Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 9 patients with motor neuron disease and lymphoma. The following several observations have not been recognized in the past: (1) Motor neuron syndromes are associated with either Hodgkin's disease or non-Hodgkin's lymphoma. (2) The syndromes are not restricted to lower motor neuron disorders; 8 of 9 patients had definite or probable upper motor neuron signs as well, qualifying for the diagnosis of amyotrophic lateral sclerosis. Corticospinal tracts were affected in both postmortem examinations. (3) The combination of motor neuron disease and lymphoma is often accompanied by paraproteinemia (3 of 7 patients studied), increased cerebrospinal fluid protein content (6 of 9 patients), and cerebrospinal fluid oligoclonal bands (3 of 9 patients). (4) In 2 patients, asymptomatic non-Hodgkin's lymphoma was found only because the discovery of paraproteinemia gave impetus to examine the bone marrow. (5) Patients with both upper and lower motor neuron signs (amyotrophic lateral sclerosis) may show physiological evidence of conduction block in peripheral nerves or autopsy abnormalities in peripheral nerves. The cause of this syndrome is not known. Both lymphoma and motor neuron disease could have a common cause, possibly a retroviral infection. The frequency of paraproteinemia suggests that an immunological disorder may play a role in the pathogenesis of the neurological disorder.
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PMID:Lymphoma, motor neuron diseases, and amyotrophic lateral sclerosis. 165 4

Motor neuron diseases (MND) associations with paraproteinemia, lymphoma, hexosaminidase A deficiency and heavy-metal intoxication are of great interest. A case of amyotrophic lateral sclerosis (SLA) associated with multiple myeloma (monoclonal IgG paraproteinemia and K light chains) is reported. The detection of abnormal protein in 1988 and the increase of its serum level during 1989 were strictly correlated with the beginning and the worsening of the neurological disease. Shy and coll. in 1986 affirmed that association of paraproteins with MND is probably not merely the fortuitous association of a common laboratory abnormality and an uncommon disease. The reported case provides elements for a causal association between paraproteinemia and MND.
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PMID:[Amyotrophic lateral sclerosis with multiple myeloma]. 210 33

From 1984 to 1988, 11 of 120 patients (9%) with motor neuron disease (MND) had paraproteins detected by serum immunofixation electrophoresis (IFE), compared with 4 (3%) by cellulose acetate gels: 1 patient had progressive spinal muscular atrophy, 5 patients had amyotrophic lateral sclerosis (ALS), and 5 patients had ALS with probable upper motor neuron signs. Four of 5 patients (80%) with cerebrospinal fluid (CSF) protein content above 75 mg/dl had paraproteins, as did 6 of 30 with values above 50 mg/dl. Four of 14 patients with cerebrospinal oligoclonal bands (OCB) also had paraproteins. Two patients with ALS, CSF protein content above 75 mg/dl, and paraproteinemia had lymphoma. We conclude the following about patients with MND: high CSF protein content (especially above 75 mg/dl) or CSF OCB makes paraproteinemia more likely; some of these patients may have lymphoma; there is an inordinately high occurrence of paraproteinemia in MND; and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins. Syndromes of paraproteinemia and high CSF protein are not restricted to the lower motor neuron but qualify as "ALS" with coexisting upper motor neuron signs.
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PMID:Motor neuron disease and amyotrophic lateral sclerosis: relation of high CSF protein content to paraproteinemia and clinical syndromes. 199 91

