| 1. |
- Daşu, Alexandru, et al.
(författare)
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The relationship between vascular oxygen distribution and tissue oxygenation
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Tumour oxygenation could be investigated through several methods that use various measuring principles and can therefore highlight its different aspects. The results have to be subsequently correlated, but this might not be straightforward due to intrinsic limitations of the measurement methods. This study describes an analysis of the relationship between vascular and tissue oxygenations that may help the interpretation of results. Simulations have been performed with a mathematical model that calculates the tissue oxygenation for complex vascular arrangements by taking into consideration the oxygen diffusion into the tissue and its consumption at the cells. The results showed that while vascular and tissue oxygenations are deterministically related, the relationship between them is not unequivocal and this could lead to uncertainties when attempting to correlate them. However, theoretical simulation could bridge the gap between the results obtained with various methods.
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| 2. |
- Daşu, Alexandru, et al.
(författare)
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Theoretical simulation of tumour oxygenation--practical applications
- 2006
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Ingår i: Advances in Experimental Medicine and Biology. - : Springer US. - 0065-2598 .- 2214-8019. ; 578, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical simulation of tissue oxygenation is a robust method that can be used to quantify the tissue oxygenation for a variety of applications. However, it is necessary that the relevant input parameters are used for the model describing the tumour microenvironment. The results of the simulations presented in this article suggest that the accuracy of the simulations depends very much on the method of calculation of the effects of the temporal change of the hypoxic pattern due to the opening and the closure of blood vessels. Thus, the use of average oxygenations might lead to dangerous overestimations of the treatment response. This indicates that care should be taken when incorporating hypoxia information into the biological modelling of tumour response.
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| 3. |
- Edlund, Jenny, et al.
(författare)
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Reduced oxygenation in diabetic rat kidneys measured by T2* weighted magnetic resonance micro-imaging
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- By applying invasive techniques for direct measurements of oxygen tension, we have reported decreased kidney oxygenation in experimental diabetes in rats. However, the non-invasive MRI technique utilizing the BOLD effect provides several advantages with the possibility to perform repetitive measurements in the same animals and in human subjects. In this study, we applied a modified single gradient echo micro-imaging sequence to detect the BOLD effect in kidneys of diabetic rats and compared the results to normoglycemic controls. All measurements were performed on inactin-anaesthetized adult male Wistar Furth rats. Diabetes was induced by streptozotocin (45 mg/kg) 14 days prior to MRI-analysis. Sixteen T2*-weighted image records (B0=1.5 T) were performed using radiofrequency spoiled gradient echo sequence with 2.6 ms step increments of TE (TE1=12 ms), while TR (75 ms) and bandwidth per pixel (71.4 Hz) were kept constant. T2* maps were computed by mono-exponential fitting of the pixel intensities. Relaxation rates R2* (1/T2*) in cortex and outer stripe of the outer medulla were similar in both groups (cortex for controls 22.3 +/- 0.4 vs. diabetics 23.1 +/- 1.8 Hz and outer stripe of outer medulla for controls 24.9 +/- 0.4 vs. diabetics 26.4 +/- 1.8 Hz; n=4 in both groups), whereas R2* was increased in the inner stripe of the outer medulla in diabetic rats (diabetics 26.1 +/- 2.4 vs. controls 18.8 +/- 1.4 Hz; n=4, P<0.05). This study demonstrates that experimental diabetes in rats induces decreased oxygenation of the renal outer medulla. Furthermore, the proposed T2*-weighted MR micro-imaging technique is suitable for detection of regional changes in kidney oxygenation in experimental animal models.
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| 4. |
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| 5. |
- Friederich, Malou, 1983-, et al.
