bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoprotective Effect of ICL670 (Deferasirox) on At20 Endocrine Cells Susceptible to Iron-Evoked Oxidative Damage.
Authors: Glickstein Hava , Nick Hanspeter , Cabantchik Zvi Loav 
Published: October 2019

Abstract
A major cause of biological damage associated with tissue iron accumulation is the cellular acquisition of circulating labile plasma iron (LPI) by endocytic mechanisms and ensuing metal-catalyzed oxidations. Endocrine cells are presumed to have endocytic abilities and/or high susceptibility to the formation of reactive oxygen intermediates (ROIs), particularly those generated in the presence of labile iron. As these properties might be implicated in the early onset of endocrine dysfunctions observed in transfusional hemosiderosis, a major goal of iron chelation therapy is to prevent iron ingress into endocrine cells and ensuing toxicity and/or removal of cell-accumulated iron. Such properties of chelators have been afforded in cardiac cells (Glickstein et al. 2006, Blood In press) by treating LPI-carrying plasma with pharmacologically attainable concentrations of orally active iron chelators in clinical practice. The latter also evoked neutralization of metal-catalyzed ROS formation, by iron chelation and extrusion from cells and thereby supported cardiac functional restoration. We explored here whether addition of ICL670 (deferasirox) could rescue acutely iron-overloaded At20 pituitary cells from iron-toxicity, using fluorescence-plate reader and microscopy-imaging for live monitoring of cell functions and assessing toxicity in terms of:cell integrity (calcein cell retention assay);metabolic activities (mitochondrial Alamar-Blue assay); andintracellular (ACTH) hormone levels. Our studies indicate that in cell culture conditions and at pharmacological chelator concentrations, ICL670 can preserve both At20 endocrine cell viability and functional properties that were compromised by iron-catalyzed formation of ROIs.
Chance Detection of CD16 Deficiency on Polymorphonuclear Neutrophils in Iron Deficiency Anemia.
Authors: Kamat Anil V. , Ezekwesili Raphael 
Published: October 2019

Abstract
Introduction CD16 (FcgRIII) is a low affinity receptor for immunoglobulin G(IgG)constitutively expressed on polymorphonuclear neutrophils, monocytes and NK-cells with various effector functions including phagocytosis of opsonized particles or of immune complexes and in antibody-dependent cellular cytotoxicity (ADCC). Congenital defect of neutrophil CD16 expression has been reported with variable phenotypic associations such as anaemia, neutropenia, autoimmune thyroiditis, recurrent infections, acute myeloid leukaemia, systemic lupus erythematosis and in mothers whose newborns have developed transient neonatal alloimmune neutropenia.
CD 16 deficiency on neutrophils -A 46 year old lady presented with extreme tiredness with her full blood count showing Hb 7.6 g/L MCV 76.0 fl MCH 23.8 pg WBC 5.9 X 10^9/L Neutrophil count 3.5 X 10^9/L Platelet count 290 X 10^9/L.Her serum ferritin level was 2.2 mcg/l with normal B12 & folate levels. Hemoglobinopathy screen was normal. Blood film was consistent with iron deficiency. She denied any history of blood loss. In view of positive faecal occult blood, she underwent upper & lower gastrointestinal tract endoscopies which failed to reveal any bleeding lesion. Red cell scan was considered but not arranged as clinically she was not bleeding at a rate more than 1 ml per minute. Capsule enteroscopy was not available. Coeliac screen was negative. Due to intolerance of oral iron supplementation, she needed parenteral iron infusions, which improved her hemoglobin.
However, the response was not sustained which prompted further work up. She underwent bone marrow aspirate & trephine biopsy which was suggestive of mild dyserythropoeisis. Cytogenetics was normal. Hemolytic screen was negative. On immunophenotyping as part of Paroxysmal Nocturnal Hemoglobinuria (PNH) screen, neutrophils showed normal expression of CD 59 (89%)& CD 66b (100%)but completely lacked CD 16 (02%). Urinary haemosiderin was negative. She had no history of increased frequency or of exceptionally severe or persistent infections. Family studies are pending. She remains iron replete on parenteral supplementation.
Conclusion- Polymorphonuclear neutrophils totally deficient in CD16 were detected by chance. CD16 deficiency has not compromised the host defence in this patient. We have not assessed CD16 specific mRNA or functional parameters such as phagocytosis of opsonized bacteria and superoxide production since the patient had no history of increased infections. The other receptors for IgG apparently can compensate for the lack of CD16. Congenital deficiencies of CD16 are very rare. The clinical relevance of congenital defect of neutrophil CD16 expression remains unclear. This case substantiates the inferences of other sporadic reports of there being no compromise of host defence resulting from isolated CD16 neutrophil expression defect.
High Levels of Soluble P-Selectin Are Associated with the Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant.
Authors: Ay Cihan , Jungbauer Lea V. , Sailer Thomas , Tengler Theres , Koder Silvia , Kaider Alexandra , Panzer Simon , Quehenberger Peter , Mannhalter Christine , Pabinger Ingrid 
Published: October 2019

