Fungal lethality, binding, and cytotoxicity of syringomycin-E

Syringomycin-E (SE) was significantly lethal to Aspergillus and Fusarium species at between 1.9 and 7.8 micrograms/ml. SE complexed with the following fungal wall constituents (in order of binding): beta-1,3-glucan > chitin > mannan > ergosterol = cholesterol. Cytotoxicity in HeLa cells was proportional to the SE concentration, while the amount required for cytotoxicity was 3 to 20 times that needed to kill 95% of the fungi tested.     

The kidneys in aging]

In this study, we investigated indoor air quality and symptoms of respiratory illness in 264 nursing workers at 28 day-care centers in Taipei. Geometric mean concentrations of indoor and outdoor bacteria were 735 colony-forming units in air (CFU/m3) and 384 CFU/m3, respectively. In addition, geometric mean concentrations of indoor and outdoor fungi were 1,212 CFU/m3 and 1,032 CFU/m3, respectively. Aspergillus, Cladosporium, and Penicillium-microfungi that occurred most commonly-were found indoors and outdoors. Geometric mean concentrations of house dust mite allergens, Der p I and Der p V, were 58 ng/g dust and 14 ng/g dust, respectively. In addition, the observed high prevalence of dampness or mold problems in the day-care centers indicated that dampness was very common in this subtropical region. We found a significant relationship between dampness and work-related sick building syndrome in the day-care-center workers. Furthermore, concentrations of fungi were lower in the day-care centers equipped with air conditioners/air cleaners than in centers that lacked such equipment. Also, Aspergillus was associated strongly with work-related sick building syndrome in the day-care-center workers.     

Home dampness, moulds and their influence on respiratory infections and symptoms in adults in Finland

The aim of this study was to analyse the prevalence of mouldy homes and their association with respiratory symptoms and diseases in a subarctic climate. A questionnaire was mailed to a random sample of 2,000 males and females, aged 25-64 yrs, living in the county of Kuopio, Finland. A total of 1,521 (76%) responded and 1,460 were selected for the final analysis. The prevalence of homes with visible mould was 4%; with the odour of mould 5%; with damp spots, visible mould or the odour of mould 15%; and with moisture/ water damage, damp spots, visible mould or the odour of mould 23%. The number of reports of bronchitis, common cold, atopy, allergic rhinitis, rhinitis, fever and chills, hoarseness, fatigue, difficulties in concentration, lumbar backache and stomach ache were strongly associated with living in a damp home. Bronchitis, hoarseness and difficulties in concentration had the strongest associations, with adjusted odds ratios (95% confidence limits) of: 2.04 (1.49-2.78), 2.23 (1.37-3.63) and 2.17 (1.35-3.50), respectively. After controlling for a possible reporting bias by excluding those subjects reporting lumbar backache and recurrent stomach pain, eye irritation and tiredness remained significant. In conclusion, living in a home with mould problems may increase the risk of respiratory infections and symptoms in adults.     

Xenograft rejection of porcine islet-like cell clusters in normal, interferon-gamma, and interferon-gamma receptor deficient mice

BACKGROUND: An increase in serum alpha-glutathione S-transferase concentration (GST) has been shown to be a more sensitive and specific marker of hepatocellular damage than equivalent increases in transaminase activities. A randomized clinical trial of 60 liver transplants in 49 patients was carried out to assess the clinical benefits of GST monitoring as a supplementary test to routine liver function tests during the first 3 postoperative months after liver transplantation. METHODS: Mortality and morbidity were compared in graft recipients who had their GST reported daily to the ward (reporting group) and graft recipients who did not. RESULTS: The 3-month survival rate was significantly greater in the reporting group (P=0.033) and the risk of graft loss was halved (relative hazard ratio=0.50; P=0.29). The reporting group also had significantly more patients who spent less than 3 weeks in the hospital throughout the follow-up period (P=0.036). In addition, the reporting group experienced a lower frequency of biopsies per graft (P=0.038), less severe rejection (P=0.015), and a lower incidence of infection episodes per graft (P=0.03). GST increased by >50% above the upper limit of the reference range at a median of 1 day before the equivalent change in alanine transaminase in association with allograft rejection in the combined groups (95% confidence interval=1 to 2 days) but was lower on the day of diagnosis of rejection in the reporting group (P=0.02). This is compatible with the earlier diagnosis of rejection in the reporting group. CONCLUSIONS: We conclude that the monitoring of GST may improve patient care, reducing both mortality and morbidity.     

