bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of CD4 by human hematopoietic progenitors [see comments]
Authors: Louache F , Debili N , Marandin A , Coulombel L , Vainchenker W 
Published: October 2019

Abstract
It has been recently reported that murine hematopoietic stem cells and progenitors express low levels of CD4. In this study, we have investigated by phenotypic and functional analysis whether the CD4 molecule was also present on human hematopoietic progenitors. Unfractionated marrow cells or immunomagnetic bead-purified CD34+ cells were analyzed by two-color fluorescence with an anti-CD4 and an anti- CD34 monoclonal antibody (MoAb). A large fraction (25% to 50%) of the CD34+ cells was weakly stained by anti-CD4 antibodies. Moreover, in further experiments analyzing the expression of CD4 in different subpopulations of CD34+ cells, we found that CD4 was predominantly expressed in phenotypically primitive cells (CD34+ CD38-/low CD71low Thy-1high, HLA-DR+/low). However, the presence of CD4 was not restricted to these primitive CD34+ cell subsets and was also detected in a smaller fraction of more mature CD34+ cells exhibiting differentiation markers. Among those, subsets with myelo-monocytic markers (CD13, CD33, CD14, and CD11b) have a higher CD4 expression than the erythroid or megakaryocytic subsets. In vitro functional analysis of the sorted CD34+ subsets in colony assays and long-term culture- initiating cell (LTC-IC) assays confirmed that clonogenic progenitors (colony-forming unit-granulocyte-macrophage, burst-forming unit- erythroid, and colony-forming unit-megakaryocyte) and LTC-IC were present in the CD4low population. However, most clonogenic progenitors were recovered in the CD4- subset, whereas the CD4low fraction was greatly enriched in LTC-IC. In addition, CD4low LTC-IC generated larger numbers of primitive clonogenic progenitors than did CD4- LTC-IC. These observations suggest that, in the progenitor compartment, the CD4 molecule is predominantly expressed on very early cells. The CD4 molecule present on CD34+ cells appeared identical to the T-cell molecule because it was recognized by three MoAbs recognizing different epitopes of the molecule. Furthermore, this CD4 molecule is also functional because the CD34+ CD4low cells are able to bind the human immunodeficiency virus (HIV) gp120. This observation might be relevant to the understanding of the mechanisms of HIV-induced cytopenias.
Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras
Authors: Kalra R , Paderanga DC , Olson K , Shannon KM 
Published: October 2019

Abstract
Children with neurofibromatosis, type 1 (NF-1) are at increased risk of developing malignant myeloid disorders and their bone marrows frequently show loss of the normal allele of the NF1 tumor-suppressor gene. NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. We used a genetic approach to test the hypothesis that NF1 negatively regulates myeloid cell growth through its effect on Ras. This model predicts that, if RAS mutations and loss of NF1 function deregulate myeloid growth by the same biomechanical mechanism, then activating RAS mutations will be restricted to children with malignant myeloid disorders who do not have NF-1. We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS. The incidence of RAS mutations was 21% (12 of 55) in patients without NF-1 and 0% (zero of 16) in children with NF-1 (P = .04). Among the 55 patients who did not have NF-1, we found RAS mutations in four of 27 with Mo 7, in five of 24 with JCML, in two of 3 with AML, and in a patient with myeloproliferative syndrome (MPS). These data from primary human cancer cells provide strong genetic evidence that NF1 limits the growth of myeloid cells by regulating Ras.
CD44 can mediate the adhesion of platelets to hyaluronan
Authors: Koshiishi I , Shizari M , Underhill CB 
Published: October 2019

