bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steady State Haemoglobin Level Increases with the Proportion of Erythrocyte Membrane n-3 Fatty Acids in Sickle Cell Anaemia.
Authors: Okpala Iheanyi , Ren Hongmei , Ibegbulam Obike , Ugochukwu Cynthia C. , Ghebremeskel Kebreab , Crawford Michael 
Published: October 2019

Abstract
Previous studies indicate that perturbation of erythrocyte and/or plasma lipids occurs in homozygous sickle cell disease (SCD), and treatment with n-3 fatty acids (FA) is beneficial to affected individuals (Tomer et al, Thromb Haemost2001; 966–974). Phosphatidylserine has a role in sickle erythrocyte-endothelial adhesion, which contributes to vessel occlusion in SCD (Setty et al, Blood2002; 1564–1571). Considering that n-3 and n-6 FA are essential structural and functional components of the red cell membrane, the objective of this study was to find out if abnormalities of these FA affect the degree of anaemia in SCD. We recruited 43 HbSS patients and 43 racially-matched, healthy, HbAA controls living in the same environment; analysed the fatty acid composition of erythrocyte membrane choline (CPG), serine (SPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SPM); and sought for relationship between steady-state Hb level in SCD and the proportion of n-3 FA in the red cell membrane. HbSS individuals had high levels of adrenic and docosapentanoic acids in CPG, EPG, SPG (p<0.001), and SPM (p<0.05). Arachidonic acid (AA) was increased in CPG (p<0.001) and EPG (p<0.005) of the patients. In contrast, linoleic acid (LA) was low in patients’ CPG, EPG, SPG and SPM (p<0.001). Both LA and AA were reduced in plasma CPG, triglycerides and cholesterol esters of SCD patients. There was significant positive correlation between steady-state Hb level and n-3 FA content of erythrocytes: docosahexaenoic (DHA, p<0.01, r = 0.63) and eicosapentanoic (EPA) acids in red cell CPG, and EPA in EPG (p<0.05, r = 0.60); figs. 1&2. The observed high AA with low DHA/EPA levels favour red cell adherence to vascular endothelium and vaso-occlusion. The data suggest that in SCD: synthesis of AA and/or membrane uptake of LA and AA may be abnormal; increased proportions of erythrocyte membrane DHA and EPA confer some resistance to haemolysis.
The Effect of Dietary Factors on Hemochromatosis Disease Expression in C282Y Homozygotes.
Authors: Phatak Pradyumna D. , Bundy Brain , Andrews Caroline , Braggins Laura , Sham Ronald L. 
Published: October 2019

Abstract
Background. Hereditary hemochromatosis (HHC) is a common inherited disorder and the vast majority of cases are associated with HFE gene mutations; about 80% are homozygous for the C282Y HFE mutation. Although homozygosity for C282Y is relatively common among individuals of northern European descent, the penetrance, as measured by clinically relevant iron overload, is low. Both environmental and genetic factors have been implicated in modulating disease expression. Most clinicians and patients attribute at least some of the observed variation to differences in dietary patterns.
Methods: 28 C282Y homozygous subjects who had completed de-ironing therapy at our center, and were on stable maintenance phlebotomy treatments, participated in a previously validated dietary survey. We examined the influence of dietary iron, heme iron, fiber, ascorbic acid and alcohol intake on disease expression as measured by liver iron, phlebotomy-mobilized iron and maintenance phlebotomy requirement.
Results. We developed a maintenance iron score (Maint Fe) which was the iron in milligrams removed per month by phlebotomy treatments in order to maintain serum ferritin in the 25–75 μG/L range. Maint Fe ranged from 36.8–203 mg/month in our patients (87.8 ± 37.7). Liver iron ranged from 30.5 to 505.4 micromoles per gram dry weight (192.7 ± 123). Phlebotomy-mobilized iron ranged from 2.35–18.03 G (6.43 ± 4.08). The Spearman’s Rank Correlation was used to compare dietary parameters with each of the above measures of disease expression. No significant correlation was found.
Conclusions. Disease expression varied considerably in our C282Y homozygous subjects as measured by liver iron, phlebotomy-mobilized iron and Maint Fe. The observed variation is not explained by variations in dietary iron, fiber, ascorbic acid or ethanol intake. Our data suggests that other unknown environmental variables or alternatively, modifier genes, may play a role in modulating disease expression in these patients. Contrary to popular belief, dietary variation does not appear to play a major role.
Chronic Aluminum Toxicity Due to Intravenous Substance Abuse Managed with Deferoxamine Chelation Therapy: Case Report.
Authors: Sreenivasan Gayatri M. , Yong Raymund L.M. , Holmes Dan 
Published: October 2019