Many different antilymphocytic antisera have been used clinically, and the properties of any particular type of ALS are not necessarily identical to those of any other type. Nevertheless, it is possible to draw certain general conclusions about the effects of ALS in human subjects. ALS administration has often been shown to reduce the number of circulating E-rosette-positive lymphocytes, although the precise mechanisms by which this reduction occurs are not known. Using a combined technique of E-rosette formation and immunofluorescence, heterologous immunoglobulin has been demonstrated on T and non-T lymphocytes from patients receiving non-selective ALS. Fifteen years' experience has failed to provide convincing support for the view that ALS (including immunoglobulin prepared from the whole antiserum) prolongs human renal allograft survival. It is not yet known whether ALS is a useful immunosuppressive agent in cardiac transplantation. One observation of possible clinical interest is that bone marrow regeneration has occurred in a number of patients with aplastic anemia who have been treated with ALS. No satisfactory method has been developed for monitoring the dose of ALS in human subjects. Appropriate studies may determine whether monoclonal antilymphocytic antibodies are clinically useful, for example in prolonging the survival of transplanted organs, in preventing or treating graft-versus-host disease, or in treating lymphoma, leukemia, or aplastic anemia.
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PMID:Clinical experience with antilymphocyte serum. 674 48

Cell surface markers of 44 cases of non-Hodgkin's lymphoma (NHL) were studied with various surface markers, especially by using antihuman B lymphocyte serum (ABS), antihuman thymocyte serum (ATS-T), and antihuman peripheral T lymphocyte serum (ALS-T), which were rendered specific for human B lymphocytes, human thymocytes, and human peripheral T lymphocytes, respectively. An immunofluorescent study with ABS, ATS-T, and ALS-T enabled us to demonstrate the histologic localization of normal or neoplastic B and T cells in preserving the original structure of lymphoid organs or tumor tissues. The proportion of cell types in NHL was B cell type 59%, T1 (ATS-T reactive) type 7%, T2 (ALS-T reactive) type 23%, and Null (non T, non B) type 11%. The relationships among cell types, histologic findings, and clinical characteristics were also investigated. Patients with T1-NHL had mediastinal tumors, which were histologically classified into "Lymphoblastic lymphoma." These facts suggest that T1-NHL may have originated in the thymus. Patients with T2-NHL showed a high incidence of skin lesions. Median survival of ten patients with T1- and T2-NHL was seven months, which was much shorter than that of B- or Null-NHL.
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PMID:A study of surface markers in non-Hodgkin's lymphoma by using anti-T and anti-B lymphocyte sera. 700 95

Recent immunocytochemical and morphometric studies with an organelle-specific antiserum against MG-160, an intrinsic membrane sialoglycoprotein of the Golgi apparatus, have shown in several patients with sporadic amyotrophic lateral sclerosis (ALS), and in a few patients with related conditions, a fragmentation of the Golgi apparatus of spinal cord motor neurons which resembles the dispersion of the organelle observed in cells treated with microtubule depolymerizing agents. In the present study we examined by morphometry the effect of tissue fixation and processing on the immunocytochemical morphology of the Golgi apparatus of motor neurons from spinal cords of five controls and in one patient with leptomeningeal lymphoma. Qualitative studies of the Golgi apparatus of spinal cord motor neurons were also carried out in two more individuals with lymphoma or leukemia with leptomeningeal involvement and in one patient with multiple myeloma associated with a chronic inflammatory demyelinating polyneuropathy. The results of this study show that it is possible to obtain optimal immunocytochemical preparations of the Golgi apparatus of spinal cord motor neurons in routinely fixed and processed tissues obtained at autopsy. This study also provides baseline values of the Golgi apparatus in normal individuals which may be useful in future studies of the organelle in human neuropathologic conditions affecting the lower motor neuron unit. Lastly, this study shows that the fragmentation of the neuronal Golgi apparatus is not limited to ALS and related disorders.
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PMID:On the significance and reproducibility of the fragmentation of the Golgi apparatus of motor neurons in human spinal cords. 774 32

