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Biomedical subjects

T Hansson

Publications and source records attributed to T Hansson.

At least 91 records · Page 5Linked to original sources

Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system.

A specific form of cytochrome P450, P450 IIE1, active in ethanol oxidation, is known to be induced about 10-fold in rat liver following ethanol treatment. This isozyme of P450 participates effectively in the metabolic activation of precarcinogens, such as N-dimethylnitrosamines, and of solvents such as carbon tetrachloride and benzene. In the present investigation, two different polyclonal antisera against P450 IIE1 were used in order to map the regional distribution of this P450 form in the rat central nervous system. The presence of P450 IIE1 in various brain regions was confirmed by Western blot analysis. The P450 IIE1-immunoreactivity was heterogeneously distributed between brain areas. Neuronal cell bodies and glial cells of presumed astroglial as well as oligodendroglial identity contained immunoreactivity. All fiber tracts harbored P450 IIE1-immunoreactive glial cells as did the ependymal lining of the ventricular wall as well as small and large vessels throughout the brain. P450 IIE1-immunoreactive glial cells were present in all areas of the neocortex, in the olfactory bulb, in the piriform cortex and in several different thalamic nuclei. In the cerebellum, P450 IIE-immunoreactivity was found in all cell layers and was exclusively localized to glial cells and their processes. Staining of blood vessels was prominent in the white matter where P450 IIE1-immunoreactive glial cells were seen to have end-feet on the vessels. A subgroup of pyramidal cells of the frontal cortex showed strong P450 IIE1-immunoreactivity, as did a component of the olfactory nerve which innervates the accessory bulb. In the hippocampal region, the pyramidal cells of all subfields were P450 IIE1-immunoreactive. Some polymorphic cells of the hilus and subfield CA stained intensely with the P450 IIE1 antibodies. A high density of P450 IIE1-immunoreactivity was detected throughout the striatal complex. The immunoreactivity was localized to neuronal cell bodies as well as the neurophil. Fibers of the nigrostriatal system were strongly P450 IIE1-immunoreactive. Mechanical lesions of this pathway showed an accumulation of P450 IIE1-immunoreactivity proximal to the lesion relative to the striatum and a depletion in the reticular part of the substantia nigra, suggesting that the antigen may be transported from the striatum to the substantia nigra. In the brain stem a high density of P450 IIE-immunoreactive neurons was detected in the substantia nigra, the pontine nucleus, lateral superior olive and the nucleus of the trigeminal nerve and facial nucleus. A great number of large- to medium-sized immunoreactive neurons were situated in the central gray and in the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Musculo-skeletal symptoms and signs and isometric strength among fishermen.

Previous studies have shown that subjective symptoms from the musculo-skeletal system are common among fishermen. In the present study, physical signs of malfunction were also found to be common in this profession. The co-existence of physical signs and subjective symptoms differed greatly between different joint systems, and the correlation was in some locations very low. The prevalence of physical health problems other than orthopaedic problems was low. Isometric lifting strength was high compared to results reported on other vocational groups.

Adult↗

Effects of dietary and intraperitoneally administered beta-naphthoflavone on mutagenicity and tissue distribution of Trp-P-1 in the rat.

