bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forssman glycosphingolipid as an immunohistochemical marker for mouse stromal macrophages in hematopoietic foci
Authors: Sadahira Y , Mori M , Awai M , Watarai S , Yasuda T 
Published: October 2019

Abstract
The immunohistochemical distribution of Forssman glycosphingolipid (GSL) in mouse hematopoietic tissue was examined by using light and electron microscopic immunoperoxidase methods with a highly specific rabbit anti-Forssman GSL antibody. Bone marrow, splenic red pulp, and thymic macrophages, which are closely associated with hematopoietic cells, were stained by the antibody, whereas hematopoietic cells, circulating cells, alveolar macrophages, Kupffer cells, peritoneal resident macrophages, and macrophages derived from granulocyte- macrophage colony-forming units cultured in the presence of L-cell- conditioned medium were not stained. In addition, thymic cortical epithelial cells, the framework of reticular cells of the cortical and medullary regions of the mesenteric lymph node and periarterial lymphoid sheath of the spleen, and some vessels of the tissues examined were also stained. After phlebotomy, the fine cytoplasmic processes of Forssman-positive splenic red pulp macrophages were distributed extensively throughout the erythroid colonies. On the other hand, after hypertransfusion, these macrophages retracted their processes, became round, and tended to aggregate. These results indicate that Forssman GSL can be used as an immunohistochemical marker for stromal macrophages in the hematopoietic foci of the bone marrow and splenic red pulp.
A second BamHI DNA polymorphism and haplotype association in the factor IX gene
Authors: Driscoll MC , Dispenzieri A , Tobias E , Miller CH , Aledort LM 
Published: October 2019

Abstract
A second BamHI DNA polymorphism has been identified in the factor IX gene in an American black population at an allelic frequency of 0.13. This site has been localized within 500 basepairs (bp) 5′ to the XmnI intron 3 polymorphic site and increases the heterozygosity of black females at the factor IX gene locus. In addition, haplotype analysis of factor IX genes at five polymorphic loci indicates that although there is conservation of sequences between the races, factor IX genes show more heterogeneity in an American black population and thus more heterozygosity is observed in black females compared with whites. This increased heterogeneity is due to DNA polymorphisms unique to black populations and to linkage equilibrium between the most 5′ and 3′ polymorphic sites in factor IX genes in blacks.
Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C)
Authors: Hill AV , Bowden DK , O'Shaughnessy DF , Weatherall DJ , Clegg JB 
Published: October 2019

Abstract
Data on the distribution of beta thalassemia among over 6,000 Melanesians reveals a major difference in the carrier rates between populations in the malarious coastal regions of New Guinea and those living in the historically malaria-free Highlands. The island of Maewo in Vanuatu has a particularly high incidence of beta + thalassemia associated with a single restriction enzyme haplotype. Direct cloning into a plasmid vector and sequence analysis demonstrate that the mutation is a G to C transversion at position 5 of intron 1 of the beta- globin gene. Oligonucleotide probe surveys indicate that this variant accounted for all cases of beta thalassemia studied from Maewo. It is also common in coastal Papua New Guinea where haplotype and oligonucleotide probe data suggest that the molecular basis of beta thalassmia is more heterogeneous.
Rheologic impairment of sickle RBCs induced by repetitive cycles of deoxygenation-reoxygenation
Authors: Nash GB , Johnson CS , Meiselman HJ 
Published: October 2019

