Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies

Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of one week and supplemented with Bordetella pertussis toxin given IV. Here, we studied the effect on the induction of EAE of depleting antibodies to CD4, CD8, or CD25 administered before either the first or the second dose of MOG p35-55. We found that anti-CD4 abolished EAE when given before the first immunization; anti-CD4 did not affect the disease when it was given before the second immunization. Anti-CD8 enhanced EAE induction when given before either of the two immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given before the first immunization, but anti-CD25 was even more effective in enhancing EAE when given before the second immunization. The anti-CD25 treatment led to significantly enhanced IFNgamma production by T cells responding to MOG p35-55 and persisting anti-MOG antibodies detectable 56 days after the first immunization. Administration of anti-CD8 or anti-CD25 abolished the need for pertussis toxin to induce EAE. These findings are compatible with the idea that CD4 T cells are required for the initial induction of EAE and that the disease is down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist prior to MOG immunization, but the CD25+ regulators appear to be further amplified by immunization.     

Lymphocytic choriomeningitis virus

Lymphocytic choriomeningitis (LCM) virus-specific complement-fixing (CF) antigen (ECFA) has been solubilized, concentrated, and partially purified. When inoculated together with Freund's adjuvant, ECFA induced CF antibody but not neutralizing antibody or protective immunity. By itself it boosted pre-existing CF antibody but not neutralizing antibody. In double diffusion tests one line developed between ECFA and its antiserum, and a corresponding line became visible when ECFA interacted with an antiserum directed against all LCM virus-specific antigens. Absorption of either serum with ECFA abolished all ECFA-precipitating qualities. Ouchterlony tests also revealed that ECFA prepared from cells and tissues of various species is immunologically identical. By a variety of procedures ECFA was not found to be represented on the surface of either the virion or the infected cell. When purified infectious LCM virus was disrupted, a CF antigen corresponding immunologically to ECFA was set free. In double diffusion tests this antigen gave a line of identity with ECFA. Thus, ECFA appears to be an internal component of the infectious LCM virus.Part of the work reported here has been published in preliminary communications [8, 10, 24, 25].     

Segmental jejunal lipomatosis--a rare cause of intestinal obstruction

A rare case of a segmental small intestinal (jejunal) lipomatosis is described. A 33-year-old male was admitted with a clinical diagnosis of an acute intestinal obstruction. A plain erect abdominal x-ray showed multiple air-fluid levels. On an exploratory laparotomy, a jejunojejunal intussusception was found secondary to a segmental submucosal lipomatosis. This was treated by a segmental resection and anastomosis, which resulted in a complete cure. Here we present this case with a review of the relevant literature.     

Assessing the effects of bupropion SR on mood dimensions of depression

BACKGROUND: We assessed the therapeutic effects of bupropion SR and placebo on mood and anxiety symptoms derived from the tripartite model of mood. Based on evidence indicating linkages between dopaminergic activity and the emotional dimension of positive affect/anhedonia, we hypothesized that the dopaminergic effects of bupropion SR would yield particularly pronounced effects on symptoms of anhedonia, relative to anxiety. METHODS: Nineteen depressed outpatients were randomly assigned to treatment with either bupropion SR 300 mg/day or placebo during a 6-week initial treatment phase. This was followed by a second open-label phase in which patients previously treated with bupropion SR had their dose increased to 400 mg/day, and the placebo group was initiated on bupropion SR 300 mg/day. RESULTS: Random regression analyses revealed that during the initial double-blind phase, bupropion SR elicited greater declines than placebo on all measures except those that assessed anxiety. By contrast, the weakest placebo effects were evident on anhedonia. Items assessing the low positive affect pole of the anhedonia dimension were more sensitive to earlier/lower dose bupropion SR treatment, whereas items assessing the high positive affect pole were more sensitive to later/higher dose bupropion SR treatment. LIMITATIONS: Replication and extension using a larger sample size are mandated. CONCLUSIONS: This study suggests that the catecholaminergic effects of bupropion SR tended to produce more robust effects on anhedonia/positive affect than placebo.     

Target-to-target interval versus probability effects on P300 in one- and two-tone tasks

The P3(00) is an electrophysiological index of neural processing that varies with such stimulus parameters as interstimulus interval (ISI) and target probability, with a common view being that it reflects an endogenous form of memory update. Building on previous research, we argue that relations between P3 amplitude and both ISI and probability may be attributable to the target-to-target interval (TTI). Employing between-subject (Experiment 1; N = 24) and within-subject (Experiment 2; N = 10) designs, the present paper addresses this by testing subjects on a standard two-tone auditory oddball task as well as a one-tone task. In both studies, P3 amplitude increased and latency decreased linearly with TTI, and these relations were relatively unaffected by ISI or probability. This suggests that ISI and probability per se do not independently affect P3 amplitude, and that TTI offers a strong explanation of the reported relations between P3 amplitude and both ISI and probability.     

Specific Pseudomonas Immunoglobulin E Antibodies in Sera of Patients with Cystic Fibrosis

Immunoglobulin E antibodies to Psuedomonas aeruginosa were demonstrated in patients with cystic fibrosis colonized with the bacterium.     

Immune and autoimmune aspects of diabetes mellitus

The immune and autoimmune aspects of diabetes mellitus are reviewed. Emphasis is given to the clinical association of diabetes with other autoimmune disease; the increased incidence of organ-specific autoimmunity in diabetic patients; the occurrence of humoral and cell-mediated antipancreas (islet) autoimmunity in diabetes; the association of HLA with juvenile-onset, insulin-dependent diabetes mellitus and with certain specific subpopulations of diabetic patients; the possible role of viruses in the etiology of diabetes; and the occurrence of alterations in humoral and cell-mediated immunity, granulocyte function, and the host defense against infectious agents in human diabetics and in animals with experimental diabetes.     

Na+ channel expression and neuronal function in the Na+/H+ exchanger 1 null mutant mouse

Mice lacking Na(+)/H(+) exchanger 1 (NHE1) suffer from recurrent seizures and die early postnatally. Although the mechanisms for seizures are not well established, our previous electrophysiological work has shown that neuronal excitability and Na(+) current density are increased in hippocampal CA1 neurons of these mutant mice. However, it is unknown whether this increased density is related to altered expression or functional regulation of Na(+) channels. In this work, we asked three questions: is the increased excitability limited to CA1 neurons, is the increased Na(+) current density related to an increased Na(+) channel expression, and, if so, which Na(+) channel subtype(s) is upregulated? Using neurophysiological, autoradiographic, and immunoblotting techniques, we showed that both CA1 and cortical neurons have an increase in membrane excitability and Na(+) current density; Na(+) channel density is selectively upregulated in the hippocampus and cortex (P < 0.05); and Na(+) channel subtype I is significantly increased in the hippocampus and Na(+) channel subtype II is increased in the cortex. Our results demonstrate that mice lacking NHE1 upregulate their Na(+) channel expression in the hippocampal and cortical regions selectively; this leads to an increase in Na(+) current density and membrane excitability. We speculate that neuronal overexcitability due to Na(+) channel upregulation in the hippocampus and cortex forms the basis of epileptic seizures in NHE1 mutant mice.