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Biomedical subjects

S D Miller

Publications and source records attributed to S D Miller.

At least 163 records · Page 9Linked to original sources
PubMed1990

Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance induction.

Intravenous administration of neuroantigen-coupled syngeneic splenocytes is an efficient regimen for Ag-specific regulation of relapsing experimental autoimmune encephalomyelitis (R-EAE) at the effector level of the disease process. Treatment of SJL/J mice with splenocytes coupled with mouse spinal cord homogenate (MSCH) or myelin proteolipid protein after immunization with mouse spinal cord homogenate in CFA, but before the onset of clinical signs specifically inhibited the expression of neuroantigen-specific delayed-type hypersensitivity responses and significantly suppressed the onset, severity, and the duration of clinical and histologic signs of R-EAE. In contrast, the clinical course of R-EAE was not affected by tolerization with myelin basic protein-coupled splenocytes, indicating that proteolipid protein-specific responses play the major role in active MSCH-induced R-EAE. To ensure a physical and temporal separation between the inductive and effector stages of the disease process, we also examined the effects of neuroantigen-coupled splenocytes on adoptive R-EAE. Treatment of recipient mice with MSCH-coupled splenocytes up to 6 days after the transfer of MBP-primed lymph node cells induced a dose-dependent, profound, and long-lasting inhibition of clinical and histologic signs of adoptive R-EAE. The demonstration that splenocytes coupled with a heterogeneous mixture of neuroantigens (i.e., MSCH) can inhibit established immune responses suggests that this methodology has potential for regulating ongoing immune responses associated with autoimmune disorders or chronic graft rejection in which the specific (auto)Ag has yet to be identified.

Animals↗
PubMed1990

Inhibition of murine relapsing experimental autoimmune encephalomyelitis by immune tolerance to proteolipid protein and its encephalitogenic peptides.

Tolerization of SJL/J mice with splenocytes coupled with proteolipid protein (PLP), the major protein component of central nervous system myelin, resulted in dramatic inhibition of relapsing experimental autoimmune encephalomyelitis (R-EAE) induced by mouse spinal cord homogenate (MSCH). Mice tolerized with splenocytes coupled with MSCH (a complex mixture of neuroantigens) or with purified PLP, but not purified myelin basic protein, were resistant to the development of clinical and histologic R-EAE. In addition, mice rendered tolerant to an encephalitogenic peptide of PLP were significantly protected, whereas mice tolerized to a nonencephalitogenic peptide of PLP were highly susceptible, to the induction of MSCH-induced R-EAE. Thus, immune responses directed against encephalitogenic regions of PLP appear to play a major role in the development of R-EAE induced by MSCH in SJL/J mice. These results also indicate that determinant-specific immune tolerance is a feasible approach to the regulation of a disease that involves autoimmune responses to a variety of Ag.

Animals↗
PubMed1990

Induction of allograft tolerance to the H-Y antigen in adult C57BL/6 mice: differential effects on delayed-type hypersensitivity and cytolytic T-lymphocyte activity.

This study describes the induction of allograft tolerance to the "male-specific," minor histocompatibility antigen, H-Y, in adult C57BL/6 female mice, and the effects of this tolerance induction on two immune parameters associated with graft rejection: delayed-type hypersensitivity (DTH) and cytolytic T-lymphocytes (CTL). B6 females tolerized to H-Y, by a single iv injection of C57BL/6 male lymphocytes, exhibited prolonged or permanent survival of B6 male tail skin grafts. Graft-induced DTH against H-Y antigen was reduced or abrogated in tolerized females. Delayed onset of graft rejection in partially tolerant females correlated with delayed onset of DTH, and eventual rejection of grafts was accompanied by an increase in H-Y-specific DTH. In contrast, H-Y-specific CTL activity was not consistent with graft status. These data demonstrate a correlation between H-Y-specific DTH and rejection of male skin grafts by B6 female mice and are most consistent with a major effector role for DTH in chronic graft rejection.

Animals↗
PubMed1990

Monocytes/macrophages isolated from the mouse central nervous system contain infectious Theiler's murine encephalomyelitis virus (TMEV).