Abstract
CD44 represents a family of glycoproteins that are present on the surfaces of some types of lymphocytes, macrophages, and epithelial cells. In the present study, we have found that CD44 is also present on murine megakaryocytes and peripheral blood platelets as judged by immunohistochemical staining. Western blotting of platelet proteins indicated that this CD44 was predominantly of the 85-kD form. This form of CD44 also had the capacity to bind hyaluronan, because detergent extracts of platelets as well as intact platelets could bind soluble [3H]hyaluronan, and this property was blocked by antibodies directed against CD44. More importantly, isolated platelets could attach to the hyaluronan-containing extracellular matrix produced by cultured rat fibrosarcoma cells. This attachment took place in the absence of divalent cations and could be blocked by pretreating the rat fibrosarcoma cells with hyaluronidase or by the addition of an antibody to CD44. These results suggested that CD44 was responsible for the attachment of platelets to hyaluronan. Histochemical staining also showed that hyaluronan was present immediately beneath the endothelial cells of many blood vessels of various tissues, such as the dermis, lamina propria of the intestinal tract, the lungs, and the pericardium. Thus, it is possible that CD44 plays an important role in the attachment of platelets to the surface of exposed connective tissue after injury to endothelial cells.
Progesterone-associated endometrial protein--a constitutive marker of human erythroid precursors
Authors: Kamarainen M , Riittinen L , Seppala M , Palotie A , Andersson LC 
Published: October 2019

Abstract
Progesterone-associated endometrial protein (PAEP/PP14) is a 28-kD glycoprotein with sequence homology to beta-lactoglobulins containing a retinol-binding motif. PAEP/PP14 is present at nanomolar concentrations in human serum. It is produced by secretory and decidualized endometrium in women and by seminal vesicle epithelium in men. We report here that PAEP mRNA is constitutively expressed in normal hematopoietic tissue. Western immunoblotting of bone marrow cells with rabbit antibodies to PAEP gave a band at 28 kD, and immunocytochemical staining with monoclonal antibodies localized PAEP into the cytoplasm of erythroid precursors representing different stages of the normoblast series. PAEP was not detected in mature red blood cells, platelets, or in cells of the myeloid lineage. Untreated K562 leukemia cells did not contain PAEP, whereas treatment of the cells with tetradecanoylphorbol acetate (TPA) induced strong expression of PAEP mRNA and synthesis of the intact protein that was found both in the cytoplasm of the differentiating cells and in the supernatant of TPA-treated cultures. These findings add a new member to the growing family of genes that are constitutively expressed both in the reproductive tract and in the hematopoietic system.
Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line
Authors: Hooper WC , Phillips DJ , Ribeiro MJ , Benson JM , George VG , Ades EW , Evatt BL 
Published: October 2019

Abstract
Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.
Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels
Authors: Mikkola H , Syrjala M , Rasi V , Vahtera E , Hamalainen E , Peltonen L , Palotie A 
Published: October 2019

Abstract
Congenital deficiency in coagulation factor XIII is a rare autosomal recessive bleeding disorder. Although the defect was characterized over 30 years ago, little is known about the molecular basis of the disorder. Here, we show two novel point mutations in the gene of the A- subunit of factor XIII in the genetically isolated population of Finland. All eight factor XIII-deficient families identified in Finland were studied. The exons of the gene of A-subunit were amplified individually by polymerase chain reaction and subsequently screened by single-strand conformation polymorphism. Sequence analysis of the abnormally migrating fragments showed two point mutations resulting in an amino acid alteration. A C-to-T transition at Arg-661 in exon XIV created a premature stop codon. This mutation was detected in six of the eight families, thus being the major alteration causing FXIII deficiency in Finland. In two of the six families, the patients were compound heterozygotes with the Arg-661-Stop mutation in one allele and either a T-to-C point mutation in exon VI or a thus far uncharacterized mutation in the other allele. The T-to-C transition in exon VI resulted in a substitution of threonine for methionine 242. The transition was found in one family only, where it was in the heterozygote form combined with the Arg-661-Stop mutation. To evaluate the consequences of these mutations, steady-state FXIII mRNA levels were quantitated by solid-phase minisequencing. In addition to the termination of translation 70 amino acids before the initial stop codon, the Arg-661- Stop mutation causes a 10- to 30-fold reduction in FXIII mRNA levels. This is also likely to result in a low translation level in the truncated polypeptide. In contrast, Met-242-Thr mutation does not seem to affect the level of mRNA. Here, the absence of a functional and immunodetectable protein is probably caused by an altered conformation of the mutant polypeptide, resulting in early degradation of the defective protein.
Regulation of stimulated integrin surface expression in human neutrophils by tyrosine phosphorylation
Authors: Naccache PH , Jean N , Liao NW , Bator JM , McColl SR , Kubes P 
Published: October 2019