To limit the genetic heterogeneity of schizophrenia, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenia probands. The hypothesis posed is that the increased prevalence among the Ashkenazim of the rare lysosomal enzyme disorders, Tay Sachs disease (TDS), caused by low levels of hexosaminidase A, and Gaucher's disease (GD), caused by low levels of glucocerebrosidase, might contribute to the demonstrated increased vulnerability to schizophrenia in this ethnic group. Signs and symptoms characterizing the candidate illnesses were systematically queried by the family history method. Rates and relative risks for symptoms characterizing these disorders and for several nonautosomal illnesses associated with TSD and/or GD (i.e., amyotrophic lateral sclerosis and Hodgkin's disease, leukemia and lymphoma) are significantly elevated in the schizophrenia pedigrees, compared to controls. The conditions with elevated rates and risks have been associated with chromosomal regions 1q21 and 15q23-q24. These areas are suggested as candidate regions for future targeted deoxyribonucleic acid (DNA) research in schizophrenia.
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PMID:Medical conditions in Ashkenazi schizophrenic pedigrees. 797 67

Several studies have addressed the issue of a possible immunological involvement in the pathogenesis of amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), particularly when the disease was associated with cancer, lymphoma or other monoclonal gammopathies or with the presence of serum antibodies to neural antigens. The hypothesis of the existence of immunologically treatable MND was reinforced by the occasional report of MND patients responding to immune or cytostatic therapies and by the identification among those with a purely lower motor neuron syndrome (LMNS) of a motor neuropathy, presently known as multifocal motor neuropathy (MMN), which almost invariably responded to immune therapies. These observations have led to several attempts to treat patients with MND or LMNS, either idiopathic or associated with the above mentioned conditions, with a number of immune or cytostatic therapies. The aim of this review is to verify whether the available data provide enough evidence to support the concept of dysimmune MND and to justify the use in these patients of potentially harmful immune cytostatic therapies.
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PMID:Are there immunologically treatable motor neuron diseases? 1146 20

Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor sodium phenylbutyrate, significantly extended survival and improved both the clinical and neuropathological phenotypes in G93A transgenic ALS mice. Phenylbutyrate administration ameliorated histone hypoacetylation observed in G93A mice and induced expression of nuclear factor-kappaB (NF-kappaB) p50, the phosphorylated inhibitory subunit of NF-kappaB (pIkappaB) and beta cell lymphoma 2 (bcl-2), but reduced cytochrome c and caspase expression. Curcumin, an NF-kappaB inhibitor, and mutation of the NF-kappaB responsive element in the bcl-2 promoter, blocked butyrate-induced bcl-2 promoter activity. We provide evidence that the pharmacological induction of NF-kappaB-dependent transcription and bcl-2 gene expression is neuroprotective in ALS mice by inhibiting programmed cell death. Phenylbutyrate acts to phosphorylate IkappaB, translocating NF-kappaB p50 to the nucleus, or to directly acetylate NF-kappaB p50. NF-kappaB p50 transactivates bcl-2 gene expression. Up-regulated bcl-2 blocks cytochrome c release and subsequent caspase activation, slowing motor neuron death. These transcriptional and post-translational pathways ultimately promote motor neuron survival and ameliorate disease progression in ALS mice. Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS.
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PMID:Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. 1593 30

Kaposi sarcoma-associated herpesvirus (KSHV) was discovered in 1994 and is now known to be a necessary but not sufficient causative agent of Kaposi sarcoma. While KSHV is likely also the causative agent of primary effusion lymphoma and multicentric Castleman's disease, its causal role has been refuted in the case of multiple myeloma, sarcoidosis, prostate cancer, and amyotrophic lateral sclerosis. The epidemiology of KSHV is both intriguing and challenging. Two epidemiologic findings are clear, but their explanation is unknown. The first is that KSHV is distributed disparately throughout the world, with the virus being common in the general population throughout Africa and the Middle East, but uncommon virtually everywhere else. The second is that even though the virus is uncommon in the general population in industrialized settings, it is disproportionately concentrated among homosexual men in these areas. KSHV has special importance to the dental profession because saliva is the body fluid that harbors it most commonly, although exactly in which ways saliva spreads the virus are not known.
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PMID:Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and Kaposi sarcoma. 2144 85


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