Biomedical subjects

T N Denny

Publications and source records attributed to T N Denny.

At least 19 recordsLinked to original sources

PubMed2001

The dynamics of bone marrow stromal cells in the proliferation of multipotent hematopoietic progenitors by substance P: an understanding of the effects of a neurotransmitter on the differentiating hematopoietic stem cell.

Communication within the hematopoietic-neuroendocrine-immune axis is partly mediated by neurotransmitters (e.g. substance P, SP) and cytokines. SP mediates neuromodulation partly through the stimulation of bone marrow (BM) progenitors. This study shows that SP, through the neurokinin-1 receptor, stimulates the proliferation of primitive hematopoietic progenitors: cobblestone-forming cells (CAFC, CD34+). This effect is optimal when macrophage is included within the fibroblast support. Indirect induction of IL-1 could be important in the proliferation of CAFC colonies by SP. Phenotypic and functional studies suggest that SP might directly interact with the CD34+/CD45(dim) population. These studies indicate that SP can initiate a cascade of biological responses in the BM stroma and stem cells to stimulate hematopoiesis.

Cell Differentiation↗

PubMed2001

Relationship between oxidative burst activity and CD11b expression in neutrophils and monocytes from healthy individuals: effects of race and gender.

Oxidative burst activity and the expression of adhesion molecules have been used as indicators of leukocyte activation status. The aim of the study was to delineate the relationship of oxidative burst activity and the expression of adhesion molecules in neutrophils and monocytes from a pool of healthy volunteers (n = 96). We also tested the potential role of gender and a racial background in the individual response differences. Basal and phorbol myristate acetate (PMA)-stimulated oxidative burst and CD11b expression were determined using dihydrorhodamine 123 and phycoerythrin (PE)-conjugated anti-CD11b monoclonal antibodies. PMA markedly increased CD11b expression and cellular oxidant content in neutrophils and monocytes in all samples. However, the responses showed considerable variability among individuals. A positive correlation was observed between the responsiveness of neutrophils and monocytes in their basal or PMA-stimulated CD11b expressions and PMA-stimulated oxidative burst activities. In contrast, no correlation was found between the level of adhesion molecule expression and cellular oxidant content in monocytes or neutrophils either under basal or under PMA-stimulated conditions. The reactivity of oxidative burst (i.e., PMA-stimulated over basal) was significantly lower in neutrophils from African American males compared with cells from African American females, white females, or white males. In contrast, reactivity of monocytes was significantly elevated in white males compared with all other groups. These findings indicate that leukocytes with a relatively high degree of adhesion molecule expression may display an average or decreased oxidative burst activity, and vice versa. Our findings also indicate that ethnic background may influence the oxidative burst activity in neutrophils and monocytes. This needs consideration in clinical studies utilizing healthy volunteers with mixed gender and ethnic backgrounds.

Black People↗

PubMed2000

NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis.

Immune-mediated mechanisms have been implicated in the etiology of idiopathic bone marrow fibrosis (IMF). However, the mechanism remains poorly defined. Compared with healthy controls, IMF monocytes are overactivated, with increased production of TGF-beta and IL-1. TGF-beta is central to the progression of fibrosis in different organs. In the lung, fibrosis is associated with up-regulation of TGF-beta-inducible genes. Because IL-1 and TGF-beta have pro- and antiinflammatory properties and neither appears to regulate the high levels of each other in IMF, we studied the mechanism of this paradigm. We focused on the role of RelA, a subunit of the transcription factor, NF-kappaB that is associated with inflammatory responses. We transiently knocked out RelA from IMF monocytes with antisense oligonucleotides and showed that RelA is central to IL-1 and TGF-beta production and to the adhesion of IMF monocytes. Because the NF-kappaB family comprises subunits other than RelA, we used aspirin and sodium salicylate to inhibit kinases that activate NF-kappaB and showed effects similar to those of the RelA knockout system. It is unlikely that RelA could be interacting directly with the TGF-beta gene. Therefore, we determined its role in TGF-beta production and showed that exogenous IL-1 could induce TGF-beta and adherence of IMF monocytes despite the depletion of NF-kappaB. The results indicate that IL-1 is necessary for TGF-beta production in IMF monocytes, but NF-kappaB activation is required for the production of endogenous IL-1. Initial adhesion activates NF-kappaB, which led to IL-1 production. Through autocrine means, IL-1 induces TGF-beta production. In total, these reactions maintain overactivation of IMF monocytes.

