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Biomedical subjects

T Hansson

Publications and source records attributed to T Hansson.

At least 127 records · Page 7Linked to original sources
PubMed1986

Isolation of rat intestinal microsomes: partial characterization of mucosal cytochrome P-450.

A procedure is presented for the isolation of subcellular fractions from small intestinal mucosal cells in the rat. The mucosal cells were detached by a scraping procedure resulting in an almost complete harvest of all types of cells as judged by light microscopy. Homogenization using a Potter-Elvehjem Teflon-glass device at high speed with ensuing sonication was found to be necessary for complete disruption of the cells. The subcellular fractions obtained after differential centrifugation--10,000g pellet, 105,000g pellet (microsomal fraction), and supernatant--were characterized with respect to different marker enzymes. The highest yield of 7-ethoxyresorufin-O-deethylase and NADPH-cytochrome c reductase activity in the microsomal fraction was achieved after resuspension and recentrifugation of the 10,000g pellet. Addition of anti-P-450 beta-naphthoflavone (BNF)-B2 antibodies to the incubation mixture resulted in almost complete inhibition of the O-deethylation of 7-ethoxyresorufin whereas addition of anti-P-450 phenobarbital (PB)-B2 had no effect. The presence of BNF-inducible isozymes was demonstrated by the Western blotting technique not only in intestinal microsomes from BNF-treated rats, but also in microsomes from untreated rats. Anti-P-450 BNF-B2 was also used in the peroxidase-antiperoxidase method for studies on the localization of cytochrome P-450. No BNF-inducible cytochrome P-450 could be detected in untreated rats, whereas BNF treatment resulted in a general staining of the whole villus.

Animals↗
PubMed1986

Age changes in the bone mineral of the lumbar spine in normal women.

The bone mineral content (BMC) and the bone mineral areal content (BMAC) were determined with dual-photon absorptiometry in the third lumbar vertebra in a random sample of 214 women between 35 and 80 years of age in the city of Göteborg, Sweden. A continuous aging decrease (1%/year) of both the BMC and the BMAC was noted after age 35. The rate at which bone loss occurred was similar for all age groups when analyzed by 5 year intervals. No clear acceleration of bone loss was noted around the usual time of the menopause.

Adult↗
PubMed1986

Pituitary regulation of cytochrome P-450-mediated metabolism of steroids and xenobiotics in rat liver microsomes.

In a previous paper we reported on the influence of sex and pituitary hormones on the selection of diethylnitrosamine-initiated, enzyme-altered cells by 0.02% (w/w) 2-acetylaminofluorene (2-AAF) and partial hepatectomy in the resistant hepatocyte model (RH-model). The islands of enzyme-altered cells in this model grew faster in male than in female rat liver and the growth rate was markedly decreased in male rats bearing ectopic pituitary grafts during the 2-AAF selection period. Male rats are also generally more susceptible to 2-AAF carcinogenesis than female rats. In order to investigate whether the sex differentiated response to 2-AAF selection and 2-AAF carcinogenesis might be due to pituitary control of xenobiotic metabolism, as previously shown for rat liver metabolism of steroid hormones, we have studied the influence of age, sex and pituitary hormones on the cytochrome P-450-mediated hydroxylations of 2-AAF and benzo[a]pyrene (B[a]P), O-deethylation of 7-ethoxyresorufin and the metabolism of 4-androstene-3,17-dione (androstenedione) in rat liver microsomes. Microsomes from prepubertal rats had a generally higher capacity to metabolize the xenobiotic compounds whereas the capacity for androstenedione hydroxylation was low. In adult rats pronounced sex differences and a marked influence of pituitary hormones were observed in the microsomal formation of several 2-AAF metabolites as well as in B[a]P and androstenedione metabolism. The results clearly show that at least the oxidative pathways of 2-AAF and B[a]P metabolism are controlled by pituitary hormones in a similar way to the rat liver metabolism of steroids. These data do not, however, provide any explanation for the previously mentioned sex differences in the RH-model or in 2-AAF carcinogenesis. We therefore suggest that the pituitary regulation of other pathways of 2-AAF metabolism must be considered in order to clarify the biochemical background behind sexually differentiated 2-AAF carcinogenesis in rat liver.

