| 1. |
- Brechensbauer Brandin, Madeleine, et al.
(author)
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Centralen : Studier i området kring Stockholms Centralstation
- 1989
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Reports (pop. science, debate, etc.)abstract
- Denna skrift handlar om Centralen i Stockholm och dess närmaste omgivningar, Centralplan, T-centralen, Vasagatan och Klarabergsgatan. Den är resultatet av Arkitekturskolans arbete läsåret 1983- 84 och innehåller förutom en rad projekt också historiska utblickar och samtidskritiska resonemang. En stor del av innehållet redovisades redan våren 1984 - det skedde genom en utställning på Arkitekturmuseet och en preliminär publikation. Materialet har sedan svällt ut med innehållsrika uppsatser om Centralen, om äldre och nyare insatser för att förena konst och arkitektur och om den föga kända, ännu obebyggda Blekholmen.
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| 2. |
- Huang, Ranyang, et al.
(author)
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Expression of a Mast Cell Tryptase in the Human Monocytic Cell Lines U-937 and Mono Mac 6
- 1993
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 38:4, s. 359-367
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Journal article (peer-reviewed)abstract
- Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood(PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
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| 3. |
- Jernelöv, Arne, et al.
(author)
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Tankar kring begreppet - Sustainable Development
- 1990
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Reports (other academic/artistic)abstract
- Begreppet 'sustainable development' har fått omfattande politisk acceptans men är inte ett operationellt koncept eftersom det är odefinierat och opreciserat. I artikeln diskuteras frågan om tidshorisont, huruvida begreppet bör avse teknologier eller projekt och hur en analys av 'sustainability' kan gå till.
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| 4. |
- Lindberg, Anne, 1957-
(author)
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Chronic obstructive pulmonary disease (COPD) : prevalence, incidence, decline in lung function and risk factors
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The Obstructive Lung Disease in Northern Sweden (OLIN) Studies started in 1985 as an epidemiological project with the aim to detect preventable risk factors for obstructive lung diseases and allergy. In recent years there has been a focus also on obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) besides asthma and allergy. The aim of this thesis was to estimate the prevalence and incidence of COPD, risk factors for COPD, and decline in lung function in relation to COPD.The OLIN cohort I (cI) was recruited in 1985/86 and consisted of all 6610 subjects born 1919-20, 1934-35 and 1949-50 in eight geographical areas of Norrbotten. A postal questionnaire survey was performed in 1985/86, 1992 and in 1996. All subjects reporting respiratory symptoms at the questionnaire in 1985/86 were invited to examination in 1986, 1996 and 2002-03. A random sample of 1500 subjects from the participants at the 1996 postal questionnaire survey was invited to examination in 1996 and 2003. The participation rate has been high, ≥85%. The OLIN cohort III (cIII) was recruited in 1992, a postal questionnaire was sent to a random sample of 5681 subjects aged 20-69 years. In 1994/95 a random sample of 970 subjects were invited to examination of whom 666 participated.The prevalence of COPD in the general population sample (cIII) in ages <45 was 4.1%, 11.6%, 9.1%, and 5.1% according to the criteria of BTS1 , ERS2 , GOLD3 , and ATS4 respectively. The corresponding figures in ages ≥45 were 9.7%, 15.4%, 17.1%, and 16.5% respectively. In the age-stratified general population sample (>45 y, cI), the prevalence was 8.1% and 14.3% according to the BTS and GOLD criteria. The prevalence was strongly associated with higher age and smoking but not gender. The prevalence among smokers 76-77 