Abstract
Aluminum toxicity first came to attention in the medical literature as a sequela of peritoneal or hemodialysis, where accumulation of aluminum in body tissues results from the use of aluminum-containing dialysate and phosphate binders. The most common clinical presentations of aluminum toxicity include anemia, bone disease, and a syndrome of encephalopathy known as the dialysis encephalopathy sydrome (DES). We present the unique case of a 42-year-old man who developed chronic aluminum toxicity from the intravenous injection of a methadone preparation intended for oral consumption. The methadone solution was concentrated for intravenous injection by heating in aluminum cookware. Experiments performed in our laboratory reproducing this technique, using weakly acidic solutions similar to popular drink mixes, confirmed that significant amounts of elemental aluminum can be leached from aluminum cookware when heated. The patient presented to medical attention with generalized seizures, profound cerebellar dysfunction, myoclonus, and speech apraxia, all of which are characteristic of DES. The peripheral blood film revealed bizarre red cell morphology, with clear features of iron deficiency and prominent coarse basophilic stippling, suggesting impaired iron utilization, which is at least one mechanism of aluminum related hematologic toxicity. A bone marrow biopsy demonstrated extensive osteosclerosis and myelosclerosis, compatible with significant metabolic bone disease. Subsequent investigations revealed a serum aluminum level of 7200 nmol/L, eighteen times the upper limit of normal (400 nmol/L). Chelation therapy with a continuous intravenous infusion of deferoxamine was started, and over a course of ten months the serum aluminum level was reduced to 2390 nmol/L with few side effects. The patient made a significant neurologic recovery and returned to life in the community. This is the first detailed account of the successful use of deferoxamine to chelate aluminum in a patient without dialysis-dependent renal insufficiency. This case also highlights heavy metal exposure as a diagnostic consideration in intravenous substance abusers presenting with multiorgan dysfunction, and the importance of performing a thorough inquiry into injection drug practices when evaluating these patients.
γδT Cell Is Impacted to Erythropoiesis Suppression in Patients with Acquired Pure Red Cell Aplastic Anemia.
Authors: Liu Ting , Liu Min , Dai Yang , Zhu Huanling , Cui Xu , Meng Wentong , Xu Caigang 
Published: October 2019

Abstract
Acquired pure red cell aplastic anemia(PRCA)is a group of heterogeneneous disorders characterized by erythropoiesis failure or disorder in bone marrow. PRCA is often associated with thymoma, large granular lymphocytic leukemia, and also some autoimmune diseases. It has been well documented that T cell subsets from the patients with PRCA often show some abnormalities either in quantum or in the effects to suppress erythropoiesis, and anemia symptom of the patients usually have a good response to cyclosporine treatment. So it suggested that activated T cell might play a key role in the pathogenesis of PRCA. This study is to explore the abnormalities of γδT cell subsets and the effects of immunosuppressive therapy in the PRCA patients.
Methods: 12 patients, whose age ranged 37~72 years old, were diagnosed as PRCA based on bone marrow smear and biopsy, and were treated with cyclosporine, and 24 healthy adults were matched as normal controls. The three-color flowcytometry technique was used for lymphocytes subsets and γδT cells analyses. Furthermore, peripheral mononuclear cells (MNC) isolated from PRCA patients were cultured in RPMI1640 medium (106 cells/ml) with 10% FCS, phytohemagglutinin(PHA, 10μg/ml), and recombinant human interleukin-2(rIL-2, 50U/ml)for two weeks, then γδT cells were isolated with the TCRγδ Microbead Kit from cultured cells. The collected γδT cells were incubated with normal control bone marrow MNC in RPMI1640 medium (37°, 5% CO2 atmosphere) for CFU-E, CFU-GM, and BFU-E clones assay.
Results: Comparing with control group, CD3+/CD8+ cells were increased significantly in the patients group (p<0.05), and the CD4+/CD8+ ratio was decreased and reversed. Furthermore, an increased Tc2 cells percentage and a decreased Tc1/Tc2 ratio were observed, and γδT cells were overrepresented in patients group(P<0.05). After treatment with cyclosporine, 10 of 12 patients got very good response (Hb recovered to over 100g/L), and in the responding patients, CD3+/CD8+ cells, Tc1 and Tc2 cells were decreased, and the ratio of CD4+/CD8+ and Tc1/Tc2 were return to normal respectively, and γδT cells were also decreased to normal range. Moreover, in vitro culture, the γδT cells isolated from PRCA patients show an inhibiting role to CFU-E and BFU-E but not to CFU-GM in a dose-dependent manner.
Conclusion: Our study suggested that γδT cells might impacted to pathogenesis of acquired PRCA, a significant improvement of anemia symptoms had been shown after cyclosporine treatment, meanwhile, the percentage of γδT cells recovered to normal range, and it is very interesting, the γδT cells isolated from PRCA patients show an inhibiting role to CFU-E and BFU-E but not to CFU-GM in vitro culture. We think that it is an effective way to treat the patients with acquired PRCA by to rectify the abnormal cellular immunity.
Mycophenolate Acid Has a Negative Effect on the Maturation and Immune Function of the Murine Bone Marrow-Derived Dendritic Cells.
Authors: Cai Zhen , Huang Wenye , Sun Wenji 
Published: October 2019

