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 14-year-old boy survived for 7 years after the initial diagnosis and treatment of acute lymphocytic leukemia. Neurologic deterioration occured repeatedly throughout his complicated clinical course but it was most severe and only partially reversible following orally administered pyrimethamine. The neuropathologic lesions were distinctive and included a diffuse reactive astrocytosis, axonal degeneration, status spongiosis, circumscribed foci of demyelination and coagulative necrosis, and mural thickening with luminal narrowing of microcirculatory vessels. This collection of findings represents the leukoencephalopathy of childhood leukemia that we and others believe results in large part from the combined effects of cranial irradiation and chemotherapy. The role of folic acid antagonists, namely methotrexate and pyrimethamine, are particularly noteworthy in this regard.
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PMID:Leukoencephalopathy in childhood leukemia. 26 50

A 65-year-old white male with acute myelogenous leukemia received whole brain irradiation (2550 rads) and intrathecal cytosine arabinoside for CNS prophylaxis. Bone marrow remission had been previously achieved with systemic chemotherapy (vincristine, Adriamycin, prednisone, and cytosine arabinoside). Two weeks following the last intrathecal cytosine arabinoside treatment, the patient developed a spastic paraparesis requiring the use of a walker. A gas myelogram was normal and CSF examination revealed a protein of 50 mg/100 ml but was otherwise unremarkable. Five months later, the patient had improved in that he could stand on his own. A relapse of his leukemia subsequently occurred and the patient died the following month. Striking degenerative changes were found in the spinal cord at postmortem examination. These included microvacuolization, axonal swellings, and loss of myelin with scattered macrophages laden with fat.
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PMID:Paraparesis following intrathecal cytosine arabinoside: a case report with neuropathologic findings. 27 Oct 37

Postmortem examination of 21 patients showed a vacuolar myelopathy resembling that associated with the acquired immunodeficiency syndrome. Underlying diseases included six cases of leukemia or lymphoma, five of carcinoma, three of systemic lupus erythematosus, two of chronic lung disease, and one each of cadaveric renal transplant, cirrhosis, diabetes, hemophagocytic syndrome, and viral encephalitis. Fourteen patients were on long-term steroid therapy and 10 of these also had immunosuppressive chemotherapy. No patient had the acquired immunodeficiency syndrome, although one received blood transfusions in 1978. Signs and symptoms consistent with myelopathy included paraparesis in seven patients, ataxia in one, and bilateral extensor plantar reflexes in one. Microscopic examination showed vacuolation in spinal cord white matter primarily located in posterior and lateral columns. Lipid-laden macrophages and axonal changes were proportional to the severity of the vacuolation, which was severe in five patients, moderate in 10, and mild in six. Eight patients had coexistent viral diseases elsewhere in the central nervous system, but viral-associated antigens or genomic material was not found in regions of vacuolated spinal cord white matter. Although the etiology of these myelopathies is unknown, their association with immune suppression and coexistent viral infection of the central nervous system suggests that an opportunistic viral infection may be important.
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PMID:Idiopathic myelopathies with white matter vacuolation in non-acquired immunodeficiency syndrome patients. 186 65

The neuronal growth associated protein GAP-43 is expressed at high levels during axonal growth and regeneration. In this report, we describe the transfection of the nerve growth factor (NGF)-responsive pheochromocytoma cell line PC12 with the human GAP-43 cDNA under the control of the Moloney murine leukemia virus long terminal repeat (MoMuLV LTR). Two PC12 subclones were isolated that constitutively expressed GAP-43 from the transfected cDNA and showed increased responsiveness to NGF. Of the two transfected PC12 subclones, the subclone expressing the most human GAP-43 RNA showed an accelerated initial neurite outgrowth response and a 10-fold increased sensitivity to NGF. Neurite regeneration was significantly enhanced in both transfected subclones and, in contrast to untreated PC12 cells, could occur transiently in the absence of added NGF. These results suggest that GAP-43 may potentiate the action of NGF on neurite initiation and regeneration.
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PMID:Transfection of PC12 cells with the human GAP-43 gene: effects on neurite outgrowth and regeneration. 215 93

