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Biomedical subjects

H Eriksson

Publications and source records attributed to H Eriksson.

At least 127 records · Page 7Linked to original sources

Growth hormone increases phosphoinositide turnover in rat adipocytes that are sensitive to the insulin-like action of the hormone.

UNLABELLED: The effect of pituitary human growth hormone (hGH) on the 32P-labelling of phosphoinositides and phosphatidic acid was studied in noradrenaline-stimulated rat adipocytes which were either responsive or non-responsive to the antilipolytic (insulin-like) effect of hGH. In cells responsive to the insulin-like effect of hGH, hormone treatment resulted in a marked increase of the 32P-labelling of phosphatidic acid and phosphatidyl inositol in the plasma membrane, high density microsomal, and low density microsomal fractions. The increased 32P-labelling most likely reflects an activation of phosphoinositide phospholipase C. ABBREVIATIONS: IP3 - Myo-Inositol 1,4,5-Triphosphate. BSA - Bovine Serum Albumin, HEPES - N-2-Hydroxyethylpiperazine-N'-2-Ethanesulphonic Acid, hGH - Human Pituitary Growth Hormone, LPC-Lysophosphatidylcholine, LPE - Lysophosphatidylethanolamine, LPI - Lysophosphatidylinositol, PA - Phosphatidic Acid, PC - Phosphatidylcholine, PE - Phosphatidylethanolamine, PI - Phosphatidylinositol, PIP - Phosphatidylinositol-4-Phosphate, PIP2-Phosphatidylinositol-4,5-Diphosphate, PS-Phosphatidylserine.

Adipose Tissue↗

Proteolysis of the heavy chain of major histocompatibility complex class I antigens by complement component C1s.

The major histocompatibility complex (MHC) class I antigens contain a light chain, beta 2-microglobulin, non-covalently associated to the transmembrane heavy alpha-chain carrying the allotypic determinants. Since the C1q complement component is known to associate with beta 2-microglobulin, and we recently found that activated C1s complement was capable of cleaving beta 2-microglobulin, we decided to investigate the proteolytic activity of C1 complement towards the heavy chain of class I antigens. Our results demonstrate that human C1s complement cleaves the heavy chain of human class I antigens into at least two fragments, with apparent molecular weights of 22,000 and 24,000 g/mol on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), under both reducing and non-reducing conditions. The cleavage of the heavy chain is inhibited by the presence of C1 esterase inhibitor. The molecular weights of the fragments are in agreement with the cleavage located in the area between the disulphide loops of the alpha 2-and alpha 3-domains of the heavy chain. In addition human C1s complement is able to cleave H-2 antigens from mouse in a similar fashion but not rat MHC class I antigen or mouse MHC class II antigen (I-Ad). Mouse MHC class I antigen-specific determinants could also be detected in supernatant from mouse spleen cells incubated with C1r and C1s. These results indicate the presence in the body fluids of a non-membrane-bound soluble form of the alpha 1-and alpha 2-domains which represent the binding site for antigenic peptides.

Animals↗

Renal 25-hydroxyvitamin D-3 1 alpha-hydroxylase in guinea-pig: activity variations during development and pregnancy.

The renal 25-hydroxyvitamin D-3-1 alpha-hydroxylase (1 alpha-hydroxylase) activity and circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in pregnant guinea-pigs and their offspring. Serum levels of 1,25(OH)2D were significantly elevated in pregnant guinea-pigs but the renal enzyme activity was not different from non-pregnant animals. The fetal renal 1 alpha-hydroxylase activity was about 6-fold higher than the maternal level, whereas circulating 1,25(OH)2D was low. Treatment with pharmacological doses of 1,25(OH)2D3 increased circulating 1,25(OH)2D and depressed the renal 1 alpha-hydroxylases both in the mother and the fetus. In newborn guinea-pigs the enzyme activity was up to 10-times that seen in adults. It declined over the first 3 weeks, showing no difference between the sexes. In sexually mature animals the males had a significantly higher 1 alpha-hydroxylase activity than the female. However, this higher enzyme activity was not correlated to serum testosterone. Around the time the animals reached sexual maturity serum 1,25(OH)2D increased in both sexes. In the males this rise was correlated to an increase in serum testosterone. It is concluded that the maternal renal 1 alpha-hydroxylase activity is unchange in late pregnancy, compared to non-pregnant females. The data indicate that the fetus produces 1,25(OH)2D, and may contribute to the maternal circulating 1,25(OH)2D. The sex difference in 1 alpha-hydroxylase activity previously demonstrated is manifest at about the time of puberty.