(författare)
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Identification and distribution of uncoupling protein isoforms in the normal and diabetic rat kidney
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - New York : Springer. - 0065-2598 .- 2214-8019. - 9780387859972 ; 645, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- Uncoupling protein (UCP)-2 and -3 are ubiquitously expressed throughout the body but there is currently no information regarding the expression and distribution of the different UCP isoforms in the kidney. Due to the known cross-reactivity of the antibodies presently available for detection of UCP-2 and -3 proteins, we measured the mRNA expression of UCP-1, -2 and -3 in the rat kidney in order to detect the kidney-specific UCP isoforms. Thereafter, we determined the intrarenal distribution of the detected UCP isoforms using immunohistochemistry. Thereafter, we compared the protein levels in control and streptozotocin-induced diabetic rats using Western blot. Expressions of the UCP isoforms were also performed in brown adipose tissue and heart as positive controls for UCP-1 and 3, respectively. UCP-2 mRNA was the only isoform detected in the kidney. UCP-2 protein expression in the kidney cortex was localized to proximal tubular cells, but not glomerulus or distal nephron. In the medulla, UCP-2 was localized to cells of the medullary thick ascending loop of Henle, but not to the vasculature or parts of the nephron located in the inner medulla. Western blot showed that diabetic kidneys have about 2.5-fold higher UCP-2 levels compared to controls. In conclusion, UCP-2 is the only isoform detectable in the kidney and UCP-2 protein can be detected in proximal tubular cells and cells of the medullary thick ascending loop of Henle. Furthermore, diabetic rats have increased UCP-2 levels compared to controls, but the mechanisms underlying this increase and its consequences warrants further studies.
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| 6. |
- Friederich, Malou, et al.
(författare)
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Uncoupling protein-2 in diabetic kidneys : increased protein expression correlates to increased non-transport related oxygen consumption
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer Berlin/Heidelberg. - 0065-2598 .- 2214-8019. ; 614, s. 37-43, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic patients have an elevated risk to develop renal dysfunction and it has been postulated that altered energy metabolism is involved. We have previously shown that diabetic rats have markedly decreased oxygen availability in the kidney, resulting from increased oxygen consumption. A substantial part of the increased oxygen consumption is unrelated to tubular transport, suggesting decreased mitochondrial efficiency. In this study, we investigated the protein expression of mitochondrial uncoupling protein (UCP)-2 in kidney tissue from control and streptozotocin (STZ)-induced diabetic rats. Protein levels of UCP-2 were measured in adult male control and STZ-diabetic Wistar Furth as well as Sprague Dawley rats in both the kidney cortex and medulla by Western blot technique. Two weeks of hyperglycemia resulted in increased protein levels of UCP-2 in kidneys from both Wistar Furth and Sprague Dawley rats. Both cortical and medullary UCP-2 levels were elevated 2-3 fold above control levels. We conclude that sustained STZ-induced hyperglycemia increases the kidney levels of mitochondrial UCP-2, which could explain the previously reported increase in non-transport related oxygen consumption in diabetic kidneys. The elevated UCP-2 levels may represent an effort to reduce the increased production of superoxide radicals which is evident during diabetes.
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| 7. |
- Hanson, Lars Åke, 1934, et al.
(författare)
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Immune function
- 2009
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Ingår i: Advances in experimental medicine and biology. - 0065-2598 .- 2214-8019. ; 639, s. 97-111
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Larsson, Lars
(författare)
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Acute Quadriplegic Myopathy : An Acquired "Myosinopathy"
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 642, s. 92-98
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Tidskriftsartikel (refereegranskat)abstract
- Acquired neuromuscular disorders have been shown to be very common in critically ill patients receiving prolonged mechanical ventilation in the intensive care unit (ICU). Acute Quadriplegic Myopathy (AQM) is a specific acquired myopathy in ICU patients. Patients with AQM are characterized by severe muscle weakness and atrophy of spinal nerve innervated limb and trunk muscles, while cranial nerve innervated craniofacial muscles, sensory and cognitive functions are spared or less affected. The muscle weakness is associated with altered muscle membrane properties and a preferential loss of the motor protein myosin and myosin-associated thick filament proteins. Prolonged mechanical ventilation, muscle unloading, postsynaptic block of neuromuscular transmission, sepsis and systemic corticosteroid hormone treatment have been suggested as important triggering factors in AQM. However, the exact mechanisms underlying the loss of thick filament proteins are not known, though enhanced myofibrillar protein degradation in combination with a downregulation of protein synthesis at the transcriptional level play important roles.
