400 research outputs found
The constant proportion of grana and stroma lamellae in plant chloroplasts
No full textThe relative proportion of stroma lamellae and grana end membranes was determined from electron micrographs of 58 chloroplasts from 21 different plant species. The percentage of grana end membranes varied between 1 and 21% of the total thylakoid membrane indicating a large variation in the size of grana stacks. By contrast the stroma lamellae account for 20.3 +/- 2.5 (SD)% of the total thylakoid membrane. A plot of percentage stroma lamellae against percentage of grana end membranes fits a straight line with a slope of zero showing that the proportion of stroma lamellae is independent of the size of the grana stacks. That stroma lamellae account for about 20% of the thylakoid membrane is in agreement with fragmentation and separation analysis (Gadjieva et al. Biochim. Biophys. Acta 144: 92-100, 1999). Chloroplasts from spinach, grown under high or low light, were fragmented by sonication and separated by countercurrent distribution into two vesicle populations originating from grana and stroma lamellae plus end membranes, respectively. The separation diagrams were very similar lending independent support for the notion that the proportion of stroma lamellae is constant. The results are discussed in relation to the composition and function of the chloroplast in plants grown under different environmental conditions, and in relation to a recent quantitative model for the thylakoid (Albertsson, Trends Plant Sci. 6: 349-354, 2001)
Two cases of 5-fluorouracil toxicity linked with gene variants in the DPYD gene
No full textObjectives: Dihydropyrimidine dehydrogenase (DPD) is the initial rate-limiting enzyme in endogenous pyrimidine catabolism and is responsible for the reduction of the pyrimidine analog 5-fluorouracil (5-FU). DPD deficiency is known to cause potentially lethal toxicity in patients receiving 5-FU. We here report a frequency analysis of one of the major splice-site mutations in the DPDY gene, and further two new DPYD gene variants. Design and methods: Restriction fragment length polymorphisin (RFLP) and DNA sequence analysis were performed on genomic DNA and mRNA. Results: In 400 patients that were diagnosed with cancer and were eligible for 5-FU treatment, 14 patients were found to be heterozygous for the splice-site mutation DPYD IVS14+1Gandgt;A, which corresponds to a population frequency of 3.5%. Two novel variants in the DPYD gene were identified. The first case was heterozygous for DPYD c. 1796Tandgt;C (p.M599T). In the second case, we observed heterozygosity for the splice-site mutation DPYD IVS14+17Aandgt;G. Conclusions: We report two new DPYD gene variants, of which DPYD c. 1796Tandgt;C is potentially pathogenic, whereas DPYD IVS14+17Aandgt;G is suggested as a variant without clinical significance.Original Publication: Anna Ofverholm, Eva Arkblad, Stanko Skrtic, Per Albertsson, Emman Shubbar and Charlotta Enerbäck, Two cases of 5-fluorouracil toxicity linked with gene variants in the DPYD gene, 2010, CLINICAL BIOCHEMISTRY, (43), 3, 331-334. http://dx.doi.org/10.1016/j.clinbiochem.2009.09.024 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/</p
Levosimendan neither improves nor worsens mortality in patients with cardiogenic shock due to ST-elevation myocardial infarction
No full textElmir Omerovic, Truls R&aring;munddal, Per Albertsson, Mikael Holmberg, Per Hallgren, Jan Boren, Lars Grip, G&ouml;ran MatejkaDepartment of Cardiology, Sahlgrenska University Hospital, Gothenburg, SwedenBackground: The aim of this study was to evaluate the effect of levosimendan on mortality in cardiogenic shock (CS) after ST elevation myocardial infarction (STEMI).Methods and results: Data were obtained prospectively from the SCAAR (Swedish Coronary Angiography and Angioplasty Register) and the RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) about 94 consecutive patients with CS due to STEMI. Patients were classified into levosimendan-mandatory and levosimendan-contraindicated cohorts. Inotropic support with levosimendan was mandatory in all patients between January 2004 and December 2005 (n = 46). After the SURVIVE and REVIVE II studies were presented, levosimendan was considered contraindicated and was not used in consecutive patients between December 2005 and December 2006 (n = 48). The cohorts were similar with respect to pre-treatment characteristics and concomitant medications. There was no difference in the incidence of new-onset atrial fibrillation, in-hospital cardiac arrest and length of stay at the coronary care unit. There was no difference in adjusted mortality at 30 days and at one year.Conclusion: The use of levosimendan neither improves nor worsens mortality in patients with CS due to STEMI. Well-designed randomized clinical trials are needed to define the role of inotropic therapy in the treatment of CS.Keywords: shock, myocardial infarction, inotropic agents, heart failure, pharmacolog
A remarkable constancy in the relative amount of stroma lamellae of chloroplasts from plants, and its functional significance
