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Biomedical subjects

L Belin

Publications and source records attributed to L Belin.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of four methods to assess fungal alpha-amylase in flour dust.

The aim of the study was to compare four different immunological methods to analyse fungal alpha-amylase in flour dust samples. Three European research groups have independently developed four immuno assay based methods to measure alpha-amylase in air samples. Three of the methods use polyclonal antibodies and one method uses monoclonal antibodies. Eighty personal samples have been collected during two to three work-shifts in four bakeries. Sampling was performed with PAS-6 inhalable dust samplers and aliquots from each sample were analysed by the three laboratories. The agreement between the four methods was high compared with agreement between immunological methods to measure other allergens in the air, e.g. for rat allergens. For the three methods with polyclonal antibodies the mean differences for individual samples was less than a factor of two. The arithmetic means (AM) of the estimated alpha-amylase exposure were 12.5, 11.3, 8.6 and 25.9ng/m(3) for the respective methods with values ranging from below the detection limit to 192, 215, 207 and 615 ng/m(3). The AM for all samples analysed by the methods with polyclonal antibodies varied by about a factor of 1.5. About one-third of the values were below or at the detection limit for all methods. In a regression analysis the squared correlation coefficients (R(2)) between the methods varied between 0.91 and 0.95 for the log transformed values. For workplace monitoring, results from the methods using polyclonal antibodies will be relatively comparable. High levels of alpha-amylase might differ in absolute numbers with a factor of two or more between the different methods but will anyway be considered as high and should result in preventive actions. On the other hand, this study also shows that despite the relative agreement between methods, there is a clear need for standardization.

Air Pollutants, Occupational↗
PubMed1999

Incidence of beta-lactam-induced delayed hypersensitivity and neutropenia during treatment of infective endocarditis.

BACKGROUND: Long-term parenteral beta-lactam treatment is often complicated by adverse reactions that necessitate drug withdrawal. OBJECTIVE: To evaluate the incidence and mechanism of beta-lactam adverse reactions during an 8-year period in all episodes of suspected infective endocarditis in patients treated at a university-affiliated institution. METHODS: Patients with 215 consecutive episodes of beta-lactam treatment for 10 days or more were prospectively enrolled during 2 periods, January 1984 through December 1988 and January 1993 through December 1995, and compared with 51 episodes of vancomycin hydrochloride treatment for 10 days or more. Incidents of adverse reactions, such as fever, rash, or neutropenia, were registered. Neutrophil counts, eosinophil counts, and penicillin antibodies were studied. Patients with delayed adverse reactions to penicillin G sodium were rechallenged with penicillin v potassium. RESULTS: Incidence of delayed adverse reactions during treatment was 33% with beta-lactams compared with 4% with vancomycin. Rates of adverse event for beta-lactams increased continuously from treatment day 15 to day 30. A 6-fold difference in capacity to induce adverse events was found with different beta-lactams. Penicillin G induced neutropenia in 14% and any adverse event in 51% of treated episodes. Mean daily doses significantly influenced the frequency of adverse events. Occurrence of hemagglutinating penicillin antibodies was significantly related to patients whose penicillin-treated episodes were complicated with adverse events. Patients with delayed adverse reactions to penicillin G were safely rechallenged with penicillin. CONCLUSIONS: Incidence of delayed adverse reactions to beta-lactams increases sharply when parenteral treatment is extended beyond 2 weeks. Penicillin G is the most frequent inducer of adverse reactions among beta-lactams studied. An immunological reaction mediated by antibodies to the penicilloyl determinant may be involved in the pathogenesis, possibly enhanced by a dose-related toxic trigger mechanism. Beta-Lactam-induced neutropenia followed a uniform pattern, occurring after, on average, 21 days of treatment, and might be due to both immunologic and toxic effects of treatment. Patients with a late adverse reaction to penicillin can safely be re-treated with penicillin, although they should remain under close surveillance if treatment extends beyond 2 weeks.

Adult↗
PubMed1998

Allergen sensitization of asthmatic and nonasthmatic schoolchildren in Costa Rica.

