Impaired immune function in children and adults with Fanconi anemia.

Background: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA.

Procedure: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies.

Peripheral Blood CD38 Bright CD8+ Effector Memory T Cells Predict Acute Graft-versus-Host Disease.

Acute graft-versus-host disease (aGVHD) is mediated by allogeneic T cell responses. We hypothesized that increases of peripheral blood-activated CD8+ effector memory T (TEM) cells would be observed after hematopoietic stem cell transplantation (HSCT) before onset of aGVHD symptoms. Blood was collected twice weekly after HSCT for 7 weeks in 49 consecutive pediatric and adult HSCT recipients.

Neutrophil CD64 as a diagnostic marker of sepsis: impact on neonatal care.

Objective: The aim of this study is to determine the validity and reliability of neutrophil CD64 in identifying infected infants and to evaluate the impact of this marker on clinical care.

Study Design: Neutrophil CD64 index was incorporated in 371 infection evaluations in 234 infants (ages 1-293 days) from 2005 to 2009 and the impact of this change on clinical care was evaluated.

Results: The sensitivity of the neutrophil CD64 assay was 87% in identifying 31 episodes of culture positive sepsis and 83% in identifying 12 infants with ventilator-associated pneumonia.

Assessment of minimal residual disease in ewing sarcoma.

Advances in molecular pathology now allow for identification of rare tumor cells in cancer patients. Identification of this minimal residual disease is particularly relevant for Ewing sarcoma, given the potential for recurrence even after complete remission is achieved. Using RT-PCR to detect specific tumor-associated fusion transcripts, otherwise occult tumor cells are found in blood or bone marrow in 20-30% of Ewing sarcoma patients, and their presence is associated with inferior outcomes.

Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations.

Human invariant natural killer T cells (iNKT cells) are a unique population of T cells that express an invariantly rearranged T-cell receptor (TCR) composed of TCRValpha24 and TCRVbeta11 chains which recognize glycosphingolipid antigens presented by the CD1d molecule. iNKT cells are absent in patients with X-linked lymphoproliferative disease (XLP) due to SH2D1A mutation, and are reported to be decreased in patients with XLP due to BIRC4 mutations. However, mice deficient in the BIRC4 gene product, X-linked Inhibitor of Apoptosis (XIAP), have normal iNKT cell populations.

A rapid flow cytometric screening test for X-linked lymphoproliferative disease due to XIAP deficiency.

Background: Deficiency of X-linked inhibitor of apoptosis (XIAP), caused by BIRC4 gene mutations, is the second known cause of X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency that often presents with life-threatening hemophagocytic lymphohistiocytosis (HLH). Rapid diagnosis of the known genetic causes of HLH, including XIAP deficiency, facilitates the initiation of life-saving treatment and preparation for allogeneic hematopoietic cell transplantation (HCT). Until now, a rapid screening test for XIAP deficiency has not been available.

Urogenital tract expression of enhanced green fluorescent protein in transgenic mice driven by a smooth muscle gamma-actin promoter.

Purpose: Our understanding of urogenital tract development and its response to disease or injury is hindered by complex interactions between epithelial and mesenchymal cells, and the difficulties in studying either component in isolation. We investigated whether transgenic mice could be generated to express enhanced green fluorescent protein (EGFP) in smooth muscle cells (SMCs) and whether such cells could then be purified using flow cytometric sorting to isolate RNA to be used in future gene expression assays.

Materials And Methods: A 13.

Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members.

Mutations in the perforin gene have been described in some patients with hemophagocytic lymphohistiocytosis (HLH), but the role of perforin defects in the pathogenesis of HLH remains unclear. Four-color flow cytometric analysis was used to establish normal patterns of perforin expression for control subjects of all ages, and patterns of perforin staining in cytotoxic lymphocytes (natural killer [NK] cells, CD8(+) T cells, CD56(+) T cells) from patients with HLH and their family members were studied. Eleven unrelated HLH patients and 19 family members were analyzed prospectively.

