Biomedical subjects
Publications and source records attributed to A Thelin.
The half-life of ubiquinone-9 in various rat tissues was determined. Rats were injected intraperitoneally with [3H]mevalonate and the decay of radioactivity incorporated into ubiquinone-9 was followed using reverse-phase HPLC. The half-life varied between 49 h (testis) and 125 h (kidney).
Long chain cis-prenyltransferase in rat liver microsomes was studied using various allylic isoprenoid substrates. Microsomes could utilize trans-geranyl pyrophosphate, but not cis-geranyl pyrophosphate for polyprenyl pyrophosphate synthesis. Both trans, trans-farnesyl pyrophosphate and trans,cis-farnesyl pyrophosphate were used as substrates with Km values of 24 and 5 microM, respectively. trans,trans,cis-Geranylgeranyl pyrophosphate could be used as substrate with an apparent Km of 36 microM. trans,trans,trans-Geranylgeranyl pyrophosphate was also utilized as substrate, but with a very low affinity. After pulse labeling for 4 min, using [3H]isopentenyl pyrophosphate and trans,trans-farnesyl pyrophosphate, the only product formed was trans,trans,cis-geranylgeranyl pyrophosphate, which, upon chasing, yielded polyprenyl pyrophosphate. Independent of the nature of the substrate used, even in the case of polyprenyl 12-pyrophosphate and all-trans-nonaprenyl pyrophosphate, the chain lengths of the products were identical, i.e. polyprenyl pyrophosphates with 15-18 isoprene residues. Microsomes were able to synthesize trans,trans-farnesyl pyrophosphate using trans-geranyl pyrophosphate as substrate. The results indicate that rat liver microsomes contain a farnesyl pyrophosphate synthase activity and that the reaction catalyzed by cis-prenyltransferase may consist of two individual steps, i.e. synthesis of trans,trans,cis-geranylgeranyl pyrophosphate and elongation of this product to long chain polyprenyl pyrophosphates.
Isolated peroxisomes were able to utilize [3H]isopentenyl diphosphate to synthesize farnesyl diphosphate, which then was utilized as substrate by both the peroxisomal squalene synthetase and cis-prenyltransferase. The specific activity of squalene synthetase in peroxisomes was as high as in microsomes, i.e. 160 pmol/mg of protein/min. If NADPH was omitted from the assay medium, presqualene diphosphate accumulated, which indicates that the reaction occurs in two steps, as in microsomes. In the presence of NADPH, incorporation from [3H]farnesyl diphosphate was stimulated 3-fold, and the major products were squalene and cholesterol. The specific activity of cis-prenyl-transferase in peroxisomes was 4-fold higher than in microsomes, i.e. 456 pmol of isopentenyl diphosphate incorporated/mg of protein/h. There were two major products formed from farnesyl diphosphate and [3H] isopentenyl diphosphate, i.e. trans,trans,cis-geranylgeranyl diphosphate and long chain polyprenyl diphosphates. The polyprenyl diphosphates had the same chain length distribution as that of dolichol derivatives in rat liver, with the dominating polyisoprenes being C90 and C95. In contrast to the microsomal enzyme, peroxisomal cis-prenyltransferase did not require detergents for optimal activity. The enzyme was associated primarily with the peroxisomal membrane after sonication of the peroxisomes.
The cytosolic fractions from rat liver, brain, kidney, spleen and testis demonstrate the capacity to synthesize two products from [3H]isopentenyl diphosphate, i.e., farnesyl diphosphate and geranylgeranyl diphosphate. The highest rate of geranylgeranyl diphosphate synthesis was found in brain, testis and spleen, accounting for up to 30% of the total incorporation of radioactivity under optimal conditions. In all tissues examined the geranylgeranyl diphosphate formed was identified as the trans,trans,trans-isomer. The ratio of geranylgeranyl diphosphate to farnesyl diphosphate produced was specific for the tissue investigated and could be altered by the addition of divalent cations. The results in this study demonstrate the presence of a specific trans,trans,trans-geranylgeranyl diphosphate synthetase showing high affinity for farnesyl diphosphate.
