| 1. |
- Leusen, JHW, et al.
(författare)
-
Disturbed interaction of p21-rac with mutated p67-phox causes chronic granulomatous disease
- 1996
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 184:4, s. 1243-1249
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic granulomatous disease (CGD) is characterized by the failure of phagocytic leukocytes to generate superoxide, needed for the intracellular killing of microorganisms. This is caused by mutations in any one of the four subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In a rare, autosomal recessive form of CGD, a 67-kD cytosolic component of this enzyme (p67-phox) is missing. We here report on a patient with a mutation in the p67-phox gene that leads to expression of a nonfunctional p67-phox protein. The purified granulocytes of this patient failed to produce superoxide and contained about half of the normal amount of p67-phox. Analysis of the cDNA and genomic DNA of this patient showed that the patient is a compound heterozygote for a triplet nucleotide deletion in the p67-phox gene, predicting an in-frame deletion of lysine 58 in the p67-phox protein and a larger deletion of 11-13 kb in the other allele. Interestingly, the 58Lys deletion in p67-phox disrupts the interaction with p21-rac1, a ras-related protein involved in the activation of the NADPH oxidase. In contrast to normal neutrophils, in which p47-phox and p67-phox translocate to the plasma membrane upon cell activation, the cells of the patient did not show this translocation, indicating that an interaction between p67-phox and p21-rac1 is essential for translocation of these cytosolic proteins and activation of the NADPH oxidase. Moreover, this CGD patient represents the first case of disease caused by a disturbed binding of a ras-related protein to its target protein.
|
|
| 2. |
- Roos, Ewa M., et al.
(författare)
-
Knee Injury and Osteoarthritis Outcome Score (KOOS) - Development of a self-administered outcome measure
- 1998
-
Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - 0190-6011. ; 28:2, s. 88-96
-
Tidskriftsartikel (refereegranskat)abstract
- There is broad consensus that good outcome measures are needed to distinguish interventions that are effective from those that are not. This task requires standardized, patient-centered measures that can be administered at a low cost. We developed a questionnaire to assess short- and long-term patient-relevant outcomes following knee injury, based on the WOMAC Osteoarthritis Index, a literature review, an expert panel, and a pilot study. The Knee Injury and Osteoarthritis Outcome Score (KOOS) is self- administered and assesses five outcomes: pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life. In this clinical study, the KOOS proved reliable, responsive to surgery and physical therapy, and valid for patients undergoing anterior cruciate ligament reconstruction. The KOOS meets basic criteria of outcome measures and can be used to evaluate the course of knee injury and treatment outcome.
|
|
| 3. |
|
|
| 4. |
- Blom, M., et al.
(författare)
-
Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2
- 1998
-
Ingår i: Blood. - 1528-0020. ; 91:8, s. 3037-3043
-
Tidskriftsartikel (refereegranskat)abstract
- Human eosinophils perform several functions dependent on phospholipase A2 (PLA2) activity, most notably the synthesis of platelet-activating factor (PAF) and leukotriene C4 (LTC4). Several forms of PLA2 have been identified in mammalian cells. In the present study, the 14-kD, secretory form of PLA2 was detected in human eosinophils by immunocytochemical staining with the specific monoclonal antibody (MoAb) 4A1. In contrast, preparations of neutrophils, monocytes, lymphocytes, and basophils did not show detectable staining. With two MoAbs in a sandwich enzyme-linked immunosorbent assay (ELISA), large amounts of sPLA2 were detected in lysates of eosinophils, that were 20-fold to 100-fold higher than in the other circulating leukocytes (ie, neutrophils, basophils, monocytes, and lymphocytes). In addition, with a commercially available sPLA2 activity assay kit, we were able to show high activity of sPLA2 in human eosinophils relative to neutrophils. Investigations at the ultrastructural level showed that sPLA2 in eosinophils is mainly located in specific granules. Immunoelectron microscopy also visualized sPLA2 within phagosomes after addition of opsonized particles to the eosinophils. However, sPLA2 was not detected in the cell-free supernatants of activated eosinophils, in contrast to eosinophil-cationic protein (ECP), which colocalizes with sPLA2 in resting eosinophils. These findings warrant further studies into the role of sPLA2 in eosinophil function.
|
|
| 5. |
- Li, Aihong, et al.
(författare)
-
Clonal rearrangements in childhood and adult precursor B acute lymphoblastic leukemia : a comparative polymerase chain reaction study using multiple sets of primers.
- 1999
-
Ingår i: European Journal of Haematology. - 0902-4441 .- 1600-0609. ; 63:4, s. 211-8
-
Tidskriftsartikel (refereegranskat)abstract
- Ig heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements were investigated by polymerase chain reaction (PCR) amplification of diagnostic tumour samples from 91 patients (57 children and 34 adults, with cut-off at age 16) with precursor B acute lymphoblastic leukemia (ALL). Using primers directed to the framework regions (FR) 1, 2 and 3 of the IgH gene, clonal IgH rearrangements were observed in 82, 58 and 58%, respectively, whereas clonality was presented in 45 and 27% using primers hybridising to the TCR delta and gamma genes. A combination of all five primer sets used resulted in 96% positive cases (children 100%, adults 88%). The frequency of clonal IgH rearrangements correlated to patient age with a significantly lower fraction of positive cases in the adult group. The concomitant usage of more than one V(H) family gene was similar for childhood and adult ALL, and an over-representation of V(H)6 rearrangements was found in childhood ALL. Twenty-five out of 91 cases (27%) displayed an oligoclonal pattern for either IgH or TCR gene rearrangements (children 37%, adults 12%). A comparative analysis of samples from different compartments was performed in 23 patients, and differences between two or three compartments were observed in seven cases. Unexpectedly large, clonally appearing PCR products of 540-715 bp were found in three leukemias and sequence analysis verified their clonal nature. In summary, using multiple sets of primers clonal rearrangements of IgH and TCR genes can be detected in a very high frequency, including previously neglected large size PCR products. A common heterogeneity was demonstrated in different compartments reflecting ongoing clonal evolution, which can make detection of minimal residual disease (MRD) in ALL troublesome. Therefore, we suggest that a minimum of three targets should be used to minimise false-negative results.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Roos, Johan, et al.
(författare)
-
From Fitness Landscapes to Knowledge Landscapes
- 1999
-
Ingår i: Systemic Practice and Action Research. - 1094-429X .- 1573-9295. ; 12:3, s. 279-293
-
Tidskriftsartikel (refereegranskat)abstract
- Based on the complexity theory concept of fitness landscapes, this article develops and discusses the concept of "knowledge landscapes." A knowledge landscape is a metaphor describing the ever-changing potential knowledge peaks and valleys that surround each one of us. Individuals, communities, and organizations move on their own knowledge landscapes by simultaneously climbing local peaks and exploring other visible peaks. The higher one climbs, the harder it is to climb still higher. Our ability to climb is also limited by our identity, who we are, which on an organizational level is linked to the tightness of organizational interconnectedness. Coevolutionary struggles between individuals and organizations can lead us to climb potential knowledge peaks faster. Moreover, our knowledge landscapes exist on many levels of scale, meaning that what appears to be one peak is actually a series of subpeaks on a smaller level of scale.
|
|
| 10. |
|
|
