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)

Feline leukemia virus is a naturally occurring, contagiously transmitted and oncogenic immunosuppressive retrovirus of cats. The effects of FeLV are paradoxical, causing cytoproliferative and cytosuppressive disease (eg, lymphoma and myeloproliferative disorders vs immunodeficiency and myelosuppressive disorders). In the first few weeks after virus exposure, interactions between FeLV and hemolymphatic system cells determine whether the virus or the cat will dominate in the host/virus relationship--persistent viremia and progressive infection or self limiting, regressive infection will develop. The outcome of these early host/virus interactions is revealed in the diagnostic assays for FeLV antigenemia and viremia. The latter, in turn, predict the outcome of FeLV infection in cats. Known host resistance factors include age and immune system functional status. Known virus virulence factors are magnitude of exposure and virus genotype. Molecular analysis of FeLV strains indicated that natural virus isolates exist as mixtures of closely related virus genotypes and that minor genetic variations among FeLV strains can impart major differences in pathogenicity. The genetic coding regions responsible for cell targeting and specific disease inducing capacity (eg, thymic lymphoma, acute immunosuppression, or aplastic anemia) have been mapped to the virus surface glycoprotein and/or long terminal repeat regions for several FeLV strains. Infection by specific FeLV strains leads to either malignant transformation or cytopathic deletion of specific lymphocyte and hemopoietic cell population, changes that prefigure the onset of clinical illness. Another notable feature of the biology of FeLV is that many cats are able to effectively contain and terminate viral replication, an important example of host immunologic control of a retrovirus infection and a process that can be selectively enhanced by vaccination. Thus, FeLV infection serves as a natural model of the multifaceted pathogenesis of retroviruses and as a paradigm for immunoprophylaxis against an immunosuppressive leukemogenic retrovirus.
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PMID:Feline leukemia virus infection and diseases. 166 70

Between 1988 and 1991, feline immunodeficiency virus (FIV) infection status was evaluated in 1,160 cats examined at an oncology referral and general practice in Los Angeles, California. Twenty-nine (2.5%) cats were FIV positive. Neoplasia was present in 18 of the 29 (62%) cats. Sampling for neoplasia was intentionally biased in the oncology referral group. However, 33% (6/18) of FIV-infected cats with neoplasia originated from the general practice. Three neoplastic processes were observed; myeloproliferative disease (MPD; 5/18), lymphoma (LSA; 5/18), and squamous cell carcinoma (SCC; 7/18). One cat had LSA and SCC. Extranodal sites of LSA were common (66%) in FIV-infected cats. Sites of LSA were submandibular and mesenteric lymph nodes, liver, kidneys, periorbital area, and diffuse (heart, pancreas, bladder). Sites of SCC were sublingual (n = 2), nasal planum (n = 3), nasal planum and eyelids (n = 1), and mandible (n = 2). Feline leukemia virus co-infection was observed in 17% (5/29) of FIV-infected cats. The FIV-infected cats with MPD were young (range, 8 months to 13 years; median, 4 years) and had short survival duration (2, 6, 21, 134, 249 days) even in response to aggressive treatment. The FIV-infected cats with LSA were older (median age, 8 years; range, 4 to 14 years) and survived 60 days if untreated. Cats administered chemotherapy survived 39, 45, 217, and 243 days; the latter 2 cats had partial remission of 2 months' duration. Older FIV-infected cats had SCC (median age, 12 years; remission range, 7 to 16 years) because of more frequent association of both diseases in older cats with outdoor environment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neoplasia associated with feline immunodeficiency virus infection in cats of southern California. 166 82

