bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benign monoclonal B cell lymphocytosis--a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients
Authors: Han T , Ozer H , Gavigan M , Gajera R , Minowada J , Bloom ML , Sadamori N , Sandberg AA , Gomez GA , Henderson ES 
Published: October 2019

Abstract
From 1951 through 1978, we have seen 20 cases of stage O chronic lymphocytic leukemia (CLL) without disease progression for 6.5–24 years. The cohort included 7 males and 13 females, aged 48–77 years at the time of diagnosis. None presented with anemia, thrombocytopenia, or neutropenia nor developed cytopenias during follow-up. Mean total lymphocyte count in these patients was 20,100/microL, with ranges from 10,000 to 43,700 at the time of diagnosis, and was 20,600, with ranges from 1,000 to 47,200, at last follow-up. Of 12 patients studied, 8 and 4 were phenotyped as heavy chain mu delta- and mu-type, respectively, with 7 kappa- and 4 gamma-type (no light chain was detectable in one patient). Of 13 patients studied, one had a slightly elevated IgG level and two had slightly depressed serum IgA and IgM levels. All patients had positive delayed hypersensitivity responses to at least one of five skin test antigens. Each of seven patients studied for an in vitro leukocyte thymidine uptake had a low level of [3H]thymidine incorporation. Nine of 12 patients studied had elevated total T cells, and the remaining 3 had normal T cell counts. In vitro unseparated lymphocyte response to phytohemagglutinin showed normal kinetics of DNA synthesis, with a peak response on day 3 or 4 of culture in 4 and slightly or moderately depressed and/or delayed kinetics in 8 patients studied. Cytogenetic analyses by Q- or G-banding techniques of polyclonal B cell mitogen-stimulated lymphocytes in all six patients studied showed normal karyotypes. These data are consistent with a previously undescribed syndrome involving a monoclonal B cell lymphocytosis, a prolonged asymptomatic or benign clinical course, and essentially normal humoral and cellular immunity and normal karyotype. Our observations indicate that these 20 patients with stage O CLL have a benign clinical course and that they may also be designated as benign monoclonal B cell lymphocytosis ( BMBL ), a benign variant of CLL.
Subpopulation heterogeneity in human acute myeloid leukemia determined by monoclonal antibodies
Authors: Pessano S , Palumbo A , Ferrero D , Pagliardi GL , Bottero L , Lai SK , Meo P , Carter C , Hubbell H , Lange B 
Published: October 2019

Abstract
The leukemic population in 63 patients with acute myeloid leukemia (AML) was studied with 15 monoclonal antibodies that detect lineage- related and stage-related antigens on normal hemopoietic cells. Indirect immunofluorescence and fluorescence-activated cell sorting showed that subpopulations of leukemic cells reacted with some or all antibodies, but the percentage of cells reacting with a single antibody varied widely among patients. The composite antigenic phenotype of the various cases, as determined by immunofluorescence assay, did not correlate with the French-American-British morphological classification. Furthermore, some cells in each case failed to express any antigen normally expressed on myelomonocytic precursors from the level of the early CFU-GM to the mature granulocyte or monocyte. In double-fluorescence experiments, the individual cells expressed none, one, or both antigens. These results demonstrate that there is considerable subpopulation heterogeneity in AML. This heterogeneity may considerably limit or complicate the use of monoclonal antibodies for diagnosis, prognosis, and treatment of acute nonlymphocytic leukemia (ANLL).
Human large granular lymphocytes and their relationship to natural killer cell activity in various disease states
Authors: Gastl G , Niederwieser D , Marth C , Huber H , Egg D , Schuler G , Margreiter R , Braunsteiner H , Huber C 
Published: October 2019

Abstract
This study investigated the numbers of large granular lymphocytes (LGL) and their relationship to natural killer (NK) function, as assessed by their capacity to lyse the human tumor target, K562. Peripheral blood mononuclear cells from 42 normal controls and from 171 patients suffering from various nonmalignant or malignant diseases were evaluated. Also studied were samples from a patient undergoing autologous bone marrow reconstitution following total body irradiation. Results suggested the existence of a close relationship between the numbers of LGL and the capacity to lyse K562 targets, further supporting the view that LGL are crucial effector cells mediating NK lysis. In certain diseases, such as malignant states, functional capacity was not simply determined by the numbers of LGL. Here preferential reduction of the capacity to lyse K562 targets was observed, indicating that additional limiting factors are involved in the determination of the cytotoxic potential. Based on the relationship between LGL and natural immune functions, as well as on the identification of leukemias affecting this cell type, we would recommend their evaluation on a large scale clinical basis.
The treatment of malignant histiocytosis
Authors: Tseng A Jr , Coleman CN , Cox RS , Colby TV , Turner RR , Horning SJ , Rosenberg SA 
Published: October 2019

