Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major histocompatibility complex (MHC) class II deficiency is an inherited autosomal recessive combined immunodeficiency, characterized by a lack of constitutive expression of the human leukocyte antigen (HLA) class II genes. The patients investigated in this study are histoidentical twin brothers with a new phenotype in MHC class II deficiency. Examination of HLA-D locus genes in their fractionated peripheral mononuclear cells (MNCs) revealed an unusual and uncoordinated mRNA pattern. Here we analyzed the distribution of pro- and anti-inflammatory cytokines expressed in these patients' adherent and nonadherent MNCs. We show that gene expression of IL-1 alpha, IL-1 beta, IL-6, granulocyte-colony-stimulating factor, and IL-10 was induced in both cell fractions, whereas increased mRNA levels of interferon-gamma and the inducible nitric oxide synthase were exclusively detected in the patients' nonadherent MNCs. As IL-10 is known to be able to downregulate transcription of MHC class II and expression of IL-10 in the patients' MNCs was increased, we investigated the regulatory function of this cytokine. Interestingly, inhibition of IL-10 protein synthesis with IL-10-specific antisense oligonucleotide DNA (IL-10-AS-ODN) induced HLA-D locus genes in these MHC class II-deficient patients. Exposure of the nonadherent cell fraction to IL-10-AS-ODN resulted in a profound induction of a previously absent DR beta 1 and DP alpha gene expression. HLA-DQ beta mRNA levels, however, were increased in both the adherent and the nonadherent MNC population. Albeit expression of HLA-D locus genes was inducible via inhibition of IL-10 translation, surface expression of HLA class II antigens on the patients' MNCs was essentially negative. The data presented support the concept of a coordinated network of pro- and anti-inflammatory cytokine regulation and this network obviously has a significant role in the cell-type-specific regulation of MHC class II expression.
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PMID:Inhibition of IL-10 protein synthesis induces major histocompatibility complex class II gene expression in class II-deficient patients. 934 39

Neonatal sepsis remains a major clinical problem in neonatology, with high morbidity and mortality rates. The host defence against infections is immature in the newborn infant, and this makes the child more susceptible to invasive infection. The neutrophil storage pool and various granulocyte functions are impaired. In addition, the levels of immunoglobulins and complement are low. The detection of raised levels of complement activation products and cytokines may be of diagnostic help at an early stage of neonatal infection. Rapid treatment with antibiotics is essential for a favourable outcome. Possible adjuvant treatment may be to reduce the relative immunodeficiency by giving immunoglobulins or colony-stimulating factors which increase the production of leukocytes. Further, the potent inflammatory reaction initiated by the microorganisms may be suppressed by various therapies. In spite of much research in this field, no such adjuvant treatment has so far been shown to improve the outcome of neonatal sepsis.
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PMID:[New diagnostic and therapeutic possibilities in neonatal sepsis]. 944 23

Partial albinism with immunodeficiency (Griscelli syndrome) is an uncommon disorder characterized by pigmentary dilution and variable immunodeficiency. Features include a silvery-gray sheen to the hair, large clumped melanosomes in hair shafts, and prominent mature melanosomes in cutaneous melanocytes with sparse pigmentation of adjacent keratinocytes. Immunologic abnormalities most often include impaired natural killer cell activity, absent delayed-type hypersensitivity, and impaired responses to mitogens. Impaired helper T cell function and hypogammaglobulinemia have also been described. The syndrome can be differentiated from Chediak-Higashi syndrome by pathognomonic light and electron microscopic features in skin and hair, and absence of consistent granulocyte abnormalities, but similarly carries a poor prognosis without bone marrow transplantation. We describe a patient with Griscelli syndrome who presented with hepatosplenomegaly, hepatitis, pancytopenia, and silvery hair in the newborn period.
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PMID:Partial albinism with immunodeficiency: Griscelli syndrome: report of a case and review of the literature. 948 1

