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)

A previously undescribed type of encephalomyelopathy after prophylactic intrathecal methotrexate (MTX) treatment for acute leukemia is reported. The patient was treated systemically with vincristine, MTX, stereoids and mercaptopurine. Radiation therapy was not given. The neurologic symptoms started 24 hours after the completion of the fifth intrathecal MTX instillation and death ensued 18 days later. The lesions consisted of superficial and sharply circumscribed areas of incomplete necrosis with astrocytosis on the base of the brain and along the insula regions, around the foramina of Luschka, and over the superior and inferior colliculi. Similar superficial lesions were found over the surface of the cerebellum and along most of the surface of the spinal cord. Most of the affected areas in the brain were located under the large subarachnoid cisterns. In the cord the lesions were most pronounced along the entrance zones of the roots. There was also a severe loss of anterior horn cells. There were no signs of meningeal leukemia, no pathological changes were caused by the intrathecal MTX treatment.
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PMID:Encephalomyelopathy following intrathecal methotrexate treatment in a child with acute leukemia. 58 Dec 72

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

Human T cell leukemia virus type I and II are endemic in South West Japan and in large parts of the equatorial belt in Central and South America, in Africa, and in some Pacific islands, areas where 1 to 5% of the general populations are infected. Pockets of high prevalence up to 15% and even 35% can be observed. The transmission of HTLV-I includes: maternal to offspring through breast feeding, sexual mainly from men to women and through blood exchange (blood transfusion, intravenous drug abusers, etc.) The diseases being proven to be caused by HTLV-I, include acute adult T cell leukemias as described in Japan, in 1977, in which the HTLV-I provirus is clonally integrated in leukemic cells, and a progressive spastic encephalomyelopathy named TSP/HAM, frequent in HTLV-I endemic areas, and in which an active viral replication takes place. No specific treatment being available, vaccine development, more feasible than for HIV, is critical since 8 to 12% of seropositive individuals develop HTLV-I associated diseases.
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PMID:[Clinical and biological epidemiology of onco-retroviral HTLV-I and II infections]. 174 24

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

The ts1 mutant of Moloney murine leukemia virus TB causes a degenerative neurologic and immunologic disease in susceptible strains of mice. This disease syndrome is characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, generalized bodywasting, and marked thymic atrophy associated with immune deficiency. The viral genetic determinants responsible for hindlimb paralysis in BALB/c and CFW/D mice have been localized to two point mutations in the env gene: one results in a Val-25----IIe substitution in the envelope precursor polyprotein gPr80env and the other, in an Arg-430----Lys substitution in the gp70. In this report we present studies showing that FVB/N mice were highly susceptible to ts1 and exhibited the shortest and most uniform latency period of all the murine strains tested. In addition, we have found that, unlike in CFW/D and BALB/c mice, only the Val-25----IIe substitution in the gPr80env is required to induce hindlimb paralysis in FVB/N mice. Our studies show that there was enhanced replication of ts1 in all tissues of FVB/N mice and that the virus titer in the spinal cord was more than 10-fold higher in FVB/N than in BALB/c mice by 30 days postinoculation, when the clinical signs of paralysis became evident in FVB/N mice. Apparently, other host factors that do not require the Arg-430----Lys substitution allowed high levels of viral replication within the central nervous system of FVB/N mice. These results, together with the finding that 100% of FVB/N mice that were inoculated with ts1 at 5 days of age developed hindlimb paralysis at 30-60 days postinoculation, whereas only 33% of 5-day-old BALB/c mice developed hindlimb paralysis with a much longer latency period, suggest that subtle virus-host interactions determine the incidence, the latency period, and the severity of the disease caused by ts1.
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PMID:High susceptibility of FVB/N mice to the paralytic disease induced by ts1, a mutant of Moloney murine leukemia virus TB. 198 56

Tropical spastic paraparesis or human T-lymphotropic virus type I (HTLV-I)-associated myelopathy is a degenerative encephalomyelopathy with pyramidal tract dysfunction affecting the lower extremities. It is associated with HTLV-I infection and found primarily in the Caribbean region and in southwestern Japan. Five cases of tropical spastic paraparesis (or HTLV-I-associated myelopathy) in Hawaii are reported. All five patients were born in Hawaii; four are women. Each of the patients has parents who were from HTLV-I-endemic areas of Japan. Two of these patients had serum antibodies to HTLV-I. Five of six of the spouses and children of the seropositive patients were also seropositive. Viral cultures of lymphocytes from both seropositive patients and two of the three seropositive children were positive for HTLV-I. None of the five patients had a history of antecedent blood transfusion, multiple sexual partners, or intravenous drug use. There is no evidence of adult T-cell leukemia or lymphoma in any of the patients or their families. Given the increasing seroprevalence of HTLV-I in the United States, clinicians need to be alert to new cases of this disorder.
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PMID:Human T-lymphotropic virus type I (HTLV-I) and tropical spastic paraparesis or HTLV-I-associated myelopathy in Hawaii. 213 54

