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Biomedical subjects

M Nurminen

Publications and source records attributed to M Nurminen.

At least 19 recordsLinked to original sources
PubMed1999

Haemolytic-uraemic syndrome caused by vero toxin-producing Escherichia coli serotype Rough: K-: H49.

The first case of haemolytic-uraemic syndrome (HUS) caused by Vero toxin-producing Escherichia coli (VTEC) which belonged to a novel serotype, Rough: K-: H49, is reported. The case was initially diagnosed as nephropathia epidemica caused by Puumala virus, but the subsequent diagnosis of HUS caused by VTEC was made after bacteriological investigation. The strain isolated fermented sorbitol produced VT2 toxin but not enterohaemolysin, nor did it carry the eaeA gene. In VTEC strains, the O antigen, the eaeA gene and enterohaemolysin production have been characterized as virulence-associated factors and believed to have an effect on pathogenesis of these strains to cause haemorrhagic colitis or HUS. The findings of this study demonstrate that there is a need for further studies to evaluate the pathogenetic mechanism of VTEC and need for easy diagnostic methods exploiting other properties than O157 antigen and non-fermentation of sorbitol to find all VTEC in human infections.

Adult↗
PubMed1999

Outer membrane permeability barrier in Escherichia coli mutants that are defective in the late acyltransferases of lipid A biosynthesis.

The tight packing of six fatty acids in the lipid A constituent of lipopolysaccharide (LPS) has been proposed to contribute to the unusually low permeability of the outer membrane of gram-negative enteric bacteria to hydrophobic antibiotics. Here it is shown that the Escherichia coli msbB mutant, which elaborates defective, penta-acylated lipid A, is practically as resistant to a representative set of hydrophobic solutes (rifampin, fusidic acid, erythromycin, clindamycin, and azithromycin) as the parent-type control strain. The susceptibility index, i.e., the approximate ratio between the MIC for the msbB mutant and that for the parent-type control, was maximally 2.7-fold. In comparison, the rfa mutant defective in the deep core oligosaccharide part of LPS displayed indices ranging from 20 to 64. The lpxA and lpxD lipid A mutants had indices higher than 512. Furthermore, the msbB mutant was resistant to glycopeptides (vancomycin, teicoplanin), whereas the rfa, lpxA, and lpxD mutants were susceptible. The msbB htrB double mutant, which elaborates even-more-defective, partially tetra-acylated lipid A, was still less susceptible than the rfa mutant. These findings indicate that hexa-acylated lipid A is not a prerequisite for the normal function of the outer membrane permeability barrier.

Acyltransferases↗
PubMed1999

Methodologic issues in epidemiologic risk assessment.

This paper reviews methodologic issues pertinent to the application of epidemiology in risk assessment and discusses concerns in the presentation of results from such an activity. Assessment of the health risks associated with occupational and environmental exposures involves four phases: hazard identification, i.e., the detection of the potential for agents to cause adverse health effects in exposed populations; exposure assessment, i.e., the quantification of exposures and the estimation of the characteristics and sizes of the exposed populations; dose-response assessment, i.e., the modeling for risk realization; and risk characterization, i.e., the evaluation of the impact of a change in exposure levels on public health effects. The risk-assessment process involves limitations of exposure data, many assumptions, and subjective choices that need to be considered when using this approach to provide guidance for health policy or action. In view of these uncertainties, we suggest that the provision of estimates of individual risk and disease burden in a population must be accompanied by the corresponding estimates of precision; risks should be presented in a sufficiently disaggregated form so that population heterogeneities are not lost in the data aggregation; and different scenarios and risk models should be applied. The methods are illustrated by an assessment on the health impacts of exposure to silica.

Decision Support Techniques↗
PubMed1998

Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung.

