Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.     

Selective polysaccharide antibody deficiency in familial DiGeorge syndrome.

A family including three children with DiGeorge syndrome is described. One child died in the neonatal period from cardiac anomalies accompanying complete DiGeorge syndrome. The two surviving siblings shared a common set of pharyngeal pouch anomalies and immunodeficiency consistent with partial DiGeorge syndrome, and other morphologic anomalies characteristic of the velocardiofacial syndrome with which familial DiGeorge syndrome is associated (reviewed in reference 1). Both had normal karyotypes. Both presented with recurrent otitis media and sinopulmonary infections, CD4+ T cell lymphopenia, and defective DCH skin test responses to recall T cell antigens. Both had low serum IgM levels and IgG4 levels at the lower limits of normal. Immunization with bacterial polysaccharides resulted in impaired IgG antibody responses to the same set of antigens (H. influenzae polyribophosphate and S. pneumoniae capsular serotypes 9N and 14), while responses to protein antigens were intact. Both siblings were treated successfully with intravenous gamma globulin. The pattern of selective antibody deficiency in these patients with familial DiGeorge syndrome suggests a heritable lesion in certain regulatory antipolysaccharide CD4+ T cell subpopulations.     

Small Conductance Ca2+-Activated K+ Channels Formed by the Expression of Rat SK1 and SK2 Genes in HEK 293 Cells

The rat SK1 gene ( rSK1 ) does not form functional Ca²⁺-activated potassium channels when expressed alone in mammalian cell lines. Using a selective antibody to the rSK1 subunit and a yellow fluorescent protein (YFP) tag we have discovered that rSK1 expression produces protein that remains largely at intracellular locations. We tested the idea that rSK1 may need an expression partner, rSK2, in order to form functional channels. When rSK1 was co-expressed with rSK2 in HEK 293 cells it increased the current magnitude by 77 ± 34 % (as compared with cells expressing rSK2 alone). Co-expression of rSK1 with rSK2 also changed the channel pharmacology. The sensitivity of SK current to block by apamin was reduced ~16-fold from an IC₅₀ of 94 p m (for SK2 alone) to 1.4 n m (for SK2 and SK1 together). The sensitivity to block by UCL 1848 (a potent small molecule blocker of SK channels) was similarly reduced, ~26-fold, from an IC₅₀ of 110 p m to 2.9 n m . These data clearly demonstrate that rSK1 and rSK2 subunits interact. The most likely explanation for this is that the subunits are able to form heteromeric assemblies.     

Susceptibility and amplification of sensitivity in contact dermatitis.

We have examined the hypothesis that people who develop contact allergies to environmental substances do so because they have heightened susceptibility. Analysis of data from 2200 consecutive patients tested with the 20 commonest antigens in a patch-test clinic showed that more people developed multiple contact allergies than would be predicted from the frequency of single allergies; the excess was too great to be explained by chance and increased with number and rarity of the combinations of sensitizers. The possibility that this was due to enhanced individual susceptibility to sensitization rather than concomitant exposure to several sensitizers was confirmed by showing that patients with multiple allergies are more readily sensitized experimentally, and to a greater degree than normal, by dinitrochlorobenzene (DNCB), an unrelated antigen. The defect involves induction rather than expression of sensitivity. Amplification of the response to DNCB is proportional to susceptibility (calculated from the ratio of observed prevalence of multiple allergies to that predicted from the prevalence of single allergies) throughout the range from normal subjects, through those with a single sensitivity, to those with rare, multiple allergies. Therefore, we conclude that individual susceptibility is an important factor in the development of contact dermatitis, and occurs by a non-antigen-specific amplification of immune sensitization.     

Loratadine-pseudoephedrine combination versus placebo in patients with seasonal allergic rhinitis

Two hundred sixty-four patients with moderate to severe seasonal allergic rhinitis were treated with loratadine 5 mg plus pseudoephedrine 120 mg twice a day or placebo in a 28-day multicenter study. Four nasal and four non-nasal symptoms were evaluated for efficacy. At the last evaluable visit, the active treatment group had significantly lower (P = .05) mean combined nasal and non-nasal symptom scores than the placebo group. Also, the physician's rating of overall therapeutic response was significantly better in the active-treatment group (P = .03). Dry mouth, insomnia, and nervousness were reported by a significantly greater proportion (P less than or equal to .04) in the active-treatment group. Sedation occurred in 7% of patients in each treatment group and 6% of patients in each group discontinued the study because of adverse experiences. Loratadine plus pseudoephedrine was safe and significantly more effective than placebo in relieving the symptoms of allergic rhinitis.     

