bluuebunny/crossref_metadata_2025_split huggingface dataset:
High numbers of CD4+ T cells showing abnormal recognition of DR antigens in lymphoid organs involved by Hodgkin's disease
Authors: Maggi E , Parronchi P , Macchia D , Bellesi G , Romagnani S 
Published: October 2019

Abstract
Purified T lymphocytes (E rosetting cells) isolated from the involved lymphoid organs (lymph nodes and spleen) of five patients with Hodgkin's disease (HD) were cloned under culture conditions (phytohemagglutinin plus interleukin-2) that allow clonal expansion of most T lymphocytes. A total number of 104 CD4+ T cell clones so obtained were tested for their ability to proliferate in response to autologous mitomycin-treated non-T cells. About half of these clones but none of 234 CD4+ T cell clones derived from normal lymphoid tissues or peripheral blood displayed a proliferative response to autologous stimulators. When clones proliferating in autologous mixed lymphocyte reaction (AMLR) were assessed for their ability to respond in allogeneic MLR (allo-MLR), most of them were found to exhibit consistent proliferation in response to more than one haplotype. Both the AMLR and the allo-MLR by HD clones were inhibited by adding monoclonal antibodies (MoAbs) reactive with monomorphic determinants of major histocompatibility complex (MHC) class II (DR) antigens to the cultures, whereas MoAbs reactive with MHC class I antigens were without effect. These studies suggest that lymphoid organs involved by HD contain high proportions of CD4 T cells showing abnormal recognition of DR antigens. These unusual cells may play an important role in the pathogenetic mechanisms occurring in HD.
Transplantation of human hairy cell leukemia in radiation- preconditioned nude mice: characterization of the model by histological, histochemical, phenotypic, and tumor kinetic studies
Authors: Faguet GB , Agee JF 
Published: October 2019

Abstract
Two cell lines (EH and HK) with hairy cell leukemia (HCL) immunophenotypes were recently derived from two HCL patients. Both cell lines were transplanted subcutaneously (2 x 10(5) or 2 x 10(6)/mouse) in male BALB/c nu/nu mice (n = 128) with a 97% success rate when coimplanted with nonproliferative HT-1080 fibrosarcoma cells (2 x 10(6)/mouse) in recipients preconditioned with total-body irradiation (200 R weekly for 3 weeks). Tumors appeared five to ten days postimplant and reached up to 25% of body weight after a mean survival of 8 weeks (range, 30 to 90 days). Tumor histology suggested large cell lymphoma. Cytochemically and immunophenotypically, tumor cells were indistinguishable from their parent cells. Species and lineage derivation of tumor cells was confirmed by antibody probes against the mouse histocompatibility antigen H-2, human T and B lymphocyte antigens, and the HCL-associated common chronic lymphocytic leukemia antigen (cCLLa). In order of decreasing frequency, metastases occurred in the spleen, lungs, pleura, lymph nodes, bone marrow, and kidneys. Up to 12% of circulating lymphoid cells in mice were cCLLa-positive, which suggested hematogenous tumor dissemination. This HCL xenotransplantation model might be useful in preclinical studies for exploring novel experimental therapies for the management of human HCL.
Subsecond calcium dynamics in ADP- and thrombin-stimulated platelets: a continuous-flow approach using indo-1
Authors: Jones GD , Gear AR 
Published: October 2019