The effect of dietary beta-naphthoflavone (BNF) on tissue retention of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was studied in the rat. Female rats, 3 weeks old, were fed a BNF-containing diet for 3 days before being dosed orally or i.v. with 14C-labelled Trp-P-1. The rats were killed at 4, 24 or 48 h after dosage and subjected to tape-section autoradiography. The tissue localization of Trp-P-1-derived radioactivity was compared to that observed in untreated rats and in rats given BNF i.p. Ethoxyresorufin-O-deethylase (EROD) activity and mutagenicity of Trp-P-1 in the Ames test, using S9 prepared from forestomach, glandular stomach, small intestine, liver and lung, were used as in vitro assays to measure the degree of cytochrome P450IA1 and/or P450IA2 induction. Dietary BNF treatment caused a 30- to 40-fold increase in EROD activity in the small intestine, but only a 2-fold increase in the liver and the lung. These inter-organ differences were not observed after i.p. administration of BNF. The increase in mutagenicity of Trp-P-1 in the Ames test could be correlated to the increase in EROD activity. The autoradiographic data showed that the route of administration of BNF as well as of Trp-P-1 were important for the tissue localization of Trp-P-1. Dietary BNF treatment caused a pronounced retention of Trp-P-1-derived radioactivity in the epithelia of the small intestine, forestomach, oesophagus and the oral cavity, regardless of the administration route of Trp-P-1; a similar though less pronounced epithelial retention was observed after i.p. injection of BNF. A clear-cut boundary of accumulated radioactivity between the forestomach and the glandular stomach where the levels were almost non-detectable was observed in rats fed the BNF-containing diet. It is concluded that dietary inducers may be important determinants of metabolism and tissue distribution of toxic compounds.

Animals↗

Compression-induced changes of the nutritional supply to the porcine cauda equina.

The effects of compression on the transport of 3H-labeled methyl glucose to spinal nerve roots were analyzed in an experimental model of the pig cauda equina. A rapid onset of compression (0.05-0.1 s) induced more pronounced effects than a slow onset (20 s) at corresponding pressure levels. There was evidence that this observed difference may be related to the magnitude of intraneural edema formed outside the compression zone. The results also indicate that the nutritional transport might be impaired at very low pressure levels and that diffusion from adjacent tissues with a better nutritional supply, including the cerebrospinal fluid, may not fully compensate for any compression-induced impairment of the intraneural blood flow.

3-O-Methylglucose↗

Factors affecting the dynamic response of the seated subject.

An impact method, combined with pins placed into the spinous process at L3, has been used to establish the dynamic response of the spine of the seated subject. The resonant frequency is at 4-5 Hz, due primarily to a vertical response of the buttocks-pelvis system. A maximum attenuation at 8 Hz occurs because of a second resonance due to pelvic rotation. The attenuation is also affected by additional load and by the addition of a helmet. Neck braces have no dynamic effect.

Adult↗

The loads on the lumbar spine during work at an assembly line. The risks for fatigue injuries of vertebral bodies.

This study was performed in an attempt to determine the total spinal compressive load during assembly line work to find a possible association with the many complaints of back pain. A flexion analyzer was used to register trunk movements, and analysis of postures and lifted weights was done from video recordings. The load on the spine at the L3 level was calculated through a biomechanical model, meant for analysis of static, sagittally symmetric postures and lifting tasks. Maximum lift tests were performed before and after a full work day. The peak load on the L3-L4 level when lifting corresponded to an average 22% of the load at the lift test. The mean load during a work cycle was 818 N. It was concluded that the many complaints of back pain could not be attributed to high peak loads, repetitivity of the lifts, or large load doses. Monotony, stress, and low job satisfaction are more likely factors of greater importance.

Adult↗

Dynamic changes in the dimensions of the lumbar spinal canal: an experimental study in vitro.

The variation in the dimensions of the lumbar spinal canal under both flexion-extension and axial compression-distraction was studied using computerized tomography (CT) scans in human cadaver lumbar spine specimens. In 3-mm-thick CT slices through the disk at L3-L4, the cross-sectional area of the spinal canal was reduced by around 40 mm2, corresponding to a 16% reduction of the initial area when the lumbar spines were moved both from flexion to extension and from distraction to compression. A corresponding reduction in the midsagittal diameter of the canal of 2 mm was found. During these motions, the ligamentum flavum did not appear to be a significant factor for the dynamic changes affecting the dimensions of the canal. This held true even after the disk had been excised in order to produce a total collapse of the disk space.

Humans↗

Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene.

Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy.

Animals↗

Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat.

Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.

Administration, Inhalation↗

The dynamic response of a subject seated on various cushions.