The differential diagnosis of mesothelioma, primary adenocarcinomas and pleural metastases frequently causes problems. We have used the comparative genomic hybridization (CGH) technique on 34 malignant mesotheliomas and 30 primary lung carcinomas (adenocarcinoma, including bronchoalveolar carcinoma and large-cell anaplastic carcinoma) to compare their copy number changes and to evaluate the use of CGH to distinguish between these two types of tumour. In mesothelioma, gains of genetic material occurred as frequently as losses, whereas gains predominated over losses in carcinoma. In mesothelioma, the most frequent changes were losses in 4q, 6q and 14q and gains in 15q and 7p, whereas gains in 8q, 1q, 7p, 5p and 6p were the most common changes in carcinoma. Amplification of KRAS2 was detected in two adenocarcinomas by Southern blot analysis. CGH showed gains in 12p in the same tumours. Statistically significant differences between the two types of tumour were detected in chromosomes X, 1, 2p, 4, 8q, 10q, 12p, 14q, 15q and 18q. When comparing the frequency of gains and losses between mesothelioma and lung carcinoma using discriminant analysis, the sensitivity of CGH to differentiate mesotheliomas from lung carcinomas was 81% and the specificity 77%. The differences in DNA copy number changes between the two types of tumour suggest that they are genetically different tumour entities. Although CGH cannot be used as a definitive discriminatory method, we were able to distinguish between mesothelioma and lung carcinoma in a large proportion of the abnormal cases.

Adenocarcinoma↗
PubMed1998

Development of the hip in diastrophic dysplasia.

We examined 50 patients with diastrophic dysplasia both clinically and radiologically. Two legally aborted fetuses were dissected. The mean age of the patients was 16.2 years (newborn to 38) and the mean follow-up was 11.4 years (3 months to 34 years). The fetal hips and MRI of newborn infants showed congruity and no significant joint deformity. Flexion contracture of the hip became evident later in 93% and was progressive. The radiological appearance of the proximal femoral ossific nuclei was delayed and in 17% of males and 28% of females the ossific nuclei had not appeared by the age of 12 years. Radiological measurements differed considerably from reference values and were related to the rapid and progressive restriction of rotational movement and the increase in flexion contracture. The typical findings were flattening and inferomedial bulking of the femoral head and a double-hump deformation. The changes in the hip led to secondary osteoarthritis before early middle age. We describe the clinical and radiological measurements which define the early degeneration of the joint.

Abortion, Legal↗
PubMed1997

An epidemiological study of patterns of condylar fractures in children.

OBJECTIVE: To find out how the site and type of condylar fracture are affected by its aetiology and the age and sex of the patient. DESIGN: Retrospective study. SETTING: Tertiary referral centre, Finland. MATERIAL: Radiographs of 101 children (aged 15 years or less) with 119 condylar fractures. MAIN OUTCOME MEASURES: Site of fracture and degree of displacement. RESULTS: A total of 26 of the 119 fractures were intracapsular (22%) and 93 (78%) extracapsular. Only among patients less than 6 years of age was there a preponderance of intracapsular fractures (7/12 fractures in 10 patients, 58%). In the older children 78% (83/107) were in the condylar neck. There were few subcondylar fractures (5/119, 4%). Only 6 fractures were displaced (5%). Dislocation of the condyle from the glenoid fossa was common in all age groups. CONCLUSION: The site of condylar fracture is age related, but not associated with sex or aetiology.

Accidents, Traffic↗
PubMed1997

Reanalysis of the occurrence of back pain among construction workers: modelling for the interdependent effects of heavy physical work, earlier back accidents, and aging.

OBJECTIVES: To re-examine the relation between heavy physical work and the occurrence of sciatic pain among construction workers reported previously to be absent in an epidemiological study. METHODS-Poisson log linear regression was used to model for the frequency of sciatic pain among concrete reinforcement workers and maintenance house painters with adjustment for the interactive effects of earlier back accidents and aging that modified the relation. RESULTS: Concrete reinforcement work not only had a direct effect on the frequency of sciatic pain, but it also contributed significantly to the risk indirectly through earlier back accidents. The risk of sciatic pain increased from age 25 to 54 in a different manner for a worker depending on his occupational group and record of back accidents. CONCLUSIONS: Epidemiological studies on low back pain need to be analysed with sound methodology. This is important in view of future meta-analyses that will be performed for the purpose of providing guidelines on the prevention of back disorders in heavy physical work.

Accidents, Occupational↗
PubMed1997

Statistical significance--a misconstrued notion in medical research.