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| 9. |
- Lavander, Moa, et al.
(författare)
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Twin arginine translocation in Yersinia
- 2007
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer. - 0065-2598 .- 2214-8019. ; 603, s. 258-267
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria utilise Twin arginine translocation (Tat) to deliver folded proteins across the cytoplasmic membrane. Disruption of Tat typically results in pleiotropic effects on e.g. growth, stress resistance, bacterial membrane biogenesis, motility and cell morphology. Further, Tat is coupled to virulence in a range of pathogenic bacteria, including species of Pseudomonas, Legionella, Agrobacterium and Mycobacterium. We have investigated this, for Yersinia, previously unexplored system, and have shown that the Tat pathway is functional and absolutely required for virulence of Yersinia pseudotuberculosis. A range of putative Yersinia Tat substrates have been predicted in silico, which together with the Tat system itself may be interesting targets for future development of antimicrobial treatments. Here we present a brief review of bacterial Tat and discuss our results concerning this system in Yersinia.
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| 10. |
- Liss, Per, et al.
(författare)
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Iodinated contrast media decrease renomedullary blood flow. A possible cause of contrast media-induced nephropathy
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 213-218
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Tidskriftsartikel (refereegranskat)abstract
- The renal medulla has been implicated as a key target for contrast media-induced nephropathy (CIN). Although the effects of contrast media (CM) on whole kidney blood flow are well characterized, the effect of CM on renal medullary blood flow has been controversial. It has been reported that an extremely high dose of a high osmolar CM (iothalamate; 2900 mg I/kg bw) injected rapidly increased the renal outer medullary blood flow (OMBF). However, more clinical relevant doses consistently result in a sustained decrease in medullary blood flow. Furthermore, simultaneous measurements using both laser-Doppler flowmetry and hydrogen washout yield similar results of a decrease in OMBF after CM administration. CM induced a transient 28% decrease in the laser-Doppler signal from the outer medulla, while the hydrogen washout rate in the same region was reduced by approximately 50%. Furthermore, CM administration consistently results in decreased medullary oxygen tension (PO2). The renal medulla works already during normal physiological conditions at the verge of hypoxia, and the majority of the studies published so far are in agreement with the hypothesis that CIN may have its origin in a further reduction in blood flow and/or oxygen availability of this region of the kidney.
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| 11. |
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| 12. |
- Nordlander, Carola, et al.
(författare)
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Recurrent Chromosome 10 Aberrations and Tp53 Mutations in Rat Endometrial Adenocarcinomas
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer. - 0065-2598 .- 2214-8019. ; 617, s. 519-525
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Tidskriftsartikel (refereegranskat)abstract
- Human genetic heterogeneity and differences in the environment and life style make analysis of complex diseases such as cancer difficult. By using inbred animal strains, the genetic variability can be minimized and the environmental factors can be reasonably controlled. Endometrial adenocarcinoma (EAC) is the most common gynecologic malignancy, ranking fourth in incidence among tumors in women. The inbred BDII rat strain is genetically prone to spontaneously develop hormone-related EAC, and can be used as a tool to investigate and characterize genetic changes in this tumor type. In the present project, BDII females were crossed to males from two nonsusceptible rat strains and F1, F2, and backcross progeny were produced. Genetic and molecular genetic analysis of tumors showed that rat chromosome 10 (RNO10) was frequently involved in genetic changes. Our data indicate that often there was loss of chromosomal material in the proximal to middle part of the chromosome followed by gains in distal RNO10. This suggested that there is a tumor suppressor gene(s) in the proximal to middle part of RNO10 and an oncogene(s) in the distal part of the chromosome with potential significance in EAC development. The Tp53 gene, located at band RNO10q24-q25, was a strong candidate target for the observed aberrations affecting the middle part of the chromosome. However, our Tp53 gene mutation analyses suggested that a second gene situated very close to Tp53 might be the main target for the observed pattern of genetic changes.
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| 13. |
- Nordquist, Lina, 1977-, et al.
