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Biomedical subjects

D E Campbell

Publications and source records attributed to D E Campbell.

At least 19 recordsLinked to original sources
PubMed1997

Caregiving to very low birthweight infants: a model of stress and immune response.

Mothers of preterm, very low birthweight (< or = 1500 g; VLBW) infants experience the stress of caring for small, fragile infants at the same time that they are recovering from the relative immunosuppression of pregnancy and when many health behaviour changes (e.g., nutrition) occur which also may influence immune status. The purpose of this study was to examine changes in anxiety and depression and in health behaviors, as well as lymphocyte proliferation and natural killer cell activity in mothers of preterm, VLBW infants compared to mothers of healthy term infants. Mothers of preterm VLBW infants have decreased in vitro lymphocyte response to mitogens compared to mothers of healthy term infants over time, and this difference could not be explained by anxiety, depression, or health behaviors. However, among mothers of VLBW infants, anxiety was related to decreased lymphocyte proliferation response at 1 month postpartum. There was no relationship between maternal depression and lymphocyte proliferative response in mothers of term infants. Natural killer cell activity did not differ between the two groups of mothers, nor was there a relationship between natural killer cell activity and maternal anxiety, depression, or health behaviors. Thus, lymphocyte proliferative response to mitogens may be an important biologic market of increased stress in mothers of VLBW infants in the first couple of months postpartum.

Adult↗
PubMed1997

Cytokines released by human peripheral blood mononuclear cells inhibit the production of early and late cytomegalovirus proteins.

Cytomegalovirus-infected human fibroblasts are susceptible to lysis by natural killer cells and cytotoxic T cells. The purpose of this study was to determine whether non-lytic mechanisms might also contribute to the control of cytomegalovirus infection. The appearance of cytomegalovirus proteins in infected fibroblasts was determined by flow cytometry. Infected fibroblasts incubated with peripheral blood mononuclear cells for 3 days expressed less early and late proteins than fibroblasts incubated without peripheral blood mononuclear cells. Supernatants generated by the cocultivation of peripheral blood mononuclear cells with cytomegalovirus-infected fibroblasts inhibited the production of cytomegalovirus early and late proteins. The soluble factors in supernatants which contributed to the inhibitory effect were identified as interferons alpha, beta and gamma, and tumor necrosis factors alpha and beta. The ability of supernatants to inhibit the production of cytomegalovirus early protein was mimicked by combinations of corresponding recombinant cytokines. The inhibition of cytomegalovirus protein production by cytokines produced by peripheral blood mononuclear cells may contribute to early containment of cytomegalovirus infection.

Antigens, Viral↗
PubMed1997

Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in response to Staphylococcus aureus and staphylococcal superantigen in childhood atopic dermatitis.

We have examined the cell-mediated immunity (CMI) to Staphylococcus aureus (S. aureus) and Staphylococcal enterotoxin B (SEB) in peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis (AD) and from non-atopic child controls by measurement of proliferative responses and production of the cytokines IFN-gamma and IL-4. PBMC from children with AD showed significantly higher proliferative responses to both S. aureus (P < 0.01) and SEB (P < 0.05). Despite this enhanced proliferation, production of IFN-gamma in response to S. aureus (P < 0.001) and SEB (P < 0.01) from these PBMC was significantly diminished. In contrast, PBMC from children with AD were significantly more likely to produce IL-4 in response to S. aureus (P < 0.01). These findings demonstrate in vitro heightened CMI to S. aureus in children with AD, and implicate S. aureus as a potent inflammatory stimulant. Impaired IFN-gamma production to S. aureus in vivo may result in failure to eradicate S. aureus from skin. The organism's persistence on skin would contribute to inflammation by causing continued T cell activation and release of pro-inflammatory mediators.

Cell Division↗
PubMed1997

Lymphocyte, monocyte, and natural killer cell reference ranges in postpartal women.