Abstract
The regulation and kinetics (less than 5 seconds) of cytosolic calcium changes ([Ca2+]i) in stimulated blood platelets have been investigated under physiological blood flow conditions. Using a newly-developed continuous-flow approach with indo-1-loaded human platelets, adenosine diphosphate (ADP, 10 mumol/L) and thrombin (5 U/mL) were equally effective in significantly increasing [Ca2+]i by 0.5 seconds. ADP induced a transient [Ca2+]i peak of 1 to 2 mumol/L near 2 seconds, whereas thrombin caused a sustained and larger response. The first phase (less than 2 seconds) was not influenced by a lack of extracellular Ca2+, in contrast to the subsequent [Ca2+]i increase that only reached about 0.7 mumol/L for either ADP or thrombin. The shear rates used in our continuous-flow apparatus were physiological (less than 1,258 sec-1) and only slightly increased the basal [Ca2+]i of 0.1 mumol/L. Platelet aggregation (less than 5 seconds), assessed by single- particle counting, was not altered in platelets loaded with indo-1/AM (2.5 mumol/L).
Defective helper function of purified T4 cells and excessive suppressor activity of purified T8 cells in patients with B-cell chronic lymphocytic leukemia. T4 suppressor effector cells are present in certain patients
Authors: Kunicka JE , Platsoucas CD 
Published: October 2019

Abstract
We investigated helper and suppressor functions to B-cell responses and T-T cell interactions of purified T4 and T8 cells from 20 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Appropriate mixtures of purified T4 or T8 cells from patients with CLL were cultured with purified B cells or T4 and B cells from normal donors for 7 days with pokeweed mitogen (PWM). IgM, IgA, and IgG produced were determined in the supernatants of these cultures by a heavy chain- specific enzyme-linked immunosorbent assay (ELISA) and compared to those obtained by the corresponding mixtures of T4, T8, and B cells from normal donors. Purified T4 cells from 14 of 20 patients with CLL exhibited defective helper function (P less than .001) to immunoglobulin (Ig) production by purified B cells from normal donors. Purified T4 cells from 6 of these 14 patients were able to suppress significantly (P less than .001) and in a concentration-dependent manner Ig production by mixtures of T4 and B cells from normal donors, in the absence of T8 cells. These suppressor effector T4 cells from certain patients were partially radiosensitive. Purified T8 cells from 8 of 20 patients with CLL exhibited excessive suppressor activity. These cells significantly suppressed (P less than .001), Ig production by mixtures of T4 and B cells from normal donors to a degree significantly higher (P less than .005) than that observed by equal numbers of T8 cells from normal donors. This inhibition was dependent on the numbers of the T8 CLL cells added to the cultures. Excessive suppressor activity by T8 CLL cells was at least in part radiosensitive in four of eight patients. These results demonstrate a wide range of immunoregulatory T-cell abnormalities in patients with CLL. Naturally occurring T4 suppressor effector cells, directly inhibiting Ig production by mixtures of T4 and B cells, in the absence of T8 cells, are present in certain patients with CLL.
Karyotype evolution and multilineage involvement of Philadelphia chromosome-positive clones in blastic transformation of two patients with chronic myelocytic leukemia
Authors: Sato Y , Kitano K , Tsunoda S , Yoshida M , Kajii E , Suda T , Sakamoto S , Motoyoshi K , Saito M , Miura Y 
Published: October 2019

Abstract
Simultaneous analysis of the cell morphology and karyotypes on single colonies was carried out in two patients with Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia in blastic transformation in order to clarify the origin of leukemic cells involved. Patient no. 1 was in a typical myeloblastic transformation and patient no. 2 in “basophilic transformation.” Both patients exhibited karyotype evolution in blastic phase (BP), so that we could differentiate BP clones with additional chromosomal abnormalities from chronic phase (CP) clones with only Ph1 among single colonies. The number of single colonies yielding two or more analyzable metaphases was 18 in patient no. 1, and 19 in patient no. 2. Among these colonies, only three in patient no. 1 and none in patient no. 2 were from CP clones and 15 in patient no. 1 and 19 in patient no. 2 were from BP clones. Morphological examination revealed that not only blasts but also mature neutrophils, eosinophils, basophils, macrophages, and erythroblasts were derived from BP clones. These results suggested that (1) BP clones developed at the pluripotent stem cell level, (2) additional chromosomal abnormalities were not restricted to occur in a specific cell line representative in BP; and (3) BP clones, if not all, may retain capacity for maturation and differentiation.
Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte
Authors: Cabanillas F , Pathak S , Trujillo J , Grant G , Cork A , Hagemeister FB , Velasquez WS , McLaughlin P , Redman J , Katz R 
Published: October 2019

