scholarly journals Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic Rebound Induced by Androgen Blockade

2018 ◽  
Vol 200 (4) ◽  
pp. 1389-1398 ◽  
Author(s):  
Pedro M. Rodrigues ◽  
Ana R. Ribeiro ◽  
Nicolas Serafini ◽  
Catarina Meireles ◽  
James P. Di Santo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Thymic Rebound ◽  
Androgen Blockade

Recovery of immune reactivity after T-cell–depleted bone marrow transplantation depends on thymic activity

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2299-2303 ◽  
Author(s):  
Etienne Roux ◽  
Florence Dumont-Girard ◽  
Michel Starobinski ◽  
Claire-Anne Siegrist ◽  
Claudine Helg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Young Patients ◽  
Immune Reactivity ◽  
Normal Numbers ◽  
Cell Repertoire ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Thymic Rebound

To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell–depleted bone marrow, we measured the appearance of CD4+CD45RA+RO−naive T cells (thymic rebound), restoration of the diversity of the T-cell–receptor (TCR) repertoire and the response to vaccinations with tetanus toxoid (TT). Repopulation by CD4+CD45RA+RO− thymic emigrants varied among patients, starting at approximately 6 months after transplantation. Young patients reconstituted swiftly, whereas in older patients, the recovery of normal numbers of naive CD4+ T cells could take several years. Restoration of TCR diversity was correlated with the number of naive CD4+CD45RA+RO− T cells. Moreover, the extent of the thymic rebound correlated with the patient's capacity to respond to vaccinations. Patients without a significant thymic rebound at the moment of vaccination (CD4+CD45RA+RO− T cells less than 30 μL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after transplantation, the absence of an immune response is due mainly to the loss of an adequate T-cell repertoire. Restoration of the repertoire can come only from a thymic rebound that can be monitored by measuring the increase of CD4+CD45RA+RO−naive T cells. This will allow postponing revaccinations to a moment when the patient will be able to respond more effectively. This may be particularly useful in the elderly patient who, owing to low thymic activity, might not yet be able to respond 1 year after transplant when revaccinations are usually scheduled.

scholarly journals Effect of Androgen Blockade on HER-2 and Matrix Metalloproteinase-2 Expression on Bone Marrow Micrometastasis and Stromal Cells in Men with Prostate Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
N. P. Murray ◽  
E. Reyes ◽  
L. Badinez ◽  
N. Orellana ◽  
C. Fuentealba ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Matrix Metalloproteinase 2 ◽  
Before And After ◽  
Bone Marrow Micrometastasis ◽  
Her 2 ◽  
Androgen Blockade

Introduction. HER-2 has been associated with castrate resistant prostate cancer and matrix metalloproteinase-2 (MMP-2) in the dissemination and invasion of tumor cells as well as activating angiogenesis. We present an immunocytochemical study of the effect of androgen blockade on the expression of HER-2 and MMP-2 in bone marrow micrometastasis and the surrounding stromal cells in men with prostate cancer.Methods and Patients. A cross-sectional study of men with prostate cancer. Touch preps were obtained from bone marrow biopsies of men with prostate cancer, before and after radical prostatectomy and during androgen blockade. Micrometastasis detected with anti-PSA immunocytochemistry underwent processing with anti-HER-2 and anti-MMP-2 immunocytochemistry. Patients were defined as HER-2 positive or negative, MMP-2 negative or an MMP-2 pattern described as border or central and stromal MMP-2 defined as positive or negative. The expression of the biomarkers was compared before and after primary treatment and during androgen blockade in relation to the serum PSA at the time of sampling and duration of androgen blockade.Results. 191 men participated, 35 men before surgery and 43 after surgery; there were no significant differences in HER-2 expression between groups, there was no MMP-2 expression centrally or stromal expression of MMP-2. In men with androgen blockade, HER-2 expression was significantly higher; there was a trend for increasing HER-2 expression up to 5 years; central MMP-2 expression significantly increased after 3 years, while stromal MMP-2 significantly increased after 6 years. MMP-2 expression both in micrometastasis and stroma was significantly associated with HER-2 expression. Expression of MMP-2 at the border of the micrometastasis was not associated with HER-2 expression and occurred in the absence of androgen blockade.Conclusions. Androgen blockade decreases serum PSA by eliminating HER-2 negative prostate cancer cells. However, there is early selection of HER-2 positive cancer cells which leads to androgen independence and to increased expression of MMP-2 activity in the micrometastasis. The increased MMP-2 activity in the micrometastasis increases the expression of MMP-2 in the surrounding stromal cells and thus could promote angiogenesis and tumor growth resulting in macrometastatic androgen independent disease.

