Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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

A immunodeficiency of natural killer cells as effectors for natural killer and lymphokine-activated killer cytotoxicities was first demonstrated in siblings. Two of three male siblings persistently lacked natural killer activity against K562 target cells as assayed by a 51Cr-release assay: percent lysis values were less than 1.0% as compared to the normal lymphocyte values of 43.5% +/- 6.2% (mean +/- SD). Their lymphocytes did not develop natural killer cell activity by changing effector to target ratios, prolonging the incubation time, or stimulating them with interferon-alpha or interleukin 2. Numbers of lymphocytes bearing Leu-7, CD16, or NKH-1 were normal but those of Leu-7-, CD16+ cells were decreased as estimated by flow cytometry. Single cell-in-agarose assays showed normal numbers of natural killer cells capable of binding to a target cell but incapable of killing it. They had depressed levels of lymphokine-activated killer activity, which was totally eliminated by the treatment with OKT3 and complement. This result indicates that the patients' natural killer cells are also defective in the capacity to work as effectors for lymphokine-activated killer activity. The patients' natural killer cells did not produce natural killer cytotoxic factor activity. Antibody-dependent cellular cytotoxicity and cytotoxic T lymphocyte cytotoxicity were normal. These results demonstrate a selective natural killer cell deficiency as effectors for natural killer and lymphokine-activated killer cytotoxicities with a familial tendency, in which there is defective killing with the absence of natural killer cytotoxic factor activity.
 ...
PMID:Natural killer cell immunodeficiency in siblings: defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities. 230 85

We performed follow-up studies in 11 patients with asymptomatic classic hemophilia, who on initial study 8 to 12 months previously had demonstrated abnormalities of lymphocyte phenotype and function. Although all subjects remained well, diminished lymphocyte proliferative responses, natural killer activity, and decreased ratios of OKT4 helper/OKT8 suppressor lymphocytes persisted. Moreover, the absolute number of OKT4 helper lymphocytes fell in the patients from a mean of 745 +/- 73/microliter in the first study to 585 +/- 50/microliter in the follow-up study, which was lower than the control value of 857 +/- 87 (P less than 0.02). Despite diminished natural killer activity, patients with hemophilia had at least normal numbers of natural killer cells as determined by the presence of the OKM1 antigens and Giemsa staining to identify large granular lymphocytes. Patients with hemophilia had more Leu 11a-positive cells than controls. Lymphocyte binding to tumor targets was not diminished, and removal of adherent cells did not increase patients' natural killer activity to control levels. Incubation of patients' lymphocytes with alpha-interferon, gamma-interferon, or interleukin-2 resulted in enhancement of natural killer activity but did not reach control levels. Thus the diminished natural killer activity in patients with hemophilia retained responsiveness to lymphokines and was caused either by an intrinsic or acquired defect in the natural killer cell or by modulation by a nonadherent cell. Subclinical immunodeficiency in patients with hemophilia is not transient and is associated with a diminished number of OKT4 helper cells, a finding often associated with clinical immunodeficiency.
 ...
PMID:Impaired cell-mediated immunity in hemophilia. II. Persistence of subclinical immunodeficiency and enhancement of natural killer activity by lymphokines. 241 May 23

Various immunological parameters were studied in 20 asymptomatic patients with hemophilia A, 3 patients with hemophilia B and 1 patient with von Willebrand disease. Patients were treated with cryoprecipitate or fresh frozen plasma. Significantly decreased mean percentage and absolute count (p less than 0.01) of peripheral blood E-rosette-forming cells compared to controls was found. There were normal mean percentages and absolute counts of lymphocytes, T-helper inducer, T-suppressor cytotoxic and natural killer cells. The proportion and absolute number of B cells was slightly increased. Significantly decreased natural killer cell activity (p = 0.02) of peripheral blood lymphocytes was observed. Our results indicate that asymptomatic patients with hemophilia may have early evidence of immunodeficiency.
 ...
PMID:Immunologic studies in asymptomatic hemophiliac patients. 243 38