Abstract
The transformation of less-dense, discoidal homozygous sickle cells (HbSS) RBCs into dehydrated, rheologically impaired cells is believed to be an important factor in the pathophysiology of sickle cell disease. We investigated this process by subjecting the less-dense fraction of HbSS RBCs, which contains a low percentage of irreversibly sickled cells (ISCs), to cyclic deoxygenation-reoxygenation for 15 hours at 37 degrees C. This incubation procedure caused cell shrinkage, shifts in intracellular Na and K content, and formation of ISCs that closely resembled endogenous ISCs found in sickle blood. The viscoelasticity of the treated cells was tested using micropipette techniques to measure the membrane shear elastic modulus (mu) and the time constant for extensional shape recovery (tc); mu represents the “static rigidity” of the cells, and the product mu.tc was taken as a measure of their “dynamic rigidity”. Density separation of the incubated cells showed that their rheologic impairment (ie, elevation of both static and dynamic rigidities) paralleled cellular dehydration and that the newly formed dense cells had viscoelastic characteristics very similar to those of endogenous dense cells. Rehydration by osmotic swelling tended to normalize the dynamic rigidities of dense cells but had no significant effect on their static rigidities. Thus, cellular dehydration contributes to the observed changes of viscoelasticity, although an irreversible alteration of membrane structure also appears to be involved. Dense ISCs could be formed without added calcium, implying that entry of external calcium is not an essential requirement for cellular dehydration; ISCs formed without calcium tended to be less rigid (ie, to have lower static and dynamic rigidities) than those formed with calcium. Our results indicate that the cyclic incubation procedure closely mimics RBC rheologic deterioration in vivo and thus suggest its usefulness as a model for investigating this phenomenon.
Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia
Authors: Huang ME , Ye YC , Chen SR , Chai JR , Lu JX , Zhoa L , Gu LJ , Wang ZY 
Published: October 2019

Abstract
Twenty-four patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (45 to 100 mg/m2/day). Of these, eight cases had been either nonresponsive or resistant to previous chemotherapy; the other 16 cases were previously untreated. All patients attained complete remission without developing bone marrow hypoplasia. Bone marrow suspension cultures were studied in 15 of the 24 patients. Fourteen of these patients had morphological maturation in response to the retinoic acid (1 mumol/L). Chloroacetate esterase and alpha-naphthyl acetate esterase staining as well as electronmicroscopic examination confirmed that retinoic acid-induced cells differentiated to granulocytes with increased functional maturation (as measured by nitroblue tetrazolium reduction, NBT). The single nonresponder to retinoic acid in vitro was resistant to treatment with retinoic acid but attained complete remission after addition of low-dose cytosine arabinoside (ara-C). During the course of therapy, none of the patients showed any abnormalities in the coagulation parameters we measured, suggesting an absence of any subclinical disseminated intravascular coagulation. The only side effects consisted of mild dryness of the lips and skin, with occasional headaches and digestive symptoms. Eight patients have relapsed after 2 to 5 months of complete remission. The others remain in complete remission at 1+ to 11+ months and are still being followed up. We conclude that all-trans retinoic acid is an effective inducer for attaining complete remission in APL.
Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17
Authors: Rosa JP , Bray PF , Gayet O , Johnston GI , Cook RG , Jackson KW , Shuman MA , McEver RP 
Published: October 2019

Abstract
Platelet aggregation requires the binding of adhesive proteins such as fibrinogen to the heterodimer of membrane glycoproteins IIb (GPIIb) and IIIa (GPIIIa). Human erythroleukemia (HEL) cells synthesize both GPIIb and GPIIIa. Using poly(A+) RNA purified from HEL cells, we constructed a cDNA library in the lambda gt10 phage vector. This library was screened with a 38mer oligonucleotide derived from a platelet GPIIIa peptide, and three overlapping cDNAs were isolated. The three inserts encompassed 3.5 kilobases (kb), including the entire coding region of mature GPIIIa (2,286 basepairs, bp) and 1.3 kb of 3′ untranslated sequence. All 222 residues determined directly from platelet GPIIIa tryptic peptides exactly matched the HEL cell-deduced amino acid sequence. The HEL cell sequence matched a previously reported endothelial cell cDNA sequence except for eight nucleotides. Five of these nucleotide differences were silent changes consistent with genetic polymorphisms. The other three differences resulted in changes in the deduced amino acid sequence of GPIIIa; reexamination of the endothelial cell cDNA sequence in these three areas revealed that it is actually identical to the HEL cell sequence. The virtual identity of the endothelial and HEL cell cDNA sequences provides direct evidence that GPIIIa is a subunit common to cell-adhesion receptors present in more than one cell type. We localized the gene for GPIIIa to chromosome 17, the same chromosome to which we had previously mapped the gene for GPIIb.
High-resolution analysis of the human gamma-globin gene promoter in K562 erythroleukemia cell chromatin
Authors: Gimble JM , Max EE , Ley TJ 
Published: October 2019

