PubMed Health⌕ Search

Biomedical subjects

C W Caldwell

Publications and source records attributed to C W Caldwell.

At least 19 recordsLinked to original sources
PubMed1992

Psychological factors, immunologic activation, and disease activity in rheumatoid arthritis.

The purpose of this study was to use structural equation modeling techniques to examine potential interrelationships among psychological factors, immunologic activation, and disease activity in rheumatoid arthritis (RA). The subjects were 80 male patients with a diagnosis of classic or definite RA. Measures included the Beck Depression Inventory, the Arthritis Helplessness Index, and the Arthritis Impact Measurement Scales (AIMS) pain score. Joint counts and immunophenotypic analyses of peripheral blood lymphocytes also were collected. Path analysis showed that percentage of HLA-DR+ cells in the peripheral blood and helplessness were related to join count. In addition, joint count had an effect upon depression. Depression had an effect upon pain, but there was no reciprocal effect of pain upon depression. This study describes a preliminary path model of interrelationships among psychological factors, immunologic activation, and disease activity in RA.

Aged↗
PubMed1992

Flow cytometry, morphometry and histopathology as biomarkers of benzo[a]pyrene exposure in brown bullheads (Ameiurus nebulosus).

Brown bullheads were given a single intraperitoneal dose of 0, 5, 25 or 125 mg kg-1 benzo[a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon, and evaluated over 18 months. Flow cytometric analyses of hepatocyte DNA content indicated an increase in DNA synthesis in BaP-exposed fish prior to day 14 post-exposure. Thereafter, all flow cytometric variables returned to initial levels. Histopathological evaluation of livers from fish sampled at 18 months revealed significant differences among treatments in the amount of hepatic macrophage ceroid pigmentation and basophilic staining intensity. No neoplasms or changes in blood cell DNA content were detected. Significant morphometric variations existed among fish, but differences between sexes overshadowed differences attributable to dose. Flow cytometry yielded no evidence of long-term DNA alterations from a single exposure to BaP; however, the differences detected by DNA analysis shortly after the toxic event suggest that flow cytometric cell cycle analysis may be useful for documenting continuing exposures.

Animals↗
PubMed1992

Expression of CD45 isoforms by Epstein-Barr virus-transformed human B lymphocytes.

CD45 is the most common protein tyrosine phosphatase (PTPase) in the membrane of white blood cells, serving as a potent regulator of lymphocyte activation and signal transduction. While the amino acid sequence of the intracellular domain of the molecule is conserved, that of the extracellular domain occurs in multiple isoforms, each of the result of alternative mRNA splicing. In T lymphocytes, the lowest relative molecular mass (Mr) form, CD45RO, is associated with acquisition of memory function, whereas the highest Mr isoform, CD45RA, occurs in "naive" T cells. Recently, B cells were also found to express CD45RO following in vitro activation. In order to more fully characterize the expression of CD45 on activated B cells, we have studied its appearance on Epstein-Barr virus-transformed (EBV-t) cells and have found heterogeneous expression of CD45RO and CD45RA. CD45RO expression was unstable with eventual loss by some EBV-t lines, and loss followed by reappearance in others. CD45RA and CD45RO varied independently whereas CD45 remained stable and high, suggesting a fluctuation in other CD45 isoforms. Immunostaining for CD45RB indicates that a probable 190-kDa isoform may be responsible for this observation. A similar bidirectional reversible shifting between CD45RA and CD45RO on T-cell lines has also been reported by Rothstein et al. In contrast to some reports on normal B cells, neither CD45RA nor CD45RO expression was associated with PCA-1 expression. Further evidence that these EBV-t lines may not correspond to a well-defined stage of B-cell differentiation is provided by the observation that a disproportionate loss of CD20 compared to CD19 was noted for several lines. The basis for the CD45 isoform switching, or any functional difference(s) in the expressed isoforms, is not yet known for human B cells.

Antigens, CD↗
PubMed1992

A controlled study of lymphocyte subsets in rheumatoid arthritis.

