scholarly journals Establishing a KSHV+ Cell Line (BCP-1) From Peripheral Blood and Characterizing Its Growth in Nod/SCID Mice

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1671-1679 ◽  
Author(s):  
Chris Boshoff ◽  
Shou-Jiang Gao ◽  
Lyn E. Healy ◽  
Steve Matthews ◽  
Alero J. Thomas ◽  
...  

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV− cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 α and β chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1671-1679 ◽  
Author(s):  
Chris Boshoff ◽  
Shou-Jiang Gao ◽  
Lyn E. Healy ◽  
Steve Matthews ◽  
Alero J. Thomas ◽  
...  

Abstract Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV− cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 α and β chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).


Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2556-2570 ◽  
Author(s):  
Johannes C.M. van der Loo ◽  
Helmut Hanenberg ◽  
Ryan J. Cooper ◽  
F.-Y. Luo ◽  
Emmanuel N. Lazaridis ◽  
...  

Mobilized CD34+ cells from human peripheral blood (PB) are increasingly used for hematopoietic stem-cell transplantation. However, the mechanisms involved in the mobilization of human hematopoietic stem and progenitor cells are largely unknown. To study the mobilization of human progenitor cells in an experimental animal model in response to different treatment regimens, we injected intravenously a total of 92 immunodeficient nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with various numbers of granulocyte colony-stimulating factor (G-CSF) –mobilized CD34+ PB cells (ranging from 2 to 50 × 106cells per animal). Engraftment of human cells was detectable for up to 6.5 months after transplantation and, depending on the number of cells injected, reached as high as 96% in the bone marrow (BM), displaying an organ-specific maturation pattern of T- and B-lymphoid and myeloid cells. Among the different mobilization regimens tested, human clonogenic cells could be mobilized from the BM into the PB (P= .019) with a high or low dose of human G-CSF, alone or in combination with human stem-cell factor (SCF), with an average increase of 4.6-fold over control. Therefore, xenotransplantation of human cells in NOD/SCID mice will provide a basis to further study the mechanisms of mobilization and the biology of the mobilized primitive human hematopoietic cell.


Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2556-2570 ◽  
Author(s):  
Johannes C.M. van der Loo ◽  
Helmut Hanenberg ◽  
Ryan J. Cooper ◽  
F.-Y. Luo ◽  
Emmanuel N. Lazaridis ◽  
...  

Abstract Mobilized CD34+ cells from human peripheral blood (PB) are increasingly used for hematopoietic stem-cell transplantation. However, the mechanisms involved in the mobilization of human hematopoietic stem and progenitor cells are largely unknown. To study the mobilization of human progenitor cells in an experimental animal model in response to different treatment regimens, we injected intravenously a total of 92 immunodeficient nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with various numbers of granulocyte colony-stimulating factor (G-CSF) –mobilized CD34+ PB cells (ranging from 2 to 50 × 106cells per animal). Engraftment of human cells was detectable for up to 6.5 months after transplantation and, depending on the number of cells injected, reached as high as 96% in the bone marrow (BM), displaying an organ-specific maturation pattern of T- and B-lymphoid and myeloid cells. Among the different mobilization regimens tested, human clonogenic cells could be mobilized from the BM into the PB (P= .019) with a high or low dose of human G-CSF, alone or in combination with human stem-cell factor (SCF), with an average increase of 4.6-fold over control. Therefore, xenotransplantation of human cells in NOD/SCID mice will provide a basis to further study the mechanisms of mobilization and the biology of the mobilized primitive human hematopoietic cell.


1989 ◽  
Vol 170 (6) ◽  
pp. 1919-1930 ◽  
Author(s):  
S M Krams ◽  
K Dorshkind ◽  
M E Gershwin

