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Biomedical subjects

G Birnbaum

Publications and source records attributed to G Birnbaum.

At least 37 records · Page 2Linked to original sources
PubMed1990

A comparison of regulatory cells in spinal fluid and blood in patients with multiple sclerosis and other neurologic diseases.

Multiple sclerosis is a disease in which immune abnormalities are present both in the CNS and peripheral blood. Whether these changes are primary or secondary to the disease process is not known. We tested T-cell clones derived from activated lymphocytes in the blood and CSF of MS patients and controls for their capacity to regulate T-cell responses to alloantigens. A wide spectrum of regulatory functions were observed, ranging from marked enhancement to almost complete suppression. Clones from different patient populations and anatomic sites were equivalent in their regulatory functions with the net effect of clones in each compartment being suppression. However, certain clones from CSF and peripheral blood had the capacity to stimulate autologous T cells. Percentages of such clones in the peripheral blood of MS patients were significantly higher than in controls, while percentages in MS and other neurologic diseases (OND) CSF were equivalent. Our data suggest that (1) functional suppressor cells are not lost from the blood or CSF or MS and OND patients, (2) lymphocytes that have entered the CNS in patients with MS and other CNS diseases have equivalent regulatory functions, (3) MS may be an illness in which peripheral immunologic events are important in perpetuating the disease process, and (4) responses to autologous antigens may also play a role in this perpetuation.

Adult↗
PubMed1989

Double-blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis.

We enrolled 116 patients in a multicenter, randomized, double-blind controlled trial of an 8-week course of 11 plasma exchange (PE) treatments in exacerbations of MS. The control group received sham PE, and both groups received identical treatment with IM ACTH and oral cyclophosphamide. Serum IgG decreased in the PE and sham treatment groups by 76% versus 22% by treatment 5, and by 64% versus 14% by treatment 11. PE also produced significant reductions in IgA, IgM, C3, and fibrinogen. PE patients had moderately enhanced improvement at 2 weeks relative to the sham group. PE patients with relapsing/remitting disease had significantly enhanced improvement at 4 weeks and there was also an increased improvement at 12 months, although this latter effect disappeared when we analyzed relapsing/remitting patients as a separate subgroup. Life table analysis showed the median time to recover preattack disability status was shorter in PE- than in sham-treated relapsing/remitting patients (4 vs. 13 weeks), a result confirmed by raw disability status scores in which there was recovery to their average preattack disability score by 3 months. PE given with ACTH plus cyclophosphamide enhances recovery from an exacerbation of disease in relapsing/remitting patients, although we observed no clear long-term benefits.

Acute Disease↗
PubMed1988

Search for autonomously proliferating spinal fluid lymphocytes in patients with multiple sclerosis.

Recently published reports have suggested that multiple sclerosis (MS) may be associated with human retrovirus infection. Indeed, an autonomously proliferating T-cell clone was isolated from the CSF of an MS patient, an observation interpreted as indicating an infection with human T lymphotropic virus I (HTLV I). In view of these findings, we undertook a systematic search for autonomously proliferating cells in the spinal fluids of MS patients and those with other neurologic diseases (OND). In vivo activated blast cells were isolated from the CSF of six MS patients and six OND controls. A total of 442 clones were grown from these cells and assayed for their ability to proliferate independently, without the need for T cell-produced lymphokines. No autonomously proliferating clones were detected. Thus, while our data do not exclude the possibility that HTLV I transformed cells may exist in the CSF of MS patients, they do suggest that such cells are exceptional.

Adult↗
PubMed1987

Immunomodulatory factors in cerebrospinal fluid of patients with multiple sclerosis and controls.

The immunomodulatory effects of cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and other neurologic diseases (OND) were determined by measuring their abilities to suppress alloantigen-specific and nonspecific (IL-2 mediated) proliferative responses. An alloantigen primed, IL-2-dependent line of human T-cells (PLT) was used as indicator. CSF from both patient groups significantly suppressed alloantigen-specific and nonspecific PLT proliferative response. However, patterns of suppression differed between the two groups. While alloantigen-specific proliferative responses were suppressed similarly by MS and controls, CSF from MS patients had significantly less suppressing effect on nonspecific lymphocyte proliferation than did control CSF. The degree of suppression of alloantigen-stimulated proliferation by MS CSF correlated with the concentrations of gamma-globulin and myelin basic protein as well as with the Ig index. Suppression of alloantigen-stimulated proliferation by control CSF correlated only with the concentration of alpha 1-globulin. Sera from 3 MS patients and 7 OND patients were also tested in our system. Only MS sera significantly suppressed the alloantigen stimulated proliferative responses of the PLT. Neither serum group affected nonspecific (IL-2 mediated) proliferation. Our data suggest that there are immunomodulatory factors present in both MS and control CSF, but MS CSF may be relatively lacking in a factor controlling nonspecific lymphocyte proliferation. Deficiency of this factor(s) may contribute to the increased numbers of activated lymphocytes in MS CSF.

