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Extracellular Enzyme Production and Synthetic Lignin Mineralization by Ceriporiopsis subvermispora.

The ability of the white rot fungus Ceriporiopsis subvermispora to mineralize C-synthetic lignin was studied under different culture conditions, and the levels of two extracellular enzymes were monitored. The highest mineralization rates (28% after 28 days) were obtained in cultures containing a growth-limiting amount of nitrogen source (1.0 mM ammonium tartrate); under this condition, the levels of manganese peroxidase (MnP) and laccase present in the culture supernatant solutions were very low compared with cultures containing 10 mM of the nitrogen source. In contrast, cultures containing a limiting concentration of the carbon source (0.1% glucose) showed low levels of both enzymes and also very low mineralization rates compared with cultures containing 1% glucose. Cultures containing 11 ppm of Mn(II) showed a higher rate of mineralization than those containing 0.3 or 40 ppm of this cation. Levels of MnP and laccase were higher when 40 ppm of Mn(II) was used. Mineralization rates were slightly higher in cultures flushed daily with oxygen, whereas laccase levels were lower and MnP levels were approximately the same as in cultures maintained under an air atmosphere. The presence of 0.4 mM veratryl alcohol reduced both mineralization rates and MnP levels, without affecting laccase levels. Lignin peroxidase activity was not detected under any condition. Addition of purified lignin peroxidase to the cultures in the presence or absence of veratryl alcohol did not enhance mineralization rates significantly.

Journal Article↗

Growth of iron(III)-reducing bacteria on clay minerals as the sole electron acceptor and comparison of growth yields on a variety of oxidized iron forms.

Smectite clay minerals are abundant in soils and sediments worldwide and are typically rich in Fe. While recent investigations have shown that the structural Fe(III) bound in clay minerals is reduced by microorganisms, previous studies have not tested growth with clay minerals as the sole electron acceptor. Here we have demonstrated that a pure culture of Shewanella oneidensis strain MR-1 as well as enrichment cultures of Fe(III)-reducing bacteria from rice paddy soil and subsurface sediments are capable of conserving energy for growth with the structural Fe(III) bound in smectite clay as the sole electron acceptor. Pure cultures of S. oneidensis were used for more detailed growth rate and yield experiments on various solid- and soluble-phase electron acceptors [smectite, Fe(III) oxyhydroxide FeOOH, Fe(III) citrate, and oxygen] in the same minimal medium. Growth was assessed as direct cell counts or as an increase in cell carbon (measured as particulate organic carbon). Cell counts showed that similar growth of S. oneidensis (10(8) cells ml(-1)) occurred with smectitic Fe(III) and on other Fe forms [amorphous Fe(III) oxyhydroxide, and Fe citrate] or oxygen as the electron acceptor. In contrast, cell yields of S. oneidensis measured as the increase in cell carbon were similar on all Fe forms tested while yields on oxygen were five times higher, in agreement with thermodynamic predictions. Over a range of particle loadings (0.5 to 4 g liter(-1)), the increase in cell number was highly correlated to the amount of structural Fe in smectite reduced. From phylogenetic analysis of the complete 16S rRNA gene sequences, a predominance of clones retrieved from the clay mineral-reducing enrichment cultures were most closely related to the low-G+C gram-positive members of the Bacteria (Clostridium and Desulfitobacterium) and the delta-Proteobacteria (members of the Geobacteraceae). Results indicate that growth with smectitic Fe(III) is similar in magnitude to that with Fe(III) oxide minerals and is dependent upon the mineral surface area available. Iron(III) bound in clay minerals should be considered an important electron acceptor supporting the growth of bacteria in soils or sedimentary environments.

Electrons↗

Bone mineral content in cystic fibrosis patients: correlation with fat-free mass.

