Granulopoiesis in Shwachman's Syndrome (Pancreatic Insufficiency and Bone Marrow Dysfunction)

PEDIATRICS ◽  
1979 ◽  
Vol 64 (4) ◽  
pp. 515-519
Author(s):  
E. Fred Saunders ◽  
Grant Gall ◽  
Melvin H. Freedman
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Proliferative Activity ◽  
Tritiated Thymidine ◽  
Pancreatic Insufficiency ◽  
Peripheral Blood Lymphocytes ◽  
Exocrine Pancreatic Insufficiency ◽  
Thymidine Uptake ◽  
Blood Leukocytes

Granulopoiesis was studied in 10 children with Shwachman's syndrome (chronic neutropenia and exocrine pancreatic insufficiency). Marrow proliferative activity assessed by determination of mitotic indices and tritiated thymidine uptake into granulocytic cells was normal. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system demonstrated normal CFU-C numbers in four patients and reduced numbers in five. The granulocyte colonies formed were indistinguishable from normal colonies morphologically. Production of colony-stimulating activity (CSA) from patients' peripheral blood leukocytes appeared normal when tested on control marrow. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow, and co-culture of patients' peripheral blood lymphocytes with control marrow did not inhibit CFU-C growth. We conclude that in Shwachman's syndrome committed granulocytic stem cells are present, and the numbers detected in vitro vary widely as does the clinical neutropenia. The proliferative activity of recognizable granulocytic cells is normal and neither a deficiency of humoral stimulators nor the presence of serum or cellular inhibitors of granulopoiesis can be demonstrated.

Characteristics of Cell Proliferation in Children's Lymphoblastic Leukemia

1968 ◽  
Vol 54 (2) ◽  
pp. 147-160 ◽  
Author(s):  
Alessandro Pileri ◽  
Renzo Pietro Tarocco ◽  
Felice Gavosto ◽  
Alberto Ponzone ◽  
Paolo Nicola
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Proliferative Activity ◽  
Tritiated Thymidine ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Cell Diameter ◽  
Acute Leukemias ◽  
Peripheral Cells

The proliferative activity of the bone marrow and peripheral cells of acute infant lymphoblastic leukemia was evaluated by « in vitro » incorporation of thymidine-H3. The proliferative activity of leukemic lymphoblasts proved roughly similar to that already observed in hemocito-myeloblastic acute leukemias of adults. Within the lymphoblastic population, incorporation of tritiated thymidine was distributed very heterogeneously and there was no labelling of the smaller blasts. In the larger blasts, the labelling index increased progressively with the increase in cell diameter. The acute leukemia population can thus be divided into two classes: proliferating and non-proliferating. A study of the proliferative activity of lymphoblasts, contemporaneously in bone marrow and peripheral cells, suggested a division of cases into two groups. In one proliferative activity in the marrow was greater than in the peripheral blood; in the other it was equal to or less than in the peripheral blood. The second group was made up of cases whose clinical features presented a much more marked hepato-splenomegaly and high peripheral leucocytosis. A more detailed study of proliferative activity considering various classes of blasts within the same population showed that, in the first group of patients, the highest percentage of large blast cells is found at bone marrow level, while in the second the percentage of large blasts in the marrow is equal to or less than that observed in the peripheral blood. It was also shown that total proliferative activity is correlated to the percentage of large blasts. On the basis of these findings, one may admit that in first group forms the leukemia cells are generated prevalently in the bone marrow, while in second group forms most leukemic cells are formed elsewhere.

scholarly journals The Remission and Relapse Status of Acute Leukemia as Studied by the In Vitro Uptake of Tritiated Thymidine by Peripheral Blood Leukocytes

Blood ◽  
1968 ◽  
Vol 32 (2) ◽  
pp. 292-304
Author(s):  
THEODORE S. ZIMMERMAN ◽  
HERMAN A. GODWIN ◽  
MARVIN ZELEN ◽  
SEYMOUR PERRY
Keyword(s):  
Acute Leukemia ◽  
Peripheral Blood ◽  
Normal Population ◽  
Tritiated Thymidine ◽  
Additional Parameter ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Normal Controls ◽  
In Vitro Uptake