The production of interferon (IFN) after stimulation of peripheral blood mononuclear cells with Sendai virus or phytohemagglutinin was studied in patients with common variable immunodeficiency (CVID) or selective IgA deficiency. Cells from CVID patients produced significantly more Sendai virus-induced (alpha) and mitogen-induced (gamma) IFN than cells from healthy control subjects. By contrast, some patients with selective IgA deficiency produced subnormal amounts of IFN-alpha. Neither IFN-alpha nor IFN-gamma was detectable in sera from the two categories of patients using radioimmunoassays with sensitivity limits of 5-10 international units per milliliter. With the aid of a more sensitive bioimmunoassay, however, antiviral activity was detected more frequently in sera from patients with CVID than in sera from control individuals. Acid treatment and absorption with anti-IFN-alpha and anti-IFN-beta sera indicated that the antiviral activity was due to IFN, with no preponderance of any particular IFN type. Determination of beta-2-microglobulin (beta 2M) concentrations revealed that CVID patients had markedly, and IgA-deficient patients moderately increased serum levels of this substance, as compared to healthy blood donors. Since IFN enhances the synthesis of beta 2M the finding of increased levels of this substance in CVID would be consistent with the observed hyperproduction of IFN. The present findings are concordant with earlier observations of increased natural killer cell activity in at least some forms of CVID and suggest that increased activity of the IFN/natural killer cell system provides a mechanism which may compensate for the defective B cell function in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interferon and beta 2-microglobulin in patients with common variable immunodeficiency or selective IgA deficiency. 244 57

To determine laboratory evidence suggesting immunological abnormalities in persons with hemophilia, we evaluated the immunological status of 75 Korean hemophiliacs, seronegative for human immunodeficiency virus (HIV) antibodies, who have been treated only with Korean factor VIII concentrates. From this study, it was shown that Korean hemophiliacs had decreased CD4 levels, increased CD8 levels, and decreased CD4:CD8 ratios. Diminished lymphocyte response to the mitogens, phytohemagglutinin and concanavalin A, and decreased natural killer cell activity were observed in the hemophiliacs. In addition, production of interleukin-II in the hemophiliacs was lower than in the healthy controls. The percentage of B lymphocytes was significantly reduced but the serum levels of immunoglobulin (Ig) G were elevated. However, the serum Ig A and Ig M levels were normal. This study demonstrated a high frequency of immunological abnormalities in HIV antibody negative Korean hemophiliacs treated only with domestic factor VIII concentrates.
 ...
PMID:A comprehensive study of immunological abnormalities in Korean hemophiliacs. 250 31

Epidemic Kaposi's sarcoma (EKS) is the most common neoplastic manifestation of acquired immune deficiency syndrome (AIDS). The underlying immune deficiency can be partially reversed in vitro with interleukin-2 (IL-2). The type 1 interferons (IFN), alpha and beta, inhibit the growth of the etiologic agent of AIDS, the human immunodeficiency virus, have antitumor activity against Kaposi's sarcoma, and are synergistic with IL-2 in stimulating natural killer cell activity. Four patients with EKS were treated three times weekly with simultaneous intravenous injections of recombinant IL-2 (5 X 10(6) Cetus units/m2) and recombinant IFN-beta (6 X 10(6) units/m2). All patients had generalized disease, were without systemic symptoms, had no prior opportunistic infection, and had stable disease at the initiation of therapy. No patient had an objective response. Three patients exhibited rapid disease progression within 2-4 weeks of starting treatment, necessitating discontinuation of therapy and early closure of the study. This adverse result may have resulted from the significant levels of gamma-interferon (IFN-gamma) that can be generated with this dose and schedule of IL-2. Investigators using IL-2 should monitor IFN-gamma levels and avoid intermediate to high-dose bolus IL-2 therapy in patients with EKS.
 ...
PMID:Exacerbation of epidemic Kaposi's sarcoma with a combination of interleukin-2 and beta-interferon: results of a phase 2 study. 266 85