Abstract
Mycophenolate mofetil (MMF) is a newly developed immunosuppressor, currently widely used in allogeneic bone marrow transplantation. Its active metabolite, mycophenolic acid (MPA) is a noncompetitive, reversible inhibitor of the enzyme inosine 59-monophosphate dehydrogenase, which plays a major role in the de novo synthesis of guanosine nucleotides. Unlike other cells that also use the salvage pathway for purine biosynthesis, proliferating B and T cells are dependent on the de novo pathway generate guanosine. Thus, MMF exerts its immunosuppressive effects of lymphocyte proliferation. Recently, some studies found that MPA could inhibit the immun immune function of antigen presenting cells. Dendritic cells (DCs), the most potent antigen presenting cells with the unique ability to prime naive T cells, play a central role in antigen processing and presentation to induce T cell response in vitro and in vivo. This study is to evaluate the effects of MPA, the in vivo active metabolite of MMF, on the maturation and immune function of murine bone marrow-derived dendritic cells, and to explore the underlying mechanisms of MMF in graft versus host disease. Bone marrow-derived dendritic cells (DC) were cultured with GM-CSF and IL-4 in the presence of MPA at doses of 0.01 and 0.1μmol/L. The ability of the allostimulatory activities of the DCs on allogeneic T cells was assessed by MLR. IL-12 production in culture supernatant and the Th1/Th2 cytokines such as IL-2, IFN-g, IL-4 and IL-10 levels in mixed lymphocyte reaction (MLR) supernatant were examined by ELISA assays. The activity of NF-κB in DCs was measured with Western blot assays. Our results showed that DCs cultured in the presence of MPA expressed lower levels of CD40, CD80 and CD86, exhibited weaker activity of stimulating the allogeneic T cell proliferation and weaker in antigen presenting function with a concurrent reduction of IL-12 production. MPA-treated DCs stimulated allogeneic T cells to secrete higher levels of Th2 cytokines IL-4 and IL-10 but lower levels of Th1 cytokines IL-2 and IFN-g than did DCs not treated with MPA. The activity of NF-κB was decreased in DCs treated with MPA in a dose-dependent manner. We conclude that MPA, and hence MMF, exerts a negative effect on the maturation and immune function of in vitro cultured DCs, and drives a shift of Th1 cytokines to Th2 cytokines in MLR. This negative effect is associated with a decrease in NF-κB activity. Say something about the significance of this finding regarding GVHD.
The Direct Cytotoxicity of Activated Human Umbilical Cord Blood Dendritic Cells to Tumor Cell.
Authors: Jun Shi , Ikeda Kazuma , Fujii Nobuhara , Kasumoto Kinuyo , Tanimoto Mitune , Xiao Li , Quan Pu 
Published: October 2019

