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E Haug

Publications and source records attributed to E Haug.

At least 37 records · Page 2Linked to original sources
PubMed2000

The Sp1 binding site polymorphism in the collagen type I alpha 1 (COLIA1) gene is not associated with bone mineral density in healthy children, adolescents, and young adults.

Up to 85% of the variance in bone mineral density (BMD) is genetically determined. A putative candidate gene involved in the regulation of bone mass is the COLIA1 gene encoding type I collagen, which is the major protein of bone. We examined possible allelic influences of a G to T COLIA1 gene polymorphism in a recognition site for the transcription factor Sp1 on: (i) gain of forearm BMD using single photon absorptiometry (SPA); and (ii), BMD of the forearm, spine, hip, and whole body with dual X-ray absorptiometry (DXA). At baseline, 269 healthy boys and girls aged 8.2-16.5 years were eligible for the study. Forearm BMD measurements obtained at baseline and after 3.8+/-0.1 years (+/-s.d.) were used to calculate the annual percentage change in BMD. Calcium intake and physical activity were determined by a detailed questionnaire at baseline and after 1 year. Essentially no significant differences in forearm BMD gain or in BMD assessed at the forearm, spine, and whole body were observed among the three COLIA1 genotypes. In conclusion, the data indicate that the polymorphism at the Sp1 site in the COLIA1 gene is not associated with BMD or gain of forearm BMD in healthy boys and girls.

Adolescent↗
PubMed2000

Perfusion system for studying peptide secretion from endocrine cells with high time resolution.

To study the secretion from endocrine cells in culture, we have developed a cell column perfusion system with a time resolution of 4 s. The core of the system is a perfusion chamber with a cell-supporting matrix of monosized polystyrene beads. The particles are solid and can withstand a high pressure gradient without deformation. The minimum amount of cell material required to obtain detectable levels of secretory products is a function of the assay sensitivity, perfusion flow, fraction volume and time resolution. The volume of the perfusion chamber is therefore adjustable to satisfy varying demands of minimum cell number. The general flow characteristics of the system were characterized using radiolabeled substances of various molecular sizes. Using the system in secretory studies of rat pituitary tumor (GH4C1) cells, we have identified differences in secretion profiles that may be related to the kinetics of the different transmembrane and intracellular mechanisms involved.

Animals↗
PubMed1999

[Hemochromatosis--a rare cause of hypogonadism].

A 28-year-old man presented in 1992 with decreased libido and erectile dysfunction. He was found to have central hypogonadism with low serum levels of testosterone, LH and FSH. Computer tomography of the cella turcica was normal. Apart from hypogonadism, the pituitary function was normal. He was successfully treated with testosterone injections. In June 1995, elevated levels of serum ferritin (4,094 micrograms/l) and transferrin saturation (94%) raised suspicion of hemochromatosis. The diagnosis was confirmed by a percutaneous liver biopsy, and treatment started with regular phlebotomies. After three years of treatment the serum levels of LH and testosterone were normalized. Hypogonadism is, except for diabetes mellitus, the most frequent endocrine disturbance in hemochromatosis. It is found almost exclusively in male patients. It is important to exclude hypogonadism in male patients with hemochromatosis, but it is also important to exclude hemochromatosis in male patients with hypogonadism.

Adult↗
PubMed1999

The urinary excretion of deoxypyridinium cross-links is higher in diabetic than in nondiabetic adolescents.