OBJECTIVE: To assess the bone mineral content in well nourished patients with cystic fibrosis and to seek a correlation with fat-free mass. METHODS: Fourteen cystic fibrosis patients aged 6 to 20 years were studied and compared to 14 healthy controls matched for gender, age, and nutritional status. Bone mineral content was determined by dual energy x ray absorptiometry (DEXA). RESULTS: Nutritional inquiry showed higher ingestion of macronutrients and micronutrients by cystic fibrosis patients than by controls. Mean whole skeleton bone mineral content was 1.184 (SD 0.536) kg in cystic fibrosis patients and 1.229 (0.576) kg in controls (p = 0.84). Mean lumbar spine bone mineral content was 0.031 (0.013) kg and 0.031 (0.016) kg, respectively (p = 0.99). Anthropometry, bioelectrical impedance analysis, and DEXA showed that fat-free mass was similar in the two groups. Bone mineral content was strongly correlated to fat-free mass. Mean blood calcium, phosphorus, serum 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), and osteocalcin were similar in both groups. CONCLUSIONS: Bone mineral content and body composition are normal in a well nourished young cystic fibrosis population. Osteopenia previously reported in cystic fibrosis patients probably has nutritional origins and is therefore not related to a primary defect in bone mineral metabolism.

Adolescent↗

Dietary calcium, sex hormones, and bone mineral density in men.

OBJECTIVE: To evaluate the factors that determine bone mineral density at axial and appendicular sites in normal men. DESIGN: Measurement of bone mineral density of the radius by single photon absorptiometry and of the lumbar spine and hip by dual photon absorptiometry to assess their relation with various determinants of bone mineral density. Dietary calcium was assessed from a questionnaire validated against a four day dietary record. SETTING: Local community, Sydney, Australia. PATIENTS: 48 Men (aged 21-79, median 44) recruited from the local community including 35 male cotwins of twin pairs of differing sex recruited from the Australian National Health and Medical Research Council twin registry for epidemiological studies on determinants of bone mineral density. MAIN OUTCOME MEASURES: Bone mineral density of the axial and appendicular skeleton and its relation to age, anthropometric features, dietary calcium intake, and serum sex hormone concentrations. RESULTS: Dietary calcium intake (g/day) was a significant predictor of bone mineral density of axial bones, explaining 24% and 42% of the variance at the lumbar spine and femoral neck respectively. This effect was independent of weight. In contrast with the axial skeleton, bone mineral density at each forearm site was predicted by weight and an index of free testosterone but not by dietary calcium intake. CONCLUSIONS: Dietary calcium intake has a role in the determination or maintenance, or both, of the axial but not the appendicular skeleton in adult men.

Adult↗

A prospective study of alcohol consumption and bone mineral density.

OBJECTIVES: To study the effects of alcohol consumption on bone mineral density in a defined population. DESIGN: Prospective study of bone mineral density, measured during 1988-91, in a cohort who had given baseline data on alcohol intake in the previous week and in the previous 24 hours and other factors affecting bone mineral density during 1973-5. SETTING: Rancho Bernardo, California. SUBJECTS: 182 men and 267 women aged 45 and over at baseline, half having been randomly selected and half having been chosen for hyperlipidaemia, who gave baseline information on alcohol intake in one week. Of these subjects, 142 men and 220 women gave information on alcohol intake in 24 hours. MAIN OUTCOME MEASURES: Bone mineral density of the radial shaft, ultradistal wrist, femoral neck, and lumbar spine. RESULTS: Men and women were considered separately, and the tertiles of alcohol consumption were used to delineate low, medium, and high values of alcohol intake. With increasing alcohol intake in one week, bone mineral density (adjusted for age, body mass index, smoking, taking exercise, and oestrogen replacement therapy in women) increased significantly in the femoral neck of men (p < 0.01) and the spine of women (p < 0.01). With increasing alcohol intake in 24 hours, adjusted bone mineral density increased significantly in the radial shaft (p < 0.05) and spine (p < 0.001) of women. Similar, but not significant, patterns were seen at the other bone sites. CONCLUSIONS: Social drinking is associated with higher bone mineral density in men and women.

