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Biomedical subjects

M K Fagerhol

Publications and source records attributed to M K Fagerhol.

At least 55 records · Page 3Linked to original sources
PubMed1992

Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study.

This study describes methods for extraction and quantification of calprotectin (L1 protein) in feces by enzyme immunoassay. This protein is a prominent antimicrobial component of neutrophils, monocytes, macrophages, and squamous epithelia. Calprotectin was stable in feces during storage for 7 days at room temperature. Small fecal samples taken from a 24-h feces collection gave a reliable estimate of calprotectin. Within-assay precision was 1.9%, and between-assay precision 14.8%. In healthy subjects (n = 33) median fecal calprotectin was 2025 micrograms/l and in hospital controls (n = 40) 10,500 micrograms/l. Median values in patients with Crohn's disease (n = 21) was 43,000 micrograms/l and in ulcerative colitis (n = 17) 40,000 micrograms/l. Fecal calprotectin was significantly correlated to fecal alpha 1-antitrypsin in the patients with Crohn's disease. Ten of 11 patients with gastrointestinal carcinomas had calprotectin level above the suggested reference limit of 6740 micrograms/l.

Adolescent↗
PubMed1992

Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity.

Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).

Adolescent↗
PubMed1991

Cardiac surgery and distribution of the leukocyte L1 protein-calprotectin.

Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and L1 (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myocardial arterio-venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of L1 increased during CPB from 344 +/- 71 micrograms/l (mean +/- SD) preoperatively to 5221 +/- 1267 micrograms/l at the end of CPB (P less than 0.001). Simultaneously, the number of circulating PMN also increased (from 4.4 +/- 0.4 x 10(9)/l to 9.1 +/- 1.2 x 10(9)/l (P less than 0.05)). There was a positive correlation between the mean number of circulating PMN and the plasma level of L1 at all sampling times during CPB (r = 0.93, P less than 0.05). A coronary sequestration of both L1 (P less than 0.006) and PMN (P less than 0.002) was found after 5 min reperfusion. This was not present at 15 and 30 min reperfusion. The coronary entrapment of L1 and PMN did not covary significantly, and was unrelated to both the time of cardioplegic arrest and the arterial levels of L1 and PMN. In conclusion, the increased plasma concentrations of PMN and L1 during CPB and the coronary sequestration of both PMN and L1 may be factors in the pathogenesis of reperfusion injury of the myocardium.

Adult↗
PubMed1991

Calprotectin (the L1 protein) during surgery in patients with rheumatoid arthritis.

Calprotectin (L1) is a major leukocyte protein which is released during activation or death of neutrophil granulocytes and monocytes. Previous studies have shown that L1 may be a useful marker of disease activity in patients with adult or juvenile rheumatoid arthritis (RA). In the present study, the plasma concentrations of L1 were analysed during shoulder-joint surgery in 16 patients with adult or juvenile RA. Decreased L1 concentrations were found 48 h postoperatively. Thereafter, the L1 concentrations were increased at 72 h, with a following decrease until day 14 postoperatively. In contrast, increased serum concentrations of both C-reactive protein (CRP) and orosomucoid (i.e. alpha 1-acid glycoprotein) were found at 48 h after surgery. Plasma samples obtained before and after surgery were analysed by gel filtration. Approximately 3/4 of the plasma L1 was found in fractions corresponding to the native molecule, while the rest was detected in higher molecular mass fractions. The distribution of L1 antigen in low and high molecular mass regions did not differ between the pre- and postoperative plasma samples. The L1 protein consists of light and heavy chains. Increased serum levels of the cystic fibrosis antigen, which is identical to L1 light chain, have been described in patients with cystic fibrosis. The existence of circulating free L1 chains was presently investigated in plasma obtained before and after surgery. After gel filtration of plasma samples, no free L1 chains were detected by use of enzyme immunoassay and dot blot.

Acute-Phase Reaction↗
PubMed1991

Calprotectin in cerebrospinal fluid of the HIV infected: a diagnostic marker of opportunistic central nervous system infection?

The calprotectin level in the cerebrospinal fluid (CSF) of 15 HIV positive patients with symptoms from the central nervous system (CNS) was measured. All 5 patients with opportunistic infections had levels above the reference range and all 10 patients with HIV associated encephalopathy had levels within the reference range. Thus, the calprotectin level in CSF can be of diagnostic value in differentiating between HIV associated encephalopathy and opportunistic infection in the HIV positive patient with symptoms from the CNS.

AIDS Dementia Complex↗
PubMed1991

The leukocyte protein L1 in plasma and synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

L1 is a major granulocyte and monocyte protein, released during activation and turnover of such cells. Blood and synovial fluid (SF) from 41 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA), were analyzed for L1 and the acute phase proteins C-reactive protein, orosomucoid, haptoglobin, alpha 1-antitrypsin and albumin as well as for differential leukocyte count. L1 levels in plasma and SF showed highly significant differences (p less than 0.0001), between the RA and OA patients. All the OA patients had normal plasma concentrations of L1 and low concentrations of L1 in SF. All the RA patients had elevated plasma levels of L1 and high L1 concentrations in SF. In the RA patients, the ratios between the protein concentrations in SF and blood were 3.29 for L1 and less than or equal to 0.64 for the acute phase proteins. In the SF, the L1 levels did not correlate with the monocyte count, while a low, positive correlation was found between L1 and the granulocyte count. The high L1 concentrations observed in SF from RA patients probably reflected an increased turnover of leukocytes in the inflamed joints. In SF from RA patients, high L1 concentrations were found in joints with a high amount of swelling. The present study suggests that L1 may represent a marker of both local and systemic inflammation.

