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- Gagnemo Persson, Rebecca, et al.
(författare)
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Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake.
- 1997
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Ingår i: Calcified Tissue International. - 1432-0827. ; 61:3, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.
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- Vertessy, Beata G., et al.
(författare)
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The complete triphosphate moiety of non-hydrolyzable substrate analogues is required for a conformational shift of the flexible C-terminus in E. coli dUTP pyrophosphatase
- 1998
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Ingår i: FEBS Letters. - 1873-3468. ; 421:1, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanism of substrate analogue interaction with Escherichia coli dUTPase was investigated, using the non-hydrolyzable 2'-deoxyuridine 5'-(α,β-imido)triphosphate (α,β-imido-dUTP). Binding of this analogue induces a difference in the far UV circular dichroism (CD) spectrum arguing for a significant change in protein conformation. The spectral shift is strictly Mg2+-dependent, does not appear with dUDP instead of α,β-imido-dUTP and is not elicited if the flexible C-terminal arm is deleted from the protein by limited tryptic digestion. Involvement of the C-terminal arm in α,β-imido-dUTP binding is consistent with the finding that this analogue protects against tryptic hydrolysis at Arg-141. Near UV CD of ligand-enzyme complexes reveals a characteristic difference in the microenvironments of enzyme-bound dUDP and α,β-imido-dUTP, a difference not observable in C-terminally truncated dUTPase. The results suggest that (i) closing of the active site during the catalytic cycle, through the movement of the C-terminal arm, requires the presence of the complete triphosphate moiety of the substrate in complex with Mg2+, and (ii) after catalytic cleavage the active site pops open to facilitate product release.
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- Bornefalk, Anna, et al.
(författare)
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Trends in breast cancer mortality among Swedish women 1953-92: analyses by age, period and birth cohort
- 1995
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Ingår i: British Journal of Cancer. - 0007-0920. ; 72:2, s. 493-497
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Tidskriftsartikel (refereegranskat)abstract
- Trends in breast cancer mortality among Swedish women were explored on the basis of all 51 048 deaths in women 30-89 years of age in Sweden during the period 1953-92. The age-standardised mortality rates were virtually unchanged during the observation period (with a mean of 32 deaths per 100 000 females and year), as were age-specific rates. In age-period-cohort analyses, age alone explained almost all of the variation in the rates. The effects of period and cohort were statistically significant, but very modest. Cohort effects seemed to explain more than period effects, and a weak downward trend starting with women born in 1883-92 was noted. A change in 1981 in the policy to classify the causes of death from the death certificates seemed to entail an artificial lowering of the mortality rates in women older than 75 years. It is concluded that breast cancer mortality in Sweden during the last 40 years has been remarkably stable, in spite of a substantial and constant increase in the incidence. This divergence between mortality and incidence reflects improved survival, which could in part be explained by earlier detection and more efficient treatment, or by an increasing occurrence of less aggressive tumours.
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- Brynhildsen, Jan, 1962-, et al.
(författare)
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Follow-Up of Patients With Low Back Pain During Pregnancy
- 1998
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Ingår i: Obstetrics and Gynecology. - : American College of Obstetricians and Gynecologists (ACOG). - 0029-7844 .- 1873-233X. ; 91:2, s. 182-186
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify the long-term risk for low back pain among women with previous severe low back pain during pregnancy.Methods: In a previous prospective study, 79 pregnant women developed low back pain severe enough to require sick leave. Twelve years later a questionnaire was sent to 62 of these women and 84 controls who did not develop severe low back pain during pregnancy. The questionnaire asked about occupation, low back pain in general and during later pregnancies, and sick leave due to low back pain. There were also questions regarding use of oral contraceptives and its possible relation to low back pain.Results: The response rate was 84% in the back pain group and 80% among controls. The two groups were similar according to the percentage of women having had another pregnancy (33 of 52 [63%] versus 39 of 67 [58%]) but ten (19%) of the women with previous low back pain stated they had refrained from another pregnancy because of their fear of low back pain compared with only one control. Almost all women (31 of 33) with previous severe low back pain experienced the same symptoms in a subsequent pregnancy, compared with 17 of 39 (44%) controls. Even when they were not pregnant, women with previous low back pain suffered more often and used more sick leave due to low back pain (44 of 52 versus 43 of 67, chi(2) = 5.68, P < .05). The location (sacroiliac joint or lumbar affection) of the previous low back pain did not affect the long-term prognosis. In a logistic regression model, previous low back pain during pregnancy was the only independent risk factor for low back pain during a subsequent pregnancy, whereas an occupation involving physical demand did not affect the results. However, together with previous low back pain during pregnancy, heavy occupation increased the risk for current nonpregnant low back pain.Conclusion: Women with severe low back pain during pregnancy have an extremely high risk for experiencing a new episode of severe low back pain during another pregnancy and when not pregnant.
