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 Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Bin Lin ◽  
Joan T. Smith ◽  
Marsha N. Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Water Consumption ◽  
Bone Marrow Cells ◽  
The Body ◽  
Photon Radiation ◽  
Vehicle Group ◽  
Spleen Weight ◽  
Histopathological Analysis ◽  
Marrow Cells

Exposure to ionizing radiation (radiation injury, RI) in nuclear-related episode is evident to be life-threatening. RI occurs at levels of organs, tissues, cytosols, or nucleus. Their mechanisms are still not fully understood. FDA approves pegylated granulocyte colony-stimulating factor (Neulasta™, Peg-G-CSF) for acute hematopoietic syndrome and has been shown to save lives after lethal RI. We aimed to test whether Ghrelin enhanced Peg-G-CSF’s efficacy to save more lives after lethal RI. B6D2F1/J female mice were used for the study. They received 9.5 Gy (LD50/30 at 0.4 Gy/min) emitted from the 60Co-γ-photon radiation facility. Peg-G-CSF was injected subcutaneously at 1 mg/kg once on days 1, 8, and 15 after irradiation. Ghrelin contains 28 amino acid and is a hunger peptide that has been shown to stimulate food intake, promote intestinal epithelial cell proliferation, elevates immunity, inhibits brain hemorrhage, and increases stress-coping. Ghrelin was injected subcutaneously at 113 μg/kg once on days 1, 2, and 3 after irradiation. Survival, body weight, water consumption, hematology, spleen weight, splenocytes, bone marrow cells, and histology of bone marrow and ileum were performed. We observed that radiation resulted in 30-days survival by 30%. RI decreased their body weights and water consumption volumes. On the 30th day post-RI, platelets and WBCs such as basophils, eosinophils, monocytes, lymphocytes, neutrophils and leukocytes were still significantly decreased in surviving mice. Likewise, their RBC, hemoglobin, hematocrit, and splenocytes remained low; splenomegaly was found in these mice. Bone marrow in surviving RI animals maintained low cellularity with high counts of fat cells and low counts of megakaryocytes. Meanwhile, ileum histology displayed injury. However, mice co-treated with both drugs 24 h after RI resulted in 30-days survival by 45% above the vehicle group. Additionally, the body-weight loss was mitigated, the acute radiation syndrome was reduced. This co-therapy significantly increased neutrophils, eosinophils, leukocytes, and platelets in circulation, inhibited splenomegaly, and increased bone marrow cells. Histopathological analysis showed significant improvement on bone marrow cellularity and ileum morphology. In conclusion, the results provide a proof of concept and suggest that the co-therapy of Peg-G-CSF and Ghrelin is efficacious to ameliorate RI.

scholarly journals Soy-enriched bread, a pilot study to determine its beneficial effects in menopause

2021 ◽  
Author(s):  
Daniela Giustarini ◽  
Comasia Ricci ◽  
Ilaria Ceccarelli ◽  
Stefano Pieretti ◽  
Paolo Andre ◽  
...  
Keyword(s):  
Experimental Tests ◽  
The Body ◽  
Many Body ◽  
Beneficial Effects ◽  
Regular Consumption ◽  
Aging Women ◽  
Before And After ◽  
Quality Of Life Index ◽  
Antioxidant Parameters ◽  
History Of

Menopause is the last step in the reproductive history of a woman. The ovaries stop producing hormones and the body reacts by lowering its functions, including the neuronal one. Phytoestrogens are plant products with estrogen-like activity able to affect many body functions. The aim of the present experiment was to study the effects of 30 days of regular consumption of a soy-enriched bread containing a known amount of phytoestrogens (genistein and daidzein). Women at climacteric, within 5 years or more than 5 years of menopause, were asked to include in their diet 200 g/day of a bread containing 40 mg of phytoestrogens. The effect on common menopausal symptoms and neurophysiological, hormonal and antioxidant parameters were determined before and after 30 days through questionnaires and experimental tests. Phytoestrogens were measured in the urine. In all groups, there was a significant increase of phytoestrogens in the urine and a decrease of the classical symptoms of menopause as well as a significant improvement in attentional performance tests, the quality of life index and pain intensity. Phytoestrogens present in the soy-enriched bread, are an important supplement in aging women due to their ability to induce estrogen-like effects without the potential side effects of estrogens.

