot Tzvee , Soreq Hermona 
Published: October 2019

Abstract
Glucocorticoid-initiated granulocytosis following trauma persists long after cortisol levels decrease, through yet unknown modulators of hematopoiesis. An intriguing candidate for such a modulatory role is the AChE-R splice variant of acetylcholinesterase. In brain and muscle a functional glucocorticoid response element (GRE) in the distal promoter of the ACHE gene induces overexpression of AChE-R following trauma. To explore the possibility that circulating and/or blood cells-associated AChE-R regulates sustained granulocytosis following stress, we employed labor and childbirth as the paradigm for acute, transient stress. In intra-partum women, increased AChE-R expression in granulocytes was observed by flow cytometry, which correlated significantly with their high cortisol levels and elevated AChE activity in plasma. In post-partum women, leukocyte counts, AChE-R positive granulocytes and AChE activity in plasma remained high for several days after cortisol levels declined. Furthermore, exposure to ARP, a synthetic peptide with the C-terminal sequence of AChE-R, promoted AChE gene expression in human CD34+ progenitors and facilitated their efficient proliferation in liquid cultures (1) in an antisense suppressible manner, supporting auto-regulatory prolongation of AChE-R expression. The intracellular interaction of the C-terminal domain of AChE-R with RACK1 and protein kinase Cε (2) supports such a mechanism. In 2 weeks cultures of CD34+ HPC, 2nM ARP induced granulocyte expansion and maturation. Additionally, exposure to ARP for 24 hours facilitated the production of pro-inflammatory cytokines interleukin (IL)-6, IL-10 and TNFα in adult PB MNC and enhanced the engraftment of CD34+ cells in NOD/SCID mice. We conclude that stress-induced AChE-R accumulation and consequent inflammatory reactions facilitate prolonged granulocytosis.
The Transcriptional Program of Terminal Granulocytic Differentiation in Man.
Authors: Borregaard Niels , Jacobsen Lars C. , Borup Rehanah , Rasmussen Thomas , Bjerregaard Malene D. , Nielsen Finn C. , Cowland Jack B. , Theilgaard-Moench Kim 
Published: October 2019

Abstract
To characterize the transcriptional program that governs terminal granulocytic differentiation in vivo, we performed comprehensive microarray analyses of human bone marrow (BM) populations highly enriched in promyelocytes (PMs), myelocytes/metamyelocytes (MYs), and neutrophils (bm-PMNs). These analyses identified 11,310 genes involved in differentiation, of which 6,700 were differentially regulated including granule proteins and surface receptors previously not identified in neutrophils. Functional clustering demonstrated that differentially expressed genes were assigened to all of the major gene categories including apoptosis, cell cycle, chaperones, enzymes, immunity proteins, kinases, motor proteins, signal transducers, structural proteins, and transcription factors. In an attempt to define the developmental distance between PM, MY, and bm-PMN populations, we assessed the Pearsons correlation coefficient (γ) by correlating the transcriptomes (=all 44.760 probe sets, Affymetrix) of BM populations. The correlation coefficients among replicates of BM populations were in the range of 0.97–0.99. On the other hand the correlation coefficients between BM populations were 0.81 (γPM - MY), 0.79 (γMY - bm-PMN), and 0.52 (γPM - bm-PMN), and thus, provided a useful quantitative measure reflecting the hierarchical relationship between the three BM populations. Additional correlation of bm-PMN and peripheral blood-PMN transcriptomes revealed a high similarity of both populations (γbm-PMN - pb-PMN=0.95) indicating a termination of granulocytic differentiation in the BM microenvironment during steady state hematopoesis. Differentiation of PMs towards MYs was accompanied by a marked decline of proliferative and general cellular activity as defined by downregulation of E2F target genes, cyclin dependent kinases 2/4/6, and various metabolic, proteasomal, and mitochondrial genes. Expression patterns of apoptosis genes indicated death control by the p53-pathway in PMs and by death receptor pathways in bm-PMNs. Effector proteins critical for host defense were expressed successively throughout granulocytic differentiation, whereas receptors and receptor ligands essential for the activation of the host defense program were terminally upregulated in bm-PMNs. The upregulation of ligand-receptor pairs, which are defined inducers as well as target genes of NF-kB, suggests a constitutive activation of NF-kB in bm-PMNs by autocrine loops. Overall, these results define a granulocytic differentiation model governed by a highly coordinated fail-safe program, which promotes completion of differentiation before cells gain responsiveness towards activating stimuli that accompany infections.
2-Chlorodeoxyadenosine (2-CdA) and Cyclophosphamide (Cy) Alone or in Combination with Rituximab (Rit) for Previously Untreated Waldenstrom’s Macroglobulinemia (WM).
Authors: Weber Donna M. , Wang Michael , Delasalle Kay B. , Gavino Maria , Alexanian Raymond 
Published: October 2019

Abstract
Between 3/96-11/03 we treated 62 consecutive, newly diagnosed pts with symptomatic WM with either 2-CdA 1.5 mg/m2 sc tid x 7d + Cy 40 mg/m2 po bid x 7d (35 pts, 3/96-2/99) or with identical doses of 2-CdA and cyclophosphamide + Rit 375 mg/m2 IV q wk x 4 wk (27 pts, 11/98-11/03). For both regimens a second and final course was repeated after 6 weeks. Partial response (PR), defined by at least 50% reduction of monoclonal IgM, adenopathy, and organomegaly, was noted in 83% (29 pts) of pts treated with 2-CdA-Cy and 81% (22 pts) with 2-CdA-Cy-Rit; complete disappearance of clonal evidence of disease (CR) by negative serum and urine immunofixation, bone marrow, and CT scan was noted in 6% (2 pts) treated with 2-CdA-Cy and 11% (3 pts) with 2-CdA-Cy-Rit. Overall response rate was 89% and 93% for 2-CdA-Cy and 2-CdA-Cy-Rit, respectively. Responding patients were followed without further treatment until relapse, defined by a 25% increase in M-protein from nadir, or recurrence of adenopathy or organomegaly. Median time to remission was similar at 2.5 mos for 2-CdA-Cy and 2.4 months for 2-CdA-Cy-Rit (p.42), but time to treatment failure (TTF) appeared longer for 2-Cda-Cy-Rit (med. 64.2 mos) than for 2-CdA-Cy (med. 31.4 mos) (p.20). Since many pts have not required retreatment for symptomatic disease at the time of relapse, we also evaluated time to retreatment (TTRT) as a separate endpoint. The median time to retreatment (TTRT) has not been reached with 2-CdA-Cy-Rit, in comparison with a median TTRT of 51.2 mos with 2-CdA-Cy (p<.01), illustrating the prolonged period of stability after limited treatment with either 2-CdA combination and the superiority of added rituximab. Median overall survival has not been reached with either regimen since only 27% of all pts have died. Both treatment regimens were associated with minimal toxicity, high response rate, long duration of unmaintained remission, even longer time to the need for retreatment, and long survival. Thus treatment with a limited 2-CdA regimen represents the therapy of choice, in our opinion, for previously untreated, symptomatic WM.