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)

Bloom's syndrome (BS) is an autosomal recessive disease characterized by short stature, sensitivity to sunlight, and telangiectasic malar erythema. It is associated to chromosomal breakage, to primary combined immunodeficiency, and to a high incidence of neoplasias. The authors report the case of two siblings with BS and associated immunodeficiency. Both patients were male and 5 (A) and 4 (B) years old at the time of diagnosis. Chronic diarrhea, recurrent otitis media, purulent rhinitis, conjunctivitis and pyodermatitis were reported by patient A. Patient B was admitted with diagnosis of bilateral neuroblastoma and had the tumor resected. Later on, he presented with oral moniliasis, herpetic stomatitis, and skin abscesses. This patient did not have recurrent infections. Immunological evaluation showed normal serum levels of CH50, C3, and C4 for both patients. Serum IgG, IgA, IgM, and salivary IgA levels were: 455 mg/dl, 15mg/dl, 20mg/dl, 0.6mg/dl for A, and 400mg/dl, 15mg/dl, 20mg/dl, and 0.2mg/dl for B, respectively. Serum antipolio antibodies (1, 2, and 3) were normal, and low levels of isohemagglutinins were observed in both patients. T cells subset determination showed: patient A--OKT3 = 66%, OKT4 = 33%, OKT8 = 32%, and 4/8 ratio = 1.0; patient B--OKT3 = 70%, OKT4 = 32%, OKT8 = 34%, and 4/8 ratio = 1.0. In vitro cellular immune response to PHA was depressed only in patient B. Patients karyotype showed chromosomal breaks with sister chromatid exchanges. Neither patient had abnormal alphafetoprotein and carcinoembryonic antigen serum levels. The rarity of such associations justifies the presentation of the cases.
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PMID:[Familial Bloom's syndrome associated with neuroblastoma]. 221 4

Understanding the biology and treatment of various cancers (including leukemia) and immunodeficiency disorders is still an ongoing and experimental process. Animal models have been and continue to be important to this process. This review will focus in on work by ourselves and others that have used murine models assessing the effects in vivo of the Friend virus complex (FVC, composed of a spleen focus forming virus and a murine leukemia helper virus) and solid tumors with metastatic potential in order to evaluate new and innovative therapies. These therapies include radiation, hyperthermia, and newly recognized naturally occurring biomolecules termed cytokines. These cytokines include, but are not limited to, the interferons, the tumor necrosis factors, the interleukins, the hematopoietic colony stimulating factors, lactoferrin and E-type prostaglandins. For example, it has been found that lactoferrin, when administered early enough, prolongs the survival of mice injected, but not yet infected, with the FVC. Of even greater potential usefulness is that mice already infected with the FVC can be completely rescued from death by treatment with split low dosage (150 cGy) total body irradiation. Irradiation treatment was associated with restoration of the T helper to T suppressor cell ratio, natural killer cell activity and marrow proliferative responses to the mitogens PHA and con A which were compromised by the FVC. More recent studies in our laboratory have demonstrated the potential of the interleukins and colony stimulating factors to decrease the metastatic potential of the B16 melanoma and the Lewis Lung Carcinoma cell lines. The cytokines can act in greater than additive fashion and combinations of therapies are possible. This review is meant to increase the awareness of these investigative animal models and the new types of combination therapies that can then be used as the basis for future clinical trials evaluating therapeutic efficacy.
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PMID:New therapeutic strategies in the treatment of murine diseases induced by virus and solid tumors: biology and implications for the potential treatment of human leukemia, AIDS, and solid tumors. 225 87

We report a familial type of monocyte dysfunction not recognized previously. This disorder was observed in a young adult man with a long clinical history of recurrent, self-limited episodes of cryptogenic fever accompanied by digestive and respiratory symptoms and repeated oral and skin infections. Lectin-induced lymphocyte transformation was reduced and skin tests revealed anergy to tuberculin and candidin. Monocytes from this patient exhibited markedly diminished expression of cytoskeletal vimentin intermediate filaments, HLA-DR antigens and immunological receptors for IgG Fc and C3b. These abnormal monocytes demonstrated impaired phagocytosis and reduced accessory cell function on PHA-mediated lymphocyte activation. Release of soluble lymphocyte-activating factors by these cells was found to be defective. Lymphocytes from the patient responded appropriately to lectin in the presence of normal monocytes. Two family members of the proband presented similar monocyte defects although they only manifested minor clinical symptoms. This syndrome underlines the interest of testing monocyte markers and function in subjects with clinical manifestations of immunodeficiency.
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PMID:Monocyte disorder causing cellular immunodeficiency: a family study. 230 28

