scholarly journals Quantification and three-dimensional microanatomical organization of the bone marrow

2017 ◽  
Vol 1 (6) ◽  
pp. 407-416 ◽  
Author(s):  
Cesar Nombela-Arrieta ◽  
Markus G. Manz

Abstract Bone marrow (BM) constitutes one of the largest organs in mice and humans, continuously generating, in a highly regulated manner, red blood cells, platelets, and white blood cells that together form the majority of cells of the body. In this review, we provide a quantitative overview of BM cellular composition, we summarize emerging knowledge on its structural organization and cellular niches, and we argue for the need of multidimensional approaches such as recently developed imaging techniques to uncover the complex spatial logic that underlies BM function in health and disease.

Author(s):  
Paul Klenerman

The immune system resists threats from outside as well as from within the body. ‘What is the immune system?’ considers the basic mechanisms of immunity and describes the specific structures in the immune system where more complex activities take place. The critical cells—‘white blood cells’ or leukocytes—are generated in the bone marrow. Leukocytes are highly diverse, each with its own specialist function, but broadly divided into the myeloid (develops in the marrow) and the lymphoid (develops in lymphoid structures including the thymus, lymph nodes, and spleen) leukocyte. We have both ‘innate’ (which we are born with) and ‘adaptive’ (which encompasses learned, very specific responses to individual infections) immunity.


1936 ◽  
Vol 64 (1) ◽  
pp. 97-120 ◽  
Author(s):  
F. R. Sabin ◽  
F. R. Miller ◽  
K. C. Smithburn ◽  
R. M. Thomas ◽  
L. E. Hummel

1. The full number of erythroid cells in the blood stream of the rabbit is reached by the 3rd week of life. 2. During this period, there is a predominance of erythrogenesis in the bone marrow. 3. During the 2nd week of life the bone marrow is in a state of hyperplasia owing to the needs of the body for blood and the small space available for the marrow. 4. This hyperplasia is reduced as the growth of the bone permits the marrow to spread. The control of the growth of the bones has an important bearing on hematopoiesis. 5. During the first 3 weeks of life, the chemical factors for the multiplication of red cells as well as for the elaboration of hemoglobin become available. 6. The amount of hemoglobin does not increase as rapidly as the number of cells, so that the macrocytic anemia of the fetus becomes reduced. The proportion of hemoglobin per red cell characteristic of the adult rabbit is reached by the 3rd month. 7. Further evidence on the intravascular origin of red blood cells is given. 8. The development of all of the white blood cells, with the exception of the monocyte, goes on at a slower rate than that of the red cells. 9. The monocytes reach their full number in the blood stream in the 1st week of life; granulocytes and lymphocytes by the 5th and 6th months. 10. Each of the three strains of white cells has a different rate of development. 11. The question as to whether the stem cell or primitive cell is identical with the lymphocyte is discussed.


2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.


Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2148-2159 ◽  
Author(s):  
Harshal H. Nandurkar ◽  
Lorraine Robb ◽  
David Tarlinton ◽  
Louise Barnett ◽  
Frank Köntgen ◽  
...  

Abstract Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.


2016 ◽  
Vol 47 (6) ◽  
Author(s):  
D. S. Dheyab

This study was conducted to investigate the effect of zinc in dose 15mg/kg.bw daily  taken by the mouth and dexamethasone 4mgIkg.Bw by injection for 30days on some hematological biochemical tests and some histological changes of liver spleen in male rabbits. Thirty rabbits were used that divided into 3 randomized groups (each group contain 10 male rabbits ). Control group was taken normal food and water, Zinc group that gave zinc at dose of 15mg/kg.BW/daily/oral on 1, 2, 3, 4 weeks. Dexamethasone with zinc group : Employ dexamethasone 4mg/Kg.Bw . I.M dialy for 1 and 2 weeks for experiment and at  3, 4th weeks they gave zn 15mg/lKg.Bw day/orally. Blood samples were taken from the heart directly in 2 and 4weeks to examine packed cell volume (pcv), white blood cells (WBCs), Red blood cells (RBCs) with differential Leuckcyte count.separation blood collection to plasma and examine glucose mg/dl , cholesterol mg/dl. In histological tests, rabbits were killed and separate their organs tissue from the body to examine liver and spleen. The results revealed  a decrease in level of RBCs, pcv after treatment with zinc 15, mg/Kg.Bw orally (zinc group) and increase in WBCs with differential leuckocyte count specially neutrophil cell, while biochemical tests show increase in glucose and cholesterol levels after treatment with dexamethasone 4mglkgBw. I/M seen increase in counts of RBCs , PCV, WBCs and differential lenkocyte count and decrease in glucose with cholesterol parameters, histological changes show change in liver after treatment by dexamethasone 4mglKg.Bw ,spleen tissue seen necrosis and pigmentation with hemorrhage after take dexamethasone 4mglkg in (dexamethasone + zinc group). Results also showed that zinc enhanced the immune system in at normal dose for limited time  because of its effect on other mineral such as copper and causes anemia , while the dexamethasone is a drug used for antianflammatory but for a short time.                                                                                                                           


2002 ◽  
Vol 45 (1) ◽  
pp. 3-5 ◽  
Author(s):  
Jiří Patočka ◽  
Miroslav Špliňo

The anthrax toxin comprises three proteins. When they work together, they can kill humans, especially after spores of the bacteria have been inhaled. One anthrax protein, called protective antigen (PA), chaperones the two other toxins into human or animal cells and shields them from the body’s immune system. The second, lethal factor (LF), destroys the white blood cells that hosts send in defence. The third toxin molecule, edema factor (EF), hijacks the signaling system in the body. This disrupts the energy balance of cells and leads to them accumulating fluid and complete destroy of cells.