Abstract
Twenty-four consecutive cases of malignant histiocytosis (MH) treated at Stanford Medical Center between 1973 and 1983 have been reviewed. Most patients presented with systemic symptoms (91%) and advanced disease (stage IV, 80%). Multiple organ involvement was common. In six cases, pathologic tissue was further characterized by frozen section immune histochemistry, using a panel of monoclonal antibodies known to react with monocytes and macrophages, as well as a variety of hematopoietic cells. One case expressed a mature monocyte/macrophage phenotype; three cases were considered null cell or primitive lesions; and two cases were identified as probable T cell lymphomas. Seven patients underwent splenectomy. Two patients died prior to any treatment. Twenty-two patients were treated with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) +/- bleomycin (B), +/- midcycle high-dose methotrexate (HD-MTX) with leucovorin rescue. Seven patients received prophylactic intrathecal MTX. Of 22 evaluable patients, there was a 68% complete response rate (CR), a 23% partial response rate (PR), and a 9% no response rate (NR). Median duration of CR was 30+ months; median duration of PR was 2.4 months. Median survival for patients attaining a CR has not been reached v 3 months for the PR and NR groups. For all 24 patients, median survival was 2 years, with a 5-year actuarial survival of 40%. Multivariate analysis revealed that a platelet count less than 150,000 (P Cox = .005) and the dose of drug delivered (P Cox = .057) were the most important prognostic factors. Prophylactic intrathecal MTX therapy and splenectomy did not influence survival. Although MH is an aggressive disease with a poor prognosis, it is potentially curable. Systematic and aggressive treatment should further improve the outcome.
Erythroid progenitors in adult chronic pure red cell aplasia: relationship of in vitro erythroid colonies to therapeutic response
Authors: Lacombe C , Casadevall N , Muller O , Varet B 
Published: October 2019

Abstract
Twenty-two cases of idiopathic chronic pure red cell aplasia (PRCA) in adults have been studied to evaluate their erythroid progenitors in vitro using the plasma clot technique. Three types of culture growth patterns were observed and classified as follows. Type I: showing a normal number of autologous CFU-E; type II: CFU-E and BFU-E were detectable but constantly decreased; type III: CFU-E and BFU-E were undetectable. The results were reproducible when patients were studied on two or more occasions. A strong correlation was found between the in vitro growth of autologous erythroid colonies and the results of immunomodulating therapy in 18 evaluable patients. A constant response to immunomodulating treatment was observed in type I patients. A constant failure of treatment was observed in type III patients, whereas results of therapy were unpredictable in type II patients. Two patients with chronic PRCA associated with thymoma and three with chronic myeloproliferative disorders were also studied. Patients with PRCA and thymoma behaved in vitro like type I patients. Patients with chronic myeloproliferative disorders exhibited very low numbers or no CFU-E or BFU-E (type II or III). These data support the hypothesis that at least two mechanisms are responsible for PRCA--one immunologically mediated and the other resulting from a stem cell defect. Moreover, they suggest that the study of erythroid progenitors in vitro might be useful in predicting the immunosuppressive therapy effect in adult chronic PRCA.
Defective interleukin 2 production in patients after bone marrow transplantation and in vitro restoration of defective T lymphocyte proliferation by highly purified interleukin 2
Authors: Welte K , Ciobanu N , Moore MA , Gulati S , O'Reilly RJ , Mertelsmann R 
Published: October 2019

Abstract
Using OKT3 monoclonal antibody as a mitogen, we have studied interleukin 2 (IL2) production and proliferation in peripheral blood mononuclear cells (PBMC) of 23 patients receiving bone marrow transplants. Twenty patients were recipients of allogeneic bone marrow for treatment of hematologic malignancies, aplastic anemias (AA), or severe combined immunodeficiencies (SCID). Three patients with Hodgkin's disease or neuroblastoma received autologous bone marrow. Endogenous IL2 production was not detectable (less than 0.2 U/mL) in PBMC of 18 patients and was very low in PBMC from five patients (0.5 to 1.5 U/mL), as compared to normal controls (median 3.5 U/mL) or pretransplant patients (median 1.5 U/mL). The low IL2 production was associated with defective OKT3-induced proliferation of PBMC in 19 of 23 patients studied. In the first 6 months after BMT, 14 of 15 patients (93%) showed defective proliferation of PBMC as compared to five of eight patients (63%) tested between 7 and 18 months after BMT (P less than .1). In all but three patients, addition of highly purified human lymphocyte IL2 (hpIL2) restored OKT3-induced proliferation of PBMC to within the normal range. This study demonstrates that PBMC in patients after BMT have a defect of IL2 production but are able to express IL2 receptors in response to OKT3 antibody and to proliferate normally upon addition of hpIL2. PBMC of all patients showed similar functional defects, whether or not they received additional therapy, including various conditioning regimens prior to BMT and immunosuppressive therapy after BMT. These observations suggest that T cell defects after BMT are most likely secondary to quantitative or qualitative defects of transplanted T lymphocytes or their precursors.
Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies
Authors: Mannucci PM , Lombardi R , Bader R , Horellou MH , Finazzi G , Besana C , Conard J , Samama M 
Published: October 2019