Recovery of immune reactivity after T-cell–depleted bone marrow transplantation depends on thymic activity

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2299-2303 ◽  
Author(s):  
Etienne Roux ◽  
Florence Dumont-Girard ◽  
Michel Starobinski ◽  
Claire-Anne Siegrist ◽  
Claudine Helg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Young Patients ◽  
Immune Reactivity ◽  
Normal Numbers ◽  
Cell Repertoire ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Thymic Rebound

Abstract To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell–depleted bone marrow, we measured the appearance of CD4+CD45RA+RO−naive T cells (thymic rebound), restoration of the diversity of the T-cell–receptor (TCR) repertoire and the response to vaccinations with tetanus toxoid (TT). Repopulation by CD4+CD45RA+RO− thymic emigrants varied among patients, starting at approximately 6 months after transplantation. Young patients reconstituted swiftly, whereas in older patients, the recovery of normal numbers of naive CD4+ T cells could take several years. Restoration of TCR diversity was correlated with the number of naive CD4+CD45RA+RO− T cells. Moreover, the extent of the thymic rebound correlated with the patient's capacity to respond to vaccinations. Patients without a significant thymic rebound at the moment of vaccination (CD4+CD45RA+RO− T cells less than 30 μL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after transplantation, the absence of an immune response is due mainly to the loss of an adequate T-cell repertoire. Restoration of the repertoire can come only from a thymic rebound that can be monitored by measuring the increase of CD4+CD45RA+RO−naive T cells. This will allow postponing revaccinations to a moment when the patient will be able to respond more effectively. This may be particularly useful in the elderly patient who, owing to low thymic activity, might not yet be able to respond 1 year after transplant when revaccinations are usually scheduled.

scholarly journals Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution after murine bone marrow transplantation

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5734-5744 ◽  
Author(s):  
Ryan M. Kelly ◽  
Steven L. Highfill ◽  
Angela Panoskaltsis-Mortari ◽  
Patricia A. Taylor ◽  
Richard L. Boyd ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Combined Treatment ◽  
Leuprolide Acetate ◽  
Allogeneic Bone ◽  
Individual Agent ◽  
T Cell Reconstitution ◽  
Androgen Blockade

Abstract Myeloablative conditioning results in thymic epithelial cell (TEC) injury, slow T-cell reconstitution, and a high risk of opportunistic infections. Keratinocyte growth factor (KGF) stimulates TEC proliferation and, when given preconditioning, reduces TEC injury. Thymocytes and TECs express androgen receptors, and exposure to androgen inhibits thymopoiesis. In this study, we have investigated whether TEC stimulation via preconditioning treatment with KGF and leuprolide acetate (Lupron), 2 clinically approved agents, given only before conditioning would circumvent the profound TEC and associated T-cell deficiency seen in allogeneic bone marrow transplant (BMT) recipients. Only combined treatment with KGF plus leuprolide acetate normalized TEC subset numbers and thymic architecture. Thymopoiesis and thymic output were supranormal, leading to the accelerated peripheral reconstitution of naive CD4 and CD8 T cells with a broad Vβ repertoire and decreased homeostatic T-cell proliferation. Combined therapy facilitated T:B cooperativity and enabled a B-cell humoral response to a CD4 T cell–dependent neoantigen challenge soon after BMT. In vivo antigen-specific CD8 T-cell responses and clearance of a live pathogen was superior with combined versus individual agent therapy. Thus, KGF combined with androgen blockade represents a novel approach to restore thymic function and facilitates the rapid recovery of peripheral T-cell function after allogeneic BMT.