Normative values for immune-cell subsets in postpartal women, who are recovering from the relative immunosuppression of pregnancy, have not been established. Considerable differences in normative values for subsets of immune cells have been demonstrated based on sociodemographic factors, such as age and race. In order to make accurate clinical decisions about postpartal women, comparisons with normal reference ranges are necessary. Therefore, flow cytometric data for 51 healthy women at 4 months postpartum are presented and changes over the first 4 postpartal months are documented. The levels of some lymphocyte cell subsets, such as CD4+/CD45RA+ and Ia on lymphocytes, remained stable over time. The levels of other lymphocyte cell subsets, such as CD4+/CD29+, increased over the first 4 postpartal months, while those of other cell subsets, such as CD8 and CD11b, increased between delivery and 2 months postpartum and then dropped again by the fourth postpartal month. The levels of two natural killer cell subsets (CD3-/CD16+ and CD3-/CD57+) rose from delivery until 1 month postpartum and then plateaued. Comparisons were made with reference ranges of nonpostpartal groups provided in the literature and in a study of healthy women being conducted in the same laboratory, and postpartal women were found to have lower values of CD8, CD3-/CD16+, CD4+/CD45RA+, CD20, and CD11b than those reported in the literature.

Adult↗
PubMed1997

Immune responses in mothers of term and preterm very-low-birth-weight infants.

Differences in the levels of immune cell subsets present in peripheral blood have been demonstrated based on sociodemographic factors such as age and race. Postpartal women, who are recovering from the immune changes that are concomitant with pregnancy, have lymphocyte and monocyte values that differ from other populations. A subgroup of postpartal women, mothers who deliver preterm very-low-birth-weight (VLBW) (< or = 1,500 g) infants, may have further differences in values of immune cell subsets and in immune functioning either because of hormonal factors or lifestyle changes or because of the stress they experience after their infant's birth and for the first few months of infant caretaking. This study examined anxiety, depression, and immune cell phenotypes in 30 mothers of VLBW infants and in 30 mothers of healthy term infants over the first 4 postpartal months to determine if mothers of preterm VLBW infants differed from mothers of healthy term infants in psychological and immunologic parameters. Additionally, lymphocyte proliferation and natural killer cell functional assays were performed in a subset of mothers. Mothers of VLBW infants had increased anxiety and decreased lymphocyte proliferation compared to mothers of term infants. When lymphocyte and monocyte subsets were compared over time between the two groups of mothers differences were found in CD8, CD20, CD3-/CD56+, CD14, and HLA class II Ia on monocytes. Mothers with high-fat diets had lower percentages of some monocytes (CD14), lymphocytes (CD4+/CD45RA+), and natural killer cells (CD3-/CD57+) during the first 4 postpartal months.

Adult↗
PubMed1996

New perspectives on inflammation in atopic dermatitis.

Recent information implicates the stimulation of T cells by Staphylococcus aureus antigens and exotoxins as a likely factor in provoking the inflammatory response in atopic dermatitis. S. aureus secrets exotoxins called superantigens, which stimulate a large proportion of T cells. In addition, protein A, a component of the cell wall of S. aureus, is a potent B cell mitogen. This understanding provides a rationale for attempting to reduce the staphylococcal skin colonization of patients with severe atopic dermatitis and correlates with the clinical observation in a number of situations of marked improvement in atopic dermatitis following antibiotic treatment.

Adult↗
PubMed1996

A comparison of electrochemiluminescence and flow cytometry for the detection of natural latex-specific human immunoglobulin E.

In vitro correlates of type 1 hypersensitivity to natural latex (NL) proteins continue to be limited by both sensitivity and specificity. Methods which have detection limits in the picogram range, namely, radioallergosorbent assays (RAST) and enzyme-linked immunosorbent assays (ELISA), are inadequate for the identification of NL hypersensitivity in certain at-risk groups, such as health care workers. A flow cytometry assay (FCA), previously shown to be comparable to RAST and ELISA in the identification of NL-sensitized pediatric patients with spina bifida, was compared with electrochemiluminescence (ECL) in the evaluation of pediatric patients with spina bifida and NL-sensitized adult health care workers. As with RAST and ELISA, ECL is capable of detecting picogram amounts of specific analyte. The ECL assay detected NL-specific immunoglobulin E (NL-IgE) in three of six health care workers with strong histories of NL hypersensitivity. All six patients were negative by FCA. Further, 2 of 11 spina bifida patients found to be NL-IgE negative by FCA were NL-IgE positive by ECL. These findings suggest that in sensitivity the ECL assay is an improvement over the FCA for the identification of NL-sensitive individuals.

