Immuno-electronmicroscopy of fimbriae-like structures on Bordetella pertussis serotype 1.3

Fimbriae-like filaments were demonstrated on the surface of Bordetella pertussis, serotype 1.3, by negative staining and electronmicroscopy. Immunoelectronmicroscopy with a monoclonal antibody specific for strains possessing agglutinogen 3, and colloidal gold, gave strong labelling of these structures. However, incubation with adsorbed polyclonal anti-agglutinogen 3 serum gave only weak labelling of the distal parts of the filaments and of the bacterial surface. The different binding patterns of the two antisera suggested that the epitopes involved were dissimilar. Thus, agglutinogen 3, as defined by conventional adsorbed sera, appeared to be associated with the fimbriae-like structures but was not necessarily identical to the fimbrial subunit protein. The monoclonal antibody, however was more likely directed against the subunits of the fimbriae-like structures on serotype 1.3 bacteria.     

Characterization of serogroup A and B strains of Neisseria meningitidis with serotype 4 and 21 monoclonal antibodies and by multilocus enzyme electrophoresis.

The reactions of serogroup A strains of Neisseria meningitidis with one monoclonal antibody specific for serotype 21 and three different monoclonal antibodies specific for serotype 4 were compared with those of serogroup B strains previously assigned to serotype 4. Antibody binding was studied by enzyme-linked immunosorbent assay (ELISA), dot blotting, and immunoblotting. Characterization of the isolates by the electrophoretic mobilities of 14 metabolic enzymes showed 50 multilocus enzyme genotypes. All except two genotypes fell into three distinct clusters: I, IIa and IIb. The enzyme genotypes of serogroup B strains were mainly in cluster I, and 88% of the serogroup A strains had genotypes in clusters IIa and IIb. Serogroup B strains generally reacted with all three serotype 4 monoclonal antibodies in ELISA and dot blotting but with only two in immunoblots. Serogroup A strains showed two different reactions in the blotting methods: either binding of the serotype 21 antibody only or binding of this and two of the three serotype 4 monoclonal antibodies. Strains of the first pattern were in clusters I and IIa, whereas all but two strains in cluster IIb were of the second pattern. In ELISA, an additional reaction of two of the serotype 4 monoclonal antibodies with serogroup A isolates was observed. The different binding of these two monoclonal antibodies in ELISA and the blotting methods appeared to result from heat inactivation of the meningococcal cells and use of detergent-containing reagents in ELISA. The results show that the serotype of serogroup A strains is distinct from serotype 4 of serogroup B strains.     

Complement components, C1 activation and disease activity in SLE

Laboratory parameters were studied in 8 systemic lupus erythematosus patients during periods of high and low disease activity, mainly as defined by clinical criteria. Renal manifestations were present in 6 patients 5 of which showed antibodies to native DNA. C-reactive protein was raised in 3 patients. Only 1 of these showed a superimposed bacterial infection. Markedly high concentrations of C1r-C1s-C1 inactivator cOmplexes (C1r-C1s-Cl IA) in the sera provided direct evidence of C1 activation independent of disease activity. During active disease. C1r-C1s-C1 IA were correlated with C1q binding immune complexes as measured by solid phase, but not by fluid phase assay. Immunochemical concentrations of C1q, C4 and C3 and functional C2 were decreased in active SLE, consistent with sequential activation of the classical pathway. Discrepancies were noted between functional and immunochemical assay for C2 but not for factor B. Although essentially within the normal range, the levels of C1s, C4 binding protein, C5 and properdin were lower during active than during inactive disease. The concentrations of the factors B, I and H did not suggest involvement of the alternative pathway. 1 exceptional patient showed low factor B, a relative decrease of factor I and the presence of Bb fragments in plasma during active SLE. Markedly high factor D values were found. This could partly be explained by reduced renal function.     

A nasal whole-cell pertussis vaccine induces specific systemic and cross-reactive mucosal antibody responses in human volunteers

A whole-cell pertussis vaccine, each dose consisting of 250 microg of protein, was given intranasally four times at weekly intervals to six adult volunteers. All vaccinees responded with increases in nasal fluid IgA antibodies to Bordetella pertussis whole-cell antigen. Three vaccinees with high nasal antibody responses also developed increased serum IgA and IgG antibodies to this antigen. Salivary antibody responses to the whole-cell antigen, as well as antibodies in serum and secretions to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were negligible, except for a moderate increase in nasal fluid antibodies to FHA. Unexpectedly, the same vaccinees developed significant rises in nasal and salivary IgA antibodies to meningococcal outer-membrane antigens, whereas corresponding serum IgA and IgG antibodies were unchanged. Thus it appears that mucosal immunisation may induce secretory antibodies with broader specificities than can be found in serum.     

Sulfonamide resistance in Neisseria meningitidis isolates of clones of the ET-5 complex

A distinctive group of genetically closely related clones, as determined by multilocus enzyme electrophoresis, the ET-5 complex, has been responsible for an epidemic of meningococcal disease in Norway since the mid-1970's. Most isolates of the ET-5 complex from Norway are sulfonamide-resistant, serogroup B, and serotype 15:P1.16. Clones of the ET-5 complex that have been identified as the causative agents of recent outbreaks and epidemics in many other parts of the world show, outside Northern Europe, different associations of serotype protein antigens. We here report the analysis of sulfonamide susceptibility of isolates of the ET-5 complex from various geographic sources. There was no difference in resistance according to geographic source, serogroup, or serotype of the isolates, demonstrating that, in contrast to serotype and serogroup, sulfonamide resistance is an essentially invariant property of clones of the ET-5 complex.     