The Latin American Group for Primary Immunodeficiencies, formed in 1993, presently includes 12 countries. One goal was to study the frequency of primary immunodeficiencies in various regions of the American continent and to enhance knowledge about these diseases among primary-care physicians, as well as allergist-immunologists. Important for this purpose was the development of a registry of primary immunodeficiencies using a uniform questionnaire and computerized database. To date, eight countries have collected information on a total of 1428 patients. Predominantly antibody deficiencies were reported in 58% of patients, followed by cellular and antibody immunodeficiencies associated with other abnormalities in 18%, immunodeficiency syndromes associated with granulocyte dysfunction in 8%, phagocytic disorders in 9%, combined cellular and antibody immunodeficiencies in 5%, and complement deficiencies in 2% of patients. The information gathered from this initial analysis of data will serve to expand the patient database to more areas within participating countries and to new countries and to increase collaboration toward better diagnosis and treatment of these diseases.
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PMID:Primary immunodeficiency diseases in Latin America: first report from eight countries participating in the LAGID. Latin American Group for Primary Immunodeficiency Diseases. 953 60

This was a phase I, multi-center study of 13 pediatric patients (median age, 11 years) to evaluate toxicity, hematopoietic recovery, and graft-versus-host disease (GVHD) after allogeneic transplantation of enriched blood CD34(+) cells obtained from genotypically haploidentical but partially HLA-mismatched related donors (8 parents and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 loci (2). With regard to GVHD, recipient HLA disparity was 0 (1), 1 (3), 2 (8), or 3 (1). The patients suffered from acute myelogenous leukemia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduce the risk of graft failure through the infusion of a large amount of stem cells, peripheral blood cells (PBC) were mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 microgram/kg/d for 5 days) and collected by 2 to 5 aphereses. To both enhance engraftment and reduce GVHD, CD34(+) cells were enriched using immunomagnetic procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Corp, Irvine, CA) and cryopreserved. After variable cytoreductive regimens, a median of 7.7 (range, 2.2 to 14) x 10(6)/kg of CD34(+) cells and 1.03 (0.05 to 2.09) x 10(5)/kg CD3(+) cells were infused. Using Center-specific posttransplant supportive care and immunosuppressive GVHD prophylaxis, two patients experienced early death; one from veno-occlusive disease at day 17 and one from sepsis at day 18. Nine of 11 patients showed signs of engraftment; however, subsequent rejection was seen in 4 patients, 2 of whom had autologous recovery. Eight patients were evaluated in the early phase of marrow recovery. The median number of days to achieve an absolute granulocyte count of 0.5 x 10(9)/L was 14 (range, 9 to 20) and that to achieve a platelet count of 20 x 10(9)/L was 17.5 (range, 12 to 23). Donor chimerism persisted in five patients until death or current survival. All of the surviving patients with functioning-donor-type hematopoiesis were given total body irradiation. De novo acute GVHD (grades II and IV) was observed in two of the eight evaluated patients. Scheduled donor lymphocyte infusion (DLI), using the CD34(-) fraction, was administered to four patients, free of de novo acute GVHD, beginning between 28 to 43 days after transplant. Three of these patients developed acute GVHD (grades I, II, and IV). Cytomegalovirus infection was a major infectious complication but was successfully managed with gamma-globulin and gancyclovir treatment with or without additional DLI. Five patients are currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of donor origin and two of autologous origin. In conclusion, our results show that enriched blood CD34(+) cells from a mismatched haploidentical donor are a feasible alternative source of stem cells, but do not appear to ensure engraftment. Because none of the patients who were administered DLI survived, the therapeutic efficacy and safety of periodic DLI, as an integrated part of such transplants, needs to be clarified in further studies.
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PMID:Partially mismatched pediatric transplants with allogeneic CD34(+) blood cells from a related donor. 978 47

