| 1. |
- Halzen, F., et al.
(författare)
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From the first neutrino telescope, the antarctic muon and neutrino detector array AMANDA, to the IceCube observatory
- 1999
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Ingår i: Proceedings of the 26th International Cosmic Ray Conference, August 17-25, 1999, Salt Lake City : Invited, Rapporteur, and Highlight Papers. - : American Institute of Physics (AIP). ; , s. 428-431
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Konferensbidrag (refereegranskat)
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Ferrari, D., et al.
(författare)
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P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death
- 1999
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Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 447:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Myeloic cells express a peculiar surface receptor for extracellular ATP, called the P2Z/P2X(7) purinoreceptor, which is involved in cell death signalling. Here, we investigated the role of caspases, a family of proteases implicated in apoptosis and the cytokine secretion. We observed that extracellular ATP induced the activation of multiple caspases including caspase-1, -3 and -8, and subsequent cleavage of the caspase substrates PARP and Iamin B. Using caspase inhibitors, it was found that caspases were specifically involved in ATP-induced apoptotic damage such as chromatin condensation and DNA fragmentation, In contrast, inhibition of caspases only marginally affected necrotic alterations and cell death proceeded normally whether or not nuclear damage was blocked. Our results therefore suggest that the activation of caspases by the P2Z receptor is required for apoptotic but not necrotic alterations of ATP-induced cell death. (C) 1999 Federation of European Biochemical Societies.
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| 6. |
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| 7. |
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| 8. |
- Los, Marek Jan, et al.
(författare)
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Cross-resistance of CD95- and drug-induced apoptosis as a consequence of deficient activation of caspases (ICE/Ced-3 proteases)
- 1997
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 90:8, s. 3118-3129
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Tidskriftsartikel (refereegranskat)abstract
- The cytotoxic effect of anticancer drugs has been shown to involve induction of apoptosis. We report here that tumor cells resistant to CD95 (APO-1/Fas) -mediated apoptosis were cross-resistant to apoptosis-induced by anticancer drugs. Apoptosis induced in tumor cells by cytarabine, doxorubicin, and methotrexate required the activation of ICE/Ced-3 proteases (caspases), similarly to the CD95 system, After drug treatment, a strong increase of caspase activity was found that preceded cell death, Drug-induced activation of caspases was also found in ex vivo-derived T-cell leukemia cells. Resistance to cell death was conferred by a peptide caspase inhibitor and CrmA, a poxvirus-derived serpin, The peptide inhibitor was effective even if added several hours after drug treatment, indicating a direct involvement of caspases in the execution and not in the trigger phase of drug action. Drug-induced apoptosis was also strongly inhibited by antisense approaches targeting caspase-1 and -3, indicating that several members of this protease family were involved. CD95-resistant cell lines that failed to activate caspases upon CD95 triggering were cross-resistant to drug-mediated apoptosis, Our data strongly support the concept that sensitivity for drug-induced cell death depends on intact apoptosis pathways leading to activation of caspases. The identification of defects in caspase activation may provide molecular targets to overcome drug resistance in tumor cells. (C) 1997 by The American Society of Hematology.
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| 9. |
- Los, Marek Jan, et al.
(författare)
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Human T cell leukemia virus-I (HTLV-I) Tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state
- 1998
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Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 161:6, s. 3050-3055
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Tidskriftsartikel (refereegranskat)abstract
- We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis, The present study demonstrates that a hormone-dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2; these changes are followed by apoptotic cell death. Additional stimulation of the CD3/TCR pathway enhances the oxidative and apoptotic effects. Both Tax-mediated apoptosis and oxidative stress can be potently suppressed by antioxidants, as is seen with the administration of recombinant thioredoxin (adult T cell leukemia derived factor) or pyrrolidine dithiocarbamate. Hormone-induced Tax activation induces a long-lasting activation of NF-kappa B, which is a major target of reactive oxygen ntermediates. The long-term exposure of Jurkat cells to hormone eventually results in a selection of cell clones that have lost Tax activity. A subsequent transfection of these apparently "nonresponsive" clones allows the recovery of Tax responses in these cells. Our observations indicate that changes in the intracellular redox status mag be a determining factor in Tax-mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.
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| 10. |
- Souliotis, G. A., et al.