Abstract
We performed high-resolution mapping studies of the DNAse I- hypersensitive sites located just 5′ to the human G gamma- and A gamma- globin genes of K562 erythroleukemia cells, in which these genes are constitutively expressed at low levels. This analysis revealed that the hypersensitive site extends from approximately -210 +/- 5 to -25 +/- 5 base pairs (bp) upstream from the transcription initiation site. Within this region, a GC-rich region located between the proximal CCAAT box and the TATA box is particularly accessible to nuclease digestion; however, the 5′ end of the hypersensitive site is less accessible to nucleases. The pattern of DNAse I cleavage does not change on either strand with hemin induction of K562 cells, which increases the rate of gamma-globin gene transcription about threefold. The region within the hypersensitive site includes all the consensus promoter elements of the gamma-globin genes as well as an octamer sequence located between -182 and -175, and a region associated with a variety of mutations that may cause hereditary persistence of fetal hemoglobin (HPFH).
Interferon alpha-2b as therapy for Ph'-positive chronic myelogenous leukemia: a study of 82 patients treated with intermittent or daily administration
Authors: Alimena G , Morra E , Lazzarino M , Liberati AM , Montefusco E , Inverardi D , Bernasconi P , Mancini M , Donti E , Grignani F 
Published: October 2019

Abstract
The authors treated a total of 82 patients with Ph′-positive chronic myelogenous leukemia (CML) with recombinant interferon alpha-2b (IFN alpha-2b). Sixty-five patients in chronic phase (CP), 28 of whom were untreated and 37 pretreated, and nine patients in accelerated phase (AP), were started on IFN three times a week. Patients in CP were randomized to receive 2 or 5 X 10(6) IU/m2, while patients in AP were all given the dose of 5 X 10(6) IU/m2, in addition to concomitant chemotherapy. Patients in CP who were unresponsive to the lower dose were crossed to the higher dose. Of 63 evaluable patients in CP, 43 (68%) responded, 29 (46%) achieved complete hematologic response (CHR), and 14 (22%) achieved partial hematologic response (PHR). The response rate appeared to be significantly influenced by the IFN dose in pretreated patients. Of the nine patients in AP, two attained PHR and one CHR. More recently, eight previously untreated CP cases were submitted to daily IFN administration at doses from 2 to 5 X 10(6) IU/m2. This daily schedule was also applied to patients who had obtained, with the intermittent treatment, a PHR persisting unmodified for six months (nine patients) or an unstable CHR (five patients). Seven of the eight previously untreated patients, and five of the nine PHR patients crossed to daily IFN reached CHR. In the total series of previously untreated patients, the response rate proved to be significantly influenced by the initial risk status. Cytogenetic improvement was seen in 37 of 53 responders (70%) treated for more than 3 months, the median of Ph′-positive cells declining from 100% to 65% (range 0% to 95%). Complete suppression of Ph′ chromosome was observed in one case. The cytogenetic response was persistent for over 6 months in 21 patients, but the lowest value of Ph′ positivity was usually unstable. At a median follow-up of 56 weeks, 23 of 36 (64%) CHR patients remain in continued disease control with IFN. A blastic transformation (BT) occurred in seven of 21 unresponsive patients and in one of the 36 CHR patients. The authors' data confirm that IFN alpha- 2b, especially at daily doses, is effective in inducing clinical and cytogenetic response in a good proportion of patients with CML in the benign phase. Longer follow-ups will define the exact influence of this agent on the natural course of the disease.
The human T-cell V gamma gene locus: cloning of new segments and study of V gamma rearrangements in neoplastic T and B cells
Authors: Chen Z , Font MP , Loiseau P , Bories JC , Degos L , Lefranc MP , Sigaux F 
Published: October 2019

