scholarly journals Beneficial effects of eculizumab regardless of prior transfusions or bone marrow disease: Results of the International Paroxysmal Nocturnal Hemoglobinuria Registry

2020 ◽  
Vol 105 (5) ◽  
pp. 561-570
Author(s):  
Alexander Röth ◽  
David J. Araten ◽  
Loree Larratt ◽  
Austin G. Kulasekararaj ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Beneficial Effects ◽  
Bone Marrow Disease

scholarly journals THE VALUE OF PENICILLIN IN THE TREATMENT OF AGRANULOCYTOSIS CAUSED BY THIOURACIL

Blood ◽  
1946 ◽  
Vol 1 (1) ◽  
pp. 53-66 ◽  
Author(s):  
MARY CATHERINE TYSON ◽  
PETER VOGEL ◽  
NATHAN ROSENTHAL
Keyword(s):  
Bone Marrow ◽  
Antibacterial Agents ◽  
Bone Marrow Cells ◽  
The Body ◽  
Bacterial Invasion ◽  
Beneficial Effects ◽  
Penicillin Therapy ◽  
History Of ◽  
Per Se ◽  
Hemopoietic System

Abstract Thiouracil has been found to be an effective drug in the treatment of hyperthyroidism. Agranulocytosis following its use occurred in nine cases, four of which terminated fatally. In five others a complete and rapid recovery took place following penicillin therapy. The latter drug is believed to be ideal for all cases of agranulocytosis, and especially those in which chemotherapy has been used and may have been responsible for the condition. Thus far we have not seen any report of any untoward effect on the hemopoietic system from the use of penicillin. The use of antibacterial agents for the treatment of agranulocytosis was suggested by Dameshek and Wolfson21 in 1942. It was believed by these authors that patients with agranulocytosis died not of the leukopenia per se but of the sepsis which developed secondarily to the lack of granulocytes. Two very severe cases of aminopyrine agranulocytosis treated with sulfathiazole made complete recoveries. For the treatment of sulfonamide agranulocytosis, it was suggested that a preparation differing from that which had already been used be given. With the discovery of penicillin, and its complete lack of possible deleterious effect on the bone marrow, its use was suggested by Dameshek17 (1944). A report on the beneficial effects of this medication in a case of sulfonamide agranulocytosis was later reported by Dameshek and Knowlton18 and similar cases by Sprague and Ferguson19 and by Meredith and Fink.20 Since sulfonamides may cause further toxic effect on the bone marrow, we feel that their use should be avoided in the treatment of agranulocytosis, especially where a history of previous use is obtained. We do not agree with others21, 22 who continue the use of sulfonamides in the treatment of leukopenia or agranulocytosis where these very drugs may have been responsible for the condition. It would seem better judgment to use penicillin, which by combating the bacterial invasion of the body and the consequent toxemia enables the patient to survive until the bone marrow cells regenerate.

scholarly journals Complement sensitivity of paroxysmal nocturnal hemoglobinuria bone marrow cells

Blood ◽  
1980 ◽  
Vol 55 (6) ◽  
pp. 1040-1046 ◽  
Author(s):  
J Tumen ◽  
LB Kline ◽  
JW Fay ◽  
DC Scullin ◽  
EG Reisner ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Cells ◽  
Myeloid Cell ◽  
Erythroid Cell ◽  
Hematopoietic Stem ◽  
Increased Sensitivity ◽  
Complement Lysis ◽  
Increased Susceptibility

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder in which erythrocytes, granulocytes, and platelets are defective, as shown by increased susceptibility of RBCs, WBCs, and platelets to complement- mediated lysis in vitro. The purpose of this study is to determine the sensitivity to complement lysis of PNH and non-PNH erythroid and myeloid precursors using the release of 59Fe and myeloperoxidase as specific markers to monitor the lytic action of complement on erythroid and myeloid cell precursors, respectively. Erythroid cell precursors in four of four PNH patients demonstrated increased sensitivity to complement-mediated lysis. Myeloid cell precursors in four of five PNH patients also exhibited increased sensitivity to complement and antibody. In addition, CFU-c growth was below normal in the marrow of seven PNH patients. These findings support the hypothesis that the defect in PNH occurs at the level of the hematopoietic stem cell.

scholarly journals Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Jung Hwan Oh ◽  
Fatih Karadeniz ◽  
Jung Im Lee ◽  
Youngwan Seo ◽  
Mi-Soon Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lipid Accumulation ◽  
Sulfonic Acid ◽  
Bone Marrow Cells ◽  
Adipogenic Differentiation ◽  
Polymerase Chain Reaction Analysis ◽  
Hydroxyl Group ◽  
Osteoporotic Bone ◽  
Ampk Activation ◽  
Beneficial Effects

Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties.

scholarly journals Syngeneic bone marrow transplantation without conditioning in a patient with paroxysmal nocturnal hemoglobinuria: in vivo evidence that the mutant stem cells have a survival advantage

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 742-750 ◽  
Author(s):  
M Endo ◽  
PG Beatty ◽  
TM Vreeke ◽  
CT Wittwer ◽  
SP Singh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Pathological Process ◽  
Survival Advantage ◽  
Hematopoietic Stem ◽  
Glycosyl Phosphatidylinositol ◽  
Normal Expression ◽  
Marrow Infusion