An impact pendulum was used to examine the dynamic response of the seated subject. The dynamic response is of interest in establishing the relationship between driving and low-back pain. Accelerometers were placed on the seat and in vivo at the L3 vertebra. The transmissibility and phase angle were obtained in the frequency domain for a variety of cushions. Soft cushions were found to increase the gain at the first natural frequency.

Acceleration↗

Neurotensin modulates the binding characteristics of dopamine D2 receptors in rat striatal membranes also following treatment with toluene.

The effects of neurotensin in vitro (1-100 nM) on the binding characteristics of [3H]N-propylnorapomorphine ([3H]NPA) were analysed in striatal membrane preparations of the adult male rat. Subsequently, it was investigated whether the modulatory effects of 10 nM neurotensin on [3H]NPA binding were altered by treatment with toluene in vivo (80 p.p.m., 3 days, 6 h day-1) and in vitro (19 mumol ml-1). Displacement of [3H]NPA binding by raclopride (IC50 about 15 nM) and SCH 23390 (without effect) indicated that [3H]NPA labelled only D2 dopamine receptors in the present study. Neurotensin was found to reduce the affinity of D2 receptors with a maximum response at 10 nM. At this concentration the KD value was increased by 30-40% without any consistent changes in the number of binding sites. The modulatory effect of neurotensin remained intact also following toluene treatment in vivo and in vitro, although at a higher KD range, since toluene alone increased the KD value of [3H]NPA binding by 40-50%. Thus, the mechanisms mediating the effects of neurotensin and toluene on the D2 receptor are likely to be different. When neurotensin and toluene treatments were combined, the KD values of [3H]NPA binding were about twice as high as in non-treated controls. These additive effects may lead to a severely decreased efficiency of dopamine D2-mediated neurotransmission in vivo.

Animals↗

Sickness absenteeism in an engineering industry--an analysis with special reference to absence for neck and upper extremity symptoms.

Neck and upper extremity symptoms (NES) are reported to increase among industrial workers. In order to quantify sickness absenteeism and relate it to some factors a questionnaire study was performed among 2,814 workers occupied at a Swedish engineering industry. Questions pertaining to age, sex, worker category, work with vibrating handtools, type of job and smoking habits were analyzed and correlated to sickness absenteeism for the previous year (1983). We found that the average days lost for personal illness was 17.2 days; 16.2 for men and 23.5 days for women. Ninety-four persons, 77 men and 17 women comprising 3.0% of all employees were sicklisted for NES corresponding to 3.3% of total sickness time lost. Blue-collar workers were sicklisted for NES five times more often than white collar workers and women in type 3 jobs (high NE stress), twice that of men occupied in the same type of job. Smokers had significantly higher absenteeism than non-smokers for any reason studied including NES. The study indicated a high prevalence of present NES problems (23%) but also that NES as a cause of leave of absence was relatively rare (3%).

Absenteeism↗

Cytochromes P-450 of sea birds: cross-reactivity studies with purified rat cytochromes.

1. Polyclonal antibodies against rat cytochrome P-450c (IA1), P-450d (IA2), P-450b (IIB1), P-450h (IIC11) and P-450j (IIE1), were used to probe liver microsomes prepared from six sea bird species collected from the Irish Sea between 1978 and 1988. 2. Significant cross-reactivity in all the sea bird species was seen only with antibodies to P450 IA1. Expression of cross-reactivity proteins was highly variable between individual birds, which show evidence of environmental induction. 3. Shared epitopes to P450 IA1 and IA2 were seen on a single protein expressed in liver microsomes from the cormorant (Phalacrocorax carbo). 4. Antibodies against members of rat P450 gene family II showed a small degree of cross-reactivity with sea bird microsomes. Antibodies against P450 IIB1 and IIC11 showed weak cross-reactivity in all species with little inter-individual variation. Antibodies to P450 IIE1 showed no cross-reactivity in any bird species. 5. P450 gene family I appears to be well represented in sea birds while P450 gene family II is not well developed in this group of lower vertebrates.

Animals↗

Mineral content and strength of lumbar vertebrae. A cadaver study.