The Effects of Yerba Maté (Ilex Paraguariensis) Consumption on IL-1, IL-6, TNF-α and IL-10 Production by Bone Marrow Cells in Wistar Rats fed a High-Fat Diet

2013 ◽  
Vol 83 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Luciana Simão Carmo ◽  
Marcelo Macedo Rogero ◽  
Mayara Cortez ◽  
Monica Yamada ◽  
Patrícia Silva Jacob ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Bone Marrow Cells ◽  
The Body ◽  
Ilex Paraguariensis ◽  
Yerba Mate ◽  
High Fat ◽  
Tnf Α ◽  
Marrow Cells

An excessive consumption of a high-fat diet (HFD) results in becoming overweight or obese, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Because of the potential for yerba maté (Ilex paraguariensis) (YM) to impact obesity, this study aimed to investigate the effects of YM consumption on the hematological response and on the production of interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, and IL-10 by bone marrow cells from Wistar rats fed a HFD. Male Wistar rats were fed a control (CON) or HFD diet for twelve weeks. At the end of this period, the rats received YM (1 g/kg/day body weight) for 4 weeks. After euthanasia, hemograms and myelograms were evaluated, while the bone marrow cells were cultured in the presence or absence of lipopolysaccharide (LPS) to evaluate the production of IL-1α, IL-6, TNF-α, and IL-10. The consumption of YM reduced the body weight, the body adiposity, and the cholesterol levels in HFD-fed rats. Bone marrow cells from the HFD group produced more IL-1α, IL-6, and TNF-α, and less IL-10, when compared to cells from the control group, and YM consumption reduced the IL-1α, IL-6, and TNF-α production by the cells. However, cells from the HFD rats that were stimulated with LPS increased their IL-1α, IL-6, and TNF-α production, but YM consumption did not change this result. In summary, the consumption of YM affects the production of IL-1α, IL-6, and TNF-α by bone marrow cells, promotes weight loss, decreases the number of white blood cells, and significantly improves serum cholesterol level in HFD-fed rats. However, the bone marrow cells from the HFD+YM-fed rats challenged with LPS did not show improvement in the inflammatory response compared to the cells from animals fed only a HFD that were also challenged with LPS.

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 BLOOD CELL FORMATION AND DISTRIBUTION IN RELATION TO THE MECHANISM OF THYROID-ACCELERATED METAMORPHOSIS IN THE LARVAL FROG

1923 ◽  
Vol 38 (5) ◽  
pp. 529-541 ◽  
Author(s):  
H. E. Jordan ◽  
C. C. Speidel
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Metabolic Rate ◽  
Cell Formation ◽  
The Body ◽  
Red Bone Marrow ◽  
History Of ◽  
Regressive Change ◽  
Mesenchymal Precursor ◽  
Hemopoietic Organ

1. Thyroid-accelerated metamorphosis in the larval frog is accompanied by changes in the hemopoietic centers and in the blood cell distribution in the various regions of the body. These changes are interpreted as results of the fundamental change in basal metabolic rate induced by the thyroid treatment. 2. There is initiation of the shift of hemopoietic locus from the kidney, the larval hemopoietic organ, to the spleen, the adult hemopoietic organ. The spleen, being chiefly an erythrocyte producer, becomes of greater importance with the transition from the lower metabolic rate to the higher, since greater erythropoiesis becomes necessary to supply the physical basis for the maintenance of the higher metabolic rate. 3. It is suggested that the appearance of red bone marrow in the later history of the frog is correlated with a still higher metabolic rate. Phylogenetically, in the vertebrate series, red bone marrow is also associated with higher metabolic rate. 4. The new metabolic rate initiated in tadpoles by thyroid administration sets up a demand for (a) erythrocytes, (b) granulocytes and lymphoid phagocytes for distribution to regions of regressive change, (c) lymphocytes, (1) as progenitors of erythrocytes, granulocytes and phagocytes, (2) for promoting growth of cells in regions of progressive change. 5. Upon the hemopoietic reserve, which in the last analysis is the lymphocyte (and its mesenchymal precursor), depends the extent to which metamorphosis will proceed. Inability on the part of the hemopoietic centers, chiefly the spleen, to keep pace with the demand for blood cells during metamorphosis results in metamorphic stasis, a condition of anemia which is usually followed by death. 6. The growth-promoting function of leucocytes, as demonstrated by Carrel, is probably to be ascribed to the lymphocyte component of leucocytes. 7. The granulocytes have probably also a glandular function, and may exert a lytic effect upon adjacent tissues in regions of regressive change.