(författare)
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Production of neutron-rich nuclides and radioactive beams by intermediate energy 238 U fission
- 1997
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Ingår i: Physical Review C. - 2469-9993 .- 2469-9985. ; 55:5, s. 2146-2149
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Tidskriftsartikel (refereegranskat)abstract
- The yields of neutron-rich fission fragments from the interaction of 20 MeV/nucleon 238U with 208Pb have been measured. The production mechanism of these fragments is consistent with sequential fission following a quasielastic or deep inelastic collision. Substantial yields of very n-rich fragments are observed. The importance of these data for generation of n-rich radioactive beams by fission of intermediate-energy projectiles is discussed.
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| 11. |
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| 12. |
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| 13. |
- Bauer, M. K. A., et al.
(författare)
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Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas) ligand expression
- 1998
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 273:14, s. 8048-8055
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Tidskriftsartikel (refereegranskat)abstract
- Activation-induced cell death of T lymphocytes requires the inducible expression of CD95 (APO-1/Fas) ligand, which triggers apoptosis in CD95-bearing target cells by an autocrine or paracrine mechanism. Although execution of the CD95 death pathway is largely independent of reactive oxygen intermediates, activation-induced cell death is blocked by a variety of antioxidants. In the present study, we investigated the involvement of redox processes in the regulation of CD95 ligand (CD95L) expression in Jurkat T cells. We show that various antioxidants potently inhibited the transcriptional activation of CD95L following T cell receptor litigation or stimulation of cells with phorbol ester and ionomycin. Conversely, a prooxidant such as hydrogen peroxide alone was able to increase CD95L expression. As detected by Western blot and cytotoxicity assays, functional expression of CD95L protein was likewise diminished by antioxidants. Inhibition of CD95L expression was associated with a decreased DNA binding activity of nuclear factor (NF)-kappa B, an important redox-controlled transcription factor. Moreover, inhibition of NF-kappa B activity by a transdominant I kappa B mutant attenuated CD95L expression. Our data suggest that, although reactive oxygen intermediates do not act as mediators in the execution phase of CD95-mediated apoptosis, they are involved in the transcriptional regulation of CD95L expression.
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| 14. |
- Belka, C., et al.
(författare)
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The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation
- 1999
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 18:35, s. 4983-4992
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Tidskriftsartikel (refereegranskat)abstract
- Induction of apoptosis is a hallmark of cytostatic drug and radiation-induced cell death in human lymphocytes and lymphoma cells. However, the mechanisms leading to apoptosis are not well understood. We provide evidence that ionizing radiation induces a rapid activation of caspase-8 (FLICE) followed by apoptosis independently of CD95 ligand/receptor interaction. The radiation induced cleavage pattern of procaspase-8 into mature caspase-8 resembled that following CD95 crosslinking and resulted in cleavage of the proapoptotic substrate BID. Overexpression of dominant-negative caspase-8 interfered with radiation-induced apoptosis, Caspase-8 activation by ionizing radiation was not observed in cells genetically defective for the Src-like tyrosine kinase Lck, Cells lacking Lck also displayed a marked resistance towards apoptosis induction upon ionizing radiation. After retransfection of Lck, caspase-8 activation and the capability to undergo apoptosis in response to ionizing radiation was restored. We conclude that radiation activates caspase-8 via an Lck-controlled pathway independently of CD95 ligand expression, This is a novel signaling event required for radiation induced apoptosis in T lymphoma cells.
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| 15. |
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| 16. |
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| 17. |
- Elihn, K, et al.
(författare)
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Nanoparticle formation by laser-assisted photolysis of ferrocene.
- 1999
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Ingår i: NANOSTRUCTURED MATERIALS. - 0965-9773. ; 12:1-4, s. 79-82
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Tidskriftsartikel (refereegranskat)abstract
- Laser-assisted formation of iron-containing nanoparticles has been performed by photolytic dissociation of ferrocene vapour by a pulsed ArF excimer laser at 193 nm. The process was carried out at atmospheric pressure, either in an inert atmosphere of argo
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| 18. |
- Engervall, K, et al.