Human PBL have been reported to reconstitute B and T cells as well as human serum Ig in mice with severe combined immunodeficiency disease (SCID). To confirm these observations and attempt the transfer of an autoimmune disease to the immunodeficient animals, groups of SCID mice received an injection of PBL from patients with primary biliary cirrhosis (PBC) or from normal volunteers. By 8 wk after the injection of 10-42 x 10(6) PBL into the mice, human lymphoid cells were detected in the spleen of approximately half of the animals and all had detectable serum levels of human IgG. Moreover, the sera of SCID mice that received cells from patients with PBC contained human antimitochondrial antibodies (AMA) to dihydrolipoamide acetyltransferase, the major mitochondrial autoantigen of PBC. Histologically, a human mononuclear cell infiltrate was present around the portal areas of the liver and inflammation, bile duct atypica, and necrosis of bile duct cells were observed. While the biliary lesions in the SCID recipients of PBC cells were more severe, a mononuclear infiltrate was clearly evident in mice that received cells from normal donors, suggesting the presence of a graft-vs.-host-like disease. While these data are the first to describe an animal model with both the humoral and cellular characteristics of PBC, they also raise an interesting question regarding the preferential localization of lymphoid cells to the biliary system.


Blood ◽  
1949 ◽  
Vol 4 (9) ◽  
pp. 1049-1067 ◽  
Author(s):  
MICHAEL A. RUBINSTEIN

Abstract The conventional points in the differential diagnosis between myeloma and leukemia have been discussed. Evidence has been brought to show that these points of distinction cannot be regarded as being of fundamental nature. Instances are abstracted where cases of multiple myeloma show the various characteristics of leukemia and vice versa. 1. Leukemic features in myeloma have been shown in: a. diffuse infiltration in multiple myeloma without circumscribed tumor formation and without any gross bone destruction; b. extraskeletal visceral myelomatous spread involving the kidney, spleen, lymph nodes, etc.; c. invasion of peripheral blood in myeloma—occasional myeloma cells (corresponding to the aleukemic forms of leukemia) may frequently be found in concentrated smears, even though they may be missed on routine examination; however, massive invasion of peripheral blood is rare; d. increased uric acid content of the blood and elevated basal metabolism, characteristic of leukemia, frequently seen also in myeloma; e. occurrence of myeloma in youth; f. symptomatology of multiple myeloma at times not referable to the osseous system. 2. Myeloma features in leukemia have been shown in: a. skeletal involvement in leukemia; b. very rare medullary forms of leukemia (without visceral involvement); c. occurrence of Bence-Jones proteinuria or d. hyperproteinemia with hyperglobulinemia in rare cases of leukemia; e. instances when the symptomatology of leukemia was referable to the osseous system. 3. Coexistence of multiple myeloma and leukemia is reviewed from the literature, and a case is reported of extensive mixed lymphocytic and plasma cell infiltration. In conclusion, the difference between myeloma and leukemia, as far as the listed conventional distinguishing features are concerned, is merely one of incidence: what is rare in one disease, is common in the other, and vice versa. Multiple myeloma is in all probability a leukemia of plasma cells.


Blood ◽  
1977 ◽  
Vol 50 (1) ◽  
pp. 55-64 ◽  
Author(s):  
CM Payne ◽  
JF Jones ◽  
OF Jr Sieber ◽  
VA Fulginiti

Abstract The ultrastructure of the lymphocytes from three children with severe combined immunodeficiency disease (SCID) is described. Parallel tubular arrays (PTA) were found in a large percentage of circulating lymphocytes (53%, 41%, and 13%) in three SCID patients when compared to age-matched controls. The size of these inclusions was quite variable, with some attaining a length of 1.7 micrometer. They contained a tubular substructure with a diameter of 36--44 nm. The PTA were mostly located in the centriolar and Golgi regions of the cytoplasm, and were sometimes membrane bound. A centriolar origin of the inclusion was suggested. A second inclusion, the tubuloreticular structure, was found in only 1.4% of the circulating lymphocytes from one SCID patient. The origin of the PTA and its occurrence in severe combined immunodeficiency disease are discussed.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20005-e20005
Author(s):  
Yekaterina Komarova ◽  
Yelena Frantsiyants ◽  
Farhad Dzhabarov ◽  
Ludmila Rozenko ◽  
Victoria Pozdnyakova

