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Biomedical subjects

S Ohlsson

Publications and source records attributed to S Ohlsson.

18 recordsLinked to original sources
PubMed2005

Increased monocyte transcription of the proteinase 3 gene in small vessel vasculitis.

Proteinase 3 (PR3) is a pleiotropic and destructive serine protease and it is also a major target for autoantibodies in systemic small vessel vasculitis. We have shown recently that patients in stable remission have increased circulating levels of PR3, independent of autoantibody titre, inflammation, neutrophil degranulation and renal function. Here we explore the possibility of increased PR3 gene transcription. RNA was purified from peripheral blood monocytes from vasculitis patients and controls. Specific mRNA was measured by TaqMan real-time polymerase chain reaction (PCR). The monocyte-like cell lines THP-1 and U937 and human peripheral blod monocytes from healthy controls were stimulated with cytokines and lipopolysaccharide (LPS) for different time periods. PR3 protein was measured in plasma with enzyme-linked immunosorbent assay (ELISA). The median result for PR3 mRNA was 9.6 (1.8-680) for 22 patients, compared to 1 (0.1-2.8) for the 15 healthy controls. Elastase expression was also significantly increased, whereas myeloperoxidase and interleukin-8 were not. Stimulation of monocytes with tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma or LPS did not result in any increase of PR3 or elastase transcription, whereas interleukin (IL)-8 transcription was increased 10-fold. Circulating monocytes from patients with systemic vasculitis display increased PR3 gene transcription compared to healthy controls and patients with sytemic lupus erythematosus (SLE). This may be important for the development of vasculitis. Our results do not favour a role for cytokines, antineutrophil cytoplasmic antibodies (ANCA) or immunosuppressive medication in the upregulation of PR3 transcription in vasculitis.

Adult↗
PubMed2003

Increased expression of the secretory leukocyte proteinase inhibitor in Wegener's granulomatosis.

The secretory leucocyte proteinase inhibitor (SLPI) is a low molecular weight, tissue-specific inhibitor of proteases, such as elastase and cathepsin G. It is the major local protease inhibitor in the upper airways. Proteinase 3, the main autoantigen in Wegener's granulomatosis (WG), can degrade SLPI proteolytically. In addition, SLPI is sensitive to oxidative inactivation by myeloperoxidase-generated free oxygen radicals. SLPI also has an antimicrobial capacity that can be of interest, as infection is considered to play a role in the pathogenesis of WG. This study focuses on SLPI expression in patients suffering from WG, something that to our knowledge has not been explored hitherto. Serum samples and nasal biopsies were obtained from 12 Swedish WG patients, while buffy coats were obtained from 33 American WG patients. SLPI levels in serum were measured by means of ELISA and the protein was detected by means of immunohistochemistry in nasal biopsies. mRNA expression was studied by means of in situ hybridization on nasal biopsies and RT-PCR on leucocytes. IL-6 or ESR were measured as markers of inflammatory activity. Cystatin C or creatinine was measured as a marker of renal filtration. White blood cell counts were registered. In serum, we found close to normal SLPI levels, without any correlation to IL-6. Two patients had greatly elevated values, both of them suffering from severe renal engagement. Strong SLPI mRNA expression was found in nasal biopsies. RT-PCR on leucocyte mRNA showed normal or greatly elevated expression of SLPI mRNA, correlating with disease activity. Leukocyte SLPI expression seems to be up-regulated in active WG. Serum levels were measured in a small number of patients and were found to be close to normal. Lack of correlation to the acute phase response indicates a specific regulation. This might be linked to an altered protease/antiprotease balance. These findings could indicate that SLPI locally participates in the anti-inflammatory and perhaps antimicrobial response in WG.

Analysis of Variance↗
PubMed2003

Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission.

In systemic small vessel vasculitides, patients form autoantibodies against neutrophil granular proteins, anti-neutrophilic cytoplasmic autoantibodies (ANCA). Some correlation is seen between ANCA titre and disease activity, but whether this is cause or effect is still unknown. It has been reported that levels of proteinase 3 (PR3), one of the main ANCA antigens, are increased in patients with active disease. An increased level of circulating antigen could mean a predisposition to autoimmunity. In order to explore this we measured PR3 levels in patients with stable disease. In addition we measured neutrophil gelatinase-associated lipocalin (NGAL) as a specific marker of neutrophil degranulation, cystatin C as a marker of renal function as well as C-reactive protein (CRP), IL-6 and sTNFr1 as markers of inflammation. PR3, NGAL, IL-6 and sTNFr1 were measured in plasma by the ELISA technique. In the PR3 ELISA, we used anti-PR3 monoclonal antibodies as capture-antibodies and affinity-purified rabbit-anti-PR3 antibodies for detection. PR3-ANCA, myeloperoxidase (MPO)-ANCA, CRP and cystatin C were measured by routine methods. PR3 was significantly raised (P < 0.0001) in vasculitis patients (median 560 micro g/l, range 110-3,940, n = 59) compared with healthy blood donors (350 micro g/l, 110-580, n = 30) as well as disease controls (360, 110-580, n = 46). No correlation was seen with disease activity, inflammation or renal function. The raised NGAL levels correlated strongly with decreased renal function (r = 0.8, P < 0.001). After correcting for this, slightly increased levels (110, 42-340, n = 59) were observed compared with healthy blood donors (81, 38-130, n = 25), but not compared with the disease controls (120, 57-260, n = 48). In the disease controls, there was a significant correlation between NGAL and proteinase 3 (r = 0.3, p < 0.05), but this was not the case in the vasculitis patients. Whether patients had PR3-ANCA or MPO-ANCA was of no significance. In our measurements, we found significantly raised levels of PR3 in plasma from patients with small vessel vasculitis, regardless of ANCA specificity. This was not due to decreased renal function, ongoing inflammation or neutrophil activation. Plausible mechanisms for this include defects in the reticuloendothelial system, genetic factors and selective neutrophil degranulation or leakage.