Abstract
The cell adhesion molecule P-selectin, which is found in the alpha granula of platelets and in Weibel-Palade bodies of endothelial cells, has been shown to play an important role in the pathophysiology of thrombosis. However, the meaning of soluble P-selectin (sP-selectin) in venous thromboembolism (VTE) is still uncertain because clinical data are limited. The purpose of this study was to investigate whether sP-selectin is associated with the risk for VTE and to elucidate the association of sP-selectin and the P-selectin gene variation (SELP) Thr715Pro in high risk patients with recurrent VTE. We recruited cases and control individuals between January 2005 and November 2005 for an analysis of sP-selectin plasma levels and the SELP Thr715Pro. Patients with a history of objectively confirmed recurrent VTE and at least one event of an unprovoked deep venous thrombosis or pulmonary embolism were enrolled. Plasma was obtained at least 3 months after the most recent event of VTE. Age and sex-matched healthy individuals served as controls. sP-selectin levels were measured with a high sensitive ELISA. The variant for the P-selectin gene was determined by a mutagenically separated PCR followed by high resolution gel-electrophoresis. Hundred-sixteen patients (53 female / 63 male; mean age +/−SD: 56 +/−12 yrs) and 129 controls (66 female / 63 male; mean age +/−SD: 53 +/−11 yrs) were enrolled. Mean concentration (+/−SD) of sP-selectin (ng/mL) was significantly higher in patients than in controls (47.28 +/−15.00 vs. 36.77 +/−11.00, p<0.001). The unadjusted odds ratio (OR) of elevated sP-selectin (cut-off level 55.10 ng/mL representing the 95th percentile of the controls) was 8.5 (95% confidence interval (CI): [3.7–23.3], p<0.001) and increased after adjustment for factor V Leiden, prothrombin G20210A variant, elevated factor VIII level, hyperhomocysteinemia and BMI (OR=11.1, 95% CI [4.3–33.0], p<0.001). Carriers of the SELP Pro715 were more prevalent among controls than patients (21.7% versus 14.7%), however, the difference was statistically not significant (p=0.19). The subgroup of carriers of the SELP Pro715 (n=45) had significantly lower sP-selectin levels than non-carriers (31.31+/−7.94 vs. 44.10+/−14.08, p<0.001). In conclusion, our study shows a highly significant association between elevated sP-selectin levels and VTE. Furthermore, sP-selectin levels correlate with genotype status and individuals carrying the SELP Pro715 have lower levels of sP-selectin.
Detection of HTLV1 in Patients with B and T-Cell Malignancies Which Are Different to Adult T-Cell Leukemia-Lymphoma: A Prospective Study.
Authors: Marquez Jose J.M. , Ortiz Natalia N.O. , Cisterna Ramon R.C. , de Heredia Jose Maria J.B. Beltran 
Published: October 2019

