bone marrow cultures
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Author(s):  
Florence Vallelian ◽  
Raphael M. Buzzi ◽  
Marc Pfefferlé ◽  
Ayla Yalamanoglu ◽  
Irina L. Dubach ◽  
...  

AbstractHeme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias, such as sickle cell disease. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Since chronic heme-stress is noxious for macrophages, erythrophagocytes in the spleen are continuously replenished from bone marrow-derived progenitors. Here, we hypothesized that adaptation to heme stress progressively shifts differentiation trajectories of bone marrow progenitors to expand the capacity of heme-handling monocyte-derived macrophages at the expense of the homeostatic generation of dendritic cells, which emerge from shared myeloid precursors. This heme-induced redirection of differentiation trajectories may contribute to hemolysis-induced secondary immunodeficiency. We performed single-cell RNA-sequencing with directional RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation of bone marrow cells towards antioxidant, iron-recycling macrophages, suppressing the generation of dendritic cells in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific CD4 T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype of macrophage expansion with concurrent dendritic cell depletion was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning of hemolytic stress as a driver of hyposplenism-related secondary immunodeficiency.


Materials ◽  
2021 ◽  
Vol 14 (22) ◽  
pp. 6920
Author(s):  
Jila Nasirzade ◽  
Zahra Kargarpour ◽  
Layla Panahipour ◽  
Reinhard Gruber

Dentin prepared from extracted teeth is used as autograft for alveolar bone augmentation. Graft consolidation involves the acid lysis of dentin thereby generating a characteristic paracrine environment. Acid lysate of dentin is mimicking this environment. Acid dentin lysate (ADL) potentially targets hematopoietic cells thereby affecting their differentiation towards macrophages and osteoclasts; however, the question remains if ADL controls macrophage polarization and osteoclastogenesis. Here, we show that ADL reduced lipopolysaccharide (LPS)-induced macrophage polarization of the pro-inflammatory (M1) phenotype, indicated by attenuated Interleukin 1 (IL1), Interleukine 6 (IL6)and cyclooxygenase 2 (COX2) expression. This decrease in M1 macrophages was confirmed by the reduced phosphorylation and nuclear translocation of p65 in the LPS-exposed RAW 264.7 macrophages. Similarly, when RAW 264.7 macrophages were incubated with other agonists of Toll-like receptor (TLR) signaling e.g., FSL1, Polyinosinic-polycytidylic acid High Molecular Weight (Poly (1:C) HMW), Pam3CSK4, and imiquimod, ADL reduced the IL6 expression. We further show herein that ADL decreased osteoclastogenesis indicated by the reduced formation of multinucleated cell expressing cathepsin K and tartrate-resistant acid phosphatase in murine bone marrow cultures. Overall, our results suggest that acid dentin lysate can affect the differentiation of hematopoietic cells to M1 macrophage polarization and a decrease in osteoclastogenesis in bone marrow cultures.


2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S98-S99
Author(s):  
I Prisneac ◽  
J Vos ◽  
R LaSala ◽  
C Randall

Abstract Introduction/Objective Sarcoidosis is a syndrome of unknown cause that may manifest with clinical, radiographic and pathological findings similar to those seen with histoplasmosis. We present a case of disseminated histoplasmosis in an immunocompetent patient previously diagnosed with sarcoidosis. Methods/Case Report A 69-year-old obese male with a history of hypertension, diabetes mellitus and long-standing sarcoidosis was admitted to the hospital for several months of intermittent fevers and pancytopenia. His sarcoidosis was diagnosed 21 years prior, initially involving the lungs and eventually showing cardiac involvement, requiring a pacemaker. He had been treated with methotrexate and prednisone. His recent medical history was also significant for COVID-19 infection, diagnosed 3 months before admission. His fevers were initially attributed to sarcoidosis and his pancytopenia to methotrexate. However, his symptoms continued despite discontinuation of his medications, and further workup was initiated. Computed tomography showed hepatomegaly, splenomegaly, and lymphadenopathy, concerning for a lymphoproliferative disorder. The patient underwent a bone marrow biopsy that showed noncaseating granulomas and microorganisms consistent with histoplasmosis on fungal stain. Bone marrow cultures were not possible as the marrow was inaspirable. The patient subsequently underwent a lymph node biopsy with both morphology and culture identifying histoplasmosis. Urine and serum histoplasma antigen also returned positive. The patient’s overall clinical picture was consistent with disseminated histoplasmosis and he was administered intravenous Amphotericin B for 3 weeks followed by oral itraconazole for 1 year. One month follow-up after discharge showed significant improvement in the patient’s condition. Results (if a Case Study enter NA) N/A Conclusion Sarcoidosis reduces T-cell activity, and treatment with steroids causes further immunosuppression and vulnerability for development of a disseminated infection. COVID-19 also presumably increases the predisposition to acquire bacterial or fungal co-infections. Clinicians and pathologists should be aware of the overlap in clinical, radiologic and pathological presentations of sarcoidosis and histoplasmosis to make the correct diagnosis and administer the appropriate treatment.