Crucial role of apopain in the peroxynitrite-induced apoptotic DNA fragmentation.

Peroxynitrite, a cytotoxic oxidant formed in the reaction of superoxide and nitric oxide is known to cause programmed cell death. However, the mechanisms of peroxynitrite-induced apoptosis are poorly defined. The present study was designed to characterize the molecular mechanisms by which peroxynitrite induces apoptosis in HL-60 cells, with special emphasis on the role of caspases.

Peroxynitrite-induced thymocyte apoptosis: the role of caspases and poly (ADP-ribose) synthetase (PARS) activation.

The mechanisms by which immature thymocyte apoptosis is induced during negative selection are poorly defined. Reports demonstrated that cross-linking of T-cell receptor leads to stromal cell activation, expression of inducible nitric oxide synthase (iNOS) and, subsequently, to thymocyte apoptosis. Therefore we examined, whether NO directly or indirectly, through peroxynitrite formation, causes thymocyte apoptosis.

Immunologic monitoring with Orthoclone OKT3 therapy.

Muromonab-CD3 monoclonal antibody (Orthoclone OKT3) was used 146 times in 123 transplant recipients to treat or prevent rejection. Reversal and prevention of rejection were evaluated 1 week and 1 year after OKT3 therapy. Eighty-one percent (73 of 90) of the rejection episodes in kidney transplant patients were reversed with 67% of these grafts functioning at 1 year.

Influence of operations with cardiopulmonary bypass on polymorphonuclear leukocyte function in infants.

To determine the effect of operations with cardiopulmonary bypass on the immunologic function of polymorphonuclear leukocytes in infants, we studied polymorphonuclear leukocyte function and immunologic profile in 16 infants undergoing repair of congenital heart lesions. An oxygen/air/high-dose fentanyl anesthetic was used for all patients. Absolute neutrophil count increased significantly (p less than 0.

Age-dependent variation of lymphocyte function in the postoperative child.

Circulating lymphocyte profiles and reactivity normally vary with age. Operation results in depression of both lymphocyte counts and blastogenesis but the relationship of age to these alterations has not been previously evaluated in the pediatric surgical patient. This report analyzes the relationship of age to lymphocyte alteration in the postoperative child.

Leukocyte survival in cerebrospinal fluid.

Delays in the laboratory examination of cerebrospinal fluid are commonly encountered in clinical medicine. The present studies were designed to evaluate changes in cerebrospinal fluid leukocyte counts relative to time elapsed before analysis. Neutrophil counts decreased most rapidly, being 68 +/- 10% (standard error of the mean) and 50 +/- 12% of initial values at 1 and 2 h, respectively.

Immunologic responses following serial skin testing.

Twenty volunteers underwent intradermal skin testing with tetanus toxoid (TT) and varicella-zoster (VZ) antigens weekly for 7 weeks. In addition to measurements of delayed hypersensitivity skin test responses, in vitro antigen specific lymphocyte stimulation and antibody levels were monitored. Data for TT exhibited more variability than VZ, demonstrating a marked boost in antibody titers after the first skin test and a shift in the kinetics of the skin test reaction to later maximum responses after the first 3 weeks.

Immunotoxicology of brown recluse spider (Loxosceles reclusa) venom.

A purified toxic protein from Loxosceles reclusa venom was assayed for its in vitro effects on the human immunological and blood clotting systems. The toxin caused inhibition of neutrophil chemotaxis, depletion of serum hemolytic complement, prolongation of the activated partial thromboplastin time and depletion of clotting factors XII, XI, IX and VIII by an average of 44% in human plasma. The prothrombin time of human plasma was also prolonged by 1.

Psychologic modulation of the human immune response to varicella zoster.

Psychoimmunology, the interrelationship between the brain/mind/psyche and the immune system, is now an established area of scientific research. Based on prior investigations we hypothesized that an experienced meditator could affect her delayed hypersensitivity reaction by a psychological process. A single-case study design was employed in which the subject was skin tested weekly with varicella zoster skin test reagent.

