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Cell-free hemoglobin

Stephan Brauckmann, Katharina Effenberger-Neidnicht, Herbert de Groot, Michael Nagel, Christian Mayer, Jürgen Peters, Matthias Hartmann
While hemolysis in patients with sepsis is associated with increased mortality its mechanisms are unknown and Toll-like receptor (TLR)-4 mediated effects, complement-mediated hemolysis, or direct cell membrane effects are all conceivable mechanisms. In this study, we tested the hypotheses that toxic lipopolysaccharide (LPS) as well as non-toxic RS-LPS evokes hemolysis (1) by direct membrane effects, and (2) independent of the complement system and TLR-4 activation. We found, that incubation with LPS resulted in a marked time and concentration dependent increase of free hemoglobin concentration and LDH activity in whole blood and washed red cells...
October 19, 2016: Scientific Reports
Gamze Ugurluer, Robert C Miller, Yexiong Li, Juliette Thariat, Pirus Ghadjar, Ulrike Schick, Mahmut Ozsahin
Primary hepatic lymphoma (PHL) is a rare malignancy. We aimed to assess the clinical profile, outcome and prognostic factors in PHL through the Rare Cancer Network (RCN). A retrospective analysis of 41 patients was performed. Median age was 62 years (range, 23-86 years) with a male-to-female ratio of 1.9:1.0. Abdominal pain or discomfort was the most common presenting symptom. Regarding B-symptoms, 19.5% of patients had fever, 17.1% weight loss, and 9.8% night sweats. The most common radiological presentation was multiple lesions...
September 5, 2016: Rare Tumors
Julia H Indik, Vineet Nair, Ruslan Rafikov, Iwan S Nyotowidjojo, Jaskanwal Bisla, Mayank Kansal, Devang S Parikh, Melissa Robinson, Anand Desai, Megha Oberoi, Akash Gupta, Taimur Abbasi, Zain Khalpey, Amit R Patel, Roberto M Lang, Samuel C Dudley, Bum-Rak Choi, Joe G N Garcia, Roberto F Machado, Ankit A Desai
Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease. ECG were analyzed from a cohort of 224 sickle patients (University of Illinois at Chicago, UIC) along with available laboratory, and echocardiographic findings, and from another cohort of 38 patients (University of Chicago, UC) for which cardiac MRI and free heme values were also measured...
2016: PloS One
Mark A DeWitt, Wendy Magis, Nicolas L Bray, Tianjiao Wang, Jennifer R Berman, Fabrizia Urbinati, Seok-Jin Heo, Therese Mitros, Denise P Muñoz, Dario Boffelli, Donald B Kohn, Mark C Walters, Dana Carroll, David I K Martin, Jacob E Corn
Genetic diseases of blood cells are prime candidates for treatment through ex vivo gene editing of CD34(+) hematopoietic stem/progenitor cells (HSPCs), and a variety of technologies have been proposed to treat these disorders. Sickle cell disease (SCD) is a recessive genetic disorder caused by a single-nucleotide polymorphism in the β-globin gene (HBB). Sickle hemoglobin damages erythrocytes, causing vasoocclusion, severe pain, progressive organ damage, and premature death. We optimize design and delivery parameters of a ribonucleoprotein (RNP) complex comprising Cas9 protein and unmodified single guide RNA, together with a single-stranded DNA oligonucleotide donor (ssODN), to enable efficient replacement of the SCD mutation in human HSPCs...
October 12, 2016: Science Translational Medicine
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
DNMT3A mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of DNMT3A mutations on a larger informative cohort of CMML patients (n=261). DNMT3A mutations were seen in 6% (n=16); 56% (n=9) male, with a median age of 64 years. Eighty-one % of DNMT3A mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (SF3B1/SRSF2/U2AF1-56%, TET2-50%, and ASXL1-25%) were seen in all patients...
October 12, 2016: American Journal of Hematology
Norbert Marschner, Michael Staehler, Lothar Müller, Arnd Nusch, Johanna Harde, Michaela Koska, Martina Jänicke, Peter J Goebell
INTRODUCTION: Because "real-life" patients often do not meet the strict eligibility criteria of clinical trials, we assessed the trial eligibility of patients with advanced or metastatic renal cell carcinoma (mRCC) in routine practice and compared the survival of "trial-ineligible" and potentially "trial-eligible" patients. PATIENTS AND METHODS: The present prospective, multicenter German cohort study is recruiting patients from 110 oncology/urology outpatient centers and hospitals at initiation of systemic first-line treatment...