Animals↗

Characterization of uterine sex steroid receptors in the pig and their variation during the oestrous cycle.

The present study establishes and validates an in vitro binding and exchange assay for tissue receptors for oestradiol (E) and progesterone (P) in pig uterus. Both hormones bound to specific cytoplasmic (Rc) and nuclear (Rn) receptor proteins with high affinity. The relative concentrations of the receptors were measured in dissected samples from endometrium and myometrium obtained at late prooestrus, oestrus, and luteal phases of the oestrous cycle. The Scatchard analysis of the oestradiol and R 5020-receptor complex displayed linearity and indicated a single class of high affinity, low capacity binding sites. Significant variations were seen in the binding of E and P to their cytosolic and nuclear receptors, following the changes in the circulating levels of the hormones in blood plasma during the oestrous cycle. Both tissue components, i.e. endometrium and myometrium followed a similar pattern when related to the stage of the oestrous cycle considered. The ERc increased from prooestrus, reaching a maximum at standing oestrus, thereafter decreasing. The concentration of ERn increased from prooestrus towards the early luteal phase, with a significant reduction by day 8 of the cycle. The amounts of PRc were maximal at standing oestrus, remaining high during the early luteal phase, while the PRn showed a linear increase from oestrus onwards throughout the luteal phase.

Animals↗

Progesterone and oestradiol-17 beta receptors in the porcine myometrium during the oestrous cycle.

The concentrations of the tissue receptors for oestradiol (E) and progesterone (P) in the porcine myometrium at different stages of the oestrous cycle have been investigated by in vitro binding and exchange methods. Both hormones bound to specific cytoplasmic (Rc) and nuclear (Rn) receptors proteins with high affinity. The amount of ERc did not vary significantly throughout the cycle. Significant variations in the amount of myometrial ERn were observed with high concentrations during late pro-oestrus. The amount of PRc reached a top value in early pro-oestrus. A significant increase in PRn levels was observed at early luteal phase, and it remained high during the rest of the luteal phase. The temporal relationships between the variations in levels of oestradiol and progesterone nuclear receptors in myometrial tissue and those of the circulating plasma levels were established. The data obtained in this study suggest a relationship between the changes in levels of oestradiol and progesterone myometrial binding and the uterine motility pattern during the oestrous cycle.

Animals↗

Variations in oestradiol and progesterone receptor levels in the porcine myometrium and cervix during pregnancy and parturition.

In vitro binding and exchange methods were used to determine the levels of oestradiol (E) and progesterone (P) receptors in cytosolic and nuclear fractions of cells obtained from the porcine myometrium and cervix during pregnancy and parturition. The concentration of oestradiol cytosolic receptors (ERc) in non-placental and placental myometrium and the cervix was low in early and mid-pregnancy, increasing at late pregnancy and was highest at parturition. The oestradiol nuclear receptors (ERn) followed the same pattern in the 3 sampling areas. The levels of PRc in non-placental regions were low in early pregnancy, increased to late pregnancy but declined during parturition. In placental regions the PRc value was high in early and mid-pregnancy, but decreased at late pregnancy and parturition. The concentration of PRc in the cervix increased significantly at mid-pregnancy and declined afterwards. In early and mid-pregnancy the PRn content was high, and decreased at late pregnancy and parturition in the 3 sampling areas. The data obtained agree with the present theories on the endocrine mechanisms regulating receptor levels in the uterus. Moreover, these data support the concept that the uterine motility during pregnancy and parturition might be influenced by changes in myometrial steroid receptor concentrations.