No full textA model is presented which gives a quantitative picture of the distribution of the photosynthetic components in the thylakoid membrane of higher plants. The model is based on fragmentation and separation analysis together with microscopy. A salient feature of the model is that over 80 per cent of the pigments are located in the grana where the two photosystems 1 and 2 produce oxygen, NADPH and ATP by the linear electron transport pathway while the stroma lamellae, which harbour less than 20 per cent of the pigments, carry out Photosystem 1 mediated cyclic electron transport coupled to ATP production. This arrangement derives from the observation that more pigments are associated with Photosystem 1 which therefore captures more quanta than Photosystem 2. The excess pigments associated with Photosystem 1 are suggested to be located in the stroma lamellae. Tentative numbers of the different photosystem and cytochrome b.f. complexes located in the different domains of the thylakoid membrane will be presented
The contribution of photosynthetic pigments to the development of biochemical separation methods: 1900-1980
No full textThe role of photosynthetic pigments in the development of separation methods in biochemistry during the period 1900-1980 is described beginning with M. Tswett who introduced separation of chlorophylls and carotenoids on columns and coined the term chromatography in 1906. In Uppsala, T. Svedberg developed the ultracentrifuge in the 1920s. A. Tiselius improved electrophoresis in the 1930s and developed chromatography of proteins in the 1940s and 1950s. Others of `The Uppsala school in separation science' include J. Porath, P. Flodin and S. Hjertén who further developed various gel chromatographic methods. Hjertén introduced free zone electrophoresis in narrow tubes, a forerunner of capillary electrophoresis. Two proteins, phycoerythrin and phycocyanin, were used as test substances in all these methodological studies. Aqueous two-phase partitioning as a separation method was introduced in 1956 by the author. In this work, chloroplast particles were used, and the method was applied for the separation and purification of intact chloroplasts, inside-out thylakoid vesicles and plasma membranes. My research was carried out in cooperation with G. Blomquist, G. Johansson, C. Larsson, B. Andersson and H.-E. Akerlund during a 20-year period, 1960-1980
The structure and function of the chloroplast photosynthetic membrane - a model for the domain organization
No full textMatrix metalloproteinases in natural killer cells. Expression of MMPs, IL-2 activation and killer cell interactions with Matrigel® and model tumours
No full textIntroduction: IL-2 activated natural killer (A-NK) cells can recognize malignant cells and exert tumouricidal activities by multiple mechanisms that require close contact with the target cells. Upon adoptive transfer, some A-NK cells accumulate in tumours by migrating from the vascular bed to a position inside the malignant tissue, forming close contacts with target cells. This process requires that naturally occurring barriers are passed, i.e. the endothelial lining with the underlying basement membrane and the adjacent extracellular matrix, ECM. Thus, tumour infiltration by A-NK cells is believed to depend in part on proteolytic matrix degradation, in analogy with malignant cell invasion during formation of metastasis. This focuses on expression, release, and possible functions of ECM degrading proteases in NK cells. Specific aims: to explore the repertoire of matrix metalloproteinases (MMPs) in NK/A-NK cells of various species; to examine whether MMPs are utilised in the process of basement membrane transmigration; to describe the morphology of A-NK cell infiltration in ECM and in model tumours as related to proteolytic mechanismsMaterials & Methods: Gelatin zymography, Western blotting and reverse transcriptase (RT-) PCR were used to detect and identify the various MMPs in NK/A-NK cell membranes and culture supernatants. Transmigration assays using Matrigel (reconstituted basement membrane ECM) covered invasion-chambers. A-NK-to-matrix and A-NK-to-tumour cell interactions were investigated by means of light and fluorescence microscopy, and electron microscopy. Model B16 melanoma tumours formed in vitro and growing intraperitoneally were used.Results: Expression and release of multiple MMPs were demonstrated in NK cells from different species. In rat MMP-2 and MMP-9 were found, in mice MMP-2, MMP-9, MMP-11, MMP-13, MT1-MMP, MT2-MMP and the specific inhibitors TIMP-1 and TIMP-2. In human NK cells MMP-2, MMP-8, MMP-9 and MT1-MMP as well as TIMP-1 were detected. A-NK cell transmigration through a basement membrane material was inhibited to about 50% (rat cells) or 90% (murine cells) by the MMP inhibitor batimastat (BB94). Human A-NK cell migrated across the membranes in a seemingly IL-2-dependent manner. Microscopy demonstrated that infiltrating A-NK cells disintegrate B16 tumour cell aggregates in vitro, which was not related to cytolysis. Further, an A-NK cell age-dependent alteration of Matrigel was detected. Short-term cultured cells caused a general digestion of the matrix material which contrasted to the effect of older A-NK cells that created large excavations around the cells with little alteration on the remaining Matrigel. A-NK cells infiltrated, but did not disintegrate, intraperitoneal tumours.Conclusions: NK/A-NK cells express and release a broad array of MMPs including their inhibitors. Further, MMPs are involved in A-NK cell basement membrane transmigration. Disintegration of tumour cell aggregates in vitro and digestion of Matrigel are interpreted as proteolytic effects. The additional matrix-dilating effect may be explained as a release of proteoglycans. The present studies confirm that intravital tumours largely resist derangement of the tumour structure in spite of A-NK cell infiltration
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