Alcohol Drinking↗

Relation of common allelic variation at vitamin D receptor locus to bone mineral density and postmenopausal bone loss: cross sectional and longitudinal population study.

OBJECTIVE: To determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss. DESIGN: Cross sectional and longitudinal population study. SETTING: Outpatient clinic in research centre. SUBJECTS: 599 healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 had bone mineral density measured once in the cross sectional study. 136 women aged 45-54 were followed up for 18 years in the longitudinal study. MAIN OUTCOME MEASURES: Bone mineral density measured at the lumbar spine, hip, and forearm and rate of bone loss at different times over 18 years in relation to vitamin D receptor genotype as defined by the endonucleases ApaI, EsmI, and TaqI. RESULTS: Vitamin D receptor genotype was not related to bone mineral density at any site. The maximum difference between homozygotes was 1.3% (P = 0.33, n = 723). Women with low bone mineral density had almost the same genotype frequencies as the women with normal bone mineral densities. Vitamin D receptor genotype was not related to early postmenopausal bone loss from age 51 to 53 (mean (SD) total loss at the lower forearm -3.6% (3.6%)), late postmenopausal bone loss from age 63 to 69 (at the hip-6.2% (8.7%)), or to long term postmenopausal loss from age 51 to 69 (at the lower forearm-24.5% (11.4%)). CONCLUSION: Common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, EsmI, and TaqI is related neither to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.

Adult↗

Screening for gastric carcinoma in coal miners.

This study aimed to determine the prevalence of dyspeptic symptoms and premalignant gastric lesions in coal miners and sex matched population control subjects. Retired coal miners and men from the general population in north Nottinghamshire were sent a dyspepsia questionnaire to fill in, and those with upper gastrointestinal symptoms were invited for gastroscopy and biopsy. A total of 1272 men from the general population and 2099 retired coal miners aged 50-75 years took part in the study. Some 977 of 1272 (76.8%) control subjects and 1715 of 2099 (81.7%) miners replied to the questionnaire. A total of 308 of 977 (31.5%) controls and 620 of 1715 (36.2%) miners were positive for at least one symptom. There was a highly significant difference between the numbers of surface mine and underground workers who reported dyspeptic symptoms (66 of 300 (22%) v 425 of 1083 (32.2%) of p < 0.0001). Histology showed that significantly more miners than controls had acute on chronic gastritis (22 v 11%; p = 0.01) and intestinal metaplasia (23 v 8%; p = < 0.0001). Coal miners may be a suitable group for gastric premalignancy screening using an upper gastrointestinal symptom questionnaire and upper gastrointestinal endoscopy.

Age Factors↗

A prospective cohort study among new Chinese coal miners: the early pattern of lung function change.

AIMS: To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. METHODS: The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. RESULTS: FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. CONCLUSION: Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

Adolescent↗

Mortality in gold and coal miners in Western Australia with special reference to lung cancer.

Cohorts of 1974 gold miners and 213 coal miners in Western Australia surveyed for respiratory symptoms, smoking habits, occupational history and radiographic evidence of pneumoconiosis have been followed up for 13-14 years. Overall, neither group had a significantly higher mortality than expected from the experience of Western Australian men in general. Lung cancer mortality was relatively high in the gold miners (59 deaths observed, 40.8 expected) but weakly and inconclusively related to the extent of their underground mining experience. Cigarette smoking may explain the excess of lung cancer in the gold miners because the prevalence of the habit in the latter (66.3%) was higher than in the coal miners (58.7%) or in other men in Western Australia (53.2%). Radiographic evidence of silicosis was present in 21.7% of the gold miners but did not appear to have contributed substantially to their mortality. The coal miners showed a lower than expected rate of lung cancer but an excess of deaths from all other forms of cancer (11 observed, 5.6 expected). This excess was not attributable to any one cancer site and cannot be explained readily.

Australia↗

Respiratory ill health among coal miners and telecommunication workers in south Wales.