(författare)
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Borreliosis as a cause of peripheral facial palsy: a multi-center study
- 1995
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Ingår i: ORL. - 0301-1569. ; 57:4, s. 202-206
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Tidskriftsartikel (refereegranskat)abstract
- Borreliosis is known to be a common cause of peripheral facial palsy in Stockholm and its vicinity. The aim of the present study was to investigate the frequency and characteristics of borreliosis among patients with peripheral facial palsy in different parts of Sweden. All serological tests were performed in one laboratory. Ten Swedish Ear Nose and Throat clinics participated in a prospective 1-year study of patients seeking medical attention for acute peripheral facial palsy. Twenty-eight (6%) out of totally 446 patients fulfilled the criteria for the diagnosis of borreliosis. The frequency varied between 1 and 16% and was highest along the southeast coast of Sweden whereas no case was reported from the northern part of the country. Borreliosis was more common among children with facial palsy than among adults. The infection occurred during all seasons although it appears to be less frequent during the spring months. Only a minority of the borrelial patients had a history of a preceding tick bite or erythema migrans. The fairly low overall frequency of this secondary stage of borreliosis in the study may be a result of better knowledge of the disease and earlier treatment of its early manifestations. In Sweden's endemic areas borreliosis is a common cause of peripheral facial palsy, and therefore all patients with facial palsy in these regions should be examined for borrelial infection.
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| 19. |
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| 20. |
- Forslind, Bo, et al.
(författare)
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Human skin physiology studied by particle probe microanalysis
- 1995
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Ingår i: Scanning Microscopy. - 0891-7035. ; 9:4, s. 1011-1025
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Tidskriftsartikel (refereegranskat)abstract
- Particle probe methods (electron probe and proton probe X-ray microanalysis) have been applied to investigate the distribution of elements and water over the different layers of the epidermis. For major elements, electron probe X-ray microanalysis (XRMA) provides the advantage of superior spatial resolution, but for trace element analysis the more sensitive proton probe (particle induced X-ray emission, PIXE) analysis has to be used. On a dry weight basis, the concentration of S is rather constant across the epidermis, whereas the concentrations of P, K, Cl and Na show gradients with high levels in stratum germinativum (basale) and stratum spinosum but low levels in the stratum granulosum and stratum corneum. Essentially, Fe and Zn are confined to the basal region in normal skin. The concentration of Ca, however, increased steadily from the basal region to the stratum corneum. The probe technique allows quantitative analysis of stratum-specific changes in elemental content in a variety of pathological conditions, e.g., changes induced by nickel, detergents and other chemicals, or in psoriatic skin. Of particular interest are findings of increased Fe and Zn in non-involved psoriatic skin. Since the different layers of the skin have different elemental concentrations and react differently under pathological conditions, the probe techniques are far superior to bulk chemical analysis in elucidating physiological and pathological processes in the skin.
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| 21. |
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| 22. |
- Frietsch, Rudyard, et al.
(författare)
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Sulphur isotopes in Lower Proterozoic iron and sulphide ores in northern Sweden
- 1995
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Ingår i: Mineralium Deposita. - 0026-4598 .- 1432-1866. ; 30:3-4, s. 275-284
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Tidskriftsartikel (refereegranskat)abstract
- The present investigation deals with sulphur isotope distribution in Lower Proterozoic iron and sulphide mineralizations in northern Sweden. The contrasting sulphur isotope patterns are indicative of different genesis. Some 267 sulphur isotope analyses of pyrite, pyrrhotite, chalcopyrite, sphalerite, galena and bornite from 23 occurrences have been performed. Some deposits exhibit uniform compositions, although the mean δ34S values are clearly different, while other mineralizations have widely fluctuating values. The δ34S values in syngenetic, exhalative sedimentary skarn iron ores, quartz-banded iron ores and sulphide mineralizations of the 2.0-2.5 Ga old (Lapponian) Greenstone group show a large spread, supporting the existence of bacteriogenic sulphate reduction processes. The spread of the sulphur isotope values (δ34S = -8 to +25‰), and the non-equilibrium conditions, point to a biogenic rather than to an inorganic reduction of seawater sulphate. The isotopic composition of the sulphides in the epigenetic Lannavaara iron ores which were formed by a hydrothermal scapolite-tourmalme-related process, indicates a sulphur source similar to that of the Greenstone group. The δ34S values of Cu-(Au) sulphide mineralizations in the Malmberget region (e.g. Aitik), which were formed by a similar process and hosted by the volcanics-volcanoclastics of the 1.9 Ga old Porphyry group, are slightly below zero ‰, indicating a magmatic origin. The existence of different sulphur compositions for these mineralization types formed by a similar hydrothermal process, probably reflects the influence of the host rock, the solutions leaching pre-existing sulphides. In southern Norrbotten, epigenetic, Cu-Zn-Pb veintype mineralizations in metavolcanics and metasediments have δ34S values close to zero ‰ indicating a magmatic origin. The sulphur isotope data of the volcanogenic, massive sulphide ores of the Skellefte district, in particular the ores of the Adak dome, are close to zero ‰. The lead and sulphur isotopic features of the sulphides in northern Sweden show that the ore-forming processes were of a different nature on both sides of the Archean-Proterozoic border, implying differences in the crustal development. Lead isotopes show that lead was mobilized from specific sources on each side of the border. The sulphur of the sulphides in the Greenstone group in NE Sweden and Finland was introduced by sedimentary processes, whereas the sulphur of the sulphide occurrences towards the SW, mainly in the Porphyry group, is dominated by a magmatic sulphur component
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| 23. |
- Fulda, S., et al.