The P-value is the significance probability of obtaining a value of the test statistic that is as extreme, in relation to the null hypothesis, as that observed. Medical researchers may, in some situations, disagree on its appropriate use or on its interpretation as a summary measure of consistency with the null hypothesis in a particular data set. More informative statistical measures such as the likelihood ratio and the Bayesian posterior probability have been suggested for drawing inferences from clinical trials and epidemiologic studies. Causal inference is not statistical in nature; rather it strives to provide scientific explanations or criticisms of proposed explanations that would describe the observed data pattern. In this context, it is important to remember that a finding may not be medically important, or a causal hypothesis may even not be true even if a study shows a significant P-value.

Bayes Theorem↗
PubMed1996

Methanol extracts LPS from deep rough bacteria.

Several rough strains of Escherichia coli, Salmonella enterica and Proteus mirabilis were cultivated in the presence of (14C)acetate, which incorporated into their phospholipids and lipopolysaccharide. Phospholipids were removed from the cells with ethanol extraction. However, as shown by thin layer chromatography, methanol additionally extracted remarkable quantities of lipopolysaccharide from deep rough strains, but not from bacteria containing complete or nearly complete core.

Chromatography, Thin Layer↗
PubMed1996

Immunization with meningococcal class 1 outer membrane protein produced in Bacillus subtilis and reconstituted in the presence of Zwittergent or Triton X-100.

Vaccines against group B meningococcal infection tested in several field trials have all been extracts of the outer membrane of the bacteria. We have developed a single component vaccine based on the class 1 outer membrane protein P1 produced in a heterologous host Bacillus subtilis, and describe here its immunizing properties. The purified and denatured protein BacP1 was solubilized in SDS, followed by addition of an excess of a second detergent (Zwittergent 3-14 or Triton X-100). Immunization of mice showed that this process led to at least partial reconstitution of the native epitopes of the P1 protein. The immunogenicity of these BacP1 detergent preparations was further improved when administered together with adjuvants (aluminium hydroxide or monophosphoryl lipid A); high titers of antibodies were thus obtained with vaccine doses as low as 2 micrograms of protein. The antibodies elicited were essentially of IgG and reactive with protective epitopes present on the surface of meningococci. The bactericidal activity of the sera showed a good correlation to antibodies of the IgG1 and IgG2 isotypes, concomitantly increased in most sera.

Animals↗
PubMed1996

Pocket-sized spirometer for monitoring bronchial challenge procedures.

Diagnosis of occupational asthma is verified by inhalation challenge testing when frequent monitoring of peak expiratory flow (PEF) or forced expiratory volume in 1 s (FEV1) is needed. FEV1 measurements also allow frequent monitoring of changes in small airways. For the follow-up of lung function of suspected occupational asthma, a reliable, personal and mobile device is needed. We studied the accuracy of a pocket-sized spirometer, Micro Plus Spirometer (MP), compared with our former combination of two devices, i.e. the values of forced expiratory volume in 1 s (FEV1) with those measured with the Vitalograph bellow spirometer (V); and the peak expiratory flow (PEF) values with the values obtained with a Wright PEF meter (W). In healthy control subjects, the values of FEV1 obtained with Micro Plus correspond well to those obtained using a bellow spirometer (R = 0.97) and the mean difference (MP-V) was -0.06 1 irrespective of the mean FEV1 value. W gives smaller PEF values than the MP; the mean difference in PEF (MP-W) was 44 1 min-1, but the values increased linearly with increasing flow. The poor relation between PEF values might be based on the low reliability of the Wright device. In patient follow-up, the FEV1 values measured with MP and V showed a good correlation (R = 0.99). The PEF values in patients increase linearly measured with W vs. MP with increasing flow values. In conclusion, we found the pocket-sized spirometer a handy and useful device for monitoring bronchial challenge procedures in patients with suspected occupational asthma. The number of exhalations during the challenge test follow-up is lessened when FEV1 and peak expiratory flow (PEF) can be measured simultaneously.

Adult↗
PubMed1996

Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma.

In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p < 0.001), between the concentrations of ABs and amphibole asbestos fibres in lung tissue (r = 0.73; p < 0.001), and between the concentration of ABs in BAL fluid and the concentration of amphibole asbestos fibres in lung tissue (r = 0.64; p < 0.001). In patients who had been exposed mainly to commercial anthophyllite, significantly higher concentrations of ABs were observed per total pulmonary amphibole fibre burden, as compared to patients whose main exposure was to crocidolite/amosite. The anthophyllite fibres in lung tissue were longer than the crocidolite/amosite fibres. The relationship between asbestos body counts in lung tissue and in bronchoalveolar lavage fluid was similar to previous international observations. When using the asbestos body count to predict the underlying total pulmonary amphibole asbestos burden in Finnish patients, however, it should be borne in mind that the relationship between the two parameters seems to be different with anthophyllite as compared to crocidolite/amosite fibres.