The prevalence of asthma among schoolchildren in Costa Rica is very high -- at the level of 20-30% -- and the reason is still unknown. A group of children from our previous epidemiologic study was randomly selected in order to establish the relation between asthma symptoms and allergy sensitization to common allergens. Serum samples from children with and without asthma were analyzed for the presence of IgE antibodies to 36 different allergens, for the presence of IgE antibodies to a pool of 10 common allergens, and for total serum IgE. The most prevalent IgE antibodies were those to mite, cockroach, dog, and house-dust allergens with MAST pipettes for the serologic measurements. Positive reactions to house dust, mite, cat, and the two molds (Alternaria and Cladosporium), and food allergens such as egg white, peanut, and shellfish were significantly more prevalent among the asthmatics than the nonasthmatics. Sensitization was equally prevalent at different ages, but the house-dust, mite, cat, dog, cockroach, Alternaria, and egg-white allergens had sensitized boys more often than girls (P < 0.01). The result of the analysis of IgE antibodies to a pool of 10 common allergens by Phadiatop supported the MAST pipette results, showing allergen sensitization in 57.7% of the asthmatic children and 42.3% in the nonasthmatic group. The concentration of IgE was significantly higher among the asthmatic children (372.2 kU/l) than among the nonasthmatic children (249.1 kU/l) (P < 0.00001). Parasitic infestations were not examined in this study, but in most of Costa Rica these have largely been eliminated and could not explain the high total IgE levels. Our data indicate that the very high prevalence of bronchial asthma in Costa Rican schoolchildren can be related to sensitization, especially to airborne indoor allergens such as those of mites, cockroaches, and dogs.

Allergens↗
PubMed1998

Guanine, mite, and cockroach allergens in Costa Rican homes.

Previous studies of schoolchildren in Costa Rica have shown an asthma prevalence of 23% and a high level of sensitization, particularly to mite allergens. As a continuation of these studies, some 400 dust samples were collected from various places in Costa Rica, and parts of these were analyzed for specific mite and cockroach allergens, as well as for the number of mites and amount of guanine. Guanine was quantified by a diazo, as well as an HPLC method, which were found to be highly correlated. The concentrations of guanine by the diazo method, Der p 1, Der f 1, and the number of mites were higher in bed dust than in bedroom floor dust, and it was possible to quantify mite allergens and guanine in almost all bed-dust samples. The mean levels were 2-3 times higher than the proposed risk level for elicitation of symptoms in mite-sensitive asthmatics. Bed and bedroom floor dust contained more guanine and mite allergen in humid (> 2000 mm rain) than in drier places (P < 0.05), but the number of mites in bed and bedroom floor dust was higher in less humid places (P = 0.01). The guanine content in bedroom floor dust was higher in areas with a temperate climate than in areas with a warmer climate (P < 0.001, Bartlett's chi square [BCS]), as was the number of mites (P < 0.01, Kruskal-Wallis [KW], 0.04, BCS) and the Der p 1 concentration (P = 0.01, BCS; P = 0.02, KW). The Der f 1 concentration in bedroom floor dust was higher in a warmer than in a temperate climate (P < 0.001, BCS). More guanine and mites were found in urban than in rural bed dust (P = 0.03, KW). Dust samples from the metropolitan area (temperate climate) of Costa Rica contained higher levels of guanine (P < 0.01) and Der p 1 (P = 0.07) than the coastal areas, but very little Der f 1. In these samples, guanine and Der p 1 allergen were closely related, and 2 micrograms of the allergen was equivalent to 0.49 mg of guanine. Two-thirds of bed and floor samples collected on cotton filters contained Bla g 2 allergen at mean levels of 1.6 and 2.1 units/g dust, respectively. Cockroach allergen was, however, absent in all bed samples from the metropolitan area, but did occur in very high concentrations in the coastal bed dust samples collected with tighter polyester filters. In conclusion, the concentration of guanine and Der p 1 was very high in the bed dust of Costa Rican homes. Some factors, such as humidity, small houses for large families, and type of bedding, probably favored the heavy mite infestation, which is probably related to the widespread occurrence of bronchial asthma in this country.

Allergens↗
PubMed1997

Syntheses and biological activities (topoisomerase inhibition and antitumor and antimicrobial properties) of rebeccamycin analogues bearing modified sugar moieties and substituted on the imide nitrogen with a methyl group.

