| 1. |
- Hagleitner, M M, et al.
(författare)
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Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
- 2008
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244. ; 45:2, s. 93-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. Results and CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
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| 2. |
- Khan, Omar M., 1980, et al.
(författare)
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Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice.
- 2011
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39
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Tidskriftsartikel (refereegranskat)abstract
- RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
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| 3. |
- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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| 4. |
- Brus, Ole, 1982-, et al.
(författare)
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Self-assessed remission rates after electroconvulsive therapy of depressive disorders
- 2017
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Ingår i: European Psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 45, s. 154-160
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Tidskriftsartikel (refereegranskat)abstract
- Background Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting. Methods Depressed patients who underwent ECT in 2011–2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0–10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics. Results Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus ≥ 0.50 ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission. Conclusions This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication. © 2017 The Author(s)
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| 5. |
- Eliassen, A Heather, et al.
(författare)
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Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.
- 2012
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 104:24, s. 1905-16
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Tidskriftsartikel (refereegranskat)abstract
- Background Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. Methods We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Results Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, β-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). Conclusions This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.
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| 6. |
- Hulten, M A., et al.
(författare)
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Trisomy 21 Mosaicism: We May All Have a Touch of Down Syndrome
- 2013
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Ingår i: Cytogenetic and Genome Research. - : Karger. - 1424-8581 .- 1424-859X. ; 139:3, s. 189-192
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Tidskriftsartikel (refereegranskat)abstract
- Ever increasing sophistication in the application of new analytical technology has revealed that our genomes are much more fluid than was contemplated only a few years ago. More specifically, this concerns interindividual variation in copy number (CNV) of structural chromosome aberrations, i.e. microdeletions and microduplications. It is important to recognize that in this context, we still lack basic knowledge on the impact of the CNV in normal cells from individual tissues, including that of whole chromosomes (aneuploidy). Here, we highlight this challenge by the example of the very first chromosome aberration identified in the human genome, i.e. an extra chromosome 21 (trisomy 21, T21), which is causative of Down syndrome (DS). We consider it likely that most, if not all, of us are T21 mosaics, i.e. everyone carries some cells with an extra chromosome 21, in some tissues. In other words, we may all have a touch of DS. We further propose that the occurrence of such tissue-specific T21 mosaicism may have important ramifications for the understanding of the pathogenesis, prognosis and treatment of medical problems shared between people with DS and those in the general non-DS population.
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| 7. |
- Svensson, Per Anders, 1959, et al.
(författare)
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Identification of genes predominantly expressed in human macrophages
- 2004
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Ingår i: Atherosclerosis. - : Elsevier BV. ; 177, s. 287-290
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Tidskriftsartikel (refereegranskat)abstract
- Identification of cell and tissue specific genes may provide novel insights to signaling systems and functions. Macrophages play a key role in many diseases including atherosclerosis. Using DNA microarrays we compared the expression of approximately 10,000 genes in 56 human tissues and identified 23 genes with predominant expression in macrophages. The identified genes include both genes known to be macrophage specific and genes previously not well described in this cell type. Tissue distribution of two genes, liver X receptor (LXR) alpha and interleukin-1 receptor antagonist (IL1RN), was verified by real-time RT-PCR. We conclude that comparison of expression profiles from a large number of tissues can be used to identify genes that are predominantly expressed in certain tissues. Identification of novel macrophage specific genes may increase our understanding of the role of this cell in different diseases.
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| 8. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
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Ingår i: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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| 9. |
- Bergdahl, IA, et al.
(författare)
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Methylmercury and inorganic mercury in serum--correlation to fish consumption and dental amalgam in a cohort of women born in 1922
- 1998
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Ingår i: Environmental research. ; 77, s. 20-24
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Tidskriftsartikel (refereegranskat)abstract
- Department of Occupational and Environmental Medicine, Lund University, Sweden. Methylmercury in serum (S-MeHg) was assessed from serum concentrations of total (S-TotHg) and inorganic mercury (S-InoHg), determined by cold vapor-atomic absorption spectrometry. The samples were collected from 135 women on two occasions, in 1968-1969 and 1980-1981. In a subgroup of 29 women, an association was found between S-MeHg and the amount of fish consumed in 1968-1969 (r = 0.38, P = 0.04). The association was stronger (r = 0.50; P = 0.006) when the individuals' mean S-MeHg from 1968-1969 and 1980-1981 were plotted vs fish consumption 1968-1969. In the group, as a whole, there was an association between S-InoHg and number of dental amalgam surfaces, in both 1968-1969 (r = 0.48, P = 0.0001) and 1980-1981 (r = 0.57, P < 0.0001). The S-InoHg increased by approximately 0.1 nmol/L per amalgam tooth surface, corresponding to an uptake of approximately 0.2 microgram/day per amalgam surface, but with considerable interindividual differences. The levels were lower in 1980-1981 than in 1968-1969 for both MeHg and InoHg. The medians and ranges (nmol/L) were for MeHg 1968-1969: 3.6 (0.3-11.9); MeHg 1980-1981, 2.0 (-0.4-8.7); InoHg 1968-1969, 3.3 (0.7-11.8); InoHg 1980-1981, 1.7 (0.1-11.8); TotHg 1968-1969, 7.2 (1.9-18.8); and TotHg 1980-1981, 3.9 (1.0-14.2). The decrease in S-MeHg is probably due to a decreased consumption of MeHg via contaminated fish. The decrease in S-InoHg may reflect a decrease in environmental exposure, but the possibility of contamination of the 1968-1969 samples at sampling and/or storage cannot be excluded. PMID: 9593624 [PubMed - indexed for MEDLINE]
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| 10. |
- Bäckbro, Kristina, et al.
(författare)
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Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor
- 1997
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 40:6, s. 898-902
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Tidskriftsartikel (refereegranskat)abstract
- Two cyclic, C2-symmetric HIV-1 protease inhibitors, one sulfamide and one urea derivative, both comprising phenyl ether groups in the P1/P1‘ positions, were cocrystallized with HIV-1 protease, and the crystal structures were determined to 2.0 Å resolution. The structure of the urea 2 showed a conformation similar to that reported for the related urea 3 by Lam et al., while the sulfamide 1 adopted an unanticipated conformation in which the P1‘ and P2‘ side chains were transposed.
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