Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis

OBJECTIVE: To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. METHODS: Interviews were used to obtain histories of the following disorders among living first- and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently. RESULTS: There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1-5.7], P < 0.000001). The prevalence of autoimmunity was increased in first-degree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6-7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families. CONCLUSION: These data demonstrate that the prevalence of autoimmunity is significantly higher among first- and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.     

How should we measure function in patients with chronic heart and lung disease?

To elucidate the characteristics of measures of function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman's rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579), and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand, correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease.     

Soluble peptide-MHC monomers cause activation of CD8+ T cells through transfer of the peptide to T cell MHC molecules

T cell receptor (TCR)-mediated activation of CD4(+) T cells is known to require multivalent engagement of the TCR by, for example, oligomeric peptide-MHC complexes. In contrast, for CD8(+) T cells, there is evidence for TCR-mediated activation by univalent engagement of the TCR. We have here compared oligomeric and monomeric L(d) and K(b) peptide-MHC complexes and free peptide as stimulators of CD8(+) T cells expressing the 2C TCR. We found that the monomers are indeed effective in activating naive and effector CD8(+) T cells, but through an unexpected mechanism that involves transfer of peptide from soluble monomers to T cell endogenous MHC (K(b)) molecules. The result is that T cells, acting as antigen-presenting cells, are able to activate other naive T cells.     

Two distinct alpha beta T-cell lineages can be distinguished by the differential usage of T-cell receptor V beta gene segments.

Avian T cells can be divided into three subpopulations based on their expression of distinct T-cell receptors (TCR1, TCR2, and TCR3), ontogeny, and tissue distribution. The TCR1 cells appear to be the equivalent of mammalian gamma delta cells, but the derivation of cells expressing TCR2 and TCR3 has been unclear. Here we report that chickens contain two families of TCR beta variable (V) gene segments, V beta 1 and V beta 2. Furthermore, TCR2 and TCR3 represent subsets of alpha beta cells that are defined by mutually exclusive usage of these two families of V beta gene segments. Sequence comparisons of V beta 1 and V beta 2 with mammalian TCR beta V segments reveal that V beta 1 gene segments encode the conserved amino acids used to define the mammalian V beta consensus subgroup I, while V beta 2 encodes the amino acids used to define the mammalian V beta subgroup II. Although the beta chains of TCR2 and TCR3 cells are encoded by the same diversity (D), joining (J), and constant (C) region segments, V beta 1 gene segments undergo rearrangement before V beta 2 gene segments during T-cell development. This may result from the fact that TCR2 cells undergo V-DJ joining by deletional rearrangement, whereas TCR3 cells undergo V-DJ joining by inversional rearrangement. These data suggest that the TCR alpha beta cells can be divided into two distinct and evolutionarily conserved lineages based on V beta gene segment usage. The clear-cut separation of these lineages in the chicken may help to define their immunologic role.     

The role of thoracic duct lymph in gastrin transport and gastric secretion

The effect of thoracic lymph diversion on gastric secretion has been studied in dogs. In addition, the concentration of gastrin in thoracic duct lymph of nine dogs and two patients has been measured before and during antral stimulation with either food or acetylcholine. The secretory studies do not support the concept that there is a significant gastric secretagogue in thoracic duct lymph. The amount of gastrin carried in thoracic duct lymph as determined by radioimmunoassay is far less than that necessary to evoke a gastric secretory response.     

Oral ganciclovir in children: pharmacokinetics, safety, tolerance, and antiviral effects. The Pediatric AIDS Clinical Trials Group

The pharmacokinetics, safety, tolerance, and antiviral effects of ganciclovir (Gcv) administered orally were evaluated in 36 children infected with cytomegalovirus (CMV) who were severely immunocompromised by infection with human immunodeficiency virus type 1. In this dose-escalation study, 30 mg/kg of Gcv administered every 8 h produced serum levels similar to the dose (1 g/8 h) effective for maintenance treatment of CMV retinitis in adults. In older children, serum Gcv concentrations were similar after the administration of capsules and suspension. All doses (10-50 mg/kg/8 h) studied were safe and, except for the volume of suspension or number of pills, were well tolerated. Oral Gcv was associated with a decrease in the detection of CMV by culture or polymerase chain reaction. CMV disease occurred in 3 children during the study: one developed Gcv resistance, another had harbored resistant virus at study entry, and a third had wild-type CMV     

Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter pylori: a possible explanation of the effect of diet on peptic ulceration.

Diets high in polyunsaturated fatty acids may protect against duodenal ulcer, possibly through inhibiting the growth of Helicobacter pylori. This hypothesis was tested in vitro by incubating H pylori microaerophilically with a range of polyunsaturated fatty acids. omega-3 Linolenic acid significantly, but reversibly, inhibited growth at 1.8, 2.5, and 5 x 10(-4) M (p < 0.01), while concentrations of 10(-3) M killed virtually all organisms, with cell lysis observed by electron microscopy. Similar inhibitory effects were seen with other polyunsaturated fatty acids, at concentrations of 2.5 x 10(-4) M the relative inhibitory potencies were oleic (C18:1) < linoleic (C18:2) < arachidonic (C20:4) < omega-3 linolenic (C18:3) = omega-6 linolenic (C18:3) = eicosapentanoic (C20:5) acid. Cell fractionation studies with 14C labelled linolenic acid showed that the linolenic acid was associated with the membrane fraction. Commonly ingested dietary polyunsaturated fatty acids inhibit the growth of H pylori in vitro, an effect which deserves further in vivo study.     

Alteration of type A behavior and reduction in cardiac recurrences in postmyocardial infarction patients

Eight hundred sixty-two postmyocardial infarction patients volunteered to be randomly selected and enrolled into: (1) a control section of 270 patients, who received group cardiologic counseling; and (2) an experimental section of 592 patients, who received group type A behavior counseling in addition to group cardiologic counseling. Reduction in type A behavior at the end of 3 years was observed in 43.8% of the 592 participants, who initially were enrolled to receive group cardiologic and type A behavioral counseling. This degree of behavioral reduction was significantly greater than that observed in participants who initially were enrolled to receive only group cardiologic counseling. The 3-year cumulative cardiac recurrence rate was 7.2% in participants who initially were enrolled to receive group cardiologic and type A behavioral counseling. This was significantly less (p less than 0.005) than that (13%) observed in participants who initially were enrolled to receive only cardiologic counseling. This difference in recurrence rates was due to a lesser incidence of nonfatal infarctions in the patients who had been enrolled in the section receiving type A behavioral as well as cardiologic counseling. These data suggest that type A behavior can be altered in a sizable fraction of postinfarction patients and that such alteration is associated with a significantly reduced rate of nonfatal myocardial infarctions.