September 8, 2016: Clinical Genitourinary Cancer
Xiang Ji, Yimin Feng, Hui Tian, Wei Meng, Weiling Wang, Na Liu, Jun Zhang, Lingshu Wang, Jian Wang, Haiqing Gao
In sickle cell disease (SCD), the inflammatory properties of high-density lipoprotein (HDL) can be changed by cell-free hemoglobin (Hb), which is released into the blood during hemolysis. Hb in the plasma of SCD patients or mice can bind with HDL specifically inducing an inflammatory reaction. In our study, we found increased amounts of inflammatory factor proteins in the chronic oxidative state of SCD with higher levels of Hb, haptoglobin (Hp) and hemopexin (Hx) in the apolipoprotein A-I (ApoA-1) particles of HDL and the role of HDL is changed from being anti-inflammatory to proinflammatory...
2016: PloS One
Anawat Pakdeesuwan, Tomohiro Araki, Sakda Daduang, Wisarut Payoungkiattikun, Nisachon Jangpromma, Sompong Klaynongsruang
The hydrolysis of proteins constitutes an invaluable tool granting access to a variety of peptide fragments with potentially interesting biological properties. Therefore, hemoglobin (Hb) hydrolysate of Crocodylus siamensis was generated by digestion under acidic conditions. The antibacterial and antioxidant activity of Hb hydrolysate were assessed in comparison with intact Hb. A disc diffusion assay revealed that the Hb hydrolysate exhibited antibacterial activity against eight strains of Gram-positive bacteria and showed a higher efficacy than intact Hb...
October 6, 2016: Journal of Microbiology and Biotechnology
Yuqing Yin, Chen Ling Gao, Qi Xiao, Guo Lin, Zian Lin, Zongwei Cai, Huang-Hao Yang
Artificial enzyme mimetics have received considerable attention because natural enzymes have some significant drawbacks, including enzyme autolysis, low catalytic activity, poor recovery and low stability to environmental changes. Herein, we demonstrated a facile approach for one-pot synthesis of hemeprotein-metal organic framework hybrid composites (H-MOFs) by using bovine hemoglobin (BHb) and zeolitic imidazolate framework-8 (ZIF-8) as a model reaction system. Surprisingly, the new hybrid composites exhibits 423% increase in peroxidase-like catalytic activity compared to free BHb...
October 4, 2016: ACS Applied Materials & Interfaces
Chengzhong Cai, Dmitry A Nedosekin, Yulian A Menyaev, Mustafa Sarimollaoglu, Mikhail A Proskurnin, Vladimir P Zharov
Control of sickle cell disease (SCD) stage and treatment efficiency are still time-consuming which makes well-timed prevention of SCD crisis difficult. We show here that in vivo photoacoustic (PA) flow cytometry (PAFC) has a potential for real-time monitoring of circulating sickled cells in mouse model. In vivo data were verified by in vitro PAFC and photothermal (PT) and PA spectral imaging of sickle red blood cells (sRBCs) expressing SCD-associated hemoglobin (HbS) compared to normal red blood cells (nRBCs)...
2016: Analytical Cellular Pathology (Amsterdam)
Charles T Quinn, Eric P Smith, Shahriar Arbabi, Paramjit K Khera, Christopher J Lindsell, Omar Niss, Clinton H Joiner, Robert S Franco, Robert M Cohen
Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation of hemolysis could be used as an objective outcome in clinical trials of new therapeutics for HbSS and would also enable better human studies of the pathogenesis of complications of HbSS that are ostensibly hemolysis-related, such as pulmonary hypertension. However, contemporary human studies in HbSS have used only surrogate markers of hemolysis rather than direct measurements of RBC survival. We directly quantified hemolysis in HbSS by measuring survival of an age cohort of RBCs labeled with a stable isotope, administered orally as (15) N-glycine, a metabolic precursor of heme...
September 20, 2016: American Journal of Hematology
Dariush Minai-Tehrani, Sara Toofani, Fatemeh Yazdi, Arash Minai-Tehrani, Hmidreza Mollasalehi, Kourosh Bakhtiari Ziabari
After red blood cells lysis, hemoglobin is released to blood circulation. Hemoglobin is carried in blood by binding to haptoglobin. In normal individuals, no free hemoglobin is observed in the blood, because most of hemoglobin is in the form of haptoglobin complex. In some diseases that are accompanied by hemolysis, the amount of released hemoglobin is higher than its complementary haptoglobin. As a result, free hemoglobin appears in the blood, which is a toxic compound for these patients and may cause renal failure, hypertensive response and risk of atherogenesis...
September 16, 2016: International Journal of Biological Macromolecules
Tigist Kassa, Sirsendu Jana, Fantao Meng, Abdu I Alayash
Despite advances in our understanding of the oxidative pathways mediated by free hemoglobin (Hb), the precise contribution of its highly reactive redox forms to tissue and organ toxicities remains ambiguous. Heme, a key degradation byproduct of Hb oxidation, has recently been recognized as a damage-associated molecular pattern (DAMP) molecule, able to trigger inflammatory responses. Equally damaging is the interaction of the highly redox active forms of Hb with other biological molecules. We determined the kinetics of heme loss from individual Hb redox states-ferrous (Fe(2+)), ferric (Fe(3+)), and ferryl (Fe(4+))-using two different heme receptor proteins: hemopexin (Hxp), a naturally occurring heme scavenger in plasma, and a double mutant (H64Y/V86F), apomyoglobin (ApoMb), which avidly binds heme released from Hb...