(författare)
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Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors
- 1997
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 57:21, s. 4956-4964
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Tidskriftsartikel (refereegranskat)abstract
- Betulinic acid CBA), a melanoma-specific cytotoxic agent, induced apoptosis in neuroectodermal tumors, such as neuroblastoma, medulloblastoma, and Ewing's sarcoma, representing the most common solid tumors of childhood. BA triggered an apoptosis pathway different from the one previously identified for standard chemotherapeutic drugs. BA-induced apoptosis was independent of CD95-ligand/receptor interaction and accumulation of wild-type p53 protein, but it critically depended on activation of caspases (interleukin 1 beta-converting enzyme/Ced-3-like proteases), FLICE/MACH (caspase-8), considered to be an upstream protease in the caspase cascade, and the downstream caspase CPP32/YAMA/Apopain (caspase-3) were activated, resulting in cleavage of the prototype substrate of caspases PARP. The broad-spectrum peptide inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, which blocked cleavage of FLICE and PARP, also completely abrogated BA-triggered apoptosis. Cleavage of caspases was preceded by disturbance of mitochondrial membrane potential and by generation of reactive oxygen species. Overexpression of Bcl-2 and Bcl-x(L) conferred resistance to BA at the level of mitochondrial dysfunction, protease activation, and nuclear fragmentation. This suggested that mitochondrial alterations were involved in BA-induced activation of caspases. Furthermore, pax and Bcl-x(s), two death-promoting proteins of the Bcl-2 family, were up-regulated following BA treatment. Most importantly, neuroblastoma cells resistant to CD95- and doxorubicin-mediated apoptosis were sensitive to treatment with BA, suggesting that BA may bypass some forms of drug resistance. Because BA exhibited significant antitumor activity on patients' derived neuroblastoma cells ex vivo, BA may be a promising new agent for the treatment of neuroectodermal tumors in vivo.
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| 24. |
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| 25. |
- Fulda, S., et al.
(författare)
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Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system
- 1998
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 76:1, s. 105-114
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Tidskriftsartikel (refereegranskat)abstract
- We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system, Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')(2) anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis, Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis, The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases, Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors. (C) 1998 Wiley-Liss, Inc.
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| 26. |
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| 27. |
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| 28. |
- Hiltonen, Thomas, et al.
(författare)
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A cDNA coding for glutathione S-transferase from the unicellular green algae Coccomyxa sp
- 1996
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Ingår i: Gene. - 0378-1119 .- 1879-0038. ; 176:1-2, s. 263-264
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Tidskriftsartikel (refereegranskat)abstract
- A cDNA coding for glutathione S-transferase (GST) was cloned and sequenced from the unicellular green algae Coccomyxa sp. The predicted 215 amino acid polypeptide (23.9 kDa, pI 5.3) is most similar to the theta-type GSTs found in a variety of different eukaryotic organisms. Within this sub-class, the Coccomyxa GST is 42% identical (63% similar) to the flatfish Pleuronectes platessa homologue, and 24 to 35% (49-57%) to other theta-type GST's.
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| 29. |
- Hiltonen, Thomas, 1960-, et al.
