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)

Mice infected with the replication-defective virus (BM5def) in the LP-BM5 murine leukemia virus (MuLV) mixture develop an immune deficiency syndrome and encephalopathy characterized by impaired spatial learning and memory as demonstrated in the Morris water maze. However, the molecular mechanism (or mechanisms) underlying this cognitive deficit remains unknown. Here we report that brain fyn kinase, which has been proposed to be involved in spatial learning and memory, was unresponsive to glutamatergic stimulation in mice with MAIDS. Thus, whereas application of glutamate to hippocampal slices from control mice increased fyn protein tyrosine kinase (PTK) activity more than 2.5-fold, these changes were significantly impaired in LP-BM5 MuLV-infected mice. Moreover, mice with MAIDS exhibited an abnormal histological distribution of fyn PTK in the hippocampus. These findings suggest that virus-associated disruption of fyn kinase-mediated signaling contributes to the cognitive deficits observed in mice with MAIDS and other retrovirus-induced encephalopathies.
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PMID:Altered brain fyn kinase in a murine acquired immunodeficiency syndrome. 864 68

We retrospectively evaluated the neurologic complications in 425 patients who underwent bone marrow transplant (BMT) (310 allogeneic, 115 autologous) for leukemia. Forty-six patients (11%) developed 47 central and three peripheral neurologic complications. The most common complications were cerebral hemorrhage (3.8%), metabolic encephalopathy (3%), and CNS infections (2%). All CNS infections occurred with allogeneic BMT. Eleven of 16 hemorrhages were subdural hematomas (69%), which were more frequent in autologous (8%) than in allogeneic (0.6%) BMT (p < 0.0001), and in patients with acute myelogenous leukemia (AML) (5%) than in the remaining leukemia patients (0.8%) (p = 0.013). Eight of 11 subdural hematomas occurred in AML patients receiving autologous BMT. When we compared patient-, disease-, and transplant-related characteristics of these patients with those without subdural hematoma, only platelet refractoriness correlated with an increased risk of subdural hematoma. The actuarial probability of developing subdural hematoma was 44% in patients with platelet-refractory disease and only 2.5% in the other patients (p < 0.0001). Ten patients with subdural hematoma did not have surgery and eight had significant clinical improvement associated with reduction or resolution of the hematoma, confirmed by CT scan in six patients. The subdural hematoma was the cause of death in only one patient. This study shows that the frequency of the different neurologic complications varies among types of BMT. Patients undergoing autologous BMT for AML with platelet refractoriness have an increased risk of subdural hematoma that may be treated with conservative measures.
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PMID:Neurologic complications of autologous and allogeneic bone marrow transplantation in patients with leukemia: a comparative study. 878 80

We report the case histories of identical twin brothers who developed concordant acute lymphoblastic leukemia at the age of 4 years and who later developed leukoencephalopathy and hydrocephalus related to central nervous system prophylaxis by, in the first case intrathecally administered methotrexate and, in the second by intrathecally administered methotrexate and cranial irradiation. The delayed encephalopathy developed 9 and 22 months respectively after the first dose of intrathecal methotrexate. Both patients underwent cerebrospinal fluid shunting mainly for their hydrocephalus. The imaging studies have shown that both hydrocephalus and leukoencephalopathy have improved significantly after ventriculoperitoneal shunt insertion. We review the pathophysiology of prophylaxis-related encephalopathy in leukemia patients and summarize its clinical, histological, and radiological characteristics. We also discuss the possible contribution of altered cerebrospinal fluid dynamics in the development of leukoencephalopathy.
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PMID:Reversal of CNS-prophylaxis-related leukoencephalopathy after CSF shunting: case histories of identical twins. 881 94

Mice infected with the LP-BM5 murine leukemia virus (MuLV) mixture develop severe immunosuppression, neurotransmitter abnormalities and cognitive impairments in the absence of significant viral or macrophage invasion of the CNS. The time-course of the changes in glial activation have been characterized in an effort to understand the cellular basis of the neurobehavioral abnormalities observed in these mice. Glial activation was determined by measuring the relative changes in F4/80 protein and GFAP immunoreactivity using immunoblots. Augmented F4/80 expression preceded that of GFAP, with global elevations of 4-6-fold at 3 weeks, sustained for up to 12 weeks after inoculation. GFAP immunoreactivity increased 2-fold only in the cerebral cortex and striatum 5 weeks postinfection, declining to control levels by 12 weeks. Immunohistochemistry revealed significant increases in microglial size and staining intensity in the cortex, corpus callosum and striatum, with the development of a unique population of highly ramified, intensely stained microglia and microglial nodules in the corpus callosum and striatum. No evidence of ameboid microglia was found. Astrocyte size and degree of ramification was increased in the hippocampus, cortex, striatum and corpus callosum. Thus, microgliosis is an early event in LP-BM5 infection, preceding astrocytosis, neurotransmitter loss, and development of cognitive deficits. Activated microglia may secrete neurotoxins leading to the neurochemical alterations and cognitive deficits observed in these mice. Because gliosis and microglial nodule formation are hallmarks of HIV-1 encephalopathy, LP-BM5 MuLV-infected C57/B16 mice may afford insights into the mechanisms contributing to the early stages of this syndrome.
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PMID:Gliosis in the LP-BM5 murine leukemia virus-infected mouse: an animal model of retrovirus-induced dementia. 911 5

Tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) have been implicated in the pathogenesis of human immunodeficiency virus (HIV)-associated encephalopathy. The effects of pentoxifylline on brain PAF levels were examined in mice infected with the LP-BM5 murine leukemia virus (MuLV). Seven weeks after viral inoculation, significant increases in serum TNF-alpha and brain PAF levels were observed. One week of treatment with pentoxifylline initiated 6 weeks postinfection significantly reduced both serum TNF-alpha and brain PAF levels. A significant positive correlation was observed between the levels of these substances (r = 0.62; P < 0.01). This study demonstrates that pentoxifylline treatment was effective in decreasing the levels of TNF-alpha in the serum and PAF levels in the brain of mice infected with the LP-BM5 MuLV.
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PMID:Pentoxifylline decreases brain levels of platelet activating factor in murine AIDS. 915 42

We report a series of four patients in whom the onset of systemic cancer was heralded by dysautonomic symptoms and a neurological non-metastatic complication mediated by immunological and endocrine factors. The series includes: a patient with acute leukaemia and autonomic sensory-motor polyradiculoneuropathy, a patient affected by colon carcinoma and autonomic neuropathy and limbic encephalitis, a patient with lung cancer and autonomic neuropathy and hypercalcaemic encephalopathy, a patient with small cell lung cancer associated with autonomic neuropathy in Lambert-Eaton Myasthenic Syndrome (LEMS) and syndrome of inappropriate ADH secretion (SIADH). We underline the prognostic importance and discuss the possible etiopathogenetic role of autonomic dysfunction, which is frequently associated with paraneoplastic neurologic syndromes of autoimmune and/or dysendocrine origin.
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PMID:Immunological and endocrinological abnormalities in paraneoplastic disorders with involvement of the autonomic nervous system. 924 63

With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures.
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PMID:Pure methotrexate encephalopathy presenting with seizures: CT and MRI features. 947 50

Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immune deficiency syndrome together with an encephalopathy characterized by impairments in spatial learning and memory. These cognitive deficits are evident before the appearance of neuron loss and lymphoid cell invasion of the brain. Nonetheless, a prominent gliosis and a variety of neurochemical changes precede the development of cognitive deficits. The neurochemical abnormalities include significant decreases in striatal Met-enkephalin and substance P (but not somatostatin), increases in concentrations of quinolinic acid and platelet-activating factor, and alterations in brain fyn kinase. At this stage of the infection, some of these neurochemical changes can be reversed by glutamate receptor antagonists, cytokine inhibitors, and anti-retroviral agents. In later stages of the infection, however, the infected mice develop irreversible neuronal loss, invasion of hematopoietic cells, and increased viral burden in the CNS. In addition, motor-neuron dysfunction (hindlimb paralysis, weakness, and ataxia) and seizures are sometimes observed during the late stages of infection. Thus, the LP-BM5 MuLV-infected mouse is a useful model for studying the chronology of neurodegenerative changes, ranging from reversible neuron dysfunction to irreversible neuron loss, that are associated with retrovirus-induced immunodeficiency.
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PMID:The encephalopathy associated with murine acquired immunodeficiency syndrome. 962 8

The purpose of this study was to determine the incidence of and pharmacokinetic parameters associated with the development of transient encephalopathy following the administration of high-dose methotrexate and intrathecal chemotherapy in children with acute lymphoblastic leukemia (ALL). Two hundred and fifty-nine children with newly diagnosed ALL treated on one of two consecutive trials were analyzed. Presenting features in patients who developed transient encephalopathy were compared with those of patients who did not experience this event. For each patient who developed transient encephalopathy, methotrexate pharmacokinetic parameters were compared with those of matched controls. The cumulative incidence of acute encephalopathy was 3% (SE 1%) at 1 year and was associated with age greater than or equal to 10 years at diagnosis. Pharmacokinetic data did not differ between patients who developed transient encephalopathy and those who did not. The majority of patients had no long-term sequelae and were able to receive further courses of methotrexate without modification. Transient focal neurologic deficits occur in about 3% of children with ALL following the administration of intravenous and intrathecal methotrexate. These events cannot be predicted by pharmacokinetic parameters Of methotrexate disposition. However, these events are generally benign, suggesting that patients who experience acute encephalopathy should continue to receive this important chemotherapeutic agent.
Leukemia 1998 Aug
PMID:Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia. 969 70

A temperature-sensitive mutant of Moloney murine leukemia virus (MoMuLV-ts1) induces immunosuppression and spongiform encephalopathy in susceptible newborn mice. The associated neuronal degeneration primarily involves the motor neurons in specific target areas of the central nervous system (CNS). Neuronal loss occurs in the absence of direct viral infection of neurons and is the most dramatic pathological change in the CNS of infected mice. To quantitatively demonstrate neuronal loss, an unbiased morphometric stereological study was undertaken using the optical disector method. Using highly susceptible FVB/N mice, neuronal loss was quantitated in the tissue sections of brain stem from infected and noninfected mice at 20 and 35 days post inoculation (dpi). Results indicated that there was no significant neuronal loss at 20 dpi, but significant (P < 0.05) at 35 dpi. In addition, histology, transmission electron microscopy and immunohistochemistry revealed Lewy body-like inclusions consisting of aggregates of neurofilaments and cellular organelles. Degenerated neurons and glial cells were heavily ubiquitinated. Together, these results suggest that significant neuronal loss occurs at the end of the disease process and that Lewy body-like formation and protein ubiquitination are part of the pathogenic process in ts1-induced encephalopathy.
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PMID:Motor neuronal loss and neurofilament-ubiquitin alteration in MoMuLV-ts1 encephalopathy. 1066 65


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