| 1. |
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| 2. |
- Alcorn, J, et al.
(författare)
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Basic instrumentation for Hall A at Jefferson Lab
- 2004
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 522:3, s. 294-346
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Tidskriftsartikel (refereegranskat)abstract
- The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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| 3. |
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| 4. |
- Osby, E, et al.
(författare)
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CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 101:10, s. 3840-3848
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to test the hypothesis that administration of granulocyte colony-stimulating factor (G-CSF; filgrastim) during induction chemotherapy with CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) or CNOP (doxorubicin replaced with mitoxantrone) in elderly patients with aggressive non-Hodgkin lymphoma (NHL) improves time to treatment failure (TTF), complete remission (CR) rate, and overall survival (OS). Furthermore, the efficacy of CHOP versus CNOP chemotherapy was compared. A total of 455 previously untreated patients older than 60 years with stages 11 to IV aggressive NHL were included-in the analysis. Patients (median age, 71 years; range, 60-86 years) were randomized to receive CHOP (doxorubicin 50 mg/m(2)) or CNOP (mitoxantrone 10 mg/m(2)) with or without G-CSIF (5 mug/kg from day 2 until day 10-14 of each cycle every 3 weeks; 8 cycles). Forty-seven patients previously hospitalized for class I to 11 congestive heart failure were randomized to receive CNOP with or without G-CSF (not included in the CHOP versus CNOP analysis). The CR rates in the CHOP/CNOP plus G-CSF and CHOP/CNOP groups were the same, 52%, and in the CHOP with or without G-CSF and CNOP with or without G-CSF groups, 60% and 43% (P < .001), respectively. No benefit of G-CSF in terms of TTF and OS could be shown (P = .96 and P = .22, respectively), whereas CHOP was superior to CNOP (TTF/OS P < .001). The incidences of severe granulocytopenia (World Health Organization grade IV) and granulocytopenic infections were higher in patients not receiving G-CSF The cumulative proportion of patients receiving 90% or more of allocated chemotherapy was higher (P < .05) in patients receiving G-CSF. Concomitant G-CSF treatment did not improve CR rate, TTF, or OS. Patients receiving CHOP fared better than those given CNOP chemotherapy. The addition of G-CSF reduces the incidence of severe granulocytopenia and infections in elderly patients with aggressive NHL receiving CHOP or CNOP chemotherapy. (C) 2003 by The American Society of Hematology.
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| 5. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 6. |
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| 7. |
- Gryparis, Alexandros, et al.
(författare)
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Acute effects of ozone on mortality from the "air pollution and health : a European approach" project.
- 2004
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 170:10, s. 1080-7
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Tidskriftsartikel (refereegranskat)abstract
- In the Air Pollution and Health: A European Approach (APHEA2) project, the effects of ambient ozone concentrations on mortality were investigated. Data were collected on daily ozone concentrations, the daily number of deaths, confounders, and potential effect modifiers from 23 cities/areas for at least 3 years since 1990. Effect estimates were obtained for each city with city-specific models and were combined using second-stage regression models. No significant effects were observed during the cold half of the year. For the warm season, an increase in the 1-hour ozone concentration by 10 mug/m3 was associated with a 0.33% (95% confidence interval [CI], 0.17-0.52) increase in the total daily number of deaths, 0.45% (95% CI, 0.22-0.69) in the number of cardiovascular deaths, and 1.13% (95% CI, 0.62-1.48) in the number of respiratory deaths. The corresponding figures for the 8-hour ozone were similar. The associations with total mortality were independent of SO2 and particulate matter with aerodynamic diameter less than 10 mum (PM10) but were somewhat confounded by NO2 and CO. Individual city estimates were heterogeneous for total (a higher standardized mortality rate was associated with larger effects) and cardiovascular mortality (larger effects were observed in southern cities). The dose-response curve of ozone effects on total mortality during the summer did not deviate significantly from linearity.
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| 8. |
- Moller, P, et al.
(författare)
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Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 101:6, s. 555-559
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Tidskriftsartikel (refereegranskat)abstract
- Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaNO) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaNO and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaNO patients, mutation carriers had 75% S-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but I relapse occurred in the I S who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
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| 9. |
- Paulsson, Kajsa M, et al.