Adult↗
PubMed1996

Production of T-helper cell subsets and cytokines by lymphocytes from patients with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of disorders characterized by recurrent and persistent superficial candidal infections. Cytokine-induced dysregulation of T-helper cell function has been described in other immune-deficient states but has not been studied in CMC patients. We studied T-helper cell subsets by flow cytometry and cytokine production by stimulated lymphocytes in six CMC patients, two healthy pediatric controls, and five healthy adult controls. Peripheral blood lymphocytes were stimulated in vitro with phytohemagglutinin or Candida albicans extract, and the production of interleukin-2R (IL-2R), IL-4, IL-10, and gamma interferon in the supernatants was measured by enzyme-linked immunosorbent assay. CMC patients had a decrease in the CD29+/CD29+ cell population compared with the numbers in controls (P < 0.02). The percentage of CD4+/CD45RA+ cells was greater in patients than in controls, but the difference was not significant. There was no difference in the production of IL-10 or gamma interferon by the patient lymphocytes. CMC patients produced more IL-4 than the controls (P < 0.001), whereas the controls tended to produce more IL-2R than the patients (P = 0.19). These findings support the concept that a decrease in CD4+/CD29+ T-helper inducer cells along with T-helper cell dysregulation may lead to defective memory responses to antigens in CMC patients and a decrease in cell-mediated immunity due to inhibition of TH1 cells by increased levels of IL-4.

Adult↗
PubMed1995

Latex hypersensitivity in children: clinical presentation and detection of latex-specific immunoglobulin E.

OBJECTIVE: To better understand the clinical characteristics, diagnosis, and possible prevention of immediate hypersensitivity reactions to latex in a hospitalized, pediatric patient population. METHODS: We performed a retrospective case analysis of the first 35 patients with latex allergy evaluated by our service over a 2-year period at our institution. Characteristics of patients and clinical reactions were analyzed and the presence of latex-specific immunoglobulin E was assessed using in vitro methods. In a limited group of patients, the success of strict environmental control and premedication with steroids and antihistamines was evaluated for the prevention of latex allergic reactions. RESULTS: The majority of our patients had life-threatening reactions. In previous reports, most pediatric patients underwent reactions in the perioperative period and belonged to two well-recognized "high-risk" patient groups (spina bifida and genitourinary malformations). In our series, 21 patients (60%) had reactions outside of the operating room setting, and 14 patients (40%) had primary diagnoses outside of the previously recognized "high-risk" groups. Many patients had a history of multiple surgical procedures, and a history of a surgical procedure in the first year of life was very common. A pre-existing clinical history of latex allergy was present in only 18 of the 35 patients, and a severe or life-threatening allergic reaction was the presenting feature of latex allergy in 11 of the 35 patients. Using in vitro assays, we were able to detect latex-specific immunoglobulin E in the sera of all but two of our patients. Latex gloves and latex-containing intravenous sets were common triggers for reactions. When exposure to latex occurs systemically, as through an intravenous line, premedication with steroids and antihistamines may fail to protect against anaphylaxis. CONCLUSIONS: Our experience indicates that the incidence of latex hypersensitivity in children is increasing, that the circumstances (patient profile, hospital location, route of exposure) in which life-threatening reactions may occur are more broad than previously reported, and that a better understanding of both environmental sources of latex antigens and host responses to latex exposure are needed for improved prevention of serious reactions.

Adolescent↗
PubMed1994

Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants.

We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I-IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells.

Adult↗
PubMed1994

Flow cytometric measurement of immunoglobulin E to natural latex proteins.

Immediate hypersensitivity to natural latex (NL) occurs in sensitized individuals after repeated exposure to products or devices containing NL components. Since allergic reactions to NL proteins are quite frequent and may be quite serious, diagnostic assays are needed to identify individuals at risk. A number of latex proteins have been considered the major antigens, but they have been incompletely characterized. There is no standard material available for skin testing. In vitro diagnostic tests, such as the radioallergosorbent test (RAST), are time consuming and their sensitivity and specificity remain to be proven. We have developed a rapid microsphere-based, fluorescence-activated flow cytometry assay for the measurement of NL protein-specific human immunoglobulin E and have compared it with both the enzyme-linked immunosorbent assay and radioallergosorbent test methods. By using the total purified NL protein fraction isolated from raw ammoniated NL sap as the antigen, the flow cytometry assay was both sensitive and specific for the detection of NL protein-specific human immunoglobulin E in the sera of sensitized pediatric patients.