(författare)
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PURIFICATION AND CHARACTERIZATION OF AN INTRACELLULAR CARBONIC-ANHYDRASE FROM THE UNICELLULAR GREEN-ALGA COCCOMYXA
- 1995
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Ingår i: Planta. - 0032-0935 .- 1432-2048. ; 195:3, s. 345-351
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Tidskriftsartikel (refereegranskat)abstract
- An intracellular carbonic anhydrase (CA; EC 4.2.1.1) was purified and characterised from the unicellular green alga Coccomyxa sp. Initial studies showed that cultured Coccomyxa cells contain an intracellular CA activity around 100 times higher than that measured in high-CO2-grown cells of Chlamydomonas reinhardtii CW 92. Purification of a protein extract containing the CA activity was carried out using ammonium-sulphate precipitation followed by anion-exchange chromatography. Proteins were then separated by native (non-dissociating) polyacrylamide gel electrophoresis, with each individual protein band excised and assayed for CA activity. Measurements revealed CA activity associated with two discrete protein bands with similar molecular masses of 80 +/- 5 kDa. Dissociation by denaturing polyacrylamide gel electrophoresis showed that both proteins contained a single polypeptide of 26 kDa, suggesting that each 80-kDa native protein was a homogeneous trimer. Isoelectric focusing of the 80-kDa proteins also produced a single protein band at a pH of 6.5. Inhibition studies on the purified CA extract showed that 50% inhibition of CA activity was obtained using 1 mu M azetazolamide. Polyclonal antibodies against the 26-kDa CA were produced and shown to have a high specific binding to a single polypeptide in soluble protein extracts from Coccomyxa. cells. The same antiserum, however, failed to cross-react with soluble proteins isolated from two different species of green algae, Chlamydomonas reinhardtii and Chlorella vulgaris. Correspondingly, antisera directed against pea chloroplastic CA, extracellular CA from C. reinhardtii and human CAII, showed no cross-hybridisation to the 26-kDa polypeptide in Coccomyxa. The 26-kDa protein was confirmed as being a CA by N-terminal sequencing of two internal polypeptide fragments and alignment of these sequences with that of previously identified CA proteins from several different species.
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| 30. |
- Hug, H., et al.
(författare)
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Rhodamine 110-linked amino acids and peptides as substrates to measure caspase activity upon apoptosis induction in intact cells
- 1999
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 38:42, s. 13906-13911
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Tidskriftsartikel (refereegranskat)abstract
- Caspases (cysteine aspartate-specific proteases) are a structurally related group of cysteine proteases that cleave peptide bonds following specific recognition sequences. They play a central role in activating apoptosis of vertebrate cells. To measure apoptosis induced by various stimuli and at an early apoptotic stage, caspases are an ideal target. This is especially the case when apoptotic cells have to be analyzed ex vivo before phagocytes remove them. A new and sensitive caspase assay is based on a substrate that contains only aspartate residues linked to rhodamine 110. With this and similar substrates, we are able to detect intracellular caspase activation by flow cytometry after apoptosis induction in intact hematopoetic cell lines.
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| 31. |
- Högstrand, K., et al.
(författare)
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DNA damage caused by etoposide and γ-irradiation induces gene conversion of the MHC in a mouse non-germline testis cell line
- 1999
-
Ingår i: Mutation research. - 0027-5107 .- 1873-135X. ; 423:1-2, s. 155-169
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Tidskriftsartikel (refereegranskat)abstract
- We have explored the effects of γ-irradiation and etoposide on the gene conversion frequency between the endogenous major histocompatibility complex class II genes Abk and Ebd in a mouse testis cell line of non-germline origin with a polymerase chain reaction assay. Both γ-rays and etoposide were shown to increase the gene conversion frequency with up to 15-fold compared to untreated cells. Etoposide, which is an agent that stabilise a cleavable complex between DNA and DNA topoisomerase II, shows an increased induction of gene conversion events with increased dose of etoposide. Cells treated with γ-rays, which induce strand breaks, had an increased gene conversion frequency when they were subjected to low doses of irradiation, but increasing doses of irradiation did not lead to an increase of gene conversion events, which might reflect differences in the repair process depending on the extent and nature of the DNA damage. These results where DNA damage was shown to be able to induce gene conversion of endogenous genes in mouse testis cells suggests that the DNA repair system could be involved in the molecular genetic mechanism that results in gene conversion in higher eukaryotes like mammals.
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| 32. |
- Högstrand, K, et al.
(författare)
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Gene conversion of major histocompatibility complex genes in the mouse spermatogenesis is a premeiotic event
- 1997
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Ingår i: Molecular Biology of the Cell. - : American Society for Cell Biology (ASCB). - 1059-1524 .- 1939-4586. ; 8:12, s. 2511-2517
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Tidskriftsartikel (refereegranskat)abstract
- The molecular genetic mechanism of gene conversion in higher eukaryotes remains unknown. We find it of considerable interest to determine when during spermatogenesis gene conversion occurs. We have therefore purified pachytene spermatocytes and haploid spermatocytes from adult mice and analyzed these fractions for the presence of gene conversion products resulting from the transfer between the major histocompatibility complex class II genes Ebd and Abk in a polymerase chain reaction assay. We have further isolated spermatogenic cells from prepubescent mice and analyzed them for the presence of the same gene conversion products. We can detect gene conversion products in testis cells as early as in 8-d-old mice where the only existing spermatogenic cells are spermatogonia. The frequency of gene conversion products remains the same as the cells reach meiosis in 18-d-old mice, and is unchanged after meiosis is completed in haploid spermatocytes. Gene conversion of this specific fragment therefore appears to be a premeiotic event and, consequently, relies on genetic mechanisms other than normal meiotic recombination.