Adult↗

PubMed2000

HIV heterosexual transmission: a hypothesis about an additional potential determinant.

Transmission rates of human immunodeficiency virus (HIV) during heterosexual intercourse vary dramatically around the world. In Asia and South America, they are extraordinarily high, whereas in the United States and Europe, rates are much lower even after a large number of unprotected contacts. The transmission rates in Africa also probably are high, but the available studies unfortunately are weak. In Thailand, female-to-male transmission rates per contact were estimated at.056 (l in 18) compared to.0002 to.0015 (1/5000-1. 5/1000) for male-to-female transmission in the United States and Europe. Male-to-female transmission in Thailand appears to show, as expected, even greater transmission likelihood compared to female-to-male rates. In general, in the United States and Europe, transmission rates within heterosexual couples range from less than 10% to 22%, whereas in Thailand and Brazil, the rates exceed 40%. The much lower transmission rate per contact in the United States and Europe is based on an assumption that HIV transmitters are a homogeneous group. Wiley and colleagues argue that transmitters are likely to be a heterogeneous group with a large percentage of very low frequency transmitters and a small percentage of high frequency transmitters. That hypothesis is given some support by a cluster of cases in rural New York State in which one man appeared to infect 31% of his many contacts.

Female↗

PubMed1999

Partial resistance to infection by R5X4 primary HIV type 1 isolates in an exposed-uninfected individual homozygous for CCR5 32-base pair deletion.

It is known that certain individuals remain persistently seronegative despite repeated exposure to HIV-1. Studies have shown that some exposed uninfected (EU) individuals who are homozygous for a 32-bp deletion in the CCR5 gene are resistant to infection with non-syncytium-inducing (R5) viruses. In the present investigation, we provide evidence that a highly exposed-uninfected individual with the CCR5 32-bp deletion (EUdelta32-1) also has partial resistance to syncytium-inducing (R5X4) HIV-1 viruses, when compared with unexposed-uninfected individuals with (UUdelta32-1 and UUdelta32-2) and without (UU-1 and UU-2) the 32-bp deletion. The partial resistance of EU cells was due neither to altered coreceptor expression, nor to specific mutation or deletion in the coding region of chemokine coreceptors CXCR4 and CCR3. While SDF-1, the ligand for CXCR4, blocked entry of R5X4 viruses to a similar extent in EUdelta32 and UUdelta32, there was a differential production of soluble factors by EUdelta32. Both CD4+ and CD8+ cells from EUdelta32-1 produced soluble factors that efficiently suppressed infection by HIV-1 R5X4 viruses when compared with supernatant from UUdelta32. These data provide evidence that additional soluble factors are involved in resistance to infection with R5X4 viruses.

CD4-Positive T-Lymphocytes↗

PubMed1999

Effect of human immunodeficiency virus infection on serum beta2-microglobulin levels in pregnant women.

OBJECTIVE: To assess serum beta2-microglobulin levels in human immunodeficiency virus (HIV)-infected and uninfected pregnant women, variations of serum beta2-microglobulin levels during pregnancy and postpartum, factors that might influence beta2-microglobulin levels in pregnant women, and the association between beta2-microglobulin and perinatal HIV-1 transmission. METHODS: We assayed 374 stored (-70C) serum samples from pregnant women enrolled in the Newark perinatal HIV-1-transmission study and 18 nonpregnant women for beta2-microglobulin using a microparticulate enzyme immunoassay. The Student t test, Wilcoxon rank test, binomial test, and Spearman correlation coefficient were used for statistical analysis, with P < .05 considered statistically significant. A linear regression model was used to assess the effect of independent variables on serum beta2-microglobulin levels. RESULTS: There were no significant differences (P = .16) in serum beta2-microglobulin levels between pregnant and nonpregnant HIV-negative women (1.07+/-0.35 versus 0.99+/-0.18 mg/L). Beta2-Microglobulin levels did not vary throughout pregnancy and postpartum, irrespective of HIV serostatus. Substance abuse did not alter beta2-microglobulin levels. Human immunodeficiency virus infection caused significant increases of this surrogate marker, but it could not discriminate among disease stages. Beta2-Microglobulin levels at delivery were lower among women who delivered HIV-infected infants. CONCLUSION: Human immunodeficiency virus infection was associated with increased serum beta2-microglobulin levels in pregnant women and was the most significant correlate of increases of that marker. Pregnancy and substance use during pregnancy did not influence levels of serum beta2-microglobulin significantly.