2-Acetylaminofluorene↗
PubMed1986

Pituitary grafts modify sex differences in liver tumor formation in the rat following initiation with diethylnitrosamine and different promotion regimens.

We previously reported on sex differences in chemical hepatocarcinogenesis studied in the resistant hepatocyte model and on the effects of implantation of ectopic pituitary grafts into male rats on the early stages of liver carcinogenesis. Marked sex differences were found in the area ratio of enzyme-altered foci (mm2 foci/cm2 liver section) in sexually mature male and female Wistar rats (male greater than female). Pituitary grafts implanted one week before 2-acetylaminofluorene selection in male rats decreased the area ratio to a level near that of sham operated females. The present study was performed in order to investigate the relevance of the results in the short-term experiment in terms of hepatoma formation. To study the importance of 2-acetylaminofluorene selection as a determinant of the observed sex differences an experiment was also performed using the Pitot-model, where male and female rats were initiated with diethylnitrosamine and promotion was performed with phenobarbital. The long-term experiments in the resistant hepatocyte model showed that male rats develop hepatomas earlier than female rats and also showed a tendency towards a prolonged latency time in male rats bearing pituitary grafts. A good correspondence was thus achieved between the short-term and the long-term experiments. The rats treated according to the Pitot-model did not develop hepatomas within the experimental period. Of the rats killed at 13 months, three (out of five) male and five (out of five) female rats had hepatocyte nodules whereas, at 19 months two (out of six) male and five (out of six) female rats had developed such lesions in this model. We therefore conclude that 2-acetylaminofluorene is the factor responsible for the sex differences in the resistant hepatocyte model and that the hypothalamo-pituitary influence during 2-acetylaminofluorene selection is an important modifier of the carcinogenetic process.

2-Acetylaminofluorene↗
PubMed1986

Activation of sexual behaviour in castrated rats: the role of oestradiol.

Sexual behaviour was induced in castrated male rats with oestradiol-17 beta- or testosterone-filled constant-release implants. Testosterone-induced sexual behaviour was unaffected by treatment with the 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one (4-MA; 16.7 mg/day) but treatment with the aromatization inhibitor 1,4,6-androstatriene-3,17-dione (ATD; 10 mg/day) prevented testosterone from inducing the behaviour. Sexual behaviour could be activated in castrated rats treated with testosterone plus ATD by treatment with 4-MA or with implants filled with a low dose of oestradiol. Lordosis behaviour induced in ovariectomized rats with testosterone-filled implants and progesterone was blocked by ATD treatment and could not be activated with 4-MA but oestradiol implants restored the display of lordosis in the testosterone plus ATD-treated females. 4-MA inhibited the in-vitro formation of [14C]5 alpha-dihydrotestosterone from [14C]testosterone by combined preoptic and hypothalamic tissue at all doses tested and a high dose of oestradiol exerted a similar effect. The results suggest that androgen aromatization is required for testosterone-activated female sexual behaviour but not for testosterone-activated male sexual behaviour. It is suggested that oestradiol normally acts to control the sexual behaviour of male rats by modifying neural androgen metabolism.

Androgens↗
PubMed1986

Effects of neonatal and adult castration on the in vitro metabolism of steroids and xenobiotics in rat liver.