years old was 45% and 50% (BTS and GOLD criteria). A majority of subjects with COPD had respiratory symptoms (in prevalent BTS 94%), most commonly cough and sputum production. Nearly a half of the subjects with COPD had contacted health care due to respiratory complaints other than common colds, but only a minority reported a physician diagnosis relevant for COPD (16% of prevalent COPD according to BTS in cIII, 31% in cI). The 10-year cumulative incidence of COPD (1986-1996) was estimated at 8.2% (BTS) and 13.5% (GOLD) in the symptomatics of cI, associated with higher age and smoking but not gender. Persistent smoking, male gender and reported chronic productive cough were associated with a faster decline in FEV1. Among incident cases of COPD a large proportion (23% of incident BTS) had a rapid decline in FEV1, >90 ml/year, corresponding to a decrease of 28 percent-units of normal value during ten years.The 7-year cumulative incidence of COPD in the random sample of cI (1996-2003) was estimated at 4.9% and 11.0% (NICE guidelines5 and GOLD) and associated with smoking but not gender. The incidence according to GOLD, but not NICE, was associated with increasing age. In multi-variate analysis most respiratory symptoms were markers of increased risk for developing COPD.In conclusion, the prevalence and the incidence of COPD were associated with age and smoking and affected by the use of different spirometric criteria. Respiratory symptoms marked an increased risk for developing COPD. A high proportion of subjects developing COPD had a rapid decline in lung function. Further, there was a substantial underdiagnosis of COPD.1 British Thoracic Society: FEV1/VC<0.70 & FEV1<80%predicted (pred), 2 European Respiratory Society: FEV1/VC<88%pred in men, <89%pred in women, 3 Global initiative for Chronic Obstructive Lung Disease:FEV1/FVC<0.70, 4 American Thoracic Society: FEV1/FVC<0.75 + symptoms or physician diagnosis, 5 The British National Institute for Clinical Excellence: FEV1/FVC<0.70 & FEV1<80%pred.
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| 5. |
- Lindberg, Anne, et al.
(author)
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Decline in FEV1 in relation to incident chronic obstructive pulmonary disease in a cohort with respiratory symptoms.
- 2007
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In: COPD. - : Informa UK Limited. - 1541-2555. ; 4:1, s. 5-13
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Journal article (peer-reviewed)abstract
- Data on the relationship between decline in lung function and development of COPD are sparse. We assessed the decline in FEV1 during 10 years among subjects with respiratory symptoms by two different methods and evaluated risk factors for decline and its relation to incident Chronic Obstructive Pulmonary Disease, COPD. A cross-sectional postal questionnaire was in 1986 sent to 6610 subjects of three age strata. All subjects reporting respiratory symptoms were invited to a structured interview and spirometry. A follow-up survey was performed 10 years later, and totally 1109 subjects performed spirometry in both 1986 and 1996. COPD was defined according to the ATS/ERS standards (FEV1/FVC < or =0.70). The decline in FEV1 was 39 ml/year in men vs. 28 ml/year in women, p = < 0.001 (-1.53 vs. -0.12 change in percent of predicted normal value over 10 years (pp), p = 0.023), among smokers 39 vs. non-smokers 28 ml/year, p < 0.001 (-3.30 vs. 0.69 pp, p < 0.001), in subjects with chronic productive cough 36 vs. not 32 ml/year, p = 0.044 (-2.00 vs. -0.02 pp, p = 0.002). Incident cases of moderate COPD (n = 83) had a decline of 62 ml/year (-12.6 pp) and 22.9% of them had a decline > 90 ml/year (-27.8 pp over 10 years). Gender-specific analysis revealed that smoking was a stronger risk factor in women than in men, while higher age was a significant risk factor in men only. In conclusion, decline in FEV1 was associated with age, smoking, and chronic productive cough, but the risk factor pattern was gender-dependent. Among incident cases of COPD the decline was steeper and close to a quarter had a rapid decline.