As a part of studies on structure-activity relationships, several potential topoisomerase I inhibitors were prepared. Different analogues of the antitumor antibiotic rebeccamycin substituted on the imide nitrogen with a methyl group were synthesized. These compounds bore either the sugar residue of rebeccamycin, with or without the chlorine atoms on the indole moieties, or modified sugar residues (galactopyranosyl, glucopyranosyl, or fucopyranosyl) linked to the aglycone via a beta- or alpha-N-glycosidic bond. Their inhibitory properties toward protein kinase C, topoisomerase I, and topoisomerase II were examined, and their DNA-binding properties were investigated. Their in vitro antitumor activities against murine B16 melanoma and P388 leukemia cells were determined. Their antimicrobial activities were tested against Gram-positive bacteria Bacillus cereus and Streptomyces chartreusis, Gram-negative bacterium Escherichia coli, and yeast Candida albicans. These compounds are inactive toward topoisomerase II but inhibit topoisomerase I. A substitution with a methyl group on the imide nitrogen led to a loss of proteine kinase C inhibition in the maleimide indolocarbazole series but did not prevent topoisomerase I inhibition. Compounds possessing a beta-N-glycosidic bond, which fully intercalated into DNA, were more efficient at inhibiting topoisomerase I than their analogues with an alpha-N-glycosidic bond; however, both were equally toxic toward P388 leukemia cells. Dechlorinated rebeccamycin possessing a methyl group on the imide nitrogen was about 10 times more efficient in terms of cytotoxicity and inhibition of topoisomerase I than the natural metabolite.

Aminoglycosides↗
PubMed1996

Structure-activity relationships in a series of substituted indolocarbazoles: topoisomerase I and protein kinase C inhibition and antitumoral and antimicrobial properties.

A series of compounds structurally related to staurosporine, rebeccamycin, and corresponding aglycones was synthesized, and their activities toward protein kinase C and topoisomerases I and II were tested together with their in vitro antitumor efficiency against murine B16 melanoma and P388 leukemia cells. Their antimicrobial activities were also examined against a Gram-negative bacterium (Escherichia coli), a yeast (Candida albicans), and three Gram-positive bacteria (Bacillus cereus, Streptomyces chartreusis, and Streptomyces griseus). To avoid side effects expected with protein kinase C inhibitors, we introduced substitution on the maleimide nitrogen and/or a sugar moiety linked to one of the indole nitrogens to obtain specific inhibitors of topoisomerase I with minimal activities on protein kinase C. As expected, these structures were inefficient on topoisomerase II, and some of them exhibited a strong activity against topoisomerase I. Generally, dechlorinated compounds were found to be more active than chlorinated analogues against both purified topoisomerase I and protein kinase C. On the other hand, opposite results were obtained in the cell antiproliferative assays. These results suggest lack of cell membrane permeability in the absence of the chlorine residue or cleavage of carbon-chlorine bonds inside the cell.

Animals↗
PubMed1996

Allergic alveolitis in a school environment.

BACKGROUND: A considerable fraction of newly constructed buildings have indoor air problems associated with health effects, usually of the nonspecific sick building syndrome variety. Specific health effects such as asthma, rhinitis, and allergic alveolitis can also occur. CASE: On 1 September 1988 a school teacher showed symptoms of an acute respiratory illness, which was first interpreted as pulmonary embolism and then later as atypical sarcoidosis. The illness slowly progressed over six years, at which time the diagnosis was revised to chronic allergic alveolitis, related to her school environment. The school had had indoor-air quality problems off and on for several years. CONCLUSIONS: The case illustrates the difficulties of diagnosing cases of chronic allergic alveolitis, especially when it appears in environments where it is not generally encountered. It also raises questions regarding a possible relation between environments associated with the sick building syndrome and the occurrence of building-associated illnesses.

Adult↗
PubMed1993

Asthma, rhinitis, and dermatitis in workers exposed to reactive dyes.

A survey was conducted at 15 textile plants with dyehouses in western Sweden. Employees with a history of work related rhinitis, asthma, or skin symptoms were offered a clinical and immunological investigation including skin prick tests, skin patch tests, and radioallergosorbent tests (RASTs) to detect specific allergy to reactive dyes. Among the 1142 employees, 162 were exposed to reactive dyes and 10 of these (6%) reported work related respiratory or nasal symptoms. An allergy to reactive dyes could be confirmed in five (3%, 95% confidence interval 1-7%). All but one had been exposed to reactive dyes for one year or less before the onset of symptoms. Positive RASTs could be detected in four of the five patients. All of the RAST positive patients were positive to remazol black B, but six out of eight additional remazol dyes also elicited positive results. RAST and RAST inhibition showed a cross reactivity between some of the dyes. Seven persons with work related dermatitis and three with urticaria or Quincke oedema were found. In one patient contact dermatitis to a monoazo dye was shown, but no positive patch test reactions to reactive dyes. IgE-mediated allergy to reactive dyes seems to be an important cause of respiratory and nasal symptoms among dyehouse employees exposed to dust from reactive dyes.

