Search PubMed⌕ Search

Biomedical subjects

S L Hauser

Publications and source records attributed to S L Hauser.

At least 109 records · Page 6Linked to original sources
PubMed1986

Failure of immunosuppression with a ten- to 14-day course of high-dose intravenous cyclophosphamide to alter the progression of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of the nervous system for which there is no known treatment. Because recent studies have suggested that there may be abnormalities of the immune function in patients with ALS and since we have found a beneficial effect from a short course of intensive immunosuppression with cyclophosphamide in progressive multiple sclerosis, we treated six patients with ALS with a ten- to 14-day course of intensive immunosuppression in a pilot study. At 18 months following therapy, all patients showed a continued progression of the disease; four of the six patients died. We conclude that this form of immunosuppression does not alter the course of ALS.

Aged↗
PubMed1986

Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions.

Immunohistochemical staining of 16 brains post mortem from patients with progressive multiple sclerosis and of two biopsy specimens from patients with acute demyelinating disease was performed using a panel of monoclonal antibodies reactive with T cells and T-cell subsets, B cells, and Ia (HLA-DR) antigens. Lymphocytic perivascular cuffs were most prominent at the edge of active plaques and were occasionally seen in areas with no evidence of demyelination or macrophage infiltration. Perivascular cuffs consisted predominantly of T cells and Ia+ cells, with many T8+ cells and variable numbers of T4+ cells. T8/T4 ratios in cuffs varied between 1:1 and 50:1. In normal-appearing white matter, cuffs were sparse and were predominantly T8+. The distribution of T cells in the parenchyma resembled that seen in perivascular cuffs, namely, predominantly T8+ cells and variable numbers of T4+ cells. Many Ia+ cells were present in active lesions, and the majority of these cells appeared, by histological criteria, to be macrophages. Tissue macrophages were also stained lightly by the anti-T4 antibody. No brain had more T4+ than T8+ cells, determined using both T4 and Leu3a monoclonal antibodies. B1+ cells were rare. These results suggest that the cellular infiltrate in multiple sclerosis consists predominantly of T cells and macrophages and that there is an overrepresentation of T8+ cells compared with T4+ cells.

Antibodies, Monoclonal↗
PubMed1986

Immunoblot analysis of circulating antibodies against muscle proteins in amyotrophic lateral sclerosis and other neurologic diseases.

Serum from patients with amyotrophic lateral sclerosis (ALS) was tested by immunoblotting for reactivity against three muscle-derived preparations: denervated chick leg muscle extracts, media conditioned by denervated rat hemidiaphragms, and a human muscle extract. For each preparation, multiple bands were present using serum from all patients and controls, and no band was unique to ALS. Against rat muscle-conditioned medium, bands in the 56,000 (56K) molecular weight range were present to an equal degree in ALS and in controls; in addition, different bands near 56K were recognized by serum from different ALS patients. These results fail to confirm a recent report suggesting that anti-56K reactivity is characteristic of ALS.

Adult↗
PubMed1985

Increased IgG secretion by unstimulated mononuclear cells in active multiple sclerosis and functional assessment of the T8 subset.

Unseparated mononuclear cells (10(5) cells/well) were cultured both in the presence and absence of pokeweed mitogen (PWM), and IgG secretion was measured by radioimmunoassay. In unstimulated cultures, levels of IgG secretion were found to be higher in a group of patients with multiple sclerosis (MS) than in control groups of healthy individuals or patients with other neurologic diseases (OND). By contrast, PWM-induced IgG secretion was similar in MS patients and in controls. In MS patients, levels of IgG secretion greater than 2500 ng/ml in unstimulated cultures were present in 29 (58%) of 50 patients with active disease and in only 3 (14%) of 21 patients with inactive MS (P less than 0.01; MS active vs inactive). Furthermore, levels of IgG secretion in unstimulated cultures were higher in patients who had abnormalities of circulating T-cell subsets consisting of reduced numbers of suppressor/cytotoxic (T8) cells and elevated helper:suppressor (T4:T8) ratios. In additional experiments using isolated populations of T-cell subsets, T8 cells from MS patients who had low percentages of circulating T8 cells were found to suppress PWM-induced IgG secretion by autologous cells to a similar extent as controls, suggesting that in vitro, T8 cells function normally in these patients. In vitro IgG secretion by unstimulated mononuclear cells in MS appears to be a further reflection of abnormal immune regulation in this disease.

Antibody Formation↗
PubMed1984

Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes.