Adult↗

PubMed1999

Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Basic fibroblast growth factor (bFGF, FGF-2), a classical transforming factor, mitogen, and survival factor in multiple cell types, and has a paradoxic role in mammary epithelial cell transformation and proliferation. We have also demonstrated that recombinant FGF-2 uncharacteristically promotes cell death in MCF-7 human breast cancer cells. In this study, we investigated the effects of FGF-2 overexpression on survival in the same MCF-7 cells. In eight breast cancer cell lines and two nontransformed mammary epithelial cell lines, we demonstrated that high levels of Bcl-2 are only expressed in cells with undetectable levels of FGF-2 on western blot. In retrovirally transduced MCF-7 cells expressing both cytoplasm- and nucleus-localizing FGF-2 species and ones expressing only cytoplasm-localizing FGF-2 species, Bcl-2 levels were strongly decreased at both the mRNA and protein levels. Immunoprecipitation of Bax demonstrated a decreased association of Bax with Bcl-2 in these cells. Levels of Bax did not correlate with expression of FGF-2 in the 10 cell lines or in MCF-7 cells. The clonogenic potential of MCF-7 cells in tissue culture was decreased by the expression of FGF-2 and was additively suppressed by the chemotherapeutic agents etoposide and 5-fluorouracil in a dose and time dependent manner. MCF-7 cells overexpressing FGF-2 had a greater rate of programmed cell death at baseline and in response to etoposide and 5-fluorouracil in a TUNEL assay by immunofluorescent microphotography and by flow cytometric quantitation. The pro-apoptotic effect of FGF-2 overexpression on the chemosensitivity of these cells was confirmed by quantitative morphologic determination. These data demonstrate that the expression of FGF-2 downregulates Bcl-2 and promotes programmed cell death in MCF-7 human breast cancer cells.

Antimetabolites, Antineoplastic↗

PubMed1999

Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion.

This study was conducted to evaluate the immunological response to an exhaustive treadmill exercise test in 20 female chronic fatigue syndrome patients compared to 14 matched sedentary controls. Venipuncture was performed at baseline and 4 min, 1 hr, and 24 hr postexercise. White blood cells were labeled for monoclonal antibody combinations and were quantified by FACsan. Cytokines were assayed utilizing quantitative RT/PCR. No group difference was seen in VO2peak (28.6 +/- 1.6 vs 30.9 +/- 1.2 ml.kg-1.min-1; P > 0.05). However, 24 hr after exercise the patients' fatigue levels were significantly increased (P < 0.05). The counts of WBC, CD3+ CD8+ cells, CD3+ CD4+ cells, T cells, B cells, natural killer cells, and IFN-gamma changed across time (P's < 0.01). No group differences were seen for any of the immune variables at baseline or after exercise (P's > 0.05). The immune response of chronic fatigue syndrome patients to exhaustive exercise is not significantly different from that of healthy nonphysically active controls.

Adult↗

PubMed1998

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis.

The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses--major depression and multiple sclerosis (MS)--and with data from healthy sedentary controls. The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables--circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers--the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b-, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3-/CD16+ and CD56+. Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values-contrary to expectation. When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS. These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.

Adult↗

PubMed1998

Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Basic fibroblast growth factor (bFGF) is a mitogen and a survival factor in fibroblasts and endothelial cells. It acts as an angiogenesis factor in breast cancer, but paradoxically inhibits proliferation in several breast cancer cell lines. In this study, we investigated the effects of bFGF on the survival of MCF-7 human breast cancer cells in order to determine if these effects were also opposite to those in fibroblasts. Incubation of NIH 3T3 cells with bFGF for 24 h caused an approximately 30% increase in day 12 +/- 2 adherent colonies while causing an approximately 50% decrease in MCF-7 colony formation. Incubation of NIH 3T3 cells with bFGF prior to etoposide or 5-fluorouracil treatment caused a proportionally smaller decrease in colony forming efficiency as a result of drug treatment, while preincubation of MCF-7 cells with bFGF caused a similar but opposite additive increase in drug-induced diminution of colony forming efficiency. These effects on MCF-7 cells were observed at variable times of incubation and doses of etoposide to 1 microM and 5-fluorouracil to 200 microM and at variable times of incubation and concentrations of bFGF to 1 ng/ml. Incubating with bFGF after drug exposure had similar effects on the reduction of cloning efficiency. The effects of bFGF were similar on programmed cell death, as determined by morphologic characteristics of apoptosis on 400 cell counts and FITC-dUTP 3'-OH DNA end labeling. Basic FGF promoted apoptosis and increased the rate of drug-induced cell death with both etoposide and 5-fluorouracil. While recombinant bFGF affected Bcl-2 protein and mRNA levels in NIH 3T3 cells only marginally and variably and had no discernible effects on Bax protein levels, it markedly downregulated Bcl-2 mRNA and protein levels in MCF-7 cells and caused an increase in Bax protein levels. These changes resulted in a decreased association of Bcl-2 with immunoprecipitable Bax and an increased association of Bax with immunoprecipitable Bcl-2 in MCF-7 cells treated with bFGF. These data suggest that bFGF may cause different phenotypic responses in breast cancer cells from those in surrounding cells and offer one possible mechanism through opposite regulation of Bcl-2 and Bax. Inhibition of colony formation by bFGF was observed in several breast cancer cells lines, demonstrating that this effect demonstrated in MCF-7 cells was more universal.