Adult↗
PubMed1992

Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.

Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.

Acute Disease↗
PubMed1992

Alterations in bronchoalveolar lavage fluid but not in lung function and bronchial responsiveness in swine confinement workers.

Testing of lung function and bronchial reactivity, bronchoalveolar lavage (BAL), and a skin prick test with a standard panel and six "swine" extracts obtained from swine and swine environment were performed in 20 randomly selected nonsmoking swine confinement workers. In addition, blood samples for detection of antibodies by the diffusion in gel-enzyme-linked immunosorbent assay (DIG-ELISA) technique and precipitating antibodies were drawn. Air samples for measurement of dust and endotoxin levels were collected. All the farmers regarded themselves as healthy. The results were compared with reference groups consisting of urban nonsmoking subjects who had not been exposed to pig farming environment. The pig farmers had normal lung function and the bronchial reactivity was not different from the reference group. In the BAL fluid of the farmers, the concentration of total cells and granulocytes was increased while the concentrations of lymphocytes and macrophages were normal. The BAL fluid concentrations of albumin, fibronectin, and hyaluronan were elevated in the farmers. Skin prick tests with swine extracts were negative in all farmers. Antibodies (assessed by DIG-ELISA) against swine dander, swine dust, and pig feed were increased and precipitating antibodies against swine dander were found in 14, against pig food in five, and against swine confinement dust in three of the 20 pig farmers. The concentration of airborne total dust was 7.4 mg/cu mm and the endotoxin concentration was 37 (22 to 60) ng/cu mm during tending the pigs and increased, during feeding, to 13.8 mg/cu mm and 315 (194 to 716) ng/cu mm, respectively. There was no correlation between exposure and lung function or lavage findings. In conclusion, randomly selected pig farmers had signs of airway inflammatory reaction and activation of the immune system without alteration in lung function and bronchial reactivity.

Adult↗
PubMed1991

Clinical and immunological responses to occupational exposure to alpha-amylase in the baking industry.

alpha-Amylase is a starch cleaving enzyme often used in the baking industry as a flour additive. It is usually of fungal origin, produced by Aspergillus oryzae. One previous report has shown IgE antibodies and positive skin prick test against alpha-amylase in asthmatic bakers. This paper describes four alpha-amylase sensitised index cases with occupational asthma or rhinitis and the results of a cross sectional study of 20 workers from the same factory who were also exposed to alpha-amylase powder. Air sampling detected airborne alpha-amylase at a concentration of 0.03 mg/m3. Significantly more work related symptoms such as rhinitis and dermatitis were found among the alpha-amylase exposed workers compared with referents. A skin prick test to alpha-amylase was positive in 30% (6/20) of the exposed workers. Most of the persons showing a positive skin prick test had work related symptoms and were also skin prick test positive to common allergens. Nasal challenge tests with amylase were performed in selected cases and validated three cases of alpha-amylase induced rhinitis. Two non-symptomatic workers had precipitins to alpha-amylase. Specific IgG antibodies were shown by two further serological techniques. The nature and relevance of these antibodies are currently being studied. It is concluded that alpha-amylase powder is a potent occupational sensitiser. Precautions should be taken when handling this allergenic enzyme.

Adult↗
PubMed1990

An optimized assay of specific IgE antibodies to reactive dyes and studies of immunologic responses in exposed workers.

Methods of assaying reactive dye-specific IgE antibodies were investigated with a RAST. Sera from three patients, occupationally exposed to a reactive dye, Remazol black B (Chemical Abstract registry number 17095-24-8), were used. Directly dyed disks, that is, disks without any carrier protein, resulted in poor and unreliable measures of specific IgE. In contrast, optimized preparation of conjugates between the dye and human serum albumin resulted in efficient binding of specific IgE. The patients' RAST results were strongly positive, whereas sera from 36 exposed workers but without symptoms and sera from unexposed subjects with high levels of total IgE were negative. The hapten and carrier specificity of the IgE antibodies was studied by direct RAST and RAST inhibition. In one patient, the antibodies were principally hapten specific, whereas another patient was found to have antibodies with a high degree of specificity to the carrier. The third patient's antibodies were intermediate between the other two patients' antibodies in this respect, suggesting that antibody specificity is dependent not only on the nature of the hapten but also on individual immune response factors. The study demonstrates that it is important to use an optimized preparation of dye-protein conjugates to elicit reliable results and a high degree of specific IgE binding in the RAST.