(författare)
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Assembly of tapasin-associated MHC class I in the absence of the transporter associated with antigen processing (TAP)
- 2001
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Ingår i: International Immunology. - : Oxford University Press (OUP). - 0953-8178 .- 1460-2377. ; 13:1, s. 9-23
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Tidskriftsartikel (refereegranskat)abstract
- The assembly of MHC class I molecules is regulated by a multi-protein complex in the endoplasmic reticules (ER) termed the loading complex. Tapasin is suggested to be one of the molecules forming this complex on the basis of its interaction with both the transporter associated with antigen processing (TAP) and MHC class I molecules. To address whether TAP is indispensable for the processing of the assembly of tapasin-associated MHC class I molecules, we studied the association of MHC class I molecules with tapasin, the assembly of tapasin-associated MHC class I with peptides and the peptide-mediated dissociation of MHC class I from tapasin in TAP-mutant T2 cells. In the absence of TAP, MHC class I heavy chain and beta(2)-microglobulin dimers were found to be properly associated with tapasin. The stable MHC class I dimer was required for its association with tapasin in the ER. In the absence of TAP, tapasin retained MHC class I molecules much longer in the ER than in the presence of TAP. This low off-rate of MHC class I from tapasin was due to the absence of high-affinity peptides in the ER of TAP-mutant cells but not to the absence of TAP per se. The introduction of peptides into permeabilized microsomes of TAP-mutant cells led to effective loading of the peptides onto tapasin-associated MHC class I and to the subsequent dissociation of MHC class I from tapasin. These results demonstrate that regulation of the assembly of tapasin-associated MHC class I is independent of the interaction of tapasin with TAP, but is dependent upon the peptides transported by TAP.
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| 10. |
- Sandell, A, et al.
(författare)
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Titanium dioxide thin-film growth on silicon(111) by chemical vapor deposition of titanium(IV) isopropoxide
- 2002
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Ingår i: Applied Physics Reviews. - : AIP Publishing. - 1931-9401. ; 92:6, s. 3381-3387
-
Tidskriftsartikel (refereegranskat)abstract
- The initial stages of TiO2 growth on Si(111) under ultra-high vacuum conditions is studied using core level photoelectron spectroscopy, x-ray absorption spectroscopy, and scanning tunneling microscopy. The TiO2 film was formed by means of chemical vapor deposition of titanium(IV) isopropoxide at a sample temperature of 500 degreesC. The thickness and composition of the amorphous interface layer and its subsequent transition to crystalline anatase TiO2 are discussed. Three different stages are identified: In the initial stage (film thickness <10 Angstrom), the oxygen atoms are coordinated mainly to Si atoms giving rise to Ti atoms with oxidation states lower than 4+. At this stage, a small amount of carbon (0.15 ML) is observed. The next stage (<25 Angstrom) is best described as an amorphous TiSixOy compound in which the oxidation state of Ti is 4+ and the x and y values vary monotonically with the film thickness, from 2 to 0 and 4 to 2, respectively. Finally (>30 Angstrom) a stoichiometric TiO2 layer starts to form. The TiO2 phase is anatase and the layer consists of particles similar to10 nm wide.
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| 11. |
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| 12. |
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| 13. |
- Anderson, H, et al.
(författare)
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Familial breast and ovarian cancer : a Swedish population-based register study
- 2000
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Ingår i: American Journal of Epidemiology. - 0002-9262. ; 152:12, s. 63-1154
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Tidskriftsartikel (refereegranskat)abstract
- A cohort of offspring of mothers with breast or ovarian cancer diagnosed in 1958-1993 was established using Swedish population-based registers. The children (n = 158,041) were born between 1941 and 1993, and their cancer incidence was followed between 1961 and 1993. A total of 3,257 tumors in 3,102 children were found. Observed numbers of cases were compared with expected numbers based on national calendar year-, age-, and sex-specific incidences. For daughters of women with breast cancer, the standardized morbidity ratios for being diagnosed with breast cancer and ovarian cancer before age 50 years were 1.99 (95% confidence interval (CI): 1.86, 2.14) and 1.28 (95% CI: 1.05, 1.54), respectively. The corresponding figures for daughters of women with ovarian cancer were 1.79 (95% CI: 1.55, 2.07) and 2.38 (95% CI: 1.77, 3.12). The risks were raised if the mother's cancer was diagnosed at a young age, the mother had multiple breast/ovarian diagnoses, or there was a sister with breast/ovarian cancer. Among all offspring, increased risks were found for thyroid cancer, testicular cancer, and malignant melanoma, while lung cancer risk was decreased if the mother had had breast cancer. The authors developed a variance estimator for the standardized morbidity ratio to cope with overdispersion due to dependency within families.