Abstract H3TdR uptake by peripheral blood leukocytes has been measured in patients with acute leukemia and in hematologically normal controls. Patients with acute leukemia in remission and relapse generally had elevated uptakes and formed populations distinct from the normal population and from each other, although overlap of values between each population was present. The measurement of H3TdR uptake may prove useful as an additional parameter for studying acute leukemia.

scholarly journals Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1121-1129 ◽  
Author(s):  
G Damia ◽  
KL Komschlies ◽  
CR Faltynek ◽  
FW Ruscetti ◽  
RH Wiltrout
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Peripheral Blood Lymphocytes ◽  
Lymphoid Cells ◽  
Blood Leukocytes ◽  
Interleukin 7 ◽  
Immature B Cells ◽  
Myeloid Progenitor Cells ◽  
Phenotype Analysis

Abstract The administration of greater than or equal to 5 micrograms interleukin- 7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resulted in a greater than 90% reduction in the frequency and total number of single lineage colony- forming unit-culture (CFU-c) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte colonies that could be cultured from the BM, but a fivefold to 15-fold increase in the number of these progenitors that could be cultured from the spleen. All of these effects were reversible with progenitor and white blood cell numbers returning to near normal by day 6. Morphologic analysis of cells obtained from the BM of IL-7-treated mice showed an increase in lymphoid cells. Surface phenotype analysis showed that most of this IL- 7-induced increase in lymphocytes was attributable to an increase in immature B cells (B220+, sIg-), while cells expressing the myelomonocytic markers 8C5 and MAC-1 decreased by twofold to threefold. Further studies showed that the administration of IL-7 to mice that had been rendered leukopenic by the injection of cyclophosphamide (Cy) or 5- fluorouracil (5FU) exhibited a more rapid recovery and/or overshoot in their peripheral blood lymphocytes when compared with mice treated with Cy or 5FU alone. These results show that IL-7 can differentially regulate myelopoiesis in the BM and spleen, while stimulating lymphopoiesis.

scholarly journals Effects of immunoregulatory drugs on human peripheral blood T lymphocytes function in vitro

2002 ◽  
Vol 10 (1) ◽  
pp. 19-23
Author(s):  
Marija Hatzistilianou ◽  
Soultana Hitoglou ◽  
Despina Gougoustamou ◽  
Alexandros Kotsis ◽  
Athanasios Kallinderes ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Lymphocyte Proliferation ◽  
Human Peripheral Blood ◽  
Tritiated Thymidine ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Dependent Manner ◽  
T Lymphocyte Subsets ◽  
Activation Antigens

BACKGROUND: The purpose of the study was to evaluate the mode of action of different immunoregulatory drugs in lymphocyte proliferation and activation METHODS: The drugs studied were prednisolone (PRED), cyclosporin A (CsA) the recombination of PRED and CsA, L-asparaginase and cytosine-arabinose (ara-C). Peripheral blood lymphocytes from normal blood donors were stimulated by phytohemagglutinin (PHA). Lymphocytes proliferation and activation were determined by tritiated thymidine ([3H]TdR) incorporation secretion of interleukin-2, level of soluble interleukin-2 receptors in the supernatant of the culture medium, and immunophenotyping analysis of T lymphocyte subsets. RESULTS: Among PRED CsA and their combination, the strongest inhibition of cell proliferation was induced by PRED while L-asparaginase and ara-C inhibited PHA stimulated T cells proliferation in concentration and time dependent manner. Among PRED, CsA and their combination, CsA induced the greatest inhibition of IL-2 production. All the immunoregulatory drugs inhibited lymphocyte proliferation and expression of activation antigens. CONCLUSION: The immunoregulatory drugs inhibit both lymphocyte proliferation and activation but in a different way.

scholarly journals Decreased ecto-5'nucleotidase activity of peripheral blood lymphocytes in human monoclonal gammopathies: correlation with tumor cell kinetics

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 530-534 ◽  
Author(s):  
M Massaia ◽  
DD Ma ◽  
M Boccadoro ◽  
F Golzio ◽  
P Gavarotti ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Linear Regression ◽  
Peripheral Blood ◽  
Tritiated Thymidine ◽  
Peripheral Blood Lymphocytes ◽  
Cell Subpopulation ◽  
Thymidine Uptake ◽  
Monoclonal Gammopathies ◽  
Normal Controls