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| 33. |
- Högstrand, K., et al.
(författare)
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Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions
- 1999
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Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 49:5, s. 446-455
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Tidskriftsartikel (refereegranskat)abstract
- We examined 32 DNA sequences of mouse and human major histocompatibility complex (MHC) genes believed to have been subjected to gene conversion events. All regions of the mouse H2 genes as well as the human HLA genes which have been implied to be involved in gene conversion events had elevated levels of CpG dinucleotides, whereas the rest of the genes showed extensive CpG suppression. Mouse MHC genes which have been suspected but not directly implied to be involved in gene conversion events also showed elevated levels of CpG dinucleotides. Moreover, both mouse and human MHC genes which have never been suspected of undergoing gene conversion had low levels of CpG throughout the genes. These results indicate that high CpG levels are correlated with gene conversion rather than with polymorphism, as non-polymorphic genes that have been implicated as gene conversion donors also have elevated levels of CpG dimers in the involved regions whereas polymorphic genes which have never been considered to undergo gene conversion events have a low level of CpG dinucleotides. We also studied the methylation pattern of CpG dimers in the Abk gene by restriction enzyme digestion of mouse testis DNA followed by Southern blot and hybridization to an Abk-specific probe. The examined CpG dimers in prepubescent mice, where the latest germline stages are spermatogonia, leptene, or pachytene, are respectively non-methylated. Accordingly, the CpG dimers appear to be non-methylated in germline DNA from the testis of prepubescent mice, where gene conversions have been reported to occur.
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| 34. |
- Josefsson, Agnetha M., et al.
(författare)
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p53 polymorphism and risk of cervical cancer
- 1998
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 396:6711, s. 531-
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Tidskriftsartikel (refereegranskat)
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| 35. |
- Karlsson, Jan, 1966-, et al.
(författare)
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A novel α-type carbonic anhydrase associated with the thylakoid membrane in Chlamydomonas reinhardtii is required for growth at ambient CO2
- 1998
-
Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 17:5, s. 1208-1216
-
Tidskriftsartikel (refereegranskat)abstract
- A 29.5 kDa intracellular α-type carbonic anhydrase, designated Cah3, from the unicellular green alga Chlamydomonas reinhardtii is the first of this type discovered inside a photosynthetic eukaryote cell. We describe the cloning of a cDNA which encodes the protein. Immunoblot studies with specific antibodies raised against Cah3 demonstrate that the polypeptide is associated exclusively with the thylakoid membrane. The putative transit peptide suggests that Cah3 is directed to the thylakoid lumen, which is confirmed further by the presence of mature sized Cah3 after thermolysin treatment of intact thylakoids. Complementation of the high inorganic carbon concentration-requiring mutant, cia-3, with a subcloned cosmid containing the cah3 gene yielded transformants that grew on atmospheric levels of CO2 (0.035%) and contained an active 29.5 kDa alpha-type carbonic anhydrase. Although, cia-3 has reduced internal carbonic anhydrase activity, unexpectedly the level of Cah3 was similar to that of the wild-type, suggesting that the mutant accumulates an inactive Cah3 polypeptide. Genomic sequence analysis of the mutant revealed two amino acid changes in the transit peptide. Results from photosynthesis and chlorophyll a fluorescence parameter measurements show that the cia-3 mutant is photosynthetically impaired. Our results indicate that the carbonic anhydrase, extrinsically located within the chloroplast thylakoid lumen, is essential for growth of C.reinhardtii at ambient levels of CO2, and that at these CO2 concentrations the enzyme is required for optimal photosystem II photochemistry.
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| 36. |
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| 37. |
- Lindén, Ola, et al.
(författare)
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Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas
- 1999
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 5:10 Suppl, s. 3287-3291
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Tidskriftsartikel (refereegranskat)abstract
- Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.
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| 38. |
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| 39. |
- Los, Marek Jan, et al.