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| 14. |
- Anderson, Leif G, 1951, et al.
(författare)
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Enhanced uptake of atmospheric CO
- 2004
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Ingår i: Journal of Geophysical Research. ; 109:C06004
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Tidskriftsartikel (refereegranskat)abstract
- The waters of Storfjorden, a fjord in southern Svalbard, were investigated in late April 2002. The temperature was at the freezing point throughout the water column; the salinity in the top 30 m was just above 34.8, then increased nearly linearly to about 35.8 at the bottom. Nutrient and oxygen concentrations showed a minimal trend all through the water column, indicating minimal decay of organic matter. Normalized dissolved inorganic carbon, fCO2, and CFCs increase with depth below the surface mixed layer, while pH decreases. In waters below 50 m, there was an increase in dissolved inorganic carbon, corrected for decay of organic matter using the phosphate profile, corresponding to about 9 g C m−2 relative to the surface water concentration. We suggest this excess is a result of enhanced air-sea exchange of CO2 caused by sea ice formation. This enhancement is suggested to be a result of an efficient exchange through the surface film during the ice crystal formation and the rapid transport of the high salinity brine out of the surface layer.
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| 15. |
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| 16. |
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| 17. |
- Annertz, Karin, et al.
(författare)
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Incidence and survival of squamous cell carcinoma of the tongue in Scandinavia, with special reference to young adults.
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 101:1, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- In several countries, increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been suspected during the last decades. Some reports indicate a lower survival rate for young patients compared to older patients. In other reports, there has not been any considerable difference in survival when comparing young adults to older patients, whereas some authors have shown better survival for young adults. This disease is rare in young adults, and early reports were based on comparable small numbers and selected patients. Our aim was first to perform a population-based study to determine if an increased incidence in SCC of the tongue could be verified in a larger population comprising the Scandinavian countries Denmark, Finland, Sweden and Norway. A second aim was to determine survival rates for young adults compared to older patients. The material was based on the annual cancer incidence and survival reports from the Scandinavian cancer registries. The study period was 1960-1994. During that period, 5,024 SCCs of the tongue were reported. Of these, 276 (5.5%) were young adults (20-39 years). The incidence increased at all ages except for women 65-79 years old. The increase was most pronounced in young adults: 0.06-0.32 for men and 0.03-0.19 for women, counted by 100,000 person-years. Relative survival was significantly better for young adults compared to older patients.
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| 18. |
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| 19. |
- Bååth, Erland, et al.
(författare)
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Comparison of soil fungal/bacterial ratios in a pH gradient using physiological and PLFA-based techniques
- 2003
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Ingår i: Soil Biology & Biochemistry. - 0038-0717. ; 35:7, s. 955-963
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Tidskriftsartikel (refereegranskat)abstract
- We have compared the total microbial biomass and the fungal/bacterial ratio estimated using substrate-induced respiration (SIR) in combination with the selective inhibition technique and using the phospholipid fatty acid (PLFA) technique in a pH gradient (3.0-7.2) consisting of 53 mature broad-leaved forest soils. A fungal/bacterial biomass index using the PLFA technique was calculated using the PLFA 18:2w6,9 as an indicator of fungal biomass and the sum of 13 bacterial specific PLFAs as indicator of the bacterial biomass. Good linear correlation (p < 0.001) was found between the total microbial biomass estimated with SIR and total PLFAs (totPLFA), indicating that 1 mg biomass-C was equivalent to 130 nmol totPLFA. Both biomass estimates were positively correlated to soil pH. The fungal/bacterial ratio measured using the selective inhibition technique decreased significantly with increasing pH from about 9 at pH 3 to approximately 2 at pH 7, while the fungal/bacterial biomass index using PLFA measurements tended to increase slightly with increasing soil pH. Good correlation between the soil content of ergosterol and of the PLFA 18:2w6,9 indicated that the lack of congruency between the two methods in estimating fungal/bacterial ratios was not due to PLFA 18:2w6,9-related non-fungal structures to any significant degree. Several PLFAs were strongly correlated to soil pH (R-2 values > 0.8); for example the PLFAs 16:1w5 and 16:1w7c increased with increasing soil pH, while i16:0 and cy19:0 decreased. A principal component analysis of the total PLFA pattern gave a first component that was strongly correlated to soil pH (R-2 = 0.85, p < 0.001) indicating that the microbial community composition in these beech/beech-oak forest soils was to a large extent determined by soil pH.