Mechanical ventilation protects one-storey single-dwelling houses against increased air humidity, domestic mite allergens and indoor pollutants in a cold climatic region

BACKGROUND: Poor ventilation in modern, highly insulated housing is an important factor in promoting indoor humidity levels to exceed 7 g/kg in cold climatic regions. OBJECTIVE: To investigate the ventilation rate in houses with different ventilation systems in relation to indoor air humidity, domestic mite allergen levels and volatile organic compounds (VOC). METHODS: Measurements were performed regarding ventilation rate, indoor temperature, air humidity, mattress mite allergen concentrations using enzyme-linked immunosorbent assay and total indoor VOC in 59 similarly constructed one-storey single-dwelling houses. In 22 of the houses, a mechanical supply and exhaust ventilation were installed after construction. RESULTS: In only five of the houses with mechanical supply and exhaust ventilation the air exchange rate per hour (ACH) was below 0. 5 compared with 24 of the 29 houses with natural ventilation (OR = 0. 06, CI 95% 0.01-0.2). None of the 23 houses with an ACH >/= 0.5 had an absolute indoor humidity (AIH) of 7 g/kg air or more, compared with 10 of the 36 houses with an ACH < 0.5 (P = 0.01 ). In none of the 23 houses with an ACH >/= 0.5 were concentrations of mite allergen exceeding 2 microg/g of dust found, compared with six of the 36 houses (17%) with an ACH below 0.5 (P = 0.04). Further, 10 of the 34 houses with a total VOC exceeding 200 microg/m3 had mite allergen in mattress dust exceeding 0.5 microg/g, compared with one of the 22 houses with VOC < 200 microg/m3 (P = 0.04). CONCLUSION: The study shows that in modern, highly insulated, one-storey single-dwelling houses in cold temperate regions, mechanical ventilation increases the possibility of reaching an ACH of >/= 5 which protects against indoor humidity levels contributing to mite survival as well as high levels of indoor air pollutants in winter.     

Expression of Msx-2 during development, regeneration, and wound healing in axolotl limbs

BACKGROUND: High exposure to house dust mite allergen during the first year of life has been found to increase the risk of subsequent asthma and mite sensitization. Environmental factors, home construction and cleaning methods used are associated with levels of dust mites in the home. OBJECTIVE: To investigate determinants of levels of Der p 1 and Der f 1 mite allergens in homes of infants in southern Tasmania. METHODS: Dust samples were collected from 72 homes of infants participating in the Tasmanian Infant Health Survey (TIHS). The Der p 1 and Der f 1 allergen concentrations in these samples were measured. The TIHS interviewers obtained information from the mothers of the infants via a questionnaire, observed specified aspects of the home environment, and took readings of bedroom temperature and humidity. The effect of each item on allergen concentration in dust from bedroom floors was examined in a variety of ways. Those items which in this study appeared to be significantly related to allergen concentrations plus items which in other studies have been found to be related to allergen concentrations were then investigated further in multivariate models. RESULTS: Der p 1 allergen concentration (microg/g) and density (microg/m2) in dust from bedroom floors were found to be related to several home environment factors. In the univariate analyses, indoor humidity, 24 h maximum temperature, number of residents and a combination of floor covering and cleaning methods appeared to have a significant effect on allergen levels. These factors remained important in the multivariate model except that indicators for mould in the bathroom and drying washing on an outside line replaced indoor humidity. CONCLUSION: Features related to home dampness, the number of residents and floor covering and cleaning were major determinants of Der p 1 levels in the bedrooms studied.     

Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility

We have cloned and sequenced the structural genes encoding the delta 5,6 sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion. The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied. Strain L5D (erg3 delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain. L5LUD (LEU2 erg11 delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth. A spontaneous aerobically viable mutant, L5LUD40R (LEU erg11 delta::URA3), obtained from L5LUD (LEU2 erg11 delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 delta::LEU2 erg11 delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C. glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae.     

House dust mite allergens and mite allergy in Copenhagen dwellings. A cross-sectional study

The aim of the study was to investigate the influence of various environmental factors on occurrence of house dust mite allergens and the influence of allergen exposure on mite allergy. Ninety-two persons from a population study filled in a questionnaire, were skin prick and lung function tested and dust samples were collected from their mattresses for analyses. Two out of five patients with asthma had a positive skin reaction to house dust mite allergen in contrast to five out of 87 non-asthmatics. Fifty-nine per cent of the dust samples contained (group 1) mite allergen > 2 micrograms/g dust. Such mattresses were older (median 7 years, range 1-22) than mattresses with less allergen (median 4 years, range 1-20). In the six bedrooms reported to be humid or mouldy, mattresses contained high concentration of mite allergens. No other parameter investigated could predict the allergen contents. In almost all cases dust analyses are crucial to be able to advise patients with house dust mite allergy.     

Sensitization to Alternaria and Cladosporium by the age of 4 years

Of 1218 children born on the Isle of Wight in 1989/90, and followed for atopy at age 4 years, 981 were skin-prick tested with a battery of allergens. Of these 61 (6%) reacted positively to Alternaria alternata and Cladosporium herbarum (47 to Alternaria, 21 to Cladosporium and seven to both). Twenty-four (39%) were asymptomatic (latent atopy) of which 12 had a single positive reaction either to Alternaria or Cladosporium. Asthma was the most common disease in children sensitized to moulds. Alternaria sensitization correlated positively with clinical diagnosis of asthma (P < 0.01), eczema (P < 0.001) and rhinitis (P < 0.05). Likewise, Cladosporium sensitivity correlated with a diagnoses of asthma, eczema and rhinitis (all P < 0.05). Age of the house correlated with reported damp and lack of central heating (both P < 0.001), but not with sensitization to moulds. An association between the presence of damp or age of the house and mould allergy was confounded by 21 children moving house in the first 4 years. Exposure to pets, passive tobacco smoking and season of birth had no bearing on mould sensitivity. At 4 years of age Alternaria and Cladosporium were the third most common causes of sensitization, i.e. after house dust mite and grass pollen.     

Childhood obesity: a risk factor for traumatic injuries to anterior teeth

The relationship between obesity and traumatic dental injuries was evaluated in a study population of 938 6- to 11-year-old schoolchildren from Rome, Italy, and it was suggested by the lifestyle and the physical activity of obese children, which, according to many authors, is different from the lifestyle of other children. The subjects were examined at school: presence and type of dental injury, overjet, incisor protrusion, upper lip incompetence and presence of obesity were recorded. Trauma predisposition was evaluated with a questionnaire investigating the behaviour which may predispose to impacts. Six out of eight questions in this questionnaire concerned the children's lifestyle and the trauma predisposition score was therefore also considered an estimate of lifestyle and physical activity. The dental injury prevalence of the study population was 21.3% and obesity prevalence was 11.4%. Of the obese children 30.8% had dental injuries vs. only 20.0% of non-obese subjects (P = 0.007). Obese children had only enamel and enamel-dentine fractures and the main reported trauma cause was indoor play; conversely, lean children also had other types of injuries and the most frequently reported cause was outdoor play. The main predisposing factors significantly affecting the probability of dental injury, evaluated with multiple logistic regression, were upper lip uncoverage (OR: 1.23; P = 0.02), overjet larger than 3 mm (OR: 1.68; P = 0.001) and obesity (OR: 1.45; P = 0.01). Surprisingly, trauma predisposition was a protective factor (OR: 0.50; P = 0.00001). The results of this study were explained by the significant inverse correlation between obesity and trauma-predisposing behaviour, thus suggesting that subjects frequently playing sports and lively games were not only less obese but also more skillful and, for this reason, less prone to trauma when they fell or sustained impacts.     