As part of a large cross sectional epidemiological study of respiratory disease in coalminers, the respiratory health of miners in one colliery in south Wales has been compared with the health of nearby telecommunication (telecom) workers. The studies were carried out in 1981 and 1982. The answers to questionnaires on respiratory symptoms and results of lung spirometry indicate a much greater frequency of respiratory ill health among the miners than the telecom workers. The frequency of symptoms of chronic bronchitis among the current employees was 31% in the miners and 5% in the telecom workers, and these symptoms were reported as frequently by younger as by older miners. Reports of other respiratory symptoms showed similarly large differences between current miners and telecom workers. These differences were seen both within non-smoking and smoking groups. Comparisons of FEV1 with predicted values (several different predictions were used) confirmed that the differences in reported symptoms were accompanied by differences in lung function; of the order of 20% of current miners had an FEV1 less than 80% of predicted compared with 10% of current telecom workers. The excess of respiratory disease shown among these miners is not necessarily a consequence of the dust concentrations currently experienced underground, nor is the colliery necessarily representative of the coal industry generally. The findings, however, indicate the continued need for measures to improve the respiratory health of these men.

Adult↗

Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.

Adenocarcinoma↗

A cross sectional study of the independent effect of occupation on lung function in British coal miners.

BACKGROUND: Chronic bronchitis and emphysema are now recognised complications of occupational exposure to coal dust, and since 1992 compensation has been available for miners with impaired lung function provided that they also have x ray film evidence of pneumoconiosis. However, many miners with heavy exposure to coal dust and impairment of lung function therefore do not qualify for compensation because they do not have simple pneumoconiosis. In the present study attempts were made to determine whether coal mining is an independent risk factor for impairment of lung function in a group of Nottinghamshire miners with no evidence of simple pneumoconiosis, by comparing these men with a group of local controls who were not occupationally exposed. METHOD: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were obtained on 1286 miners with no evidence of pneumoconiosis on x ray film. Lung function data were also obtained from a random sample of 567 men aged between 40 and 70 living in a district of Nottingham and who had never worked in the mining industry or in any other dusty occupation. Multiple linear regression in SPSS was used to estimate the mean independent effect of mining on FEV1 and FVC after adjustment for age, height, and smoking, in all miners and controls, and in a subgroup of men of 45 and under. In men of 45 and under, the independent effects of mining and smoking on the probability of a deficit of one litre or more from modelled predicted FEV1 values were computed with logistic regression in EGRET. RESULTS: There was a significant mean effect of mining on FEV1 after adjustment for age, height, and smoking of -155 ml (95% confidence interval (95% CI) -74 to -236 ml, P < 0.001), but the size of effect was inversely related to age such that in men of 45 and under the estimated mean effect of mining was -251 ml (95% CI -140 to -361 ml, P < 0.001). In this subgroup of younger men, 4.7% of miners and 0.7% of controls had a deficit of one litre or more from predicted FEV1 values, and in logistic regression, there was a marginally significant independent effect of both smoking (P = 0.05) and mining (P = 0.07) for a deficit of this magnitude. CONCLUSIONS: Occupational exposure to coal dust is associated with a small mean deficit in lung function even in the absence of simple pneumoconiosis, and independently from the effects of smoking. The requirement that miners should have evidence of pneumoconiosis to qualify for compensation for impaired lung function is therefore unjustified.

Adult↗

Role of protozoa in microbial acclimation for mineralization of organic chemicals in sewage.