In this study, 30 AIDS patients without Mycobacterium avium infection were randomized to receive treatment with azithromycin (1200 mg), granulocyte-monocyte colony-stimulating factor (GM-CSF; 250 microg/m2/day for 5 days), or both agents. The M. avium killing capacity of neutrophils and monocytes harvested from each patient before intervention and during (day 4), and after therapy (day 8) was assessed. The mean virus load change in the groups receiving GM-CSF was +0.14 log human immunodeficiency virus RNA. After GM-CSF therapy, neither neutrophils nor monocytes could significantly reduce M. avium growth (P=.96 and.31, respectively). Bone pain, myalgia, presyncope, or fever occurred in 55% of patients receiving GM-CSF. Thus, the GM-CSF regimen used in this study did not affect virus load, frequently caused adverse reactions, and did not improve the M. avium killing capacity of neutrophils and monocytes. Future studies using a different GM-CSF regimen are indicated.
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PMID:Killing of Mycobacterium avium by neutrophils and monocytes from AIDS patients treated with recombinant granulocyte-macrophage colony-stimulating factor. 1035 87

An important aspect of vaccine development involves delivery of antigens to antigen-presenting cells for the induction of potent antigen-specific T lymphocyte responses. We investigated the effect of a cationic liposome, lipofectin, on delivery of whole proteins to human dendritic cells (DCs) derived from blood mononuclear cells by culture in interleukin 4 and granulocyte-monocyte colony-stimulating factor for stimulation of human immunodeficiency virus type 1 (HIV-1)-specific memory cytotoxic T lymphocyte (CTL) responses. Delivery of HIV-1 Gag, Pol, and Env proteins to DCs by lipofectin stimulated greater anti-HIV-1 memory CTL responses in cells from HIV-1-infected subjects than those induced by DCs loaded with protein alone. The CTLs were CD8+ and HLA class I restricted. Antigen presentation was enhanced by chloroquine, but blocked by brefeldin A and peptide aldehyde inhibitors of proteasomes, indicating that the classic MHC class I cytosolic pathway was used for processing and presentation of HIV-1 protein by the DCs. Stimulation of anti-HIV-1 CTLs by this safe, inexpensive, and broadly applicable approach may be used in DC-based therapies for HIV-1 infection.
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PMID:Delivery of liposome-encapsulated HIV type 1 proteins to human dendritic cells for stimulation of HIV type 1-specific memory cytotoxic T lymphocyte responses. 1044 13

Patients with advanced cancer often develop immunodeficiency which may be associated with granulocytosis. The granulocytes have the potential to deplete cytotoxic T cells, resulting in accelerated tumor growth and metastasis. To study the elimination of excess granulocytes using granulocyte apheresis in patients with elevated granulocyte to lymphocyte ratios, 2 patients with recurrent metastatic tumors, were selected. Granulocyte apheresis was performed by extracorporeal vein-to-vein circulation with the G-1 granulocyte and monocyte/macrophage apheresis column filled with cellulose acetate beads, each 2 mm in diameter to adsorb granulocytes and monocytes/macrophages. The patients received 1 or 2 apheresis of 30 to 50 min duration per week, at a flow rate of 30-50 ml/min, with 15 sessions constituting one therapeutic course. Apheresis markedly reduced tumor size and prolonged patient survival time without causing any serious adverse events. The results of the present study suggest that granulocyte and monocyte/macrophage apheresis may be beneficial in patients with metastasizing tumors.
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PMID:Granulocyte apheresis as a possible new approach in cancer therapy: A pilot study involving two cases. 1046 94

