Local production of IgA- and IgM-rheumatoid factors in adult periodontal disease

The enzyme-linked immunospot assay was used to enumerate both the number and the frequency of spontaneous IgG, IgA, and IgM immunoglobulin-secreting cells and IgA- and IgM-rheumatoid factor (RF)-producing cells present in the gingivae and peripheral blood of adult periodontitis patients. Cells from 29 patients were incubated on plates coated with human IgG, Fc, or F(ab)₂ fragments and on plates coated with class-specific antihuman antibodies and secreted antibodies were subsequently visualized by means of an immunoenzymatic procedure. The data indicate that (1) IgA-RF- and IgM-RF-secreting cells are frequently present in the gingiva of adult periodontitis patients; (2) production of RF in gingivae of adult periodontitis patients occurs in the absence of demonstrable RF production by simultaneously obtained peripheral blood mononuclear cells, suggesting that local autoimmune reactions may occur in this disease; and (3) lack of correlation between IgA-RF and IgM-RF production in diseased gingiva suggests that the two RF isotypes are regulated independently of each other.     

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the β-frequency band (15–35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non-invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in β-band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in β-band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or β-band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.     

The Effect of End Group Modification on the Transparency of Vinyl Addition Norbornene Polymers at 193 nm

Summary: Homopolymers of a bis‐trifluorocarbinol substituted norbornene ( 1 ) (α,α‐bis(trifluoromethyl)bicyclo[2.2.1]hept‐5‐ene‐2‐ethanol or HFANB) and copolymers of 1 with t‐butyl ester of 5‐carboxylic acid ( 2 , t‐BuEsNB) were produced using palladium catalysts and olefinic chain transfer agents such as 1‐hexene and ethylene to control molecular weight. However, these low‐molecular‐weight polymers exhibited relatively low optical transparencies at 193 nm. In fact, the opacity (measured as optical densities in absorbance units per micron) of thin films of these homo‐ and co‐polymers was inversely proportional to their molecular weight. This relationship is consistent with an end group contribution to the film opacity. Spectroscopic analysis of these polymers by ¹H NMR and MALDI‐TOF MS confirmed that 1‐hexene and ethylene chain transfer agents generated olefin‐terminated vinyl addition polymers. The olefinic end group contribution to optical density can be eliminated by appropriate chemical modification. Both epoxidation and hydrogenation of the polymer olefinic end groups generated very low optical density materials, independent of molecular weight, that are suitable as 193‐nm photoresist binder resins.

End group modification of vinyl and hexenyl‐terminated homopolymers of 1 by epoxidation or hydrogenation.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients.

Increased levels of rheumatoid factors (RF) have been observed in the serum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9.7 ng/ml IgA RF, 11.6 ng/ml IgM RF and 64.6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21.4 ng/ml IgA RF, 21.4 ng/ml IgM RF, and 108.15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198.3 ng/ml of IgA anti-Fc(IgG) from involved versus 50.0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF (7.1 ng/ml IgA RF, 6.2 ng/ml IgM RF, and 42.3 ng/ml IgA anti-Fc(IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened state of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF.     

A 1463 gene cattle-human comparative map with anchor points defined by human genome sequence coordinates

A second-generation 5000 rad radiation hybrid (RH) map of the cattle genome was constructed primarily using cattle ESTs that were targeted to gaps in the existing cattle-human comparative map, as well as to sparsely populated map intervals. A total of 870 targeted markers were added, bringing the number of markers mapped on the RH(5000) panel to 1913. Of these, 1463 have significant BLASTN hits (E < e(-5)) against the human genome sequence. A cattle-human comparative map was created using human genome sequence coordinates of the paired orthologs. One-hundred and ninety-five conserved segments (defined by two or more genes) were identified between the cattle and human genomes, of which 31 are newly discovered and 34 were extended singletons on the first-generation map. The new map represents an improvement of 20% genome-wide comparative coverage compared with the first-generation map. Analysis of gene content within human genome regions where there are gaps in the comparative map revealed gaps with both significantly greater and significantly lower gene content. The new, more detailed cattle-human comparative map provides an improved resource for the analysis of mammalian chromosome evolution, the identification of candidate genes for economically important traits, and for proper alignment of sequence contigs on cattle chromosomes.     

Comparison of chlorhexidine and tincture of iodine for skin antisepsis in preparation for blood sample collection

Rates of contamination of blood cultures obtained when skin was prepared with iodine tincture versus chlorhexidine were compared. For iodine tincture, the contamination rate was 2.7%; for chlorhexidine, it was 3.1%. The 0.41% difference is not statistically significant. Chlorhexidine has comparable effectiveness and is safer, cheaper, and preferred by staff, so it is an alternative to iodine tincture.     