We have measured the urinary excretion of deoxypyridinium (D-Pyr) crosslinks, a sensitive and specific marker of bone resorption, in morning urine in 102 healthy, nonhospitalized, Caucasian subjects (8-18 years) and in 18 diabetic subjects (12-17 years). The free D-Pyr crosslinks were measured using the Pyrilinks D-Assay. In the diabetic subjects, plasma glucose was regulated throughout the night by a constant infusion of insulin and a variable infusion of 24% glucose. In the nondiabetic subjects, the excretion of D-Pyr increased until 12-14 years of age, and thereafter decreased, and the excretion of D-Pyr/hour was correlated with the height Z-score. The excretion of D-Pyr/hour and the D-Pyr/creatinine ratio was higher in the diabetic adolescents than in the nondiabetic adolescents. In subjects over the age of 12, the D-pyr/creatinine ratio was higher in males than in females. In conclusion, in healthy children and adolescents, the excretion of D-Pyr peaks at 12-14 years of age. The D-Pyr excretion is higher in diabetic than in nondiabetic adolescents, suggesting increased bone resorption in diabetic adolescents.

Adolescent↗
PubMed1999

Androgen replacement and quality of life in patients treated for bilateral testicular cancer.

Gonadal hormones and quality of life (QL) were assessed in bilaterally orchiectomized patients with testicular cancer who received intramuscular androgen replacement (ARP). 43 patients were to have serum analyses of testosterone LH, FSH and SHBG, preferably performed at the end of the interval between two intramuscular injections. They also completed a QL questionnaire consisting of the EORTC QLQ-C30, GHQ-28, IES and PAIS (sexuality). 17 of 31 evaluable patients had subnormal testosterone levels, and 9 highly elevated LH. Blood levels indicating hypogonadism were more often observed in the 25 patients whose ARP was scheduled at > or = 3 week intervals than in the 18 patients with < or = 2 weeks between ARP injections. A total of 11 patients reported hot flushes. The patients' QL was similar to that of a control group. However, 8 (20%) patients were 'cases' according to GHQ-28/IES, independent of their hormone levels. Current standard intramuscular ARP is not optimal in approximately 1/3 of the patients who have undergone bilateral orchiectomy for testicular cancer, particularly if scheduled at > or = 3 week intervals. Schedules for ARP have to be improved. In spite of intermittent hypogonadism most patients are psychosocially and sexually well adjusted to their health situation.

Adult↗
PubMed1999

High prevalence of the hemochromatosis-associated Cys282Tyr HFE gene mutation in a healthy Norwegian population in the city of Oslo, and its phenotypic expression.

BACKGROUND: Previous studies have shown that 5%-10% of white subjects are heterozygous for the HFE gene C282Y mutation, which is associated with hemochromatosis. The aim of our study was to determine the prevalence of heterozygosity and homozygosity for the C282Y HFE gene mutation and its phenotypic expression in a group of healthy Norwegians. METHODS: Fasting blood samples were obtained from 505 unrelated hospital employees. Serum iron, transferrin, and serum ferritin were measured. Transferrin saturation was calculated. The presence of HFE gene mutation was determined with a polymerase chain reaction-based analysis. RESULTS: Two of the 505 subjects (0.4%) were homozygous and 75 (14.9%) were heterozygous for the C282Y mutation. Median serum ferritin among the heterozygotes was 59 microg/l, compared with 47 microg/l among individuals without the C282Y mutation (P = 0.12). Median transferrin saturation among the heterozygotes was 31%, compared with 24% among individuals without C282Y mutation (P < 0.001). Twenty-three individuals (4.6%) had a serum ferritin level > 200 microg/l. Eight of these (35%) had the C282Y mutation: two homozygotes and six heterozygotes. Transferrin saturation > 50% was observed in 25 individuals (5.0%). Twelve of these (48%) had the C282Y mutation; two were homozygotes and 10 heterozygotes. Only eight individuals (1.6%) had a transferrin saturation > 60%: one homozygote, five heterozygotes, and two individuals without mutation. CONCLUSIONS: Fifteen per cent of a healthy Norwegian population is heterozygous for the HFE gene mutation C282Y. This is among the highest reported prevalence values among healthy individuals. Half of the subjects with transferrin saturation greater than 50% were carriers of the C282Y mutation.

Adult↗
PubMed1999

Vitamin D: a hormonal regulator of the cAMP signaling pathway.

