Biomedical subjects

J Svensson

Publications and source records attributed to J Svensson.

At least 19 recordsLinked to original sources

PubMed2001

Stress-induced accumulation and tissue-specific localization of dehydrins in Arabidopsis thaliana.

Stress-induced accumulation of five (COR47, LTI29, ERD14, LTI30 and RAB18) and tissue localization of four (LTI29, ERD14, LTI30 and RAB18) dehydrins in Arabidopsis were characterized immunologically with protein-specific antibodies. The five dehydrins exhibited clear differences in their accumulation patterns in response to low temperature, ABA and salinity. ERD14 accumulated in unstressed plants, although the protein level was up-regulated by ABA, salinity and low temperature. LTI29 mainly accumulated in response to low temperature, but was also found in ABA- and salt-treated plants. LTI30 and COR47 accumulated primarily in response to low temperature, whereas RAB18 was only found in ABA-treated plants and was the only dehydrin in this study that accumulated in dry seeds. Immunohistochemical localization of LTI29, ERD14 and RAB18 demonstrated tissue and cell type specificity in unstressed plants. ERD14 was present in the vascular tissue and bordering parenchymal cells, LTI29 and ERD14 accumulated in the root tip, and RAB18 was localized to stomatal guard cells. LTI30 was not detected in unstressed plants. The localization of LTI29, ERD14 and RAB18 in stress-treated plants was not restricted to certain tissues or cell types. Instead these proteins accumulated in most cells, although cells within and surrounding the vascular tissue showed more intense staining. LTI30 accumulated primarily in vascular tissue and anthers of cold-treated plants. This study supports a physiological function for dehydrins in certain plant cells during optimal growth conditions and in most cell types during ABA or cold treatment. The differences in stress specificity and spatial distribution of dehydrins in Arabidopsis suggest a functional specialization for the members of this protein family.

Arabidopsis↗

PubMed2001

Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children.

Ibutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH) secretagogue, stimulates GH release through a pituitary and hypothalamic receptor that is different from the GH-releasing hormone receptor. We evaluated the safety and tolerability and the GH-insulin-like growth factor (IGF) responses to two dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to 8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height < 10th percentile for age, and a maximum GH response of < or = 10 microg/L to two different GH stimulation tests. The children were assigned as follows to one of three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days (days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day 15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in groups I and II were studied first to assess safety at the low dose before advancement to the high dose. Hormonal profiles were evaluated on day -1 (baseline) and day 15, and the results were expressed as the change from baseline within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8 days (group III), the median increases (on day 15) from baseline were as follows: 3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3 microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to 116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum cortisol, and insulin concentrations or 24-hour urinary free cortisol after administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We conclude that short-term administration of ibutamoren mesylate can increase GH, IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound is applicable for testing its effect on growth velocity.

Administration, Oral↗

PubMed2001

Changes in biochemical markers of bone metabolism and BMD during the first year after a hip fracture.

We measured the levels of biochemical markers of bone formation and bone resorption in hip fracture patients preoperatively and after 6 and 12 months. Bone densitometry was done with quantitative computer tomography (QCT), dual-energy X-ray absorptiometry (DXA) and heel ultrasound. After 6 months, the biochemical markers of bone formation and bone resorption had increased. The levels remained high after 1 year and no change occurred between 6 and 12 months. We found no correlations between biochemical bone markers and bone density/stiffness on admission and change in bone mineral density (BMD) during the first postoperative year, despite the changes in bone markers and bone density. In our opinion, biochemical bone markers can not be used to predict bone loss in the individual patient after a hip fracture.

Absorptiometry, Photon↗

PubMed2001

Comparison of some different methods for analysis of thyroid autoantibodies: importance of thyroglobulin autoantibodies.