The purpose of this study was to determine if patients with rheumatoid arthritis (RA) exhibited unique patterns of peripheral blood lymphocyte (PBL) subsets in comparison to patients with osteoarthritis (OA) and, further, if such differences related to disease activity or nondisease factors. Data from 63 RA patients and 47 OA patients revealed that the RA patients had lower absolute numbers of CD2+ and CD4+ lymphocytes. Small differences also were found in selected B-cell subsets and subsets of lymphocytes expressing CD16 and/or CD57 antigens. Further analysis revealed that these differences were due primarily to the effects of cytotoxic medications in the RA group. However, there were also alterations in some subsets independent of medication groups. PBL subsets in RA patients did not relate to chronic low-dose prednisone or measures of disease activity. This study demonstrated the need to control carefully for variables such as age and medication in immunophenotypic investigations of RA.

Aging↗
PubMed1991

Relationship between CD45 antigen expression and putative stages of differentiation in B-cell malignancies.

The cell-surface antigen CD45 is a complex family of high-molecular-weight glycoproteins expressed on all lymphohematopoietic cells, but not in the same molecular isoform. This antigen complex is known to exhibit protein tyrosine phosphatase (PTPase) activity and appears to have a role in regulation of cell differentiation. In that CD45 expression parallels stages of differentiation in normal bone marrow B cells, it was of interest to evaluate this process in malignant B cells. Monoclonal antibodies (MoAbs) were used to investigate the quantitative expression of CD45 and CD45RA on the B cells of lymphoid leukemias. Employing standardized flow cytometric methods, it was found that the fluorescence intensity (FI) of immunostained malignant B cells, as a reflection of the antigen content, demonstrated correlations with the putative stage of cell differentiation for malignancies at the earlier stages, but at the later stages, a progressive loss of CD45 was observed. Since this antigen family has been found to display PTPase activity, further investigation of CD45 alterations in malignancies may provide insight into potential regulatory disturbances.

Adolescent↗
PubMed1991

Translocation of CD45RA in neutrophils.

The CD45 family of high-Mr glycoprotein antigens is expressed in some molecular form on all lymphohematopoietic cells. Different cell types express various isoforms in a precisely programmed fashion. In addition to cell surface CD45 antigens, we recently demonstrated a cytoplasmic granule-associated pool of CD45RA, the highest Mr isoform, in mature neutrophils that is generally absent from the cell surface under nonstimulatory conditions. Under such conditions, the major cell surface form is CD45RO, the low-Mr isoform. In the present study, we demonstrate the ability of calcium ionophore A23187 to induce translocation of cytoplasmic CD45RA to the cell surface as well as to increase the cell surface expression of CD45RO and CD45. This process was calcium dependent and rapid, occurring within 5 min. A series of experiments using chemical antagonists of protein kinases suggest that this up-regulation may be mediated via the calmodulin system rather than via protein kinase C. Although the exact function(s) of the various isoforms of CD45 is not known, this translocation suggests a role for CD45RA in neutrophil activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Expression of the low Mr isoform of CD45 (CD45RO) in B-cell non-Hodgkin's lymphomas.

The CD45 antigen family consists of multiple molecular isoforms ranging from 180 to 220 relative molecular mass (Mr). The highest Mr isoforms are recognized by monoclonal antibodies (MoAbs) designated CD45RA, while those recognizing the low Mr isoform are designated CD45RO. About half of the T-cells in peripheral blood express CD45RA while the remainder express CD45RO. A switch from the high to the low Mr isoform of CD45 has been found in association with the process of T-cell stimulation and acquisition of "memory." B-cells normally express CD45RA, but not CD45RO. However, under stimulatory conditions, B-cells may be capable of undergoing an isoform switch and expressing CD45RO. The expression of this low Mr isoform of CD45 was investigated in lymphomas composed of monoclonal B-cells to determine if such a switch occurs in malignant B-cell populations. The vast majority (110/117 cases) of B-cell lymphomas expressed only CD45RA, while a very small number (7/117 cases) expressed CD45RO, but not CD45RA. There was no relationship between the CD45RO expression and the histologic subtype. The physiological significance of this unusual expression of CD45RO in a subpopulation of B-cell lymphomas is not clear. In that CD45RO, as defined by the MoAb UCHL 1, is typically used as a marker of T-cells in tissue sections, caution must be exercised in interpretation, since not all T-cells are reactive and some B-cell lymphomas are reactive.

