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R J Fallis

Publications and source records attributed to R J Fallis.

17 recordsLinked to original sources
PubMed1989

Chronic relapsing experimental allergic encephalomyelitis. Cytotoxicity effected by a class II restricted T cell line specific for an encephalitogenic epitope.

We have examined the possibility that Ag-specific CTL responses may play a role in the pathogenesis of CREAE by using an effector T cell line (LN400) specifically reactive to the SJL encephalitogenic epitope defined by myelin basic protein MBP residues(90-101). The LN400 cell line was capable of adoptively transferring CREAE to naive SJL mice and proliferated specifically to synthetic peptides corresponding to MBP residues(90-101) and an N-acetylated analogue of this epitope, as well as MBP. Moreover, the cell line generated Ag-specific CTL responses only against syngeneic targets that had been pulsed with these Ag. Targets pulsed with irrelevant Ag were not lysed. These CTL responses were MHC restricted to H-2s and were inhibited if targets were preincubated with mAb specific for relevant class II Ag. No inhibition was seen if targets were preincubated with mAb specific for class I Ag, indicating that the CTL responses generated by this L3T4+ Lyt-2.2- cell lines were class II restricted. Studies designed to detect nonspecific CTL through a bystander mechanism failed to demonstrate significant lysis of bystander targets by this Ag-specific cell line. These findings have relevance in defining potential mechanisms of disease induction in this model autoimmune disease.

Animals↗
PubMed1989

Chronic relapsing experimental allergic encephalomyelitis in SJL mice following the adoptive transfer of an epitope-specific T cell line.

Chronic relapsing experimental allergic encephalomyelitis (CREAE) was induced in SJL mice following the adoptive transfer of a T cell line derived from mice immunized with a synthetic peptide corresponding to residues 89-100 of the guinea pig myelin basic protein (MBP) molecule. This cell line proliferated to both the peptide and MBP and induced CREAE characterized by a series of relapses with eventual stabilization. Central nervous system (CNS) inflammation and demyelination were prominent neuropathologic features of both the acute and relapsing phase of the disease. The chronic phase was characterized by CNS lesions containing chronically demyelinated fibers with remyelination and some fiber drop-out, but little inflammation. The induction of CREAE in SJL mice by a cell line specific for residues 89-100 demonstrates that T cell recognition of this epitope is required for successful disease induction in this strain of mouse.

Animals↗
PubMed1987

Immunoregulatory abnormalities induced by experimental reovirus infection: functional alterations in T-cell subpopulations.

A primary anti-sheep red blood cell (SRBC) plaque assay system was used to analyze the effect of reovirus infection on immunoregulatory T-cells. A decrease in the plaque-forming cell (PFC) response of splenic lymphocytes was observed within 24 hr of infection with 10(9) or 10(11) particles of reovirus type 1 or reovirus type 3 and persisted for more than 7 days. In coculture experiments, T-cells from infected mice were found to produce less help to control B-cells and to suppress helper function mediated by control T-cells. This suppression did not require the presence of an Lyt1,2,3 cell. In addition, isolated Lyt1 cells from reovirus-inoculated mice provided less help than did Lyt1 cells from normal controls. These abnormalities were more marked following inoculation with reovirus type 3 than with type 1. Live virus was not required for these effects, as T-cells from mice inoculated with ultraviolet (uv)-inactivated reovirus when added to normal B-cells reproduced the effects of infection with live virus. Furthermore, these changes were not the result of alterations in the percentages or numbers of distinct Lyt-bearing T-cell subpopulations in the spleens of inoculated mice. Thus, humoral hyporesponsiveness following reovirus infection of adult mice is associated both with active T-cell suppression of B-cell help and with decreased help mediated by the Lyt1 subset.

Animals↗
PubMed1987

Adoptive transfer of murine chronic-relapsing autoimmune encephalomyelitis. Analysis of basic protein-reactive cells in lymphoid organs and nervous system of donor and recipient animals.