Abstract
Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11–21, and 8q22–24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.
Sizing of the human T cell receptor alpha locus and detection of a large deletion in the Molt-4 cell line
Authors: Roth MS , Collins FS , Ginsburg D 
Published: October 2019

Abstract
The human T cell receptor alpha (TCR-alpha) chain gene consists of discontinuous DNA segments encoding multiple variable (V), multiple joining (J), and one constant (C) region. Unlike other immunoglobulin or TCR genes, however, the TCR-alpha locus exhibits an unusual dispersal of J segments that occupy a region of greater than 50 kilobases (kb) upstream of the C region, with the exact size still unknown. We report here the study of the TCR-alpha genetic locus by using pulsed-field gel electrophoresis (PFGE), which permits the separation of large DNA fragments. Analysis of DNA prepared from normal peripheral blood mononuclear cells, human endothelial cells, and a B cell line demonstrates that both V and C sequences are contained within a single 400-kb SfiI restriction fragment. PFGE analysis of the T cell line Molt 4 suggests a greater than 600-kb deletion involving the TCR- alpha gene.
Significance of extra 18q- chromosome in Japanese t(14;18)-positive lymphoma
Authors: Fukuhara S , Ohno H , Amakawa R , Edamura S , Tomono N , Nasu K , Doi S , Yamabe H , Abe M , Wakasa H 
Published: October 2019

Abstract
Karyotype evolution of t(14;18)-positive lymphoma was studied in 13 Japanese patients. The extra 18q- chromosome, found in six of ten patients with complex karyotypes, was the most common change subsequent to a t(14;18)(q32;q21) chromosome translocation. The additional change was interpreted as being a duplication of an 18q- derived from a t(14;18). The six patients had transformed histology of follicular small cleaved cell lymphoma or diffuse large cell lymphoma, and five of them had extranodal expansion associated with a poor prognosis. These findings indicate that the extra 18q-, together with other chromosome abnormalities, is closely associated with the advanced grade disease of t(14;18)-positive lymphoma, and the extra chromosome is evolutionally comparable with the second Philadelphia (Ph1) chromosome often found in the blastic phase of chronic myelocytic leukemia carrying a t(9;22)(q34;q11). In addition, since the extra 18q- is rarely found in American patients with t(14;18)-positive lymphoma, there appears to be a difference in the karyotype evolution between Japanese and American patients.
The pathophysiology and clinical relevance of platelet heterogeneity
Authors: Thompson CB , Jakubowski JA 
Published: October 2019

Abstract
Recent studies on platelet heterogeneity support the hypothesis that platelet production is regulated to maintain a constant functional platelet mass. In concept this form of regulation is analogous to the manner by which RBC production is controlled to maintain the oxygen- carrying capacity of blood. The platelet mass appears to correlate more closely with platelet function than the platelet count alone, since several factors in addition to the platelet count have been shown to influence the platelets' hemostatic function. These factors include platelet size, density, age, and previous hemostatic interactions. Application of these concepts to clinical problems has provided important insights into platelet physiology and reactivity. Failure to account for differences in platelet heterogeneity among individuals may introduce significant errors in the interpretation of data from laboratory and clinical investigations. However, despite advances, a number of practical issues remain to be resolved before measurements of platelet heterogeneity become accepted as routine clinical tests and are used in the diagnosis of pathologic states.
Decreased plasma gelsolin levels in patients with Plasmodium falciparum malaria: a consequence of hemolysis?
Authors: Smith DB , Janmey PA , Sherwood JA , Howard RJ , Lind SE 
Published: October 2019

