bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catheter-related thrombosis: lifeline or a pain in the neck?
Authors: Kamphuisen Pieter W. , Lee Agnes Y. Y. 
Published: October 2019

AbstractCentral venous catheters (CVCs) are used extensively in cancer patients for the administration of therapy and phlebotomy. An important complication of CVCs is the development of catheter-related thrombosis (CRT), which becomes symptomatic in approximately 5% of the patients. Several factors, such as insertion location and position of the catheter tip, increase the risk of CRT. Prevention of CRT with systemic anticoagulant prophylaxis has largely been ineffective. In addition, the optimal diagnostic strategy and anticoagulant treatment are unclear due to the lack of well-designed studies. The most recent American College of Chest Physicians guidelines recommend (color) Doppler ultrasound more than venography as the initial diagnostic test in patients with suspected arm thrombosis. Only if the ultrasound is negative and clinical suspicion is high is further testing with D-dimer, serial ultrasound, or venography advocated. In case of CRT, removal of the catheter is not necessary if it is functional and needed for chemotherapy. Anticoagulant treatment of CRT consists of treatment with low-molecular-weight heparin (LMWH) followed by vitamin K antagonists for at least 3 months. Whether long-term treatment with LMWH is more effective than vitamin K antagonists in cancer patients with CRT is unknown, but LMWH may be advocated following the recommendations in lower limb thrombosis and cancer. In addition, the effect of new anticoagulants in CRT has not been studied.
B- and T-cell prolymphocytic leukemia: antibody approaches
Authors: Dearden Claire 
Published: October 2019

Abstract
B- and T-cell subtypes of prolymphocytic leukemia (PLL) are rare, aggressive lymphoid malignancies with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features. Prognosis for these patients remains poor, with short survival times and no curative therapy. The advent of mAbs has improved treatment options. In B-PLL, rituximab-based combination chemoimmunotherapy is effective in fitter patients. TP53 abnormalities are common and, as for chronic lymphocytic leukemia, these patients should generally be managed using an alemtuzumab-based therapy. Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival. Consolidation of remissions with autologous or allogeneic stem cell transplantation further prolongs survival times, and the latter may offer potential cure. The role of allogeneic transplantation with nonmyeloablative conditioning needs to be explored further in both T- and B-PLL to broaden the patient eligibility for what may be a curative treatment.
Recent insights into the role of the contact pathway in thrombo-inflammatory disorders
Authors: van Montfoort Maurits L. , Meijers Joost C.M. 
Published: October 2019

Abstract
The contact pathway of coagulation consists of the proteins factor XI, factor XII, prekallikrein, and high-molecular-weight kininogen. Activation of the contact system leads to procoagulant and proinflammatory reactions. The contact system is essential for surface-initiated coagulation, as exemplified by aPTT, but there is probably no role for the contact system in initiating physiologic in vivo coagulation. However, over the last few years, there has been renewed interest, especially because of experimental evidence suggesting that the contact system contributes to thrombosis. Knockout mice deficient in one of the contact proteins were protected against artificially induced thrombosis. Furthermore, inhibiting agents such as monoclonal antibodies, antisense oligonucleotides, and small molecules were found to prevent thrombosis in rodents and primates in both venous and arterial vascular beds. Although it remains to be established whether targeting the contact system will be effective in humans and which of the contact factors is the best target for anticoagulation, it would constitute a promising approach for future effective and safe antithrombotic therapy.
STANDARDIZATION OF THE QUICK PROTHROMBIN TEST
Authors: AGGELER PAUL M. , HOWARD JOAN , LUCIA S. P. , CLARK WILLIAM , ASTAFF ALEXIS 
Published: October 2019