Previous studies in our laboratory have shown that the sex-differentiated metabolism of 4-androstene-3,17-dione and of several other steroid hormones in adult rat liver is "feminized" following neonatal castration of male rats, due to an influence via the hypothalamo-pituitary-liver axis. The metabolism of many xenobiotics is also sex differentiated, and an important question is whether endocrine ablations might alter hepatic carcinogen metabolism in a way explaining, for example, the decreased tendency of castrated male rats [Y.C. Toh, In: Shanmagarathnam et al. (eds.), Liver Cancer, Cancer Problems in Asian Countries, Proceedings of the Second Asian Cancer Conference, pp. 167-171. Singapore: Singapore Cancer Society, 1976] to form liver tumors following 2-acetylaminofluorene treatment. The results presented in this paper clearly show that neonatal castration of male rats, much more efficiently than adult castration, feminizes the cytochrome P-450-dependent, sex-differentiated, liver microsomal formation of 7-hydroxy-2-acetylaminofluorene, 9-hydroxy-2-acetylaminofluorene, 5-hydroxy-2-acetylaminofluorene, 1-hydroxy-2-acetylaminofluorene, and N-hydroxy-2-acetylaminofluorene from 2-acetylaminofluorene as well as the total microsomal formation of benzo(a)pyrene metabolites (male greater than female). O-Deethylation of 7-ethoxyresorufin was neither sex differentiated nor affected by castration. The capacity for in vitro sulfation of N-hydroxy-2-acetylaminofluorene in the postmicrosomal supernatant, markedly sex differentiated in the rat (male greater than female), was completely feminized by neonatal but not by adult castration. The results suggest that the influence of endocrine ablations on chemical carcinogenesis in rat liver might be mediated via the hypothalamo-pituitary regulation of certain pathways of hepatic xenobiotic metabolism.

2-Acetylaminofluorene↗
PubMed1985

Neonatal exposure to toluene: effects on the development of liver microsomal cytochrome P-450 and serum hormone levels in the rat.

Lactating Sprague-Dawley rats and their pups were exposed on postnatal days 1-7, 6 h/day, to 80, 500 and 1000 ppm toluene, respectively, by inhalation. Exposure to 80 ppm toluene decreased the liver microsomal AHH activity and the rate of 7 alpha- and 6 beta-hydroxylation of androstenedione in 8-day-old-pups. On the other hand, neonatal exposure to 500 or 1000 ppm toluene resulted in a significant increase in AHH and 7-ethoxyresorufin O-deethylase activities and in the formation of 16-oxygenated metabolites of androstenedione in 8-day-old animals. Exposure to toluene increased the cytochrome P-450 content at all 3 dose levels in male but not in female pups. Twenty-one days after neonatal exposure no such effects were seen in young animals of either sex. In 56-day-old male rats, however, neonatal exposure to 80 ppm toluene resulted in a decreased rate of 6 beta-hydroxylation of androstenedione and a reduced AHH activity. No such effects were seen in female rats of the same age. Neonatal exposure to toluene affected the body and liver weights in 8-day-old pups of both sexes but had no effect on these parameters in 21-day-old animals of either sex. Exposure to 80 ppm toluene during the neonatal period gave a significantly increased body weight of 56-day-old male but not of female rats of the same age although this treatment increased liver weight in both sexes at this age. Serum testosterone levels were decreased in 21-day-old male rats following neonatal exposure to 80 or 500 ppm toluene and in 56-day-old male rats exposed neonatally to 1000 ppm toluene. In conclusion, exposure to toluene during the first week of life caused significant changes in various liver microsomal cytochrome P-450 dependent enzyme activities in 8-day-old pups, whereas the long-term effects on liver metabolism of the adult animal were small.

Androstenedione↗
PubMed1985

The lumbar lordosis in acute and chronic low-back pain.

To evaluate a possible relationship between the amount of lumbar lordosis in asymptomatic as well as subjects with acute and chronic low-back pain, the amount of lordosis was determined from spinal roentgenograms of 600 men between 20 and 63 years of age. The angle between a line parallel to the cranial end-plate of L1 and S1 was defined as the lordosis angle. The amount of lordosis was distributed similarly according to age within each of the three groups and was also similar in comparisons between the groups. The men were randomly selected to represent three different groups. Each group included 200 age-matched subjects with similar occupation. The first group consisted of men claiming no previous back-pain history who underwent spinal x-ray as a part of a preemployment examination. The second group consisted of men who had a spinal x-ray examination after claiming their first low-back injury, but not preemployment screening. The third group consisted of x-ray examination of men evaluated for chronic low back disability. The findings thus indicated that the distribution and range of lordosis as viewed by clinicians and radiologists does not vary in the acute or with chronic low-back pain, more than in men without back pain of the same age.