Prevalence and distribution of indoor allergens in Singapore

BACKGROUND AND AIMS: Immediate hypersensitivity to indoor allergens is known to be associated with allergic asthma. This study evaluated the prevalence and distribution of six indoor allergens in 956 dust samples obtained from homes, childcare centres, schools, and a hospital in tropical Singapore. Seasonality of mite allergens was also assessed. METHODS: The major allergens of the Dermatophagoides spp. dust mites, Der p 1 and Der f 1; major cat and dog allergens, Can f 1 (dog) and Fel d 1 (cat); and cockroach, Bla g 1, were measured by specific enzyme immunoassays. Allergen levels of the storage mite, Blomia tropicalis (Blo t), were measured by a fluorescent allergosorbent test (FAST) inhibition assay. RESULTS: Our results showed that homes had significantly higher concentrations and prevalence of allergens compared with the other locations, except for Bla g 1, where higher mean levels were found in schools. Within the homes, the highest concentrations of mite allergens were found in mattresses (geometric mean: 1.2 microg/g dust Der p 1; 2717 Allergen Units per gram dust [AU/g] Blo t), and carpets (1.5 microg/g Der p 1; 1620 AU/g Blo t), whilst Bla g 1 was mainly concentrated in the storerooms (geometric mean = 3.5 units/g) and kitchens (geometric mean = 5.1 units/g). The major cat and dog allergens were well distributed and not confined to homes with pets. Their highest levels were found in dust of soft furnishings, carpets and mattresses. There was an absence of significant seasonal variation in Der p 1, Der f 1 and Blo t levels in the homes over a 1 year period. CONCLUSION: The results indicate that compared with public places, the home consitutes a major reservior of indoor allergens. Allergens of the storage mite, B. tropicalis, should be considered as a major allergenic component of dust in Singapore.     

Dermatophagoides sp. and IgE anti-D. pteronyssinus and D. farinae detection in a Venezuelan community at more than 2000 m above the sea level

BACKGROUND: It has been reported that the concentration of Dermatophagoides sp. population, the main trigger of asthma in sensitized atopic subjects, is inversely related with altitude and probably directly with humidity and that this population are scarcely found over 1750 m above sea level. OBJECTIVE: We studied the presence of Dermatophagoides sp. in a Venezuelan community between 2040 and 2600 m above sea level, and also the IgE response to D. pteronnyssinus and D. farinae in atopic subjects living on that region. METHODS: The presence of Dermatophagoides sp. was determined by microscopic identification of mites in dust, obtained by brushing the mattresses surface in 93 randomly selected houses between 2040 and 2600 m above sea level. The indoor relative humidity was also measured. The specific IgE serum levels were studied in 65 subjects classified as asthmatics, allergic non-asthmatics and non-allergic. RESULTS: A mean concentration of 188 mites/g of room dust was determined in 82.4% of houses with an indoor relative humidity ranging from 89% and 92% independently of altitude. The density of Dermatophagoides sp. was sufficiently high to sensitize the atopic subjects, IgE levels were 6.8 PRU mean value for asthmatic, against 0.38 PRU in non-atopic. CONCLUSIONS: We conclude that: (a) Dermatophagoides sp. can be found up to 2600 m above sea level in a Venezuelan neotropical region where a high indoor relative humidity is characteristic of most dwellings; (b) sensitization by D. pteronyssinus and D. farinae were demonstrated in atopic subjects resident at that region.     