Knowledge of the cells in which Theiler's murine encephalomyelitis virus (TMEV) persists is crucial to understanding the pathogenesis of TMEV-induced demyelinating disease; however, it is still uncertain whether oligodendrocytes or macrophages are the primary target for persistence. In this study, mononuclear cells (MNC) isolated directly from central nervous system (CNS) inflammatory infiltrates of TMEV-infected mice on discontinuous Percoll gradients were found to contain infectious TMEV. Macrophages appeared to be the principal MNC infected as determined by two-color immunofluorescence. Infectious center assay and double immunostaining together indicated the presence and possible synthesis of TMEV in approximately 1 in 225 to 1 in 1000 CNS macrophages, with 1 to 7 PFU produced per macrophage. On the basis of these findings, limited replication in macrophages is consistent with the total CNS virus content detected at any time during the persistent phase of the infection as well as the slow pace of the infection.

Animals↗
PubMed1990

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. III. Failure of neuroantigen-specific immune tolerance to affect the clinical course of demyelination.

Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible mouse strains produces a chronic demyelinating disease in which mononuclear cell-rich infiltrates in the central nervous system (CNS) are prominent. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility complex (MHC) class II-restricted delayed-type hypersensitivity (DTH) responses in which lymphokine-activated macrophages mediate bystander demyelination. The present study examined the possibility that concomitant or later-appearing neuroantigen-specific autoimmune T cell responses, such as those demonstrated in chronic-relapsing experimental allergic encephalomyelitis (R-EAE), may contribute to the demyelinating process following TMEV infection. T cell responses against intact, purified major myelin proteins (myelin basic protein (MBP) and proteolipid protein (PLP], and against altered myelin constituents were readily demonstrable in SJL/J mice with R-EAE, but were not detectable in SJL/J mice with TMEV-induced demyelinating disease. TMEV-infected mice also did not display T cell responses against the peptide fragments of MBP(91-104) and PLP(139-151) recently shown to be encephalitogenic in SJL/J mice. In addition, induction of neuroantigen-specific tolerance to a heterogeneous mixture of CNS antigens, via the i.v. injection of syngeneic SJL/J splenocytes covalently coupled with mouse spinal cord homogenate, resulted in significant suppression of clinical and histologic signs of R-EAE and the accompanying MBP- and PLP-specific DTH responses. In contrast, neuroantigen-specific tolerance failed to alter the development of clinical and histologic signs of TMEV-induced demyelinating disease or the accompanying virus-specific DTH and humoral immune responses. These findings demonstrate that TMEV-induced demyelinating disease can occur in the apparent absence of neuroantigen-specific autoimmune responses. The relationship of the present results to the immunopathology of multiple sclerosis is discussed.

Animals↗
PubMed1990

Rapid biotin-avidin method for quantitation of antiviral antibody isotypes.

A rapid and efficient method is described for isotype quantitation of antiviral antibodies in mice infected with Theiler's murine encephalomyelitis virus (TMEV). Serum antibodies were reacted with fluorochrome-labeled TMEV in a modified fluid-phase particle concentration fluorescence immunoassay (PCFIA). Biotin and avidin were used to attach anti-immunoglobulin isotype antibodies to polystyrene particles by the separate incubation of biotinylated goat anti-mouse isotypes (IgG1-, IgG2a-, IgG2b-, IgG3-, or IgM-specific) with avidin coupled polystyrene particles. These anti-isotype particles captured the virus-antibody complexes. Mouse myeloma proteins were used to quantitate and standardize isotype profiles of normal mouse serum using fluorescein isothiocyanate (FITC)-labeled, goat anti-mouse isotypes and polystyrene particles coated with goat anti-mouse. These assays quantitated the affinity-purified mouse serum antiviral antibodies for the standardization of antiviral isotype assays. Immunoglobulin of all serum isotypes as well as the amount of virus-specific isotypes can be quantitated rapidly and accurately.

Animals↗
PubMed1990

Klebsiella pneumoniae bacteraemia at an urban general hospital.

Of 47 patients with Klebsiella pneumoniae bacteraemia admitted to the Hillbrow Hospital, Johannesburg during a period of 18 months, 31 were males and 16 were females. Features predisposing to illness were found in 89.4% patients, chronic alcoholism, neoplastic disease and diabetes mellitus being the most common. Twenty-five infections were acquired in hospital and 22 in the community. Most patients (59.6%) had pneumonia. All isolates of K. pneumoniae were resistant to ampicillin (100%); several (42.6%) were resistant to other antibiotics also. The overall mortality rate was 55.3%. A higher mean initial blood pressure and lower concentrations of serum urea and bilirubin were found in survivors. None of the 28 patients, surviving more than 48 h who received combined therapy with an aminoglycoside and a beta-lactam antibiotic (to which the organism was susceptible) died. Among the remaining patients treated with either an appropriate beta-lactam agent alone, an appropriate aminoglycoside alone or ciprofloxacin the combined mortality rate was 83.3% (P = 0.007).