Abstract
A large specimen of human brain, obtained at autopsy, was dehydrated and stored in an evacuated desiccator. Portions of the material were removed when needed and the desiccator was re-evacuated. Under these conditions there was no loss of thromboplastic potency over a period of two years.
See PDF for Table
See PDF for Table
The dry oxalate mixture (6 mg. of ammonium oxalate and 4 mg. of potassium oxalate) was used as an anticoagulant in order to obtain plasma for the prothrombin tests.
With the specimen of thromboplastin used in these experiments, normal standards for the Quick prothrombin test were found as shown in table 8. These results do not necessarily mean that the normal range of prothrombin concentrations is from 75 to 140 per cent of the actual amount of prothrombin in the plasma of the average normal subject. They mean only that with the methods here employed, values within this range may be expected to occur.
There was no significant difference between the prothrombin values obtained in a group of normal subjects by methods using diluted or undiluted plasma. In repeated tests on the same subject there appeared to be slightly greater accuracy when the tests were performed on diluted plasma, but there was no significant difference between the results obtained with plasma diluted to 50 or to 25 per cent of its original concentration.
Repeated tests on diluted and undiluted plasma from the same normal subject produced the range of normal variation about the various prothrombin concentrations shown in table 9.
The normal variation that may be expected to occur at any given prothrombin level must be considered in interpreting the variations that appear after administration of vitamin K or dicumarol.
The use of a single specimen of blood from one random normal subject as a normal standard may lead to considerable error, because of unavoidable technical variables and because of differences in the prothrombin concentrations of different normal subjects. To establish reliable normal standards, the blood of at least 5 normal subjects should be individually tested with the same specimen of thromboplastin and the results averaged.
CELLULAR CHANGES PRODUCED BY EXTRACTS OF HUMAN ORGANS
Authors: ERF L. A. , TURNER D. L. , MILLER F. R. 
Published: October 2019

Abstract
By the injection of lipoid extracts of organs (liver, spleen, and lymph nodes) of 5 patients with leukemia, 1 with Hodgkin's disease, and of 4 "control" cases (3 of heart disease and 1 of cerebral tumor) into 28 guinea-pigs, it was observed that:
a. extracts from human myeloid leukemic organs produced "myeloid reactions" or infiltrations in guinea-pigs;
b. extracts from lymphoid leukemic organs produced "lymphoid reactions";
c. extracts from organs involved with Hodgkin's disease produced "Hodgkin's reactions"; and
d. extracts from "normal" organs produced slight lymphoid or monocytoid infiltrations.
Evidence that Platelet Accelerator (Platelet Factor 1) Is Adsorbed Plasma Proaccelerin
Authors: HJORT PETER , RAPAPORT SAMUEL I. , OWREN PAUL A. 
Published: October 2019

Abstract
1. Human platelets possess an accelerator activity equal to about six per cent of the proaccelerin activity of normal citrated plasma. This accelerator activity is only slightly reduced by 10 washings.
2. Thrombin increases platelet accelerator activity as much as ten fold. This means that platelet accelerator activity behaves like proaccelerin (plasma Acglobulin) rather than accelerin (serum Ac-globulin).
3. Platelets from a patient with parahemophilia (congenital proaccelerin deficiency) possess only a trace of accelerator activity. They acquire a normal amount of accelerator activity after contact with normal platelet-poor plasma.
4. Trypsin destroys 90 per cent or more of the platelet accelerator activity of normal platelets without altering their appearance. Trypsinized platelets regain normal accelerator activity upon incubation with normal platelet-poor plasma.
5. These findings strongly suggest that the platelet accelerator (platelet factor 1) is adsorbed plasma proaccelerin.
The Cytophotometric Estimation of the Desoxyribonucleic Acid (DNA) Content of Individual Plasma Cells from Multiple Myeloma and Nonspecific Plasmacytoses
Authors: PETRAKIS NICHOLAS L. , FOLSTAD LOIS J. 
Published: October 2019

Abstract
The cytophotometric technic employing the Feulgen reagent was used to determine the relative amount of DNA in the nuclei of individual myeloma and plasma cells aspirated from the bone marrow. Individual myeloma cells were found to contain markedly elevated amounts of DNA as compared to that in the plasma cells of non-specific plasmacytoses. Myeloma cells were found to contain geometric multiples (2, 4, 8) of the amount of DNA present in normal lymphocytes, and the degree of DNA "ploidy" was related to the morphologic stage of immaturity. Polyploid DNA values were not found in the non-specific plasmacytoses. The possible mechanisms of formation were discussed. The findings are interpreted as suggesting the presence of a basic alteration in the quantitative DNA-chromosome relationship in myeloma cells, and they offer additional support for the separation of the myeloma plasmacytoses from nonspecific plasmacytoses.
Hemolytic Transfusion Reaction Due to Anti-Lea
Authors: MATSON G. ALBIN , COE JOHN , SWANSON JANE 
Published: October 2019