Recipients of autologous BMT demonstrate clinically significant immune deficiency, particularly involving the T lymphocytes. While quantitatively the immune system generally returns to normal during the first 3 months, there is a prolonged delay in the recovery of qualitative immune functions. T cell proliferation is impaired immediately after transplantation and slowly recovers over a period of more than 1 year. In addition, a defect has been documented in IL-2 producing cells and may be of major importance in the pathophysiology of this immunodeficiency. However, post-ABMT, PHA-stimulated T cells are TAC+ and are able to respond to exogenous IL-2 in vitro. Very early after ABMT, NK and LAK activities of PBMC normalize but are significantly increased in vitro by IL-2. On this basis, a clinical assessment of rIL-2 administration on the immunological reconstitution of ABMT patients and as consolidation immunotherapy against minimal disease has been initiated in a phase I/II study.
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PMID:Interleukin-2 after autologous bone marrow transplantation as consolidative immunotherapy against minimal residual disease. 234 79

Even though they possess normal to increased numbers of circulating natural killer (NK) cells, patients with chronic myelogenous leukemia (CML) have a functional NK-cell deficiency which is restorable in vitro in the presence of recombinant IL-2. We therefore measured the level of IL-2 production by both T-helper and NK cells from CML patients as compared to normal controls using PHA-stimulated peripheral blood mononuclear cells (PBMs) as well as FACS-sorted CD4+ (OKT4+) lymphoid cells and FACS-sorted CD16+ (B73.1+) lymphoid cells. Peripheral blood mononuclear cells from CML patients demonstrated markedly defective IL-2 production as compared to normal controls (4.0 +/- 1.6 and 5.9 +/- 1.4 units/ml after 24 hr of 5 and 10 micrograms/ml PHA stimulation as compared with 40.7 +/- 10.3 and 69.3 +/- 15.1 units/ml for normal subjects). In addition to the decreased relative percentage of CD4+ (OKT4+) lymphoid cells in CML patients, FACS-sorted CD4+ (OKT4+) cells also demonstrated a significant defect in IL-2 production, (10.8 +/- 3.6 units/ml as compared to 39.0 +/- 5.8 units/ml after 24 hr stimulation with 10 micrograms/ml PHA). FACS-sorted CD16+ (B73.1+) lymphoid cells from CML patients also demonstrated significantly decreased IL-2 production after 24 hr incubation with increasing concentrations of PHA or with the NK-sensitive target K562 as compared to normal controls. Defective IL-2 production by PBMs, CD4+ (OKT4+), and CD16+ (B73.1+) cells from CML patients was also evident after 48 hr of PHA stimulation. Although the percentages of both T4+2H4+ and T4+4B4+ subsets are significantly decreased in CML patients, CML patients have normal ratios of T4+4B4+/T4+2H4+ subsets as compared to normal controls. These and previous results support the hypothesis that decreased IL-2 production by both T-helper and NK cells from CML patients may be mechanistically related to the observed NK-cell immunodeficiency in CML patients.
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PMID:Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. III. Defective interleukin-2 production by T-helper and natural killer cells. 252 12

In 30 patients with definite multiple sclerosis a combined clinicoimmunological investigation was performed. The results of estimation of T-lymphocyte subpopulations by means of flow cytometry and monoclonal antibodies; of proliferative responses to PHA, PWM and Con A, to PHA with autoserum; of synthesis and reception of IL-2 containing material is discussed. A hypothesis of a cyclic course of the immunopathologic process is suggested (autoimmune and immunodeficiency stages).
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PMID:[Characteristics of cellular immunity in multiple sclerosis]. 252 43

Alloreactive mixed lymphocyte reaction (MLR), mitogen-induced response (MR), and suppressor cells against these responses in murine bone marrow chimeras were examined, to clarify the mechanisms of immunological tolerance and immunodeficiency after bone marrow transplantation (BMT). Between 35 and 70 days after BMT, there was no response of spleen cells from allogeneic chimeras against host (C3H/He) and donor (BALB/c) cells, although responses against third party (C57BL/6) cells were detected, thus indicating that these allogeneic chimeras were immunologically tolerant. The activity of suppressor cells against alloreactive responses was increased 35 to 55 days after BMT, so that these suppressor cells appeared to be related to immunological tolerance. Some of the suppressor cells against alloreactive responses were Thy1+. Among them some were Lyt1+ or Lyt2+, and others were Lyt1+2+. Plastic dish non-adherent cells had slightly weaker suppressor activity than adherent cells. Proliferative responses to Con A, PHA, and PWM were decreased 13 to 15 days after BMT, and gradually increased. The responses to LPS differed from those to the former three mitogens, showing an enhanced response 21 to 25 days after BMT. The increased response to LPS did not appear to be simply due to the increased number of non-T cells in the spleen of allogeneic chimeras. The alloantigen specific suppressor cells may play an important role in the induction and maintenance of immunological tolerance, while the alloantigen nonspecific suppressor cells and suppressor cells against MRs may be related to immunodeficiency after BMT.
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PMID:[Alloreactivity and mitogen-induced responses in allogeneic murine bone marrow chimeras]. 253 28