Frequency analysis of myelin basic protein (MBP)-reactive lymphocytes was performed in the chronic relapsing murine experimental allergic encephalomyelitis (EAE) model induced by the adoptive transfer of myelin basic protein (MBP)-primed lymphocytes to naive recipients. During the first attack, MBP-reactive cell frequencies were: 1/41,700 in spleen, 1/328,000 in lymph nodes, 1/64,500 in the peripheral blood. After recovery from a second attack, the frequencies were: 1/11,000 in spleen, 1/46,000 in lymph node, and 1/195,000 in the blood. In addition, lymph node cells obtained from animals following a second attack had increased encephalitogenic properties. CNS-derived lymphocytes analyzed during the first attack were 50% Lyt 1.2+ and 16% Lyt 2.2+. After recovery from the second attack, phenotypes were 20% Lyt 1.2+ and 49% Lyt 2.2+. There were only minimal responses to MBP in CNS-derived lymphocytes. Susceptibility to adoptively transferred EAE was in general predicted by whether a proliferative response to MBP occurred following immunization and was not solely H-2 linked. These studies demonstrate an accumulation of autoreactive cells in the spleen and lymph nodes and a shift of the phenotype of cells in the target organ as EAE becomes chronic and suggest there are dynamic immunologic processes, both in the peripheral immune system and target organ associated with relapsing EAE.

Animals↗
PubMed1987

Serial analysis of peripheral blood T-cell phenotypes and myelin basic protein reactivity in experimental allergic encephalomyelitis.

We have serially analyzed peripheral blood T-cell phenotypes and reactivity to myelin basic protein (MBP) during the course of acute experimental allergic encephalomyelitis (EAE) in the Lewis rat and have correlated changes with the onset of clinical disease. A reduction in total T cells (W3/13+), due primarily to a reduced helper/inducer (W3/25+) subpopulation, preceded the onset of EAE. Circulating MBP-reactive lymphocytes were only transiently present in the blood at the time EAE was clinically evident. Our findings demonstrate that in EAE, immunologic abnormalities in the peripheral blood are transient and can begin before clinical disease is evident.

Animals↗
PubMed1986

Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis.

Peripheral blood lymphocytes (PBL) from active and stable multiple sclerosis (MS) patients, patients with other neurologic diseases (OND), and control subjects were tested for sensitization to two myelin antigens not previously examined in multiple sclerosis, using a [3H]thymidine incorporation assay. The antigens investigated were myelin-associated glycoprotein (MAG) and proteolipid protein (PLP). In addition, sensitization to myelin basic protein (MBP) was also tested. Lymphocyte stimulation indices in active MS patients that were greater than 2 standard deviations above controls were as follows: 9/30 for MAG, 0/17 for PLP, and 8/81 for MBP. No control subjects responded to MAG or PLP, and only 1/29 control subjects responded to MBP. Three of the patients that responded to MAG also responded to MBP. Although the mean proliferative response to MAG and to MBP was greater in the population of active MS patients than in stable MS, ONDs, or controls, the difference was not statistically significant. The OND group was the only population which proliferated to PLP (6/16). The only statistically significant differences among the groups for all myelin antigens tested were the proportion of individuals with active MS vs. controls that responded to MAG (P less than 0.05), and OND vs. controls and active MS that responded to PLP (P less than 0.025). The greatest individual responses to the three antigens tested were to MBP in active MS patients. Elimination of the T8 (cytotoxic/suppressor) subset amplified the responses to myelin antigens in some patients and ONDs studied. These studies have demonstrated reactivity to MAG but not PLP in some patients with active MS, and reactivity to PLP in some patients with other neurologic diseases.

Antibodies, Monoclonal↗
PubMed1986

Immunologic responses of progressive multiple sclerosis patients treated with an anti-T-cell monoclonal antibody, anti-T12.