(författare)
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Effects of proinsulin C-peptide on oxygen transport, uptake and utilization in insulinopenic diabetic subjects : a review
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - New York : Springer US. - 0065-2598 .- 2214-8019. - 9780387859972 - 9780387859989 ; 645, s. 193-198
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Tidskriftsartikel (refereegranskat)abstract
- Exogenous C-peptide administration has beneficial effects in many of the tissues commonly affected by diabetic complications. Diabetes-induced circulatory impairments such as decreased blood flow are prevented by C-peptide, possibly via Ca2+-mediated effects on nitric oxide release. C-peptide also improves diabetes-induced erythrocyte deformability, which likely improves oxygen availability and uptake in affected tissues. Furthermore, C-peptide prevents diabetic neuropathy via improvements of endoneural blood flow and by preventing axonal swelling. In the kidney, C-peptide normalizes the diabetes-induced increase in oxygen consumption via inhibition of the Na+/K+-ATPase. Surprisingly, C-peptide has also been shown to prevent complications in patients with type II diabetes. Taken together, these results may indicate that C-peptide treatment has the potential to reduce the prevalence of diabetic complications. In this paper, the current knowledge regarding these beneficial effects of C-peptide administered to diabetic subjects will be reviewed briefly.
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| 14. |
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| 15. |
- Palm, Fredrik, et al.
(författare)
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Diabetes-induced decrease in renal oxygen tension : effects of an altered metabolism
- 2006
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Ingår i: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 578, s. 161-166
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Tidskriftsartikel (refereegranskat)abstract
- During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.
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| 16. |
- Palm, Fredrik, et al.
(författare)
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Nitric oxide in the kidney : Direct measurements of bioavailable renal nitric oxide
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. - 9780387717630 ; 599, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Increasing efforts have been directed towards investigating the involvement of nitric oxide (NO) for normal kidney function. Recently, a crucial role of NO in the development of progressive renal dysfunction has been reported during diabetes and hypertension. Indirect estimation of renal NO production include urinary nitrite/nitrate measurements, but there are several disadvantages of indirect methods since production and bioavailability of NO rarely coincide. Thus, direct measurement of in vivo NO bioavailability is preferred, although these methods are more time consuming and require highly specialized equipment and knowledge. This review focuses on two techniques for in vivo measurement of bioavailable NO in the kidney. We have applied Whalen-type recessed NO microsensors for measurement of NO in the kidney cortex, whereas the hemoglobin-trapping technique seems to be more suitable for NO measurement in the renal medulla. Both methods are robust and reliable, and we discuss advantages and shortcomings of each method.
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| 17. |
- Rönnelid, Johan, et al.
(författare)
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Immune complex-mediated cytokine production is regulated by classical complement activation both in vivo and in vitro
- 2008
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Ingår i: Advances in experimental medicine and biology. - New York, NY : Springer US. - 0065-2598 .- 2214-8019. ; 632, s. 187-201, s. 187-201
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Immune complexes (IC) induce a number of cellular functions, including the enhancement of cytokine production from monocytes, macrophages and plasmacytoid dendritic cells. The range and the composition of cytokines induced by IC in vitro is influenced by the availability of an intact classical complement cascade during cell Culture, as we have showed in our studies on artificial IC and on cryoglobulins purified from patients with lymphoproliferative diseases. When IC purified from systemic lupus erythematosus sera were used to stimulate in vitro cytokine production, the amount of circulating IC and IC-induced cytokine levels depended both on in vivo classical complement function as well as on the occurrence of anti-SSA, but not on anti-dsDNA or any other autoantibodies. Collectively these findings illustrate that studies on IC-induced cytokine production in vitro requires stringent cell culture conditions with complete control and definition of access to an intact classical complement pathway in the cell cultures. If IC are formed in vivo, the results have to be interpreted in the context of classical complement activation in vivo as well as the occurrence of IC-associated autoantibodies at the time of serum sampling.
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| 18. |
- Samuelson, Emma, et al.