Acute Disease↗
PubMed1985

The bone mineral content of the lumbar spine in patients with chronic low-back pain.

The bone mineral content (BMC) of the third lumbar vertebra was determined in 43 patients with chronic low-back pain. No correlation was found to sex, height, pain experience, functional disability, or alcohol consumption. A positive correlation was found between the BMC and body weight and between the BMC and smoking in men (but not in women). A statistically significant negative correlation was found between the BMC and the overall duration of the back problem, ie, the longer duration the lower the BMC.

Adult↗
PubMed1984

Influence of sex steroids on the catecholamine biosynthesis in chromaffin tissue from rainbow trout, Salmo gairdneri.

The in vitro activities of dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyl transferase (PNMT) were determined in the chromaffin tissue (head kidney) of sex steroid-treated rainbow trout, Salmo gairdneri. In addition, the DBH and PNMT activities were measured in fish at different sexual states. Steroid treatment increased the wet weight of the head kidney, while both DBH and PNMT activities decreased. Although no sex difference in the enzyme activities was detected, a possible correlation between DBH and PNMT activities and increased GSI values was indicated. The presented data suggest that changes in sex steroids during development may affect the catecholamine synthesis in the chromaffin tissue in S. gairdneri.

Androgens↗
PubMed1984

Central catecholamine neurons and exposure to dichloromethane. Selective changes in amine levels and turnover in tel- and diencephalic DA and NA nerve terminal systems and in the secretion of anterior pituitary hormones in the male rat.

Subacute exposure of male rats to various concentrations (70-1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the anterior periventricular hypothalamic area and with the highest concentration an increase of NA turnover in the anteromedial frontal cortex. DCM reduced NA levels dose-dependently in the posterior periventricular hypothalamic area and also reduced NA levels in the dorsomedial hypothalamic nucleus (1000 ppm). Following tyrosine hydroxylase inhibition DCM produced an inversely dose-related increase of serum LH levels and at the highest concentration an increase of ACTH secretion was observed. It is suggested that DCM can produce discrete changes in amine storage and turnover in catecholamine (CA) nerve terminal systems of the tel- and diencephalon, some of which may contribute to the DCM induced disturbances of the secretion of anterior pituitary hormones but actions on other transmitter-identified neurons involved in neuroendocrine regulation must also be considered.

Animals↗
PubMed1984

On mechanisms of sex differences in chemical carcinogenesis: effects of implantation of ectopic pituitary grafts on the early stages of liver carcinogenesis in the rat.

The resistant hepatocyte model was used to investigate the influence of pituitary factors on the early events of chemical carcinogenesis in rat liver. Diethylnitrosamine (DEN), 200 mg/kg body weight, was used as an initiator of enzyme altered foci. Two weeks after initiation the rats were placed on a 0.02% (w/w) 2-acetylaminofluorene (2-AAF) diet for two weeks. Partial hepatectomy (70%) was performed three weeks after initiation. The rats were killed four to six weeks after DEN initiation. Sex differences in area/foci as well as in area ratio (mm2 foci/cm2 liver section) were found in liver sections from sexually mature male and female rats (male greater than female) of both the Sprague-Dawley and Wistar strains. Ectopic pituitary grafts (PG:s) implanted under the kidney capsule of male Wistar rats one week before DEN initiation and removed by unilateral nephrectomy one week after initiation did not influence the number or area of enzyme altered foci as compared with sham operated male rats. On the other hand, PG:s implanted one week before 2-AAF selection in male Wistar rats and allowed to remain until the rats were killed two weeks after the 2-AAF selection period, decreased the area ratio to a level close to that of sham operated female rats, whereas no effect on the number of enzyme altered foci was found. The results suggest that the hypothalamo-pituitary axis may be involved in the regulation of early stages of liver carcinogenesis.