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| 6. |
- Looman, Camilla, 1977-
(author)
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The ABC of KRAB zinc finger proteins
- 2003
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Doctoral thesis (other academic/artistic)abstract
- All living organisms consist of cells and the identity of a cell is defined by the genes it expresses. To assure proper function, a cell receives continuous information on which genes to turn on and off. This information is, to a large extent, provided by transcription factors. Krüppel-related zinc finger proteins probably constitute the largest family of transcription factors in mammals and many of these proteins carry a potent repressor domain called Krüppel-associated box (KRAB). The human genome alone encodes more than 200 KRAB zinc finger proteins but still very little is known about their biological functions. The Krüppel-related zinc finger genes appear to have been involved in a massive expansion throughout evolution. To unravel some of the secrets underlying this evolutionary success, we studied the molecular evolution of KRAB zinc finger genes. We show that the frequently occurring duplications of these genes are accompanied by a low sequence constraint in their zinc finger region. In addition, we show that the number of zinc finger motifs carried within these proteins is far from fixed. New zinc finger motifs are frequently added while others are inactivated or even discarded from the coding region. The structurally independent Krüppel zinc finger motif has, through these mechanisms, served as a highly adaptive building block for the generation of new transcriptional regulators. The mouse, rat and human genomes carry four different variants of the KRAB domain – KRAB(AB), KRAB(Ab), KRAB(AC) and KRAB(A). This thesis presents the identification of a novel KRAB domain, KRAB C, as well as a functional analysis of the different KRAB domains. We conclude that all different KRAB domains share a common co-repressor, TIFβ, and effectively repress transcription. These functions are mainly mediated by the KRAB A box but are clearly influenced by the presence of a KRAB B, b or C box. Furthermore, we show that all KRAB zinc finger gene subfamilies originate from the KRAB(AB) zinc finger genes.In addition, this thesis includes a structural and functional analysis of four novel mouse and human KRAB zinc finger genes; MZF6D, HKr18, HKr19 and HZF12. Whereas HKr18 and HZF12 seem to be ubiquitously expressed, MZF6D and HKr19 show a more restricted expression pattern. Northern blot and in situ hybridisation analyses of MZF6D showed that the expression of this gene is restricted to meiotic germ cells. MZF6D might thus be involved in the formation of male gametes. The expression of HKr19, on the other hand, seems to be restricted to lymphoid cells, indicating a possible role for this KRAB zinc finger gene in the regulation of lineage commitment.
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| 7. |
- Lundbäck, Bo, et al.
(author)
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Not 15 But 50% of smokers develop COPD?—Report from the Obstructive Lung Disease in Northern Sweden Studies
- 2003
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 97:2, s. 115-122
-
Journal article (peer-reviewed)abstract
- Background: The prevalence of chronic obstructive pulmonary disease (COPD) according to guidelines of today seems considerably higher than has been reported also in recent literature.Aim: To estimate the prevalence of COPD as defined by British Thoracic Society (BTS) criteria and the recent global initiative for chronic obstructive lung disease (GOLD) criteria. Further aims were to assess the proportion of underdiagnosis and of symptoms in subjects with COPD, and to study risk factors for COPD.Methods: In 1996, 5892 of the Obstructive Lung Disease in Northern Sweden (OLIN) Study's first cohort could be traced to a third follow-up survey, and 5189 completed responses (88%) were received corresponding to 79% of the original cohort from December 1985. Of the responders, a random sample of 1500 subjects were invited to a structured interview and a lung function test, and 1237 of the invited completed a lung function test with acceptable quality.Results: In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, while it was 14% according to the GOLD criteria. The absolutely dominating risk factors were increasing age and smoking, and approximately a half of elderly smokers fulfilled the criteria for COPD according to both the BTS and the GOLD criteria. Family history of obstructive airway disease was also a risk factor, while gender was not. Of those fulfilling the BTS criteria for COPD, 94% were symptomatics, 69% had chronic productive cough, but only 31% had prior to the study been diagnosed as having either chronic bronchitis, emphysema, or COPD. The corresponding figures for COPD according GOLD were 88, 51, and 18%.Conclusions: In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, and it was 14% according to the GOLD criteria. Fifty percent of elderly smokers had developed COPD. The large majority of subjects having COPD were symptomatic, while the proportion of those diagnosed as having COPD or similar diagnoses was small.
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| 8. |
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| 9. |
- Agarwal, Prasoon, et al.
