Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Young AKR mice grafted i.v. with 10(1) or 10(3) cells from spontaneous AKR thymomas were treated with repeated i.v. injections of BCG or subcutaneous injections of irradiated AKR thymoma cells. BCG often cured mice from graft leukemia, whereas the effect of irradiated thymoma cells was less effective. Mice that did not develop graft-leukemia after graft of 10(1) leukemia cells and BCG treatment showed a spontaneous leukemia in 30% of the cases later. Ninety percent of nongrafted mice developed spontaneous leukemia whether BCG-treated or not. General immune reactivity as assessed in individual mice by T and B lymphocyte mitogen tests as well as the hemolytic plaque-forming cell assay had no clear correlation to the effects of immune adjuvants in respect to survival. In contrast, occurrence of self-directed immune reactions were clearly correlated to survival and cure of grafted and BCG-treated mice as revealed by assays both in vitro and in vivo. However, 13 to 25% of the mice apparently cured of leukemia developed a wasting-like syndrome that sometimes terminated in death. The immplications of self-directed immune reactions as mediators of the anti-neoplastic effects of immunoadjuvants.
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PMID:Immunoadjuvant treatment of primary grafted and spontaneous AKR-leukemia. I. Treatment efficiency correlated to autoimmune reactivity. 37 5

Infant cats were inoculated intracranially with rabies or feline leukemia viruses in an experimental study of wasting syndrome. The daily pre- and postinoculation body weights were recorded until kittens were moribund. Affected animals in both groups manifested growth failure or wasting syndrome. Immunodepression, manifested by a conspicuous depletion of thymic cortex, the thymus dependent areas of the spleen, and growth hormone producing-alpha adenopituicytes was significantly (p less than 0.01) related to the wasting status of the animals. The ability of pituitary glands from these animals to produce growth hormone was studied by in situ immunoperoxidase staining and showed a significant (p less than 0.01) difference between healthy and wasted animals. Rabies and feline leukemia viruses were each found responsible for the low immunoreactivity of growth hormone producing alpha adenopituicytes. Because the hypothalamus and the hypophysis were both found infected, it was concluded that regardless of the triggering agent in primary wasting, the hypothalamic-hypophyseal-thymic axis was always involved through a decrease in growth hormone production.
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PMID:The microepidemiology of wasting syndrome, a common link to diarrheal disease, cancer, rabies, animal models of AIDS, and HIV-AIDS YHAIDS). The feline leukemia virus and rabies virus models. 132 Aug 42

A variant strain of Rauscher leukemia virus (RLV-A) obtained from a transplantable murine monomyelocytic leukemia causes a disease characterized by frank anemia, wasting, hepatosplenomegaly and erythroblastosis. The involvement of platelets in this disease are reported here. The RLV-A induced a severe thrombocytopenia (25 percent of control level) at the terminal stage of disease. This thrombocytopenia was not associated with disseminated intravascular coagulopathy since the prothrombin times were always within normal limits. The partial thromboplastin time was elevated in the terminal stages of disease and was found to be associated with factor deficiencies, possibly owing to the presence of anti-factor antibodies, in the intrinsic coagulation pathway, especially factor VIII. Further, splenectomy did not abolish the thrombocytopenia, since splenectomized, virally infected animals also developed severe thrombocytopenia (29 percent of control levels). The ensuing splenomegaly during progression of disease was not the cause of the thrombocytopenia. A physiological response to the severe thrombocytopenia was the production of larger size platelets. At terminal stages of the disease, platelet volume increased to 4.2 mu 3 (normal is 3.0 mu 3). An increase in platelet volume was also observed in splenectomized, virally infected animals. Electron microscopy indicated that these circulating platelets contained c-type viral particles. Viral infection was associated with decreased life span of circulating platelets, as measured by 75Se-methionine at mid and terminal stages of the disease. Our results suggest that direct viral infection of platelets and/or megakaryocytes with subsequent cell lysis is a possible cause of the observed thrombocytopenia observed in RLVA-induced disease and may also occur in other retrovirally-induced diseases.
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PMID:Thrombocytopenia in a retrovirally-induced murine erythroleukemia. 145 28