In the rat thyroid FRTL-5 cell line calcitriol, the biologically most active of the naturally occurring vitamin D metabolites, attenuates both TSH-stimulated cAMP production and the effects of cAMP. Calcitriol treatment abolishes the upregulation of the TSHR number occurring in cells cultivated in the absence of TSH. In addition, the level of G(i-2)alpha increases, which may further attenuate the transmembrane signaling of TSH and facilitate the effects of IGFs. The effect of cAMP on PKAI stimulation is inhibited by increasing the level of the PKA subunit RIIbeta. Regulation of TSHR, G(i-2)alpha and RIIbeta is associated with altered cell proliferation and differentiation in several cells and tissues. Effects of calcitriol on these proteins indicate how the vitamin D endocrine system may regulate cAMP signaling in both classical and nonclassical target tissues.

Animals↗
PubMed1999

Low serum calcidiol concentration in older adults with reduced muscular function.

OBJECTIVE: To examine the association between muscular function and the serum concentrations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol). DESIGN: A randomized population survey. Baseline measurements of serum calcidiol and calcitriol concentrations and assessment of muscular function (hand grip strength, ability to climb stairs, outdoor activity, and fall occurrence). SETTING: The Medical department, Aker University Hospital, Oslo, and subjects' homes. PARTICIPANTS: Two hundred forty-six recently hospitalized older patients and 103 randomly selected older people living at home. MEASUREMENTS: Serum concentration of calcidiol and calcitriol in relation to muscle function. MAIN RESULTS: Reduced muscle function was associated with low calcidiol levels. In both the hospital group and the home group, calcidiol concentrations correlated positively to arm muscle strength (r = .22, P < .001; r = .37, P < .001), ability to climb stairs (r = -.16, P < .05; r = -.42, P = < .001), physical activity (r = -.27, P < .001; r = -.31, P < .001), and the absence of fall occurrences (r = -.27, P < .001; r = -.31, P = .004). Calcitriol showed an association with physical activity in the hospital group (r = -.19, P < .05), and with fall last month in the home group (r = -.22, P < .05). CONCLUSIONS: Older people with reduced muscle function often had reduced levels of calcidiol serum concentration. Low levels of calcidiol were not associated with signs of general undernutrition, such as low body mass, or with reduced arm-muscle circumference or triceps skinfold thickness. This finding may suggest a physiological role for calcidiol in muscle function. Reduced muscle strength increased disability in our older subjects, which may be improved by vitamin D supplementation in vitamin D-deficient subjects.

Activities of Daily Living↗
PubMed1999

Two human osteoblast-like osteosarcoma cell lines show distinct expression and differential regulation of parathyroid hormone-related protein.

Parathyroid hormone (PTH)-related protein (PTHrP) acts as a local regulator of osteoblast function via mechanisms that involve PTH/PTHrP receptors linked to protein kinase A (PKA) and C (PKC). However, the regulation of PTHrP production and mRNA expression in human osteoblasts is poorly understood. Here we have characterized alternative PTHrP mRNA 3' splicing variants, encoding PTHrP isoforms of 139, 141, and 173 amino acids, and studied the regulation of PTHrP and its mRNAs by activated PKA and PKC in two human osteoblast-like cell lines (KPDXM and TPXM). Using exon-specific Northern analysis and reverse transcriptase-coupled polymerase chain reaction, we identified mRNAs encoding PTHrP(1-139) and PTHrP(1-141) in both cell lines. PTHrP(1-139) mRNAs predominated in TPXM cells and PTHrP(1-173) mRNAs were only detected in TPXM cells. Activation of PKA or PKC resulted in different effects on PTHrP and its mRNAs in the two cell lines. In TPXM cells, peptide-specific immunoassays detected high basal levels of PTHrP, increasing by 2-fold in cell extracts and 4-fold in culture media at 7 h and 24 h after exposure to forskolin, respectively, paralleling changes in PTHrP mRNA expression. Phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA), a PKC activator, had no effect. In KPDXM cells, PTHrP was not detected in culture media under basal experimental conditions, and barely detectable amounts were present in cell extracts of TPA-treated cells, although the mRNA levels increased substantially in response to TPA. In the responsive cell lines, the effects on mRNA levels were dose dependent, and increased by 6.9- to 10.5-fold and 2.0- to 4.1-fold at 4 h in TPXM and KPDXM cells after exposure to 10 microM forskolin and 150 nM TPA, respectively. PTHrP mRNA levels then declined but were sustained above controls also at 12 h in both cell lines, albeit at considerably higher levels in TPXM cells. The different responsiveness to agents activating PKA- and PKC-dependent pathways may depend on the cellular state of differentiation, or alternatively, cancer cell line-specific defects. Our data demonstrating distinct differences in mRNA species and the amounts of PTHrP produced by the two cell lines as compared with roughly equivalent overall mRNA levels may suggest that post-transcriptional mechanisms play an important role in limiting the production of intracellular and secreted PTHrPs in human osteoblastic cells.