The role of protozoa in affecting the length of the acclimation period for the mineralization of organic compounds in sewage was investigated. The acclimation periods for the mineralization of 2 ng of p-nitrophenol, 100 ng of 2,4-dichlorophenoxyacetic acid, and 100 ng of 2,4-dichlorophenol per milliliter were markedly shortened or eliminated when the indigenous protozoa were inhibited with cycloheximide and nystatin. The extent of mineralization of the test compounds decreased when the protozoa were suppressed. Inhibition of the protozoa increased the total number of bacteria and the density of organisms able to mineralize 2 ng of p-nitrophenol/mL of sewage. Addition of Tetrahymena thermophila to sewage in which the indigenous protozoa were not active lengthened the acclimation period for the mineralization of p-nitrophenol. The addition of T. thermophila to a culture containing a low density of a p-nitrophenol-degrading Pseudomonas sp. did not affect the acclimation period prior to mineralization of the substrate, but the ciliate increased the acclimation period in the presence of high densities of Enterobacter aerogenes added as an alternative prey species. We suggest that protozoan grazing may be responsible for the acclimation period prior to the mineralization of certain organic compounds in sewage.

Animals↗

Vitamin D is not directly necessary for bone growth and mineralization.

To determine whether vitamin D has a direct action on bone growth and mineralization, severely vitamin D-deficient rats were infused continuously for 10 days with calcium and phosphorus solutions intrajugularly to maintain plasma calcium and phosphorus levels equal to those in rats on the same diet given vitamin D. Rats from the same litters identically treated were given 75 IU of vitamin D3 every 3 days and infused with saline for the 10-day period for comparison. Infusion of calcium and phosphorus to the vitamin D-deficient rats induces bone growth and mineralization equal to that of the rats given vitamin D as revealed by femur length, femur weight, total femur ash, percent femur ash, and epiphyseal plate width. The mineral deposited had a calcium-to-phosphorus ratio of 1.6 identical to the mineral deposited in the rats given vitamin D and unlike controls maintained in the vitamin D-deficient state without infusions. The vitamin D-deficient rats infused with calcium and phosphorus had greater amounts of mineral and matrix in their femurs than did those treated with vitamin D. This result demonstrates that some form of vitamin D does have a direct effect on bone. The most likely possibility is that bone resorption in relation to modeling or calcium mobilization for calcium homeostasis or both are compromised in extreme vitamin D deficiency. The above results strongly support the concept that vitamin D is not necessary for and does not stimulate directly bone growth and mineralization. Vitamin D therefore supports bone growth and mineralization indirectly by elevating plasma calcium and phosphorus levels.

Animals↗

Regulation of bone mineral loss during lactation.

The effects of varying dietary calcium and phosphorus content, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation were examined in rats. Unless otherwise stated, the diet contained 0.47% calcium and 0.3% phosphorus and the rats were given 26 nmol of vitamin D3. Femur ash weights were determined after 21 days of lactation and on age-matched nonlactating rats. Decreasing dietary calcium to 0.02% caused an increased loss of bone mineral, whereas increasing dietary calcium to 1.4% increased plasma calcium levels to 12 mg/100 ml but did not diminish the bone mineral loss observed during lactation. Varying dietary phosphorus did not have a major effect on bone mineral loss during lactation. In vitamin D-deficient rats, bone mineral loss during lactation was independent of dietary calcium levels and slightly greater than the loss observed in vitamin D-replete rats fed the normal calcium diet. Oophorectomy and adrenalectomy did not produce changes in femur ash weights of nonlactating rats or reduce bone mineral loss during lactation. Rats mated during their postpartum estrus and thus simultaneously pregnant and lactating, lost the same amount of bone mineral as caused by lactation alone.

Adrenalectomy↗

Collagen and non-collagenous proteins in different mineralization stages of human femur.

Mineralized tissues exhibit varying degrees of mineralization in different areas within the same bone. Using the technique of density gradient fractionation, bone powder from the diaphysis of human femur has been separated in different fractions corresponding to the degree of mineralization. Isolated bone fractions were analysed for their content in collagen and non-collagenous proteins. The results showed marked differences between compact and spongy bones, this latter containing higher proportions of little mineralized bone particles than the former (p less than 0.01). The ethylenediaminetetra-acetic acid (EDTA) extractability and the bone matrix size decreased relative to the decrease in specific gravity of bone particles. Among the matrix components of different fractions, sialoprotein consistently increased with the increase in specific gravity while proteoglycan decreased in reverse manner to the increase in collagen. However, in the most mineralized fraction (specific gravity: 2.33 g/cm3), the proteoglycan amount increased while collagen decreased. In conclusion, this study of bone maturation in human femur confirms the suitability of the technique of density gradient fractionation in the studies of bone matrix-mineral interactions. Apart from the fraction with the highest specific gravity, the analytical results obtained in fractions are similar to those observed in age-related bone changes, suggesting that the increase in mineralization degree of bone particles may be related to their age.