Antigens, Differentiation↗
PubMed1991

Surface and cytoplasmic expression of CD45 antigen isoforms in normal and malignant myeloid cell differentiation.

The CD45 family contains protein tyrosine phosphatase (PTPase) activity and is expressed in one or more of its isoforms on all lymphohematopoietic cells. Considerable work has focused on CD45 expression by lymphoid cells, but minimal work has involved granulocytes. Granulocytic, or myeloid, cell differentiation is accompanied by a number of morphologic and immunophenotypic changes. This study used flow cytometric and immunocytochemical methods in conjunction with morphologic assessment to investigate the expression of CD45 isoforms during differentiation of normal and malignant granulocytic cells. On normal bone marrow cells, the quantity of surface CD45 did not change during earlier stages but did increase significantly at the terminal stages (bands and polymorphonuclear leukocytes [PMNs]). CD45RO (the low relative molecular mass [Mr] isoform) was very dimly expressed on immature cells but became increasingly brighter beginning at approximately the myelocyte stage. The high Mr isoform (CD45RA) was virtually absent from the cell surface at all stages. Only a small percentage (3-15%) of PMNs expressed surface CD45RA. However, there was a cytoplasmic pool of each isoform associated with membrane-bound granules found throughout differentiation, with remarkable increases in expression at the terminal stages. In the case of acute myeloid leukemias (AMLs), most cases expressed surface CD45RA with, or without, CD45RO, regardless of their French-American-British (FAB) classification. This appeared to be a stable process at diagnosis and relapse in individual patients and may therefore serve as a diagnostic aid. The biologic significance of this aberrant expression of CD45RA by malignant cells is unknown but raises important questions regarding the cellular processes of phosphorylation/dephosphorylation in normal and malignant cells.

Adult↗
PubMed1991

B-cell precursors in normal pediatric bone marrow.

A number of studies have been published pertaining to "normal" lymphocyte subsets in bone marrow. However, these studies are based on normal adult marrow or marrows of children with leukemia in remission or other systemic illness. Data on hematologically normal children are lacking. This study demonstrates that, compared with that of adults, bone marrow of hematologically normal children has an increased percentage of B cells and B-cell precursors. Dual-parameter flow cytometric methods demonstrated subpopulations of B cells at various stages of differentiation; the percentage of cells in these subsets is highest in the very young and decreases with increasing age. Caution must be exercised when searching for early leukemic relapse in pediatric marrows because these normal immature B-cell precursors immunophenotypically resemble leukemic blasts.

Adolescent↗
PubMed1991

Expansion of immature thymic precursor cells in peripheral blood after acute marrow suppression.

Leukemoid reactions occur in response to a number of infectious agents and sometimes may be associated with bone marrow suppression. After acute suppression of the bone marrow, a resurgent hyperplasia occurs that may appear as synchronous maturation of a single cell type. The authors describe the case of a 13-year-old child in whom a remarkable lymphocytosis developed during a period of pancytopenia associated with a febrile syndrome resembling Ehrlichiosis. Most of these lymphoid cells were morphologically similar to large granular lymphocytes (LGLs), but many appeared to be less mature. Immunophenotypic studies demonstrated most of these lymphoid cells to be immature T cells at an "intermediate" or "transitional" stage of thymocyte differentiation characterized by the CD1-CD3+CD4-CD8- phenotype, as well as positivity for nuclear terminal deoxynucleotidyl transferase. In T-cell ontogeny, this stage represents a transition between thymic precursors and mature thymocytes. Their presence in the peripheral blood of this child is thought to represent a lymphocytic leukemoid response to his infection. Cases such as this may be confused with malignancy.

Acute Disease↗
PubMed1990

Expression of CD45 isoforms in lymph node reactive hyperplasia.

The CD45 antigen family consists of multiple molecular isoforms ranging from 180 to 220 kDa. The highest Mr isoforms are recognized by monoclonal antibodies (MoAbs) designated CD45RA, while those recognizing the low Mr isoforms are designated CD45RO. T cells expressing CD45RA are "naive" or unprimed, while those expressing CD45RO have "memory." Further, stimulation of CD45RA+ T cells induces an isoform switch to the CD45RA-/CD45RO+ phenotype. The present study examined this in vitro process by determining the in vivo CD45 isoform expression of T cells from human hyperplastic lymph nodes. Hyperplastic, as opposed to nonhyperplastic, lymph nodes exhibited the expected CD45 isoform switch from CD45RA+ to CD45RO+ T cells that has been described in vitro. The percentage of CD45RO+ T cells did not correlate with other parameters of lymphoid activation. Thus, CD45RO expression probably represents a marker of differentiation and acquisition of "memory" or late cellular activation.