It has been shown that the autosomal recessive mutation, gray tremor (gt) was associated in the homozygous state (gt/gt) with a rapidly fatal spongiform encephalopathy. Heterozygotes (+/gt) developed mild asymptomatic spongiform brain lesions as did recipient inbred mice inoculated with gt/gt brain homogenates, some of whom also showed behavioral abnormalities [Sidman, R. L., Kinney, H. C. & Sweet, H. O. (1985) Proc. Natl. Acad. Sci. USA 82, 253-257]. In these studies, inbred NFS/N mice inoculated intracerebrally at birth or as adults with gt/gt or first passage gt brain homogenates developed a progressive disease characterized by tremor, ataxia, and spasticity. The symptoms were milder and more slowly progressive than in the gt/gt homozygote, in the paralytic syndrome that followed neonatal inoculation of NFS/N mice with a wild murine leukemia virus (Cas-Br-M MuLV), or in the rapidly progressive ataxia and terminal bradykinesia that followed scrapie inoculation of NFS/N mice. The noninflammatory spongiform encephalopathy in affected NFS/N mice resembled that observed in gt/gt homozygotes, +/gt heterozygotes, and asymptomatic recipient inbred mice inoculated with gt/gt brain homogenates. Neither infectious MuLV nor MuLV proteins were detected in gt/gt brain homogenates or in affected recipient mouse brains. Scrapie-associated fibrils, readily identifiable in subcellular fractions of brains from scrapie-inoculated NFS/N mice, were not detected in similar brain fractions from NFS/N mice inoculated with gt brain homogenates. These results confirm and extend the suggestion that gt spongiform encephalopathy has both heritable and transmissible properties. Moreover, the transmissible agent of gt disease differs from both Cas-Br-M MuLV and scrapie in its disease-inducing properties in NFS/N mice. The capacity of NFS/N mice to express transmitted gt encephalopathy as clinical disease, to rapidly express Cas-Br-M MuLV spongiform encephalomyelopathy, and to develop mouse-adapted scrapie after a very short incubation time suggest a distinct sensitivity of NFS/N mice to transmissible spongiform encephalopathy.
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PMID:Transmission in NFS/N mice of the heritable spongiform encephalopathy associated with the gray tremor mutation. 347 86

Recombinants of amphotropic murine leukemia virus (A-MuLV) have found widespread use in retroviral vector systems due to their ability to efficiently and stably infect cells of several different species, including human. Previous work has shown that replication-competent recombinants containing the amphotropic env gene, encoding the major SU envelope glycoprotein that determines host tropism, induce lymphomas in vivo. We show here that these viruses also induce a spongiform encephalomyelopathy in mice inoculated perinatally. This fatal central nervous system disease is characterized by noninflammatory spongiform lesions of nerve and glial cells and their processes, and is associated with moderate astro- and microgliosis. The first clinical symptoms are ataxia, tremor, and spasticity, progressing to complete tetraparesis and incontinence, and finally death of the animal. Sequences within the amphotropic env gene are necessary for disease induction. Coinfection of A-MuLV recombinants with nonneuropathogenic ecotropic or polytropic MuLV drastically increases the incidence, degree, and distribution of the neurodegenerative disorder. The consequence of these results in view of the use of A-MuLV recombinants in the clinic is discussed.
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PMID:Amphotropic murine leukemia viruses induce spongiform encephalomyelopathy. 915 61

The ts1 Moloney murine leukemia virus causes a degenerative neurologic disease in mice characterized by the development of noninflammatory spongiform encephalomyelopathy. To determine whether gag and pol gene products and viral replication are necessary for the ts1-env gene product to cause neurodegeneration, we generated transgenic mice harboring only ts1-env. Neuropathological lesions were observed in mice expressing the transgene in the central nervous system. This implies that gag and pol gene products and viral replication are not necessary for ts1-env to cause a mild form of neurodegeneration in mice.
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PMID:Development of pathological lesions in the central nervous system of transgenic mice expressing the env gene of ts1 Moloney murine leukemia virus in the absence of the viral gag and pol genes and viral replication. 929 Dec 35

Amphotropic Moloney-murine leukemia virus recombinants (Mo-AmphoV) induce a severe spongiform encephalomyelopathy in newborn mice. We show here that a coisogenic recombinant with a 10A1-MuLV host range (Mo-10A1V) also induces a neurodegenerative disease, clinically characterized by mild tremor and ataxia. Spongiform lesions are most severe in the metencephalon and mesencephalon but extend into the prosencephalon and spinal cord. Significantly, the quality of histopathology was indistinguishable between Mo-AmphoV and Mo-10A1V, probably reflecting a final common pathogenic pathway. Common receptor use thus may be an important determinant in the pathogenicity of these viruses. These results have implications for the clinical use of retroviral pseudotypes that use phosphate transporters for cell entry.
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PMID:Murine leukemia virus recombinants that use phosphate transporters for cell entry induce similar spongiform encephalomyelopathies in newborn mice. 987 10


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