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Biomedical subjects

M Thorén

Publications and source records attributed to M Thorén.

At least 37 records · Page 2Linked to original sources
PubMed1995

Growth hormone (GH) treatment up-regulates GH receptor mRNA levels in adipocytes from patients with GH deficiency and Prader-Willi syndrome.

We have investigated the effect of growth hormone (GH) treatment on GH receptor mRNA expression in five prepubertal children with Prader-Willi syndrome and in eight patients with GH deficiency. An adipose tissue needle biopsy was taken before and after 2-4 mo of GH treatment, and RNA was isolated from adipose tissue and from adipocytes. GH receptor mRNA levels were determined by an RNase protection/solution hybridization assay. To further assess the specificity of the assay for GH receptor mRNAs, RNA extracted from human adipose tissue was subjected to Northern blot analysis. GH treatment significantly increased GH receptor mRNA levels in adipose tissue and isolated adipocytes. Our results indicate that GH may have an important role in regulating the GH receptor in humans.

Adipocytes↗
PubMed1995

Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects.

To investigate whether previously reported increased levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in GH-deficient patients only reflect decreased levels of insulin or are elevated in relation to insulin, diurnal profiles of IGFBP-1 and insulin were determined in plasma from patients with GH levels below 0.2 microgram/L throughout 24 h (n = 23) and compared to profiles from patients with insulin-dependent diabetes mellitus (IDDM; n = 9) and healthy subjects (n = 12). Samples were drawn using a continuous withdrawal technique at 20-min intervals. Levels of IGF-I were determined in one morning sample. As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as well as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning. Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 micrograms/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 micrograms/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 micrograms/L, respectively). Fasting levels of IGFBP-1 correlated to 24-h mean values of IGFBP-1 in all groups separately and in the combined group (r = 0.931; P < 0.001). An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001). Corresponding values for healthy subjects were r = -0.548; P = 0.065 and r = -0.712; P < 0.01, respectively, whereas in IDDM patients the relationship was nonsignificant. Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05). When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared. However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively). The majority of the IDDM patients had values in the same range as the GH-deficient patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy.

To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therapy, 68 adults (25 females and 43 males) aged 22-61 (mean 44.2 +/- 1.2) years with GH deficiency (GHD) were studied. Fifty-eight patients had panhypopituitarism, three had isolated GHD and in seven patients at least one additional pituitary function was affected. Twenty-one patients had childhood onset GHD. The patients were randomized to receive either GH in daily injections (0.125 IU.kg-1. week-1 for the first 4 weeks and subsequently 0.25 IU.kg-1. week-1) or placebo for 6 months. The trial continued as an open study with GH treatment for 6 to 12 months, with data presented as compiled data of 12 months of GH treatment in 64 patients. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry and bone turnover was assessed by serum markers of bone metabolism (osteocalcin, procollagen I peptide, cross-linked telopeptide of type I collagen and alkaline phosphatase activity), In women with adult onset GHD (N = 19) and in men with childhood onset GHD (N = 15), total body, spine and hip BMD was significantly reduced at baseline compared to Swedish age- and sex-matched control material. In men with adult onset of GHD (N = 28), BMD did not differ from male controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Activation of MAP kinase in Swiss 3T3 fibroblasts by insulin-like growth factor-I.

A peak of cytosolic myelin basic protein kinase activity was observed at 2-5 min after addition of 10 nM insulin-like growth factor-I (IGF-I) to Swiss 3T3 fibroblasts. Analysis of the induced kinase activity by chromatography, immunodetection and in situ kinase assay suggests that this represents a 1.8- to 3.5-fold increase in the activity of p42 mitogen-activated protein kinase. Addition of insulin at 10 nM also resulted in an increased kinase activity in these respects, however, only to approximately 60% of that induced by IGF-I. A similar quantitative relation between the effects of insulin and IGF-I was found for induction of lipid and glycogen synthesis from [14C- (U)]-D-glucose. However, incorporation of 3H-L-leucine into protein was stimulated to the same extent by the two agents. The effect of 10 nM insulin on proliferation, measured as tetrazolium dye reduction, was only 18% of that induced by 10 nM IGF-I. The obtained data suggest that cytosolic mitogen-activated protein kinase activation may constitute a signalling pathway for glucose metabolism, and especially glycogen synthesis, induced by peptides of the insulin superfamily.