3T3 Cells↗

PubMed1997

Effect of vasoactive intestinal peptide (VIP) on cytokine production and expression of VIP receptors in thymocyte subsets.

Intrathymic T cell precursors undergo a programmed sequence of developmental changes resulting in the production of mature, self-MHC restricted, single positive T lymphocytes which migrate to the periphery. The intrathymic T cell development is controlled by various factors, including cytokines and possibly neuroendocrine hormones. Our previous studies indicate that vasoactive intestinal peptide (VIP) inhibits IL-2 and IL-4 production in thymocytes through different molecular mechanisms. Thymocytes acquire the competence to express IL-2 and IL-2R during thymic development in a maturation-dependent manner. In this study we investigate the effect of VIP on IL-2 production, and the expression of VIP-R1 and VIP-R2 mRNA in different thymocyte subsets in comparison to T cell lines. All thymocyte subsets and T cell lines tested express VIP-R2. In contrast, only single positive, CD4+8- and CD4-8+ thymocytes express VIP-R1. VIP inhibits IL-2 production in CD4+8+ and single positive CD4+8- and CD4-8+ thymocytes and in TH1 cells stimulated through the TCR. No inhibition is observed in CD3-4-8- and single positive CD4+8- and CD4-8+ thymocytes, or in TH1 cells stimulated by a combination of calcium ionophores and phorbol esters. These findings suggest that VIP inhibits IL-2 production through VIP-R2, and that it interferes with a TCR-connected transduction pathway. We also investigate the expression of VIP mRNA in thymocyte subsets and T cell lines, and conclude that thymocytes as well as antigen-specific T cells may function as VIP sources within the lymphoid organs.

Animals↗

PubMed1997

Lymphocyte shedding from genital tract of human immunodeficiency virus-infected women: immunophenotypic and clinical correlates.

OBJECTIVE: Our purpose was to describe the lymphocyte subpopulations in genital tract samples from human immunodeficiency virus-infected women and the clinical correlates associated with lymphocyte shedding. STUDY DESIGN: Genital tract samples of women infected with human immunodeficiency virus-1 were processed for immunophenotyping analysis with a FACScan flow cytometer. Immunologic and virologic characteristics of women with and without lymphocyte shedding were compared with t test, Wilcoxon rank test, or Fisher's exact test. RESULTS: The rate of genital lymphocyte shedding among human immunodeficiency virus-1-infected women was 39%. Genital shedding was not related to age, race, use of antiretroviral therapy, or positive human immunodeficiency virus-1 culture. A negative rank correlation (r = -0.71, p = 0.047) between CD3+ CD4+ counts in peripheral blood and genital tract was observed. The majority of the lymphocyte cells were CD3+ CD8+, and > 80% of the CD3+ CD4+ cells were memory cells. CONCLUSION: The immune profile of the genital tract lymphocytes is suggestive of a local mucosal immune response.

Adult↗

PubMed1996

Quantitative determination of surface antibody binding capacities of immune subsets present in peripheral blood of healthy adult donors.