Adolescent↗
PubMed1990

A comparative study of spectinomycin and erythromycin in the treatment of chancroid.

In a randomized, controlled study, 55 patients with genital ulcerations, culture-positive for Haemophilus ducreyi, were treated with a single intramuscular injection of 2 g spectinomycin. A further 61 patients were treated with a five-day oral course of erythromycin base (500 mg, three times daily). Treatment failure occurred in seven patients who received spectinomycin (13%), whilst no treatment failures were recorded among patients who received erythromycin. This difference in efficacy was statistically significant. In contrast, spectinomycin proved significantly more effective than erythromycin in the treatment of the lymphadenopathy associated with primary chancroid lesions.

Administration, Oral↗
PubMed1990

Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease.

Theiler's virus-induced demyelinating disease results from a chronic infection in the white matter of the central nervous system and provides an excellent model for human multiple sclerosis. Like multiple sclerosis, there are genetic risk factors in disease development, including genes associated with the major histocompatibility complex and with those encoding the beta chain of the T-cell receptor. Comparisons of the susceptible DBA/2 and resistant C57BL/6 strains have indicated an important role for the H-2D locus and for a non-H-2 gene (not involving the beta chain of the T-cell receptor) in differential susceptibility. In the present report, analysis of recombinant-inbred strains (BXD) between the DBA/2 and C57BL/6 strains indicated that this non-H-2 locus is located at the centromeric end of chromosome 3 near (4 +/- 4 centimorgans) the carbonic anhydrase-2 (Car-2) enzyme locus.

Animals↗
PubMed1990

Structured interview data on 102 cases of multiple personality disorder from four centers.

Patients with multiple personality disorder (N = 102) at four different centers were interviewed with the Dissociative Disorders Interview Schedule. The presenting characteristics of the patients at all four centers were very similar. The clinical profile that emerged included a history of childhood physical and/or sexual abuse in 97 (95.1%) of the cases. The subjects reported an average of 15.2 somatic symptoms, 6.4 Schneiderian symptoms, 10.2 secondary features of the disorder, 5.2 borderline personality disorder criteria, and 5.6 extrasensory experiences; their average score on the Dissociative Experiences Scale was 41.4. The results indicate that multiple personality disorder has a stable, consistent set of features.

Borderline Personality Disorder↗
PubMed1989

A rapid method for quantitation of antiviral antibodies.

This paper examines the parameters necessary for the efficient measurement of anti-Theiler's murine encephalomyelitis virus (TMEV) antibodies in an affinity-dependent manner using a variation of a solid-phase particle concentration fluorescence immunoassay (PCFIA). By allowing antibody to react with fluorochrome-labelled virus in fluid phase and subsequently capturing the resulting virus-antibody complexes with anti-immunoglobulin coated polystyrene particles (fluid-phase PCFIA), the present assay allows for both greater sensitivity, specificity and preservation of conformational viral epitopes than do solid-phase immunoassays. Fluid-phase PCFIA proved to be a more rapid quantitative assay than ELISA and significantly diminished non-specific binding by both untreated and heat-inactivated normal mouse sera. This methodology also allowed us to perform competition assays and to determine the dissociation kinetics of anti-viral antibody preparations, investigations which cannot generally be performed as solid-phase immunoassays. Thus fluid-phase PCFIA is a rapid and efficient immunoassay with excellent reproducibility and great versatility.

Animals↗
PubMed1989

Cerebral phaeohyphomycosis caused by Xylohypha bantiana.

Cerebral phaeohyphomycosis is a rare fungal infection of man. There are approximately 53 published cases to date. Xylohypha bantiana has been shown by histology or culture to be the aetiological agent in 28 of these cases. Two cases of cerebral abscess caused by Xylohypha bantiana are presented. One patient was alive eight months after surgery and antifungal drug therapy. His was the first recorded case of cerebral phaeohyphomycosis treated with itraconazole. His course was complicated by adhesive arachnoiditis. The second patient died post-operatively without appropriate treatment.

Adult↗