Abstract
The control of the adhesive properties of human neutrophils is an essential element of their defense function. One level at which this control is exerted involves the upregulation of the surface expression of beta 2-integrins. In this study, we have examined the potential involvement of tyrosine phosphorylation in the latter process. Two inhibitors of tyrosine kinases with differing modes of action, erbstatin and herbimycin A, were found to inhibit the expression of CD11b and CD18 stimulated by chemotactic factors (fMet-Leu-Phe or leukotriene B4) or growth factors (tumor necrosis factor alpha). This inhibition was not shared by an inactive analog of erbstatin or by the protein kinase C inhibitor Ro 31–8330. Erbstatin also inhibited the unveiling of activation-specific neoepitopes detected by antibody CBRM1/5. Pretreatment of neutrophils (but not of endothelial cells) with erbstatin inhibited the stimulation of neutrophils' adherence to endothelial cells induced by fMet-Leu-Phe. Augmentation of tyrosine phosphorylation by inhibiting tyrosine phosphatases using hydroperoxyvanadate led to an increased surface expression of CD11b and CD18 and enhanced the adhesion of neutrophils to endothelial cells. Finally, the leumedin NPC 15669, which had previously been shown to inhibit stimulated CD11b expression and neutrophil adherence to endothelial cells and to exhibit anti-inflammatory properties in various in vivo models of inflammation, inhibited the stimulation of tyrosine, phosphorylation induced by fMet-Leu-Phe. Taken together, these data establish a strong correlation between tyrosine phosphorylation and integrin upregulation in stimulated human neutrophils.
The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease
Authors: Castro O , Brambilla DJ , Thorington B , Reindorf CA , Scott RB , Gillette P , Vera JC , Levy PS 
Published: October 2019

Abstract
The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within- person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.
Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation
Authors: Ljungman P , Lewensohn-Fuchs I , Hammarstrom V , Aschan J , Brandt L , Bolme P , Lonnqvist B , Johansson N , Ringden O , Gahrton G 
Published: October 2019

Abstract
A total of 124 patients who had survived at least 2 years after allogeneic bone marrow transplantation (BMT) were studied. Serum was collected at least once yearly. IgG antibodies were determined by enzyme-linked immunosorbent assay for measles and mumps. Rubella antibodies were analyzed by radial hemolysis. Antibody levels were interpreted as representing immunity, seronegativity, or seropositivity, but with uncertain immunity. The median follow-up of the patients was 6.5 years (range, 2 to 13.5 years). The calculated probabilities of being immune to measles at 3, 5, and 7 years from BMT were 47%, 27%, and 20%, respectively. The corresponding probabilities for mumps were 37%, 12%, and 6%, respectively; and for rubella, 47%, 33%, and 28%, respectively. The probabilities for being seronegative for measles, mumps, and rubella at 5 years after BMT were 60%, 73%, and 52%, respectively. When compared with those patients who had experienced previous natural measles disease (P < .05), the only factor that was important for immunity to measles after BMT was whether the patient had been immunized before BMT. There was no influence of donor seropositivity on the probability of becoming seronegative to mumps during follow-up. We conclude that most allogeneic patients will become seronegative to measles, mumps, and rubella during follow-up. Therefore, long-term B-cell memory function is not maintained, regardless of the immune status of the donor.
Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail
Authors: Ghetie MA , Tucker K , Richardson J , Uhr JW , Vitetta ES 
Published: October 2019

Abstract
Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia.
Hodgkin's disease with a B-cell phenotype often shows a VDJ rearrangement and somatic mutations in the VH genes
Authors: Tamaru J , Hummel M , Zemlin M , Kalvelage B , Stein H 
Published: October 2019

