| 1. |
- Eriksson, Peter S, 1959, et al.
(författare)
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Neurogenesis in the adult human hippocampus
- 1998
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Ingår i: Nat Med. - 1078-8956. ; 4:11, s. 1313-7
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Tidskriftsartikel (refereegranskat)abstract
- The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.
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| 4. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The immunohistochemical expression of DNA-PKCS and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity
- 1999
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Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 45:4, s. 1005-10
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The DNA-PK complex is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. This study evaluated the relationship between the immunohistochemical expression of the individual components of DNA-PK and cellular radiosensitivity in head and neck cancers. METHODS AND MATERIALS: Biopsies from patients with previously untreated squamous cell carcinomas of the head and neck were assessed for inherent tumor radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft agar clonogenic assay. Paraffin-embedded tumor material from 64 successfully grown specimens was immunohistochemically stained for expression of DNA-PKcs and Ku (p70/p80). The same tumor material was previously analyzed for the immunohistochemical expression of p53. RESULTS: A significant correlation was found between the degree of expression of DNA-PKcs and Ku (p70/p80) (r = 0.55, p<0.001). There were no overall significant differences in the levels of expression of DNA-PKcs and Ku (p70/p80) in tumors from patients of either sex, different sites, histologies, and stages. No relationship was found between SF2 and the expression of either DNA-PKcs (r = 0.22, p = 0.081) or Ku (p70/p80) (r = 0.064, p = 0.62). Comparison with previous immunohistochemical characterization showed no significant correlations between the expression levels of p53 and either DNA-PKcs (r = 0.093, p = 0.46) or Ku (p70/p80) (r = -0.17, p = 0.17). CONCLUSIONS: This study suggests that determining the immunohistochemical expression of DNA-PK in head and neck cancers from multiple sites does not have a role as a predictive assay of tumor in vitro radiosensitivity.
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| 5. |
- Björk, Thomas, et al.
(författare)
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The prognostic value of different forms of prostate specific antigen and their ratios in patients with prostate cancer
- 1999
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 84:9, s. 1021-1027
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the prognostic value for patient survival of different forms of PSA and ratios thereof, before treatment for prostate cancer, by considering the forms and ratios both as independent markers and by comparing them with other commonly used prognostic markers, e.g. tumour grade, local stage (T-stage) and absence or presence of skeletal metastases (M-stage). PATIENTS AND METHODS: Blood samples were collected consecutively from men diagnosed with prostate cancer at our department in 1988. From this group, 66 men were followed until death, or for >/=9 years. Twenty-five patients died from their prostate cancer and 21 from other causes during the follow-up period. Forty-eight patients received hormonal treatment, whereas 18 remained untreated or received no treatment for their cancer before they died from other causes. Assays measuring the serum levels of free prostate specific antigen (fPSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT), and total PSA (tPSA) were used to calculate the percentage of free to total PSA (f/tPSA) fPSA/ACT and ACT/tPSA at diagnosis. Based on the initial levels or ratios of the PSA forms, the patients were divided into three numerically comparable groups (tertiles) for survival analysis. Prognostic factors predicting patient survival were evaluated using univariate (Kaplan-Meier life-tables with the log-rank test) and multivariate techniques (Cox proportional hazards regression model). RESULTS: Univariate analysis using the log-rank test showed that the serum level of each molecular form of PSA, i.e. tPSA (P=0.001), PSA-ACT (P<0.001) and fPSA (P<0.001), as well as grade (P<0.001), T-stage (P=0.00355) and M-stage (P<0.001), provided statistically significant prognostic information. Log-rank tests showed that none of the ratios, i.e. f/tPSA, fPSA/ACT and ACT/tPSA, were informative of prognosis (P>0.05). However, in a multivariate analysis regression model, not only M-stage (risk ratio 4.2; P=0. 026) and grade (risk ratio 2.6; P=0.022), but also f/tPSA (risk ratio 1.8; P=0.037), provided significant prognostic information. CONCLUSION: The values of tPSA, fPSA and PSA-ACT, as well as grade and T- and M-stage, are all independent prognostic factors of prostate cancer survival. In a multivariate analysis, not only M-stage and grade but also f/tPSA provided significant prognostic information.