Blood samples from 141 children and adolescents were used to evaluate differences between commercial kits and radioimmunoassay (RIA) methods for detecting thyroid autoantibodies. Thyroglobulin autoantibodies (Tg-Ab) were analyzed with a hemagglutination kit and a RIA; thyroid peroxidase autoantibodies (TPO-Ab) were measured with a gelagglutination assay and a RIA. The results of the antibody tests were compared with thyroid function tests (triiodothyronine [T3], thyroxine [T4], thyrotropin [TSH]) and with the results of ultrasound of the thyroid in antibody-positive patients. The correlation of antibody levels between the two methods was higher for TPO-Ab than for Tg-Ab. Moderate to high levels of TPO-Ab correlated to elevated TSH levels. Autoimmune thyroiditis (AIT) was found in 6 of the 141 children. The RIA-based thyroglobulin assay was the only test that identified autoantibodies in all 6 cases. In contrast, the hemagglutination kit thyroglobulin assay failed to identify 4 of the 6 AIT cases.

Adolescent↗

PubMed2001

Body composition and quality of life as markers of the efficacy of growth hormone replacement therapy in adults.

Growth hormone (GH) replacement therapy in GH-deficient adults should be initiated with a low dose, independent of body weight or body surface area. Measurements of serum insulin-like growth factor I (IGF-I) concentrations, as well as clinical examinations aimed at detecting signs of fluid excess, are important as safety markers to avoid overtreatment with GH. At present, there is no optimal marker for the long-term efficacy of GH replacement therapy. The long-term maintenance dose of GH should, therefore, be titrated in each individual based on the clinical response, with the aim of normalizing body hydration, other measurements of body composition, quality of life and well-being, and biochemical indices such as serum IGF-I concentration.

Adult↗

PubMed2001

A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices.

GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.

Adult↗

PubMed2001

Baseline characteristics and the effects of five years of GH replacement therapy in adults with GH deficiency of childhood or adulthood onset: a comparative, prospective study.

The consequences of GH deficiency may differ if the disease is childhood onset or adulthood onset. In this single-center, prospective study, 21 consecutive adults with childhood onset GH deficiency and 21 adults with adulthood onset GH deficiency, matched for age, gender, body mass index, and number of anterior pituitary hormonal deficiencies, were included. Baseline differences and differences in the responses in body composition, muscle strength, bone mass, and metabolic indices during 5-yr GH replacement were determined. The duration of GH deficiency was longer and serum IGF-I level and body height were lower in the childhood onset patients than in the adulthood onset patients. Body fat (observed/predicted ratio) was increased, and lean mass and muscle strength were decreased, in the childhood onset patients. Total body and lumbar (L2-L4) bone mineral content and bone mineral density were lower in the childhood onset patients. Serum total cholesterol level was higher in the adulthood onset patients. The childhood onset and adulthood onset patients received a similar dose of GH. After adjustment for body weight, however, the dose of GH was higher in the childhood onset patients. The treatment responses were more marked in the childhood onset patients in lean mass, knee extensor strength, left-hand grip strength, and in total body and lumbar (L2-L4) bone mineral content and bone mineral density. The reduction in serum total cholesterol concentration was more marked in the adulthood onset patients. At study end, no differences remained between the two study groups after the correction for body height in the statistical analysis. In conclusion, the baseline analysis suggests more decreased lean mass, muscle strength, and bone mass in the childhood onset patients whereas the lipid profile was more disturbed in the adulthood onset patients. The 5-yr GH replacement eliminated all the anthropodometric and metabolic differences between the two groups.

Adolescent↗

PubMed2001

Effects of growth hormone and its secretagogues on bone.

The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.

Adult↗

PubMed2000

[Drug addicts with severe mental disorders can be helped by programs using moderate means. Good results when psychiatric, social and drug abuse services cooperate].

Dependency disorders are more common than expected in psychiatric populations. Untreated, dual diagnosis leads to severe social and psychiatric deterioration. Nine treatment resistant, homeless, drug addicts suffering from chronic psychotic disorders were selected to take part in a case management program, integrating social services with regular psychiatric treatment. All but one were greatly improved in general terms as well as regarding their ability to maintain an ordered life style. The need for institutional care decreased dramatically.