Animals↗

Regulation of the uterine expression of messenger ribonucleic acids encoding the oestrogen receptor and IGF-I peptides in the pig uterus.

The acute effects of oestradiol-17 beta on the expression of the oestrogen receptor (ER) and insulin-like growth factor I (IGF-I) in the endometrium of ovariectomized pigs were examined. The steroid receptor level was assayed by hormone binding techniques and specific mRNAs analyzed by solution hybridization using 35S-labelled RNA probes complementary to the ligand-binding domain of the ER receptor gene and a 160 bp PanI-Pvul fragment of the IGF-I gene. One hour after a single injection of oestradiol (1 micrograms/kg BW), the nuclear oestrogen receptor (ERn) mean level was increased 3-fold whereas the ER mRNA content had not changed significantly. After 3 hours the ERn mean concentration was still high; the mean ER mRNA level had decreased by 15% and the mean IGF-I mRNA had increased 3-fold above that in the samples collected prior to treatment from these ovariectomized animals. Six hours after the injection the ERn content had returned to the basal level and stayed there during the following six hours. The ER mRNA concentration continued to decline, reached its lowest value after six hours and had increased slightly by twelve hours. The IGF-I mRNA level increased steadily during the course of the experiment. At twelve hours after the injection it had increased 3-fold. From these data we conclude that in the pig uterus oestradiol down-regulates its own receptor and acts as a potent stimulator of endometrial growth by inducing IGF-I expression.

Animals↗

Effects of a tocolytic oxytocin analogue on lipid and carbohydrate metabolism.

The effect of a newly developed tocolytic oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on lipid and carbohydrate metabolism was investigated. Oxytocin and vasopressin both stimulated lipogenesis in isolated rat adipocytes, an effect which was dose-dependently inhibited by the oxytocin analogue. In vivo, intravenous injection of 10 nmol/kg body weight of the analogue to 11 healthy subjects caused an initial, but insignificant peak after 4 min in both plasma glucose and glycerol, which thereafter remained at basal level. It is concluded that although an antagonistic effect of the analogue on vasopressin- and oxytocin-stimulated lipogenesis could be demonstrated in vitro, the effect on lipid and carbohydrate metabolism in vivo in humans is insignificant.

Adipose Tissue↗

Extracellularly applied ATP alters the calcium flux through dihydropyridine-sensitive channels in cultured chick myotubes.

Extracellularly applied ATP mediates a biphasic calcium signal in cultured chick myotubes. A rapid and transient increase in cytosolic calcium was independent of extracellular calcium while a second signal, slower in onset and decay, was absent without extracellular calcium. In depolarized myotubes, the cytosolic [Ca2+] was increased more than ten times above baseline level. Addition of ATP to the incubation medium immediately increased the rate of return of cytosolic Ca2+ levels to baseline. The ATP effect was half-maximal at about 10 microM ATP and was mimicked by ATP S. This ATP-sensitive calcium influx was also rapidly stopped by addition of dihydropyridines such as PN 200-110, suggesting that it is the voltage operated Ca2+-channel that was inactivated by ATP.

Adenosine Triphosphate↗

Stimulatory effect of testosterone on renal 25-hydroxyvitamin D-3 1 alpha-hydroxylase in guinea pig.