Splenic lymphocytes from adult C57BL/6 mice infected with purified reovirus type 1 or 3 particles were fused with NS1 myeloma cells. Approximately 300 clones were obtained from each fusion (type 1 or type 3) and the supernatants from these clones were screened by radioimmunoassay for their ability to bind virus, T lymphocytes, brain, liver, lung tissues and isolated oligodendrocytes and ependymal cells. Approximately 10% of clones (33 and 26 clones, respectively) were positive for each fusion. For reovirus type 1:21% of positive clones bound only virus, 64% bound one of the normal tissues but not virus, and 15% bound both virus and one or more of the normal tissues. For reovirus type 3: 19% of positive clones bound only virus, 73% bound normal tissue only, and 8% bound both virus and normal tissue. Only 3 positive clones were obtained from uninfected control animals. These experiments demonstrate that (a) during the course of an immune response to a virus, autoantibodies are generated which react with a large variety of normal tissues and that (b) there are shared antigenic structures between viral determinants and normal tissue that can be identified by monoclonal antibodies. Although these results suggest two mechanisms by which an autoimmune response may develop following viral infection, the biological significance of these autoreactive monoclonal antibodies remains to be elucidated.

Animals↗
PubMed1984

Altered blood T-cell subsets in patients with multiple sclerosis.

We have found an alteration in T-cell subsets in patients with active multiple sclerosis, specifically an increase in the T4:T8 ratio. These findings have been reproducibly obtained over the past four years, occurring in the majority of acute patients tested early in the course of an attack and in between 25 and 40% of chronic progressive patients, depending on their stage of illness. These changes correlate with pleocytosis in spinal fluid and with other abnormalities of immune function, such as spontaneous immunoglobulin production. They have been helpful in assessing disease activity in patients being treated on a variety of protocols and as part of research studies of immunoregulatory abnormality in multiple sclerosis, but have not been helpful as a diagnostic test for multiple sclerosis. The decrease of these cells in the peripheral blood of patients with active disease may be secondary to migration of these cells to the central nervous system, where they are sequestered.

Animals↗
PubMed1984

Lymphocytapheresis in chronic progressive multiple sclerosis: immunologic and clinical effects.

We studied the effects of lymphocytapheresis in five patients with chronic progressive MS. Ten lymphocytapheresis treatments were given in 2 weeks, followed by 1 treatment every 2 weeks for 2 to 6 months. Four of five patients had a fall in the circulating lymphocyte count during the initial treatment, and in three patients a modest lymphopenia was sustained with maintenance therapy. In patients with abnormal T4:T8 ratios, no improvement in the T4:T8 ratio occurred. There was no apparent clinical effect in this pilot study.

Adult↗
PubMed1984

Lyt-1 cells mediate acute murine experimental allergic encephalomyelitis.

Adult SJL/J mice were depleted of T lymphocytes and were reconstituted with Lyt-1, Lyt-2, or Lyt-1 + Lyt-2 cells. After immunization with MSCH, severe acute EAE developed in the Lyt-1- and the Lyt-1 + Lyt-2-reconstituted mice. Only 25% of the Lyt-2-reconstituted mice developed signs of EAE, and in those EAE onset was delayed. Thus, Lyt-1 cells mediate EAE in the mouse.

Acute Disease↗
PubMed1984

Redistribution of Lyt-bearing T cells in acute murine experimental allergic encephalomyelitis: selective migration of Lyt-1 cells to the central nervous system is associated with a transient depletion of Lyt-1 cells in peripheral blood.

Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mice by using two injections of spinal cord homogenate in incomplete Freund's adjuvant supplemented with mycobacteria. Analysis of circulating Lyt-bearing subsets by indirect immunofluorescence during the course of acute EAE revealed the following: 1) during the pre-clinical phase of EAE (1 to 2 days before the onset of paralysis), there was a decrease in the percentage of Lyt-1- but not of Lyt-2-bearing cells in peripheral blood, and of both Lyt-1- and Lyt-2-bearing cells in spleen; 2) with the onset of clinically evident EAE, there was a decrease in both Lyt-1 and Lyt-2 cells in peripheral blood and an increase in the percentage of Lyt-1-bearing cells in pooled inguinal and axillary lymph node; and 3) after these early changes, there was a rapid reconstitution of the percentages of total Lyt-bearing cells and of both Lyt-1- and Lyt-2-bearing cells in peripheral blood. Immunohistochemical analysis of the central nervous system infiltrate revealed that the earliest lesions consisted predominantly of Lyt-1 T lymphocytes, with few Lyt-2 cells present. These results demonstrate that the influx of cells of the Lyt-1 inducer subset to the central nervous system in acute EAE is accompanied by a transient decrease in Lyt-1 cells in peripheral blood.

Acute Disease↗
PubMed1984

Prevention of experimental allergic encephalomyelitis (EAE) in the SJL/J mouse by whole body ultraviolet irradiation.

The cellular requirements for the in vivo induction of experimental allergic encephalomyelitis (EAE) were investigated in the SJL/J mouse. Exposure of mice to whole body ultraviolet (UV) irradiation, a treatment that has been shown in other systems to interfere selectively with antigen-presenting cell function, prevented the development of clinical and pathologic signs of acute EAE. Splenic T cells from UV-treated animals did not adoptively transfer resistance to EAE, making it unlikely that UV irradiation resulted in the generation of a specific suppressor cell population responsible for protection from EAE. UV irradiation was effective in preventing EAE when administered before initial immunization; UV irradiation was ineffective in modifying ongoing EAE or in preventing relapses of EAE induced by reimmunization. In additional experiments, adult thymectomized, lethally x-irradiated mice reconstituted with syngeneic marrow cells depleted of mature T lymphocytes were found to be resistant to the induction of EAE. Susceptibility was restored by the addition of splenic T cells, demonstrating that EAE induction is T cell-dependent in the mouse. The prevention of an experimental autoimmune demyelinating disease by whole body UV irradiation suggests that interference with the function of Ia-bearing accessory cells may represent an approach for immunotherapy in autoimmune disorders.