Shared epitope homozygosity' is strongly associated with rheumatoid arthritis in Turkey. Istanbul Rheumatology Study Group

OBJECTIVE: Associations with HLA-DRB alleles, implicated in the aetiopathogenesis of rheumatoid arthritis (RA), are found to be different in various ethnic groups. This study aimed to investigate DRB1 alleles in RA patients in Turkey. METHODS: The DRB region of the MHC was screened by polymerase chain reaction/sequence-specific oligonucleotide (PCR/SSO) hybridizations in 101 seropositive RA patients and compared with 101 healthy controls. RESULTS: Significant differences were in the frequencies of DRB1*0404 (12 vs 1, P = 0.003, OR = 13.5), *0401 (19 vs 4, P = 0.001, OR = 5.6) and *0408 (5 vs 0, P = 0.06, OR = 11.6) between RA patients and controls. The shared epitope (SE) was present in 70.2% of RA patients compared to 31.6% of controls (P < 0.0001, OR = 5.1). A double dose of SE was considerably more frequent in the RA group (21 vs 1, P < 0.0001, OR = 26.5). CONCLUSION: These results support the reported positive association of RA with SE in seropositive patients in Turkey, and emphasize 'SE homozygosity' as the most strongly associated genetic susceptibility marker for RA.     

Hemodialysis and hemoperfusion for treatment of valproic acid and gabapentin poisoning

OBJECTIVES: Genotoxic risk was evaluated for spray painters possibly exposed to polyester resins and acrylic enamel-based paints in automotive body repair shops. METHODS: DNA (deoxyribonucleic acid) strand breaks and alkali-labile sites were measured in peripheral mononuclear blood cells ex vivo using the alkaline elution method. Samples of venous blood were taken on Monday after a free weekend and again on Friday from 38 male and 1 female spray painters and compared with the blood samples from 36 male and 3 female referents. The elution rate of each DNA sample was standardized by dividing it by the elution rate obtained from simultaneously sampled untreated Chinese hamster V79 cells. RESULTS: The spray painters showed a significantly (P < 0.001) higher mean level of strand breaks and alkali-labile sites in the Friday samples [2.05 (SE 0.17)] compared with the Monday samples [1.38 (SE 0.07)]. The Monday results of the spray painters were not distinguishable from the referents' [1.41 (SE 0.10)]. The increase in DNA damage was numerically higher, but only weakly significant (use of masks, P < 0.05) or nonsignificant (use of spray booths), when fewer safety provisions were taken. CONCLUSIONS: A significant increase in DNA strand breaks and alkali-labile sites was found in spray painters after a week's work. However, DNA damage seems to be reversible. The use of modern safety equipment seems to affect DNA damage only marginally. There is an urgent need to identify the genotoxic chemicals in the occupational environment of spray painters and to develop corresponding satisfactory safety measures.     

Cockroach allergy: a study of its prevalence using skin tests with commercial extracts

Cockroaches have been increasingly recognized as an important source of indoor allergens. In this study we assessed the prevalence of cockroach sensitization among an outpatient population observed at our Department (155 patients with a mean age of 29 +/- 12 years), based on skin "prick" tests with four commercial cockroach extracts along with a common battery of standardized inhalant allergens. We found a positive wheal to at least one of these four extracts in 27 patients: 26 (96.2%) to Blatta orientalis, 10 (37%) both to Blatella germanica and 1 (3.7%) exclusively to Blatella germanica, with no significant concordance between them. We also observed in patients with cockroach positive skin "prick" test an association with atopy (p < 0.001) and with cutaneous reactivity to other indoor allergens, namely house dust mites (p = 0.02), danders (p = 0.01) and fungi (p = 0.01). These data confirm the higher risk of cockroach sensitization among the atopic population sensitized to indoor allergens. However, the heterogeneity of the positive cutaneous responses obtained in this study, possibly reflecting the incomplete standardization of cockroach extracts, questions the real prevalence and clinical significance of this particular sensitization.     

The effect of felodipine on endothelin-1 levels, peripheral vasoconstriction and flap survival during microvascular breast reconstruction

