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Sökning: swepub > Umeå universitet > (2000-2004) > Medicin och hälsovetenskap

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1.
  • Aspholm-Hurtig, Marina, et al. (författare)
  • Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
  • 2004
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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2.
  • Schölin, Anna, et al. (författare)
  • Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults : a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden
  • 2004
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:3, s. 384-391
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • ObjectivesTo establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later.DesignPopulation-based cohort study.SettingNationwide from all Departments of Medicine and Endocrinology in Sweden.SubjectsA total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88.Main outcome measurePlasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies – cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies – were measured.ResultsAmongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m−2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up.ConclusionsSixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.
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3.
  • Schölin, Anna, et al. (författare)
  • Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes
  • 2004
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 21:5, s. 447-455
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Aim To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM).Methods In Sweden, 362 patients (15–34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis.Results Remissions were seen in 43% of the patients with a median duration of 8 months (range 1–73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab+), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20–24.9 kg/m2) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab+ remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions.Conclusion In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.
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4.
  • Jestin, P, et al. (författare)
  • Elective surgery for colorectal cancer in a defined Swedish population.
  • 2004
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 30:1, s. 26-33
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The aim of this study was to describe variability in compliance to clinical guidelines in colorectal cancer surgery related to hospital structure.METHODS: All patients registered in the databases of the Regional Oncologic Centre, operated upon electively for colon cancer between the start of the register in 1997 until 2000 (n=1771) and for rectal cancer between the start of the register in 1995 until 2000 (n=1841) were selected for analysis.RESULTS: There was no difference in 5-year survival rate between colon and rectal cancer (mean follow-up 2.6 and 3.0 years, respectively; p=0.22). There was a significant difference in frequency of preoperative liver scan depending on hospital category with an increase in colon cancer from 39 to 46% (p=0.02) and in rectal cancer from 42 to 64% (p<0.001). For colon cancer there was no difference, according to hospital category, in quotient sigmoid and high anterior resection to left-sided resection. Furthermore, high anterior resection was more common at university and general district hospitals (8%) compared with district hospitals (4%) (p=0.01). Sphincter-saving surgery was more common at university hospitals and district general hospitals than at district hospitals (low anterior/abdomino-perineal resection quotients 2.3, 2.4 and 1.6, respectively; p<0.001).CONCLUSIONS: Population-based audit forms an appropriate and valuable basis for quality assurance projects. In addition to describing compliance to guidelines and pointing to process steps that can be improved, such investigations may also indicate changes due to scientific development. Linked to case-costing data, such results may form an important basis for decisions about modifications in health care.
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5.
  • Tuvemo, Torsten, et al. (författare)
  • Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty
  • 2004
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 93:11, s. 1456-1462
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. Methods: Forty-six girls with early or precocious puberty (age ≤9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue. Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS). Conclusion: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.
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6.
  • Lampic, Claudia, et al. (författare)
  • Attainment and importance of life values among patients with primary breast cancer
  • 2003
  • Ingår i: Cancer Nursing. - : Lippincott Williams & Wilkins. - 0162-220X .- 1538-9804. ; 26, s. 295-
  • Tidskriftsartikel (refereegranskat)abstract
    • The main aims of this study were to investigate the extent to which women with recently diagnosed primary breast cancer (N = 29) and matched control subjects without cancer (N = 29) differ in perceived attainment and importance of life values and to study prospectively life value ratings during 1 year in a large group of recent attendees at mammography screening (N = 706). Life values were assessed by a study-specific version of a life value questionnaire, including ratings of the perceived attainment and importance of seven life value dimensions. Women with a recent diagnosis of primary breast cancer were found to attribute significantly more importance to positive relations than healthy controls. No other differences between these groups were found regarding the attainment or importance of life values. Perceptions of life values were found to vary as a function of age, marital or cohabitation status, and parenthood, and to be stable over a 9-month period in screening attendees. The implications of the current findings for the understanding of women's psychological adaptation to breast cancer are discussed.
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7.
  • Brage, Monica, et al. (författare)
  • Osteoclastogenesis is decreased by cysteine proteinase inhibitors.