The properties of rat liver cis-prenyl transferase, mediating the synthesis of polyisoprenoid pyrophosphate from trans,trans-farnesyl pyrophosphate and [3H]isopentenyl pyrophosphate were studied. The Km values for farnesyl pyrophosphate and isopentenyl pyrophosphate were found to be 25 microM and 4.4 microM, respectively. Appropriate conditions were established to measure the condensation reaction, which was linear during the first hour using 1 mg microsomal protein. Various detergents could solubilize the enzyme, but the presence of Triton X-100 was required during the incubation to obtain full activity. There was also an absolute requirement for Mg2+ and the pH maximum was 7.0. Inorganic phosphate, especially pyrophosphate, proved to be inhibitory. cis-Prenyl transferase is associated mainly with the cytoplasmic surface of rough microsomes and, to some extent, also with smooth I microsomes, but was almost absent from smooth II microsomes. At all localizations, the product is polyprenyl pyrophosphate and to some extent, also polyprenyl monophosphate. The isoprenoids formed contain 15-18 units in the presence of detergents and 16-20 units in the absence of detergents.
Rats were injected via the portal vein with (RS)-[5-3H]-mevalonolactone and the lipids were extracted. From fractions of liver homogenate, all labeled dolichol, cholesterol and ubiquinone could be extracted, but about 40% of microsomal and lysosomal dolichyl phosphate was only released after alkaline hydrolysis. Only a small amount of the non-extractable radioactivity was found to be associated with alpha-unsaturated polyprenyl phosphate. There was no difference in the polyisoprenoid pattern when the two pools of dolichyl phosphate were compared. On the other hand, the specific activity of the bound lipid was only half that of the extractable form. After phenyl-Sepharose chromatography, a peak of protein was isolated exhibiting a 25-fold enrichment in bound radioactive dolichyl phosphate. Treatment with a non-specific protease, followed by chromatography, gave polypeptide fragments associated with bound lipids. On SDS/PAGE a major protein band at 23 kDa and some minor bands with higher molecular masses were found to be associated with this lipid. The results indicate the presence of covalently bound dolichyl phosphate in rat liver.
A number of epidemiological studies have shown that farmers have low mortality rates. To examine morbidity risks for male and female farmers in Sweden, the national hospital care registry was updated with information on occupation derived from the census of 1980. The cause-specific morbidity of farmers was compared with the morbidity of all economically active individuals in the same areas. A total of 60,515 farmers and 2,843,217 controls have been studied. The morbidity rates of the farmers were generally low. Male farmers had a significantly lower risk for cancer diseases, mental diseases, cardiovascular diseases, diseases of the digestive system, the uro-genital system, and skin diseases. Female farmers had a lower risk for diseases of the respiratory system, uro-genital system, skin diseases, diseases of the locomotor system, and accidents. A notable discrepancy between males and females concerning cardiovascular diseases was observed Male farmers had a significantly lower risk than other men while female farmers had the same risk level as other economically active women. The relative risk of hospitalization for mental disease was also low. Male farmers had a risk for alcohol-dependent diseases and attempted suicides which was less than one-third of the risk for all economically active men. Concerning work-environment-related diseases in farming, it was shown that young male farmers had low rate ratios. However, the risks were found to increase with every decade, indicating that occupational health risks contribute to morbidity with advancing age.
Explore the source record for details and available documents.
Observations among Swedish farmers indicate that coxarthrosis is a common disorder in farming populations. In this case-referent study, we describe relationships between farming and hip joint arthrosis. The case-group consisted of 105 persons who have had surgery because of coxarthrosis and the referents consisted of 222 randomly selected persons. Non-responders totaled 9%. Farming was significantly more common in the case group. The ratio varied between 2.1 and 3.2, varying with the length of time in farming. Longer exposure did not seem to result in greater risk. There was no risk elevation related to forestry or transportation work. Nor was there any over-representation of accidents with injuries to the lower extremities in the case group. Heavy work load did not seem to be related to the genesis of coxarthrosis. Farming is an amalgamation of different types of work. However, we develop the hypothesis from this study that tractor driving may be related to hip arthrosis. Unfavorable angles in the hip joints may occur during tractor driving. Other studies support this hypothesis, as it has been found that unsuitable conditions for the hip joints may be related to arthrosis.