OBJECTIVE: To collect questionnaire data from patients in a large clinical population that would allow for an estimate of the prevalence of self-reported symptoms of dry eyes. METHODS: A 13-point questionnaire (The Canada Dry Eye Epidemiology Study, CANDEES) was mailed to all optometric practices in Canada in October 1994, with the request that it be completed by 30 successive nonselected patients. RESULTS: Four hundred fifty sets of questionnaires (total, 13,517) were analyzed (a 15.7% return rate) from patients aged from < 10 years to > 80 years; 55% were in the 21- to 50-year age group; 60.7% were female; and 24.3% were contact lens wearers. A total of 28.7% reported dry eye symptoms, of whom 24.2% reported concurrent dry mouth, 24.5% had worse symptoms in the morning, 30.3% reported concurrent lid problems, and 35.7% reported a history of allergies. Of the 3716 patients reporting symptoms, 62 (1.6%) were in the "severe" category and 290 (7.8%) were in the "constant but moderate" category. Contact lens wear, concurrent allergies, dry mouth, lid problems, or use of medications increased the chance of a patient reporting dry eye symptoms. CONCLUSIONS: The prevalence of patients reporting any level of symptoms of dry eyes was approximately 1 in 4; severe symptoms were reported by 1 in 225 patients.     

Heparan sulfate staining of the glomerular basement membrane in relation to circulating anti-DNA and anti-heparan sulfate reactivity: a longitudinal study in NZB/W F1 mice

BACKGROUND: Pyroglyphid mites are considered a major cause of house dust allergy. The occurrence and possible pathogenic role of other biologic components of house dust, in particular bacteria, has received less attention. OBJECTIVE: The aim of this study was to examine bacteria present in the samples of house dust from beds, in comparison to fungi and mites recovery. METHODS: Samples of bed dust were collected from 40 homes in Upper Silesia (Poland). Of these, 19 came from the homes of people with asthma caused by house dust and 21 from the homes of people without allergy. The concentrations of bacteria, fungi, mites, and endotoxin and species composition of microflora and acarofauna were determined. RESULTS: The overall mean concentrations of mesophilic bacteria, thermophilic bacteria and fungi, including yeasts, were, respectively, 1.6 x 10(6), 1.7 x 10(3), and 1.6 x 10(4) CFU/g. Samples contained an average of 8.4 mites/g and the ten samples assayed for bacterial endotoxin averaged 80.4 ng/mg. A total of 55 species of bacteria, 40 of fungi and 13 of mites were found. Gram-positive cocci (mostly Staphylococcus spp.) were the predominant mesophilic bacteria, followed by corynebacteria and Bacillus spp. Thermophilic bacteria were represented only by actinomycetes, with Thermoactinomyces vulgaris predominant. The most numerous fungi were Penicillium spp. and Aspergillus spp. followed by yeasts. The most abundant mites were Dermatophagoides spp. which formed > 85% of the total count. There were no significant differences between the homes of allergic and nonallergic people in the concentrations of total bacteria, fungi, and mites. Bacillus, Aspergillus and total filamentous fungi (molds), but not yeasts, were significantly more numerous in the homes of people with asthma caused by house dust. CONCLUSION: The results suggest that some species of bacteria and filamentous fungi should be considered potential causes of house dust allergy.     

Characterization of the Saccharomyces cerevisiae ERG26 gene encoding the C-3 sterol dehydrogenase (C-4 decarboxylase) involved in sterol biosynthesis

All but two genes involved in the ergosterol biosynthetic pathway in Saccharomyces cerevisiae have been cloned, and their corresponding mutants have been described. The remaining genes encode the C-3 sterol dehydrogenase (C-4 decarboxylase) and the 3-keto sterol reductase and in concert with the C-4 sterol methyloxidase (ERG25) catalyze the sequential removal of the two methyl groups at the sterol C-4 position. The protein sequence of the Nocardia sp NAD(P)-dependent cholesterol dehydrogenase responsible for the conversion of cholesterol to its 3-keto derivative shows 30% similarity to a 329-aa Saccharomyces ORF, YGL001c, suggesting a possible role of YGL001c in sterol decarboxylation. The disruption of the YGL001c ORF was made in a diploid strain, and the segregants were plated onto sterol supplemented media under anaerobic growth conditions. Segregants containing the YGL001c disruption were not viable after transfer to fresh, sterol-supplemented media. However, one segregant was able to grow, and genetic analysis indicated that it contained a hem3 mutation. The YGL001c (ERG26) disruption also was viable in a hem 1Delta strain grown in the presence of ergosterol. Introduction of the erg26 mutation into an erg1 (squalene epoxidase) strain also was viable in ergosterol-supplemented media. We demonstrated that erg26 mutants grown on various sterol and heme-supplemented media accumulate nonesterified carboxylic acid sterols such as 4beta, 14alpha-dimethyl-4alpha-carboxy-cholesta-8,24-dien-3be ta-ol and 4beta-methyl-4alpha-carboxy-cholesta-8,24-dien-3beta-o l, the predicted substrates for the C-3 sterol dehydrogenase. Accumulation of these sterol molecules in a heme-competent erg26 strain results in an accumulation of toxic-oxygenated sterol intermediates that prevent growth, even in the presence of exogenously added sterol.     

