Cross-reactivity between Chlamydiazyme and Acinetobacter strains.
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Biomedical subjects
Publications and source records attributed to M Nurminen.
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Peripheral blood lymphocytes were incubated with glutaraldehyde-fixed Salmonella bacteria. This resulted in rapid activation of nonspecific cytotoxic potential of the lymphocytes. Both originally noncytotoxic, high-density Percoll-fractionated cells, and cytotoxic natural killer (NK) cell-enriched low-density cells were activated. The induction of originally noncytotoxic cells into activated killer (AK) cells was apparently independent of interferon (IFN), whereas the activation of the NK cell-enriched fractions also involved IFN production. Neither the AK nor NK activity were associated with significant bactericidal activity. The IFN-independent induction of AK activity was not dependent on the O-antigenic polysaccharide part of the lipopolysaccharide (LPS) on the bacterial cell surface, because both smooth (S) strains with differing O-antigenic structures (S-4,12 and S-6,7) and a rough (Re) strain without O-antigen were effective inducers. Isolated LPS, and especially alkali-hydrolyzed (O-deacylated, detoxified) LPS (ALPS) interfered with the induction of cytotoxicity. At concentrations of 10 to 30 micrograms/ml, ALPS totally inhibited the induction of AK activity without affecting the endogenous NK activity. Thus contact with bacteria can lead to the emergence of AK cells, and a bacterial product can effectively block this activation. These phenomena stress the complexity of interactions with host defenses that can take place during bacterial infection.
The antibodies responsible for the protective effect of sera obtained by immunizing rabbits with the major outer membrane protein porin of Salmonella typhimurium complexed with LPS (Kuusi et al., Infect. Immun., 1981; 34:328-332) were found to be directed to the O antigen. They were effective in very small concentration which probably accounted for our failure to identify them before or now by in vitro methods. Although both the porin and the LPS in the complexes used for immunization were isolated from rough (R) form organisms devoid of O antigen by all usually applied criteria, the antigen contained a small amount of smooth form LPS, most probably derived from a slight leakiness of the rfa mutation responsible for the R character. The small amount of contaminating O antigen was apparently rendered highly immunogenic by complexation with the outer membrane protein.
A fresh human isolate of Yersinia enterocolitica serotype 03, and its derivative that had lost the virulence-associated 46-Md plasmid, were grown under defined conditions and compared for their outer membrane protein and cell surface structure. Under these conditions, the virulent strain grown at 37 degrees C expressed one major outer membrane protein (47 kd) not present in the plasmidless strain or in either strain grown at room temperature. A 200-kd protein also seen in the same preparations was shown to be an oligomer composed of the 47-kd protein subunits. Four different electron microscopic techniques showed tack-like projections covering the surface of those bacteria that expressed the 47-kd protein. These were specifically labeled with antibody to the 47-kd protein. This surface structure appeared to mediate aggregation (auto-agglutination) of the bacteria bringing their surfaces into unusually close apposition.
The antigenic properties of the lipopolysaccharide (LPS) of Chlamydia trachomatis L2 were investigated. By means of passive hemolysis, passive hemolysis inhibition, and absorption experiments, it was shown that antiserum raised against chlamydial elementary bodies contained at least two different antibody specificities which reacted with different antigenic determinants of chlamydial LPS. One of these antibodies cross-reacted with enterobacterial Re LPS, recognizing a structure which is shared by both LPSs, whereas the reactivity of the second antibody was restricted to chlamydial LPS. The former antibody could be absorbed with Salmonella minnesota Re LPS, whereas the latter was not affected by this absorption. Therefore, chlamydial LPS possesses two distinct antigenic determinants, one of which is C. trachomatis specific, the other of which is responsible for the cross-reactivity with enterobacterial Re-type LPS. Both antigenic determinants were destroyed during mild acid-catalyzed hydrolysis. It was further shown that free chlamydial lipid A exhibits antigenicity that cross-reacts with free enterobacterial lipid A. This antigenicity, however, as in enterobacterial LPS, is present in a cryptic form, i.e., it is unmasked only after acid hydrolysis of LPS.