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| 6. |
- Estrada, S, et al.
(författare)
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The contribution of N-terminal region residues of cystatin A (stefin A) to the affinity and kinetics of inhibition of papain, cathepsin B, and cathepsin L.
- 1999
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 38:22, s. 7339-45
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Tidskriftsartikel (refereegranskat)abstract
- The affinity and kinetics of binding of three N-terminally truncated variants of the cysteine proteinase inhibitor cystatin A to cysteine proteinases were characterized. Deletion of Met-1 only minimally altered the inhibitory properties of the protein. However, deletion also of Ile-2 resulted in reduced affinities of 900-, >/=3-, and 200-fold for papain and cathepsins L and B, respectively. Further truncation of Pro-3 substantially increased the inhibition constants to approximately 0.5 microM for papain and cathepsin L and to 60 microM for cathepsin B, reflecting additionally 2 x 10(3)-, 2 x 10(4)-, and 400-fold decreased affinities, respectively. The reductions in affinity shown by the latter mutant indicate that the N-terminal region contributes about 40% of the total free energy of binding of cystatin A to cysteine proteinases. Moreover, Pro-3 and to a lesser extent Ile-2 are the residues responsible for this binding energy. The reduced affinities for papain and cathepsin L were due only to higher dissociation rate constants, whereas both lower association and higher dissociation rate constants contributed to the decreased affinity for cathepsin B. These differential effects indicate that the N-terminal portion of cystatin A primarily functions by stabilizing the complexes with enzymes having easily accessible active-site clefts, e.g., papain and cathepsin L. In contrast, the N-terminal region is required also for an initial binding of cystatin A to cathepsin B, presumably by promoting the displacement of the occluding loop and allowing facile interaction of the rest of the inhibiting wedge with the active-site cleft of the enzyme.
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| 7. |
- Granlund, Thomas, et al.
(författare)
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A polythiophene microcavity laser
- 1998
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Ingår i: Chemical Physics Letters. - : Elsevier. - 0009-2614 .- 1873-4448. ; 288:5-6, s. 879-884
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Tidskriftsartikel (refereegranskat)abstract
- We report photopumped lasing in a microcavity device with a polythiophene layer as the emitter. These microcavity devices are built by joining two polymer coated dielectric mirrors at elevated temperature. When photopumping the film, a lasing threshold is observed at 120 nJ/cm(2). Comparative studies with fast pump-probe spectroscopy of thin polythiophene films and the same polymer in photopumped lasing studies, indicate that the gain coefficient is 80 +/- 20 cm(-1), and that the exciton concentration is 2 X 10(17) cm(-3) at the lasing transition, well below the exciton-exciton recombination level. (C) 1998 Elsevier Science B.V. All rights reserved.
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| 8. |
- Granlund, Thomas, et al.
(författare)
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Lasing in substituted polythiophene between dielectric mirrors
- 1999
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Ingår i: Synthetic metals. - : Elsevier. - 0379-6779 .- 1879-3290. ; 102:1-3, s. 1038-1041
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Tidskriftsartikel (refereegranskat)abstract
- We report photopumped lasing in a microcavity device with a polythiophene layer as emitter. The microcavity is made of a polymer film between two dielectric Bragg reflecting mirrors (DBR). The:microcavity devices is built by joining two polymer coated DBR mirrors at elevated temperature. When photopumping the film,a lasing threshold is observed at 120 nJ/cm(2). Comparative studies with fast pump-probe spectroscopy of thin polythiophene films, and the same polymer in photopumped lasing studies, indicate that the gain coefficient is 80 +/- 20 cm(2) and that the exciton concentration is 2X10(17) cm(2) at the lasing transition, well below the exciton-exciton recombination level.