Community Mental Health Services↗

PubMed2000

Purification of recombinant Arabidopsis thaliana dehydrins by metal ion affinity chromatography.

In this study we describe a novel method for purification of Arabidopsis thaliana dehydrins overproduced in Escherichia coli. The cDNAs corresponding to the four dehydrin genes RAB18, LTI29, LTI30, and COR47 were inserted into a bacterial expression vector under an isopropyl beta-d-thiogalactopyranoside (IPTG) inducible bacterial promoter. After IPTG induction all four proteins accumulated in high amounts. The recombinant proteins were efficiently purified to over 95% purity with a three-step purification scheme: heat fractionation, immobilized metal ion affinity chromatography (IMAC), and ion exchange chromatography. In this study we introduce the novel use of IMAC as an efficient purification method for native dehydrins. Characterization of the purified proteins was done by Edman degradation, mass spectrometry, reverse-phase chromatography, and analytical gel filtration under native and denaturing conditions. Yields of purified proteins were between 2.8 and 12.5 mg per liter of bacterial culture, sufficient for further biochemical studies.

Arabidopsis↗

PubMed2000

Growth hormone and ageing.

The proportion of elderly people is steadily growing in Western societies. The result is a disproportionate accumulation of the oldest and most vulnerable sector of the population, suffering from frailty-associated disorders and cardiovascular diseases. Growth hormone (GH) secretion declines progressively during adulthood. In ageing and severe GH deficiency, an individual's muscle mass, muscle strength and bone mass are decreased, and the relative proportion of total and visceral fat is increased. An association between reduced GH levels and the catabolism of ageing has been suggested. GH or GH secretagogue treatment could be of value to minimize the health-related consequences associated with the ageing process.

Aged↗

PubMed2000

The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men.

OBJECTIVE: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. RESEARCH METHODS AND PROCEDURES: Fifty non-diabetic, middle-aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. RESULTS: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin-releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. DISCUSSION: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.

Adipose Tissue↗

PubMed2000

A nine-month, placebo-controlled study of the effects of growth hormone treatment on lipoproteins and LDL size in abdominally obese men.

Abdominal/visceral obesity is associated with blunted growth hormone (GH) secretion and an unfavourable lipoprotein pattern. In this study, the effect of GH treatment on LDL size and on serum lipoprotein concentrations was determined in abdominally obese men. Thirty men, aged 48-66 years, with a body mass index (BMI) of 25-35 kg/m(2)and a waist:hip ratio of >0.95, received treatment with GH (9. 5 microg/kg/day) or placebo for 9 months. Serum concentrations of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) were reduced (P<0.05, P<0.05 and P<0.001 vs placebo, respectively). Serum lipoprotein(a) [Lp(a)] concentration increased (P<0.05 vs. placebo). Mean low density lipoprotein (LDL) particle diameter was marginally increased by active treatment as compared with placebo (P =0.08). No changes were observed in the serum concentrations of high density lipoprotein-cholesterol (HDL-C), apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE). In conclusion, 9 months of GH treatment in abdominally obese men beneficially reduced serum concentrations of TC, LDL-C and apoB, and marginally increased mean LDL diameter, while serum Lp(a) increased. The ultimate effect of GH therapy on the cardiovascular risk remains, however, to be determined.

Abdomen↗

PubMed2000

Biochemical bone markers and bone density in hip fracture patients: weak correlation in 106 women.

Biochemical markers of bone formation and bone resorption were measured preoperatively, within 18 hours after a hip fracture (n 106) and bone mineral density (BMD) was measured with quantitative computer tomography (QCT), dual-energy x-ray absorptiometry (DXA) and heel ultrasound in 63 hip fracture patients. Patients with pertrochanteric fractures had more osteoporosis in all measurements than patients with femoral neck fractures. We found no differences in biochemical markers of bone formation or bone resorption in patients with femoral neck fractures and in those with pertrochanteric fractures. Correlations between biochemical bone markers and bone density, bone mass and stiffness on admission were weak.

Absorptiometry, Photon↗

PubMed2000

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n=7), GHRP-6 (0.5 mg/kg per day; n=8), GH (3.5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.