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- Dauter, Zbigniew, et al.
(författare)
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Crystal Structure of dUTPase from Equine Infectious Anaemia Virus; Active Site Metal Binding in a Substrate Analogue Complex
- 1999
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 285:2, s. 655-673
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Tidskriftsartikel (refereegranskat)abstract
- The X-ray structures of dUTPase from equine infectious anaemia virus (EIAV) in unliganded and complexed forms have been determined to 1.9 and 2.0 A resolution, respectively. The structures were solved by molecular replacement using Escherichia coli dUTPase as search model. The exploitation of a relatively novel refinement approach for the initial model, combining maximum likelihood refinement with stereochemically unrestrained updating of the model, proved to be of crucial importance and should be of general relevance.EIAV dUTPase is a homotrimer where each subunit folds into a twisted antiparallel @b-barrel with the N and C-terminal portions interacting with adjacent subunits. The C-terminal 14 and 17 amino acid residues are disordered in the crystal structure of the unliganded and complexed enzyme, respectively. Interactions along the 3-fold axis include a water-containing volume (size 207 A3) which has no contact with bulk solvent.It has earlier been shown that a divalent metal ion is essential for catalysis. For the first time, a putative binding site for such a metal ion, in this case Sr2+, is established. The positions of the inhibitor (the non-hydrolysable substrate analogue dUDP) and the metal ion in the complex are consistent with the location of the active centre established for trimeric dUTPase structures, in which subunit interfaces form three surface clefts lined with evolutionary conserved residues. However, a detailed comparison of the active sites of the EIAV and E. coli enzymes reveals some structural differences. The viral enzyme undergoes a small conformational change in the uracil-binding @b-hairpin structure upon dUDP binding not observed in the other known dUTPase structures.
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- Engström, Carl-Peter, 1945, et al.
(författare)
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Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.
- 1996
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Ingår i: Thorax. - 0040-6376. ; 51:8, s. 825-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Self-assessment questionnaires which measure the functional and affective consequences of chronic obstructive pulmonary disease (COPD) give valuable information about the effects of the disease and may serve as important tools with which to evaluate treatment. METHODS: A cross sectional comparative study was performed between patients with COPD (n = 68), stratified according to pulmonary function, and a healthy control group (n = 89). A battery of well established clinical and quality of life measures (the Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression scale (HAD)) was used to examine in which functional and affective aspects the patient group differed from the control group and how these measures related to pulmonary function and smoking habits. RESULTS: Compared with the controls, COPD affected functional status in most areas, not just those requiring physical activity. Forty six patients with forced expiratory volume in one second (FEV1) below 50% predicted showed particularly high levels of dysfunction in ambulation, eating, home management, and recreation/ pastimes (SIP). Despite this, their level of psychosocial functioning and mood status was little different from that of the healthy controls. Among the patients, a subgroup reported substantial psychological distress, but mood status was only weakly, or not at all, related to pulmonary function. Smoking habits did not affect functional status or well being. CONCLUSIONS: Quality of life is not significantly affected in patients with mild to moderate loss of pulmonary function, possibly due to coping and/or pulmonary reserve capacity. This suggests that generic self-assessment questionnaires are of limited value for detecting the early consequences of COPD. However, in later stages of the disease they are sensitive enough to discriminate between patients with different levels of pulmonary dysfunction. The low correlations between the indices of pulmonary function and the indices of affective status suggest that well being depends, to a large extent, on factors outside the clinical domain.
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