Abstract
Human T-lymphotropic virus type I (HTLV-I), is the pathogenic agent of adult T-cell leukemia-lymphoma (ATLL), which always shows monoclonal HTLV-I provirus DNA integration. HTLV-I is rarely associated with B-cell disorders. The gen Tax of a human T-cell leukemia virus type I (HTLV-I) induces the expression of several cellular genes that are involved in T cell activation and proliferation. In the current study was to analyze prospectively HTLV-I proviral DNA presence in peripheral blood mononuclear cells (PBMCs) in patients with leukemia or lymphoma which are different to ATLL. Following this pattern we have studied in 61 patients with T and B-cell malignancies the presence of the virus HTLV-I on the during our service between April 2004 and May 2006.
A real time PCR assay using SYBR Green intercalation was established. Primer and hybridization probes targeting tax region were standardized against MT2 cell line DNA for HTLV-I. The assay reliably detected a single copy of HTLV-I proviral genome in DNA from 1X106 PBMCs. Also included for each sample the HLA-DQ alpha gene (a measure of genomic DNA), We have detected the presence of HTLV-I in five patients: 2 patients with B-CLL (lymphocytes count: 1.3 x 109/L and 16,8 respectly), one patient with T-ALL CD4 and CD8 positive; other with NHL and one with B-ALL Ph+. As an interesting data, one of the patients with B-CLL presented as complication a immune thrombocytopenia after Fludarabine therapy. Two patients were died and the two cases with B-CLL show stable sickness. Only the patient with T-ALL achieved complete remission after chemotherapy. In conclusion, we have detected on our series, in a unsuspected way, the presence of HTLV-I on some of the patients with lymphoid malignancies, which are different to the ATLL, showing in these cases an atypical clinic course. After knowing the repercussion of HTLV-I over the immune competition of the infected patients it seems suggestive speculate on the possible implication of the virus in a deterioration of the immunity favouring the progress of neoplasia and/or a greater propensity to infections and immunological upheavals, like the observed ones in our series.
The Effects of Glycoprotein IIb/IIIa Antagonist RGDS on Platelet Aggregation and Release Reaction In Vitro.
Authors: Xie Shuangfeng , Yin Songmei , Nie Danian , Li Yiqing , Wang Xiuju , Ma Liping , Yang Guolei 
Published: October 2019

Abstract
Platelet activation, including platelet adhesion, platelet aggregation and platelet release reaction, played an important role in thrombogenesis. We all knew that Platelet glycoprotein IIb/IIIa antagonist was the most effective drug for anti-aggregation, while we don’t know clearly its effect on platelet release reaction and the relations between its effects on platelet aggregation and release reaction. Platelet release reactions included α-granules and dense granules releasing. When α-granules were released, its membrane glycoprotein CD62p was expressed in the platelet membrane. We used the CD62p expression as the index of platelet release reaction. In the current study, the 4-peptides RGDS (Arg-Gly-Asp-Ser) was used as glycoprotein IIb/IIIa antagonist. We detected the effects of RGDS on platelet aggregation and CD62p expression induced by adenosine diphosphate (ADP) (finial concentration, 5μmol/L) in vitro. 50, 100, 200, 400 and 800μmol/L RGDS were used separately in the test. RGDS of each concentration could significantly inhibited maximal platelet aggregation (PAG(M)) induced by ADP, the 50% inhibiting concentration was approximately 200μmol/L. 800μmol/L RGDS could inhibited PAG(M) by 80.48±8.18%. Only ≥200μmol/L RGDS could significantly inhibited platelet CD62p expression. 800μmol/L RGDS could inhibit platelet CD62p expression by 27.31±9.74%. The inhibiting effect of RGDS on PAG(M) and platelet CD62p expression had significantly correlation (r =0.976, P<0.05). These results indicated that RGDS in low concentration (<200μmol) had little negative effect on platelet release reaction induced by ATP, while in relatively high concentration (≥200μmol) RGDS could inhibit platelet release reaction. When RGDS concentrations were same its effect on platelet release reaction was much less than that on platelet aggregation, which indicated that platelet glycoprotein IIb/IIIa compound could only partly participated in the platelet release reaction but fully participated in platelet aggregation induced by ADP.
Use of CSGE, TspRI- RFLP and Western Blot in Carrier Detection in an Indian Family with Type I Glanzmann Thrombasthenia.
Authors: Kannan Meganathan , Ahmad Firdos , Kumar Rajive , Choudhry Ved P. , Saxena Renu 
Published: October 2019