Lymphocyte subpopulations of blood and alveolar lavage in blastomycosis.

Patients with blastomycosis were found to have differing lymphocyte populations depending on the extent of disease manifestations and whether or not therapy had been started. Patients with recovering pulmonary blastomycosis who had been receiving antifungal treatment for at least four weeks had lymphocyte subpopulations no different from control donors. Patients with treated extrapulmonary blastomycosis had similar T helper (TH) to T suppressor (TS) ratios compared to recovering pulmonary patients and control subjects; this ratio gives a false impression because extrapulmonary blastomycosis patients had a reduced absolute number of lymphocytes with either marker.

Intravenous immune globulin for hypogammaglobulinemia: a comparison of opsonizing capacity in recipient sera.

Twelve severely hypogammaglobulinemic patients received infusions of alkylated immune globulin and two other native nonalkylated products. Administration was separated by an interval of 3 weeks. Serum was obtained prior to and at 24 hr and 3 weeks after each infusion for measurement of total IgG, specific and opsonizing antibodies.

Intracellular growth and phagocytosis of Blastomyces dermatitidis by monocyte-derived macrophages from previously infected and normal subjects.

Blastomyces dermatitidis evokes responses of human cellular immunity typical of other intracellular fungal pathogens. Differences in growth rates of intracellular Blastomyces yeast and the differences in amounts of yeast phagocytized by macrophages were determined for macrophages derived from peripheral blood monocytes from 11 persons with treated blastomycosis and 11 normal, healthy persons. Cellular immunity was examined by lymphocyte uptake of [3H]thymidine in response to a specific antigen of Blastomyces yeast.

Surgically induced immunologic alterations in the child.

Surgery is generally believed to be an immunodepressant. This assumption is based, in part, upon studies of compromised patients undergoing major operation. Similar studies in normal adults following elective procedures are contradictory and little information is available regarding the pediatric surgical patient.

Immunologic aspects of human endometriosis.

General and specific immune function were examined in women with endometriosis. Nonspecific parameters included total leukocyte and differential counts, quantitative immunoglobulin (IgG, IgA, and IgM) determinations, total hemolytic complement, C3, C4, mitogen-induced lymphocyte stimulation, and human leukocyte antigen (HLA) typing; no differences were observed when data were compared to age-matched controls without endometriosis. In contrast, the specific immune response T-lymphocyte-mediated cytotoxicity to autologous endometrial cells was significantly reduced (P less than 0.

Comparison of flow cytometric analysis and [3H]thymidine incorporation for measurement of the effects of drug toxicity on lymphocyte stimulation.

Human mononuclear cells were exposed to three antiviral agents, stimulated with phytohemagglutinin, and assayed for DNA synthesis with [3H]thymidine uptake and flow cytometric analysis. Cytosine-arabinoside demonstrated inhibition of blastogenic reactivity by both [3H]thymidine uptake and flow cytometric analysis, whereas acyclovir showed no significant suppression. In contrast, (E)-5-(2-bromovinyl)-2'-deoxyuridine, a thymidine analog, demonstrated a lack of correlation between the two methods.

Fatty acids and the inhibition of mitogen-induced lymphocyte transformation by leukemic serum.

The effects of sera from 23 patients with acute lymphocytic leukemia on mitogen-induced transformation of normal human lymphocytes were examined. All sera (100%) at diagnosis and 70% of those obtained during the induction of remission demonstrated inhibition of mitogen-induced lymphocyte transformation as evidenced by decreased uptake of [3H]thymidine. The inhibition could not be overcome by an increase in the mitogen concentration.

Cellular immunotoxicity of amyl nitrite.

Functional deficits in lymphocyte interaction following occasional or chronic exposure to inhaled nitrites may be a potential contributing but not the etiologic factor in the acquired immunodeficiency syndrome (AIDS). We evaluated the effect of amyl nitrite vapors on mononuclear cell function and demonstrated functional deficits and structural alterations in these cells. In this closed, in vitro system, exposure of cells to amyl nitrite for up to 30 minutes did not effect cell viability.