Adolescent↗
PubMed1994

Effect of hematopoietic growth factors on human blood monocytes/macrophages in in vitro culture.

The production of mature monocytes/macrophages is regulated by a group of hematopoietic growth factors, or colony-stimulating factors (CSF). We investigated the in vitro effect of human hematopoietic growth factors on human blood monocyte/macrophage differentiation and proliferation in short- and long-term in vitro cultures. The addition of macrophage CSF, granulocyte-macrophage CSF, and granulocyte CSF and interleukin-6 and interleukin-3 growth factors to monocyte/macrophage cultures induced morphological changes in cultured cells, including enhancement of cell growth and the formation of multinucleated giant cells, spindle-like cells, and fibroblast-like cells. In addition, CD4 and HLA-DR antigen expression was down regulated by the addition of growth factors without a change in the expression of other surface antigens, including CD3, CD11B, CD14, CD15, NK H1, and B1. The proliferating cell nuclear antigen was not detected in growth factor-treated nonadherent monocytes/macrophages in long-term cultures. Bromodeoxyuridine was incorporated in the adherent monocytes/macrophages, and intense staining in the small rounded cells which occur above the adherent cells in these cultures was observed after a 72-h pulse, indicating that monocytes/macrophages are slowly dividing cells.

Antigens, CD↗
PubMed1994

Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.

Adult↗
PubMed1994

In vitro and in vivo effects of granulocyte colony-stimulating factor on neutrophils in glycogen storage disease type 1B: granulocyte colony-stimulating factor therapy corrects the neutropenia and the defects in respiratory burst activity and Ca2+ mobilization.

Children with glycogen storage disease (GSD) type 1b are susceptible to recurrent bacterial infections and have chronic neutropenia accompanied by phagocytic cell dysfunction including decreased superoxide anion (O2-) generation, calcium (Ca2+) mobilization, and chemotactic activity. Granulocyte colony-stimulating factor (G-CSF), a cytokine that corrects neutropenia in other diseases, in vitro enhances f-Met-Leu-Phe-triggered neutrophil O2- generation. Short-term pretreatment (15 min) of GSD 1b neutrophils with G-CSF increased the rate of O2- production (p < 0.01); however, this rate was still significantly below the rate of O2- production in control neutrophils. Recombinant human G-CSF (5 micrograms/kg/d) was administered s.c. to a GSD 1b patient. Before treatment, absolute neutrophil counts were < 500/mm3. Two d after G-CSF administration, the absolute neutrophil counts increased to 1333 and remained in the normal range during a 12-mo follow-up period. In vivo, G-CSF therapy increased f-Met-Leu-Phe-stimulated O2- production to 52% of control after 1 mo, and by mo 4, O2- production reached control levels. Our previous studies (J Clin Invest 56:196-202, 1990) demonstrated that decreased O2- production in neutrophils was associated with impaired Ca2+ mobilization. In vivo administration of G-CSF increased f-Met-Leu-Phe-triggered Ca2+ mobilization by neutrophils to 43% of control by mo 1 of G-CSF therapy and to 93% of control by mo 4, thus paralleling the improvements in O2- generation. In contrast, G-CSF therapy had no effect on the defective neutrophil chemotaxis. In summary, G-CSF therapy produced a rapid increase in circulating neutrophils and a gradual correction of O2- production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Cytofluorographic analysis of effects of interferons on expression of human cytomegalovirus proteins.

The appearance of cytomegalovirus (CMV) proteins in infected fibroblasts was determined by flow cytometry. The sequential production of immediate early (IE), early (E), and late (L) proteins reacting with respective monoclonal antibodies (mAbs) E13, 58/5, and 24/4 was determined in fibroblasts infected with the AD-169 strain of CMV. The percentage of cells expressing CMV proteins and the intensity of fluorescence within cells were determined from day 1 to day 7 post-infection. The effect of interferons (IFNs) alpha, beta, gamma on expression of CMV proteins was analyzed using flow cytometry. IFNs inhibited E and L protein production at days 3 and 6 post-infection in a dose-dependent manner. This inhibitory effect on protein expression was associated with a reduction in release of infectious CMV into culture media. The method described here for detection of CMV proteins using flow cytometry may be useful for basic studies of gene expression and for diagnostic purposes.

Antibodies, Monoclonal↗