(author)
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MYCN Amplification Is Associated with Reduced Expression of Genes Encoding gamma-Secretase Complex and NOTCH Signaling Components in Neuroblastoma
- 2023
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:9
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Journal article (peer-reviewed)abstract
- Amplification of the MYCN oncogene is found in similar to 20% of neuroblastoma (NB) cases and correlates with high-risk disease and poor prognosis. Despite the plethora of studies describing the role of MYCN in NB, the exact molecular mechanisms underlying MYCN's contribution to high-risk disease are not completely understood. Herein, we implemented an integrative approach combining publicly available RNA-Seq and MYCN ChIP-Seq datasets derived from human NB cell lines to define biological processes directly regulated by MYCN in NB. Our approach revealed that MYCN-amplified NB cell lines, when compared to non-MYCN-amplified cell lines, are characterized by reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. More specifically, we found genes encoding members of the gamma-secretase complex, which is known for its ability to liberate several intracellular signaling molecules from membrane-bound proteins such as NOTCH receptors, to be down-regulated in MYCN-amplified NB cell lines. Analysis of MYCN ChIP-Seq data revealed an enrichment of MYCN binding at the transcription start sites of genes encoding gamma-secretase complex subunits. Notably, using publicly available gene expression data from NB primary tumors, we revealed that the expression of gamma-secretase subunits encoding genes and other components of the NOTCH signaling pathway was also reduced in MYCN-amplified tumors and correlated with worse overall survival in NB patients. Genetic or pharmacological depletion of MYCN in NB cell lines induced the expression of gamma-secretase genes and NOTCH-target genes. Chemical inhibition of gamma-secretase activity dampened the expression of NOTCH-target genes upon MYCN depletion in NB cells. In conclusion, this study defines a set of MYCN-regulated pathways that are specific to MYCN-amplified NB tumors, and it suggests a novel role for MYCN in the suppression of genes of the gamma-secretase complex, with an impact on the NOTCH-target gene expression in MYCN-amplified NB.
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| 10. |
- Agarwal, Prasoon, et al.
(author)
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MYCN Amplification Is Associated with Reduced Expression of Genes Encoding γ-Secretase Complex and NOTCH Signaling Components in Neuroblastoma
- 2023
-
In: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 24:9
-
Journal article (peer-reviewed)abstract
- Amplification of the MYCN oncogene is found in ~20% of neuroblastoma (NB) cases and correlates with high-risk disease and poor prognosis. Despite the plethora of studies describing the role of MYCN in NB, the exact molecular mechanisms underlying MYCN’s contribution to high-risk disease are not completely understood. Herein, we implemented an integrative approach combining publicly available RNA-Seq and MYCN ChIP-Seq datasets derived from human NB cell lines to define biological processes directly regulated by MYCN in NB. Our approach revealed that MYCN-amplified NB cell lines, when compared to non-MYCN-amplified cell lines, are characterized by reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. More specifically, we found genes encoding members of the γ-secretase complex, which is known for its ability to liberate several intracellular signaling molecules from membrane-bound proteins such as NOTCH receptors, to be down-regulated in MYCN-amplified NB cell lines. Analysis of MYCN ChIP-Seq data revealed an enrichment of MYCN binding at the transcription start sites of genes encoding γ-secretase complex subunits. Notably, using publicly available gene expression data from NB primary tumors, we revealed that the expression of γ-secretase subunits encoding genes and other components of the NOTCH signaling pathway was also reduced in MYCN-amplified tumors and correlated with worse overall survival in NB patients. Genetic or pharmacological depletion of MYCN in NB cell lines induced the expression of γ-secretase genes and NOTCH-target genes. Chemical inhibition of γ-secretase activity dampened the expression of NOTCH-target genes upon MYCN depletion in NB cells. In conclusion, this study defines a set of MYCN-regulated pathways that are specific to MYCN-amplified NB tumors, and it suggests a novel role for MYCN in the suppression of genes of the γ-secretase complex, with an impact on the NOTCH-target gene expression in MYCN-amplified NB.
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