Antibodies, Monoclonal↗
PubMed1990

Suppressed peripheral blood lymphocyte blastogenesis in pre- and postpartal sheep by chronic heat-stress, and suppressive property of heat-stressed sheep serum on lymphocytes.

Phytohemagglutinin (PHA) and concanavalin A (Con A)-induced blastogenesis of peripheral blood lymphocytes was examined in heat-stressed pre- and postpartal sheep. The peak responses of lymphocytes to PHA and Con A in heat-stressed sheep revealed significant reduction before and after parturition compared with those in the corresponding control animals kept under thermoneutral conditions. Furthermore, the effect of serum from control or heat-stressed sheep on PHA-induced lymphocyte blastogenesis was examined. Supplementation of serum from heat-stressed sheep significantly suppressed the blastogenesis of lymphocytes obtained from healthy sheep, bovine, and human donors. Unlike dexamethasone, heat-stressed sheep serum did not inhibit IL-2 production by PHA-stimulated human peripheral blood lymphocytes. These results indicate that the immunosuppression of heat-stressed sheep is in part mediated by serum factor(s) that can modulate T-cell function in a species nonspecific manner.

Animals↗
PubMed1990

Acute leukemia/lymphoma of plasmacytoid T-cell type.

Plasmacytic morphologic characteristics are usually associated with cells of B-lymphocyte origin. Recently, plasmacytoid T-cells have been described in reactive lymph nodes and a rare form of lymphoma characteristically associated with myeloproliferative disorders. This report documents a case of plasmacytoid T-cell malignancy that initially presented as an acute leukemia in an elderly man with a longstanding myelodysplastic syndrome. The tumor replaced bone marrow and involved lymph nodes. Despite aggressive therapy, he died quickly of his leukemia/lymphoma. This case illustrates the need for complete cellular analysis in the diagnosis of morphologically plasmacytic malignancies and raises additional questions about the relationship of this peculiar type of T-cell to the hematopoietic marrow.

Acid Phosphatase↗
PubMed1987

Relationship between T200 antigen expression and stages of B cell differentiation in resurgent hyperplasia of bone marrow.

Using monoclonal antibodies (MoAbs) and dual-parameter flow cytometric techniques, bone marrow mononuclear cells (MMC) from patients with resurgent hyperplasia were analyzed for their coexpression of HLe-1 (T200) and antigens normally associated with particular stages of B cell differentiation. The marrow from those with resurgent hyperplasia contained increased numbers of B cell precursors in multiple stages of differentiation compared to controls, thus providing a useful model system for studies of B cell differentiation. These studies indicate that the quantitative expression of T200 is differentiation-related on normal and malignant B cells and B cell precursors. Immature cells express low amounts of T200, while increasing levels of maturity correlated with increasing amounts of the antigen. This study increases the understanding of relationships between B cell surface antigens and T200 and further demonstrates that B cell hyperplasia occurs commonly in association with bone marrow reactive or resurgent processes. The quantitative, rather than only the qualitative, expression of T200 is therefore a useful marker of B cell differentiation in reactive hyperplasia and in further investigation of B cell malignancy.

Adolescent↗
PubMed1977

Enzyme immunoassay for hepatitis B and its comparison to other methods.

A solid-phase enzyme immunoassay for the qualitative detection of hepatitis B surface antigenemia is presented and the results compared to the counter-immunoelectrophoresis and radioimmunoassay methods for detection of the same antigen. The enzyme-antibody conjugate was prepared from horseradish peroxidase coupled with antibodies to three sub-types of hepatitis B virus. Polystyrene plastic tubes were used as the solid-phase support. The results of the enzyme immunoassay compare favorably with radioimmunoassay and exceed counterimmunoelectrophoresis in sensitivity.

Counterimmunoelectrophoresis↗