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| 20. |
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| 21. |
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| 22. |
- Gunnarsson, B-M, et al.
(författare)
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The immigrant and the workplace
- 2004
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Ingår i: SS 15 (Sociolinguistics Symposium 15), Workshop, April, 1-4, Newcastle upon Tyne, UK.
-
Konferensbidrag (refereegranskat)
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| 23. |
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| 24. |
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| 25. |
- Holmberg, Lars, et al.
(författare)
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Stopping HABITS
- 2004
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Ingår i: Lancet. ; 363, s. 1476-
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Tidskriftsartikel (refereegranskat)
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| 26. |
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| 27. |
- Jones, Dylan T, et al.
(författare)
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Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis.
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 101:8, s. 3174-80
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Tidskriftsartikel (refereegranskat)abstract
- Activation of the phosphatidylinositol 3- kinase/AKT pathway antagonizes apoptosis in diverse cellular systems. We previously showed that human plasma activated AKT and potently blocked the ability of chlorambucil or gamma radiation to induce apoptosis of B-chronic lymphocytic leukemia (CLL) cells. Here we report experiments that identify albumin as the major component of plasma that blocks CLL cell killing by chlorambucil or radiation. Intact plasma depleted of albumin by chromatography on Cibacron blue-Sepharose or plasma from a subject with analbuminemia failed either to activate AKT or to protect CLL cells from chlorambucil-induced apoptosis. Both functions were restored by re-addition of albumin. The protective action of albumin as well as AKT activation was compromised by the binding of lipids. Fluorescence-activated cell sorter (FACScan) analysis demonstrated the uptake of fluoresceinated albumin by CLL cells. Accumulation of albumin in intracellular vesicles was also shown by confocal microscopy. Indirect inhibition of AKT activation by the phosphatidylinositol 3-kinase inhibitor LY294002 reversed the blockade of chlorambucil-induced killing by plasma albumin. The data suggest that activation of AKT consequent to binding of albumin by CLL cells blocks chlorambucil- and radiation-induced apoptosis. Strategies designed to block albumin-induced antiapoptotic signaling may, therefore, be of value in enhancing cytotoxic drug action on CLL cells.
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| 28. |
- Joos, G. F., et al.
(författare)
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Indirect airway challenges
- 2003
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Ingår i: Eur Respir J. ; 21:6
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Tidskriftsartikel (refereegranskat)abstract
- Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving. Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.
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| 29. |
- Joos, GF, et al.
(författare)
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Indirect airway challenges
- 2003
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 21:6, s. 1050-1068
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Tidskriftsartikel (refereegranskat)
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| 30. |
- Kyle, RA, et al.
(författare)
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Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 121:5, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.
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| 31. |
- Larsson, L C, et al.
(författare)
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Enhanced survival of porcine neural xenografts in mice lacking CD1d1, but no effect of NK1.1 depletion
- 2001
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 10:3, s. 295-304
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of embryonic porcine neurons may restore neurological function in patients with Parkinson's disease, if immunological rejection could be prevented. This study was performed to investigate the role of natural killer cells (NK cells) and NK1.1+ T cells (NK T cells) in the rejection of neural xenografts. A cell suspension was prepared from the ventral mesencephalon of 26-27-day-old pig embryos, and 2 microl was implanted in the right striata of mutant CD1d1 null (CD1.1-/-) mice, NK1.1-depleted mice, and controls. The CD1.1-/- mice are deficient in NK T cells and the antigen-presenting molecule CD1d1. Graft survival and host responses were determined immunohistochemically using markers for dopamine neurons, CD4-, CD8- cells, microglia, and macrophages. At 2 weeks, the grafts were significantly larger in CD1.1-/- mice, 0.09 +/- 0.02 microl (mean +/- SEM), compared with controls, 0.05 +/- 0.01 microl. There was no significant difference between NK1.1-depleted mice, 0.02 +/- 0.01 microl, and controls. At 5 weeks, two grafts were still present in the CD1-/- mice, whereas only scars remained in the controls and in the NK1.1-depleted mice. Immune reactions were strong at 2 weeks and less pronounced at 5 weeks in all groups. Microglial activation was lower in NK-depleted mice than in the controls at 2 weeks. In contrast to organ xenografting, NK1.1+ cells do not seem to be important mediators of the rejection of discordant cellular neural xenografts. However, our results suggest that the antigen-presenting molecule CD1d1 may be involved in the rejection process.