Functional studies were performed on human peripheral blood T lymphocytes stained with goat anti-5'-nucleotidase antibodies and separated into ecto-5'-nucleotidase (ecto-5'-NT)-positive and -negative populations using the FACSTAR fluorescence-activated cell sorter. On the average, ecto-5'-NT+ T cells contained 34 +/- 13% CD4+ and 55 +/- 15% CD8+ cells, whereas ecto-5'-NT-T cells contained 65 +/- 12% CD4+ and 23 +/- 8% CD8+ cells. Staining with anti-5'-NT antibodies did not significantly alter the ability of unseparated T cells to proliferate in response to PHA or PMA, or in a MLR. However, prior incubation with anti-5'-NT antibodies did inhibit the ability of irradiated T cells to provide help for PWM-stimulated Ig synthesis by as much as 55%. In five separate experiments, ecto-5'-NT-T cells demonstrated an equal or better ability to incorporate [3H]TdR after PHA stimulation or in a MLR, as compared with ecto-5'-NT+ T cells. Similarly, ecto-5'-NT- T cells were not diminished in their ability to provide help for autologous B cells in a PWM-driven system. Clearly, the inability of ecto-5'-NT- T cells from patients with a variety of immunodeficiency diseases to function in these assays cannot be explained solely by their lack of ecto-5'-NT activity. In contrast, ecto-5'-NT-positive and -negative T cells showed markedly different dose-response curves for proliferation in response to PMA. Ecto-5'-NT+ T cells responded to lower doses of PMA (1.0 ng/ml) than did ecto-5'-NT- T cells and showed a two- to eight-fold greater rate of [3H]TdR incorporation at 3 to 10 ng of PMA per ml. Ecto-5'-NT+ T cells may have a protein kinase C that is more accessible or more easily activated or may utilize an alternate pathway of activation when stimulated with low concentrations of PMA.
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PMID:Functional characterization of ecto-5'-nucleotidase-positive and -negative human T lymphocytes. 253 56

Details of the molecular interactions between human immunodeficiency virus (HIV-1) and its host cell during the infection process are not entirely clear. Building on recent reports by Lehr and Zimmer (1986, DMW 111, 1001-1002) that the membrane-reactive, anti-epileptic drug diphenylhydantoin (dilantin or phenytoin) (PHT) inhibited binding of HIV to lymphocytes, we hypothesized that understanding the relevant effects of this drug on cells may shed light on aspects of HIV-1 infection. We found that PHT inhibited, in a dose-dependent manner, de novo infection of various T-cell lines as well as a monocytic cell line. Moderate inhibition of HIV-1 infection was observed with drug concentrations that are therapeutic in vivo for epilepsy (approximately 20 micrograms/ml), and no concentrations used induced deleterious effects on cell growth or viability. Surprisingly, treatment of chronically infected H9 cells reduced HIV p24 expression within 1-6 weeks according to dose. This apparent induction into latency was not inhibited by cotreatment of the chronically infected cells with 5-azacytidine, which indicated that PHT was not inducing latency by induction of methylation of the viral DNA. Flow cytometric analysis demonstrated that PHT did not significantly reduce cell-surface expression of CD4. The possibility remained that the drug inhibited HIV infection due to its known effects on calcium-dependent cellular processes. Subsequent measurements of intracellular calcium demonstrated that an increase of [Ca2+]i occurred at least 24 hr postinfection, prior to synthesis of detectable viral structural protein p24, and that this virus-induced increase in [Ca2+]i was not due to binding of HIV to the cell. This HIV-induced rise in [Ca2+]i was significantly inhibited by PHT. PHT demonstrated variable inhibitory effects on infection of normal PHA-stimulated PBLs cultured in vitro, but it was synergistic to low-dose AZT (0.01 microgram/ml) in inhibiting infection of cell lines. Because of the known inhibitory effects of PHT on calcium-dependent biochemical processes in the cell, inhibition of HIV-1 infection by PHT suggests that calcium may play a role in HIV infection and maintenance. The drug may also be a candidate therapy for individuals infected with HIV.
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PMID:Inhibition of human immunodeficiency virus (HIV-1) infection by diphenylhydantoin (dilantin) implicates role of cellular calcium in virus life cycle. 257 18

The paper is concerned with immunological evaluation of different stages of combined therapy with local UHF hyperthermia in children with osteogenic sarcoma. Combined therapy (polychemo- and radiotherapy) was shown to cause a decrease in the number of immunocompetent cells, to enhance imbalance of immunoregulatory T-lymphocytes, to weaken T-lymphocyte function on PHA; immunosuppressive action of combined therapy did not depend on a tumor site. The incorporation of UHF-hyperthermia in the therapeutic scheme weakened the manifestations of secondary immunodeficiency, got back to normal the structure of T-lymphocyte population. A favorable immunomodulating effect of hyperthermia was more frequently observed in patients with crural bone tumors. The effect of hyperthermia was revealed after direct influence of thermotherapy but it was absent in continuation of combined treatment.
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PMID:[The immunomodulating action of combined therapy together with local UHF hyperthermia in osteogenic sarcoma in children]. 260 92


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