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)

A low-molecular leukocyte dialysate, suppressor transfer factor (STF), exerting a stimulating effect on CD8 subpopulations in man, was administered to 17 patients with amyotrophic lateral sclerosis (ALS). Following three s.c. injections of STF, activation of CD8 subpopulations was noted in 11 patients while a decrease in CD4 in seven. Progression of the disease was found to slow in nine outpatients administered STF injections at an interval of 3-4 weeks. No therapeutic effect was seen in four patients in whom STF injection failed to show stimulating activity on lymphocyte subpopulations. Remission of the stimulating effect of STF occurs within four weeks. No side effects were seen in any of the patients treated. The effect of STF on immune reactivity and on the clinical course of ALS supports the hypothesis of autoimmune character of the disease.
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PMID:[Low-molecular transfer factor and its use in the treatment of amyotrophic lateral sclerosis]. 180 21

Serum and CSF from 32 patients with idiopathic ALS, 30 age-matched controls and 30 MS patients were investigated regarding immunoglobulin concentration and virus-specific antibodies, the lymphocytes in the peripheral blood and lymphocyte subsets were also investigated. ALS patients' results were compared with findings in MS and controls. The ALS patients had significantly higher IgG concentration in serum than the controls, marked lymphopenia, reduction of CD2, CD8 and Leu 7 positive cells and increase of the CD4/CD8 ratio and of SIg-positive lymphocytes. Compared with the MS patients, the ALS patients showed similarity in T-subset distribution with a lower standard deviation. No HTLV-I and HIV antibodies were found in any group and no significant differences in antibody distribution to Toxoplasma G, herpes simplex, cytomegalovirus, measles and mumps viruses were evident. All ALS patients were investigated at an early disease stage, therefore, our findings seem to support the conclusion that the immune alterations are related to the mechanisms of the disease and not to complications of its evolution.
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PMID:Immunity assessment in the early stages of amyotrophic lateral sclerosis: a study of virus antibodies and lymphocyte subsets. 326 63

Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed.
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PMID:Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders. 767 46

Normal human myoblasts were cloned and transplanted in the tibialis anterior of immunodeficient nude and SCID mice and in mdx mice under different immunosuppressive treatments (cyclosporine A, CsA; antilymphocyte serum, ALS) or not immunosuppressed. This permitted us to show the interaction of the immune system in the myoblast transplantation. The graft success was assessed by verifying signs of humoral and cellular immune reactions and the presence of dystrophin produced by the fusion of the donor myoblasts. This study showed that clones of human myoblasts were able to fuse and produce dystrophin in injected muscles of immunodeficient mice and mdx mice receiving an effective immunosuppressive treatment (i.e., ALS+CsA). However, the same pool of human myoblasts injected in mdx mice inadequately immunosuppressed (i.e., CsA alone or ALS alone) triggered an immune reaction and was rejected. Cells expressing CD4 and CD8 antigens were observed in the injected muscles of mice treated with CsA alone. Therefore, evidence of humoral and cellular rejection was observed following human myoblasts transplantation.
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PMID:Human myoblast transplantation in immunodeficient and immunosuppressed mice: evidence of rejection. 811 93

By using quantitative multiparameter microscopic imaging we demonstrate concentration of two peripheral mononuclear blood leukocyte types expressing the Fc gamma RIII receptor for immunoglobulin G in a clinical subgroup of amyotrophic lateral sclerosis (ALS, n = 9) showing bulbar palsy (ALSBP) and/or predominant involvement of the upper motor neuron (ALSC). Triple fluorescence staining and overlay with phase contrast images (4 parameters) reveals that cell type 1 co-expresses Fc gamma RIII (CD16), CD8 and CD57 surface antigens (ALSC 50 +/- 33.6 cells/microliters, P = 0.0012; ALSBP 16.5 +/- 32.4, P = 0.029). This cell type is not observed in healthy individuals (n = 8) and is only insignificantly increased (P > 0.05) in neurological disease controls (stroke, n = 3, 2.1 +/- 3.7; polymyositis, n = 6, 1.5 +/- 4.0 cells/microliters) and in ALS cases with peripheral symptoms (ALSP n = 12: 7.6 +/- 8.7). Cell type 2 co-expresses Fc gamma RIII (CD16) and CD8, but is negative for CD57 (ALSC 60.1 +/- 19.3; ALSBP 24.2 +/- 28.0 cells/microliters). These findings are consistent with previous reports on IgG isotype changes and immune-cell invasion of the motor system in ALS.
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PMID:Detection by 4-parameter microscopic imaging and increase of rare mononuclear blood leukocyte types expressing the Fc gamma RIII receptor (CD16) for immunoglobulin G in human sporadic amyotrophic lateral sclerosis (ALS). 857 89

Forty amyotrophic lateral sclerosis (ALS) patients were treated with suppressor factor. The therapy led to the normalization of the immunoregulatory index in approximately two thirds of the patients. The responder patients had a better clinical response, i.e. the degenerative process slowed down or it was even arrested. This favourable effect was accompanied with a significant increase in the patients' life span. When the therapy had no effect on the CD8 cells, it was discontinued. Stopping the therapy led to disease progression and death; thus, in some patients, therapy was carried out despite its failure to increase the CD8 cell numbers. Substantial clinical improvement was noticed in these patients. The mean survival of patients with ALS was 2-3 years, whereas ALS patients treated with the suppressor factor survived on the average more than 5 years.
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PMID:An attempt to inhibit the course of amyotrophic lateral sclerosis (ALS) by suppressor factor. 899 72