Abstract
Glanzmann Thrombasthenia (GT) is an inherited, autosomal recessive, bleeding disorder which is characterized by absent/reduced platelet Glycoprotein IIb/IIIa. The sub classification of GT into Types I, II and III is based on the levels of GPIIb/IIIa by flow cytometry. Type I is the most severe form of GT and is found to be most common in north Indian population. Since not much study is available on carrier detection based on western blot analysis, it is suggested to confirm the defect in carriers by molecular diagnosis. Here we present a carrier status using TspRI in a family with Glanzmann Thrombasthenia patient. Glanzmann Thrombasthenia was diagnosed in a patient with bleeding manifestations accompanied by absent platelet aggregation, secondary to ADP, ADR, Arachidonic acid and collagen. The patient was sub typed as Type I based on flow cytometry analysis as he had absent GPIIb/IIIa. Patient’s DNA was analyzed for mutation in both the gpIIb and gpIIIa genes by CSGE, followed by sequencing. The patient was found to have mutation, CTG>CCG at exon 12 of GPIIb gene. The mutation caused amino acid change from Leu to Pro in the GPIIb protein. The same mutation was looked for in all the family members (Both parents and two siblings) using CSGE and by TspRI- RFLP analysis. Both the parents and siblings were heterozygous for this mutation, where as patient was homozygous (Fig 1). As this mutation is not present in the normal individuals and is not reported earlier, this considers being a novel mutation. Presence of abnormal protein in the family members was revealed by western blot analysis for GPIIb (Fig 2). The same mutation is being looked for in more number of patients with Glanzmann Thrombasthenia using TspRI- RFLP. So far, a total of two out of 25 GT patients found to carry this mutation. It is possible that abnormal GPIIb protein by western blot in family members may reflect their carrier status. It is also postulated that western blot and CSGE of GPIIb and IIIa in parents/siblings may detect carrier status in Glanzmann Thrombasthenia.
Fig 1: Carrier detection by restriction digestion using TspRI Fig 1:. Carrier detection by restriction digestion using TspRI Fig 2: Immunoblot followed by chemiluminescent detection shows absent/reduced protein in patient and abnormal band pattern in the family members Fig 2:. Immunoblot followed by chemiluminescent detection shows absent/reduced protein in patient and abnormal band pattern in the family members
Rituximab in Children with Autoimmune Thrombocytopenia Complicating Underlying Congenital or Acquired Immunodeficiency State.
Authors: Junagade Pritesh S. , Height Susan , Ruiz Gary , Hadzic Dino , Ball Colin , Rees David 
Published: October 2019

Abstract
Rituximab (chimeric anti-CD20 monoclonal antibody) has been reported to be effective in various autoimmune conditions, especially in autoimmune cytopenias, but there are few reports of its use in paediatric population with underlying immunodeficiency states. We report three cases of autoimmune cytopenias (Evan’s syndrome in DiGeorge syndrome, autoimmune thrombocytopenia in a HIV positive patient and lastly autoimmune thrombocytopenia in a post liver transplant patient) where rituximab was effective in reversing the cytopenias. First patient (11yrs) had DiGeorge syndrome which was complicated by Evan’s syndrome. It was treated with multiple courses of steroids and immunosuppressive agents, with resultant recurrent systemic bacterial and fungal infections. She had rituximab as a last resort, which resulted in sustained improvements in her Haemoglobin and platelet count. Second patient (12yrs) was diagnosed with HIV in 1993. She had sudden onset Intra-cranial bleed as a result of immune thrombocytopenia. She was treated with Intravenous immunoglobulin (IVIg) and subsequently with prednisolone with no response. She however responded to rituximab and then went on to have rituximab for a further 2 courses, each 12 months apart. The third patient (14yrs) had auxiliary liver transplant in 2002. He developed immune thrombocytopenia and neutropenia in which remission was sustained only for a maximum of 6 weeks following IVIg. As he was already on immunosuppression, he was given rituximab to which he has had a sustained remission. Side effects: The patient with DiGeorge syndrome had recurrent chest infection which was thought to be due to aspiration as a result of her hiatus hernia. The other patients did not have major side-effects. Immunoglobulin levels in all three patients were in normal range. Thus, in our experience rituximab is a useful adjunct in management of autoimmune cytopenias with an underlying immunodeficiency state and should be considered early in steroid refractory cases, as it leads to sustained remissions in the blood counts. It is well tolerated without major infections in patients who are already immunosuppressed due to their immunodeficiency state and the fear of immuneparesis is not seen.
A Case Control Study of Deep Venous Thrombosis in Relation to Factor V G1691A (Leiden) and A4070G (HR2 Haplotype) Polymorphisms.
Authors: Almawi Wassim Y. , Borgi-Bouaziz Lobna , Nathalie Hezard , Philipe Nguyen , Touhami Mahjoub 
Published: October 2019