September 2016: FEBS Open Bio
Kokou Idoh, Amegnona Agbonon, Yao Potchoo, Messanvi Gbeassor
INTRODUCTION: Clerodendrum capitatum (Willd) Schumach. & Thonn (Lamiaceae) is used in African traditional medicine for the treatment of malaria, hypertension, obesity, jaundice and diabetes however there is lack of experimental data on its possible toxicity. This study investigated the acute and 28 days sub-chronic toxicity of C. capitatum in Wistar rats. METHODS: In acute toxicity tests, a single administration of the hydroethanolic C. capitatum leaf extract (5 g/kg) was given orally to 5 female rats...
2016: Pan African Medical Journal
Fabian Bock, Gary Lu, Samer Srour, Sameh Gaballa, Heather Y Lin, Veerabhadran Baladandayuthapani, Medhavi Honhar, Maximilian Stich, Nina Das Shah, Qaiser Bashir, Krina Patel, Uday Popat, Chitra Hosing, Martin Korbling, Ruby Delgado, Gabriela Rondon, Jatin J Shah, Sheeba K Thomas, Elisabet E Manasanch, Berend Isermann, Robert Z Orlowski, Richard E Champlin, Muzaffar H Qazilbash
The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH)...
September 13, 2016: Biology of Blood and Marrow Transplantation
Avishay Sella, M Dror Michaelson, Ewa Matczak, Ronit Simantov, Xun Lin, Robert A Figlin
BACKGROUND: The Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models categorize patients with 1 or 2 risk factors as intermediate prognosis (INTMP). This category encompasses 15 and 19 permutations of the MSKCC and IMDC risk factors, respectively. The purpose of the present retrospective analysis of data from INTMP patients in 6 clinical trials was to determine whether this heterogeneity influences the response to sunitinib...
August 18, 2016: Clinical Genitourinary Cancer
Patrick D Carroll, Robert D Christensen, Vickie L Baer, Mark J Sheffield, Erick Gerday, Sarah J Ilstrup
BACKGROUND: Our previous retrospective study suggested that red blood cell (RBC) transfusion of preterm neonates can be associated with an increase in bilirubin, but this has not been tested prospectively. STUDY DESIGN AND METHODS: We studied neonates before and after RBC transfusions, recording serial bilirubin levels and whether they qualified for phototherapy. Because lysed RBCs release plasma-free hemoglobin (Hb), a precursor to bilirubin, we also measured plasma free Hb and bilirubin from the donor blood...
September 7, 2016: Transfusion
Jeff Spector, Gayani C Kodippili, Ken Ritchie, Philip S Low
Sickle cell disease (SCD) is caused by an inherited mutation in hemoglobin that leads to sickle hemoglobin (HbS) polymerization and premature HbS denaturation. Previous publications have shown that HbS denaturation is followed by binding of denatured HbS (a.k.a. hemichromes) to band 3, the consequent clustering of band 3 in the plane of the erythrocyte membrane that in turn promotes binding of autologous antibodies to the clustered band 3, and removal of the antibody-coated erythrocytes from circulation. Although each step of the above process has been individually demonstrated, the fraction of band 3 that is altered by association with denatured HbS has never been determined...
2016: PloS One
Lauren N Whiteman, Carlton Haywood, Sophie Lanzkron, John J Strouse, Adrian H Batchelor, Anthony Schwartz, Rosalyn W Stewart
OBJECTIVES: Poor oral health can have a negative impact on overall health. This is especially concerning for individuals with sickle cell disease (SCD), an inherited blood disorder that affects hemoglobin and can lead to an increased risk of infection and hyperalgesia. Because the majority of individuals with SCD have Medicaid insurance and no dental coverage, we provided free basic dental care to individuals with SCD to determine whether it decreased overall healthcare utilization. METHODS: Through a contract with a private dental office, we provided free basic dental care (eg, cleanings, fillings, x-rays) to individuals with SCD...
September 2016: Southern Medical Journal
Antonio Paciello, Giuseppe Amalfitano, Alessandro Garziano, Francesco Urciuolo, Paolo A Netti
In this study, a novel micrometric biomaterial acting as a cyclic oxygen releasing system is designed. Human hemoglobin (Hb) is conjugated to the surface of gelatin microspheres (GM) to produce gelatin hemoglobin oxygen depot (G-HbOD). G-HbOD is obtained by means of two different conjugation strategies. The degree of conjugation of GM surfaces in terms of free amino groups by using HPLC is first evaluated. By following the strategy A (G-HbOD_A), Hb is conjugated to GM by means of the formation of a polyurethane linker...
September 5, 2016: Advanced Healthcare Materials
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