The physiologic mechanisms that influence plasma levels of von Willebrand factor (vWF) are poorly understood but include race, blood group, age, pregnancy, exercise, and adrenergic and neurohumoral stimuli. Inherited abnormalities in von Willebrand's disease (vWD) are associated with a defect of the vWF gene on chromosome 12, but in some cases, coexistence of impaired response of plasminogen activator and telangiectasia suggests the presence of a regulatory defect or more extensive endothelial perturbation. Three broad types of vWD are recognized; in addition, a platelet-type vWD (pseudo-vWD) is due to an abnormal platelet receptor for vWF. The prevalence of vWD, which is difficult to determine because of variations in severity even within a kindred, is reportedly as high as 1%. In a survey of European patients, the prevalence of treated vWD varied from 4.5 to 24 per million. Preliminary results of an international survey of vWD indicate that about 3% of treated patients have seroconversion to human immunodeficiency virus, 50% of whom have symptoms. Inhibitor of vWF occurs in type III vWD after treatment and is associated with the presence of gene deletions. Acquired vWD may complicate lymphoproliferative and autoimmune disorders, and proteolytic degradation of vWF complicates myeloproliferative disorders. The level of vWF is increased during pregnancy and in vascular and other disorders; it may be involved in the pathogenesis of atherosclerosis. High-molecular-weight multimers of vWF and a cofactor are thought to promote the formation of microthrombi in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Thus, study of vWD has shed light on pathogenetic mechanisms in a wide range of disorders.
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PMID:von Willebrand factor: clinical features of inherited and acquired disorders. 207 62

Feline immunodeficiency virus (FIV; formerly, feline T-lymphotropic lentivirus) is a typical lentivirus resembling human and simian immunodeficiency viruses in morphologic features, protein structure, and reverse transcriptase enzyme. It is antigenically dissimilar, however. The virus is tropic for primary and permanent feline T-lymphoblastoid cells and Crandell feline kidney cells. The virus did not grow in other permanent feline non-lymphoblastoid cells that were tested, or in lymphoid and non-lymphoid cells from man, dogs, mice, and sheep. During short-term inoculation studies in cats, the feline immunodeficiency-like syndrome found in nature was not experimentally induced, but a distinct primary phase of infection was observed. Fever and neutropenia were observed 4 to 5 weeks after inoculation; fever lasted several days, and neutropenia persisted from 1 to 9 weeks. Generalized lymphadenopathy that persisted for 2 to 9 months appeared at the same time. Antibodies to FIV appeared 2 weeks after inoculation and then plateaued. Virus was reisolated from the blood of all infected cats within 4 to 5 weeks after inoculation and persisted indefinitely in the face of humoral antibody response. Virus was recovered from blood, plasma, CSF and saliva, but not from colostrum or milk. Contact transmission was achieved slowly in one colony of naturally infected cats, but not between experimentally infected and susceptible specific-pathogen-free cats kept together for periods as long as 4 to 14 months. The infection was transmitted readily, however, by parenteral inoculation with blood, plasma, or infective cell culture fluids. In utero and lactogenic transmission were not observed in kittens born to naturally or experimentally infected queens. Lymphadenopathy observed during the initial stage of FIV infection was ascribed to lymphoid hyperplasia and follicular dysplasia. A myeloproliferative disorder was observed in 1 cat with experimentally induced infection.
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PMID:Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. 245 96