Abstract
A case is reported in which a transfusion of whole blood of group Le (a+b-) produced a severe hemolytic transfusion reaction in a patient of group Le (a-b-). The anti-Lea in the patient's serum had apparently been stimulated by previous transfusions. No other antibody was demonstrable by us in this case.
Differences in Susceptibility of Polymorphonuclear Leukocytes from Several Species to Alteration by Systemic Lupus Erythematosus Serum: Application to a More Sensitive L. E. Phenomenon Test
Authors: CARRERA ANA E. , REID MAY VIRGINIA , KURNICK N. B. 
Published: October 2019

Abstract
In the article by Carrera, Reid, and Kurnick: Differences in Susceptibility of Polymorphonuclear Leukocytes from Several Species to Alteration by Systemic Lupus Erythematosus Serum: Application to a More Sensitive L. E. Phenomenon Test (Blood 9: 1165, 1954), the following footnote, pertaining to Dr. Carrera, was inadvertently omitted: Fellow, American Cancer Society, recommended by the Committee on Growth, National Research Council.
Electron Microscope Observations of the Platelet-Fibrin Relationship in Blood Clotting
Authors: DE ROBERTIS E. 
Published: October 2019

Abstract
The behavior of stretched out human platelets in different stages of blood clotting has been observed with the electron microscope. In the early stages of coagulation the morphologically intact platelets apparently act as centers of orientation and condensation of the fibrin fibrils. This effect is not found in platelets which have previously undergone extensive damage or disintegration. In more advanced stages of clotting, many platelets remain normal, showing their attachment to the fibrin, while others have disintegrated and appear as residual dense bodies.
The probable action of platelets in the retraction and syneresis of the blood clot is discussed. It is suggested that at the surface of the morphologically intact platelets, adhesion forces develop which hold and orient the molecular chains of fibrin increasing the number of interacting junctions and producing syneresis. On the contrary, the platelets which have suffered an injury which alters these surface adhesive properties do not interact with the fibrin fibrils and, as a result, the mechanism of clot retraction is impaired.
Hematologic Observations of the Course of Erythroblastosis Fetalis
Authors: DESFORGES JANE F. , O’CONNELL LIAM C. 
Published: October 2019

Abstract
Serial studies revealed characteristic changes in the peripheral blood of infants with erythroblastosis fetalis. In the presence of elevated nucleated red cells and reticulocytosis, replacement transfusion brought about a momentary decline to normal levels followed by a second rise during the succeeding three days before the values returned to low levels. Platelet counts diminished within a day after replacement and only gradually rose toward normal after approximately three days. Such a picture was not seen in the mildly affected babies who did not receive replacement therapy, in whom the platelet values varied.
Within the first three months in both groups anemia developed in the presence of little evidence of compensating marrow activity. After a decline of the hemoglobin to an average level of 7.6 Gm. per cent, erythropoiesis became adequate for return to normal levels. This hypoplastic defect could not be correlated with any other parameter of the disease.
Abnormalities were noted in the osmotic and mechanical fragility of the red cells in this disease. The major population of cells was found to be more susceptible to osmotic stress while the limits of hemolysis were within the normal range. The osmotic curves of the blood of those patients who were not transfused returned to normal within 4 weeks. Mechanical fragility of the red cells was increased in a significant number, and this abnormality was observed until the time when minimal hemoglobin values were reached. There was no correlation of these variations in fragility with other laboratory or clinical manifestations of the disease.
Unique Evidence for Autosomal Dominant Inheritance of Severe Congenital Neutropenia.
Authors: Boxer Laurence A. , Stein Steven , Buckley Danielle , Subramanian Sandhya , Bolyard Audrey Anna , Olson Maynard V. , Dale David C. 
Published: October 2019