Evidence from correlative studies and Winn-type assays in syngeneic murine models has suggested that natural antibodies contribute to resistance against tumors in vivo. The B cell deficit associated with the X-linked immunodeficiency of CBA/N strain mice provided a genetic model in which to further test this question. RI-28, a radiation-induced T cell leukemia of the CBA/H strain acquired reduced levels of fluorescence-detected natural antibodies from the serum of X-linked immunodeficiency-bearing CBA/N and male (CBA/N x CBA/J) F1 mice compared with the serum from normals. Threshold s.c. inocula of the RI-28 appeared sooner and produced higher tumor frequencies in the X-linked immunodeficiency-bearing animals. This data coupled with the lack of correlating deficiencies in natural killer cell or activated macrophage activity provide the first genetic evidence for the hypothesis.
 ...
PMID:Low natural antibody and low in vivo tumor resistance, in xid-bearing B-cell deficient mice. 278 60

The destruction of proliferating lymphoid cells within germinal centers with subsequent replacement by histiocytoid cells has been described in infants and children dying of viral and bacterial infections. The etiology and significance of "epithelioid germinal centers" (EGCs) are unknown. The cells implicated in forming EGCs have included histiocytes and dendritic reticulum cells. We have studied four children at autopsy who died at ages ranging from 10 months to 7 years. Three contracted fatal infections, one with fulminant meningococcemia, one with bacterial sepsis, and one with viral hepatitis. The fourth child contracted viral pneumonitis and died of acetaminophen toxicity. Epithelioid germinal centers were found in numerous lymphoid organs (spleen, lymph nodes, and Peyer's patches) in all four cases. Avidin-biotin complex immunohistochemical analysis performed on formalin-fixed splenic tissue from the first three cases and snap-frozen splenic tissue from the second case revealed an absence of B cells in the follicular centers. The mantle zones surrounding follicles were thin but intact. The histiocytoid cells expanding the germinal centers were positive for S100 and R4/23 (dendritic reticulum cells) and negative for numerous histiocyte markers (alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme). Increased numbers of killer cells (Leu-7) were present within the affected germinal centers in the three cases in which material was available for immunohistochemical studies. Overwhelming infections in these patients seem to result in anomalous natural killer cell activation resulting in localized nonselective destruction of follicular centers similar to anomalous natural killer cell activity reported to occur in fatal infectious mononucleosis. This may lead to an acquired immunodeficiency that precludes long-term survival in affected patients.
 ...
PMID:Epithelioid germinal centers in overwhelming childhood infections. The aftermath of nonspecific destruction of follicular B cells by natural killer cells. 284 41

In a previous study of asymptomatic homosexual men, we found that CD8+ T-cell levels were higher in homosexual men infected with the human immunodeficiency virus (HIV) than in uninfected homosexual men because of higher numbers of CD8+ T cells that do not express the Leu15 marker, a phenotype associated with cytotoxic function. Among infected men, there was a positive correlation between the number of CD8+Leu15- T cells and the number of CD4+ T cells. If CD4+ T-cell levels are taken as a measure of severity of HIV infection and immunodeficiency, these results suggested that higher CD8+Leu15- cells may represent a phenotypic profile associated with less severe infection or better control of infection. In the present study, we extend the analysis to include a group of men who progressed to AIDS but were studied well before the onset of AIDS, and we compare results of CD8 subset analyses with results of infected men who have not progressed to AIDS. Phenotypic subsets associated with helper, suppressor, cytotoxic, and natural killer cell function were determined by two-color immunofluorescence. The only phenotypic subset that distinguished men who progressed to AIDS from those who have not was lower numbers of CD4+ T cells in the former group. If CD8+Leu15- cell numbers (or other phenotypic subsets examined) reflect effective control of HIV infection, the relationship is not strong enough to be of prognostic or predictive value with respect to outcome of infection.
 ...
PMID:Phenotypic distribution of T cells of patients who have subsequently developed AIDS. 295 Oct 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>