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Biomedical subjects

M Nurminen

Publications and source records attributed to M Nurminen.

At least 19 recordsLinked to original sources
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

Health status and exposure of workers at a pilot brown coal liquefaction plant in Australia, 1985-1991.

In 1985, Brown Coal Liquefaction (Victoria) Pty Ltd (BCLV) commenced operation of a pilot plant that investigated the feasibility of producing oil from brown coal. The plant operated for five years. This study aimed to use exposure and health information routinely collected by the company to characterize various health parameters of the workforce and to investigate whether any adverse health measures were exposure-related. About 1680 persons were employed at some time or other by BCLV, and the primary study population consisted of 408 workers who had a medical examination at the end of employment and who consented to being in an epidemiological study. Reported photosensitivity was associated with higher cumulative skin exposure (RR = 1.85; 95% CI = 1.22-2.78), with an exposure-response relationship of increasing risk with increasing skin exposure being suggested. There was no consistent evidence that chemical exposure at BCLV had any negative effect on the haematological, biochemical, endocrine or lung function of workers at the plant. However, the maximum follow-up period of less than eight years limits the ability of the study to detect any emerging chronic effects.

Adult↗
PubMed1994

Determination of 24 variously sulfated galactosaminoglycan- and hyaluronan-derived disaccharides by high-performance liquid chromatography.

In this report we describe a very sensitive high-performance liquid chromatographic method for the determination of 24 nonsulfated and variously sulfated disaccharides present in chondroitin sulfates, dermatan sulfates, and hyaluronic acid. The method is superior to others in that monosulfated disaccharides at either C-2 or C-3 of the uronic acid moieties and mono-, di-, and trisulfated disaccharides containing N-sulfated galactosamine as well as non-, mono-, and oversulfated disaccharides derived from iduronic acid can be determined. Following chondroitinase digestions of tissue extracts or purified hyaluronic acid, chondroitin sulfate, and dermatan sulfate, the non-, di-, and trisulfate delta-disaccharides, are separated by direct injections into HPLC, whereas the monosulfated delta-disaccharides are chromatographed after a simple reduction of the galactosamine carbonyl group with sodium borohydride. The various sulfated delta-disaccharides are separated on an amino column (Econosphere NH2) and recorded at 231 nm. The column is eluted isocratically with 5 mM sodium dihydrogen orthophosphate, pH 2.55, for nonsulfated delta-disaccharides; 50 mM sodium dihydrogen orthophosphate, pH 2.50, for reduced monosulfated; and 50 mM sodium sulfate-10 mM sodium acetate, pH 5.0, for the separation of di- and trisulfated delta-disaccharides. A linear detector response was obtained for injections up to 50 micrograms of delta-disaccharides. As little as 5-8 ng of nonsulfated, 8-11 ng of monosulfated, 12-15 ng of disulfated, and 25-30 ng of trisulfated delta-disaccharides can be reliably detected. Application of this HPLC method to the analysis of various glycosaminoglycans in conjunction with chondroitinase AC, ABC, or B digestions and sulfatase hydrolysis adds to the knowledge of the structural spectrum of the galactosaminoglycans. It was thus possible to identify 24 different disaccharides in chondroitinase-susceptible glycosaminoglycans, including all C-5 epimeric disaccharides and those sulfated at C-2 or C-3 of the uronic acids and at the amino group of the galactosamine.

Animals↗
PubMed1994

Risk factors predicting chronic rejection of renal allografts.

