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M9490101.TXT
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1994-09-03
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Document 0101
DOCN M9490101
TI Differential recovery of polymorphonuclear neutrophils, B and T cell
subpopulations in the thymus, bone marrow, spleen and blood of mice
following split-dose polychemotherapy.
DT 9411
AU Talmadge JE; Jackson JD; Borgeson CD; Perry GA; University of Nebraska
Medical Center, Department of Pathology; and Microbiology, Omaha
68198-5660.
SO Cancer Immunol Immunother. 1994 Jul;39(1):59-67. Unique Identifier :
AIDSLINE MED/94320119
AB In these studies, we examined the effect of a maximum-tolerated,
split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and
1,3-bis(2-chloroethyl)-1-nitrosourea carmustine on neutrophil and
lymphocyte, subpopulations in the peripheral blood (PBL), thymus, bone
marrow and spleen. It was found that this protocol of polychemotherapy,
modeled after the induction protocol used with autologous bone marrow
transplantation for breast cancer, suppressed both B and T cell
populations and T cell function at times when the absolute neutrophil
count had returned to normal or supernormal numbers. In the peripheral
blood, 7 days following initiation of chemotherapy, there was a twofold
increase in the percentage of granulocytes as compared to the level in
control animals on the basis of a differential count. The
polymorphonuclear neutrophil (PMN) frequency in the bone marrow was
increased on day 14 and statistically identical to that in control mice
on all other days analyzed. In contrast to the bone marrow cells and PBL
on day 7, the frequency of PMN in the spleen and thymus was depressed. B
cells (B220+) were depressed in the pBL, spleen and bone marrow and took
18-32 days to return to their normal frequency, while the frequency of B
cells in the thymus was increased owing to a loss of immature T cells.
The percentage of CD3+ cells in the thymus, spleen and bone marrow was
significantly increased and required 10-18 days to return to normal
levels, while the absolute number of CD3+ cells in the blood varied
around the normal value. The ratio of CD4+ to CD8+ cells in all the
organs studied varied only slightly owing to a similar reconstitution of
CD4+ and CD8+ cells. In contrast to the phenotypic recovery of the CD3+,
CD4+, and CD8+ cells, the ability of the splenic lymphocytes to respond
to concanavalin-A was depressed and remained depressed, despite the
phenotypic reconstitution of the T cell subsets, on the basis of both
percentage and absolute cell number. These results show a selective T
and B cell depression following multi-drug, split-dose chemotherapy in
tissue and blood leukocyte populations and a chronic depression in T
cell function.
DE Animal Antineoplastic Agents, Combined/*TOXICITY B-Lymphocyte
Subsets/*DRUG EFFECTS B-Lymphocytes/DRUG EFFECTS/PHYSIOLOGY Bone
Marrow/*CYTOLOGY/*DRUG EFFECTS Carmustine/ADMINISTRATION & DOSAGE Cell
Separation Cisplatin/ADMINISTRATION & DOSAGE Comparative Study
Concanavalin A/PHARMACOLOGY Cyclophosphamide/ADMINISTRATION & DOSAGE
CD4-CD8 Ratio/DRUG EFFECTS Female Flow Cytometry Mice Mice, Inbred
BALB C Neutrophils/*DRUG EFFECTS/PHYSIOLOGY Spleen/*CYTOLOGY/*DRUG
EFFECTS Stimulation, Chemical Support, Non-U.S. Gov't T-Lymphocyte
Subsets/*DRUG EFFECTS T-Lymphocytes/DRUG EFFECTS/PHYSIOLOGY Thymus
Gland/*CYTOLOGY/*DRUG EFFECTS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).