Fifty-two cadaveric spine-motion segments were tested in compression alone and in combined compression-flexion to determine whether the compressive strength of lumbar vertebrae varied with the direction of the applied load, that is, whether similar relationships existed between the compressive strength and the amount of bone mineral depending on the direction of the loading. The bone mineral content (BMC) ranged between 1.6 and 5.8 g/cm and the ultimate strength between 810 and 10,090 N. The BMC of the motion segments was correlated with their strength irrespective of degree of flexion during testing (0-15 degrees). For compression-flexion within physiologic limits, the first part of the motion segment to fail was, with few exceptions, the end plate and the adjacent spongy bone.

Adolescent↗

The correlation between work environment and the occurrence of cervicobrachial symptoms.

The correlation between symptoms from the neck and upper extremities and some individual and work-related factors was analyzed in 2814 industrial workers. Physical stress by type of job was the factor most strongly correlated with ongoing cervicobrachial symptoms. Symptoms from the neck and upper extremities were twice as common in workers who used vibrating hand tools. Mental stress at the onset of the symptoms was associated with an increased prevalence of trapezius myalgia and with lateral humeral epicondylitis and "radial tunnel syndrome" in the dominant arm. Women had about double the rate of cervicobrachial symptoms as did men. Short stature increased the rate of symptoms from the neck, shoulders, and hands as did overweight. Playing of racquet sports decreased the risk of symptoms from the neck and hands.

Analysis of Variance↗

Perinatal opiate exposure. Effects on metabolism of xenobiotics and steroids in adult rat liver.

The effects of perinatal or neonatal morphine exposure on the hepatic steroid and xenobiotic metabolism in adult rats were studied. Early morphine exposure did not affect the 16 alpha-hydroxylation or 5 alpha-reduction of androstenedione in either sex, but decreased the 7 alpha- and 6 beta-hydroxylations in both sexes. Morphine exerted a suppressive effect on the ethoxyresorufin-O-deethylase activity and increased the ethoxycoumarin-O-deethylase activity in both sexes. Morphine exposure did not significantly affect its own N-demethylation or the total cytochrome P-450 content in the liver. Neonatal morphine exposure caused a significant decrease in body and testes weight in the adult male rat. We conclude that the effects of morphine are not confined to sex-differentiated pathways and are similar in both sexes.

Animals↗

Effects of chronic toluene exposure on central monoamine and peptide receptors and their interactions in the adult male rat.

The effects of chronic toluene exposure (CTE) (80 ppm, 6 h/day, 5 days/week, 3 months) were studied on neuropeptide and 5-hydroxytryptamine receptors, on protein phosphorylation levels and on catecholamine levels in various brain regions in the 15-month-old male rat. Behavioral parameters and serum levels of hypophyseal hormones and corticosterone were also analyzed. CTE selectively reduced [3H]neurotensin [( 3H]NT) binding in the basal layers of the orbital cortex. Instead, CTE increased the binding of [3H]etorphine in the nucleus accumbens and of [125I]vasoactive intestinal polypeptide [( 125I]VIP) in the area postrema and hypoglossal nucleus. Acute treatment with the irreversible monoamine receptor antagonist N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) increased the binding of [3H]NT in the orbital cortex in toluene exposed rats as compared with the reduced [3H]NT binding obtained in air exposed rats treated with EEDQ. Furthermore, the EEDQ induced increase in [125I]VIP binding in the area postrema and the hypoglossal nucleus was replaced by a reduced binding of [125I]VIP in EEDQ-treated CTE rats. CTE produced an overall increase in calcium-induced back phosphorylation and an overall decrease in cyclic adenosine monophosphate-induced back phosphorylation in the frontoparietal cortex. Noradrenaline stores tended to be reduced within various hypothalamic subnuclei and the serum prolactin levels were increased following CTE. However, no marked effects of CTE were seen on the behavioral parameters. In conclusion, the regional selectivity of CTE in disturbing [3H]NT and [125I]VIP binding may be due to the demonstrated vulnerability of monoamine-neuropeptide interactions to toluene.

Animals↗