Nasal symptoms and indices of nasal inflammation in flour-dust-exposed bakers

OBJECTIVE: To analyze whether indices of nasal airway inflammation in bakers were related to nasal symptoms and exposure to airborne flour dust. METHODS: A cross-sectional study was performed in 12 currently flour-exposed bakers. They were examined by nasal lavage (NAL), visual inspection, a test of mucociliary clearance, and nasal peak expiratory flow (nasal PEF). NAL fluid was analyzed according to the inflammatory markers eosinophil cationic protein (ECP), indicating eosinophilic activity; myeloperoxidase (MPO), indicating active neutrophils; hyaluronic acid (HA) from active fibroblasts; tryptase, indicating activation of mast cells; and albumin, indicating plasma exudation. The bakers were also questioned about respiratory symptoms and working history. Their current and cumulative exposure to inhalable flour dust was estimated after exposure measurements and information about earlier work tasks. Office workers (n=16) without occupational exposure to dust or any other known nasal irritant or sensitizer served as controls. RESULTS: Personal inhalable dust measurements among the bakers working as dough makers or bread formers ranged from 1.0 to 3.8 mg/m3. Of the 12 bakers, 10 reported at least 1 nasal symptom (crusts, blockage, or a runny nose), a proportion significantly greater than that of the controls (P=0.009). Bakers with nasal symptoms had higher concentrations of markers of inflammation in their NALs as compared with nonsymptomatic bakers. The difference was significant for MPO (P=0.02) and HA (P=0.04) in relation to a runny nose. Tryptase was detected in only one NAL of the bakers. There was a positive correlation between the cumulative dose of inhalable flour dust and concentrations of MPO and HA in NAL. Two bakers were sensitized to wheat; they had the highest NAL concentrations of inflammatory markers. CONCLUSIONS: Our results indicate that flour dust exposure in bakers at levels below the current occupational exposure limit causes nasal mucosal inflammation, which, in turn, is related to nasal symptoms. We propose that the inflammation may be nonallergic, characterized by activation of neutrophils and fibroblasts.     

Human electroencephalographic (EEG) response to olfactory stimulation: two experiments using the aroma of food

The present studies sought to examine the effect of olfactory stimulation on human Central Nervous System activity. In the first experiment (n = 21), EEG response to the 'synthetic' odours of chocolate, spearmint, almond, strawberry, vegetable, garlic and onion, and cumin or no odour was recorded from 19 electrodes (F3, F4, F7, F8, Fz, T3, T4, T5, T6, P3, P4, Pz, O1, O2, C3, C4, Cz) in all EEG frequencies (delta, theta, alpha, beta1 and beta2). Exposure to the odour of chocolate was associated with significant reductions in theta activity when compared with the odours of almond and cumin, with a trend towards significance when compared with no-odour control. Exposure to the odour of spearmint was associated with a significant reduction in EEG theta when compared with the no-odour control. No significant effects were observed in other frequencies. In a second experiment (n = 15), EEG response to the odours of real foods (chocolate, baked beans, rotting pork) and two controls (no odour and hot water) was recorded as in Experiment 1. The odour of chocolate was associated with significantly less theta activity than was any other stimulus. It is hypothesised that the alterations in theta reflect shifts in attention or cognitive load during olfactory perception, with a reduction in theta indicating a reduced level of attention.