Feline immunodeficiency virus (FIV) (formerly feline T-lymphotropic lentivirus or FTLV) was first isolated from a group of cats in Petaluma, California in 1986. The virus is a typical lentivirus in gross and structural morphology. It replicates preferentially but not exclusively in feline T-lymphoblastoid cells, where it causes a characteristic cytopathic effect. The major structural proteins are 10, 17 (small gag), 28 (major core), 31 (endonuclease?), 41 (transmembrane?), 52 (core precursor polyprotein), 54/62 (reverse transcriptase?), and 110/130 (major envelope) kilodaltons in size. The various proteins are antigenically distinguishable from those of other lentiviruses, although serum from EIAV-infected horses will cross-react with some FIV antigens. Kittens experimentally infected with FIV manifest a transient (several days to 2 weeks) fever and neutropenia beginning 4 to 8 weeks after inoculation. This is associated with a generalized lymphadenopathy that persists for up to 9 months. Most cats recover from this initial phase of the disease and become lifelong carriers of the virus. Complete recovery does not occur to any extent in nature or in the laboratory setting. One experimentally infected cat died from a myeloproliferative disorder several months after infection. The terminal AIDS-like phase of the illness has been seen mainly in naturally infected cats. It appears a year or more following the initial infection in an unknown proportion of infected animals. FIV has been identified in cats from all parts of the world. It is most prevalent in high density populations of free roaming cats (feral and pet), and is very uncommon in closed purebred catteries. Male cats are twice as likely to become infected as females. Older male cats adopted as feral or stray animals are at the highest risk of infection, therefore. The infection rate among freely roaming cats rises throughout life, and reaches levels ranging from less than 1% to 12% or more depending on the area. Clinically affected cats tend to be 5 years or older at the time of hospitalization. Experimental and seroepidemiologic studies suggest that FIV is transmitted mainly by bites. Intimate, non-traumatic contact (mutual grooming, shared use of food, water and litter pans) is inefficient in transmitting the infection. In utero and venereal transmission could not be demonstrated in laboratory settings. There is no statistical linkage between FIV and feline leukemia virus (FeLV) infections in nature. The FeLV infection rate in FIV-infected animals is the same as it is for non-FIV-infected cats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Feline immunodeficiency virus infection. 254 90

In view of the possibility that immunological dysfunctions may be involved in initiating or contributing to the pathogenesis of myeloproliferative disease, we investigated quantitative and functional activity of natural killer (NK) cells in patients with polycythemia vera, essential thrombocythemia and myelofibrosis, and have demonstrated, especially in myelofibrosis, a measurable cytotoxic defect in the ability of their peripheral blood mononuclear cells to efficiently kill the standard NK target, K-562. Furthermore, highly purified, FACS-sorted CD16+ lymphoid cells from patients with myelofibrosis were consistently defective in their ability to lyse K-562 targets, and could not be augmented substantially with recombinant interleukin (IL)-2. Only patients with myelofibrosis had significantly lower percentages and absolute numbers of CD16+ cells as compared to patients with essential thrombocythemia and polycythemia vera. Further experiments demonstrated that patients with myelofibrosis, although having fewer CD16+ NK cells, had a significantly increased proportion of CD16+ cells with detectable platelet-derived growth factor (PDGF) on their surface. In contrast, surface PDGF was barely detectable on CD16+ cells from patients with polycythemia vera and essential thrombocythemia, as well as from normal controls. Having previously reported that physiologic quantities of PDGF significantly inhibit human NK cell cytotoxicity, and that patients with myelofibrosis and essential thrombocythemia have significantly elevated circulating levels of plasma PDGF, we now have demonstrated that pretreatment of normal NK cells with concentrated, PDGF-containing, platelet-poor plasma from patients with these diseases significantly inhibits NK cytotoxicity. This inhibitory effect was reversed by neutralization of plasma PDGF with anti-PDGF (coupled to Sepharose resin). Both the NK defects demonstrated in this study, and the abnormal plasma PDGF results reported earlier, are most striking in myelofibrosis and least abnormal in polycythemia vera, with an intermediate degree of abnormality in essential thrombocythemia. Our new findings suggest a causal correlation between abnormal platelet release, plasma accumulation of PDGF, and the observed NK immunodeficiency in these myeloproliferative patients.
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PMID:Quantitative and functional studies of impaired natural killer (NK) cells in patients with myelofibrosis, essential thrombocythemia, and polycythemia vera. I. A potential role for platelet-derived growth factor in defective NK cytotoxicity. 832 37