The group-specific antigen of Chlamydia trachomatis serotype L2 was chemically analyzed. It is composed of typical lipopolysaccharide (LPS) components, i.e., D-glucosamine, long-chain 3-hydroxy fatty acids, 2-keto-3-deoxyoctonic acid, and phosphate in a molar ratio of approximately 2:5:3:2.6, respectively, resembling enterobacterial LPS of the Re chemotype. For the first time, 3-hydroxydocosanoic acid (3-OH C22:0) was found as an LPS constituent.
The value of several serological tests was assessed by studying sera from 30 women with clinical findings of perihepatitis and a high chlamydial antibody titre in the indirect immunofluorescence antibody test (IFAT). The other tests included the complement fixation test and enzyme immunoassays in which the antigen comprised either partially purified particles (EIA kit) or purified major outer membrane protein (MOMP EIA) of Chlamydia trachomatis L2 or lipopolysaccharide isolated from an Re mutant of Salmonella (Re LPS EIA). High IgG titres were noted in most (88-96%) of the patients by MOMP EIA and EIA kit, and in fewer patients (50%) by Re LPS EIA or complement fixation test. Seroconversion was found in 11-44% of the patients for IgG and in 28-36% for IgM; high IgG titre was thus the best diagnostic indicator for each test. The enzyme immunoassay tests have the advantage of being automated either with partially purified corpuscular or purified MOMP antigen and would allow a sensitive easy screening for chlamydial aetiology of women with pain of the right upper quadrant.
The cardiovascular mortality of a cohort of 343 Finnish men exposed for at least five years to carbon disulphide (CS2) in a viscose rayon plant has been monitored prospectively from 1967 to 1982. The results from the first five years of follow up in 1972 showed a 4.7-fold excess mortality for ischaemic and other heart diseases (ICD A83-A84) compared with a comparable reference cohort of paper mill workers. After 1972 a preventive intervention programme instituted at the rayon plant included removing all workers with coronary risk factors from exposure. Thus only 19% of the exposed cohort continued to be exposed in 1977 compared with 53% in 1972. Moreover, exposure levels were reduced after 1972 in compliance with the set hygienic standard of 10 ppm. These measures were reflected in a normalisation of the risk of cardiovascular death; the relative risk was 1.0 in the period after the intervention (1 July 1974 to 30 June 1982), whereas it had previously been 3.2 (from 1 July 1972 to 30 June 1974). The risk of a fatal heart attack remained at 11.6% throughout the 15 year follow up period (95% confidence limits 8.5%-15.4%) among the exposed compared with 7.8% (5.3%-11.2%) among the unexposed. The entire risk difference of 3.8% was accumulated during the first seven years of follow up. Thus we can estimate that 59 CS2-related cardiovascular deaths would have occurred during the next eight years (instead of the actual 19 deaths) had there been no preventive action. Calculations yielded a preventive fraction of 68%.
A case-referent study was undertaken to investigate the associations between formaldehyde exposure and respiratory and related cancers. Fifty-seven such cancers from a retrospective cohort of male woodworkers formed the case group. They were matched by year of birth with 171 referents. Exposure to formaldehyde was assessed with job-exposure matrices. The median of the time-weighted average concentration was about 1 ppm, and the mean duration of exposure was 10 years among the exposed. Odds ratios (OR) were calculated for formaldehyde exposure (1.44), peak exposure to formaldehyde (1.26), and exposure to formaldehyde-containing wood dust (1.22). None of the values exceeded unity with statistical significance. Allowance was also made for a 10-year period from the onset of exposure. Birth year, cigarette smoking and exposure to wood dust, chlorophenols, pesticides, and terpenes were controlled by stratification. The adjusted ORs did not change appreciably. The highest OR was 1.95 for formaldehyde exposure without allowance for minimum latency, adjusted for exposure to terpenes. No exposure-response relation was observed for the level, duration, or dose (ppm-years) of formaldehyde exposure. The result is nonpositive and may be explained by absence of effect, by too short a follow-up, or by insufficient power for detecting a mild excess risk.