Absence of circulating antineutrophil cytoplasm antibodies (ANCA) in severe vasculitis associated with rheumatoid arthritis

Sixteen patients with classical rheumatoid arthritis (RA) complicated by severe vasculitis were studied and compared with a matched control group of 17 RA patients without vasculitis. A control group of 24 patients with unrelated disease was also included. Neither antineutrophil cytoplasmic antibodies (C-ANCA) nor anti-myeloperoxidase (anti-MPO) were found. Granulocyte specific antinuclear antibodies ("GS-ANA") were found in a higher frequency in the vasculitis group (75%) than in the RA control group (41%), but the difference was not statistically significant. No patient in the control group without RA had "GS-ANA".     

Outbreak of meningococcal disease in western Norway due to a new serogroup C variant of the ET-5 clone: effect of vaccination and selective carriage eradication

A new sulphonamide resistant (SR) C: 15:P1.7,16 meningococcal strain, a variant of the ET-5 clone, dominated in an outbreak of 22 cases in western Norway commencing in 1995. The first eight patients were 15-21 years old from the Nordhordland area, initiating a carrier study in the local high schools. Carriage of SR serogroup C meningococci was detected by routine methods and treated with a single dose of ofloxacin 400 mg. Of 20 treated carriers, 14 harboured the outbreak strain C: 15:P1.7,16. Vaccination of 4000 children, adolescents and close contacts of patients was also performed. After the intervention, 14 additional cases of meningococcal disease occurred, 8 due to the outbreak strain. However, incidence rates dropped from 180 to 30 per 100000 per year in the student population, but increased from 0 to 13 in the rest of the population in Nordhordland. Carriage eradication is not generally recommended in Norway. However, tracing and treating meningococcal carriage may have reduced transmission and disease in this outbreak situation.     

The role of viral infection in sudden deafness (author's transl)

A series of 35 patients with various degrees of sudden deafness were investigated in regard to recent or coexistent viral infection. The virological studies included 1) viral isolation by nasopharyngeal and faecal cultures; 2) viral serology for 20 different species of virus and the Paul Bunnel test; and 3) immunocomplex tests. In only two patients could a viral infection (a viral parotitis and an adenoviral infection) be proven (i.e. 6%). Immunocomplexes were found in 15 of 22 patients. Our studies, using conventional viral diagnostic tests, do not support the belief that viral infection is a common cause of sudden deafness. To solve the question whether viral infections play a part in the occurrence of sudden deafness these diagnostic aids must be complemented with modern immunological methods.     

Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency

OBJECTIVE: To analyse rheumatological manifestations, organ damage and autoimmune responses in a large cohort of patients (n = 45) with homozygous C2 deficiency (C2D) and long-term follow-up. METHODS: Medical records were reviewed and were supplemented with a mailed questionnaire for assessment of cardiovascular disease (CVD) risk factors. Organ damage was evaluated using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Causes for disability pensions were investigated. Autoantibodies were determined with established methods. RESULTS: Patients with rheumatological diseases had systemic lupus erythematosus (SLE, n = 12), undifferentiated connective tissue disease (n = 5) or vasculitis (n = 3). Judging from annual SLICC/ACR DI, C2D patients with SLE run a similar risk of development of severe disease as other patients with SLE. An increased rate of CVD was observed not explained by Framingham-related risk factors. Disability pensions were mainly related to rheumatological disease. The prevalence of anti-nuclear antibodies in C2D with SLE and of anti-SS-A was 25% while anti-RNP was found in 45%. Only one patient showed antibodies to dsDNA. Formation of anti-cardiolipin antibodies (aCL) appeared to be increased in C2D despite the absence of an anti-phospholipid syndrome. The prevalence of antibodies to the collagen-like region of C1q (C1qCLR) was also remarkably high and was not related to rheumatological manifestations. CONCLUSIONS: Severity of SLE in C2D is similar to that of SLE in other patients. Conventional risk factors do not explain the occurrence of CVD in C2D. The high prevalence of aCL and anti-C1qCLR indicates mechanisms through which impaired complement function promotes formation of autoantibodies.     

Comorbidity burden is not associated with higher mortality after out-of-hospital cardiac arrest*

Abstract

Objectives. We investigated whether comorbidity burden of comatose survivors of out-of-hospital cardiac arrest (OHCA) affects outcome and if comorbidity modifies the effect of target temperature management (TTM) on final outcome. Design. The TTM trial randomized 939 patients to 24?h of TTM at either 33 or 36?°C with no difference regarding mortality and neurological outcome. This post-hoc study of the TTM-trial formed a modified comorbidity index (mCI), based on available comorbidities from the Charlson comorbidity index (CCI). Results. Bystander cardiopulmonary resuscitation (CPR) decreased with higher comorbidity group, p?=?0.01. Comorbidity groups were univariately associated with higher mortality compared to mCI0 (HR_mCI1: 1.55, CI: 1.25–1.93, p?<?0.001, HR_mCI2: 2.01, CI: 1.55–2.62, p?<?0.001, HR_mCI ≥ 3: 2.16, CI: 1.57–2.97, p?<?0.001). When adjusting for confounders there was a consistent, nonsignificant association between level of comorbidity and mortality (HRm_C11: 1.17, CI: 0.92–1.48, p?=?0.21, HR_mCI2: 1.28, CI: 0.96–1.71, p?=?0.10, HR_mCI ≥ 3: 1.37, CI: 0.97–1.95, p?=?0.08). There was no interaction between comorbidity burden and level of TTM on outcome, p?=?0.61. Conclusion. Comorbidity burden was associated with higher mortality following OHCA, but when adjusting for confounders, the influence was no longer significant. The association between mCI and mortality was not modified by TTM. Comorbidity burden is associated with lower rates of bystander cardiopulmonary resuscitation after OHCA.