2-Acetylaminofluorene↗
PubMed1983

Effects of hypophysectomy and cortisol on the catecholamine biosynthesis and catecholamine content in chromaffin tissue from rainbow trout, Salmo gairdneri.

The in vitro activities of dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) were determined in the chromaffin tissue of hypophysectomized and cortisol-treated rainbow trout, Salmo gairdneri. In addition, the content of adrenaline and noradrenaline was estimated. DBH activity increased after both hypophysectomy and cortisol administration. The increased activity after hypophysectomy was restored with administration of pituitary extract, ADP. The PNMT activity seemed to increase slightly after hypophysectomy, while the activity remained unchanged after cortisol administration. A small decrease in catecholamine content was seen after hypophysectomy or treatment with cortisol but the A/NA ratio was not changed. A regulation of the biosynthesis of catecholamines in trout chromaffin tissue is suggested and discussed in relation to mammalian conditions.

Animals↗
PubMed1983

Effects of hypophysectomy on the plasma ionic and osmotic balance in rainbow trout, Salmo gairdneri.

The effects of hypophysectomy on the plasma ionic and osmotic balance in juvenile rainbow trout (Salmo gairdneri) kept in 1/3 sea water for various periods were studied. Hypophysectomy caused a decrease in the plasma levels of ionized calcium and chloride within a week after the operation. At 2-5 weeks after hypophysectomy, the plasma levels of ionized calcium and chloride were still significantly lower in hypophysectomized fish when compared to sham-operated controls. Hypophysectomy had no effects on the plasma levels of sodium, total calcium, total magnesium, inorganic phosphate, plasma proteins, or plasma osmolality. When 1/3 sea water adapted (1-4 weeks), hypophysectomized and sham-operated fish were exposed to fresh water for 2 weeks, the plasma levels of ionized calcium, chloride, sodium, and plasma osmolality were significantly lower in hypophysectomized fish when compared to sham-operated fish, while the plasma levels of total calcium, total magnesium, and proteins were higher. No effects were noted on the plasma levels of potassium and inorganic phosphate. The presented data indicate that the pituitary gland plays a significant role in the regulation of plasma calcium and chloride levels in S. gairdneri, while its role in the regulation of plasma magnesium and sodium is less clear. The pituitary gland seems to play a minimal role in the plasma regulation of inorganic phosphate and potassium.

Animals↗
PubMed1983

In vitro metabolism of estradiol-17 beta by liver microsomes from juvenile rainbow trout, Salmo gairdneri.

The metabolism of [4-14C]estradiol-17 beta by liver microsomes from, Salmo gairdneri, was studied in vitro. The following metabolites were identified by gas chromatography--mass spectrometry: estrone, estra-1,3,5(10)-triene-3,16 beta,17 beta-triol, and estra-1,3,5(10)-triene-3,7 alpha,17 beta-triol. The presence of additional polar metabolites hydroxylated at positions 6 alpha and 6 beta was indicated. The formation of the hydroxylated metabolites was inhibited by CO indicating the participation of cytochrome P-450-dependent enzymes.

Animals↗
PubMed1983

Effects of subacute treatment with toluene on central monoamine receptors in the rat. Reduced affinity in [3H]5-hydroxytryptamine binding sites and in [3H]spiperone binding sites linked to dopamine receptors.

Subacute treatment with toluene leads to a dose-related reduction of affinity in the [3H]spiperone binding sites labeling striatal dopamine (DA) receptors of the D2 type and cortical [3H]5-hydroxytryptamine (5-HT)-binding sites. It is suggested that these results represent a down regulation of activity at striatal DA and cortical 5-HT synapses, since they now may operate at higher concentrations of transmitters. The reduced affinity may be caused by the physicochemical properties of toluene leading to changes in membrane fluidity and thus in the regulation of DA and 5-HT receptors in the local circuits of the striatum and the dorsal cerebral cortex.

Animals↗