Abstract Ecto-5′nucleotidase (5′NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5′NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5′NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5′NT on LI% which was statistically significant: the higher the LI%, the lower the 5′NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5′NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5′NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5′NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5′NT deficiency of unseparated T lymphocytes.

scholarly journals Decreased ecto-5'nucleotidase activity of peripheral blood lymphocytes in human monoclonal gammopathies: correlation with tumor cell kinetics

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 530-534
Author(s):  
M Massaia ◽  
DD Ma ◽  
M Boccadoro ◽  
F Golzio ◽  
P Gavarotti ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Linear Regression ◽  
Peripheral Blood ◽  
Tritiated Thymidine ◽  
Peripheral Blood Lymphocytes ◽  
Cell Subpopulation ◽  
Thymidine Uptake ◽  
Monoclonal Gammopathies ◽  
Normal Controls

Ecto-5′nucleotidase (5′NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5′NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5′NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5′NT on LI% which was statistically significant: the higher the LI%, the lower the 5′NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5′NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5′NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5′NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5′NT deficiency of unseparated T lymphocytes.

scholarly journals Diurnal Variation of Proliferative Activity in the Human Bone Marrow

Blood ◽  
1965 ◽  
Vol 26 (1) ◽  
pp. 1-7 ◽  
Author(s):  
ALVIN M. MAUER ◽  
Virginia Fisher ◽  
Ruth Scheib
Keyword(s):  
Bone Marrow ◽  
Diurnal Variation ◽  
Proliferative Activity ◽  
Bone Marrow Cells ◽  
Tritiated Thymidine ◽  
Precursor Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Erythroid Precursor

Abstract A study was made of the possible diurnal variation of proliferative activity of human bone marrow cells. A distinct diurnal variation of mitotic indices was present in 5 of 6 normal subjects. The average number of mitotic figures per 1000 nucleated cells in the 6 subjects was 7.6 at 6:00 a.m., 9.5 at noon, 10.5 at 6:00 p.m., and 13.1 at midnight. An assessment of diurnal variation in the per cent of cells synthesizing deoxyribonucleic acid was made in 4 additional subjects by means of incubation of aspirated marrow samples with tritiated thymidine in vitro. By this method, no consistent variation of synthesis could be found in erythroid precursor cells, but the per cent of myeloid precursor cells incorporating the label was lowest at midnight in each subject.

scholarly journals Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1121-1129 ◽  
Author(s):  
G Damia ◽  
KL Komschlies ◽  
CR Faltynek ◽  
FW Ruscetti ◽  
RH Wiltrout
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Peripheral Blood Lymphocytes ◽  
Lymphoid Cells ◽  
Blood Leukocytes ◽  
Interleukin 7 ◽  
Immature B Cells ◽  
Myeloid Progenitor Cells ◽  
Phenotype Analysis

The administration of greater than or equal to 5 micrograms interleukin- 7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resulted in a greater than 90% reduction in the frequency and total number of single lineage colony- forming unit-culture (CFU-c) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte colonies that could be cultured from the BM, but a fivefold to 15-fold increase in the number of these progenitors that could be cultured from the spleen. All of these effects were reversible with progenitor and white blood cell numbers returning to near normal by day 6. Morphologic analysis of cells obtained from the BM of IL-7-treated mice showed an increase in lymphoid cells. Surface phenotype analysis showed that most of this IL- 7-induced increase in lymphocytes was attributable to an increase in immature B cells (B220+, sIg-), while cells expressing the myelomonocytic markers 8C5 and MAC-1 decreased by twofold to threefold. Further studies showed that the administration of IL-7 to mice that had been rendered leukopenic by the injection of cyclophosphamide (Cy) or 5- fluorouracil (5FU) exhibited a more rapid recovery and/or overshoot in their peripheral blood lymphocytes when compared with mice treated with Cy or 5FU alone. These results show that IL-7 can differentially regulate myelopoiesis in the BM and spleen, while stimulating lymphopoiesis.

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