Twelve patients with progressive MS were treated with a murine IgM pan-T-cell monoclonal antibody reactive against T12, a determinant present on most post-thymic T-cells. Circulating T12+ cells could not be detected from days 1 to 7, although T3+T11+T12- cells appeared by day 3. Human anti-mouse antibodies were detected in 78% of patients by day 7 and correlated with a decrease in anti-T12 MAb blood levels and the reappearance of T12+ cells in the blood. Although there were high levels of anti-T12 MAb in the serum, there were only barely detectable levels in the CSF and no decrease in the proportion of T12+ cells in the CSF with treatment. Immunologic studies demonstrated a decrease of in vitro pokeweed mitogen-driven Ig synthesis on day 3 with an increase on day 10 that consisted in part of human anti-mouse antibodies. Eleven of 12 patients completed therapy. Prednisone was administered with the treatment after mild allergic reactions occurred in the first two patients. Because this was an open phase one study and patients were treated with prednisone, the effect of treatment on the progression of disease is difficult to assess, and no definitive conclusions concerning clinical effects can be made.

Adult↗
PubMed1985

Cerebral vasculitis and hemorrhage associated with phenylpropanolamine.

A 20-year-old woman using an oral diet aid preparation containing phenylpropanolamine presented with an intracerebral hemorrhage and angiographic evidence of cerebral vasculitis. Gas chromatography demonstrated phenylpropanolamine in the urine. Even when used within recommended guidelines, phenylpropanolamine usage should be included in the differential diagnosis of patients presenting with intracranial hemorrhage.

Adult↗
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↗
PubMedDate not supplied

Alterations in T cell antigen specificity and class II restriction during the course of chronic relapsing experimental allergic encephalomyelitis.

In order to assess T cell antigen specificities and class II restriction requirements during the course of chronic relapsing experimental allergic encephalomyelitis (CREAE), (SJL x PL)F1 mice were used as a model. EAE can be passively transferred in these mice by F1 T cells incubated with Ia-positive antigen-presenting cells (APC) from either parent SJL (H-2s) or PL (H-2u) and MBP fragments 89-169 or 1-37, respectively. T cells purified from F1 mice immunized with MBP fragment 1-37 were positively selected for I-Au-supported proliferation by culture in the presence of irradiated Iau-positive PL spleen cells as APC. I-As-supported proliferation and proliferation to residues 89-169 were not detected following selection. Adoptive transfer of this T cell line induced CREAE in naive recipient F1 mice and 2 weeks after the second attack of EAE recipient proliferative responses were measured. Recipient T cells proliferated to both fragment 1-37 and fragment 89-169. Moreover, proliferation was supported by I-As-positive as well as I-Au-positive macrophages. These findings demonstrate that T cells with novel epitope specificities and class II restriction requirements can be generated during the course of CREAE and suggest the possibility that such cells may be involved in the pathogenesis of this chronic autoimmune illness.

Animals↗
PubMedDate not supplied

A double blind trial of naloxone in the treatment of acute stroke.

Naloxone has been reported to have potential benefit in the treatment of stroke. We evaluated the effect of naloxone in a double-blind trial conducted with 15 stroke patients whose deficits ranged from 8 to 60 hours in duration. All but one patient sustained a cerebral infarction. Neurologic function was assessed before and five minutes after each of two injections given to each patient in a double-blind fashion. The injections consisted of naloxone (0.4 mg in 3 patients and 4.0 mg in 12 patients) and saline. Prior to the trial, samples of plasma were obtained for determination of immunoreactive beta-endorphin for each patient. Four patients showed minimal improvement following injection of naloxone, while five patients exhibited a slightly greater improvement following saline injection. There were no significant elevations of plasma beta-endorphin among stroke patients. We conclude that naloxone may not have a significant therapeutic role for stroke in the clinical setting.

Acute Disease↗
PubMedDate not supplied

Ischemic chiasmal syndrome and hypopituitarism associated with progressive cerebrovascular occlusive disease.

Two interesting patients are described with unique clinical and radiographic manifestations of progressive bilateral stenosis-occlusion of the distal internal carotid arteries. Their clinical presentations, ischemic chiasmal syndrome and hypopituitarism, are extremely rare, despite extensive occlusion of the circle of Willis. In one of these patients, the configuration of collateral vessels around the optic chiasm on computed tomography (CT) was so rounded and discrete that it actually had an appearance suggesting a pituitary tumor or an aneurysm. In the second patient, a pseudoaneurysm and a very large intracerebral hematoma with a ring of contrast enhancement were the radiographic manifestations.

Adult↗