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| 32. |
- Larsson, L C, et al.
(författare)
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Porcine neural xenografts in rats and mice : donor tissue development and characteristics of rejection
- 2001
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 172:1, s. 14-100
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic ventral mesencephalic tissue from the pig is a potential alternative donor tissue for neural transplantation to Parkinson's disease patients. For stable graft survival, the host immune response has to be prevented. This study was performed in order to analyze the mechanisms and dynamics of neural xenograft rejection, as well as neurobiological properties of the donor tissue. Adult normal mice and rats, and cyclosporin A-treated rats, received intrastriatal transplants of dissociated embryonic ventral mesencephalic pig tissue that was 27 or 29 embryonic days of age (E27 and E29). The animals were perfused at 2, 4, 6, and 12 weeks after grafting and the brains were processed for immunohistochemistry of dopaminergic (tyrosine hydroxylase positive) neurons, CD4(+) and CD8(+) lymphocytes, natural killer cells, macrophages, microglia, and astrocytes. Thirty-five rats received daily injections of BrdU for 5 consecutive days at different time points after transplantation and were perfused at 6 weeks. These animals were analyzed for proliferation of cells in the donor tissue, both in healthy and in rejecting grafts. No tyrosine hydroxylase-positive cells proliferated after grafting. Our results demonstrated that E27 was superior to E29 donor tissue for neurobiological reasons. Cyclosporin A immunosuppression was protective only during the first weeks and failed to protect the grafts in a long-term perspective. Grafts in mice were invariably rejected between 2 and 4 weeks after transplantation, while occasional grafts in untreated rats survived up to 12 weeks without signs of an ongoing rejection process. CD8(+) lymphocytes and microglia cells are most likely important effector cells in the late, cyclosporin A-resistant rejection process.
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| 33. |
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| 34. |
- Lindholm, Lars H, et al.
(författare)
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Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial
- 2001
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Ingår i: The Lancet. - 1474-547X. ; 358, s. 539-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Is cancer related to hypertension and blood pressure? Do antihypertensive drugs promote cancer? Do antihypertensive drugs protect against cancer? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency of cancer in these patients. METHODS: We randomly assigned 6614 elderly patients with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one of three treatment strategies: conventional drugs (diuretics or b-blockers), calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age, sex, and calendar-year-specific reference frequencies for the general Swedish population. We also compared the number of cancers between the three treatment groups. FINDINGS: At baseline, 607 (9%) patients had previous malignant disease. Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients. During follow-up, there were 625 new cases of cancer in 590 patients. The frequency of cancer did not differ significantly between the treatment strategies, including all cancers and those at individual sites. The standardised incidence ratios (SIRs) for all cancers were also close to unity: 0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. INTERPRETATIONS: No difference in cancer risk was seen between patients randomly assigned to conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer.
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| 35. |
- Loden, M, et al.
(författare)
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A double-blind study comparing the effect of glycerin and urea on dry, eczematous skin in atopic patients
- 2002
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 82:1, s. 45-47
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Tidskriftsartikel (refereegranskat)abstract
- Moisturizing creams have beneficial effects in the treatment of dry, scaly skin, but they may induce adverse skin reactions. In a randomized double-blind study, 197 patients with atopic dermatitis were treated with one of the following: a new moisturizing cream with 20% glycerin, its cream base without glycerin as placebo, or a cream with 4% urea and 4% sodium chloride. The patients were asked to apply the cream at least once daily for 30 days. Adverse skin reactions and changes in skin dryness were assessed by the patient and a dermatologist. Adverse skin reactions such as smarting (a sharp local superficial sensation) were felt significantly less among patients using the 20% glycerin cream compared with the urea-saline cream, because 10% of the patients judged the smarting as severe or moderate when using glycerin cream, whereas 24% did so using urea-saline cream (p
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| 37. |
- Malmström, Per, et al.
(författare)
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Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.
- 2003
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Ingår i: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39, s. 1690-
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Tidskriftsartikel (refereegranskat)abstract
- The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.
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| 38. |
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| 39. |
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| 40. |
- Perlet, C, et al.