Farmers' health and safety are critical public health problems that have historically been ignored in the United States and in many countries by health policy developers. The challenges to reduce the hazards are significant. However, by mobilizing the resources, the public will, and the structure to carry out preventive programs, progress is possible. Sweden has shown that research, education, engineering, and regulation have resulted in significant reductions of tractor rollover deaths, chainsaw injuries, and hearing loss.
Explore the source record for details and available documents.
Airborne dust and endotoxin levels on poultry farms, were determined for various working processes known to involve a heavy exposure. Forty-seven workers at different sites were studied by questionnaires for work-related symptoms. Lung function measurements were made before and after work. Dust levels exceeded the standard for organic dust, and endotoxin levels exceeded those known to cause respiratory and other symptoms. The average decrease in FEV1 over the working day(s) ranged from 0.07-0.19 litres. Upper airway irritation was present in one third of the workers, and about 10% complained of chest tightness. The effect may have been due to the high amounts of dust causing a general respiratory irritation as well as to the endotoxin.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: Several studies have shown an increased risk of congenital foot derformities after early amniocentesis. These studies have comprised amniocenteses performed before 13 completed gestational weeks. In this study, the risk of foot deformities after amniocentesis performed at 12-14 completed gestational weeks was determined. METHODS: 3,469 genetic amniocenteses in singleton pregnancies performed before 15 completed gestational weeks were studied. The intention was to perform the amniocenteses at 12-14 weeks of gestation, but 32 amniocenteses were performed at the gestational age 11 weeks + 5 days or 11 weeks + 6 days. The pregnancies were followed up with regard to fetal loss and leakage of amniotic fluid. After birth, newborns with a diagnosis of foot deformity were identified from the Swedish Medical Birth Registry. The observed number of foot deformities was then compared with the expected number which was calculated stratified for delivery hospital, year of birth, and maternal age. RESULTS: The observed number of foot deformities was significantly higher than the expected: exact odds ratio 1.74 (exact 95% confidence interval 1.06-2.69). The rate of spontaneous abortions after the procedure was 1.8%, and the rate of leakage of amniotic fluid was 1.9%. There was a significant trend for all complications to decrease with increasing gestational age at amniocentesis. CONCLUSION: Women undergoing amniocentesis at 11+5 to 14+6 gestational weeks have an increased risk of giving birth to a child with a congenital foot deformity.
To investigate whether differences in the use of health care facilities and the distribution of risk factors were related to the accessibility of occupational health services, 912 farmers in a large research project were studied. Information was collected from nine different localities in rural areas, using questionnaires, standardized interviews, physical examinations, and blood tests. The results showed that there was hardly any difference in the use of general health care facilities between the groups. Those with occupational health services generally had more medical visits, but also had fewer diagnoses of cardiac disease. Known risk factors were present more often in the group without occupational health services. The work of the occupational health care service and the individual's interest in health questions appeared to be of significance in the way the risk factors were distributed.
To determine whether membership in an occupational health service program varies with correlation with psychosocial risk factors, this study was carried out among farmers in connection with a larger investigation of salutogenic factors. The study was based on information collected via questionnaires (answered on location) and standardized interviews. The material consists of 364 farmers or persons engaged in agriculture who had occupational health care and 548 without it. There were clear differences in psychosocial patterns between the groups. Those with occupational health care were less often single and had more education and more social contacts than did those without such care. Eating times were more regular and meals were better in those with occupational health care. Karasek-Theorell's indices for psychological demands and decision latitude at work were also higher in this group. Better-educated farmers and those with larger farms were more often members of an occupational health care program. In addition, this group had fewer psychosocial risk factors.