| 1. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Model of the complex of Parathyroid hormone-2receptor and Tuberoinfundibular peptide of39 residues
- 2010
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Ingår i: BMC Reseach Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 3:270
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R) and its ligand the tuberoinfundibular peptide of 39 residues (TIP39) by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) are compared with the complex to examine their interactions.FindingsIn the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation.ConclusionsA model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.
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| 2. |
- Nordling, Erik, et al.
(författare)
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Colonic amyloidosis, computational analysis of the major amyloidogenic species, Serum Amyloid A
- 2012
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Ingår i: Computational biology and chemistry (Print). - : Elsevier. - 1476-9271 .- 1476-928X. ; 39, s. 29-34
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Tidskriftsartikel (refereegranskat)abstract
- Amyloidosis is characterized by misfolding of proteins. The clinical gastrointestinal manifestations of amyloidosis may mimic other disease, such as inflammatory bowel disease or colonic cancer. As these patients have a high risk for bleeding and poor wound healing following surgery it is important to diagnose them correctly and do a careful preoperative assessment. The most common form of colonic amyloidosis is caused by Serum Amyloid A (SAA), an acute phase protein of unknown function. It is expressed in response to inflammation and the increased levels may lead to amyloidosis. The main treatment is to suppress the acute phase response and thereby reduce production of SAA. less thanbrgreater than less thanbrgreater thanAs no structure for SAA is available we aim to perform an in silico assessment of its structural and fibrillation properties. In the paper we propose an ab initio model of the structure of SAA, which consists of a five membered helical bundle with a fold related to the tetratricopeptide repeat domain. As there are uncertainties relating to the packing of the helices, each helical region is subjected to triplicate molecular dynamics simulations to assess the integrity of the structural region. The first helix, stretching from residues 1 to 13, is the least stable according to the simulations: almost all of the helical conformation is lost during the 10 ns simulations, whereas the other helices maintain portions that remain in an helical conformation in at least 80% of the simulations. All helices are also subjected to a single 100 ns simulation to investigate how the secondary structure develops over time. In them helix 1 adopts a beta-hairpin structure similar to other fibril forming proteins. The beta-hairpin can in turn multimerise and form a mature fibril structure. The mechanism behind the conformational transition appears to be driven by interactions of side chains of charged residues, particularly Arginine 1. It exchanges interaction partners in the simulation and stabilizes intermediate conformations on the folding pathway to the final beta-hairpin.
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| 3. |
- Abraham Nordling, Mirna
(författare)
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Hyperthyroidism : incidence and long term quality-of-life
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hyperthyroidism is a common disorder which in general affects approximately 2 % of women and 0.2 % of men. There are three main types of hyperthyroidism, caused by increased thyroid hormone production: Graves disease, toxic multinodular goitre and solitary toxic adenoma. Three main treatment modalities are common for Graves hyperthyroidism: surgery, radioiodine, or antithyroid drugs. The aim of this thesis was to investigate the incidence of hyperthyroidism and the possible influence of the choice of treatment for Graves hyperthyroidism on health-related aspects of quality of life after 14-21 years, furthermore, to study whether patients with a history of hyperthyroidism, especially Graves disease, have an increased risk of committing suicide later in life. In the first study, the total, age-specific incidence and the incidence of subgroups of hyperthyroidism in the county of Stockholm were determined during the years 2003-2005. They were identified by the clinical status, the thyroid hormone and antibody levels and in some cases by thyroid scintigraphy. Eight specialised units/hospitals in the county of Stockholm participated in the registration. During this period 1431 new well defined cases of hyperthyroidism on adults, >= 18 years of age were diagnosed. The total annual incidence was found to be 32.7/100 000. The annual incidence of Graves disease was 24.5/100 000, of toxic nodular goitre 3.3/100 000 and of solitary toxic adenoma 4.9/100 000. In the second and third, studies we focused on long-term differences in health-related aspects of quality of life of patients who had been randomised in 1983-1990 to treatment with antithyroid drugs, surgery, or radioiodine for Graves hyperthyroidism. The treatment groups were compared with an age-and sex-matched Swedish reference population and with one another. We also addressed the question whether the quality of life was influenced by the current thyroidal hormonal status or the level of thyroxine (T4) substitution. Two quality of life questionnaires (36-item Short Form Health Status Survey (SF-36) and Quality of Life 2004 (QoL2004)) were answered by the patients and hormonal status was recorded. The results showed a lower SF-36 score on mental aspects of quality of life (p< 0.05) and vitality (p< 0.05) compared with a reference Swedish population. There were no differences in quality of life score between the three modes of treatment for Graves hyperthyroidism. We also found that the results obtained with SF-36 were not related to the current serum levels of thyroid hormones, as subjects with suppressed S-TSH reported QoL scores above as well as below the average score for the general reference population in both physical component summary and mental component summary. In the fourth study, the risk of suicide among patients with a history of hyperthyroidism was investigated, since a pilot study had indicated an elevated suicide rate among patients previously treated for Graves hyperthyroidism. A comprehensive retrospective cohort study was therefore performed. The cohort included 43 633 patients who had been treated with radioiodine or surgically for hyperthyroidism in the years 1950-2005. The number of observed deaths in the cohort was compared with the expected, based on the suicide death rate in the age-, gender- and calendar period-matched general Swedish population, yielding standardised mortality ratios (SMR). The total SMR was 1.24 (95% CI, 1.04-1.47). The overall SMR among men and women with a history of Graves disease was 1.35 (95% CI, 1.07 - 1.66). A likely increase in risk of suicide among patients with a history of hyperthyroidism was observed.