Abstract
In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS- agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.
Kinetics and mechanism of the bactericidal action of human neutrophils against Escherichia coli
Authors: Hamers MN , Bot AA , Weening RS , Sips HJ , Roos D 
Published: October 2019

Abstract
A mutant strain of Escherichia coli (E. coli ML-35) was used to follow the kinetics of phagocytosis, perforation of the bacterial cell envelope, and inactivation of bacterial proteins by human neutrophils. This particular E. coli mutant strain has no lactose permease, but constitutively forms the cytoplasmic enzyme beta-galactosidase. This implies that the artificial substrate ortho-nitrophenyl-beta-D- galactopyranoside cannot reach the beta-galactosidase unless the bacterial cell envelope has been perforated. Thus, the integrity of the E. coli envelope can be measured simply by the activity of beta- galactosidase with this substrate. Indeed, ingestion of E. coli ML-35 by human neutrophils was followed by perforation of the bacteria (increase in beta-galactosidase activity). Subsequently, the beta- galactosidase activity decreased due to inactivation of the enzyme. With a simple mathematical model and a curve-fitting computer program, we have determined the first-order rate constants for phagocytosis, perforation, and beta-galactosidase inactivation. With 32 normal donors, we found an interdonor variation in these rate constants of 20% to 30% (SD) and an assay variance of 5%. The perforation process closely correlated with the loss of colony-forming capacity of the bacteria. This new assay measures phagocytosis and killing in a fast, simple, and accurate way; it is not hindered by extracellular bacteria. Moreover, this method also measures the postkilling event of inactivation of a bacterial protein, which permits a better detection of neutrophils deficient in this function. The assay can also be used for screening neutrophil functions without the use of a computer program. A simple calculation suffices to detect neutrophil abnormalities. Neutrophils from patients with chronic granulomatous disease (CGD) showed an impaired rate of perforation and thus also of inactivation. Neutrophils from myeloperoxidase-deficient patients or from a patient with the Chediak-Higashi syndrome only showed a retarded inactivation of beta-galactosidase, but normal ingestion and perforation. The role of myeloperoxidase in the killing process is discussed. Although myeloperoxidase does not seem to be a prerequisite for perforation, it probably plays a role in bacterial destruction by normal cells, because the inactivation of bacterial proteins seems strictly myeloperoxidase dependent.
Immunologic status of hemophilia patients treated with cryoprecipitate or lyophilized concentrate
Authors: Gjerset GF , Martin PJ , Counts RB , Fast LD , Hansen JA 
Published: October 2019

Abstract
We evaluated 37 patients with moderate or severe hemophilia A and six patients with severe factor IX deficiency for clinical or laboratory evidence of immune abnormalities. Patients were assigned to one of four groups according to the type of clotting factor replacement. Twenty patients had received only cryoprecipitate during the two years preceding the evaluation (group I); 11 additional patients were treated predominantly with cryoprecipitate but had also received up to nine bottles of factor VIII concentrate (group II); six patients received factor VIII concentrate (group III); six patients received factor IX concentrate (group IV). There was no clinical or laboratory evidence of immunodeficiency among the 43 patients. The mean absolute number of Th cells was normal in all patient groups, but the mean absolute number of Ts cells was increased compared with controls, both in patients treated with cryoprecipitate and in patients treated with factor VIII or factor IX concentrate. There was no correlation between the Th/Ts ratio and patient age, alanine aminotransferase level, hepatitis serology, in vitro lymphocyte function, or amount of clotting factor administered. Our observations demonstrate that the volunteer or commercial origin of clotting factor replacement cannot fully explain the alterations in lymphocyte subset distribution previously described in patients with hemophilia A.
Chromosome abnormalities in mice with Hertwig's anemia
Authors: Eppig JT , Barker JE 
Published: October 2019