The ts1 mutant of Moloney murine leukemia virus TB (MoMuLV-TB) causes a degenerative neurologic and immunologic disease in mice characterized by development of spongiform encephalomyelopathy that results in hind-limb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. T cells, particularly CD4+ helper T cells, play a key role in the pathogenesis of the disease induced by ts1. Therefore, ts1 is unique among the described murine retroviruses in its ability to afflict both the central nervous system (CNS) and the T-cell compartment of the immune system in the same host. This particular ability to cause degenerative diseases involving both the CNS and immune system is shared by the lentiviruses responsible for development of the acquired immunodeficiency syndromes of humans and macaques. Our goal has been to elucidate the specific cellular and molecular mechanisms that underlie this neuro- and immunopathogenicity of ts1. We have previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-Ile, in the precursor envelope protein gPr80env. Further, at the restrictive temperature, the Val-25-Ile substitution did not prevent oligomerization of the gPr80env proteins; however, the structure of the oligomer was incompetent for transport from the ER to the Golgi. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to accumulation of the gPr80env oligomers in the ER. Since glial cells are targets of ts1 infection in vivo, primary astrocytic cultures were established and the cytopathic effect of ts1 and MoMuLV-TB on these cells assessed. Both viruses replicate well in astrocytes and their replication is cytopathic, albeit to different degrees. The ts1 mutant appears to produce greater cell killing than the wild-type virus. Furthermore, it was found that the rate of processing of gPr80env of ts1 in astrocytes is slower than that of MoMuLV-TB. Therefore, the inefficient transport and processing of gPr80env of ts1 appears to correlate with its cytopathic effect in these cells. Electron microscopic studies of the ts1-infected astrocytes revealed large numbers of aberrant particles in the ER. The in vitro cytopathic effect of ts1 on astrocytes may reflect what happens in vivo. An indirect mechanism of neuronal-cell killing by ts1 is proposed.
Leukemia 1992
PMID:Murine leukemia virus induced central nervous system diseases. 160 15

Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1). Inhibition of this cytokine has been a strategy for studying disease and for new drug development. A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms. IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.
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PMID:Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. 183 80

The ts1 mutant of Moloney murine leukemia virus TB causes degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. To investigate the pathogenesis of the thymic atrophy caused by ts1, we constructed a chimeric virus, ts1-Cas(NS), in which a major portion of the U3 region of the long terminal repeat of ts1, a T-lymphotropic and neurovirulent murine leukemia virus, was replaced by the corresponding U3 region of Cas-Br-E, a B-lymphotropic and neurovirulent murine leukemia virus. In FVB/N mice, ts1-Cas(NS) induced paralytic and wasting disease with incidence, severity, and latency similar to that induced by ts1, but it failed to cause thymic atrophy as severe as that observed in ts1-infected mice. Furthermore, thymocytes cultured from ts1-Cas(NS)-infected mice died at a much slower rate than those of ts1-infected mice. The U3 substitution in ts1-Cas(NS) specifically diminished the ability of the virus to replicate in the thymus, whereas viral replication in the spinal cord was not significantly affected; thus, neurovirulence was not changed. The correlation of reduced thymic atrophy with decreased thymic viral titers and the decreased ability of ts1-Cas(NS) to cause thymocyte death in mice suggest strongly that the marked thymic atrophy in ts1-infected mice is not an indirect effect occurring secondary to neurodegenerative and wasting disease but is a direct cytopathic effect of high-level viral replication in the thymus.
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PMID:Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB. 192 61