The objective of this study was to quantitate the antibody binding capacity (ABC) of CD3, CD4, CD8, CD16, and CD19 on lymphocytes and CD4 on monocytes from healthy adult donors. Peripheral blood was collected over three consecutive days and repeated in the same format two weeks later for comparison to initial measurements. Immune subsets were labeled by direct single or two-color staining in whole blood followed by lysis of erythrocytes. Fluorescence intensity measurements were made by carefully calibrating the flow cytometer and then measuring the intensity of monoclonal antibody staining on labeled cells and on Quantum Simply Cellular Microbeads. The effect of paraformaldehyde fixation on intensity measurements and coefficient of variation of thirty replicates for each phenotype were also studied. We found a small change in calculated ABC following overnight fixation with a greater change following 48 h of fixation prior to flow cytometric analysis. We found excellent precision could be achieved for measuring the ABC of most markers with some improvement desirable for expression of CD4 on monocytes and CD16+ lymphocytes. Between donors we found a high-low range of CD3+ = 134,349-45,905; CD4+ (lymphocytes) = 54,174-36,106; CD4+ (monocytes) = 9,246-3094; CD8+ = 268,868-190,622; CD3+CD8+ = 269,858-212,024; CD16+ = 38,307-336; and CD19+ = 25,252-11,689. For the total donor group, the observations at week 1 and week 2 were not significantly different (alpha = .05) for any of the immunophenotypes we studied. The data presented here continue to show that it is possible to perform quantitative intensity measurements of immune subsets when performing immunophenotyping studies.

Adult↗

PubMed1996

Enhanced HIV-1 activity in bone marrow can lead to myelopoietic suppression partially contributed by gag p24.

Similar to other lymphoid organs, the bone marrow (BM) is a potential reservoir for HIV-1. Although hematologic abnormalities are common in AIDS patients, the mechanisms by which HIV-1 contributes to these abnormalities are poorly understood. Hemapoietic suppression can be mediated by HIV-1 and some of its associated proteins. We have previously reported that AIDS peripheral blood sera inhibit normal CFU-granulocyte macrophage (GM). In this study, we have found that sera obtained from AIDS BM patients are more inhibitory to CFU-GM than those from peripheral blood (p < 0.05). To determine a candidate suppressor factor, we studied the role of p24 and found that it exerts varying degrees of suppression to CFU-GM, but minimal inhibition on erythroid colonies. We have found that the suppressive levels of p24 in in vitro assays are similar to the average circulating levels in AIDS patients. We have also observed that most of the inhibition caused by p24 is mediated by soluble factor(s) produced by the BM stroma. Cross-linking studies with membrane proteins from normal BM stroma and CD34+ cells indicated a putative 26-kDa p24 receptor, indicating that p24 binds to a receptor present on normal BM cells. These results implicate another HIV-1 protein, p24, in hemapoietic suppression and add another plausible mechanism by which HIV-1 contributes to BM failure in AIDS. Furthermore, these findings suggest a potential risk for similar in vivo suppression in the early phase of HIV-1 infection when viremia is elevated, and also in long-term survivors who have low, although persistent, HIV-1 replication.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Lymphocyte immunoregulatory cells present in semen from human immunodeficiency virus (HIV)-infected individuals: a report from the HIV Heterosexual Transmission Study.

The purpose of this study was to determine the types and distribution of immune subsets present in semen from human immunodeficiency virus (HIV)-infected (HIV+) individuals and to compare these values with those measures in semen from HIV-negative (HIV-) individuals. To accomplish this, a direct three-color monoclonal antibody labeling technique was employed to identify immune cells in fresh ejaculates. Once labeled, the percent of each immune subset present in the ejaculate was determined by flow cytometric analysis. The percent of CD3+ cells present in the semen of the HIV+ group showed no significant difference when compared with semen from the HIV- group. Analysis of the CD4+ subset yielded a significantly lower percent in the HIV+ group than in the HIV- group. The analysis of the CD8+ subset yielded a higher percent of cells present in semen from HIV+ individuals. The CD8 higher value along with lower CD4 value results in a lower CD4/CD8 ratio in the HIV+ group. Further subset studies showed that the percent of cells expressing naive (CD4+ CD45RA+) and memory (CD4+ CD45RO+) markers was lower in the HIV+ group. This study provides additional data supporting the utility of flow cytometry and monoclonal antibodies to immunophenotypic cells present in semen ejaculates. It is also the first reported application of the technique to a disease-based model and may be useful to better understand issues of mucosal immunity and transmission of sexually transmitted diseases such as HIV.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Development of a multiplex PCR assay for the simultaneous detection and discrimination of HIV-1, HIV-2, HTLV-I and HTLV-II.