Do semantic categories activate distinct cortical regions? Evidence for a distributed neural semantic system

A key issue in cognitive neuroscience concerns the neural representation of conceptual knowledge. Currently, debate focuses around the issue of whether there are neural regions specialised for the processing of specific semantic attributes or categories, or whether concepts are represented in an undifferentiated neural system. Neuropsychological studies of patients with selective semantic deficits and previous neuroimaging studies do not unequivocally support either account. We carried out a PET study to determine whether there is any regional specialisation for the processing of concepts from different semantic categories using picture stimuli and a semantic categorisation task. We found robust activation of a large semantic network extending from left inferior frontal cortex into the inferior temporal lobe and including occipital cortex and the fusiform gyrus. The only category effect that we found was additional activation for animals in the right occipital cortex, which we interpret as being due to the extra visual processing demands required in order to differentiate one animal from another. We also carried out analyses in specific cortical regions that have been claimed to be preferentially activated for various categories, but found no evidence of any differential activation as a function of category. We interpret these data within the framework of cognitive accounts in which conceptual knowledge is represented within a nondifferentiated distributed system.     

A manual bead assay for the determination of absolute CD4+ and CD8+ lymphocyte counts in human immunodeficiency virus-infected individuals.

CD4+ T lymphocytes are currently the most common surrogate marker indicating disease progression in individuals infected with human immunodeficiency virus (HIV). Since the cost of enumerating lymphocyte phenotypes is quite high, an inexpensive bead assay analyzed by light microscopy (cytosphere assay; Coulter Corporation, Hialeah, Fla.) was developed as an alternative method for counting CD4+ and CD8+ T lymphocytes. To evaluate the reliability of the cytosphere assay, heparinized blood was collected from 117 HIV-infected individuals and tested for both CD4+ and CD8+ lymphocytes by flow cytometry and the cytosphere assay. The Pearson correlation coefficient of the cytosphere assay compared with that of flow cytometry for CD4+ T lymphocytes was 0.93, with mean values +/- standard deviations of 534 +/- 509 by flow cytometry and 499 +/- 477 by the cytosphere assay. The correlation coefficient for CD8+ T lymphocytes was 0.86, with mean values of 831 +/- 543 by flow cytometry and 746 +/- 472 by the cytosphere assay. The sensitivity and specificity of the cytosphere assay in determining absolute CD4+ T-lymphocyte counts of less than 200/microliters were 97.6 and 94.7%, respectively. The positive predictive value was 90.9%, and the negative predictive value was 98.6%. The cytosphere assay was highly correlative to flow cytometry in determining CD4+ and CD8+ T-lymphocyte counts among HIV-infected patients. The ease and limited resources needed to perform this test make it ideal in developing countries and other areas where technology and finances are limited.     

Human infections caused by Brevibacterium casei, formerly CDC groups B-1 and B-3.

Forty-one clinical strains of CDC coryneform groups B-1 and B-3 were compared biochemically, by analysis of cell wall sugars, amino acids, and cellular fatty acids, and by DNA relatedness to the type strains of Brevibacterium casei, Brevibacterium epidermidis, and Brevibacterium linens. Twenty-two strains were shown to be B. casei, while five other strains formed a phenotypically inseparable genomospecies in the same genus. The remaining isolates were genetically heterogeneous, and most are probably members of the genus Brevibacterium. They were not further identified, but they were biochemically distinguishable from B. casei. Eleven of the clinical strains of B. casei were isolated from blood, and two each were isolated from cerebrospinal fluid and from pleural fluid. At least five isolates were from multiple blood or cerebrospinal fluid cultures. To our knowledge, these strains are the first described clinical isolates identified as B. casei, which was previously considered to be a nonpathogenic species.     

Phenotypic characteristics, fatty acid composition, and isoprenoid quinone content of CDC group IIg bacteria.

Eleven strains of eugonic, nonoxidative, gram-negative rods isolated from clinical specimens formed a distinct group that was designated CDC group IIg. Five of the 11 isolates were from wounds. The phenotypic characteristics of CDC group IIg were most similar to those of Weeksella species, with the major difference being that CDC group IIg strains grew on MacConkey agar in 1 to 2 days, did not hydrolyze gelatin, and did not produce urease. All 11 strains of CDC group IIg possessed a distinct fatty acid profile that was characterized by large amounts (19 to 29%) of 18:1 omega 7c, 16:0, and 16:1 omega 7c, moderate amounts (6 to 10%) of 3-OH-14:0 and 14:0, and smaller amounts (1 to 2%) of 18:2, 18:0, and 3-OH-16:0. This fatty acid profile differs from those of Weeksella species by the absence of branched-chain fatty acids. CDC group IIg contains ubiquinone-8, as opposed to menaquinone-6 in Weeksella species. The isolates were susceptible to a variety of antimicrobial agents, including the aminoglycosides, tetracyclines, quinolones, sulfonamides, and polymyxin B.