2021 ◽  
Author(s):  
Florence Vallelian ◽  
Raphael M Buzzi ◽  
Marc Pfefferle ◽  
Ayla Yalamanoglu ◽  
Andreas Wassmer ◽  
...  

Heme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias, such as sickle cell disease. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Since chronic heme-stress is noxious for macrophages, erythrophagocytes in the spleen are continuously replenished from bone marrow-derived progenitors. Here, we hypothesized that adaptation to heme stress progressively shifts differentiation trajectories of BM progenitors to expand the capacity of heme-handling monocyte-derived macrophages at the expense of the homeostatic generation of dendritic cells, which emerge from shared myeloid precursors. This heme-induced redirection of differentiation trajectories may contribute to hemolysis-induced secondary immunodeficiency. We performed single-cell RNA sequencing with directional RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation of bone marrow cells towards antioxidant, iron-recycling macrophages, suppressing the generation of dendritic cells in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific CD4 T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype of macrophage expansion with concurrent dendritic cell depletion was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning of hemolytic stress as a driver of hyposplenism-related secondary immunodeficiency.


2021 ◽  
Vol 14 (2) ◽  
pp. e239498
Author(s):  
Arnav Agarwal ◽  
Jennifer A Losie ◽  
Dylan Kain ◽  
Rupert Kaul

While blastomycosis is endemic to eastern USA and northwestern Ontario, acquisition is an anomaly in urban settings. We present a 54-year-old immunocompetent man from the greater Toronto area with no travel, who presented with a 3-week history of chest pain and dyspnoea. Initial radiographic workup revealed a mass-like opacification in the right apical mediastinum. Extensive investigations including bronchoscopy with bronchoalveolar lavage, mediastinal mass biopsy with fungal and mycobacterial cultures and multiple stains, and CT were unrevealing. The patient progressed to respiratory failure over 4 months. Ultimately, sputum and bone marrow cultures confirmed a diagnosis of disseminated blastomycosis. The patient required prolonged extracorporeal membrane oxygenation and ongoing ventilation postdecannulation. Our case highlights diagnostic challenges with blastomycosis, particularly in immunocompetent individuals with no travel to recreational areas, and emphasises the importance of maintaining a high index of suspicion and sending fungal cultures of appropriate specimens and/or cytopathology in clinically compatible cases.


2020 ◽  
Vol 13 (12) ◽  
pp. e237076
Author(s):  
George Vatidis ◽  
Eirini I Rigopoulou ◽  
Konstantinos Tepetes ◽  
George N Dalekos

Hepatic brucelloma (HB), a rare manifestation of brucellosis, refers to liver involvement in the form of abscess. A 35-year-old woman stockbreeder was admitted due to 1-month history of evening fever, sweating and weight loss, while she was on 3-week course of rifampicin/doxycycline for suspected brucellosis. On admission, she had hepatosplenomegaly and a systolic murmur, while cholestasis, increased inflammation markers and a strong-positive Wright-Coombs test were the main laboratory findings. As blood and bone marrow cultures were unrevealing, further investigation with CT imaging showed a central liver calcification surrounded by heterogeneous hypodense area being compatible with HB. Material from CT-guided drainage tested negative for Brucella spp. After failure to improve on a 10-week triple regiment, surgical excision was decided and Brucella spp were identified by PCR. Our case highlights challenges in establishing HB diagnosis, which should be considered on the right epidemiological context and when serological and radiological evidence favour its diagnosis.