(författare)
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Amplification Studies of MET and Cdk6 in a Rat Endometrial Tumor Model and Their Correlation to Human Type I Endometrial Carcinoma Tumors
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer. - 0065-2598 .- 2214-8019. ; 617, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is known to be a genetic disease that is both polygenic and heterogeneous, in most cases involving changes in several genes in a stepwise fashion. The spectrum of individual genes involved in the initiation and progression of cancer is greatly influenced by genetic factors unique to each patient. A study of complex diseases such as cancer is complicated by the genetic heterogeneous background and environmental factors in the human population. Endometrial cancer (EC) is ranked fourth among invasive tumors in women. In Sweden, approximately 1300 women (27/100,000 women) are diagnosed annually. To be able to study the genetic alterations in cancer, the use of an animal model is very convenient. Females of the BDII strain are genetically predisposed to EC and 90% of female BDII rats develop EC during their lifetime. Thus, BDII rats have been used to model human EC with respect to the genetics of susceptibility and of tumor development. A set of rat EC tumors was analyzed using conventional cytogenetics and comparative genome hybridization (CGH). Chromosomal aberrations, i.e., gains, were found on rat chromosome 4 (RNO4). Using FISH analysis, we concluded that the Met oncogene and Cdk6 (cyclin-dependent kinase 6) were amplified in this set of EC tumors. The data from this investigation were used to analyze a set of human endometrial tumors for amplification of Cdk6 and Met. Our preliminary data are indicative for a good correlation between our findings in the BDII rat model for EAC and the situation in human EC. These data provide strong support for the use of animal model systems for better understanding and scrutinizing of human complex disease of cancer.
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| 19. |
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| 20. |
- Toma-Dasu, Iuliana, et al.
(författare)
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Quantifying tumour hypoxia by PET imaging : a theoretical analysis
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- Information on tumour oxygenation could be obtained from various imaging methods, but the success of incorporating it into treatment planning depends on the accuracy of quantifying it. This study presents a theoretical analysis of the efficiency of measuring tumour hypoxia by PET imaging. Tissue oxygenations were calculated for ranges of biologically relevant physiological parameters and were then used to simulate PET images for markers with different uptake characteristics. The resulting images were used to calculate dose distributions that could lead to predefined tumour control levels. The results have shown that quantification of tumour hypoxia with PET may lead to different values according to the tracer used and the tumour site investigated. This would in turn be reflected into the dose distributions recommended by the optimisation algorithms. However, irrespective of marker-specific differences, focusing the radiation dose to the hypoxic areas appears to reduce the average tumour dose needed to achieve a certain control level.
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| 21. |
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| 22. |
- Toma-Dasu, Iuliana, et al.
(författare)
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Theoretical simulation of tumour hypoxia measurements
- 2006
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Ingår i: Advances in Experimental Medicine and Biology. - : Springer US. - 0065-2598 .- 2214-8019. ; 578, s. 369-374
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Tidskriftsartikel (refereegranskat)abstract
- Our simulations suggested that measurements performed in a limited number of points in the tumour can be representative for the situation in the whole tumour. It has further been shown that the polarographic electrode cannot be used to measure small regions of hypoxia. In fact it has been suggested that the most important factor that determines the efficiency of the polarographic electrode is the spatial distribution of the hypoxic cells and not their type, and therefore the polarographic electrode cannot be used to make the distinction between acute and chronic hypoxia. The simulations have also shown that it is reasonable to assume that the electrode measurement can be correlated to the situation in the whole tissue, even though the correlation is only qualitative. And because the electrode measurements are greatly influenced by the averaging process, the quantitative use of the electrode measurements may lead to erroneous results, especially for modelling the treatment response.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Hallgren, Oskar, et al.
(författare)
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Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).
- 2008
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer New York. - 0065-2598. ; 606, s. 217-240
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Forskningsöversikt (refereegranskat)abstract
- HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.
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| 30. |
- Hammarstrom, L, et al.
(författare)
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Targeted antibodies in dairy-based products
- 2008
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Ingår i: Advances in experimental medicine and biology. - New York, NY : Springer New York. - 0065-2598. ; 606, s. 321-343
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Tidskriftsartikel (refereegranskat)
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| 31. |
- Hanson, Lars Åke, 1934
(författare)
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Macy-György Prize Lecture: My milky way
- 2009
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Ingår i: Advances in experimental medicine and biology. - Dordrecht : Springer Netherlands. - 0065-2598. ; 639, s. 283-90
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 32. |
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| 33. |
- Holmquist Mengelbier, Linda, et al.