Colforsin↗
PubMed1998

[Vitamin D deficiency among hospitalized and home-bound elderly].

Vitamin D status, measured as serum calcidiol concentration, was studied in a group of 273 recently hospitalised patients at Aker University Hospital and compared to a group of 98 persons living in their own homes, all living in Oslo and all above 70 years of age. We found lower serum calcidiol concentrations in the hospital group than among people living in their own homes, in men as well as in women (mean +/- SD, 40.4 nmol/l +/- 23.2 vs 59.6 nmol/l +/- 28.9 in men and 37.5 nmol/l +/- 22.6 vs 48.5 +/- 20.3 in women). 34% of the men and 49% of the women in the hospital group had vitamin D deficiency (se. calcidiol < 20 nmol/l). There was no seasonal variation in the hospitalised group; the group living at home did show seasonal variations, with highest levels in late autumn (62.2 nmol/l) and lowest levels in February (42.7 nmol/l). The low levels of calcidiol concentration may contribute to the high prevalence of hip-fracture among elderly in Oslo.

Aged↗
PubMed1998

No neuronal regulation of murine bone marrow function.

Bone marrow is innervated by efferent (sympathetic) and afferent nerves, but it is not clear whether these nerves affect cell formation or release in any significant way. To elucidate this problem, we studied mice neonatally sympathectomized with 6-hydroxydopamine and adult mice in which one hind limb was surgically denervated. Progenitor and transit cell numbers and proliferative activity were estimated in bone marrow, blood, and spleen. In addition, we performed unilateral electrical stimulation of nerve fibers to tibial marrow and applied a cell mobilizing stimulus (bleeding, granulocyte colony-stimulating factor injection, or intraperitoneal injection of a chemotactic substance) to investigate cell egress from the marrow. Blood flow to hindleg bone marrow was assessed with the radioactive microsphere technique. Except for a smaller bone marrow cell population and lower body weight in neonatally sympathectomized mice, we found no clear indications that bone marrow innervation influenced cell production. Also, the innervation did not detectably affect cell release from the marrow. Electrical stimulation of hind limb nerves did not change the blood flow to the marrow, whereas it markedly decreased blood flow to the overlying muscle. We therefore conclude that no obvious function can be ascribed to tibial marrow innervation in the mouse.

Animals↗
PubMed1998

[Thyroid hormone resistance. Clinical, biochemical and genetic study of a family].