Abstract
The authors have analyzed the involvement of V gamma and J gamma segments in TRG gamma rearrangement from a series of 40 acute lymphoblastic leukemia (ALL), including 25 T- and 15 B-lineage cases, in which TRG gamma are rearranged. Sixty-five rearranged alleles were studied. The authors first describe the cloning and sequencing of two variable segments, V gamma 11 and psi V gamma 12, which rearrange in T- and B-neoplastic cells. To date three subgroups of translatable V gamma segments have been described. The authors show that V gamma 11 is the unique member of a new fourth V gamma subgroup that also rearranges in normal polyclonal T cells and that psi V gamma 12 is located at 5- kilobase (kb) downstream to V gamma 11. As shown by DNA sequence analysis, V gamma 11 shares a 60% homology with V gamma 10 (third subgroup) and a 50% homology with V gamma 9 (second subgroup) but no appreciable homology with the V gamma segments from the first family. In contrast to psi V gamma 12, V gamma 11 is translatable. In this paper the authors have also attempted to determine which V gamma segments were rearranged in the ALL cases by hybridization with a J gamma probe and genomic probes specific of the four subgroups. In the 54 instances in which the rearrangement was consistent with J gamma 1 or J gamma 2 involvement, the authors have identified the corresponding V gamma segments and have not found any other rearrangements suggestive of the existence of further V regions. The V gamma segments, belonging to the first subgroup, were the most frequently used (41 alleles). V gamma 9, V gamma 10, V gamma 11, and psi V gamma 12 were found rearranged in cases 3, 4, 5, and 1, respectively. No cases using the pseudo psi V gamma 1, psi V gamma 5, and psi V gamma 6 segments were found. Pseudo V gamma segments were not found rearranged in T cells, while V gamma 2 and V gamma 4, segments are frequently used. In contrast to the V gamma I gene rearrangement, the involvement of the V gamma II, V gamma III, and V gamma IV subgroups was most frequently observed in T-ALL with stage II differentiation (CD7+, CD4+, and/or CD8+, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-) and stage III (CD7+, CD4+/-CD8+/-CD3+).(ABSTRACT TRUNCATED AT 400 WORDS)
Serum levels of CD8 antigen in childhood lymphoid malignancies: a possible indicator of increased suppressor cell activity in poor-risk patients
Authors: Pui CH , Ip SH , Dodge RK , Carrabis S , Brown M , Crist WM , Berard CW , Kung P , Dahl GV , Murphy SB 
Published: October 2019

Abstract
Serum concentrations of CD8 antigen were measured at diagnosis with an enzyme-linked immunoassay in children with acute lymphoblastic leukemia (n = 344) or non-Hodgkin's lymphoma (n = 65). All patients had detectable levels of the serum antigen, which in its soluble nonreduced form appeared to be a 52-Kd homodimer as compared with the 66-Kd surface membrane component on most thymocytes and on a subset of functionally distinct T cells (suppressor/cytotoxic). Increased serum levels of CD8 in leukemia patients were significantly related to recognized high-risk prognostic features: high leukocyte count, large liver and spleen size, high serum lactic dehydrogenase level, T-cell immunophenotype, presence of a mediastinal mass, pseudodiploid karyotype, DNA index less than 1.16, and chromosomal translocation. Children with serum CD8 levels greater than or equal to 450 U/mL were more likely to fail treatment than were those with lower levels (P = .002), even in the group with non-T-cell leukemia (P = .003). In a multivariate analysis, serum CD8 antigen contributed independent prognostic information beyond that conveyed by age, leukocyte count, and race (P = .02). High serum CD8 antigen levels also correlated with advanced stages of disease in children with non-Hodgkin's lymphoma or B- cell leukemia. Children with higher serum CD8 antigen levels (greater than or equal to 700 U/mL) had a poorer treatment outcome (P = .003), even after results were adjusted for disease stage and serum lactic dehydrogenase level (P = .05). Measurement of serum levels of CD8 antigen not only has important prognostic value in childhood lymphoid malignancies but also could be useful in assessing the immunoregulatory role of T cells in patients with cancer.
2-Chlorodeoxyadenosine: an effective new agent for the treatment of chronic lymphocytic leukemia
Authors: Piro LD , Carrera CJ , Beutler E , Carson DA 
Published: October 2019