Adult↗
PubMed2001

Novel distribution of the secretory leucocyte proteinase inhibitor in kidney.

The secretory leucocyte proteinase inhibitor (SLPI) is a low molecular weight, tissue-specific inhibitor of, for example, elastase and cathepsin G, which also have antimicrobial capacity. SLPI has been localised to the respiratory, gastrointestinal and genital tracts, but so far not to the kidney. The presence of SLPI in renal tubuli cells was demonstrated using immunohistochemistry and, by means of in situ hybridisation on human renal biopsies, we were able to demonstrate SLPI production. In various inflammatory conditions in the kidneys, the protease-antiprotease balance is disturbed. For this reason, as well as the possible role in the defence against ascending urinary tract infections, it is interesting to establish a source of SLPI in renal tubuli cells.

Biopsy↗
PubMed2001

An eye movement study of insight problem solving.

The representational change theory of insight claims that insight problems cause impasses because they mislead problem solvers into constructing inappropriate initial representations. Insight is attained when the initial representation is changed. In the present study (N = 24), we tested three specific implications of these hypotheses against eye movements recorded while participants solved matchstick arithmetic problems. The results were consistent with the predictions, providing converging evidence with prior findings using solution rates and solution times. Alternative theories of insight can explain individual findings, but only the representational change theory accounts for both the performance data and the eye movement data. The present study also suggests that eye movement recordings provide an important new window into processes of insight problem solving.

Adult↗
PubMed2000

Computational predictions of binding affinities to dihydrofolate reductase: synthesis and biological evaluation of methotrexate analogues.

The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase, and a reference ester (more structurally related to methotrexate) were synthesized. As deduced from the measured IC(50) values, the calculated ranking of the ligands was correct although a greater difference in affinity was indicated by the experimental measurements. Among the new antifolates the most potent inhibitor exhibited a similar pharmacokinetic profile to methotrexate but lacked activity in a complex antiarthritic model in rat in vivo.

Animals↗
PubMed1998

Persistent B19 parvovirus infection in pediatric malignancies.

BACKGROUND AND PROCEDURE: The frequency and clinical importance of parvovirus B19 infection were studied in children investigated or treated for various malignancies and cytopenias. RESULTS: B19 infection was thus demonstrated in six out of 53 unselected children with malignancies by bone marrow examination, using the B19, DNA-specific, polymerase chain reaction (PCR). Examinations using the PCR in serum samples were equally or less sensitive than in bone marrow samples. One of the children had a persistent B19 infection during maintenance therapy for acute lymphoblastic leukemia. She developed a prolonged and severe cytopenia, and the clinical signs included facial rash, chills, high undulating fever, and pharyngitis. She also seroconverted and became B19 IgM-antibody positive during the study period. CONCLUSIONS: Parvovirus B19 infection was detected in 10% of the children and was either asymptomatic or was associated with severe and prolonged cytopenia. Bone marrow examinations are recommended for the detection of B19 DNA in immunosuppressed children.

Adolescent↗
PubMed1997

Distribution of the secretory leucocyte proteinase inhibitor in human articular cartilage.

The secretory leucocyte protease inhibitor, SLPI, is a low molecular weight inhibitor of proteases such as elastase and cathepsin G, which are released from leucocytes during phagocytosis. The purpose of this study was to show whether or not SLPI is produced in articular chondrocytes. In articular disorders, the protease-antiprotease balance is disturbed. For this reason it would be interesting to establish the source of SLPI. The presence of SLPI was demonstrated using immunohistochemistry and in situ hybridization, hence we conclude that SLPI is produced in the chondrocytes of human articular cartilage.

Arthroplasty, Replacement, Hip↗
PubMed1995

An intelligent interactive system for delivering individualized information to patients.

This paper is a report on the first phase of a long-term, interdisciplinary project whose goal is to increase the overall effectiveness of physicians' time, and thus the quality of health care, by improving the information exchange between physicians and patients in clinical settings. We are focusing on patients with long-term and chronic conditions, initially on migraine patients, who require periodic interaction with their physicians for effective management of their condition. We are using medical informatics to focus on the information needs of patients, as well as of physicians, and to address problems of information exchange. This requires understanding patients' concerns to design an appropriate system, and using state-of-the-art artificial intelligence techniques to build an interactive explanation system. In contrast to many other knowledge-based systems, our system's design is based on empirical data on actual information needs. We used ethnographic techniques to observe explanations actually given in clinic settings, and to conduct interviews with migraine sufferers and physicians. Our system has an extensive knowledge base that contains both general medical terminology and specific knowledge about migraine, such as common trigger factors and symptoms of migraine, the common therapies, and the most common effects and side effects of those therapies. The system consists of two main components: (a) an interactive history-taking module that collects information from patients prior to each visit, builds a patient model, and summarizes the patients' status for their physicians; and (b) an intelligent explanation module that produces an interactive information sheet containing explanations in everyday language that are tailored to individual patients, and responds intelligently to follow-up questions about topics covered in the information sheet.

Anthropology, Cultural↗
PubMed1992

Involving patients in health care: explanation in the clinical setting.

The long-term goal of our research is to improve the overall effectiveness of physicians' time, by improving the information exchange between physicians and chronic-care patients, initially migraine patients. The computer system we are constructing has a partial knowledge base about migraines, common therapies, and common side effects of those therapies. The system consists of two main programs: data collection and explanation. The design of our system is based on empirical data concerning patients' information needs.

Humans↗