BACKGROUND: Multiplex polymerase chain reaction (PCR) has been established as a general technique for the simultaneous amplification of different target sequences. Uses of multiplex include pathogens identification, linkage analysis and genetic disease diagnosis. The high sensitivity of PCR may produce false-positive results due to contamination with previously amplified material. OBJECTIVES: To develop a multiplex PCR technique that can simultaneously detect and discriminate human immunodeficiency virus types 1 and 2 (HIV-1/2) and human T-lymphotropic virus types 1 and 2 (HTLV-I/II) proviral sequences. Such a method should incorporate a system that prevents the occurrence of false-positive results. STUDY DESIGN: Combinations of four primer pairs, one for each retrovirus, were assayed in order to determine the combination of oligonucleotides as well as the PCR conditions that yield the most specific and sensitive coamplification of proviral sequences. To prevent contamination with DNA from previous PCR amplifications, the uracil N-glycosylase (UNG) system was incorporated into the coamplification format. RESULTS: A combination of primer pairs from the gag region of HIV-1, env of HIV-2, pol of HTLV-I and tax of HTLV-II yielded specific and sensitive coamplification of proviral sequences. The UNG system was incorporated and shown to be efficient in the degradation of contaminating DNA. In the evaluation of a serologically well established panel of singly and dually infected individuals, the assay detected 20/22 HIV-1, 8/10 HIV-2, 8/8 HTLV-I and 8/8 HTLV-II infections.

Cell Line↗

PubMed1996

Ranitidine improves lymphocyte function after severe head injury: results of a randomized, double-blind study.

OBJECTIVE: To study the immunomodulatory effect of the histamine receptor antagonist, ranitidine, in patients admitted to the intensive care unit after severe head injury. DESIGN: Randomized, prospective, double-blind study. SETTING: Surgical intensive care unit of a university Level I trauma center. PATIENTS: Twenty patients admitted with a Glasgow Coma Scale score of < 10 who were enrolled as part of a prospective, multicenter trial to assess the impact of multiple risk factors and ranitidine prophylaxis on the development of stress-related upper gastrointestinal bleeding. INTERVENTIONS: Continuous infusion of ranitidine at 6.25 mg/hr (n = 9) or placebo (n = 11) for a maximum of 5 days. MEASUREMENTS AND MAIN RESULTS: Before the patients were enrolled in the study and on completion of treatment, lymphocyte cell-surface antigen expression was determined by flow cytometry (n = 14 patients); mitogen-stimulated interferon-gamma and interleukin-2 production were measured by enzyme-linked immunosorbent assay (n = 19 patients). Treatment with ranitidine, but not placebo, was associated with a significant increase in CD4+ lymphocytes (33% to 49%; p < .05) and a significant decrease in CD8+ lymphocytes (41% to 27%; p < .05). Also, the mitogen-stimulated interferon-gamma production increased from 121 to 269 pg/mL (p < .05) in patients treated with ranitidine, but not in patients treated with placebo. There were no significant differences in interleukin-2 production or circulating B-cell concentrations between both groups. CONCLUSION: This study demonstrates an immunostimulatory effect of the histamine-2-receptor antagonist, ranitidine, both at the cellular and mediator levels in patients after head injury.

Adult↗

PubMed1995

Evaluation of T-lymphocyte subsets present in semen and peripheral blood of healthy donors: a report from the heterosexual transmission study.

The purpose of this study was to accurately determine the T-lymphocyte subsets found in semen from healthy volunteers, to evaluate the impact of repeated ejaculation on the frequency or type of immune cells present in semen, and to compare subset analysis in semen to that in the peripheral blood. To accomplish this, a flow cytometric method was developed to identify and count immunophenotypically distinct cells present in semen. Fresh semen samples and peripheral blood were collected over three consecutive days from nine healthy donors. Donors had normal ejaculate volume, sperm count, sperm motility, morphology, and leukocyte count. No significant intra-donor differences were seen in these parameters over time. No significant differences were observed in the percentage of CD3+ cells, CD4+ cells, CD8+ cells, and the CD4:CD8 ratio in semen on consecutive days. However, within the CD4+ subset, when naive and memory CD4+ cells were measured, some day to day variability was suggested. No significant differences in CD3+, CD4+, CD8+, CD4/CD8 ratio, or naive and memory subsets were seen in the peripheral blood between sampling days. When semen was compared to peripheral blood some differences in immune subset values were observed, with an increase in the percentage of memory CD4+ cells in semen being the most striking. This finding may be relevant to HIV transmission, since others have shown that this cell may be preferentially infected with HIV and is the primary reservoir for virus in infected individuals.

Adult↗