Chronic rejection is clinically defined as a gradual but progressive impairment of renal allograft function in the absence of other specific causes. The risk factors predisposing to chronic rejection are incompletely known. In this prospective single-center project, logistic regression analysis was used to study the long-term outcome of 94 consecutive first renal allografts in relation to 10 potential risk factors. Whether serum lipid levels, histopathological changes or the mode of immunosuppressive therapy had a predictive value for chronic rejection was of special interest. The risk factors for renal allograft outcome were determined 2 years after the transplantation, when graft function was still normal, and the results were evaluated 2 years later. Occurrence of acute rejections, cold ischemia time, the high-density lipoprotein cholesterol level, and the high-density lipoprotein and total cholesterol ratio were not significant predictors of graft outcome. In a univariate analysis, triglyceride, total cholesterol, and low-density lipoprotein cholesterol level, and donor age were significantly related to graft outcome. In a logistic regression analysis, triple immunosuppressive therapy was better than any double-drug regimen in preventing the deterioration of renal allografts. Incipient histological changes in graft biopsy, quantitated as the "chronic allograft damage index," was the most important single predictor of chronic rejection. The effect of both the histological changes and low-density lipoprotein cholesterol on adverse graft outcome was level dependent.

Adult↗
PubMed1994

Is there an association between pleural plaques and lung cancer without asbestosis?

OBJECTIVES: A recent review or meta-analysis of epidemiologic studies concluded that persons with asbestos-related pleural plaques do not have an increased risk of lung cancer in the absence of parenchymal asbestosis. The reviewer inferred that this conclusion provided indirect supportive evidence for the proposition that asbestosis is a necessary precursor of asbestos-related lung cancer. The objective of the present communication is to contest these claims. METHODS: Finnish epidemiologic data and population statistics were used to estimate the apparent risk ratio of lung cancer associated with radiographic signs of pleural plaques. Power calculations were applied to compute the needed population sizes to demonstrate that the association is statistically significant. RESULTS: Unrealistically large population studies would be needed to observe the statistical relation between pleural plaques and lung cancer, quantitated as a risk ratio of 1.1, resulting from relatively low levels of environmental asbestos exposure. In realistic and valid epidemiologic studies on heavily exposed subpopulations, a two- or threefold risk can be identified. CONCLUSIONS: Uninformative studies should not be interpreted as providing suppressive evidence that pleural plaques are a noncausal risk indicator of lung cancer. Even for the null hypothesis, the inference that asbestosis is a necessary causal link between asbestos and lung cancer is illogical.

Adult↗
PubMed1994

Clinical utility of liquid-chromatographic analysis of effusions for hyaluronate content.

A previously described HPLC method for determining hyaluronate in effusions was used to analyze a consecutive series of effusions from 1039 patients with pleural fluids and from 571 patients with peritoneal fluids. A mesothelioma was verified histologically in 50 of the cases. The results were used to estimate the clinical utility of the analysis. With a cutoff of 75 mg/L for hyaluronate-derived uronic acid, assay specificity for a malignant mesothelioma was 100% and the sensitivity 56%. Only 20% of the effusions from the mesothelioma patients showed no evidence of increased production of hyaluronate. Cytological smears from the associated cell pellets were evaluated as malignant or suspicious for malignancy in only 28% or in a further 46% of the mesothelioma cases, respectively, leaving 30% of the pellets as cytologically false-negative. We also analyzed effusions from selected cases submitted from other hospitals, 154 of which had been diagnosed histologically as mesotheliomas. Concentrations of hyaluronate were increased in these cases too, but a considerable proportion of the samples showed evidence of losses of hyaluronate; consequently, the sensitivity of the assay in these samples was lower.

Ascitic Fluid↗
PubMed1992

Localized pleural plaques and lung cancer.

In a mass chest radiography survey conducted in 1971 for 7,986 residents of three Finnish communities, 604 subjects (7.6%) with pleural plaques but not other asbestos-related radiographic signs were identified. The same number of referents, each individually matched to each plaque carrier on sex, birth year, and community, was selected from among persons in the same source population with no pleural plaques. The two groups were followed for investigation of incidence of lung cancer during 1972-1989. Twenty-eight of those with plaques and 25 referents contracted lung cancer (crude conditional RR = 1.1; CL95 = 0.7, 1.9). The application of the proportional hazards model, with adjustment for sex, age, and residence, resulted in a hazard ratio of 1.1 (CL = 0.6, 1.8). The risk ratio estimate may be biased; hence, the result is inconclusive in regard to the predictive assessment of lung cancer risk among carriers of pleural plaques.