Although human retroviruses seem plausible agents of motor neuron diseases, there are only few reports of patients infected by the human immunodeficiency virus, with documented motor neuron disorder. That retroviral infections may cause motor neuron pathology by various mechanisms in animals and humans is known. Neurological symptoms potentially attributed to damage of lower motor neurons are often described during the course of HIV-1 infection and AIDS, however, it is often difficult to establish whether the disorder is primarily affecting the perikarya of lower motor neurons, or whether it is due to a focal proximal axonopathy, or to a dying-back process. We report a 30-year-old heroin abuser, HIV-1 positive, who presented a rapidly progressive limb weakness, muscle wasting, and bulbar signs, in absence of sensory loss of cerebellar and pyramidal signs. Imaging studies were negative. CSF showed increased protein content, negative cytology, and no oligoclonal bands. Serum protein electrophoresis, urinary heavy metal, and viral researches were negative. CD4 cells were counted 340 mm3 with a CD4-CD8 ratio equal to 0.4. Electrophysiology showed acute and chronic neurogenic changes, confirmed by muscle biopsy. Conduction studies along motor and sensory nerves fell within normal range. Biopsy of sural nerve revealed mild myelinated and unmyelinated fiber loss, occasional degeneration and regeneration, unremarkable inflammation. Despite treatment with AZT, zalcitabine, and steroids, the patient died after 3-month illness. Neuropathology showed normal cortical cell Betz's, and hemispheric white matter. Brain stem motor nuclei (inferior olival, dorsal motor of the vagus, hypoglossal) showed atrophy and intracytoplasmatic lipofuscin accumulation. Vacuolization, central chromatolysis, and neuronophagia were rarely seen. As associated pathology, in the fourth ventricle there were two small subependymal foci of demyelination, with reactive astrocytes and vascular proliferation. A possible crucial role of the HIV-1 infection in the development and progression of our patient's illness is considered in view of the known altered immunity proved in MND and ALS cases.
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PMID:Motor neuron disease and HIV-1 infection in a 30-year-old HIV-positive heroin abuser: a causal relationship? 962 4

Polymyositis (PM) is a cell-mediated autoimmune disease. Perforin (PF), Fas ligand (FasL) and TNF-alpha are considered to be important factors in cytotoxic T lymphocyte-mediated cell injury, and several studies have established a role of lymphotoxin (LT) in T helper type 1 (Th1)-induced cell-mediated autoimmune diseases. In the present study, to determine how LT, PF and FasL are involved in the pathogenesis of PM, we used immunohistochemical staining (IHC), reverse transcription polymerase chain reaction (RT-PCR), and in situ hybridization (ISH) on muscle specimens from patients with PM, amyotrophic lateral sclerosis (ALS), myotonic dystrophy (MyD) and controls (NC). There were many mononuclear cells (MNCs) immunoreactive for LT and some for PF and FasL within the fasciculus in PM muscles. On the other hand, only few or no LT-, PF- and FasL-positive cells were detected in MyD, ALS and NC muscles. The results of mRNA expression of these three molecules with RT-PCR were consistent with those using IHC methods. The number of MNCs positive for LT with ISH was far higher in PM compared to MyD, ALS and NC (P < 0.05 or 0.01). The MNCs located in the connective tissue or in the vicinity of necrotizing or non-necrotizing muscles were mainly LT mRNA and CD4 positive, while MNCs invading the non-necrotic fibers were mainly LT mRNA and CD8 positive. Our results indicated that the expression of LT was up-regulated in PM, and LT plays an important role in muscle injury and orchestrating the inflammatory reaction in PM.
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PMID:The role of lymphotoxin in pathogenesis of polymyositis. 1104 74

The cause of amyotrophic lateral sclerosis is still unknown. In the paper CD2, CD4 and CD8 markers on mononuclear cells as well as levels of TNF-alpha and IL-2 in sera from 15 patients with ALS were evaluated. There was a significant increase of TNF-alpha in sera of ALS patients in comparison with control group. This is the first such observation. It supports the concept that immune mechanisms may play a role in the pathogenesis of ALS.
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PMID:[Surface CD2, CD4, CD8 markers and IL-2 and TNF-alpha cytokines in amyotrophic lateral sclerosis]. 1146 17

Amyotrophic lateral sclerosis (ALS) is a target for cell-replacement therapies, including therapies based on human neural stem cells (NSCs). These therapies must be first tested in the appropriate animal models, including transgenic rodents harboring superoxide dismutase (SOD1) mutations linked to familial ALS. However, these rodent subjects reject discordant xenografts. In the present investigation, we grafted NSCs from human embryonic spinal cord into the ventral lumbar cord of 2-month-old SOD1-G93A transgenic mice. Animals were immunosuppressed with FK506, FK506 plus rapamycin, FK506 plus rapamycin plus mycophenolate mofetil, or CD4 antibodies. With FK506 monotherapy, human NSC grafts were rejected within 1 week, whereas combinations of FK506 with one or two of the other agents or CD4 antibodies protected grafts into end-stage illness (i.e., more than 2 months after grafting). The combination of FK506 with rapamycin appeared to be optimal with respect to efficacy and simplicity of administration. Graft protection was achieved via the blockade of CD4- and CD8-cell infiltration and attenuation of the microglial phagocytic response from the host. Surviving NSCs differentiated extensively into neurons that began to establish networks with host nerve cells, including alpha-motor neurons. Immunosuppressed animals with live cells showed later onset and a slower progression of motor neuron disease and lived longer compared with immunosuppressed control animals with dead NSC grafts. Our findings indicate that combined immunosuppression promotes the survival of human NSCs grafted in the spinal cord of SOD1-G93A mice and, in doing so, allows the differentiation of NSCs into neurons and leads to the improvement of key parameters of motor neuron disease.
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PMID:Combined immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice. 1664 22


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