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| 4. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005
- 2008
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 158:6, s. 823-827
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the incidence of hyperthyroidism in Stockholm County in those patients who were diagnosed with hyperthyroidism for the First time during the years 2003-2005. Design: All new cases of hyperthyroidism >= 18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves' disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology. oncology, nuclear medicine or surgery. Results: Duringa 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (>18 years of age) of in average 1 457 036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100 000. The incidence of GD was 24.5/100 000 per year. toxic nodular goitre was 3.3/100 000 per year and STA was 4.9/100 000 per year. Conclusions: The total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100 000 per year. of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre.
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| 5. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Sweden
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100000 inhabitants per year. This extended study has evaluated the incidence for similar to 40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods:All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows:clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results:A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion:The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.
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| 6. |
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| 7. |
- Lantz, Mikael, et al.
(författare)
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Immigration and the incidence of Graves' thyrotoxicosis, thyrotoxic multinodular goiter and solitary toxic adenoma
- 2009
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 160:2, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Environmental and genetic factors influence thyrotoxicosis, but how population migration affects the disease panorama is not known. fit an urban area in southern Sweden, during the years 1990 until 2003, the population increased from 232 000 to 267 000. In parallel, the proportion of inhabitants born outside Sweden increased. The aim was to investigate whether the incidence of Graves' thyrotoxicosis (GD), toxic multinodular goiter (TMNG), and solitary toxic adenoma (STA) has changed in Malmo since 1990 and to Study the influence of geographic origin. Design and method: An open label prospective registration of thyrotoxicosis, gender, age, smoking habits, and ethnic background during 2003-2005 in an urban area in southern Sweden (Malmo) was undertaken. Results: The total incidence of thyrotoxicosis has changed from 43 to 41.6 cases/100 000/year from the years 1988-1990 to 2003-2005(p-value 0.72). GD increased from 22 to 29.6 (p-value 0.0051). TMNG decreased from 16 to 9.9 (p-value 0.0011) and STA from 4.8 to 2.1. (p-value 0.0054)/100 000/year. The total incidence of GD was higher in inhabitants born Outside Sweden up to the age of 69 years and age-specific incidence showed a peak in women aged 50-59 years old in both groups. The greatest difference between immigrants and Swedes up to the age of 69 years was observed in women aged 20-29 years old. Conclusion: The incidence of GD has increased and of TMNG has decreased in Malmo since 1990. Geographic origin seems to affect the incidence of GD. Whether the observed peak in age-related incidence in women 50-59 years is explained by menopausal changes has to be further investigated.
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| 8. |
- Mahmood, Mahmood W., et al.
(författare)
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High intake of dietary fibre from fruit and vegetables reduces the risk of hospitalisation for diverticular disease.
- 2019
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Ingår i: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 58, s. 2393-2400
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDS AND AIMS: High intake of dietary fibres has been associated with a reduced risk of DD. However, reports on which type of dietary fibre intake that is most beneficial have been conflicting. The aim of this study was to investigate the association between different dietary fibres and hospitalisation due to diverticular disease (DD) of the colon.METHODS: This was a major cohort study. The Swedish Mammography Cohort and the Cohort of Swedish Men were linked to the Swedish Inpatient Register and the Causes of Death Register. Data on the intake of dietary fibre were collected through questionnaires. The effect of intake (in quartiles) of different types of dietary fibre on the incidence of hospitalisation due to DD was investigated using multivariable Cox regression. Estimates were adjusted according to age, BMI, physical activity, co-morbidity, intake of corticosteroids, smoking, alcohol intake and education level.RESULTS: Women with intake of fruit and vegetable fibres in the highest quartile (median 12.6 g/day) had a 30% decreased risk of hospitalisation compared to those with the lowest intake (4.1 g/day). Men within the highest quartile (10.3 g/day) had a 32% decreased risk compared to those with a low intake (2.9 g/day). High intake of fibres from cereals did not affect the risk.CONCLUSION: A high intake of fruits and vegetables may reduce the risk of hospitalisation due to DD. Intake of cereals did not influence the risk.
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| 9. |
- Mahmood, Mahmood Wael, et al.
(författare)
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Identification of diverticular disease in Swedish healthcare registers : a validation study
- 2024
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 59:2, s. 176-182
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Swedish National Patient Register (SNPR) is frequently used in studies of colonic diverticular disease (DD). Despite this, the validity of the coding for this specific disease in the register has not been studied.Methods: From SNPR, 650 admissions were randomly identified encoded with ICD 10, K572-K579. From the years 2002 and 2010, 323 and 327 patients respectively were included in the validation study. Patients were excluded prior to, or up to 2 years after a diagnosis with IBD, Celiac disease, IBS, all forms of colorectal cancer (primary and secondary), and anal cancer. Medical records were collected and data on clinical findings with assessments, X-ray examinations, endoscopies and laboratory results were reviewed. The basis of coding was compared with internationally accepted definitions for colonic diverticular disease. Positive predictive values (PPV) were calculated.Results: The overall PPV for all diagnoses and both years was 95% (95% CI: 93-96). The PPV for the year 2010 was slightly higher 98% (95% CI: 95-99) than in the year 2002, 91% (95% CI: (87-94) which may be due to the increasing use of computed tomography (CT).Conclusion: The validity of DD in SNPR is high, making the SNPR a good source for population-based studies on DD.
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| 10. |
- Träisk, Frank, et al.
(författare)
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Thyroid-Associated Ophthalmopathy after Treatment for Graves´Hyperthyroidism with Antithyroid Drugs or lodine-131
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:10, s. 3700-3707
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO). Objectives: The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs. Design: We conducted a randomized trial (TT 96) with a follow-up of 4 yr. Patients, Setting, and Intervention: Patients with a recent diagnosis of Graves' hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T-4 was given in both groups. Main Outcome Measure: Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001). Results: The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment(23patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism. Conclusions: Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.
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