e20005 Background: Result of scientific research testify that particularities of endocrinal status might play a role in etiology and pathogenesis of illness. In connection to this, studying of particularities of hormonal homeostasis in patients having skin melanoma becomes relevant, as on the background of the former, the tumor develops this or that reaction to remedial measures. Methods: Content of triiodothyronine (T3) in peripheral blood was studied in 40 patients of both sexes having disseminated melanoma of skin (pT2-3N1-2M0) before and after chemoradiation. Chemotherapy consisted of dacarbazine in course dose of 1000 mg/m2, radiotherapy – total boost dose was 55+5,4 Gy. Results: Assessment of direct clinical result of the complex of antitumor measures has demonstrated that in the group of patients under control the treatment proved inefficient in 15 people and was not accompanied by decrease of tumor formation sizes, while in 25 people the curative effect was manifested in 25-50% (15 cases) regress of tumor lesions and in over 50% (10 cases) regress. Conclusions: The results of chemoradiation were analyzed depending on the initial content of general T3 in the blood of the patients. It has been discovered that absence of effect from treatment was featured in patients having low content of the hormone – from 0,52 to 1,10 nmole/l, normal oscillations of its level in healthy people being 1,2 to 2,8 nmole/l. Contrary to that, in patients having regress of tumor, the initial concentration of the hormone ranged from 1,35 to 1,70 nmole/l, i.e. within the physiological norm.


2003 ◽  
Vol 77 (6) ◽  
pp. 3859-3865 ◽  
Author(s):  
Wang Sheng ◽  
Gisèle Decaussin ◽  
Audrey Ligout ◽  
Kenzo Takada ◽  
Tadamasa Ooka

ABSTRACT Spontaneous loss of the Epstein-Barr virus (EBV) genome in the BL cell line Akata led to loss of tumorigenicity in SCID mice, suggesting an important oncogenic activity of EBV in B cells. We previously showed that introduction of the BARF1 gene into the human B-cell line Louckes induced a malignant transformation in newborn rats (M. X. Wei, J. C. Moulin, G. Decaussin, F. Berger, and T. Ooka, Cancer Res. 54:1843-1848, 1994). Since 1 to 2% of Akata cells expressed lytic antigens and expressed the BARF1 gene, we investigated whether introduction of the BARF1 gene into EBV-negative Akata cells can induce malignant transformation. Here we show that BARF1-transfected, EBV-negative Akata cells activated Bcl2 expression and induced tumor formation when they were injected into SCID mice. In addition, when EBV-positive Akata cells expressing a low level of BARF1 protein were injected into SCID mice, the expression of BARF1, as well as several lytic proteins, such as EA-D, ZEBRA, and a 135-kDa DNA binding protein, increased in tumor cells while no latent LMP1 and late gp220-320 expression was observed in tumor cells. These observations suggest that the BARF1 gene may be involved in the conferral of tumorigenicity by EBV.


Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1800-1810 ◽  
Author(s):  
Sergey Yurasov ◽  
Tobias R. Kollmann ◽  
Ana Kim ◽  
Christina A. Raker ◽  
Moshe Hachamovitch ◽  
...  

To develop an in vivo model wherein human hematopoiesis occurs, we transplanted severe combined immunodeficiency (SCID) mice with either human fetal bone marrow (HFBM) or human fetal liver (HFL). After transplantation of SCID mice with cultured HFBM (BM-SCID-hu mice) or HFL cells (Liv-SCID-hu mice), significant engraftment of the mouse bone marrow (BM) and population of the peripheral blood with human leukocytes was detected. Human colony-forming unit–granulocyte macrophage and burst forming unit-erythroid were detected in the BM of the BM-SCID-hu and Liv-SCID-hu mice up to 8 months after transplantation. When the HFBM or HFL cells were transduced with a retroviral vector before transplantation, integrated retroviral sequences were detected in human precursor cells present in the SCID mouse BM and in leukocytes circulating in the peripheral blood (PB) up to 7 months after transplantation. The PB of the BM-SCID-hu mice also became populated with human T cells after implantation with human thymic tissue, which provided a human microenvironment wherein human pre-T cells from the BM could mature. When the HFBM was retrovirally transduced before transplantation, integrated retrovirus was detected in sorted CD4+CD8+ double positive and CD4+ single positive cells from the thymic implant and CD4+ cells from the PB. Taken together, these data indicated that the BM of our BM-SCID-hu and Liv-SCID-hu mice became engrafted with retrovirally transduced human hematopoietic precursors that undergo the normal human hematopoietic program and populate the mouse PB with human cells containing integrated retroviral sequences. In addition to being a model for studying in vivo human hematopoiesis, these mice should also prove to be a useful model for investigating in vivo gene therapy using human stem/precursor cells.


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