Aging↗

Ultrastructure of mineralized nodules formed in rat bone marrow stromal cell culture in vitro.

Rat bone marrow stromal cells were cultured in vitro. At days 14-15 of culture, dense clusters of polygonal cells were formed, and they mineralized 2-3 days later. The cells resembling osteoblasts or young osteocytes were histologically observed to be embedded in mineralized or unmineralized extracellular matrices of the nodules. Next, these mineralized nodules were electron-microscopically examined. The osteoblastic cells associated with the nodules had a well-developed rough endoplasmic reticulum, an evident Golgi apparatus and some mitochondria as their intracellular organellae. Some lysosomes and microfilaments were also visible in the cytoplasms. Moreover, some cells protruded cell processes toward the neighboring cells through the extracellular matrix. The extracellular matrix consisted of numerous collagen fibrils which were striated with 60-70 nm axial periodicity and which was similar to bone tissue collagen. A large number of matrix vesicles were scattered among the collagen fibrils in the unmineralized area of the nodules. In contrast, in the mineralized area, numerous matrix vesicles at different stages of maturation and many calcified spherules were observed. That is the mineralization in this culture system was considered to be initiated in association with the matrix vesicles and to progress along the collagen fibrils. From these findings, it was confirmed by the present study that the mineralized nodules formed in this bone marrow stromal cell culture were ultrastructurally similar to bone and that the mineralization also proceeded by going through the normal calcification process. This culture system is considered to be available to study osteogenic differentiation and calcification mechanisms.

Alkaline Phosphatase↗

Systemic sclerosis in German uranium miners under special consideration of autoantibody subsets and HLA class II alleles.

Systemic sclerosis (scleroderma) is a connective tissue disease with a wide range of clinical manifestations, with high or low degrees of skin and internal organ involvement together with different antinuclear antibody (ANA) specificities. Several studies provide evidence that males, who are rarely affected by systemic sclerosis, have an increased risk when working in mines. Therefore we reinvestigated 21 male subjects and 6 cases of deceased male patients who had been engaged in East German uranium mines and had shown evidence of this disease in medical examinations. Dermatological investigations, evaluation of chest X-rays and autoantibody estimation were performed. PCR-sequence-specific oligonucleotide typing was used to study the genetic association of HLA-D alleles with autoantibodies typical for scleroderma in these uranium miners suffering from systemic sclerosis and in patients with idiopathic systemic sclerosis. The determined HLA phenotype frequencies and the following statistical analysis (Fisher's exact test (2-sided)) revealed that in comparison with randomly selected controls, alleles DRB1*0300 (DR3) and DQB1*0201 (DQ2) were distinctly increased in the group of affected uranium miners, especially in those with anti-Scl-70 positivity. In contrast, we did not observe significant differences between affected and unaffected miners. Comparing anti-Scl-70-positive affected uranium miners with anti-Scl-70-positive idiopathic systemic sclerosis cases. DRB1*0300 as well as DQB1*0201 were also significantly enhanced in the former group. ACA-positive systemic sclerosis miners had significantly elevated frequencies in DRB1*0100 (DR1) and DRB1*0800 (DR8) only in comparison with unaffected miners and unexposed controls. Our genetic and immunological data lead to the assumption that a different set of HLA-D alleles in combination with exogenous factors is involved in the induction of anti-Scl-70 antibodies in uranium miners that might influence their susceptibility to the disease, whereas the same occupational exposure seems to have no influence on the induction of ACA antibodies.

Adult↗