Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 52-year-old human immunodeficiency virus type 1-seropositive bisexual black man was evaluated at UCLA because of the recent onset of progressive lower-extremity weakness. Initial neurologic examination showed that the patient's distal weakness was greater than his proximal weakness, with bilateral foot drop and electrophysiologic evidence of denervation in the distal lower extremities. Magnetic resonance imaging of the brain and spinal cord disclosed no abnormalities. Subsequent neurologic evaluation 8 months later showed a myelopathy, with progression of lower-extremity weakness, spasticity, and flexor spasms, and urinary incontinence, as well as the peripheral neuropathy noted previously. A second magnetic resonance imaging scan of the brain showed patchy foci of increased signal intensity in white matter and cortex, with mild generalized cerebral and cerebellar atrophy and no lesions in the spinal cord. Specimens of the patient's serum and cerebrospinal fluid contained antibodies to human immunodeficiency virus type 1. Additionally, specimens of his serum and cerebrospinal fluid were tested for antibody to human T-cell leukemia virus type I by Western blotting and radioimmunoprecipitation, and found to be positive for human T-cell leukemia virus type I gag, env, and tax antibodies. The primary cause of severe myelopathy in this patient may be infection with human T-cell leukemia virus type I rather than with human immunodeficiency virus type 1. Treatment with prednisolone resulted in improvement of the lower-extremity weakness, reduction in flexor spasms, and slower but significant improvement in urinary symptoms. Patients who are infected with human immunodeficiency virus type 1 and have unusual motor findings should be tested for concomitant human T-cell leukemia virus type I infection.
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PMID:A patient with progressive myelopathy and antibodies to human T-cell leukemia virus type I and human immunodeficiency virus type 1 in serum and cerebrospinal fluid. 232 40

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

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraperesis (HAM/TSP) is a slowly progressive neurologic disorder following infection with HTLV-I. It is characterized by spasticity and hyper-reflexia of the lower extremities, urinary bladder disturbance, lower extremity muscle weakness, and sensory disturbances. HTLV-I, as an inducer of a strong humoral and cytotoxic response, is a well-known pathogenic factor for the progression of HAM/TSP. Peptides derived from proviral tax and env genes provide epitopes recognized by T cells. We herein report an accumulation of distinct clonotypes of alpha/beta TCR+ peripheral blood T lymphocytes from HAM/TSP patients in comparison with that observed in both asymptomatic carriers and healthy controls, using the reverse-transcriptase PCR/single-strand conformation polymorphism method. We also found that some of the accumulated T cell clones in the peripheral blood and cerebrospinal fluid are HTLV-I Tax(11-19) peptide specific. Such clones were found to expand strongly after being cultured with an HTLV-I Tax(11-19) peptide. Moreover, the cultured samples exhibited a strong MHC class I-restricted cytotoxic activity against HTLV-I Tax(11-19) peptide-expressing targets, and therefore most likely also include the disease-associated T cell clones observed in the patients. This is the first report of a direct assessment of Ag-specific T cell responses in fresh PBL and cerebrospinal fluid.
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PMID:Accumulation of human T lymphotropic virus (HTLV)-I-specific T cell clones in HTLV-I-associated myelopathy/tropical spastic paraparesis patients. 925 72

In 1980, Human T cell leukemia/lymphoma virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. HTLV-1 belongs to the Retroviridae family, the Orthoretrovirinae subfamily and to the deltaretrovirus genus. HTLV-1 preferentially infects CD4(+) lymphoid cells in vivo. Three molecules have been identified for binding and/or entry of HTLV-1: heparan sulfate proteoglycans, neuropilin-1, and glucose transporter 1. An efficient transfer of the virus from an infected cell to a target cell can occur through the formation of a viral synapse and/or by virofilm structure. As for all retroviruses, HTLV-1 genome possesses three major ORFs (gag, pol and env) encoding the structural and enzymatic proteins. HTLV-1 encodes also some regulatory and auxillary proteins including the tax protein with transforming activities and the HBZ protein which plays a role in the proliferation and maintenance of the leukemic cells. HTLV-1 is present throughout the world with clusters of high endemicity including mainly Southern Japan, the Caribbean region, areas in South America and in intertropical Africa. The worldwide HTLV-1 infected population is estimated to be around 10-20 million. HTLV-1 has three modes of transmission: (1): mother to child, mainly linked to prolonged breast-feeding; (2): sexual, mainly occurring from male to female and (3): contaminated blood products. HTLV-1 possesses a remarkable genetic stability. HTLV-1 is the etiological agent of mainly two severe diseases: a malignant T CD4(+) cell lymphoproliferation, of very poor prognosis, named Adult T cell Leukemia/Lymphoma (ATLL), and a chronic neuro-myelopathy named Tropical spastic paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). The lifetime risk among HTLV-1 carriers is estimated to be around 0.25 to 3%. TSP/HAM mainly occurs in adults, with a mean age at onset of 40-50 years and it is more common in women than in men. Blood transfusion is a major risk factor for TSP/HAM development. Clinically, TSP/HAM is mainly defined as a chronic spastic paraparesis and minor sensory signs. The onset is insidious with often gait disturbance and urinary symptoms. In more than 90% of the cases, the neurological features involve: spasticity and/or hyperreflexia of the lower extremities, urinary bladder disturbance, lower extremity muscle weakness, and in around 50% of the cases, sensory disturbances with low back pain. Central functions and cranial nerves are usually spared. The clinical course is generally progressive without remission. High levels of antibodies titers directed against HTLV-1 antigens are present in blood and cerebrospinal fluid (CSF). A high HTLV-1 proviral load is frequently observed in the blood. Mild to moderate increase of proteins may be present in the CSF. However, intrathecal production of specific HTLV-1 antibody index provides additional data to support the diagnosis. Brain white matter lesions on magnetic resonance imaging are frequent. A mild atrophy of the thoracic spinal cord can also be observed. Pathologically, it is characterized by a chronic inflammation with perivascular lymphocytic cuffing and mild parenchymal lymphocytic infiltrates. The cells are mostly CD4(+) in early disease and mostly CD8(+) in latter disease. Pyramidal tract damage with myelin and axonal loss, mainly in the lower thoracic spinal cord are observed. TSP/HAM pathogenesis is still poorly understood and viral and host factors as the proviral load and the cellular immune response play a major role in disease progression. TSP/HAM can be associated with other HTLV-1 associated symptoms (uveitis, myositis, infective dermatitis). Therapy of TSP/HAM remains disappointing and symptomatic treatment remains still the mainstay of therapy.
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PMID:Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects. 2240 61