2019 ◽  
Vol 10 (2) ◽  
pp. 39-48
Author(s):  
Eman Mostafa ◽  
Heba A. Tag El-Dien

Leukemia is a blood cancer which is defined as an irregular augment of undeveloped white blood cells called “blasts.” It develops in the bone marrow, which is responsible for blood cell generation including leukocytes and white blood cells. The early diagnosis of leukemia greatly helps in the treatment. Accordingly, researchers are interested in developing advanced and accurate automated techniques for localizing such abnormal blood cells. Subsequently, image segmentation becomes an important image processing stage for successful feature extraction and classification of leukemia in further stages. It aims to separate cancer cells by segmenting the microscopic image into background and cancer cells that are known as the region of interested (ROI). In this article, the cancer blood cells were segmented using two separated clustering techniques, namely the K-means and Fuzzy-c-means techniques. Then, the results of these techniques were compared to in terms of different segmentation metrics, such as the Dice, Jac, specificity, sensitivity, and accuracy. The results proved that the k-means provided better performance in leukemia blood cells segmentation as it achieved an accuracy of 99.8% compared to 99.6% with the fuzzy c-means.


2020 ◽  
Vol 17 (10) ◽  
pp. 2050009
Author(s):  
Sisi Tan ◽  
Mingze Xu

Numerical modeling of whole blood still faces great challenges although significant progress has been achieved in recent decades, because of the large differences of physical and geometric properties among blood components, including red blood cells (RBCs), platelets (PLTs) and white blood cells (WBCs). In this work, we develop a three-dimensional (3D) smoothed particle hydrodynamics (SPH) model to study the whole blood in shear flow. The immersed boundary method (IBM) is used to deal with the interaction between the fluid and cells, which provides a possibility to model the RBCs, PLTs and WBCs simultaneously. The deformation of a small capsule, comparable to a PLT in size, is first examined to show the feasibility of SPH model for the PLTs’ behaviors. The motion of a single RBC in shear flow is then studied, and three typical modes, tank-treading, swinging and tumbling motions, are reproduced, which further confirm the reliability of the SPH model. After that, a simulation of the whole blood in shear flow is carried out, in which the margination trend is observed for both PLTs and WBC. This shows the capability of SPH model with IBM for the simulation of whole blood.


Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1209 ◽  
Author(s):  
Muhammad Abdul Basit ◽  
Arifah Abdul Kadir ◽  
Teck Loh ◽  
Saleha Abdul Aziz ◽  
Annas Salleh ◽  
...  

This research was conducted to estimate the effects of Persicaria odorata leaf meal (POLM) on haematological indices, serum biochemical attributes, and internal organs parameters, including histomorphological features of the liver, in broiler chickens. A total of 120 one-day-old male broiler chicks (Cobb-500) were randomly allocated into four experimental groups. The dietary treatments were basal diet (BD), which served as the control (C), along with BD + 2 g/kg POLM (Po2), BD + 4 g/kg POLM (Po4), BD + 8 g/kg POLM (Po8), which were the supplemented groups. The body weight gain (BWG) showed a linear increase and feed conversion ratio (FCR) showed a linear decrease with increasing POLM dosage at day 42 (p ˂ 0.05) and for the overall growth performance period (p ˂ 0.01). On day 21 and day 42, the values of red blood cells (RBCs), white blood cells (WBCs), haemoglobin (Hb), and packed cell volume (PCV) showed linear increases (p ˂0.05) as the dosage of POLM increased in the diet. On day 21, dietary supplementation of POLM linearly decreased (p ˂ 0.05) the serum activity of alkaline phosphatase (ALP), aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), and serum levels of urea and creatinine. On the other hand, serum levels of total protein (TP), albumin, and globulin showed a linear increase (p ˂ 0.05) as the POLM dosage increased. On day 42, the serum activity of AST and ALT and serum levels of glucose, cholesterol, triglycerides, urea, and creatinine showed linear decreases (p ˂ 0.05) with increased levels of POLM in the diet. However, POLM supplementation linearly increased (p ˂ 0.05) the serum levels of TP and globulin. Dietary inclusion of POLM did not influence the organ parameters and showed no adverse effects on the liver histomorphology. In conclusion, supplementation of POLM increased the growth performance, improving haematological indices and serum biochemistry profiles of broiler chickens without any deleterious effects on the liver histomorphology. The results of the present study provide evidence that POLM can be safely used at a dose rate of 8 g/kg of feed as an alternative to conventional antimicrobial growth promoters (AGPs).


Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 3882-3890 ◽  
Author(s):  
Elizabeth A. Jacobsen ◽  
Richard A. Helmers ◽  
James J. Lee ◽  
Nancy A. Lee

Abstract Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?”


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