Adult↗
PubMed1992

Assessment of excess risks in case-base studies.

Miettinen and Caro (J Clin Epidemiol 1989; 42: 325-331) [6] put forth principles of non-experimental assessment of excess risks in case-base studies; in such a design, risk difference is assessed by estimating the denominators of the proportions of cases among exposed and comparable unexposed subjects by means of a representative sample from the base population of the study. They provided appropriate formulations for the point estimation of risk differences for various exposure patterns with allowance for covariables by means of stratified analysis. However, in small samples point estimates can be uncertain. In this paper, first, likelihood-based statistics are derived which can be used for interval estimation (and also point estimation and significance testing) of risk differences. The unified approach generalizes to stratified analysis. Second, the procedure is parameterized for inferences about risk ratios using a chi-square function in analogy with the profile likelihood method for full cohort analysis. Third, the approach is extended from the study of a binary exposure variable to a risk function analysis under the Poisson regression model. The suggested estimation procedure is conceptually clear and computationally simple in that the modelling, unlike the models considered by Prentice (Biometrika 1986; 73: 1-11) [3] for the analysis of case-base data, focuses directly on the comparison of risks between exposure categories in the study base and thus involves no covariance between the cases and the base sample.

Case-Control Studies↗
PubMed1992

The class 1 outer membrane protein of Neisseria meningitidis produced in Bacillus subtilis can give rise to protective immunity.

The class 1 outer membrane protein of Neisseria meningitidis B:15:P1.7,16 was expressed in Bacillus subtilis in high yield as intracellular aggregates. These were easy to isolate and the protein (called BacP1) could be solubilized under denaturing conditions. Sera of mice immunized with thus-solubilized BacP1 contained high titres of antibodies that reacted with the class 1 protein of the meningococcal envelope in immunoblots but did not react with native meningococcal envelope in enzyme immunoassays (EIA) or with intact meningococci in bactericidal assays. However, when the BacP1 protein was complexed with heterologous (Salmonella) lipopolysaccharide, the ensuing sera reacted with meningococcal envelope preparations in both EIA and immunoblots, showed subtype-specific bactericidal activity, and were protective in an infant rat meningitis model.

Amino Acid Sequence↗
PubMed1992

Bacterial motility is a colonization factor in experimental urinary tract infection.

In an experimental urinary tract infection of the mouse, colonization of the urinary bladder by isogenic strains of Salmonella enterica serovar Typhimurium was found to depend on the motility of the bacteria. Strains were obtained by genetic recombination between a highly motile O-6,7 and a poorly motile O-4,5,12 strain. The O antigen did not interfere with the colonization, whereas motility did; flagellated and motile O-6,7 and O-4,5,12 bacteria colonized the bladder equally well.

Animals↗
PubMed1992

Prediction of silicosis and lung cancer in the Australian labor force exposed to silica.

Empirical models for risk, based on recently published epidemiologic data, and simple prediction formulas were used to predict the occurrence of silicosis and lung cancer in the Australian labor force currently exposed to crystalline silica dust. As a result of an 0.9 (range 0.4-1.9)% average lifetime risk, approximately 1010 (range 380-2410) silicosis cases were predicted for the next 40 years among the estimated 136,400 men exposed at current silica dust levels [0.01-0.8 (average 0.094) mg.m-3]. Approximately 630 extra lung cancer cases (95% confidence interval 120-1320) would appear with an average excess risk of 0.5 (interval 0.1-1.1)%, the proportion of silica-induced lung cancer cases being about 15%. Currently 77% of the at-risk labor force is exposed to silica dust levels of < or = 0.1 mg.m-3. With this level as the limit, about 440 (range 140-1210) silicosis cases and 410 (interval 90-780) extra lung cancer cases would occur in 40 years. Adopting this level as the national exposure standard would reduce the risk of silicosis cases by 52% and the excess risk of lung cancer by 36%.

Adult↗
PubMed1991

The role of the O antigen in adjuvant activity of lipopolysaccharide.