Abstract
Severe congenital neutropenia was originally described as an autosomal recessive disorder characterized by severe neutropenia and recurrent bacterial infections from birth, but other reports indicate that autosomal dominant inheritance occurs. Several report now indicate that most, but not all, patients with severe congential neutropenia have heterozygous mutation in the gene for neutrophil elastase (NE or ELA2). We recently investigated an unusual series of cases of severe congenital neutropenia occurring when the same sperm donor was utilitized by four different families to impregnate mothers by either artificial insemination or in vitro fertilization. Three sets of twins were conceived and a single child in the four families. Collectively one set of twins and one child each from the other two families conceiving twins and the single child were all found to have severe congenital neutropenia. The mean for their median blood neutrophils (ANC) at diagnosis was 84 +/−32 x109/L (range 0–166 x 109 /L); and their other blood counts were remarkably similar. On treatment with G-CSF (mean dose 6.7+/− 1.3 SEM mcg/kg/day) the mean for the median ANC increased to 3290 +/−1410 x109/L( range 420–8600 x 109 /L )
To determine whether the sperm donor was responsible for transmitting severe congenital neutropenia, geonomic DNA from peripheral blood leukocytes was used to sequence the gene for neutrophil elastase in the affected children and their mothers using standard techniques. None of the mothers had a mutation in their NE gene but all five affected children had the same mutation effecting the fourth exon at site S97L. Since it was not possible to perform genetic analysis on biological samples from the donor, more detailed genetic linkage analysis was performed on the affected children and their mothers. Linkage mapping analysis of 22 microsatellite markers on chromosome 14 and 19 confirmed that all affected children possessed one of the two paternal alleles. For an 11 centiMorgan region immediately adjacent to the NE gene on chromosome 19, all affected children shared a single paternal allele, and 4 of 5 affected children shared a single paternal allele for a 20 centiMorgan region adjacent to the NE gene. The studies indicate that the father of the affected children provided consistent haplotypes that led to the expression of severe congenital neutropenia in all of the affected children. This investigation strongly implicates that autosomal dominant inheritance for severe congenital neutropenia. It also raises important questions for the evaluation of subjects in sperm donor programs.
Uric Acid Induces High Mobility Group Box1 Protein Release in Monocytes/Macrophages through P38 MAPK, ERK1/2, JNK and AP-1 Activation.
Authors: Biswas Kamal K. , Oyama Yoko , Abeyama Kazuhiro , Hashiguchi Teruto , Maruyama Ikuro 
Published: October 2019

Abstract
Uric acid, a final metabolite of purine metabolism has gained attention for its pathogenic role in the development of hypertension, vascular disease, renal disease, and cardiovascular events. Recent studies have shown that soluble uric acid induces proliferation as well as synthesis of proinflammatory chemokine, monocyte chemoattractant protein 1 in rat vascular smooth muscle cells. It also stimulates human monolayer cells to produce IL-1B. IL-6 and TNF alpha. However, high mobility group box 1(HMGB1), a non histone DNA binding protein which is recently identified as a proinflammatory cytokine and can be released from cells of the macrophage/monocyte lineage by proinflammatory stimuli or by cells undergoing necrotic cell death pathway. In the present study, we hypothesized that soluble uric acid may stimulates monocytes/macrophages to release HMGB1. Here we demonstrate that crystal and endotoxin free uric acid triggers the release of HMGB1 in a time and dose dependant fashion in mouse macrophage cells, Raw 264.7, human leukemic promonocytes(THP-1 cells) as well as in macrophages but not in fibroblast obtained from synovial fluid of rheumatoid arthritis patients. Moreover, translocation of HMGB1 to the cytoplasm before secreted in the extracellular milieu was significantly detected within 6h of Uric acid exposure. No loss of cell viability was observed in our experimental condition as judged by trypan blue exclusion, MTT reduction and LDH release assays, indicating that HMGB1 release was not due to cell death. Uric acid treatment resulted in the activation of p38 mitogen activated protein kinase(MAPK), c-Jun N terminal kinase(JNK) and extracellular regulatroy kinase (ERK1/2). Inhibition of each of p38 MAPK, ERK1/2 and JNK by using potent and selective inhibitors, SB203580, U0126 and SP60012 respectively, almost completely blocked uric acid-induced HMGB1 release. Furthermore, Curcumin, a potent inhibitor of the transcription factor, activator protein 1(AP-1) strongly suppressed HMGB1 release, indicating that these signaling patways are essential for the induction of HMGB1 release in response to uric acid. In conclusion, our data suggest that uric acid may regulate critical proinflammatory pathways at least in part through its action as a monocyte/macrophage derived potent proinflammatory cytokine, HMGB1 release. This may play pathologic role for hyperuricemia-induced morbidities including arthritis, atherosclerosis, renal disease and so on.
Minimal Residual Disease (MRD) Kinetics after Autologous Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL) Correlate to IgH VH Mutational Status and Predict Post Transplant Outcome: Real Time ASO-IgH PCR Results of the GCLLSG CLL3 Protocol.
Authors: Ritgen Matthias , Dreger Peter , Stilgenbauer Stephan , von Neuhoff Nils , Greinix Hildegard T. , Hertenstein Bernd , Schmitz Norbert , Emmerich Berthold , Hallek Michael , Döhner Hartmut , Kneba Michael 
Published: October 2019