Abstract
Besides their role as antigen presenting cells, human peripheral blood mononuclear cell and CD34+ cell-derived dendritic cells (DCs), now have been demonstrated to exert cytotoxicity against some tumor cells, and their tumoricidal activity can be enhanced by some stimili. However, there have been no reports concerning the tumor-cell killing activity by human cord blood cell-derived dendritic cells (CBDCs). We report here that human cord blood monocyte-derived DCs aquire the ability to kill tumor cells after activation with lipopolysaccharide (LPS) or interferon-γ(IFN-γ), associated with the enhanced TNF-α-related apoptosis-inducing ligand (TRAIL) expression in CBDC cytoplasm. The CD14-positive cells collected from cord blood from healthy volunteers were cultured with interleukin-4 and granulocyte-machrophage colony- stimulating factor for seven days to induce CBDCs, which showed no cytotoxicity. However, after activation with IFN-γ for additional 12 hours, CBDCs exhibited cytotoxicity against HL60 and Jurkat cells, while activation with LPS for 12 hours induced cytotoxicity against Daudi and Jurkat cells as we detected in human peripheral blood monocytes- drived DCs (PBDCs). IFN-γ or LPS stimulation enhanced intracellular but not cellular surface TRAIL, and neither intracellular nor cellular surface Fas Ligand as analyzed by flow cytometry. Our results suggest that activated CBDCs can serve as immunological effectors against tumor cells, through TRAIL- dependent and Fas-independent mechanisms.
Macrophage Motility Dysfunction in a Patient with Recurrent Infections.
Authors: Jubinsky Paul T. , Short Mary , Ashton Anthony , Cox Diane , Pixley Fiona 
Published: October 2019

Abstract
Three members of a family with normal parents had a common constellation of findings that included absent corpus callosum and recurrent bacterial infections. The older male and female siblings both died from infection at an early age. The patient’s CBC was significant for elevated numbers of monocytes that were large and vacuolated. Her T- and B-cell function was normal. These preliminary findings suggested a defect in innate immunity. Evaluation of the patient’s peripheral blood monocytes by flow cytometry showed normal size and maturity. Phagocytosis and activation of peripheral blood derived macrophages by cytokines were also similar to controls. In contrast, the patient’s cultured macrophages were significantly more spread than those from normal individuals and contained a disordered actin cytoskeleton when cultured on fibronectin. The ability of the macrophage to transmigrate across an endothelial cell barrier was impaired. However examination by time-lapse videomicroscopy showed that the mutant macrophages had increased protrusional activity and movement. This is the first report describing a genetic macrophage motility disorder that results in an increased susceptibility to infection.
TEL/PDGFβR Tyrosine Kinase Fusion Specifically Activates Myeloid Differentiation Programs, and Converts Lymphoid Progenitors into the Myeloid Lineage.
Authors: Shigematsu Hirokazu , Iwasaki Hiromi , Mizuno Shin-ichi , Sternberg David W. , Huntly Brian J.P. , Gilliland D. Gary , Akashi Koichi 
Published: October 2019

Abstract
Acute leukemias are classified into myeloid and lymphoid subtypes according to their phenotypic characteristics. Leukemic cells, however, sometimes co-express myeloid and lymphoid phenotypes, or switch their phenotype from myeloid to lymphoid lineages and vice versa. The conventional classification of leukemias is based mainly upon the concept that leukemic phenotype reflects a progenitor stage at which leukemic transformation occurs, or that it represents a stage at which transformed hematopoietic stem cells (HSCs) become incapable of further differentiation. Here we propose another possibility that phenotype of leukemias could be determined by instructive signals from the leukemic transformation mechanism itself. We found that TEL/PDGFβR (T/P), a tyrosine kinase fusion isolated from chronic myelomonocytic leukemia, can instruct myeloid lineage commitment and conversion at stem and progenitor stages of hematopoiesis. The T/P gene was transduced into purified progenitors or HSCs by using a retrovirus carrying a green fluorescent protein reporter. HSCs transduced with T/P (T/P+ HSCs) spontaneously formed GM colonies without cytokines. Furthermore, T/P+ HSCs were incapable of differentiation into B cells on OP9 stromal layer in the presence of IL-7. To test the effect of T/P on lymphoid commitment more precisely, we transduced T/P into purified common lymphoid progenitors (CLPs) that normally differentiate only into T, B and NK lineages. In a limiting dilution assay, 1 in 7 control-GFP transduced CLPs generated B cell progeny in vitro, while only 1 in 500 T/P+ CLPs differentiated into B cells. Instead, surprisingly, the majority of T/P+ CLPs and even T/P+ thymic proT cells quickly differentiated into granulocytes and monocytes in vitro. We then transplanted T/P+ CLPs into lethally irradiated congenic mice. T/P+ CLPs again differentiated into Gr-1+ granulocytes and monocytes in vivo. Gene expression analyses showed that T/P+ CLPs upregulated GM-related molecules including C/EBPα and GM-CSFRα immediately after T/P transduction, while transduction of either C/EBPα or GM-CSFRα also reprogrammed CLPs into the myeloid lineage as we reported previously. Thus, T/P signaling can activate these critical GM-related molecules in lymphoid progenitors to convert them into the myeloid lineage. These data collectively suggest that at least some types of oncogenic tyrosine kinase fusions can specify leukemic phenotypes, through activating critical signals for lineage commitment.
A Study of Effects of 2A-1-1 on Platelet Function in Hypertension Patients.
Authors: Nie Danian , Zeng Furen , Xie Shuangfeng , Li Yiqing , Yin Songmei , Ma Liping , Wu Yudan 
Published: October 2019