We here present a family where three individuals in three generations had varying degrees of goiter, tachycardia, fatigue, hyperactivity, and learning disability. Serum T3 and free T4 were elevated, whereas TSH was normal or slightly increased. The clinical findings in combination with the hormone values led to several supplementary investigations and therapies being carried out, but they had no beneficial influence on the patients' symptoms. The commonest form of thyroid hormone resistance (RTH) is an autosomal dominantly inherited disorder with varying degrees of hypo- and hyperthyroidism, including the hormonal changes described above. Several mutations, particularly in exons 9 and 10 of the thyroid hormone receptor beta gene, have been described and shown to be responsible for RTH. Exons 7, 8, 9, and 10 in the thyroid hormone receptor beta gene were amplified by polymerase chain reaction and analyzed by DNA sequencing. A heterozygous point mutation in nucleotide 1244 in exon 9 was demonstrated in the two patients with RTH that were available for the study. The guanidine to thymidine point mutation changed the codon for arginine in position 320 in the receptor protein to leucine. This mutation has previously been shown to decrease receptor affinity for T3; it has been demonstrated in some patients with RTH, and it is probably the cause of RTH in the family described in this study.

Adult↗
PubMed1998

The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome.

In this study we examined the possible correlation between insulin metabolism and outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women who were entered into the study in a consecutive fashion. Following performance of the CIGMA (continuous infusion of glucose with model assessment) test, 17 women were classified as insulin resistant and 25 women as non-insulin resistant. Each woman received up to two cycles of low-dose follicle stimulating hormone (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70 cycles performed. The insulin resistant PCOS women required more gonadotrophin and a longer time to achieve follicular maturation. By multiple regression gonadotrophin consumption correlated best with CIGMA value but not with fasting insulin concentration or body mass index. In the insulin resistant PCOS women 10 out of 29 cycles were cancelled due to a multifollicular response, while only one of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the non-insulin resistant PCOS women. In conclusion, in PCOS women insulin resistance seems to be an unfavourable condition resulting in an elevated cancellation rate and a low conception rate following low-dose FSH stimulation.

Adult↗
PubMed1998

Hypochondroplastic dwarfism in the Irish setter.

Two test matings in the irish setter were performed, and genetic, clinical, morphometric, radiographic, bone histological and plasma and urine biochemical features of dwarfism were studied. All offspring were phenotypically normal at birth and weaning, but at the age of 2.5 to 4 months the longitudinal growth of the spine and leg bones was retarded in the dwarfs compared with the normal littermates. Most dwarfs performed well, even in the field. Radiographic and histological evaluations revealed a hypochondroplasia. A morphometric diagnostic method for Irish setter dwarfism was developed. A single autosomal recessive mode of inheritance was verified.

Achondroplasia↗
PubMed1998

Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis.

The serum level of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D], the biologically most potent metabolite of vitamin D, is tightly regulated within narrow limits in human healthy adults. 1,25-(OH)2D deficiency is rare and is associated with disturbances in calcium and bone metabolism. We have previously reported a marked decrease in serum levels of 1,25-(OH)2D in human immunodeficiency virus (HIV)-infected patients. The present study was designed to further examine the causes and consequences of severe 1,25-(OH)2D deficiency in these patients. The design was a prospective cohort study. Fifty-four HIV-infected patients clinically classified according to the revised criteria from Centers for Disease Control and Prevention and healthy controls were studied. Parameters related to vitamin D and calcium metabolism as well as immunological and nutritional status were determined. Twenty-nine of the patients (54%) had serum levels of 1,25-(OH)2D below the lower reference limit, and 18 of these had undetectable levels. In contrast, HIV-infected patients had normal serum levels of 25-hydroxyvitamin D and vitamin D-binding protein. HIV-infected patients as a group had modestly depressed serum calcium and PTH levels. There were, however, no correlations between these parameters and serum levels of 1,25-(OH)2D. There were no differences in serum calcium or PTH levels or nutritional status when patients with severe 1,25-(OH)2D deficiency were compared to other patients, but patients with undetectable 1,25-(OH)2D had significantly elevated serum phosphate levels. Furthermore, patients with undetectable 1,25-(OH)2D levels were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor necrosis factor-alpha (TNFalpha). We conclude that inadequate 1alpha-hydroxylation of 25-hydroxyvitamin D seems to be the most likely cause of 1,25-(OH)2D deficiency in HIV-infected patients, possibly induced by an inhibitory effect of TNFalpha. The low 1,25-(OH)2D and high TNFalpha levels observed may impair the immune response in HIV-infected patients both independently and in combination and may represent an important feature of the pathogenesis of HIV-related immunodeficiency. Markedly depressed 1,25-(OH)2D serum levels are also present in certain other disorders characterized by immunological hyperactivity. Thus, the findings in the present study may not only represent a previously unrecognized immune-mediated mechanism for induction of 1,25-(OH)2D deficiency in human disease, but may also reflect the importance of adequate serum levels of 1,25-(OH)2D for satisfactory performance of the immune system in man.