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| 9. |
- Lilja, Hans, et al.
(författare)
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Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy
- 1999
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Ingår i: Journal of Urology. - 1527-3792. ; 162:6, s. 2029-2035
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We studied plasma concentrations and elimination rates of prostate specific antigen (PSA) complexed to alpha1-antichymotrypsin and alpha2-macroglobulin, free PSA, total PSA (free PSA plus PSA alpha1-antichymotrypsin) and human glandular kallikrein 2 before, during and after radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: Plasma was collected and frozen within 10 minutes after sampling from 18 patients undergoing radical retropubic prostatectomy for prostate cancer. One sample was drawn preoperatively. Subsequent sampling intervals were 5 to 20 minutes perioperatively, 2 to 4 hours during the first 12 postoperative hours and 24 to 48 hours until postoperative day 14. Free PSA, PSA alpha1-antichymotrypsin, total PSA, PSA alpha2-macroglobulin and human glandular kallikrein 2 were measured with time resolved immunofluorometric assays. RESULTS: Preoperatively PSA alpha2-macroglobulin was undetectable (less than 2 ng./ml.) in 17 of 18 patients. Human glandular kallikrein 2, free PSA and total PSA but not PSA alpha1-antichymotrypsin were significantly higher in patients with extraprostatic cancer (pT3a-pT4a, pN1) compared to those with organ confined cancer (pT2a/b). Surgical manipulation of the prostate caused no detectable elevation of human glandular kallikrein 2, PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. In contrast, a mean 9.6-fold increase (range 3.4 to 22) in free PSA was noted 5 minutes after prostatectomy. Free PSA was eliminated from plasma in a biphasic exponential pattern with an early plasma half-life of 55 minutes and a late plasma half-life of 18 hours. PSA alpha1-antichymotrypsin decreased slowly, whereas human glandular kallikrein 2 was detectable only 12 hours after prostatectomy. PSA alpha2-macroglobulin remained at insignificant, nondetectable concentrations during the entire perioperative and postoperative period. CONCLUSIONS: Release of free PSA contributes to the elevation of plasma total PSA after prostatectomy. Free PSA is enzymatically inactive as the release does not result in subsequent elevation of PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. Biphasic exponential elimination of free PSA may be explained by rapid extracellular redistribution (early half-life) and glomerular filtration in the kidneys (late half-life). Our data suggest rapid metabolism of human glandular kallikrein 2 but do not support suggestions of the significance in vivo of complex formations with alpha2-macroglobulin as a major means to eliminate PSA from plasma in patients with clinically localized prostate cancer.
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| 10. |
- Nordgren, Bengt, et al.
(författare)
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Postpolio muscular dysfunction : relationships between muscle energy metabolism, subjective symptoms, magnetic resonance imaging, electromyography, and muscle strength
- 1997
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Ingår i: Muscle and Nerve. - 0148-639X .- 1097-4598. ; 20:11, s. 1341-1351
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Tidskriftsartikel (refereegranskat)abstract
- Eleven patients with previous polio were studied. The concentration of energy-related metabolites and energy charge was measured from the vastus lateralis muscle, as was isometric muscle strength of knee extension. Cross-sectional area of the quadriceps femoris muscle was calculated from magnetic resonance imaging. Reinnervation was studied using macroelectromyography. Muscle weakness, pain, and newly acquired muscle weakness in the legs was estimated by the patients. The findings in the legs in which the patients experienced new loss of muscle function were compared with the stable legs. There were no significant differences between these groups in any of the objectively measured variables. Only hip pain correlated with new loss of muscle function. Creatine phosphate was decreased in 5 patients. The symptoms and subjective muscle strength did not correlate with any of the objective measurements. There were no significant relationships between energy-related metabolites and postpolio symptoms.
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