3T3 Cells↗
PubMed1994

Immunoreactive proinsulin-like growth factor-II levels in healthy subjects, patients with growth hormone deficiency, and patients with type 1 diabetes: effects of insulin-like growth factor-I and insulin.

Proinsulin-like growth factor-II (IGF-IIE), with an E-peptide elongation at the C-terminal, is found in the circulation and in different body fluids with mol wt between 10-16 kilodaltons compared to native 7.4-kilodalton IGF-II. Some tumors overexpress IGF-II and IGF-IIE with increased levels in patients serum, sometimes causing hypoglycemia (nonislet cell tumor-induced hypoglycemia). We have developed a RIA for a 15-amino acid part of the E-peptide. By using the E16-peptide as the labeled ligand, this RIA is unaffected by the presence of IGF-binding protein in the samples. Gel chromatography under acid and neutral conditions revealed that all IGF-IIE was detected without prior separation of serum. Using recombinant IGF-IIE21 as standard, we determined normal levels in 70 males and 67 females between 20-70 yr of age. The average was 46.6 +/- 1.1 micrograms/L, and the 95% confidence interval was between 21.4-71.9 micrograms/L. A significantly higher level was found in males (49.0 +/- 1.6 micrograms/L) compared to females (44.2 +/- 1.3 micrograms/L). In two nonislet cell tumor-induced hypoglycemia patients, levels of immunoreactive (ir) IGF-IIE were 2.5-3 times normal levels. GH-deficient patients had normal levels, but daily sc injections of recombinant human IGF-I decreased serum irIGF-IIE by 40%. Insulin-dependent diabetic patients undergoing liver venous catheterization had normal basal levels of irIGF-IIE in peripheral blood. A 180-min insulin infusion decreased the levels significantly in the vena hepatica, but no splanchnic gradient was observed.

Adult↗
PubMed1993

Serological cross-reactions between Moraxella (Branhamella) catarrhalis and other oropharyngeal bacteria.

Oropharyngeal bacteria belonging to different species were tested for serological cross-reactions with Moraxella catarrhalis using sera from immunized rabbits. Sera were tested using immunofluorescence, an enzyme immunoassay (EIA) and immunoblotting. On immunofluorescence, significant cross-reactions were demonstrated with beta-hemolytic streptococci group A and group G, as well as with streptococci of the viridans group. Some cross-reactions were also noted with Neisseria meningitidis. In the EIA, strong cross-reactions were demonstrated with beta-hemolytic streptococci. No cross-reactions were obtained with Streptococcus pneumoniae, Haemophilus influenzae or common oral Neisseria. The results are of importance for the interpretation of serological tests to detect infections with Moraxella catarrhalis, and for the development of methods for detection of antigens in samples from the respiratory tract.

Animals↗
PubMed1993

Effects of recombinant human insulin-like growth factor I administration in adults with growth hormone deficiency.

Recombinant human insulin-like growth factor I (IGF-I), 40 micrograms/kg/body weight, was administered subcutaneously at 08.00 hours to six adult patients with growth hormone deficiency (GHD). The mean maximal IGF-I concentrations were found 2-6 hours after injection. Concentrations then gradually declined, though mean values were still above basal 24 hours after the injection. Only one patient maintained IGF-I levels above the lower normal range throughout 24 hours. There was a significant decrease in mean IGF-II concentrations when measured 4 and 24 hours after injection of IGF-I. The diurnal variations of insulin and IGF binding protein-1 were preserved. There were no side-effects, and blood glucose remained normal. These results show that in patients with low IGF-I levels resulting from GHD, it is necessary to administer IGF-I at intervals of less than 24 hours to obtain IGF-I levels that are within the normal range.

Adult↗
PubMed1993

Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.

Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6). Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min. IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)]. The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations. When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001). In GH-deficient patients, serum GH concentrations remained undetectable (< 0.2 micrograms/L), and IGF-I concentrations were unchanged after the glucagon injection. In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min. In conclusion, glucagon increased serum IGFBP-1 concentrations in spite of increases in glucose and insulin. These results suggest that glucagon is a stimulator of IGFBP-1.

Adult↗
PubMed1993

Insulin-like growth factor (IGF) I and II and IGF binding protein (IGFBP) 1, 2 and 3 in serum from patients with Cushing's syndrome.