(författare)
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Multicenter study for the evaluation of a dedicated biopsy device for MR-guided vacuum biopsy of the breast
- 2002
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 12:6, s. 1463-1470
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this multicenter study was to determine the accuracy and clinical value of a dedicated breast biopsy system which allows for MR-guided vacuum biopsy (VB) of contrast-enhancing lesions. In five European centers, MR-guided 11-gauge VB was performed on 341 lesions. In 7 cases VB was unsuccessful. This was immediately realized on postinterventional images or direct follow-up combined with histopathology-imaging correlation; thus, a false-negative diagnosis was avoided. Histology of 334 successful biopsies yielded 84 (25%) malignancies, 17 (5%) atypical ductal hyperplasias, and 233 (70%) benign entities. Verification of malignant or borderline lesions included re-excision of the biopsy cavity. Benign histologic biopsy results were verified by retrospective correlation with the pre- and postinterventional MRI and by subsequent follow-up. Our results indicate that MR-guided VB, in combination with the dedicated biopsy coil, offers the possibility to accurately diagnose even very small lesions that can only be visualized or localized by MRI.
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| 41. |
- Planck, M, et al.
(författare)
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Increased cancer risk in offspring of women with colorectal carcinoma : a Swedish register-based cohort study
- 2000
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Ingår i: Cancer. - 0008-543X. ; 89:4, s. 9-741
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background.METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference.RESULTS: A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population.CONCLUSIONS: This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.
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| 45. |
- Shiao, Y. H., et al.
(författare)
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VHL down-regulation and differential localization as mechanisms in tumorigenesis
- 2003
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Ingår i: Kidney International. - Malden, USA : Blackwell Publishing. - 0085-2538 .- 1523-1755. ; 64:5, s. 1671-1674
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Tidskriftsartikel (refereegranskat)abstract
- Background: The von Hippel-Lindau (VHL) gene has been widely analyzed in many tumors. Early studies in animal tumors suggest that changes in VHL protein level and localization may be also important in tumorigenesis. In this study, we determined the role of VHL protein in human renal cell carcinomas. METHODS: Seventy-five human renal cell carcinomas, predominantly of clear cell type (60 of 75), were examined for VHL protein by immunohistochemistry. The level and pattern of protein expression were then compared to VHL mutations and tumor characteristics.Results: An apparent decline of VHL level (positive in <50% of tumor cells) was observed in 49 (65%) tumors, a change more frequent than VHL mutations (28 of 75) (37%). In tumors, VHL was localized to the cytoplasm and/or the cell membrane. The occurrence of a predominantly membranous signal was significantly associated with missense mutations (9 of 14 tumors with missense mutations versus 14 of 61 tumors with no or nonmissense mutations, P = 0.0025) and tumor stage (23 of 60 tumors with stage TI versus 0 of 15 tumors with TII and TIII, P = 0.0034).Conclusion: This study provides the first evidence of the role of VHL protein level and intracellular localization in tumorigenesis in humans.
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| 46. |
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| 47. |
- Wang, P, et al.
(författare)
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Inhibition of the transcription factors AP-1 and NF-kappaB in CD4 T cells by peroxisome proliferator-activated receptor gamma ligands
- 2001
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Ingår i: International Immunopharmacology. - 1567-5769. ; 1:4, s. 12-803
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Tidskriftsartikel (refereegranskat)abstract
- The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily, is essential for adipocyte differentiation and glucose homeostasis. PPARgamma has been found recently to regulate macrophage activation in response to mitogens and inflammation. Our study shows PPARgamma to be preferentially expressed in the nuclei of resting T cells and to increase upon activation of T cells by either anti-CD3 and anti-CD28 or phorbol myristyl acetate (PMA). We also found the PPARgamma ligand ciglitizone to attenuate the activation of T cells by inhibiting cytokine gene expression and anti-CD3 and anti-CD28 or PMA-induced proliferative responses. Inhibition of both the proliferative response and inflammatory cytokine expression in CD4 T cells was correlated with suppression of the activated transcription factors AP1 and NF-kappaB. PPARgamma ligands also strongly inhibited SEA-induced Vbeta3 T cell activation in vivo. These results, together with previous findings of the inhibitory effect of PPARgamma ligands on activated macrophages, provide clear evidence for PPARgamma as a negative regulator of the inflammatory activation of both macrophage and T cells. PPARgamma may thus be a potential therapeutic target for the treatment of autoimmunity.
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