Sera from 30 infants with suspected chlamydial pneumonitis were studied by enzyme immunoassay (EIA) with three antigens: reticulate bodies (RB), purified major outer membrane protein ( MOMP ) of Chlamydia trachomatis strain L2, and purified lipopolysaccharide from Re mutants of Salmonella (Re LPS), which shows complete cross-reaction with chlamydial glycolipid. The immunofluorescence test (I/RB IFAT), which detected IgM antibodies (titer of greater than or equal to 1:64) in 16 patients whose clinical picture was consistent with chlamydial pneumonitis, was the standard method. EIA measured IgM antibodies to the purified antigens but not to RB; 15 sera were positive with the MOMP antigen and two with the Re LPS antigen. High-titered IgG antibodies were detected by I/RB IFAT in 15 and by MOMP EIA in 13 of the 30 sera. By the RB EIA, 17 sera were positive. The MOMP EIA was thus as sensitive and specific as the I/RB IFAT. Because the EIA can be automated, it would make possible the screening of all children younger than six months of age with respiratory-tract symptoms and IgM antibodies to Chlamydia.
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The lipopolysaccharides (LPS) of Chlamydia trachomatis, Acinetobacter calcoaceticus var. anitratus, and Re mutants of Salmonella sp. were shown to share related immunodeterminants , as demonstrated by double immunodiffusion and immunoblotting from sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. The cross-reactive material in the extracellular slime of A. calcoaceticus var. anitratus was shown to be released LPS. The Acinetobacter LPS was found to separate in sodium dodecyl sulfate-polyacrylamide gel electrophoresis into three fractions. The cross-reactive component was the fraction migrating fastest, at a rate identical to Re-type LPS of Salmonella sp. The Acinetobacter LPS could be used as antigen in complement fixation assays performed on paired sera of patients with chlamydial pneumonia; it gave results identical to those of the chlamydial complement fixation glycolipid antigen conventionally used in such assays in 9 of 10 patients.
The career and work arduousness of a population of retired iron ore miners and their contemporaries who continued to work were investigated to find out what aspects of work history were associated with disability pensioning. The retired group had entered the mining industry at a more advanced age than the referents. The retired miners had also started at more strenuous tasks. Later they changed to lighter tasks, but were less often promoted in their career. The risk of early retirement seems thus to be related to the essential indicators of one's progress in the mining vocation.
A strong immunological cross-reaction between a major glycolipid antigen of Chlamydia and the innermost (Re) core of the lipopolysaccharide of enteric bacteria was demonstrated with the aid of mutants in which the Re structure is exposed. The chlamydial glycolipid resembled the Re lipopolysaccharide in molecular size, solubility, and endotoxic properties and may thus be functionally equivalent to lipopolysaccharide, an essential and characteristic component of the outer membrane of Gram-negative bacteria.
Exposure to noise, the availability and the use of ear protectors, and the adequacy of the medical surveillance of noise-exposed workers were surveyed in the small industry of Finland in order to provide information for the development of occupational health care. One hundred workplaces were chosen by random sampling to represent the small industry (personnel 5-49) in the province of Uusimaa. About a third (32%) of the workers (n = 1181) were exposed to a noise level of at least 85 dB (leq) when at work. However, the prevalence of noise exposure varied greatly, from 3 to 82% according to the type of industry. One in five workers exposed to noise was under periodic medical surveillance (audiogram). Ear protectors were available to about a half of the workers. Fewer than half of the workers with ear protectors at their disposal actually used them. Preventive measures are discussed with respect to noise-induced hearing loss among the personnel working in small industry.
One hundred firms were chosen by random sampling in order to survey the conditions of illumination in the small industry of Finland. The illumination of each worker's (N = 1181) work level was measured with a cosine corrigated luxmeter. Blend, the evenness of illumination, and the location of the light source were additional criteria used to evaluate illumination. Of the workers, 23% had moderately poor and 20% had poor illumination. Great differences in the prevalence of poor illumination were found for different industries and occupations. Work requiring precision was illuminated better than coarser work. The results of this study indicate that improved illumination in small industry would prevent undue work load and increase productivity.
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Etiologic research is easily invalidated by wrong conclusions based on the use of dubious methods of study design or data analysis. This paper discusses three central types of validity concepts, namely, selection bias, information bias, and confounding bias. Bias is defined in statistical terms as a misrepresentation of an effect measure, such as disease rate ratio. The discussion is presented basically within the framework of fourfold frequency table data to investigate the dependence of the presence or absence of a disease on a dichotomous exposure variate. A brief review of the statistical strategies and techniques available for controlling confounding is given. The issue of properly measuring a true confounder is dealt with in some detail because of its importance for the avoidance of biased estimates. The presentation concentrates on pointing out the direction and magnitude of the distortion caused by the operation of these sources of error.