Adjuvant activities of isogenic Salmonella enterica, serovar Typhimurium, O-6,7 and O-4,5,12 lipopolysaccharide (LPS), lipid A and Bordetella pertussis LPS were compared by immunizing groups of mice subcutaneously with diphtheria and tetanus toxoid vaccine alone or mixed with one of the LPS derivatives. Five weeks later the mice were bled and the tetanus and diphtheria antibodies in the sera were measured. All the LPS derivatives efficiently increased the antibody responses when compared to the vaccine alone, but the mannose-rich O-6,7 LPS and lipid A were significantly more potent than O-4,5,12 LPS and B. pertussis LPS. We conclude that the quality of the O antigen influences the adjuvant activity of LPS.

Animals↗
PubMed1991

Acute closed angle glaucoma and sunshine.

STUDY OBJECTIVE: The aim was to examine a possible association of amount of sunshine and risk for acute closed angle glaucoma. DESIGN: This was a retrospective analysis of hospital discharge registry data, linked to meteorological data for the same period. SETTING: The study was a national survey using hospital discharge data for the whole of Finland over a 10 year period. PARTICIPANTS: All subjects with the acute closed angle glaucoma diagnosis from the hospital discharge registry were collected for the years 1972 to 1982. A total of 1796 patients were found. MEASUREMENTS AND MAIN RESULTS: Meteorological data from two cities in Finland, Helsinki and Oulu, were collected for the same years from the Finnish Meteorological Institute. A peak incidence of acute closed angle glaucoma was noted whenever the number of hours without sunshine increased. A regression analysis including incidence of acute closed angle glaucoma as a dependent variable, and sex, mean temperature, mean air pressure, mean humidity, total amount of rain per month, and mean sunshine hours as independent variables, was constructed. Sex and sunshine hours best explained the variation in incidence in a covariate model. No other meteorological variate could improve the model fit. CONCLUSIONS: The result confirms that the number of hours without sunshine is positively associated with the incidence of acute closed angle glaucoma, when other meteorological variables are controlled for.

Female↗
PubMed1990

1990 Volvo Award in clinical sciences. Lumbar spinal pathology in cadaveric material in relation to history of back pain, occupation, and physical loading.

The occurrence of symmetric disc degeneration, anular ruptures, end-plate defects, vertebral body osteophytosis, and facet joint osteoarthrosis was examined radiographically and osteologically in 86 male cadavers for whom occupational, physical loading, and back pain histories were obtained from the men's families. History of back pain and the parameters of spinal pathology were related to the highest and lowest degrees of physical loading. In multivariate analyses, history of back injury was related to the occurrence of symmetric disc degeneration, anular ruptures, and vertebral osteophytosis. Symmetric disc degeneration was associated with sedentary work, and vertebral osteophytosis was related to heavy work. History of back pain was related to occupational physical loading after control for the effects of the other covariates. The results indicate that the least pathology stemmed from moderate or mixed physical loading, but the least back pain was associated with sedentary work.

Adult↗
PubMed1989

Analysis of epidemiologic case-base studies for binary data.

Recent developments in statistical methods for epidemiology have revived the application of sampling techniques in the design and analysis of cohort studies. The 'case-base' design involves sampling of both the cases and the cohort base of the study. This paper reviews some data-analytic imperfections of the approaches to risk ratio estimation, and modifies and advances a consistent likelihood-based procedure-analogous to Miettinen and Nurminen's proposal for a full cohort design--for interval estimation (and also point estimation and significance testing) in the context of binary case-base data. First, the procedure avoids the use of Taylor-series approximations to derive variance estimators for non-linear functions of parameters. Second, the asymptotic condition effects a simple computational expression for the chi-square function of risk ratios that is universally applicable to small samples. The statistical modelling underlying the method allows inferences about risk ratios without the assumption of rare disease either for the general population or for a particular base. The paper also extends the analysis to encompass stratified data. Finally, a numerical evaluation evinced the accurate small-sample properties of the proposed method.

Binomial Distribution↗