Abstract
2-Chlorodeoxyadenosine, a new lymphocyte-selective, anti-neoplastic drug was administered to 18 patients with advanced chronic lymphocytic leukemia of B-cell origin. All patients were resistant to conventional treatment. A total of 44 courses of 2-chlorodeoxyadenosine were completed with minimal toxicity. An overall response rate of 55% was achieved with four of 18 patients demonstrating partial response and six of 18 patients experiencing clinical improvement. Only minor bone marrow suppression occurred during administration of the drug, indicating a high degree of lymphocyte selectivity. Reduction of lymphocyte infiltration in bone marrow occurred in treated patients including one patient who experienced normalization of the bone marrow. Three of four patients with concurrent autoimmune hemolytic anemia experienced resolution of hemolysis, as indicated by elimination of transfusion requirement, fall in reticulocyte count, elevation of hemoglobin, and ability to taper prednisone without recurrence of hemolysis. Duration of responses ranged from 2 to 15 months without maintenance therapy.
The putative factor IX gene promoter in hemophilia B Leyden
Authors: Reitsma PH , Bertina RM , Ploos van Amstel JK , Riemens A , Briet E 
Published: October 2019

Abstract
Hemophilia B Leyden is characterized by low levels of factor IX antigen and activity before the age of 15, whereas after puberty factor IX levels rise at a rate of about 5% per year. A single base substitution (-A----T) at position -20 was identified in the putative promoter of the gene cloned from a patient with hemophilia B Leyden. This nucleotide change was confirmed in a second patient from the same pedigree and was also found in a patient from a second Dutch pedigree with the same hemophilic phenotype. The results indicate that the two Dutch kindreds are related and point to the functional significance of the -20 position for the expression of the human factor IX gene.
Treatment with monocyte-derived partially purified GM-CSF but not G-CSF aborts the development of transplanted chloroleukemia in rats
Authors: Jimenez JJ , Yunis AA 
Published: October 2019

Abstract
We have previously demonstrated that cultured rat chloroleukemia cells, MIA C51, will terminally differentiate to macrophages when treated with rat lung-conditioned medium in vitro and in vivo. In the present study we fractionated rat monocyte-conditioned medium by ultrafiltration according to molecular size. The fraction with molecular weight (mol wt) 30 to 50 Kd containing partially purified granulocyte-macrophage colony-stimulating factor (GM-CSF) activity caused the differentiation of C51 cells to macrophages in vitro and in diffusion chambers in vivo. Treatment of young rats with this fraction aborted the development of chloroleukemia from transplanted C51 cells. In contrast, the fraction with mol wt 10 to 30 Kd containing virtually all the G-CSF activity exhibited no differentiation activity either in vitro or in vivo. It is concluded that in this rat myelogenous leukemia model partially purified GM-CSF but not G-CSF contains the effector molecule(s) causing terminal differentiation of C51 cells and tumor cell rejection.
Release of C8 binding protein (C8bp) from the cell membrane by phosphatidylinositol-specific phospholipase C
Authors: Hansch GM , Weller PF , Nicholson-Weller A 
Published: October 2019

Abstract
Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) are abnormally sensitive to complement. Two membrane proteins, the C8 binding protein (C8bp) and the decay accelerating factor (DAF), which are expressed on normal cells, function to restrict lysis by homologous complement, and both of these proteins are absent from PNH erythrocytes. DAF is anchored to the plasma membrane on normal cells by a phosphatidylinositol linkage. The investigators found that a purified phosphatidylinositol-specific phospholipase C cleaved C8bp from the surface of normal lymphocytes and monocytes. This finding indicates that the abnormal complement sensitivity of PNH erythrocytes arises from a common defect, the inability to attach the phosphatidylinositol- containing anchor that is necessary for the membrane expression of both membrane complement regulatory proteins, the C8bp, and DAF.
Effect of alpha-interferon therapy on bone marrow fibrosis in hairy cell leukemia
Authors: Laughlin M , Islam A , Barcos M , Meade P , Ozer H , Gavigan M , Henderson E , Han T 
Published: October 2019

Abstract
Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha- IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.