Phase Variation of Campylobacter jejuni 81-176 Lipooligosaccharide Affects Ganglioside Mimicry and Invasiveness In Vitro

The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM(2) and GM(3) gangliosides, with minor amounts of structures mimicking GD(1b) and GD(2). Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM(2) to GM(3) ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM(3) ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells.     

Hemagglutination of Human Type O Erythrocytes, Hemolysin Production, and Serogrouping of Escherichia coli Isolates from Patients with Acute Pyelonephritis, Cystitis, and Asymptomatic Bacteriuria

The purpose of this investigation was to study potential virulence factors associated with Escherichia coli urinary pathogens isolated from patients with urinary tract infection. These factors were compared with characteristics of normal-flora E. coli isolated from stool specimens of healthy individuals without a history of urinary tract infection. The potential virulence factor focused on in this study was hemagglutination (HA) of human type O erythrocytes by E. coli urinary pathogens. A total of 265 strains of E. coli isolated from patients with urinary tract infections were tested for their ability to hemagglutinate human type O erythrocytes; of these, 148 (56%) were HA positive. Only 6 of 36 fecal E. coli strains (17%) isolated from healthy controls were HA positive. This significant association of the presence of hemagglutinin on E. coli that causes urinary tract infections indicates the likelihood that HA is a marker of virulence. Only 12% (5 of 43) of Proteus mirabilis and 3% (3 of 104) of Klebsiella pneumoniae urinary isolates were HA positive. There was a trend for HA-positive E. coli to be isolated from patients with kidney infections and positive tests for antibody-coated bacteria rather than bladder infections and negative tests for antibody-coated bacteria, although the difference was not statistically significant. There was a significant correlation (P < 0.025) between hemolysin production and HA; 67% (69 of 103) of the isolates that produced hemolysin also hemagglutinated human type O erythrocytes. There was no significant correlation between HA and motility, although there was a trend for flagellated organisms to be non-hemagglutinators. There was a marked correlation between the presence of hemagglutinin and the serogroup of the E. coli isolate; serogroups O4, O7, and O50 were almost always HA positive (57 of 63; 90%). In contrast, serogroups O8 and O25 were rarely HA positive (2 of 30; 7%).     

Respiratory syncytial virus associated illness in high-risk children and national characterisation of the circulating virus genotype in South Africa.

BACKGROUND: There is limited information about respiratory syncytial virus (RSV) in high-risk children from developing countries or on the genotype characterisation of the circulating virus. OBJECTIVE: To define the proportion of children with RSV associated lower respiratory tract infections (LRTI) that had risk factors for severe disease and to genotype the circulating RSV strains across the country. STUDY DESIGN: A prospective study was performed in four distinct regions. During April 2000-December 2000 (period 1), all children, with LRTI or without underlying high risk factors for severe RSV disease were enrolled. During January to September 2001 (period 2), only children with LRTI with underlying high risk factors were enrolled. Nasopharyngeal aspirates were evaluated for RSV infection using an ELISA test. RSV isolates were also subtyped and genotyped. RESULTS: Fifty three (24%) of 220 children enrolled during period 1 had risk factors for severe RSV disease; in addition to which a further 38 high-risk children were enrolled during 2001. RSV was isolated from 16 (30%) of 53 and 37 (22%) of 167 high-risk and non-high risk children, respectively, P=0.31. High-risk children were more likely to require intensive unit care (25 vs. 2.7%, P=0.02) and were also more likely to be hospitalised for a longer duration (median 7 vs. 5 days, P=0.06) than non high-risk infants. Overall (periods 1 and 2), RSV was isolated from 34 (37.4%) of the 91 high-risk infants enrolled. Among high-risk children, those from whom RSV was isolated were more likely to require hospitalisation (73.5 vs. 54.4%, P=0.07) and admission to an intensive care unit (14.7 vs. 1.8%, P=0.03) than those from whom RSV was not isolated. Of 40 isolates subtyped during period one, 92.5% were subtype A. Further, 27 (83.3%) of 30 subtype A isolates genotyped during period 1 clustered with GA2. CONCLUSION: RSV is an important cause of LRTI among high-risk infants in a developing country such as South Africa. For the season in question, the genotype that was dominant in Johannesburg was isolated throughout the country, suggesting that successful genotypes may have the ability to spread nationwide.