Glycogen in guinea pig neutrophils: Ultrastructural study of neutrophils at the intradermal site of BCG injection

1983 ◽  
Vol 41 ◽  
pp. 726-727
Author(s):  
Corazon D. Bucana
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Electron Density ◽  
Peritoneal Cavity ◽  
Ultrastructural Study ◽  
Guinea Pigs ◽  
Random Distribution ◽  
Glycogen Content ◽  
Polymorphonuclear Neutrophils ◽  
Ultrastructural Studies

In the circulating blood of man and guinea pigs, glycogen occurs primarily in polymorphonuclear neutrophils and platelets. The amount of glycogen in neutrophils increases with time after the cells leave the bone marrow, and the distribution of glycogen in neutrophils changes from an apparently random distribution to large clumps when these cells move out of the circulation to the site of inflammation in the peritoneal cavity. The objective of this study was to further investigate changes in glycogen content and distribution in neutrophils. I chose an intradermal site because it allows study of neutrophils at various stages of extravasation.Initially, osmium ferrocyanide and osmium ferricyanide were used to fix glycogen in the neutrophils for ultrastructural studies. My findings confirmed previous reports that showed that glycogen is well preserved by both these fixatives and that osmium ferricyanide protects glycogen from solubilization by uranyl acetate.I found that osmium ferrocyanide similarly protected glycogen. My studies showed, however, that the electron density of mitochondria and other cytoplasmic organelles was lower in samples fixed with osmium ferrocyanide than in samples fixed with osmium ferricyanide.

Mammalian Bone Marrow Acetylcholinesterase

1982 ◽  
Vol 40 ◽  
pp. 44-45
Author(s):  
Ezzatollah Keyhani
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Common Property ◽  
Extracellular Medium ◽  
The Central Nervous System ◽  
The Common ◽  
Mammalian Bone

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.

The structure of pre-mRNA and mRNA from erythroid cells

1978 ◽  
Vol 36 (2) ◽  
pp. 234-235
Author(s):  
A.-M. Ladhoff ◽  
B.J. Thiele ◽  
Ch. Coutelle ◽  
S. Rosenthal
Keyword(s):  
Bone Marrow ◽  
Structural Transformation ◽  
Electron Micrographs ◽  
Ammonium Acetate ◽  
Bone Marrow Cells ◽  
Erythroid Cells ◽  
Globin Mrna ◽  
Ordered Structures ◽  
Rabbit Bone ◽  
Rabbit Reticulocytes

The suggested precursor-product relationship between the nuclear pre-mRNA and the cytoplasmic mRNA has created increased interest also in the structure of these RNA species. Previously we have been published electron micrographs of individual pre-mRNA molecules from erythroid cells. An intersting observation was the appearance of a contour, probably corresponding to higher ordered structures, on one end of 10 % of the pre-mRNA molecules from erythroid rabbit bone marrow cells (Fig. 1A). A virtual similar contour was observed in molecules of 9S globin mRNA from rabbit reticulocytes (Fig. 1B). A structural transformation in a linear contour occurs if the RNA is heated for 10 min to 90°C in the presence of 80 % formamide. This structural transformation is reversible when the denatured RNA is precipitated and redissolved in 0.2 M ammonium acetate.

Sinusoidal Cells in Bone Marrow Take Up BSA-Au Conjugates in the Presence of an Artificial Blood Substitute

1985 ◽  
Vol 43 ◽  
pp. 700-701
Author(s):  
J.S. Geoffroy ◽  
R.P. Becker
Keyword(s):  
Bone Marrow ◽  
Los Angeles ◽  
Iliac Artery ◽  
Blood Substitute ◽  
Sprague Dawley ◽  
Coated Pits ◽  
Sinusoidal Cells ◽  
Artificial Blood ◽  
Left Common Iliac Artery