(författare)
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Effect of hypoxia on the tumor phenotype: the neuroblastoma and breast cancer models
- 2006
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Ingår i: Advances in experimental medicine and biology. - 0065-2598. ; 587, s. 179-193
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Konferensbidrag (refereegranskat)abstract
- The tumor oxygenation status associates with aggressive behavior. Oxygen shortage, hypoxia, is a major driving force behind tumor vascularization, and hypoxia enhances mutational rate, metastatic spread, and resistance to radiation and chemotherapy. We recently discovered that hypoxia promotes dedifferentiation of neuroblastoma and breast carcinoma cells and development of stem cell-like features. In both these tumor forms there is a correlation between low differentiation stage and poor outcome, and we conclude that the dedifferentiating effect of lowered oxygen adds to the aggressive phenotype induced by hypoxia. With neuroblastoma and breast carcinoma as human tumor model systems, we have addressed questions related to hypoxia-induced molecular mechanisms governing malignant behavior of tumor cells, with emphasis on differentiation and growth control. By global gene expression analyses we are currently screening for gene products exclusively expressed or modified in hypoxic cells with the aim to use them as targets for treatment.
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| 34. |
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| 35. |
- Lundstig, Annika, et al.
(författare)
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Serological diagnosis of human polyomavirus infection
- 2006
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Ingår i: Polyomaviruses and human diseases. - New York, NY : Springer New York. - 0387292330 ; 577, s. 96-101
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Measurement of antibody titres to the human polyomaviruses BK and JC has for many years had to rely on Hemagglutination inhibition. In recent years, viral serology based on virus-like particles (VLPs) in enzyme immunoassays (EIAs) has become widely used for a variety of viruses. We sought to establish a modern method for serological diagnosis of BK and JC viruses, by using purified VLPs containing the VP1 major capsid proteins. Antibody titres in assays based on VLPs of BKV (strain SB) showed no correlation to the titres in similar JCV assays. BKV (SB) seropositivity increases rapidly with increasing age of the children and reaches a 98 % seroprevalence at 7–9 years of age, whereas JCV seroprevalences increase more slowly with increasing age reaching 51% positivity among children 9–11 years of age. The antibody levels are almost identical in serial samples taken up to 5 years apart, suggesting that both BKV and JCV VLP seropositivitities are usually stable over time and can be used to measure cumulative exposure to these viruses. Serology using SV40 VLPs showed strong cross-reactivity with human polyomaviruses, in particular with BKV strain AS, and establishing a specific VLP-based serology assay for SV40 required blocking with several hyperimmune sera to the human polyomaviruses. SV40-specific seropositivity also increased with increasing age of children, reaching 14% seroprevalence among children 7–9 years of age, but had limited stability over time in serial samples.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Przyrembel, Hildegard, et al.
(författare)
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From innovation to implementation.
- 2005
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Ingår i: Adv Exp Med Biol. - 0065-2598. ; 569, s. 49-53
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Requirements for the safety and nutritional adequacy of infant formula are set by legislation and aim for the best possible substitute for human milk with regard to growth, development and biological effects. This is, however, a continuous process and has to be supported by science-driven innovative activities of manufacturers and be confirmed by adequate clinical studies performed according to agreed standards.
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| 42. |
- Ringborg, U
(författare)
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Harmonizing cancer control in Europe
- 2006
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Ingår i: Advances in experimental medicine and biology. - Dordrecht : Springer Netherlands. - 0065-2598. ; 587, s. 87-93
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Tidskriftsartikel (refereegranskat)
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| 43. |
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| 44. |
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| 45. |
- Tivesten, Åsa, 1969, et al.
(författare)
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Cardiovascular and respiratory systems.
- 2005
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Ingår i: Advances in experimental medicine and biology. - 0065-2598. ; 567, s. 149-66
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Forskningsöversikt (refereegranskat)
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