Author(s):  
Nida Anwar ◽  
Muhammad Nadeem ◽  
Sana Khurram ◽  
Naveena Fatima ◽  
Tahir Shamsi ◽  
...  

Abstract Objectives: To evaluate the presence and characteristics of additional karyotype abnormalities in chronic myeloid leukaemia cases. Method: The cross-sectional study was conducted at the Department of Cytogenetics and Molecular Pathology, National Institute of Blood Diseases and Bone Marrow Transplant, Karachi, from May 2010 to September 2016 and comprised diagnosed chronic myeloid leukaemiapatients regardless of age and gender.Baseline cytogenetic evaluation was done on overnight, 24-hrs un-stimulated and 72-hrs stimulated bone marrow cultures, and karyotypes were defined according to the International System for Human Cytogenetic Nomenclature2013. Data was analysed using SPSS 23. Results: There were 222 cases with a median age of 38 years (range: 12-84 years). The male-to-female ratio was 1.8:1. Chronic myeloid leukaemiawas detected in 18(8.1%) patients havingadditional cytogenetic abnormalities. Among the patients found positive, cytogenetic type was minor in 10(55.55%), major 3(16.66%), complex 3(16.66%), and variant 2(11.11%). . Conclusion: Additional cytogenetic abnormalitieswere found in 8% of the sample. Key Words: Additional cytogenetic abnormalities, Chronic myelogenous leukaemia, Bone marrow, Cytogenetics.


2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Vo Trieu Ly ◽  
Nguyen Tat Thanh ◽  
Nguyen Thi Mai Thu ◽  
Jasper Chan ◽  
Jeremy N Day ◽  
...  

Abstract Talaromyces marneffei causes fatal invasive mycosis in Southeast Asia. Diagnosis by culture has limited sensitivity and can result in treatment delay. We describe the use of a novel Mp1p enzyme immunoassay (EIA) to identify blood culture–negative talaromycosis, subsequently confirmed by bone marrow cultures. This EIA has the potential to speed diagnosis, enabling early therapy initiation.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S386-S386
Author(s):  
Ahnika Kline ◽  
Harry Porterfield ◽  
A Zelazny

Abstract Background Bone marrow biopsies are often performed on patients with unclear diagnoses and cultures may be ordered for both routine bacterial, mycobacterial and fungal pathogens. They are performed in semi-sterile conditions and involve needle penetration through the skin, posing an increased risk of skin contamination. These cultures also require a substantial amount of laboratory personnel time. Methods Cultures collected from 2001-2020 were surveyed in the lab electronic record. We assessed the culture type (fungal, bacterial, mycobacterial), and the presence of pathogens and contaminants. An organism was deemed a contaminant if it was consistent with skin flora or listed as a contaminant in the report given to the physician. Organisms for which the role in bone marrow disease is unclear were included as possible pathogens. For questionable non-contaminant organisms, clinical significance was determined based on if patient was treated for the organism. For all bone marrow cultures, growth of the same organism within 1 month of the bone marrow specimen was surveyed to determine whether the organism would have been found by alternative methods. Results Of 483 bacterial bone marrow cultures, there were 110 (23%) positives, of which 76 (69%) were deemed contaminants. Twenty (18%) of the 76 contaminants grew in the routine bacterial culture. However, 49 (65%) contaminants grew in the AFB culture, of which 10 also grew in the bacterial culture. For the 34 non-contaminant organisms, 26 were determined to be clinically significant. Nineteen of the 26 had a matching culture (usually blood) growing the organism within 1 month. The majority of pathogens were mycobacteria (18 of the 34). Fungal organisms represented 5 cultures and 11 were bacterial. Of the 11 bacterial organisms, 1 was a Helicobacter species (grown in special media), and 4 had a matching positive blood culture. Only 4 (1% of 483) bacterial non-contaminants grew in the routine bacterial culture. Given an unknown number of true negatives, we can only conclude a positive predictive value (PPV) of 0.16 for routine bacterial cultures. Including AFB and fungal cultures, the PPV increased to 0.30. Conclusion Our findings indicate that routine bacterial bone marrow culture is unlikely to yield a novel result and is likely a poor use of lab resources. Disclosures All Authors: No reported disclosures


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