Abstract
Mammalian plasma contains a high-affinity actin-binding protein, plasma gelsolin, that severs actin filaments. Destruction of erythrocytes could result in the release of erythrocyte cytoskeletal actin into the plasma where it could bind to gelsolin. If the clearance of actin- gelsolin complexes exceeds its synthesis, lowering of the plasma gelsolin concentration might follow. To test this hypothesis, we measured plasma gelsolin levels in patients with falciparum malaria, a disease where at least part of the hemolysis takes place in the intravascular space and that is usually not accompanied by dysfunction of other organs. Two functional gelsolin assays showed that the mean plasma gelsolin concentration of 18 Nigerian children with Plasmodium falciparum malaria was less than 50% (P less than .001) of healthy Nigerian control subjects tested at the same time. Patients with pneumonia and febrile seizures also had depressed gelsolin levels, which indicates that factors other than hemolysis can lower gelsolin concentrations. Gelsolin levels were measured in 11 patients from The Gambia with P falciparum malaria before and approximately 3 weeks after treatment. In all cases the gelsolin level increased after treatment. To confirm the hypothesis that hemolysis can result in a lowering of plasma gelsolin levels, hemolysis was induced in rabbits, either acutely (by the injection of human serum) or subacutely (by the administration of phenylhydrazine). A fall in plasma gelsolin levels was seen, the rate of fall differing with the extent of hemolysis. Affinity adsorption of plasma from animals undergoing acute hemolysis with Sepharose beads coupled to the actin-binding protein DNase I, followed by immunoblotting of adherent proteins with antiactin antiserum demonstrated the presence of actin in circulating rabbit plasma. These studies suggest that under some conditions components of the red cell cytoskeleton are exposed to plasma proteins and that accelerated clearance of actin-gelsolin complexes may explain in part the depressed plasma gelsolin levels seen in patients with falciparum malaria.
Bivariate flow karyotyping in human Philadelphia-positive chronic myelocytic leukemia
Authors: Arkesteijn GJ , Martens AC , Hagenbeek A 
Published: October 2019

Abstract
Chromosome analysis on clinical leukemia material was done by means of flow cytometry (flow karyotyping) to investigate the applicability of this technique in the detection of leukemia-associated abnormalities. Flow karyotyping was performed on blood or bone marrow samples from eight patients with chronic myelocytic leukemia (CML) after a culture period of four days and arresting the cells in metaphase during the last 16 hours. Discontinuous density gradient centrifugation proved to be essential in removing debris and dead cells from the cell suspensions. By this procedure the mitotic index increase ranged from 2 to 80 times initial values. Chromosomes were isolated and stained with two base pair-specific fluorochromes, ie, chromomycin A3 and Hoechst 33258, and run through a specially designed dual-laser beam flow cytometer. Generally, 20,000 chromosomes or more were measured. The data were computer stored in list mode. Besides the clear detection of the specific Philadelphia chromosome, trisomies and other additional chromosomal aberrations [like an i(17q)] were visualized. Quantitative analysis revealed the percentage of subclones containing a certain chromosomal anomaly. Conventional cytogenetic analysis confirmed these findings. In seven of eight cases, CML could be diagnosed on the basis of the presence of a Philadelphia chromosome in the flow karyogram. In one of these seven, the conventional cytogenetic analysis was unknown at that time. The remaining six all matched the standard cytogenetics. The one failure out of eight could be attributed to the specific stimulating conditions in the culture. Although it is impossible by this technique to determine the position of the breakpoint, the involved chromosomes in the translocation event could be identified. In some cases, low percentages of aberrations could not be detected. This study shows that CML can be diagnosed on the basis of flow karyotypic results. Additional chromosomal aberrations can be detected provided that changes in the amount of DNA per chromosome have occurred. Exact quantification of the composition of subclones in the case of mosaicism appear difficult.
Distinct variants of erythrocyte protein 4.1 inherited in linkage with elliptocytosis and Rh type in three white families
Authors: McGuire M , Smith BL , Agre P 
Published: October 2019