Adjuvants, Immunologic↗
PubMed1986

Disparate responses of lymphocyte clones to cells of monozygotic twins discordant for multiple sclerosis.

Spinal fluid and peripheral blood lymphocytes from patients with multiple sclerosis (MS) and other neurologic diseases (OND) were stimulated with a pool of allogeneic MS lymphocytes. Responding cells were cloned and assayed for their proliferative responses to peripheral blood lymphocytes from monozygotic twins discordant for MS. As expected, most (greater than 90%) responding clones proliferated equally well to cells from both members of a twin set. However, some clones were noted that responded to cells from one but not the other of the twin set. These differences could not be explained on the basis of a decreased stimulatory capacity of the twin cells. We cannot definitively explain our observations but they may suggest that environmental factors, perhaps exposure to a virus, could have altered the antigenic phenotypes of cells from identical twins discordant for MS. Further evaluation of the nature of these differences may lead to an understanding of the pathogenesis of the disease.

Clone Cells↗
PubMed1986

Recognition of major histocompatibility complex antigens on murine glial cells.

Recognition of autologous major histocompatibility complex (MHC) antigens by T cells is an essential step in the induction of an immunologic reaction to either endogenous or exogenous antigens. We investigated the ability of murine glial cells of different ages to stimulate clones of allospecific T lymphocytes. We also investigated the effects of supernatants from cultures of activated T cells on the immunologic recognition of MHC antigens on murine glial cells. Lymphocyte clones specific for Class I, Class II and non-MHC, background antigens were obtained from C57B1/6J-anti-DBA/2 mixed lymphocyte cultures. Glial cell cultures were prepared from newborn syngeneic (C57B1/6J) and allogeneic (DBA/2) mouse brains. Glial cultures 1-4 weeks of age were able to stimulate alpha-Class I-specific clones. No stimulation of alpha-Class II or alpha-background clones was noted. Incubation of glial cells with supernatants from cultures of alloantigen-activated spleen cells (C57B1/6J-anti-DBA/2) resulted in a decreased ability of glial cells to stimulate alpha-Class I responses. In contrast supernatant-treated cultures acquired the capacity to stimulate alpha-Class II-specific clones. No responses were noted in clones responsive to non-MHC antigens. The ability to stimulate alpha-Class II-specific clones was most prominent with one-week-old glial cultures and was lost by four weeks of culture. The increased susceptibility of younger glial cultures to the modulatory effects of lymphokines from activated T cells may be a factor in the increased susceptibility of the immature central nervous system to persistent viral infections and the development of autoimmune phenomena.

Animals↗
PubMed1984

Radiographic parameters in adult epiglottitis.

A retrospective study was undertaken to define precise radiographic criteria for the diagnosis of epiglottitis in the adult. We reviewed the standard lateral neck films of six patients over the age of 18 with epiglottitis and five with a normal epiglottis. Radiographic anatomy measured included the angle of the valleculae, retropharyngeal soft tissue width at C2, retrotracheal soft tissue width at C6, width of the epiglottis, width of the aryepiglottic folds, and the hypopharyngeal to tracheal air column ratio. The measurement differences were significant between the groups only for the width of the epiglottis and aryepiglottic folds (P less than .01). Width of the epiglottis greater than 8 mm and of the aryepiglottic folds greater than 7 mm seem highly suggestive of epiglottitis in the adult.

Acute Disease↗
PubMed1984

Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.