(författare)
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Hydrogen-Peroxide as a Potent Activator of T-Lymphocyte Functions
- 1995
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 25:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- During inflammatory processes infiltrating cells produce large amounts of reactive oxygen intermediates (ROI). Increasing evidence suggests that ROI besides being cytotoxic may act as important mediators influencing various cellular and immunological processes. In this study, we have investigated the effects of hydrogen peroxide on several aspects of lymphocyte activation. In ESb-L T lymphoma cells, micromolar concentrations of hydrogen peroxide rapidly induced activation of the transcription factor NF-kappa B, whereas DNA-binding activity of the transcription factor AP-1 was virtually not affected. In addition, hydrogen peroxide induced early gene expression of interleukin-2 (IL-2) and the IL-2 receptor alpha chain. The stimulation of IL-2 expression was found to be conferred by a kappa B-like cis-regulatory region within the IL-2 gene promoter. In contrast to these activating effects, addition of hydrogen peroxide was largely inhibitory on cell proliferation which is consistent with a general requirement of thiol compounds for lymphocyte proliferation. However, hydrogen peroxide significantly increased T cell proliferation when applied for a short period under reducing conditions. These data indicate that ROI may act as an important competence signal in T lymphocytes inducing early gene expression as well as cell proliferation.
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| 40. |
- Los, Marek Jan, et al.
(författare)
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Il-2 Gene-Expression and Nf-Kappa-B Activation Through Cd28 Requires Reactive Oxygen Production by 5-Lipoxygenase
- 1995
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Ingår i: EMBO Journal. - 0261-4189 .- 1460-2075. ; 14:15, s. 3731-3740
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Tidskriftsartikel (refereegranskat)abstract
- Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase Az and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-KB activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway.
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| 41. |
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| 42. |
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| 43. |
- Nyström, Elisabeth, et al.
(författare)
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Autogenous onlay bone grafts fixed with screw implants for the treatment of severely resorbed maxillae. Radiographic evaluation of preoperative bone dimensions, postoperative bone loss, and changes in soft-tissue profile.
- 1996
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - 0901-5027 .- 1399-0020. ; 25:5, s. 351-359
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Tidskriftsartikel (refereegranskat)abstract
- Thirty patients with severely resorbed edentulous maxillae underwent combined treatment of iliac bone onlay graft and titanium implants. The patients were followed for 3 years. They were radiographically examined before surgery to evaluate the bone volume at the intended implant sites. Only 13/156 implant sites were suitable for implant insertion. The bone level at the implant surfaces was evaluated after 6 months and 1, 2, and 3 years, respectively. There was a continuing decrease of the bone level throughout the follow-up period with a mean loss of 4.9 mm after 3 years and with no difference between sexes. Twenty-six implants were radiographically examined before removal, and only three of these implant sites showed radiographic signs of failure. The soft-tissue profile was analyzed cephalometrically by the subtraction technique. The upper lip generally moved inward and the apex of the nose and the columella downward and inward. The anterior facial height increased in most of the patients, resulting in a downward and inward change of the lower lip, the mentolabial sulcus, the soft-tissue pogonion, and the soft-tissue gnathion.
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| 44. |
- Obrant, Karl, et al.
(författare)
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The proportion of carboxylated to total or intact osteocalcin in serum discriminates warfarin-treated patients from control subjects
- 1999
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 14:4, s. 555-560
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the serum concentration of gamma-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0-3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 +/- 3.8 (+/- 1 SD) ng/ml compared with the controls 13.1 +/- 9.7 (p < 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum gamma-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.
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| 45. |
- Oscarsson, Jan, 1960, et al.
(författare)
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GH but not IGF-I or insulin increases lipoprotein lipase activity in muscle tissues of hypophysectomised rats.