Abstract
Mice with the recessive hereditary disease, Hertwig's anemia (an/an), exhibit a persistent mild macrocytic anemia and reduced fertility. We examined mitotic figures from bone marrow and kidney cells of adult mice and from liver cells of fetal mice that were genetically normal or had Hertwig's anemia. Uniformly normal mitotic figures were observed in the nonanemic mice (+/+ or +/an). In contrast, 5% to 15% of the mitotic figures were abnormal in mice homozyous for Hertwig's anemia (an/an). These aberrant cells were hyperploid, containing more than the normal complement of c40 chromosomes, but fewer than 80 chromosomes. Cells with abnormal numbers of chromosomes may show decreased viability or proliferative capacity. The occurrence of such abnormal cells in an/an mice could explain (1) the loss of progenitor stem cells during erythroid maturation, resulting in an anemic phenotype; and (2) the depletion of germ cells during ontogeny, resulting in reduced fertility.
Hemin-induced conversion of pyruvate kinase isozymes in K562 cells
Authors: Takegawa S , Shinohara T , Miwa S 
Published: October 2019

Abstract
The effects of hemin on the conversion of pyruvate kinase (PK) isozymes from the M2-type to the L-type in K562 cells were investigated. Immunofluorescence, ion exchange chromatography, and electrophoretic studies showed that the untreated K562 cells contained only the M2-type PK, while eight to 20 days after induction with hemin, concomitant with hemoglobin F synthesis, L-type PK levels increased while M2-type PK levels decreased. Electrophoretic study revealed three hybrid isozymes of the L-type and M2-type PK. We conclude that the conversion of PK isozymes from the M2-type to the L-type in erythroid precursor cells occurs in the early stage of maturation.
Platelet secretion defect associated with impaired liberation of arachidonic acid and normal myosin light chain phosphorylation
Authors: Rao AK , Koike K , Willis J , Daniel JL , Beckett C , Hassel B , Day HJ , Smith JB , Holmsen H 
Published: October 2019

Abstract
We describe four patients with impaired platelet aggregation and 14C- serotonin secretion during stimulation with adenosine diphosphate (ADP), epinephrine, collagen, and platelet-activating factor. The response to arachidonic acid was normal in all patients with regard to aggregation and in three of the four with regard to 14C-serotonin secretion. The total platelet adenosine triphosphate (ATP) and ADP content and the ATP to ADP ratio was normal in all patients, thereby excluding storage pool deficiency as the cause of the secretion defect. Studies with 3H-arachidonic acid-labeled platelets revealed that the thrombin-induced liberation of arachidonic acid from membrane-bound phospholipids was impaired in these patients. Further, platelet thromboxane B2 production, measured using a radioimmunoassay, was diminished during stimulation with ADP and thrombin, but was normal with arachidonic acid, indicating that the oxygenation of arachidonic acid was normal and that the diminished thromboxane production was due to a defect in the liberation of arachidonic acid. Release of arachidonic acid is mediated by phospholipases that are Ca++ dependent. To examine whether these patients may have a defect in making intracellular Ca++ available, another Ca++-dependent process, myosin light chain phosphorylation, was studied during thrombin stimulation. Platelets from three of the patients were found to behave the same as normal ones, suggesting that the deficiency in phospholipase activity may not be due to impaired Ca++ mobilization. Our studies demonstrate a novel group of patients with platelet secretion defects associated with impaired liberation of arachidonic acid from phospholipids. These patients exemplify a congenital defect, other than deficiencies of cyclooxygenase and thromboxane synthetase, by which thromboxane production may be impaired in platelets.
5-Aza-2'-deoxycytidine induces terminal differentiation of leukemic blasts from patients with acute myeloid leukemias
Authors: Pinto A , Attadia V , Fusco A , Ferrara F , Spada OA , Di Fiore PP 
Published: October 2019

Abstract
In this study, the effects of 5-aza-2′-deoxycytidine on differentiation of human leukemic cells in primary suspension culture are reported for the first time. Morphological and functional differentiation was induced in cells from two acute monoblastic leukemias and two of three acute myeloid leukemias following repeated exposures to 1 mumol/L 5-aza- 2′-deoxycytidine. The observation that nontoxic concentrations of the drug are able to induce the in vitro differentiation of both monoblastic and myeloblastic leukemic cells into mature elements may encourage the exploitation of the differentiating properties of 5-aza- 2′-deoxycytidine in chemotherapy protocols for acute non-lymphoblastic leukemias.
Partial deletion of the 5' beta-globin gene region causes beta zero- thalassemia in members of an American black family
Authors: Padanilam BJ , Felice AE , Huisman TH 
Published: October 2019

Abstract
Restriction endonuclease mapping defined a partial deletion of about 1.35 kb in the beta-globin gene of a black American patient with hemoglobin S-beta zero-thalassemia and in his uncle with a beta zero- thalassemia trait. The 5′ endpoint of the deletion is about 600 bases upstream from the cap site, and the 3′ endpoint lies within about 500 bases from the 5 splice junction of the second intervening sequence. The deletion is different from that of a previously reported Indian beta zero-thalassemia allele, where 0.6 kb is deleted at the 3′ end of the beta-globin gene.