The pattern of BSA-Au uptake in vivo by endothelial cells of the venous sinuses (sinusoidal cells) of rat bone marrow has been described previously. BSA-Au conjugates are taken up exclusively in coated pits and vesicles, enter and pass through an “endosomal” compartment comprised of smooth-membraned tubules and vacuoles and cup-like bodies, and subsequently reside in multivesicular and dense bodies. The process is very rapid, with BSA-Au reaching secondary lysosmes one minute after presentation. (Figure 1)In further investigations of this process an isolated limb perfusion method using an artificial blood substitute, Oxypherol-ET (O-ET; Alpha Therapeutics, Los Angeles, CA) was developed. Under nembutal anesthesia, male Sprague-Dawley rats were laparotomized. The left common iliac artery and vein were ligated and the right iliac artery was cannulated via the aorta with a small vein catheter. Pump tubing, preprimed with oxygenated 0-ET at 37°C, was connected to the cannula.

Neutrophil pseudoplatelets in subgingival plaque and crevicular fluid samples from periodontal diseased sites

1989 ◽  
Vol 47 ◽  
pp. 862-863 ◽  
Author(s):  
J Hanker ◽  
E.J. Burkes ◽  
G. Greco ◽  
R. Scruggs ◽  
B. Giammara
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Gingival Crevicular Fluid ◽  
Light And Electron Microscopy ◽  
Subgingival Plaque ◽  
Staining Reaction ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Crevicular Fluid

The mature neutrophil with a segmented nucleus (usually having 3 or 4 lobes) is generally considered to be the end-stage cell of the neutrophil series. It is usually found as such in the bone marrow and peripheral blood where it normally is the most abundant leukocyte. Neutrophils, however, must frequently leave the peripheral blood and migrate into areas of infection to combat microorganisms. It is in such areas that neutrophils were first observed to fragment to form platelet-size particles some of which have a nuclear lobe. These neutrophil pseudoplatelets (NPP) can readily be distinguished from true platelets because they stain for neutrophil myeloperoxidase. True platelets are not positive in this staining reaction because their peroxidase Is inhibited by glutaraldehyde. Neutrophil pseudoplatelets, as well as neutrophils budding to form NPP, could frequently be observed in peripheral blood or bone marrow samples of leukemia patients. They are much more prominent, however, in smears of inflammatory exudates that contain gram-negative bacteria and in gingival crevicular fluid samples from periodontal disease sites. In some of these samples macrophages ingesting, or which contained, pseudoplatelets could be observed. The myeloperoxidase in the ingested pseudoplatelets was frequently active. Despite these earlier observations we did not expect to find many NPP in subgingival plaque smears from diseased sites. They were first seen by light microscopy (Figs. 1, 3-5) in smears on coverslips stained with the PATS reaction, a variation of the PAS reaction which deposits silver for light and electron microscopy. After drying replicate PATS-stained coverslips with hexamethyldisilazane, they were sputter coated with gold and then examined by the SEI and BEI modes of scanning electron microscopy (Fig. 2). Unstained replicate coverslips were fixed, and stained for the demonstration of myeloperoxidase in budding neutrophils and NPP. Neutrophils, activated macrophages and spirochetes as well as other gram-negative bacteria were also prominent in the PATS stained samples. In replicate subgingival plaque smears stained with our procedure for granulocyte peroxidases only neutrophils, budding neutrophils or NPP were readily observed (Fig. 6).

Application of Spurr, LX112, LX112/ARALDITE 502, POLY/BED 812 and Effapoxy Embedding Media to in Vitro Agar-Cultured Bone Marrow Colonies.

1980 ◽  
Vol 38 ◽  
pp. 646-647
Author(s):  
Glenn M. Buchanan ◽  
Dennis A. Stewart
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Cell Cell

In vitro bone-marrow derived colonies cultured in agar and prepared in Epon 812 for electron microscopy occassionally produce blocks that are too soft for sectioning. We attribute this softness to the retention, after standard dehydration, of water by the agar and to the relatively slow penetration of the agar by Epon-based embedding media. The agar cannot be removed or replaced since this would disrupt the colony integrity and prevent the study of cell-cell relationships. This paper describes the procedures and results of more extensive specimen dehydration and of embedding with Epon-replacement formulations.

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