Absorptiometry, Photon↗

PubMed2000

Differences between work methods and gender in computer mouse use.

OBJECTIVES: The aim of this study was to investigate whether gender or different methods of operating a computer mouse have an effect on performance and musculoskeletal load in the use of a computer mouse. METHODS: Thirty experienced computer mouse users, 15 men and 15 women, participated in the study. Electromyography (right first dorsal interossei, right extensor digitorum and right and left trapezius), a force-sensing mouse, and subjective ratings were used to register muscular load. An electrogoniometer was used to register the wrist movements. The subjects worked with 3 different methods, their own, a wrist-based method and an arm-based method. Gender comparisons were made when the subjects used their own method. RESULTS: The women worked with greater extension and range of motion and tended to work with a greater ulnar deviation of the wrist. They also applied higher forces to the mouse when expressed as a percentage of a maximum voluntary contraction and had higher muscular activity in the right extensor digitorum. When using the arm-based method, the subjects worked with greater wrist extension, had higher muscular activity in the right and left trapezius muscles, and had the highest ratings of perceived exertion in the neck and shoulder. The wrist-based method resulted in higher forces being applied to the sides of the mouse and the highest ratings of perceived exertion in the wrist and hand-fingers. CONCLUSIONS: Gender differences were found for musculoskeletal load, and for most of the measured variables the women worked with higher loads than the men. The work method affected performance and musculoskeletal load. Finally, subjective measures appeared to have some utility in characterizing muscular load.

Adolescent↗

PubMed1999

Image artifacts due to a time-varying contrast medium concentration in 3D contrast-enhanced MRA.

The purpose of this work was to study image effects due to time-varying contrast medium concentration in contrast-enhanced three dimensional (3D) magnetic resonance angiography (MRA) images. Two different simulation models (1D and 3D) and two different contrast medium variation schemes were used. Phantom measurements were also performed. Experiments were performed for several different bolus timings. Similar sequence and image object parameters were used in both simulations and measurements (TE/TR 2. 1/7.8 mses, flip angle 30 degrees, T1/T2 1200-80/150-40 msec, flow velocity 100 cm/sec). A small variation in bolus timing yielded large variations in the appearance of the image effects, especially if the center of k-space was sampled in the vicinity of rapid contrast medium concentration variation. For a typical bolus injection in a patient, a severe signal loss but only minor ringing and edge artifacts appeared if the bolus injection was poorly timed. Effects of pulsatile flow were minor. The 3D model proved to be a useful tool in these studies. J. Magn. Reson. Imaging 1999;10:919-928.

Aorta↗

PubMed1999

Screening for mutations in candidate genes for hypospadias.

Hypospadias. a condition with a frontally placed urethral orifice on the penis, is the most common malformation in males. During fetal development several components are necessary for normal male genital development. Testosterone and dihydrotestosterone act via the androgen receptor but a defective receptor function results in different degrees of genital malformations. Testosterone-5alpha-reductase converts testosterone to dihydrotestosterone, which is crucial for normal differentiation, and a total lack of this enzyme results, in syndromes with hypospadias. The Wilms' tumour 1 (WT1) gene is expressed in the fetal gonad and genital malformations can occur due to WT1 gene mutations. These genes are therefore strong candidate genes for hypospadias. We have analysed 35 boys with hypopadias and one girl diagnosed as with complete androgen insensitivity syndrome, using exon by exon polymerase chain reaction (PCR) amplification of the AR, WTI and 5alpha-reductase genes and screened for point mutations and performed subsequent DNA sequencing. No mutations in any of these genes were found in the 26 patients with isolated hypospadias. Two patients with severe hypospadias with cryptorchidism were found to carry mutations in the androgen receptor gene. Also the girl with clinically diagnosed complete androgen insensitivity was found to be homozygous for a splice mutation in the 5alpha-reductase gene. In summary, mutations in the WT1, AR and 5alpha-reductase genes are not common causes of isolated hypospadias.

Base Sequence↗