In the present study of twenty-two patients with Cushing's syndrome, serum insulin-like growth factor (IGF)-I concentrations were normal to high with an increased mean IGF-I concentration, 40% above that of healthy subjects of the same age (p < 0.001). Serum IGF-II concentrations were normal. The morning serum IGF binding protein (IGFBP)-1 concentrations were within the range of healthy controls. IGFBP-1 was inversely correlated to the IGF-I concentration (p < 0.001) and to the 24 h urinary cortisol excretion (p < 0.005) with a combined R squared value of 0.58. In contrast to IGFBP-1, serum IGFBP-2 and IGFBP-3 concentrations were elevated by 1.89 +/- 1.78 SD and 0.92 +/- 0.78 SD (mean +/- 2 SD), respectively. Although increased, the serum IGFBP-2 concentration was inversely correlated to the IGF-I concentration (r = -0.67, p < 0.001). Immunoreactive IGFBP-3 was increased in proportion to IGF-I and the molar ratio [IGFBP-3]:[IGF-I] + [IGF-II] was close to unity (1.04 +/- 0.14), as that of healthy subjects. In serum from patients with Cushing's syndrome, with increased immunoreactive IGFBP-3, there was a corresponding increase in intact glycosylated 40-43 kDa IGFBP-3 as determined by Western ligand blotting. Neutral size chromatography of serum from patients with Cushing's syndrome showed that IGF-I and IGFBP-3 immunoreactivity were predominantly found at the elution volume of the ternary 150 kDa IGF-I/IGFBP-3/acid labile subunit complex and a similar pattern was displayed by normal serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Preliminary study of the effects of growth hormone substitution therapy on bone mineral density and serum osteocalcin levels in adults with growth hormone deficiency.

In order to evaluate the consequences of pituitary insufficiency on bone mineral status, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 33 patients (aged 22-65 years) with pituitary insufficiency. BMD of the lumbar spine and femoral neck was decreased. Twenty of the patients were randomized to receive either recombinant human growth hormone (GH), 0.25 IU/kg/week for 6 months (0.125 IU/kg/week during the first month), or placebo. Serum osteocalcin levels increased significantly during GH administration. In the GH-treated group, there was no change in lumbar spine BMD and a small but significant decrease in femoral neck BMD (p < 0.05) after 6 months. Treatment periods longer than 6 months are needed to evaluate the potential beneficial effect of GH on BMD. This is in accordance with our previous findings of an increase in forearm BMD after 12 months of GH substitution therapy.

Adult↗
PubMed1992

Variability of surface-exposed antigens of different strains of Moraxella catarrhalis.

For serological diagnosis of infection with Moraxella (Branhamella) catarrhalis it is important to determine if there is variability of antigenic properties among different strains. Cross-reactions of nine strains were investigated by an immunofluorescence test using sera from immunized rabbits. All titres but one were 1:256 or higher, the highest being 1:4096. Thus a high degree of antigenic similarity was demonstrated among different strains of Moraxella catarrhalis. However, the homologous titres of six sera were 2 to 16 times higher than the titres for other strains indicating strain variations in antigenic properties of some surface components. There was no correlation between lipopolysaccharide type and titre in the immunofluorescence test.

Animals↗
PubMed1992

Glucocorticoid receptor abnormalities in fibroblasts from patients with idiopathic resistance to dexamethasone diagnosed when evaluated for adrenocortical disorders.

A retrospective survey was accomplished on 420 consecutive patients who had undergone dexamethasone suppression tests between 1975-1988 due to suspected adrenal disorders. We found 7 patients in whom glucocorticoid resistance was apparent. They showed 4-6 abnormalities of the 7 investigations used: insensitivity to dexamethasone inhibition (n = 7), increased urinary cortisol (n = 3), glucocorticoid receptor (GR) thermolability (n = 4), decreased number of glucocorticoid receptors (n = 4), abnormal ligand affinity of GR (n = 4), abnormal basal GR mRNA expression (n = 4), and abnormal down-regulation of basal GR mRNA levels by dexamethasone (n = 1). The four patients with GR thermolability also showed increased basal GR mRNA levels. In the other patients the number of GR per cell was decreased without an up-regulation of GR mRNA. It is concluded that the syndromes of glucocorticoid resistance vary notably, clinically as well as biochemically; in patients evaluated for adrenocortical disorders the syndrome is apparently encountered in 1-2% of the patients.

Adrenal Cortex Diseases↗
PubMed1992

Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism.