Antibody Specificity↗
PubMed1990

An in vitro method for predicting sensitizing properties of inhaled chemicals.

A method for monitoring chemical reactivity in aqueous solutions, at neutral pH and 37 degrees C, was developed. The chemical was allowed to react with a lysine-containing peptide, and the reaction was monitored with high-performance liquid chromatography. Simple acids, bases, and solvents did not react with the peptide, whereas isocyanates, anhydrides, and chloramine-T, substances well known for their sensitizing and asthma inducing properties, did. Thus a positive test strongly suggested that the chemical had the potential to act as a hapten and cause sensitization when inhaled. Prepolymers of diphenylmethane diisocyanate were considerably more reactive than prepolymers of toluene diisocyanate or hexamethylene diisocyanate. Isocyanates blocked with caprolactam, butanone oxime, malonic acid diethylester, or isononyl phenol showed no reactivity. This result suggested a significantly reduced risk of respiratory reactions when such blocked isocyanates are handled at room temperature. One blocked isocyanate showed, however, considerable reactivity.

Administration, Inhalation↗
PubMed1989

Immunologic specificity of isocyanate-induced IgE antibodies in serum from 10 sensitized workers.

A procedure for the preparation of RAST disks used to assay isocyanate-specific IgE antibodies was developed. The outcome of the RAST was found to be strongly dependent on how the isocyanate test antigen was synthesized. Specific IgE from selected workers with isocyanate asthma reacted optimally to conjugates with less than or equal to 10 isocyanate molecules bound per molecule of human serum albumin. Further haptenization resulted in decreased specific binding and increased nonspecific binding because of high levels of total IgE. The hapten and carrier specificity of isocyanate-induced IgE antibodies were studied by direct RAST and RAST inhibition. The existence of new antigenic determinants related to both the isocyanate hapten and the carrier could be demonstrated. It was important to use a test antigen prepared from the same isocyanate as that to which the worker had been exposed, since the cross-reactivity between different isocyanate haptens was partial and varied from one patient to another. It was confirmed that isocyanate-specific IgE antibodies can be demonstrated only in a subgroup of workers with isocyanate-related bronchial asthma.

Antibody Specificity↗
PubMed1989

Immunological specificity of chloramine-T-induced IgE antibodies in serum from a sensitized worker.

A procedure for the preparation of chloramine-T (CT) conjugates used to assay IgE antibodies was developed using response surface methodology and serum from a subject occupationally exposed to the substance. The conjugates, synthesized by reacting CT with human serum albumin (HSA) and other protein carriers, were used as antigens in a radio-allergosorbent test (RAST). Human serum albumin was found to be a suitable carrier, although other protein carriers also gave specific IgE-binding of a similar extent. The CT-HSA conjugates used in the RAST were characterized by high performance liquid chromatography, electrophoresis, immunodiffusion and ammonium sulphate precipitation. However, no strong correlation was seen between the ability of the conjugates to bind IgE and their physical or immuno-chemical properties. The hapten and carrier specificity of CT-induced IgE antibodies in the subject's serum were studied by direct RAST and RAST inhibition. No existence of new antigenic determinants related to the carrier could be demonstrated. Although HSA as a carrier was altered immunochemically by CT, the IgE antibodies were found to be specific to hapten only. Chloramine-T-specific IgG antibodies could not be demonstrated in the subject's serum.

Adult↗
PubMed1989

Environmental and health studies of farm workers in Swedish swine confinement buildings.

The relation between the health of workers and the environment in swine confinement buildings was investigated in a study of 57 workers on 30 swine farms in southern Sweden and 55 matched controls. Swine workers reported significantly higher frequencies of respiratory symptoms, more frequent colds and absence due to chest illness, and a history of pneumonia. The increased frequency of symptoms of respiratory disease was related to the number of years and percent of the day spent working with swine. Symptoms were also associated with respirable dust, total dust, endotoxin in total dust, and number of microbes in the air of the work environment. In a multiple regression analysis of the relation between 16 different environmental parameters to work period shifts of five pulmonary function parameters, endotoxin was found to be significantly related to the FEV1 in a dose dependent way.

Agricultural Workers' Diseases↗