  • 2004
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 34:3, s. 412-24
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of cystatin C and other cysteine proteinase inhibitors on osteoclast formation and differentiation have been investigated. Cystatin C decreased osteoclast formation stimulated by parathyroid hormone (PTH), 1,25(OH)2-vitamin D3 or interleukin-6 (IL-6) (in the presence of its soluble receptor) as assessed by the number of tartrate-resistant acid phosphatase (TRAP+) multinucleated cells in mouse bone marrow cultures. The inhibitory effect was associated with decreased mRNA expression for the calcitonin receptor as well as decreased number of specific binding sites for 125I-calcitonin, and without any effect on the mRNA expression of receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL). Similarly, the cysteine proteinase inhibitors leupeptin, E-64 and benzyloxycarbonyl-Phe-Ala-diazomethane (Z-FA-CHN2) decreased PTH-stimulated formation of TRAP+ multinucleated cells and binding of 125I-calcitonin. A peptidyl derivative synthesized to mimic part of the proteinase-binding site of cystatin C (benzyloxycarbonyl-Arg-Leu-Val-Gly-diazomethane, or Z-RLVG-CHN2) also decreased PTH-stimulated osteoclast formation. In a 9-day culture, addition of cystatin C during the last 5 days was sufficient to cause substantial inhibition of osteoclast formation. Cystatin C-induced decrease of osteoclast formation was associated with enhanced number of F4/80-positive macrophages and increased mRNA expression of the macrophage receptor c-fms in the bone marrow culture. Osteoclast formation in mouse bone marrow cultures as well as in mouse spleen cell cultures, stimulated by macrophage colony-stimulating factor (M-CSF) and RANKL was also decreased by different cysteine proteinase inhibitors. In addition, cystatin C inhibited M-CSF/RANKL induction of calcitonin receptor mRNA in spleen cell cultures. The inhibitory effect by cystatin C in spleen cells was associated with decreased mRNA expression of RANK and the transcription factor NFAT2. It is concluded that cysteine proteinase inhibitors decrease formation of osteoclasts by interfering at a late stage of pre-osteoclast differentiation.
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8.
  • Brand, H S, et al. (författare)
  • Family 2 cystatins inhibit osteoclast-mediated bone resorption in calvarial bone explants.
  • 2004
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:3, s. 689-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoclastic bone resorption depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteine proteinases. Biochemical studies have shown that cystatins, naturally occurring inhibitors of these enzymes, inhibit bone matrix degradation. Since the mechanism by which cystatins exert this inhibitory effect is not completely resolved yet, we studied the effect of cystatins on bone resorption microscopically and by Ca-release measurements. Calvarial bone explants were cultured in the presence or absence of family 2 cystatins and processed for light and electron microscopic analysis, and the culture media were analyzed for calcium release. Both egg white cystatin and human cystatin C decreased calcium release into the medium significantly. Microscopic analyses of the bone explants demonstrated that in the presence of either inhibitor, a high percentage of osteoclasts was associated with demineralized non-degraded bone matrix. Following a 24-h incubation in the presence of cystatin C, 41% of the cells were adjacent to areas of demineralized non-degraded bone matrix, whereas in controls, this was only 6%. If bone explants were cultured with both PTH and cystatin C, 60% of the osteoclasts were associated with demineralized non-degraded bone matrix, compared to 27% for bones treated with PTH only (P < 0.01). Our study provides evidence that cystatins, the naturally occurring inhibitors of cysteine proteinases, reversibly inhibit bone matrix degradation in the resorption lacunae adjacent to osteoclasts. These findings suggest the involvement of cystatins in the modulation of osteoclastic bone degradation.
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9.
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10.
  • Lerner, Ulf H (författare)
  • New molecules in the tumor necrosis factor ligand and receptor superfamilies with importance for physiological and pathological bone resorption
  • 2004
  • Ingår i: Critical Reviews in Oral Biology and Medicine. - Alexandria : International association for dental research (IADR). - 1045-4411 .- 1544-1113. ; 15:2, s. 64-81
  • Forskningsöversikt (refereegranskat)abstract
    • Osteoclasts are tissue-specific polykaryon bone-resorbing cells derived from the monocyte/macrophage hematopoietic lineage with specialized functions required for the adhesion of the cells to bone and the subsequent polarization of the cell membrane, secretion of acid to dissolve mineral crystals, and release of proteolytic enzymes to degrade the extracellular matrix proteins. Most pathological conditions in the skeleton lead to loss of bone due to excess osteoclastic bone resorption, including periodontal disease, rheumatoid arthritis, and osteoporosis. In rare cases, most of them genetic, patients with osteopetrosis exhibit sclerotic bone due either to a lack of osteoclasts or to non-functional osteoclasts. Mainly because of phenotypic findings in genetically manipulated mice or due to spontaneous mutations in humans, mice, and rats, several genes have been discovered as being crucial for osteoclast formation and activation. Recent breakthroughs in our understanding of osteoclast biology have revealed the critical roles in osteoclast differentiation played by RANKL, RANK, and OPG, three novel members of the tumor necrosis factor ligand and receptor superfamilies. The further study of these molecules and downstream signaling events are likely to provide a molecular basis for the development of new drugs for the treatment of diseases with excess or deficient osteoclastic bone resorption.
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