Abstract
Hereditary elliptocytosis is a heterogeneous disorder resulting from defects in the erythrocyte membrane skeleton. Although some cases of elliptocytosis result from defects in spectrin, the specific structural abnormality has yet to be identified in the majority of cases. Protein 4.1 plays an essential role in erythrocyte membrane physiology, and deficiencies have been implicated in only a few rare cases of elliptocytosis. By using 4.1 immunoblots and a 4.1 radioimmunoassay we identified distinct variants of protein 4.1 in 15 elliptocytic members of three US white families with the Rh-linked form of elliptocytosis. Elliptocytic members of family G were heterozygotes for a low-molecular weight (mol wt) 4.1 variant (65,000 to 68,000 daltons; normal, 80,000) inherited in linkage with the Rz phenotype. Elliptocytic members of family C expressed a simple partial deficiency of protein 4.1 (63% of the normal level) that was inherited in linkage with the r phenotype. Elliptocytic members of family N were heterozygotes for a high-mol wt 4.1 variant (100,000 daltons) also inherited in linkage with the r phenotype. These studies indicate that mutant forms of protein 4.1 are not uncommon in elliptocytosis among whites and that different kindreds probably express different mutations. The observed linkage of elliptocytosis and Rh blood type most likely results from the close proximities of the 4.1 gene (site of the mutation) and the Rh gene, which is located nearby on the short arm of chromosome 1.
Glycoprotein IIb-IIIa and RGD(S) are not important for fibronectin- dependent platelet adhesion under flow conditions
Authors: Nievelstein PF , Sixma JJ 
Published: October 2019

Abstract
Previous studies have indicated that activated blood platelets interact with fibronectin through binding of fibronectin to the glycoprotein IIb- IIIa complex (GPIIb-IIIa). The cell attachment site of fibronectin with its crucial arg-gly-asp(-ser) [RGD(S)]sequence is involved in these bindings. We studied the importance of these interactions for the fibronectin dependence of platelet adhesion under flow conditions. An RGDS-containing hexapeptide (GRGDSP) was compared with a nonreactive control peptide (GRGESP). The GRGDSP-peptide inhibited thrombin-induced aggregation and adhesion under static conditions at 0.1 mmol/L. This concentration had no effect on platelet adhesion to nonfibrillar collagen type I in flow. GRGDSP at 1 mmol/L had a significant inhibitory effect at 1,500 s-1, but not at the lower shear rates of 800 and 300 s-1 where platelet adhesion is also fibronectin dependent. On the matrix of cultured human umbilical vein endothelial cells, 1 mmol/L GRGDSP had no effect on platelet adhesion. The relation between GPIIb- IIIa and fibronectin dependence was investigated with platelets of a patient with Glanzmann's thrombasthenia and monoclonal antibodies to GPIIb-IIIa using endothelial cell matrix (ECM) as a surface. Platelets of normal controls or a patient with Glanzmann's thrombasthenia showed a similar inhibition of adhesion in the presence of fibronectin-free plasma after the ECMs had been preincubated with antifibronectin F(ab')2 fragments. Incubation of platelets with anti-GPIIb-IIIa showed inhibition of platelet adhesion at high shear rates. Dependence on fibronectin for platelet adhesion was still observed even though separate experiments had shown that these anti-GPIIb-IIIa antibodies could block binding of radiolabeled fibronectin to thrombin-activated platelets. These data suggest the existence of another binding system for the interaction of platelets with fibronectin that may only appear when fibronectin is present on a surface.
Bone marrow origin of a B-cell lymphoma
Authors: Bertoli LF , Kubagawa H , Borzillo GV , Burrows PD , Schreeder MT , Carroll AJ , Cooper MD 
Published: October 2019

Abstract
To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.