Castration of male guinea pigs reduced the activity of the renal mitochondrial 25-hydroxyvitamin D-3 1 alpha-hydroxylase by about 50% without affecting the apparent Km for the reaction. Testosterone substitution for 10 days after castration increased the activity to about the same level as that of sham-operated animals. Ovariectomy of female guinea pigs had no effect on the 1 alpha-hydroxylase activity. Administration of testosterone to ovariectomized female guinea pigs increased the activity by about 50%, again without affecting the apparent Km. The different manipulations had no significant effect on circulating levels of 1,25-dihydroxyvitamin D or vitamin D-binding protein (DBP). It is concluded that testosterone may be a regulator of the 25-hydroxyvitamin D-3 1 alpha-hydroxylase in guinea pigs.

Animals↗

Concentration and turnover of estradiol in the rat uterus in vivo.

The concentrations and turnover of estradiol isolated from cytosolic and nuclear fractions of uteri from ovariectomized rats given estradiol, either in single injections or in continuous infusion, were analyzed by gas chromatography-mass spectrometry. The analytical method was validated for different organs and lower limits of analysis were established. After infusion of 20 ng x h-1 for 18-22 h, mean estradiol levels were 2.0-2.4 fmol x mg-1 uterine wet weight in the nuclear fraction, and 1.2-1.5 fmol x mg-1 in the cytosolic fraction. The concentrations were about five times higher after a single injection of one microgram estradiol but the distribution between nuclear and cytosolic fractions was almost the same. The concentrations of estradiol in nuclei from liver and spleen were 50-200 times lower than those in uterus. Taken together with previous knowledge, the results indicate that the distributions of estradiol and its receptor are not the same and that hormone response cannot be predicted from the concentration of receptors alone. The exchange of estradiol molecules in the uterus was followed after a change of the infusion from unlabelled to [11,12,12-2H3]-labelled estradiol, or vice versa. The uterine uptake of estradiol was calculated to be about 0.7 fmol x h-1 x mg-1 uterine wet weight. The half-life time was calculated to be at least 4 h for estradiol molecules isolated from the nuclear fraction and 3 h (significantly shorter) for those isolated from the cytosolic fraction. The results indicate an uptake of 40-90% of all estradiol passing through the uterus in proestrus with only about 10% of available receptors becoming occupied. When the infusion was changed from estradiol to ethynylestradiol, estradiol disappeared from the uterus at the same rate as in the experiments above. Ethynylestradiol was taken up at a rate of about 0.3-0.4 fmol x h-1 x mg-1 tissue. The percentage of total steroid found in the nuclear fraction was higher for ethynylestradiol, about 70%, than for estradiol, about 60%, indicative of a more stable association of receptor to nuclear binding sites when ethynylestradiol is the ligand.

Animals↗

Improving the detection and diagnosis of congestive heart failure.

Early detection of heart failure requires criteria by which to define the initial stages of a syndrome which often has an insidious onset and which may progress slowly for many years. The most specific definitions of heart failure are those obtained towards the end of the disease process, but reliance upon these means that, although few cases are misclassified, only manifest cases can be detected. Since prevention is the ultimate goal, early detection of subjects at risk and a wider understanding of the pathophysiological mechanisms and risk factors are necessary. The principal causes of heart failure in the Western world are coronary artery disease and hypertension; valvular heart disease and other cardiac disorders are relatively uncommon causes. The major risk factors are obesity, tobacco smoking and diabetes mellitus, and in a prospective large-scale study we have also shown that individuals who develop manifest symptoms of heart failure often have a long history of exercise-induced dyspnoea. Clearly, identification of the early symptoms of heart failure and prompt treatment of risk factors such as hypertension and obesity are important objectives. However, a better understanding of the underlying biochemical and structural abnormalities would help to define more appropriate preventive treatments.

Aged↗

Risk factors for heart failure in the general population: the study of men born in 1913.