- 1999
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 160:2, s. 247-55
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Tidskriftsartikel (refereegranskat)abstract
- Changes in GH secretion are associated with changes in serum lipoproteins, utilisation of fuels and body composition. Since lipoprotein lipase (LPL) is a key enzyme in the regulation of lipid and lipoprotein metabolism, changes in LPL activity may contribute to these effects of GH. The present study was undertaken to investigate the role of GH and the GH-dependent growth factor, IGF-I, in the regulation of LPL in heart, skeletal muscle and adipose tissue. Female rats were hypophysectomised at 50 days of age. One week later, hormonal therapy was commenced. All hypophysectomised rats received l-thyroxine and cortisol. Adipose tissue, the heart, soleus and gastrocnemius muscles were excised after 1 week of hormonal therapy. The effect of insulin injections on adipose tissue and heart LPL activity was also studied. In separate experiments, LPL activity in post-heparin plasma was measured. Hypophysectomy had no effect on adipose tissue LPL activity, whereas activity was reduced in heart, soleus and gastrocnemius muscle tissues. GH treatment had no significant effect on LPL activity in adipose tissue or soleus muscle, but increased the LPL activity in heart and gastrocnemius muscle. GH treatment increased post-heparin plasma LPL activity. Recombinant human IGF-I treatment (1.25 mg/kg per day) markedly reduced LPL activity in adipose tissue, but had no effect in muscle tissues. The effect of IGF-I treatment on adipose tissue LPL was not reflected by a decrease in post-heparin plasma LPL activity. Daily injections of insulin for 7 days increased LPL activity in adipose tissue but had no effect on heart LPL activity. In adipose tissue, LPL mRNA levels tended to decrease as a result of IGF-I treatment. In the muscle tissues, no significant effects of hypophysectomy, GH or IGF-I treatment on LPL mRNA levels were observed.%It is concluded that GH increases heart and skeletal muscle tissue LPL activity, which probably contributes to an increased post-heparin plasma LPL activity. The effect of GH on muscle LPL activity is probably not mediated by IGF-I or insulin. Insulin and IGF-I have opposite effects on LPL activity in adipose tissue.
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| 46. |
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| 47. |
- Proff, S, et al.
(författare)
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Electromagnetic polarizabilities of nucleons bound in 40Ca, 16O and 4He
- 1999
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Ingår i: Nuclear Physics A. - 0375-9474. ; 646:1, s. 67-82
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Tidskriftsartikel (refereegranskat)abstract
- Differential cross sections for elastic scattering of photons have been measured for 40Ca at energies of 58 and 74 MeV and for 16O and 4He at 61 MeV, in the angular range from 45° to 150°. Evidence is obtained that there are no significant in-medium modifications of the electromagnetic polarizabilities except for those originating from meson exchange currents.
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| 48. |
- Schulze-Osthoff, Klaus, et al.
(författare)
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Role of ICE-related and other proteases in Fas-mediated apoptosis
- 1996
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Ingår i: Cell Death and Differentiation. - 1350-9047 .- 1476-5403. ; 3:2, s. 177-184
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Forskningsöversikt (refereegranskat)abstract
- Interleukin-1 beta-converting enzyme (ICE)-like proteases comprise a novel family of unusual cysteine proteases which have been implicated in programmed cell death in both invertebrates and mammals. Current available evidence indicates a role of ICE proteases as central executioners of apoptosis triggered by the cell surface receptor Fas (APO-1). The presence of multiple mammalian ICE proteases with partially overlapping but distinct activities suggests a complex proteolytic cascade which is induced upon Fas ligation. The precise role of single members of the ICE family in Fas-mediated apoptosis, however, is still unclear. Here, we summarize the present knowledge about the relevance of ICE proteases, their potential targets, and interaction with unrelated proteases in cell death mediated by Fas and other apoptotic stimuli.
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| 49. |
- Sjögren, Klara, 1970, et al.
(författare)
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Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.
- 1999
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 96:12, s. 7088-92
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Tidskriftsartikel (refereegranskat)abstract
- The body growth of animals is regulated by growth hormone and IGF-I. The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.
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| 50. |
- Smith, M.L., et al.
(författare)
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The spontaneous hemin release from Lumbricus terrestris hemoglobin
- 1997
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Ingår i: Comparative Biochemistry and Physiology. P. A, Physiology. - 1096-4940. ; 118:4, s. 1241-1245
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Tidskriftsartikel (refereegranskat)abstract
- The slow, spontaneous release of hemin from earthworm, Lumbricus terrestris, hemoglobin has been studied under mild conditions in the presence of excess apomyoglobin. This important protein is surprisingly unstable. The reaction is best described as hemin released from the globin into water, followed by quick engulfment by apomyoglobin. The energetics of this reaction are compared with those of other types of hemoglobins. Anomalously low activation energy and enthalpy are counterbalanced by a negative entropy. These values reflect significant low frequency protein motion and dynamics of earthworm hemoglobin and may also indicate an open structure distal to the heme. This is also supported by the infrared spectrum of the carbonyl hemoprotein, which indicates several types of distal interactions with the bound CO. The reported low heme to polypeptide ratio for this protein may be due to facile heme and hemin release by the circulating protein.
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