An autopsy case of HTLV-I associated myelopathy (HAM) combined with adult T-cell leukemia (ATL) was reported. Although HAM and ATL are reported to be caused by an identical virus, a combination of these two conditions is extremely rare. This is the first report of an autopsy of the case. A 42-year-old female born in Kumamoto noticed gait disturbance at age 20. Dysesthesia in her lower limbs and bladder bowel disturbance (BBD) gradually appeared at age 29 and at age 39, respectively, and slowly progressed. Neurological examination revealed spastic paraparesis, sensory disturbance in her lower limbs in all modalities and BBD. Furthermore, titers of the anti HTLV-I antibody were increased both in serum and CSF. She was diagnosed as HAM at this stage. She responded to the oral administration of prednisolone. Ten months after the initiation of prednisolone therapy, a tumor shadow appeared in the right lung and characteristic ATL cells were found in the pleural effusion. She died with respiratory failure. ATL cells were not found either in the peripheral blood or CSF throughout the course of her illness. Autopsy revealed solid tumors in both lungs, liver, kidneys, spleen, thyroid gland and para-aortic lymphnodes, composed of ATL cells with extensive necrosis. The spinal cord showed a marked loss of myelin and axons, and perivascular fibrosis in the lateral and anterior columns. These changes were most severe at the 6th and 7th thoracic segments. No ATL cell was found in the spinal cord. Concerning the sensory system, the posterior root, ganglion and posterior column were preserved, whereas the axonal degeneration was found in the biopsied specimen of the sural nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of HTLV-I associated myelopathy (HAM) with adult T-cell leukemia (ATL)]. 224 29

The presence of antibodies to human T-cell lymphoma/leukemia virus Type I (HTLV-I) has been associated with chronic progressive myelopathy. We attempted to isolate the virus from the blood and spinal fluid of patients with chronic progressive myelopathy and to define the clinical, radiologic, and electrophysiologic features of this disease. Ten of 13 patients from tropical countries and 2 of 8 from the United States had serum antibodies to HTLV-I. The virus was detected in cultures of peripheral-blood lymphocytes from three of seven patients by means of Southern blot hybridization. Using a sensitive in vitro enzymatic gene-amplification technique, we detected HTLV-I sequences in fresh peripheral-blood mononuclear cells of all of 11 patients tested who were positive for the antibody, and in cell cultures of the spinal fluid from 3 of the 11 tested. Magnetic resonance imaging of the cranium revealed periventricular lesions in the white matter of 3 of the 12 antibody-positive patients. Five of these patients had mild axonal sensorimotor polyneuropathy, and one had bilateral lumbar radiculopathy. Visual evoked potentials were abnormal in three seropositive patients, and brain-stem evoked responses were abnormal in two. The detection of the DNA and proteins of HTLV-I strengthens the proposition that this virus is involved in the pathogenesis of a subset of cases of chronic progressive myelopathy.
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PMID:Detection of human T-cell lymphoma/leukemia virus type I DNA and antigen in spinal fluid and blood of patients with chronic progressive myelopathy. 289

Transient or permanent paraplegia after the use of intrathecal (IT) methotrexate (MTX) or cytosine arabinoside (Ara-C) for treatment or prophylaxis of patients with meningeal leukemia is an unusual complication, with an incidence of less than 3% among such patients. Only 15 cases involving IT MTX have been documented and even fewer with IT Ara-C. Three patients were studied who developed permanent or ascending myelopathy from treatment of their leukemia or rhabdomyosarcoma with IT chemotherapy. The patients' ages ranged from 7 to 62 years. Two of the three patients had electromyographic examinations. These revealed a primary motor neuron degeneration or a polyradiculopathy, superimposed on a mild axonal peripheral neuropathy associated with vincristine therapy. This is consistent with other electromyographic studies. Two of the patients showed an elevation of the cerebral spinal fluid (CSF) protein before development of paraplegia; one also showed a rise in myelin basic protein associated with his myelopathy. Neuropathologic findings suggest demyelination as the primary process leading to myelopathy. Increasing evidence has shown that total CSF protein, or more specifically, the myelin basic protein, may be elevated before development of paraplegia. Routine serial testing of the CSF for total protein could be used as a screening test during therapy.
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PMID:Paraplegia and quadriplegia after intrathecal chemotherapy. 321 64