Abstract
The purpose of the present study was (1) to assess the quantitative impact of myeloablative therapy with autologous stem cell transplantation (SCT) on MRD levels in patients with CLL; (2) to assess the predictive value of post transplant MRD kinetics for clinical outcome; and (3) to study the influence of the IgH VH mutational status on MRD kinetics. Blood and bone marrow (BM) samples were obtained from patients from a prospective multicenter trial of the German CLL Study Group (GCLLSG CLL3 protocol) after informed consent. MRD monitoring was performed by real-time quantitative IgH PCR using allele-specific primers (ASO RQ-PCR).
Results: As of July 2004, 476 blood samples from 46 patients who had an informative primer and repeated follow-up material available were analyzed by ASO RQ-PCR with a minimum sensitivity of 1E-4. In 145 cases, BM samples obtained on the same occasion were analyzed in parallel. Blood and BM showed highly significant correlating MRD values (p=.0001; slope 0.9, r<.0001), with a tendency to higher MRD levels and higher sensitivity in BM. Myeloablative treatment with SCT resulted in a strong reduction of the CLL load (median MRD level 6.6E-3 pretransplant vs. 1.0E-4 at 90–180 days post transplant; p<.0001) with no significant difference between patients with mutated and unmutated VH, respectively. Whereas MRD levels had no prognostic impact during the first 6 months after SCT, stable or decreasing MRD kinetics below 1E-4 between 6 and 12 months after SCT were strongly predictive for a favourable outcome (4-year progression-free survival (PFS) 100%). In contrast, PFS of those patients who had increasing MRD levels at this time was significantly poorer (4-year PFS 37%; p 0.02; n = 25). Patients with increasing MRD levels early post transplant almost exclusively belonged to the subgroup with unmutated VH.
Conclusions: Myeloablative SCT can lead to substantial additional reduction of the tumor load in patients with CLL in remission. The cause of the dismal post transplant outcome of patients with unmutated VH is faster regrowth of the leukemic clone rather than less effective reduction of MRD levels immediately after SCT.
Activation of VEGFR-2 in Hematopoietic Progenitor Cells Leads to Accumulation of Myeloid Cells through Up-Regulation of GM-CSF.
Authors: Larrivee Bruno , Pollet Ingrid , Karsan Aly 
Published: October 2019

Abstract
VEGF is a secreted growth factor that mediates its biological effects by binding to two transmembrane tyrosine kinase receptors, VEGFR-1 and VEGFR-2. VEGF has previously been shown to be critical in the establishment of cells of the hematopoietic and endothelial lineages. VEGF and its receptors are expressed on subsets of hematopoietic cells, and are also expressed in some hematopoietic malignancies. However, the requirement for each of the VEGF receptors, and whether the effects of VEGF are due to autocrine or paracrine signals remains unclear. We have designed a strategy that allows us to specifically study the unique effects of VEGFR-2 signaling in hematopoietic cells in vivo. By using a VEGFR-2 cytoplasmic domain fusion protein that can be dimerized with a synthetic drug, we were able to specifically study the effects of VEGFR-2 signaling in isolation. Using mice transplanted with bone marrow transduced with the inducible VEGFR-2 fusion construct, we demonstrate an expansion of myeloid progenitors by CFC assay, as well as increases in Gr-1+ and CD11b+ cells in the bone marrow. VEGFR-2 activation did not affect the proportion of lymphoid and erythroid cells. We show, by RT-PCR and ELISA, that VEGFR-2 activation can up-regulate granulocyte/macrophage-colony stimulating factor (GM-CSF) in bone marrow cells. Using activation and blocking experiments, we show that the VEGFR-2 activity is due to autocrine effects as well paracrine effects through the induction of GM-CSF in bone marrow cells.