We describe a case of essential thrombocythemia observed in a 67-year-old woman with severe IgA-deficiency. The the best of our knowledge, this is the first report concerning the onset of a chronic myeloproliferative disease (CMPD) in a patient affected with primary immunodeficiency, in particular IgA-defect. The association may be merely coincidental; otherwise hemopoietic growth factors acting on myeloid progenitor cells could play a role in this relationship. It has recently been shown that serum levels of many cytokines are elevated in patients with CMPD and probably contribute to enhance proliferation of the malignant clones; on the other hand interleukin-6 seems to account for reactive thrombocytosis, and significant amounts of circulating interleukin-4 and interleukin-6 have been detected in IgA-deficient patients. Overproduction of the two cytokines may depend on recurrent infections, but it could also represent a primary abnormality, with a putative role in the pathogenesis of the immune defect. These findings suggest that high levels of growth factors could induce myeloid hyperproliferation and so expose stem cells to genetic mutations responsible for malignant transformation.
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PMID:[Primary thrombocythemia in a female carrier of IgA deficiency]. 902 53

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.
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PMID:Human immunodeficiency virus infection, Part II. 988 69

Among risk groups for GB virus C (GBV-C)/HGV infection, patients with haematological diseases are particularly exposed due to the combination of transfusional support and immunodeficiency status. To examine any association between GBV-C/HGV positivity and different malignancy potential of hematological diseases, we investigated two groups of patients, one with clonal stem cell disease with long latency period (myelodysplasia, myeloproliferative disease) and one with malignant haematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia, multiple myeloma). Virus positivity was compared with the data from cytogenetic analysis at first diagnosis. The frequency of GBV-C/HGV infection in these patients was studied using reverse transcription-polymerase chain reaction (RT-PCR) and E2 antibody assay. Serum GBV-C RNA was found in 29/47 (62%) patients. The prevalence of GBV-C RNA in the group of oncological cases (72%) was significantly higher (P= .02) than in the patients with clonal stem cell diseases (28%). Among the GBV-C negative cases, only 25% had malignant haematological diseases. The data from GBV-C/ HGV tested cases for which cytogenetic analysis was carried out indicated an association of GBV-C/HGV positivity with genomic destabilization in general. Of the cases with numerical and structural aberrations, 64% were GBV-C positive. A correlation could not be confirmed between GBV-C/HGV and liver enzyme levels, blood transfusions, chemotherapy treatment, or viral coinfection. These findings suggest a high risk of GBV-C/HGV infection in patients with haematological disorders especially in the group of malignant diseases. These observations may indicate that the persistence of GBV-C/HGV in these patients could be associated with susceptibility to genomic destabilisation.
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PMID:Association of GB virus C (GBV-C)/hepatitis G virus (HGV) with haematological diseases of different malignant potential. 1008 47

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder in which there is a deregulated amplification of CML progenitors at intermediate stages of their differentiation along the myeloid, erythroid and megakaryocyte pathways. Such cell populations are routinely quantified using standard in vitro colony-forming cell (CFC) assays. The excessive production of leukemic CFC that is seen in most CML patients at diagnosis may be explained at least in part by their increased proliferative activity. An anomalous cycling behavior in vivo has also been found to extend to more primitive CML progenitor populations detectable as long-term culture-initiating cells (LTC-IC). Although the molecular basis of these changes in CML progenitor regulation is not fully understood at the level of the primitive CFC compartment, a selective inability of CML progenitors to be inhibited by certain -C-C-type chemokines has been demonstrated. Failure of the CML stem cell compartment to expand in vivo at the same rate as later progenitor cell types may be explained by their unique additional possession of an intrinsically upregulated probability of differentiation. Such a mechanism would be consistent with the observed loss of LTC-IC activity by CML cells incubated in vitro under conditions that sustain or expand normal LTC-IC populations. Initial clinical studies undertaken at our center established the feasibility of exploiting the differential behavior of primitive normal and CML cells in vitro as a potential purging strategy for reducing the leukemic stem cell content of CML marrow autografts. The results of a larger, second trial now in progress on a group of unselected patients are encouraging. Future studies of nonobese diabetic/severe-combined immunodeficiency mice engrafted with CML cells should provide another useful preclinical model for evaluating treatments that may more effectively eradicate the neoplastic clone in vivo.
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PMID:Differences between normal and CML stem cells: potential targets for clinical exploitation. 1101 49


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