The syndrome of inappropriate secretion of antidiuretic hormone is a rare but well-recognized neurotoxic side effect of vincristine therapy. The first neuropathological report of a case is presented. A 6-month-old boy with skin leukemia developed inappropriate secretion of antidiuretic hormone caused by vincristine. Postmortem examination revealed axonal spheroids in the ansa lenticularis and the area surrounded by the substantia innominata, amygdala and supraoptic nucleus. The lesion was confined to that area and the neurosecretory neurons were intact with well preserved neurophysin. The pathological findings suggest that these fibers play a role in the development of inappropriate secretion of antidiuretic hormone caused by vincristine therapy.
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PMID:Syndrome of inappropriate secretion of antidiuretic hormone caused by vincristine therapy: a case report of the neuropathology. 619 29

Three adult patients with leukemia and a patient with cutaneous melanoma were treated with a variety of therapeutic agents administered systemically. Three of these patients received either cytosine arabinoside or thio-TEPA, by intrathecal injection and radiotherapy to the cranium or spine. Three patients developed progressive motor and sensory deficits and the fourth became confused and disoriented. These symptoms were chronologically related to the time when chemotherapy was begun. Death occurred 11/2, 2, 5 and 7 months, respectively, after the beginning of neurologic deficit. The spinal white matter showed vacuolation, myelin disintegration, axonal swelling, fibrillary gliosis, and infiltration by macrophages. Vesicular disintegration of the myelin lamellae seems to be the earliest lesion affecting both central and peripheral myelin. Gliosis and macrophages were visible only in the two patients who survived at least five months from the time of the neurologic deficit.
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PMID:Central and peripheral myelinopathy associated with systemic neoplasia and chemotherapy. 679 25

Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukaemia antigen CD10 (CALLA), is a cell surface Zn2+ metalloprotease that regulates peptide-induced responses in different tissues, including the nervous and immune systems. In the peripheral nervous system, high levels of the enzyme are present in all neonatal and early postnatal Schwann cells, while as myelination proceeds it is gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. In the present study we have investigated the effects of transection, crush and regeneration of the adult rat sciatic nerve on the expression of the endopeptidase by Schwann cells in situ. Endopeptidase-24.11 was monitored by immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. For comparison, a parallel study was carried out with a monoclonal antibody directed against the rat nerve growth factor receptor. We found that (i) all Schwann cells of the distal segment re-expressed endopeptidase-24.11 as early as 4 days after axotomy, the level of immunostaining reaching a maximum after 2 weeks, (ii) axonal regeneration repressed Schwann cell expression of endopeptidase-24.11, and (iii) the induction of the nerve growth factor receptor followed a similar pattern to that of endopeptidase-24.11 in the transected and crushed nerve. Enzymatic amplification of endopeptidase-24.11 cDNA from normal and axotomized adult rat sciatic nerve confirmed the expression of endopeptidase-24.11 in these tissues. Our results show that the expression of endopeptidase-24.11 in Schwann cells, as is the case with the nerve growth factor receptor, is induced by the loss of the normal axon-Schwann cell contact. The significant increase in the expression of endopeptidase-24.11 by Schwann cells after axonal damage suggests that the enzyme could play a role in axonal regeneration.
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PMID:Expression of endopeptidase-24.11 (common acute lymphoblastic leukaemia antigen CD10) in the sciatic nerve of the adult rat after lesion and during regeneration. 761 30


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