Adult↗
PubMed1996

Pulmonary asbestos bodies and asbestos fibers as indicators of exposure.

OBJECTIVES: The aim of the study was to analyze the correlation between pulmonary concentrations of asbestos bodies and asbestos fibers and to characterize asbestos body counts from lung tissue of Finnish patients occupationally exposed and unexposed to asbestos. METHODS: Ninety-nine surgically treated lung cancer patients were investigated. The number of asbestos bodies in iron-stained 5-micrometers histological lung tissue sections was determined by optical microscopy, and the pulmonary concentration of asbestos fibers was assessed by scanning electron microscopy. The correlation between asbestos body and asbestos fiber counts was calculated with linear regression. The asbestos body and asbestos fiber concentrations were also compared with exposure history according to a personal interview of the patients. RESULTS: The average number of asbestos bodies ranged from < 0.1 to 750 asbestos bodies per tissue section. All the cases with definite exposure showed an average of at least one asbestos body per tissue section. An average of at least one asbestos body per section was, however, detected in 34% of the patients with unlikely exposure. The regression equation log (AF) = -0.429 + 0.600.log (AB) was found to predict the concentration of asbestos fibers (AF, 10(6) fibers.g-1) corresponding to a given number of asbestos bodies (AB) in a section of lung tissue. CONCLUSIONS: The background level of asbestos bodies in the lungs of patients with no specific asbestos exposure seems to be higher in Finland than in other countries. In medicolegal cases, the methodological variation involved in asbestos fiber and asbestos body counting must be recognized and all available exposure data should be used to produce the best possible estimate of the exposure.

Adult↗
PubMed1995

Heterologous production of the P1 porin of Neisseria meningitidis in bacillus subtilis: the effect of an N-terminal extension on the presentation of native-like epitopes.

The major outer membrane protein P1 (class 1) of Neisseria meningitidis has been produced as inclusion bodies in Bacillus subtilis with the aim to develop a vaccine based on it. The protein produced in high yield in B. subtilis contained an N-terminal extension of 11 amino acid residues which was found to be necessary for expression in the production system. In the present study we asked whether or not the removal of this extension would effect the conformation of this protein in liposomes as judged by its immunogenic properties. A methionine was engineered in front of the mature P1 protein to provide a chemical cleavage site for CNBr to remove the extension. The CNBr-cleaved protein, complexed with phospholipids, elicited high titers of antibodies binding to the meningococcal cells similarly to the noncleaved protein. This suggests that the BacP1 protein can serve as an effective vaccine component irrespective of the presence, or absence, of this N-terminal extension.

Animals↗
PubMed1995

The Neisseria meningitidis outer membrane protein P1 produced in Bacillus subtilis and reconstituted into phospholipid vesicles elicits antibodies to native P1 epitopes.

Class 1 outer membrane protein (P1) of Neisseria meningitidis group B is considered a promising vaccine candidate because P1 subtype-specific antibodies have been shown to be protective in an animal model. We have previously described the production of P1 in the Gram-positive Bacillus subtilis as intracellular inclusion bodies, from which the protein (BacP1) is easily purified (Nurminen et al., Mol. Microbiol., 1992, 2499-2506). We show here that the purified BacP1 can be reconstituted into phospholipid vesicles with the formation of the native immunodominant surface epitopes. The detergent-solubilized, completely denatured BacP1 was fused with phospholipid-detergent micelles during detergent removal by dialysis or gel filtration to yield protein-lipid vesicles (liposomes). When mice were immunized with these liposomes, they produced high titers of antibodies reacting in a P1 subtype-specific manner with meningococcal cells indicating the presence of conformation-dependent P1-specific epitopes in the liposomes. The results suggest that a vaccine candidate for meningococcal disease could be developed from the BacP1-liposomes. They furthermore demonstrate the feasibility of refolding a denatured outer membrane protein, which has never been exposed to lipopolysaccharide, into a native-like conformation.

Amino Acid Sequence↗