Familial Mastocytosis: Identification Of KIT K509I Mutation and Its In Vitro Sensitivity To Imatinib, Dasatinib and PKC412

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5267-5267 ◽  
Author(s):  
Paula De Melo Campos ◽  
João Agostinho Machado-Neto ◽  
Adriana Silva Santos Duarte ◽  
Renata Scopim-Ribeiro ◽  
Flavia Fonseca de Carvalho Barra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Bone Marrow Cells ◽  
Systemic Mastocytosis ◽  
History Of ◽  
Primary Bone ◽  
Primary Bone Marrow ◽  
Apoptosis Ratio

Abstract Background Mast cell diseases are myeloproliferative neoplasms characterized by an abnormal proliferation and accumulation of mast cells in different tissues. The clinical presentation of mastocytosis is heterogeneous, ranging from skin-limited disease to more aggressive variants that may be associated with multiorgan dysfunction/failure and shortened survival. In a relatively high proportion of cases, the clonal nature of the disease can be established on the basis of the demonstration of gain-of-function mutations involving the tyrosine kinase (TK) domain of KIT in skin lesions and BM cells and by the factor-independent proliferation and transforming abilities of these mutations. The tyrosine kinase inhibitor Imatinib is a treatment available for mastocytosis patients; however, some KIT mutations, specially KIT D816V, confer resistance to this drug. Aims To characterize the clinical phenotype and molecular mutations of 2 relatives with diagnosis of systemic mastocytosis (WHO 2008). We also aimed to test the in vitro sensitivity of primary bone marrow (BM) cells from both patients to tyrosine kinase inhibitors. Patients and methods Four individuals were included in the study; two patients (case 1 [mother], and case 2 [daughter]), and the parents of case 1. DNA samples were obtained from total BM cells, CD3+ BM cells and oral mucosa of patients, and from peripheral blood of all individuals. KIT (exons 1 to 21) was submitted for Sanger sequencing analysis. Primary bone marrow cells (5X104) from the 2 patients were cultured and treated with Imatinib (5uM), Dasatinib (80nM) and PKC 412 (100nM) or with vehicle only (control cells) and submitted for proliferation (MTT) and apoptosis assays (Annexin-V/PI) at days 4, 8 and 12 of culture. Results Case 1 was a 33 year-old woman with a chronic history of pruritic skin rash who was referred to our outpatient service for evaluation of massive splenomegaly (25 centimeters in length) and pancytopenia. She had neither comorbidities nor any familial history of hematological malignancies. The patient had no siblings and had only one daughter (case 2). At biopsy, she showed extensive skin and bone marrow infiltration by mast cells. During follow up, the patient presented with spontaneous splenic rupture and had to undergo splenectomy, which led to the resolution of pancytopenia. She was diagnosed with Aggressive Systemic Mastocytosis. Her daughter (case 2), a 17 year-old woman, was also evaluated for an insidious history of diffuse skin rash. Skin and bone marrow biopsies showed massive infiltration by atypical mast cells and a diagnosis of Indolent Systemic Mastocytosis was made. The rare KIT K509I mutation was found in all DNA samples obtained from both patients, but not from the parents of case 1. This suggests that the KIT K509I was a germ line mutation acquired de novo by patient 1 that was subsequently transmitted to her daughter (patient 2). In vitro treatment of primary bone marrow cells harboring the KIT K509I mutation from patients 1 and 2 resulted in variable clinical response rates according to the drug used and the treatment duration. Imatinib treatment resulted in a significant reduction in proliferation (days 4, 8 and 12 of culture) and an increase in apoptosis (days 8 and 12) in cases 1 and 2 (all p≤0.03). Although Dasatinib resulted in decreased proliferation in both patients at day 12 (all p≤0.008), a significantly higher apoptosis ratio was observed only for patient 1 at day 12 of culture (p=0.03). PKC412 had a negative effect over cell growth in patient 1 (days 4 and 8) and in patient 2 (day 4) (all p≤0.03); however, no effect in apoptosis ratio was seen. Conclusions We herein provide a report of a KIT K509I mutation in familial mastocytosis. This mutation has been previously described in the literature in one case of familial mastocytosis. Although rare, the screening for KIT K509I mutation should be considered in all cases of familial mastocytosis. Based on in vitro studies, mastocytosis patients harboring the KIT K509I mutation could benefit from treatment with Imatinib, Dasatinib and PKC 412. However, Imatinib may be more effective in inducing neoplastic mast cells apoptosis. Both patients described were started on Imatinib in June 2013. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Philadelphia chromosome in human macrophages

Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 367-370 ◽  
Author(s):  
DW Golde ◽  
C Burgaleta ◽  
RS Sparkes ◽  
MJ Cline
Keyword(s):  
Bone Marrow ◽  
Natural History ◽  
Cell Line ◽  
Bone Marrow Cells ◽  
Philadelphia Chromosome ◽  
Mononuclear Phagocyte ◽  
Chronic Myelocytic Leukemia ◽  
Human Macrophages ◽  
Myelocytic Leukemia ◽  
History Of

Three patients with chronic myelocytic leukemia in different phases of the natural history of the disease were studied. Their bone marrow cells were cultured under conditions favoring macrophage proliferation, and parallel cytogenetic and cytochemical studies were performed. All cell metaphases examined contained the Ph1 chromosome at a time when more than 80% of these metaphases were in identifiable macrophages. We conclude that the mononuclear phagocyte cell line contains the abnormal chromosome in Ph1-positive chronic myelocytic leukemia.

scholarly journals New Xenograft Model of Multiple Myeloma and Efficacy of a Humanized Antibody Against Human Interleukin-6 Receptor

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2437-2444 ◽  
Author(s):  
Toshiaki Tsunenari ◽  
Yasuo Koishihara ◽  
Akito Nakamura ◽  
Miki Moriya ◽  
Hiroyuki Ohkawa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Tumor Progression ◽  
Interleukin 6 ◽  
Bone Marrow Cells ◽  
Severe Combined Immunodeficiency ◽  
Xenograft Model ◽  
Scid Mice ◽  
The Body ◽  
M Protein

Abstract A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 × 106 KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti–IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6–dependent KPMM2 cells.

Association of Extensive Brain Calcifications, Myelofibrosis, and Retinopathy in a 12-Year-Old Child

2008 ◽  
Vol 11 (2) ◽  
pp. 148-151 ◽  
Author(s):  
Diana Negrón ◽  
Lillian Colón-Castillo ◽  
Ilia Morales-Melecio ◽  
María Correa-Rivas
Keyword(s):  
Bone Marrow ◽  
Fluorescent In Situ Hybridization ◽  
Bone Marrow Cells ◽  
Multiorgan Failure ◽  
Rare Condition ◽  
Chromosome 7 ◽  
Neurological Deficits ◽  
Hybridization Study ◽  
History Of

We report a case of a 12-year-old boy with history of myelofibrosis and retinopathy who developed sudden neurological deficits associated with coagulopathy, multiorgan failure, and death. A fluorescent in situ hybridization study revealed monosomy of chromosome 7 in 21% of the bone marrow cells in support of his diagnosis of myelofibrosis. Postmortem neuropathology examination revealed multiple coarse and microcalcifications and cerebral hemorrhages, explaining the patient's neurological deterioration. The findings of myelofibrosis, retinopathy, and cerebral calcifications indicate that this could be a case of a rare condition known as Revesz syndrome.

scholarly journals THE RELATION OF CHROMATIN TO HEMOGLOBIN AND BILIRUBIN

1929 ◽  
Vol 49 (6) ◽  
pp. 937-943 ◽  
Author(s):  
Herman H. Riecker
Keyword(s):  
Bone Marrow ◽  
Iron Content ◽  
Bone Marrow Cells ◽  
The Body ◽  
Bile Pigment ◽  
Hemoglobin Production ◽  
Marrow Cells

1. Attention is directed to the diversity of opinion among investigators regarding the site and manner of hemoglobin formation in the body and its relation to bile pigment metabolism. 2. It is probable that in forming new hypotheses on this subject the earlier work of A. B. Macallum on the relation of chromatin to hemoglobin formation has not received sufficient consideration. 3. It has been shown by means of microchemical iron stains of the bone marrow cells, that the iron content of the hematoblast is increased during rapid hemoglobin production in simple anemia. 4. This fact is compatible with the work of Macallum who believed that hemoglobin is derived from the chromatin of the hematoblast. It does not support a theory that hemoglobin is formed as a part of a circulating pigment. 5. It is suggested that bilirubin is derived from the chromatin of body cells through the intermediary stages of the respiratory pigments, hemoglobin and cytochrome, from erythrocytes and other cells, respectively.

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