Abstract
Activated protein C resistance (APCR) is a significant risk factor for venous thromboembolism (VTE), and the factor V (FV) gene mutations G1691A (FV-Leiden) account for the majority of inherited APCR cases. An additional FV gene mutation, the A4074G (FV-HR2), was recently reported to induce a risk of VTE by some but not all groups. The aim of this study was to determine the prevalence of single and combined SNPs in 126 patients with documented deep venous thrombosis (DVT), and 197 control Tunisian subjects. The frequencies of FV-Leiden A allele (p <0.001; OR = 5.031), and HR2 G allele (p = 0.014; OR = 2.463) were significantly higher among DVT patients. Genotype differences were found between FV-Leiden G/A (p <0.001; OR = 3.936) and A/A (p = 0.013; OR = 11.529), but not HR2 A/G genotypes (p = 0.862; OR = 1.166), between patients and controls. While no linkage disequilibrium was noted between the FV 1691A and 4070G or A alleles, higher prevalence of the 1691G/4070G (p = 0.002; OR = 5.189) and the 1691A/4070A (p = 0.007; OR = 3.670) were noted among DVT patients than in control subjects. Collectively, this indicates that FV-Leiden, and to a lower extent HR2 haplotype, are important independent risk factors for DVT, and that their coinheritance does not increase significantly the DVT risk imparted by either.
Factor V-Leiden and HR2 Haplotype Allele and Genotype Analysis Cases Controls P OR Factor V-Leiden G 0.8492 0.9670 0.004 0.087 A 0.1508 0.0609 <0.001 5.031 G/G 0.754 0.939 <0.001 0.199 G/A 0.190 0.056 <0.001 3.936 A/A 0.056 0.005 0.013 11.529 HR2 Haplotype A 0.8913 0.9492 1.000 0.352 G 0.1087 0.0508 0.014 2.463 A/A 0.855 0.873 0.862 0.858 A/G 0.145 0.127 0.862 1.166 G/G 0.000 0.000
The Residual Risk of Transfusion-Transmitted HIV Infection in a Public Brazilian Blood Center.
Authors: Pinto Ana Cristina S. , Valente Vanderléia B. , Ubiali Eugênia Maria A. , Angulo Ivan L. , Covas Dimas T. 
Published: October 2019

Abstract
Estimating risks of transfusion-transmitted infections is essential for monitoring blood safety and for helping physicians and patients decide about the risks/benefits of an allogeneic transfusion. In 2000, the residual risk of HIV in our institution was estimated in 1/325,000 units transfused and the prevalence of HIV among all blood donors was 0.06%. The goal of this study was to calculate the current residual risk of transfusion-transmitted HIV infection in the Regional Blood Center of Ribeirão Preto, University of São Paulo, Brazil. We evaluated 292,587 repeated donations of a total of 403,568 donations between january/2002 and december/2005. During this period, we identified 43 seroconversions among the repeated donors. The serological tests performed were 2 different enzyme immunoassays (EIA): HIV 1/2 and a conjugated p24 antigen/antibody as screening tests and Western Blot as a confirmatory test for all positive samples. In order to calculate the residual risk, we used the incidence rate/window period (IR/WP) model, developed in parallel by investigators from the National Heart, Lung and Blood Institute-sponsored Retrovirus Epidemiology Donor Study (REDS), the CDC and the American Red Cross. The IR takes into account the number of incident cases (numerator), the total number of repeated donations and the mean interdonation interval length (multiplication of the last two entities provides the number of person-years at risk or denominator). The mean interdonation interval length can be substituted for the mean seroconversion interval length for all incident cases if the first one can not be accurately measured, so we used this alternative. Once the IR is known, we calculated the residual risk dividing the IR by 365.25 days and then multiplying by the WP of the test used (p24=15 days). Our results are: IR= 43 cases/292,587 repeated donations × 3.2 years = 4.59×10−5. The current residual risk is (IR/365.25 days) × 15 days= 1.5/million units transfused or 1/667,000 units. The prevalence of HIV among all blood donors in 2005 was 0.035%. Although we know that the correlation between prevalence and residual risk is not straightforward, they have a certain degree of correlation and they both have declined since 2000. During these last 5 years, we have made some modifications in our donor selection towards a more rigorous donor screening and since january/2002 we have introduced the p24 antigen/antibody EIA as part of the screening serological tests. We concluded that the more stringent donor risk factor screening and the introduction of the p24 antigen test have substantially reduced the residual risk of transfusion-transmitted HIV infection in our institution.