Adolescent↗
PubMed1998

Biochemical markers of bone metabolism in benign human osteopetrosis: a study of two types at baseline and during stimulation with triiodothyronine.

Biochemical markers of bone remodelling were used to evaluate bone turnover in two types of autosomal dominant osteopetrosis (ADO) at baseline and during stimulation with triiodothyronine (T3). Eight patients with Type I (aged 23-61 years, mean 40.4 years) and nine patients with Type II ADO (aged 20-49 years, mean 32.8 years) were compared with 10 normal controls (aged 22-54 years, mean 35.4 years). The participants were treated with 100 microg T3 daily for 7 days and followed for a total of 16 weeks. Serum concentrations of T3 increased and corresponding suppression of TSH was observed in all participants. Both formative and resorptive bone markers were normal at baseline. After stimulation with T3, a significant increase was seen in all groups for the formative markers used. Secondary increments were observed at the end of the observation period for all groups, indicating activation of bone remodelling. A variety of resorptive markers was assessed, but no differences between patients and controls were seen. After stimulation, highly significant responses were found in all parameters in all groups, in accordance with stimulation of existing resorptive cells. However, no secondary increments were seen at the end of the observation period. A more pronounced response was found in crosslinks-related assays. The study demonstrates that it is possible to stimulate bone resorptive and formative cells with thyroid hormones in both types of ADO. Moreover, it indicates that the remodelling process is activated by a short course of T3 treatment.

Adult↗
PubMed1998

Hormone receptor measurements and survival in 1335 consecutive patients with primary invasive breast carcinoma.

The distribution of estrogen and progesterone receptors (ER, PR) was assessed in the primary tumour in 1335 of 2704 (49%) consecutive new breast carcinoma patients (HORMREC). In a subgroup of 757 radically treated patients without systemic adjuvant treatment (RADOP) the relation of the ER and PR content to relapse and survival was evaluated. Three levels were defined for ER: ER-: <10 fmol/mg protein, ER+: moderate ER content >/= 10-99 fmol/mg protein, and high ER content >/= 100 fmol/mg protein. In 1288 patients of the HORMREC group who were evaluable for ER, 1061 (82%) had ER+ tumours, 685 (65%) of moderate content and 376 (35%) of high content, respectively. Among 917 patients, evaluable for PR, 723 (79%) tumours were PR+ (>/= 20 fmol/mg protein), of them 352 (49%) with a moderate content (>/= 20-99 fmol/mg protein) and 371 (51%) with a high content ( >/= 100 fmol/mg protein). The median ER content was significantly increased among the post-menopausal women as compared to the premenopausal women, whereas the median PR content showed no such differences. For the RADOP patients, no correlation between ER status and the first site of relapse was seen, whereas PR+ tumours tended to relapse more often locally than PR- tumours. In the univariate analysis the five-and 10-year tumour-related survival rates for all patients were not correlated with ER or PR positivity. One subgroup of patients with favourable outcome was identified on the basis of hormone receptors: Premenopausal women with tumours of moderately elevated ER content. In the multivariate analysis tumour size and axillary node status were the only independent predictors of survival. Measurements of hormone receptor status give weak prognostic information in radically treated patients with breast cancer as long as no adjuvant systemic treatment is applied. As todays' adjuvant treatment is based on the knowledge of hormone receptor status of the primary tumour, this information should be obtained routinely.

Breast Neoplasms↗