In this survey for the presence of the feline leukaemia virus (FeLV) in the Singapore domestic cat population, the sera of two different groups of unvaccinated mainly short haired cats which were over 6 months old were sampled. The FeLV enzyme-linked immunoadsorbent assay (ELISA) diagnostic test kit was used to detect the presence of the FeLV group specific (gs) antigens in the blood of cats. Of the 345 clinically healthy cats surveyed, 34 sera (9.9%) were found to be positive and of the group of 123 cats with clinical signs such as chronic wasting, marked by anaemia, anorexia and lethargy, 33 sera (26.8%) were found to be positive. From the time of diagnosis of a viraemia, 70% of cats will die within 20 months. The results are therefore indicative that annually a small proportion of cats in the local environment will die from a FeLV infection. This survey reflects the natural distribution of an infectious oncovirus in a susceptible host population which is unaffected by any control programme to interfere with the normal sequence of events of host virus interactions.
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PMID:A survey of the feline leukaemia virus in Singapore. 256 Mar 57

BALB/c mice infected with ts1, a mutant of Moloney murine leukemia virus-TB, develop generalized body wasting, profound neurologic disorders, severe thymic atrophy and lymphopenia due to destruction of T lymphocytes and drastic immunodeficiency. ts1 was found not only able to infect T lymphocytes but also to impair their function. In addition, ts1 also infects and induces syncyntia formation in macrophages. The genetic determinant(s) responsible for ts1's ability to induce immunodeficiency has been localized to the env gene.
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PMID:ts1, a mutant of Moloney murine leukemia virus-TB, causes both immunodeficiency and neurologic disorders in BALB/c mice. 272 46

Hypokalemia has been noted as a frequent complication of acute leukemia. To our knowledge, an association of this electrolyte disturbance with chronic myelogenous leukemia (CML), not in blast crisis, has never been reported. We report a unique case of hypokalemia that complicated the clinical course of a patient with nonblastic CML. The pathogenesis of the hypokalemia was shown to be inappropriate hyperkaluresis, which appeared to be related to lysozymuria and a large tumor burden. We discuss the pathogenesis of hypokalemia in leukemia. We think that the unusual features associated with CML in this case make a large tumor burden their most likely underlying cause. This may help explain the still confusing and unresolved relationship between lysozymuria and potassium wasting in leukemia.
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PMID:Hypokalemia in nonblastic chronic myelogenous leukemia. 694 May 17

Drug resistance is a critical problem in the therapy of hematologic malignancies. Recent advances in the transplantation of human normal and transformed hematopoietic cells into severe combined immunodeficient (SCID) mice provide an opportunity to study the biologic and molecular events that mediate resistance. We studied the engraftment of several human myelogenous leukemia cell lines sensitive and resistant to amsacrine (mAMSA), vincristine, hycamptamine, methotrexate, or doxorubicine (KBM3/AMSA, K562/Vcr, HL60/Hy10, K562/MTX, HL60/Dox). The distribution and growth potential of these cells was evaluated using molecular and histologic techniques. Inoculation of 2 x 10(7) leukemic cells led to manifestation of disease, and subsequent tissue analysis showed evidence of leukemia. The survival of mice varied from 21 to 135 days. Terminally, the animals showed symptoms of wasting, development of local tumors, or both. Massive leukemic dissemination with infiltration of bone marrow and various organs including lungs, spleen, liver, ovaries, and brain was detected in most cases. No differences were observed in the tissue distribution of sensitive as compared to resistant leukemia cells. These findings demonstrated that human leukemic cells retain, in SCID mice, the clinico-pathologic picture of the original disease in humans. The development of numerous drug-resistant phenotypes in vitro does not alter the subsequent behavior of resistant cells in vivo when compared with sensitive counterparts. The levels of resistance are not modified by passage through SCID mice. This model offers an opportunity for developing new preclinical in vivo systems for modulation of drug resistance, and the combination of this in vivo model with gene transfer methods will also provide an important system for testing the molecular alterations involved in drug resistance and leukemic progression.
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PMID:Growth of sensitive and drug-resistant human myeloid leukemia cells in SCID mice. 786 Apr 33


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