Glucocorticoid gene regulation can be carried out through direct binding of glucocorticoid receptor to glucocorticoid responsive elements (GRE), regulating directly gene transcription and modulating some signaling pathways. The human immunodeficiency virus type 1 (HIV-1) expression can be activated by different immunomodulators through binding of particular nuclear factors to its long terminal repeat (LTR). In order to investigate the effect of glucocorticoids in pathways that activate HIV-1 expression, we transfected promonocyte (U937) and T lymphocyte (CEM-T4) cell lineages with a plasmid containing the chloramphenicol acetyl transferase (CAT) reporter gene under the control of the HIV-1 LTR. In U937 cells, dexamethasone (DEX) downregulates CAT expression induced by either phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNFalpha) or granulocyte/macrophage-colony stimulating factor (GM-CSF). In CEM-T4 cells the CAT activity was slightly upregulated by DEX following the induction by either PMA or TNFalpha. Interestingly, in both cell lines transactivation of this reporter gene by transactivator protein (TAT) was downregulated by DEX. When the CAT gene was under control of HIV-1 enhancer isolated from its LTR background, the CAT activity induced by PMA was not affected by the presence of glucocorticoids. In all experiments, comparable data were obtained when DEX was replaced by hydrocortisone (HC). Our results show that, depending on the cell line, glucocorticoids can differently affect HIV-1 expression, probably by interfering in cellular pathways involved in virus expression. Moreover, the target of this regulation in LTR is probably not the enhancer region itself.
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PMID:HIV-1 long terminal repeat modulation by glucocorticoids in monocytic and lymphocytic cell lines. 1050 Feb 86

To identify potential roles of cytokines in retroviral pathogenesis, we used reverse transcription-quantitative competitive polymerase chain reaction (RT-qcPCR) assays to characterize mRNA levels of 19 different lymphokines, chemokines, monokines and hematopoietic growth factors in three feline cell lines productively infected with subgroup A feline leukemia virus (FeLV-A) or various feline immunodeficiency virus (FIV) strains. Infection of a CD8+, CD5- large granular lymphocyte (LGL) cell line with FeLV-A activated expression of interleukin-7 (IL-7), induced modest (4-fold) increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and leukemia inhibitory factor (LIF) transcripts, and decreased transforming growth factor-beta (TGF-beta) mRNA (4-fold). The LGL cells were not susceptible to infection by FIV. Infection of MYA-1 cells, a CD4+ T-lymphoblastoid cell line, with FeLV-A activated expression of macrophage inflammatory protein-1alpha (MIP-1alpha), increased transcript levels of GM-CSF (8-fold), macrophage CSF (M-CSF) (16-fold) and stem cell factor (SCF) (250-fold), and decreased (4-fold) expression of IL-10 and tumor necrosis factor-alpha (TNF-alpha). Productive infection with four different FIV molecular clones caused progressive MYA-1 cell death; however, the mRNA expression profiles were unchanged except for 2- to 4-fold increases in M-CSF and 16- to 500-fold increases in SCF. Thus, FIV-induced MYA-1 cytopathicity was not associated with dysregulation of pro-apoptotic or survival factor transcript levels. Lastly, productive infection of PNI cells, a marrow-derived fibroendothelial cell line, with FeLV-A or any of three FIV strains induced 4-fold higher levels of IL-12p40 transcripts and variably higher levels (4- to 64-fold) of GM-CSF. Two viral strains, the FIV-14 molecular clone and the clinical isolate FIV-5122, caused syncytia formation and unique activation of IL-1beta and stromal cell-derived factor-1 (SDF-1) expression, suggesting a potential role for those factors in viral spread and/or cytopathicity. In addition, infection with FIV-5122, but not the other FIV strains or FeLV-A, induced significant increases in mRNA levels of the hematopoietic inhibitors TNF-alpha and MIP-1alpha, along with increased concentrations of soluble proteins in culture supernatants. Consistent with this, supernatant from FIV-5122 infected PNI cells suppressed hematopoietic progenitor growth in colony assays, compared to supportive activities in supernatants from other infected or uninfected PNI cell cultures. Together, these data demonstrate that feline retroviruses alter cytokine mRNA levels in general and strain-specific patterns. These changes may result in specific alterations in cell function and contribute to retroviral pathogenesis. Our observations provide a basis for directed studies of candidate factors within the hematopoietic, thymic and lymphoid microenvironments.
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PMID:The effects of feline retroviruses on cytokine expression. 1062 77


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