Abstract
Objective To study the effects of 2A-1-1, a purified component from Panax notoginsengs which is considered to be a blocker of ROC (Receptor-operated Ca2+ channel), on platelet aggregation in hypertension patients with Nifedipine and 1-{β-[3-(4-methoxyphenyl) propoxy]- 4-methoxyphenethyl}- 1H - imidazole hydrochloride (SK and F96365) in contrast.
Methods Platelet rich plasma (PRP) was made in routine way from venous blood samples which taken from 30 essential hypertension patients and 30 normal people. PRP was incubated with different concentrations of 2A-1-1, Nifedipine and SK&F96365 for 3 minutes. Therefore, maximal platelet aggregation rate (PAGmax) induced by ADP had been measured on TYXN-91 aggregometer.
Results 1. PAGmax in essential hypertension group was 88.48±5.36%, higher than that in normal group which was 67.54±8.46%( P<0.01). 2. Nifedipine (10μmol/L and 20μmol/L) had no effect on PAGmax in neither essential hypertension group nor normal group( P>10;0.05). 3. 2.5μmol/L, 5μmol/L, 10μmol/L and 20μmol/L SK&F96365 could reduce the PAGmax in essential hypertension group by 14.32%) 17.9%) 30.26%) 78.23% respectively; 5μmol/L, 10μmol/L and 20μmol/L SK&F96365 could reduce the PAGmax in normal group by 21.57%) 22.85%) 59.38% respectively. 4. 2.5μmol/L, 5μmol/L, 10μmol/L and 20μmol/L 2A-1-1 could reduce the PAGmax in essential hypertension group by 24.83%) 27.56%) 48.73%) 92.77% respectively; 5μmol/L, 10μmol/L, 20 μmol/L 2A-1-1 could reduce the PAGmax in normal group by 47.06%) 53.47%)71.52% respectively.
Conclusions 1. PAGmax in essential hypertension patients is higher than normal people remarkably, suggesting that the high reactive status of platelets is an important factor for the development of thrombus in hypertension patients.2. Nifedipine has no effects on PAGmax, therefore it can not inhibit platelet aggregation.3.SK and F96365 can reduce the platelet aggregation.4. 2A-1-1 can inhibit platelet aggregation, therefore, it has the definite effect of anti-platelet.
Propofol-Induced Bleeding Dyscrasia: A Case Report.
Authors: Fahed Rabih C. , Schulz2 Thomas K. 
Published: October 2019

Abstract
Propofol is one of the most commonly used anesthetic drugs, with rapid induction, maintenance and recovery times. Its relative safety has resulted in it becoming a popular choice for general anesthesia.
A 56 y o woman with no prior history of bleeding underwent laparoscopic cholecystectomy. Postoperatively she experienced bleeding to the degree that open laparotomy was required to achieve hemostasis.Two years later, she underwent open sigmoid resection under propofol anesthesia for refractory diverticulitis. Severe postoperative bleeding ensued, necessitating IV fluid resuscitation and transfusion of packed red blood cells.Template bleeding time was repeatedly greater than 20 minutes on the first postoperative day. Platelet count, coagulation studies, von Willebrand disease assays, fibrinogen level and fibrinolytic system assays were found to be normal. Platelet aggregation in response to arachidonic acid was decreased at 9% (reference 60 - 120 %). The patient received platelet transfusions; hemostasis was achieved and the template bleeding time returned to normal on the second postoperative day and remained normal on repeat testing several weeks later.
A few reports have shown an increased bleeding with propofol, which is thought to be related to inhibition of thromboxane A2 synthesis and increased synthesis of leucocyte nitric oxide. Some studies show increased bleeding even without any change in the template bleeding time.
In summary, we report a case of a propofol-induced life threatening bleeding dyscrasia associated with a prolonged template bleeding time and platelet aggregation studies consistent with decreased response to arachidonic acid. This rarely reported complication should always be in the differential diagnosis of postoperative bleeding given the widespread usage of propofol anesthesia in major surgeries.