Animals↗
PubMed1983

Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH.

Fifty-eight patients with severe, progressive multiple sclerosis were prospectively randomized to one of three treatments: 20 received intravenous ACTH, 20 received high-dose intravenous cyclophosphamide plus ACTH, and 18 were placed on a regimen consisting of plasma exchange, low-dose oral cyclophosphamide, and ACTH. The three groups were similar in age, sex, duration and type of disease, and degree of disability. Before treatment and six months and one year after treatment, a disability-status score, ambulation index, and functional-status score were determined, and a quantitative neurologic examination was performed. In the ACTH group, the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year; in the cyclophosphamide-ACTH group, 18 of 20 at six months and 16 of 20 at one year; and in the plasma exchange group, 11 of 18 at six months and 9 of 18 at one year. High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at both 6 and 12 months (at 12 months, cyclophosphamide-ACTH vs. ACTH, P = 0.0004; cyclophosphamide-ACTH vs. plasma exchange, P = 0.087). Thus, progressive multiple sclerosis may be stabilized by short-term, intensive immunosuppression with cyclophosphamide plus ACTH.

Administration, Oral↗
PubMed1983

Immunoregulatory T-cells and lymphocytotoxic antibodies in active multiple sclerosis: weekly analysis over a six-month period.

Immunoregulatory T-cell subsets were measured at weekly intervals over a 4 to 6 month period using monoclonal antibodies (anti-T4 = inducer cell; anti-T8 = suppressor/cytotoxic cell) in a group of 6 patients with multiple sclerosis (MS) and in 4 age- and sex-matched controls. Decreases in the T8 subset and increases in the T4:T8 ratio were present in 4 of the patients with MS but not in controls. Two patients who were neurologically stable during the study period had no changes in the T4:T8 ratio; 2 patients with intermediate disease activity of the relapsing-remitting type had elevated ratios on 3 and 4 occasions respectively; the patient with the most clinically active MS had an abnormal ratio 12 of 27 times. One patient with chronic-progressive MS had an elevated ratio on each occasion tested. No abnormalities in T-cell subsets were present in any of the controls. On three occasions an elevated T4:T8 ratio appeared to precede an acute relapse by 1.5 to 7 days. Lymphocytotoxic antibodies (LCA) against whole lymphocytes or against isolated T-cell subsets were measured in these patients and in a larger group of MS patients, and were not found to correlate with changes in T-cell subsets. This report extends previous findings linking changes in T-cell subsets to disease activity in patients with MS.

Adult↗
PubMed1983

Immunohistochemical staining of human brain with monoclonal antibodies that identify lymphocytes, monocytes, and the Ia antigen.

Using immunoperoxidase histochemistry, human brain sections obtained at biopsy were labeled with monoclonal antibodies which identify human lymphocyte subsets, monocytes, and the Ia antigen. Staining of a population of cells in white matter was present with the anti-Ia and the anti-M1 (monocyte-associated) antibodies but not with any of the 8 monoclonal antibodies which react with human T-cell subsets (anti-T1, 3, 4, 5, 6, 8, 10 and 12). The Ia antigen was present on 1-2% of cells in white matter, and approximately 5% of cells in white matter were M1-positive. Ia-positive cells demonstrated a pattern of diffuse surface membrane staining, whereas the M1 antigen appeared to cluster at proximal cell processes. Definitive identification of these cells as microglial cells, astrocytes or oligodendrocytes was not possible. These findings demonstrate that: (1) cells which bear the Ia and M1 determinants can be found in histologically normal human white matter, and (2) human oligodendrocytes do not react with monoclonal antibodies (anti-T5 and anti-T8) that identify human suppressor/cytotoxic cells.

Animals↗
PubMed1983

CSF cells in multiple sclerosis: monoclonal antibody analysis and relationship to peripheral blood T-cell subsets.

Mononuclear cells were analyzed in CSF and blood of 102 patients with MS. In CSF, the majority (78%) of cells were T lymphocytes (T3+), and the ratio of inducer (T4+) to suppressor/cytotoxic (T8+) cells was 2:1. No characteristic alterations in CSF phenotypes could be related to changes in circulating T8 cells or to disease activity. In a group of 75 patients, CSF cell count was higher in patients with low numbers of circulating T8 cells than in those with normal T8 cells. Thus, decreases in suppressor cells in the blood of MS patients are associated with CSF pleocytosis but not with fluctuations in the ratio of different subsets in CSF. Furthermore, large numbers of T8 cells are not sequestered in CSF when these cells are decreased in peripheral blood.

Antibodies, Monoclonal↗