In 1963 a sample of 973 men, all 50 years old, was drawn from the population register of Gothenburg, Sweden. These men have been followed up for 17 years with repeated examinations regarding a number of variables possibly related to cardiovascular disease. The latest examination, at the age of 67 years, focused on congestive heart failure (CHF). The incidence rate of manifest CHF varied from 1.5 to 10.2 cases (1000 population)-1 yr-1, depending on which age group was being studied. For the age group 50-67 years the incidence of manifest CHF was 5.5 (1000)-1 yr-1. A large number of factors associated with the risk of acquiring CHF were identified. In multivariate regression analyses, hypertension and smoking were the major independent risk factors. Body weight, heart volume, T-wave abnormalities, heart rate variability, peak expiratory flow rate, psychological stress and Fy-antigen (a genetic marker?) were also independent risk factors. Possible strategies for prevention are discussed.

Aged↗

A cross-sectional analysis of glucose tolerance and cardiovascular disease in 67-year-old men.

The relationship between degree of glucose tolerance and cardiovascular disease has been studied in a cross-sectional population survey of 644 men born in 1913, randomly sampled and examined at the age of 67. The cohort was divided into different groups according to current diagnostic criteria for diabetes and impaired glucose tolerance. An almost 2-fold higher prevalence of hypertension, myocardial infarction, angina pectoris, and congestive heart failure was found in the group with impaired glucose tolerance compared to the group with a normal glucose tolerance. Fifty per cent of the men with impaired glucose tolerance were being treated with some drug for cardiovascular disease, usually diuretics for hypertension. Intermittent claudication showed a 2.5-fold higher prevalence among the diabetic patients. A computerized 12-lead exercise-ECG test, with a unique accuracy in measuring ST-segment changes, was performed in a subset of 135 men. This showed no association between ST-segment depression and different degrees of glucose tolerance, even when accounting for confounding factors such as treatment with beta-blocker agents or digoxin, pathological Q-waves, and differences in maximal heart rate.

Aged↗

Regulation of uterine insulin-like growth factor I mRNA and insulin-like growth factor II mRNA by estrogen in the rat.

IGF-I and IGF-II are peptides with mitogenic properties. In this study mRNA for IGF-I and IGF-II was analysed in rat uterine tissue after different endocrine manipulations and the possibility of an estrogenic regulation of IGF expression was investigated. Both IGF-I and IGF-II mRNA were present in uterine tissue. The level of IGF-I mRNA, but not IGF-II mRNA, was reduced following ovariectomy. Administration of estradiol (2.5 micrograms/day for 4 days) to ovariectomized rats increased IGF-I mRNA 8-fold to levels seen in intact animals. In adult animals hepatic IGF-I mRNA did not appear to be increased by estrogen treatment. Low levels of IGF-II mRNA were detected in the uterus, but showed no dependence on estrogen. The inductive effect of estrogen on uterine IGF-I mRNA could not be substituted for by growth hormone administration (0.5 mg/100 g, ip for 6 h). The present results suggest IGF-I as a potential candidate for a mediator of estrogen-induced growth. Both estrogen and GH induce IGF-I mRNA and a tissue specificity for these hormones is indicated where GH regulates hepatic and estrogen uterine IGF-I mRNA.

Animals↗

CHD in Sweden: mortality, incidence and risk factors over 20 years in Gothenburg.

Mortality from coronary heart disease (CHD) increased among Swedish men between 1968 and 1981, but after that, began to decline. CHD mortality in women decreased slightly, mostly among older women. From 1980, the incidence of non-fatal myocardial infarction (MI) started to decrease among men. Among middle-aged women, however, there was a significantly increased incidence. Mortality during the two years following hospital discharge decreased both in men and women between 1968 and 1985 in Gothenburg. Between one-sixth and one-fifth of major CHD events occur among patients with previous MI or angina pectoris. Serum cholesterol and smoking habits increased among middle-aged men from 1963 to 1973, but decreased thereafter. Blood pressure decreased, and the percentage of people on treatment increased. Blood pressure and serum cholesterol decreased among middle-aged women, but smoking and triglycerides increased. These different trends might explain an increasing CHD incidence among younger women but decreasing incidence and mortality among older women.

Age Factors↗