A 10-year-old girl with paroxysmal nocturnal hemoglobinuria (PNH) received an infusion of syngeneic bone marrow without preparative marrow ablation or immunosuppression. Following transplant, the patient became asymptomatic in concordance with an increase in the percentage of peripheral blood cells with normal expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). However, molecular analysis suggested engraftment of a relatively small number of donor stem cells and persistence of an abnormal stem cell with mutant PIG-A. During 17 months of observation, the percentage of cells with normal GPI-AP expression gradually decreased, while intravascular hemolysis progressively increased. Approximately 16.5 months post-transplant, the patient once again became symptomatic. Together, these results indicate that syngeneic marrow infusion provided a clinical benefit by increasing the proportion of erythrocytes with normal expression of GPI- anchored complement regulatory proteins without supplanting the abnormal stem cells. However, evidence of insidious disease progression following the marrow infusion implies that the abnormal stem cells have a survival advantage relative to the transplanted stem cells. Thus, these studies contribute in vivo data in support of the hypothesis that PNH arises as a consequence of a pathological process that selects for hematopoietic stem cells that are GPI-AP-deficient.

scholarly journals Acquired XO/XY clones in bone marrow of a patient with paroxysmal nocturnal hemoglobinuria (PNH)

Blood ◽  
1976 ◽  
Vol 47 (4) ◽  
pp. 611-619 ◽  
Author(s):  
J Whang-Peng ◽  
T Knutsen ◽  
EC Lee ◽  
B Leventhal
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Y Chromosome ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Hematopoietic Stem ◽  
Cytogenetic Studies ◽  
History Of ◽  
Aging Phenomenon

Abstract Cytogenetic studies showed both 45XO and 46XY clones in the bone marrow of a 76-yr-old male with a 17-yr history of paroxysmal nocturnal hemoglobinuria (PNH). 55Fe incorporation studies demonstrated that both clones involved the hematopoietic stem cells. The loss of the Y chromosome may reflect an aging phenomenon, rather than be related to the PNH.

scholarly journals MPL Y252H and MPL F126fs mutations in essential thrombocythemia: Case series and review of literature

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Ahmed G. Elsayed ◽  
Aeesha Ranavaya ◽  
Muhammad Omer Jamil
Keyword(s):  
Bone Marrow ◽  
Somatic Mutation ◽  
Essential Thrombocythemia ◽  
Adult Population ◽  
Case Series ◽  
Clinical Importance ◽  
The Other ◽  
Review Of Literature ◽  
Bone Marrow Disease ◽  
Stat Pathway

Essential thrombocythemia (ET) is a clonal bone marrow disease, characterized by increased production of platelets along with other clinical and bone marrow findings. Most patients with ET will have a somatic mutation in one of the known gene locations of JAK2, CALR , or MPL that can upregulate the JAK-STAT pathway. MPL mutation is present in 5% of cases with the most common mutations being W515L and W515K. In this report we describe 2 cases of patients with clinical and laboratory picture of ET. One patient carried MPLY252H mutation which is previously unreported in the adult population but has been shown to be a gain-of-function mutation. The other patient carried MPL F126fs mutation which is not known to be of clinical importance and has not been previously reported.

scholarly journals Bone marrow transplantation for paroxysmal nocturnal hemoglobinuria: eradication of the PNH clone and documentation of complete lymphohematopoietic engraftment

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1247-1250 ◽  
Author(s):  
JH Antin ◽  
D Ginsburg ◽  
BR Smith ◽  
DG Nathan ◽  
SH Orkin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Conditioning Regimen ◽  
Erythroid Cell ◽  
Polymorphism Analysis ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Pnh Clone

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) involves the proliferation of an abnormal and possibly premalignant hematopoietic stem cell. Successful treatment of PNH by marrow grafting requires that the PNH clone be eradicated by the pretransplant conditioning regimen. Four patients with PNH-associated marrow aplasia were transplanted with marrow from their HLA-matched, MLR-nonreactive siblings. Three patients were conditioned with cyclophosphamide, procarbazine, and antithymocyte serum (CTX/PCZ/ATS), and one was conditioned with busulfan/CTX/PCZ/ATS. Persistent complete engraftment of myeloid, lymphoid, and erythroid cell lines was demonstrated in all four patients by DNA sequence polymorphism analysis or cytogenetics, and RBC typing. There was no recurrence of the abnormal clone of cells for up to five years after transplantation despite the use of a conditioning regimen in three of them, which is not usually associated with permanent marrow aplasia. Bone marrow transplantation is a curative therapy in patients whose illness is severe enough to warrant the risk.

scholarly journals Oxymetholone Treatment for the Anemia of Bone Marrow Failure

Blood ◽  
1972 ◽  
Vol 40 (3) ◽  
pp. 353-365 ◽  
Author(s):  
Raymond Alexanian ◽  
Judith Nadell ◽  
Clarence Alfrey
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Failure ◽  
Cell Mass ◽  
Iron Concentration ◽  
Response To Therapy ◽  
Red Cell ◽  
Bone Marrow Disease ◽  
Subsequent Response ◽  
Red Cell Mass ◽  
Complicating Factors

Abstract Oxymetholone was given to 28 adults with chronic anemia from bone marrow disease. Changes in hematocrit and red cell mass were correlated with serial assessments of erythropoietin and erythropoiesis. Erythropoietin excretion was enhanced more than five-fold over the level expected for the hematocrit in 70% of the patients. Only 23% of the patients with an evaluable treatment trial increased their red cell mass by at least 20%. In all responders, the T½ of 59Fe disappearance ranged from 86-136 min and erythron iron turnover exceeded 0.25 mg/100 ml blood/day. A decline in serum iron concentration to the 50-100 µg/100 ml range after 1 mo of oxymetholone was frequently associated with a subsequent response to therapy. Patients with severe bone marrow failure, for whom frequent red cell transfusions were required, did not improve. The failure of other patients to respond was attributed to complicating factors that either impaired maximal erythropoietin production or restricted iron supply to the bone marrow. Hepatic toxicity was detected in less than 10% of treated patients. Results support the use of oxymetholone in the treatment of patients with moderate degrees of bone marrow failure and symptomatic anemia.

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