Spinal fluid lymphocytes from multiple sclerosis (MS) patients and controls were stimulated with either autologous non-T cells or with allogeneic non-T cells followed by stimulation with autologous non-T lymphocytes. Cells responding to these stimuli were cloned and their proliferative responses to autologous and allogeneic MS and normal non-T cells were measured. Large numbers of clones with specific patterns of reaction to both autologous and allogeneic cells were obtained from lymphocytes in MS cerebrospinal fluid (CSF), but only occasionally from cells in control CSF. Patterns of responses among clones from a particular CSF were similar and often identical, which suggested that cells in MS CSF were relatively restricted in their specificities. Surface antigen phenotyping of the clones showed them to be predominantly OKT4+, with 13% OKT8+ and 11% OKT4+8+. Peripheral T cells that were stimulated and cultured in parallel with CSF cells were different in that they usually did not give rise to as many clones nor were their patterns of response similar. Many CSF clones were heteroclitic, that is they responded to particular allogeneic cells but not autologous cells. Lymphocytes in MS CSF thus appear to represent a selected population of cells with a high frequency of responsiveness to autologous and allogeneic antigens. Such responses may be evidence for immune regulation within the central nervous system or could represent responses to altered-self antigens.

Adolescent↗
PubMed1983

B-cell differentiation in multiple sclerosis and the effect of intravenous ACTH.

B-cell differentiation was studied in patients with MS and in age- and sex-matched controls, using a pokeweed mitogen (PWM)-stimulated in vitro culture system. Peripheral blood lymphocytes were obtained and separated into T-cell and non-T-cell fractions. Autologous and allogeneic combinations of T cells and B cells were cultured in the presence of pokeweed mitogen for 7 days. Numbers of plaque-forming cells (PFC) were measured at the end of the culture period. T cells from MS patients before and after a 10-day course of adrenocorticotropic hormone (ACTH) were able to cooperate fully in the generation of PWM-generated PFC. B cells from MS patients showed a decreased ability to differentiate into PFC in the presence of either autologous or allogeneic T cells. No significant change in differentiation was observed after a 10-day course of intravenous ACTH. We were thus unable to demonstrate any alteration in T-cell function in MS but were able to demonstrate a decreased ability of MS B cells to differentiate into immunoglobulin-secreting cells. ACTH had no significant effect on these abnormalities.

Adrenocorticotropic Hormone↗
PubMed1981

Autologous lymphocyte proliferation in multiple sclerosis and the effect of intravenous ACTH.

The proliferative response of peripheral blood T cells to autologous non-T cells, a reaction called the autologous mixed lymphocyte reaction (MLR), was significantly increased in 17 patients with active multiple sclerosis (MS) compared to age- and sex-matched individuals with other neurological diseases (OND). Following a 10-day course of intravenous adrenocorticotropic hormone (ACTH) therapy the values were reduced to control levels. No differences were noted between MS patients and controls in their response to alloantigens. The increased autologous MLR in patients with active MS appeared to result from an increased stimulatory capacity of non-T cells rather than from an intrinsically greater T cell proliferative potential. ACTH appeared to induce a change in the populations of circulating non-T cells such that these cells had a decreased stimulatory capacity in both autologous and allogeneic MLR. The decrease in stimulatory capacity in autologous MLR was, however, significantly greater than the decrease in allogeneic stimulatory capacity, suggesting a functional decrease of specific non-T cell-enriched subpopulations. No significant changes in the numbers of myeloperoxidase-positive (MP+) cells were noted in the blood of MS patients before and after ACTH therapy. Since the autologous MLR results in generation of cells that regulate immune responsiveness, the changes noted provide additional evidence for abnormal immune regulation in MS.

Adrenocorticotropic Hormone↗
PubMed1981

Human suppressor lymphocytes. II. Changes in concanavalin A inducible suppressor cells with age.

Suppressor cells were induced in peripheral blood mononuclear cells from young and old individuals by two day culture with Concanavalin A (Con A). Suppressor activity was quantitated using an alloantigen driven cytotoxicity assay. The proliferative responses of lymphocytes from young and old individuals to Con A and alloantigens were also determined. Results demonstrated that the numbers of Con A inducible suppressor cells were markedly decreased but equivalent proliferative responses to Con A were reduced compared to young individuals but equivalent proliferative responses to alloantigens were noted. Even though not statistically significant, alloantigen-induced cytotoxic responses were slightly increased in older persons. The increased alloantigen-induced cytotoxic responses of individuals noted in the present study may be related to the decreased numbers of suppressor cells in this group.

Adult↗