Six patients (21-50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatotropin, 0.04-0.1 U.kg.body wt-1.day-1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0 +/- 0.6 (SEM)% and 3.8 +/- 1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were -2.4 +/- 0.6% and -1.9 +/- 0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean +2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.

Adult↗
PubMed1991

Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormone-producing pituitary tumors.

Stereotactic radiosurgery on the pituitary given with the cobalt-60 gamma unit was used in the treatment of 21 patients with growth hormone (GH)-producing pituitary adenomas and acromegaly. All but one patient had locally invasive macroadenomas, and in the majority of cases, there was parasellar growth. Radiosurgery was the initial treatment for seven patients. Fourteen patients were previously treated by pituitary surgery, eight of whom had undergone conventional external pituitary irradiation as well. All patients had clinical signs of active acromegaly before radiosurgery. The radiation doses given to the previously untreated patients or those who only underwent surgery were 40 to 70 Gy in each of one to three irradiations. The patients with previous external irradiation received a lower dose of 30 to 50 Gy in each of one or two irradiations. The patients were observed during a period of 1 to 21 years from the first radiosurgical session. Two young patients had a clinical remission with a substantial decline of GH levels to near normal serum profiles. Another eight patients obtained reduction of GH levels and clinical activity. More than half of the patients (11 of 21) had minor or no effects from the treatment. There were no complications from the radiosurgery except the development of pituitary insufficiency in 2 of 13 patients who did not undergo previous conventional external irradiation. The remission rates were lower than the results previously reported by us for radiosurgery for Cushing's disease. This may be a result of the predominance in the present study of invasive macroadenomas and single treatments and to the lower radiation doses used in the patients who underwent conventional irradiation previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1991

Basal and ACTH-stimulated cortisol and aldosterone release from adrenocortical adenomas in vitro.

Basal and ACTH-stimulated release of aldosterone and cortisol was studied in slices of adrenocortical adenomas and adrenal cortex from 16 consecutive patients with Conn's syndrome (n = 7), Cushing's syndrome (n = 5) or no signs of steroid hypersecretion (n = 4). Clinical data were reviewed and histologic examination was repeated. The adrenal cortex and all tumours but one (non-hyperfunctioning) secreted cortisol. Cortisol release increased after addition of ACTH in 13/15 tumours and all cortex slices. Aldosterone was secreted from the adrenal cortex in all patients and was increased by ACTH in 75% of the tissue specimens. Adenomas from patients with hyperaldosteronism showed the highest basal aldosterone secretion. This secretion was further increased by ACTH. Tumours from patients without signs of corticosteroid excess also released steroids and responded to ACTH. It is concluded that in vitro studies of steroids released from adrenocortical tumours contribute to their diagnostic and functional evaluation.

Adenoma↗
PubMed1990

Hypothalamic-pituitary-adrenal axis interaction with prostaglandins.

1. The major PGE2 plasma metabolite, 15-keto-13, 14-dihydro-PGE (PGEM) was measured during metyrapone, dexamethasone and ACTH tests in order to elucidate if plasma PGE was affected by short term changes of the hypothalamic-pituitary adrenal axis function in man. 2. Plasma PGEM, serum cortisol and serum 11-deoxycortisol were determined by RIA. 3. Metyrapone (an inhibitor of adrenal 11 beta-hydroxylase), 250-1000 mg was given orally at 4 hour intervals for 20 hours. PGEM, cortisol and 11-deoxycortisol were measured before and 10 and 22 hours after the start of metyrapone in 10 patients evaluated for pituitary disease. 4. Dexamethasone, 1 mg orally, was given at 23 hours on day one and 25 IU (1-24) ACTH were given iv at 8 hours on day two. Blood was drawn for determination of PGEM and cortisol at 8 hours day one, and 8 hours day two. After the ACTH injection, blood was drawn at 90 minutes (for PGEM) and at 120 minutes (for PGEM and cortisol). 10 subjects aged 21-62 years were studied. 5. Plasma PGEM levels were significantly increased after metyrapone, concomitantly with the lowering of serum cortisol levels. 6. No difference in the PGEM increase between patients with normal or subnormal 11-deoxycortisol response was found. 7. A significant increase in plasma PGEM levels was found when serum cortisol was suppressed 9 hours after dexamethasone administration. 8. Glucocorticoids inhibit synthesis of eicosanoids and the present results suggest that short term decrease in cortisol may stimulate PG synthesis.

17-Hydroxycorticosteroids↗