Abstract
The nature of Hodgkin and Reed-Sternberg (HRS) cells remains in question. Immunophenotypic studies favor a relation to the lymphoid lineage with the existence of B- and T-cell types. However, studies on the detection of antigen (Ag) receptor gene rearrangements provided inconsistent results. They concur in that rearranged Ig and T-cell receptor (TCR) genes are not demonstrable in most Hodgkin's disease (HD) cases. To clarify whether this is because of the insensitivity of the method of detection or a real absence of clonal Ig heavy chain (IgH) rearrangements, a polymerase chain reaction (PCR) method with high sensitivity was applied, allowing the detection of less than 50 cells with clonally rearranged IgH genes in a mixture of 100,000 germline or individually rearranged cells. In 67 cases of HD, most of those (67%) with B-Ag+ HRS cells express clonal VDJ rearrangements of the IgH gene. No cases with T-cell Ag+ HRS cells harbored detectable clonal VDJ rearrangements. Of 10 sequenced rearranged IgH genes, the VH segment of six contained considerable somatic mutations. These results suggest that the demonstrated VDJ rearrangements stem from the HRS cells themselves and that the HRS cells of cases with rearranged IgH genes are B-cell related and correspond in their differentiation stage either to naive pregerminal center B cells or (more commonly) to germinal center/postgerminal center-derived memory B cells.
Identification of new mutations in two phosphoglycerate kinase (PGK) variants expressing different clinical syndromes: PGK Creteil and PGK Amiens
Authors: Cohen-Solal M , Valentin C , Plassa F , Guillemin G , Danze F , Jaisson F , Rosa R 
Published: October 2019

Abstract
Phosphoglycerate kinase (PGK) deficiency is generally associated with chronic hemolytic anemia, although it can be accompanied by either mental retardation or muscular disease. Genomic DNAs of two PGK- deficient patients previously described in France were sequenced directly after polymerase chain reaction amplification. The PGK Creteil variant arises from a G-->A nucleotide interchange at position 1022 in cDNA (exon 9), resulting in amino acid substitution 314 Asp-->Asn in the C-terminal domain, which contains the nucleotide binding site. It is associated with rhabdomyolysis crises but not with hemolysis or mental retardation. In the other case, which is associated with chronic hemolytic anemia and mental retardation (PGK Amiens), an A-->T nucleotide interchange was found at position 571 in cDNA (exon 5); this leads to amino acid substitution 163 Asp-->Val in the N-terminal domain, which contains the catalytic site for phosphoglycerate binding. These results corroborate the kinetic data observed. In the two cases, the mutations are distinct from others previously reported and no significant relationship could be observed between the location of the amino acid substitution and its clinical consequences.
Normal cations and abnormal membrane lipids in the red blood cells of dogs with familial stomatocytosis-hypertrophic gastritis
Authors: Slappendel RJ , Renooij W , de Bruijne JJ 
Published: October 2019

Abstract
Examination of the red blood cells (RBCs) of eight dogs with familial stomatocytosis-hypertrophic gastritis (FS-HG), a multiorgan disease associated with hemolytic anemia, hereditary stomatocytosis (HSt), and hypertrophic gastritis resembling Menetrier's disease in man, showed abnormal osmotic fragility, normal mean corpuscular volume, slightly increased cell water, and normal cation content and cation fluxes. Cholesterol was decreased in RBC and increased in plasma. In both RBCs and plasma, total phospholipid (PL) was normal, phosphatidylcholine (PC) decreased, and sphingomyelin increased. The palmitic acid content of PC was increased, and the stearic acid content of PC was decreased. Sodium dodecyl sulfate electrophoresis of RBC membrane proteins was normal. These findings have not been described previously in HSt. They suggest that in FS-HG, abnormal composition of the PL in RBCs secondary to abnormal PL in plasma causes defective membrane function and stomatocytic shape-change. This conclusion was supported by a shortened half-life of 51Cr-labeled RBCs from normal dogs after transfusion in dogs with FS-HG. It was concluded (1) that not all hereditary forms of stomatocytosis are necessarily associated with an intrinsic structural defect of the RBC membrane, but that the change in shape of RBC may also be induced by abnormal composition of the plasma; (2) that stomatocytosis may be caused by loss of membrane surface area rather than by the increased cation uptake such as has been shown in some human kindreds with HSt, (3) that FS-HG is a disorder of lipid metabolism, and by consequence, (4) that abnormal lipid metabolism might be involved in the pathogenesis of Menetrier's disease.