Acute-Phase Proteins↗
PubMed1991

The L1 protein as a new indicator of inflammatory activity in patients with juvenile rheumatoid arthritis.

L1 is a major granulocyte and monocyte protein with Mr 36.5 kDa. It is released during leukocyte activation and detected in plasma by use of an enzyme immunoassay. In our study, L1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid and haptoglobin were analyzed in 127 patients with juvenile rheumatoid arthritis (79 pauci, 33 poly and 15 systemic). L1, ESR and the acute phase proteins were all found to have positive correlations with the clinical joint assessments, with L1 having the strongest correlations. High correlation coefficients were found between L1 and orosomucoid (r = 0.83), ESR (r = 0.72), haptoglobin (r = 0.71) and CRP (r = 0.65), with p less than 0.001 for all the correlations.

Antigens, Surface↗
PubMed1990

Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin.

The calcium binding L1 protein was found to inhibit growth of blood culture isolates of Candida spp and cerebrospinal fluid isolates of Cryptococcus neoformans. Minimum inhibitory concentrations (MIC) were 4-128 mg/l, and concentrations 2-4 times the MIC were fungicidal. Blood culture isolates of Escherichia coli, Klebsiella spp, Staphylococcus aureus, and Staphylococcus epidermidis had MIC values of 64-256 mg/l. Antibacterial activity was strongly influenced by the nature of the culture medium. In view of the biological activity of L1, the name calprotectin is proposed to describe this antimicrobial protein with calcium binding properties.

Antifungal Agents↗
PubMed1990

L1, a major granulocyte protein; isolation of high quantities of its subunits.

L1 is a major granulocyte and monocyte protein with a Mr of 36.5 kDa. It is found mainly in the cytosol of these cells. Purified L1 is shown, on two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), to contain three subunits. In this study, 6 mol/l concentration of urea was found to be sufficient for disassembly of the polypeptides, and urea-containing preparative isoelectric focusing gel was used for separation of high quantities of the subunits. The pI of the eluted subunits were 5.8, 6.1 and 7.1. When tested on 2D-PAGE, the isolated subunits were found at their typical locations. Polyclonal rabbit antibodies were produced against the subunits, and the antisera were, on dot-blot, found to react with the different subunits as well as the purified L1.

Antigens, Surface↗
PubMed1990

Heterozygous MZ alpha-1-antitrypsin deficiency in adults with chronic liver disease.

Pi phenotype was determined in 335 patients with liver diseases and compared with the results in 2830 healthy blood donors. Eleven of 335 patients had phenotype MZ (3.3%, compared with 2.9% in healthy blood donors (NS]. None of 53 patients with autoimmune chronic active hepatitis had the MZ phenotype, but it was found in 2 of 18 patients (11.1%) with cryptogenic cirrhosis, 3 of 78 (3.8%) with alcoholic liver cirrhosis, 2 of 36 (5.6%) with primary sclerosing cholangitis, and 1 of 26 (3.9%) with primary biliary cirrhosis. Altogether, 3 of 335 patients were homozygous for Pi ZZ and had cirrhosis. One of them (a male) developed a hepatoma and died. We conclude that the reported association between Pi MZ phenotype and chronic non-B active hepatitis does not seem to include patients with autoimmune chronic active hepatitis, whereas the possibility of an association between cryptogenic cirrhosis and the MZ phenotype cannot be excluded.

Adult↗
PubMed1989

A longitudinal study of the leukocyte protein L1 as an indicator of disease activity in patients with rheumatoid arthritis.

L1 is a major granulocyte and monocyte protein. It is released during leukocyte activation, and the plasma level is thought to reflect the inflammatory activity. Fifteen patients with classical or definite rheumatoid arthritis were examined monthly during one year. The laboratory tests included L1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid, haptoglobin, ceruloplasmin, alpha 1-antitrypsin, immunoglobulins and blood cell counts. The clinical tests included articular index, grip strength, morning stiffness and pain. The L1 protein was found to have highly significant correlations (p less than 0.0001) with orosomucoid (r = 0.86), CRP (r = 0.79), ESR (r = 0.78), haptoglobin (r = 0.75), alpha 1-antitrypsin (r = 0.63) and ceruloplasmin (r = 0.44). Significant correlation was also found between L1 and IgA. None of the laboratory variables showed significant correlation with pain, but when they were correlated with articular index, grip strength and morning stiffness, L1 was found to have the highest average correlation coefficient (p less than 0.0001).

Adult↗
PubMed1988

Mac 387 antibody and detection of formalin resistant myelomonocytic L1 antigen.

The murine monoclonal antibody Mac 387 was raised against a purified protein fraction obtained from human monocytes. By immunoblotting experiments, Mac 387 was shown to react with a previously defined antigen called L1; this is a multichain myelomoncytic protein of about 36 Kd which shows sequence homology with the cystic fibrosis antigen. The L1 protein is present in the cytoplasm of virtually all resting peripheral neutrophils and monocytes; it is also variably expressed on the plasma membrane of these cells, possibly as a secretory product. Because the L1 antigen is resistant to denaturation by formalin, its tissue distribution can be studied in routinely processed biopsy material. In a wide variety of specimens Mac 387 was shown by immunohistochemical analysis, to produce a cytoplasmic staining pattern concordant with that of a well defined polyclonal antibody to the L1 antigen. Cytoplasmic reactivity was obtained with granulocytes and infiltrating macrophages but generally not with several categories of dendritic cells. In addition, squamous epithelium of mucous membranes was strongly positive, in contrast to normal epidermis.

Antibodies, Monoclonal↗
PubMed1988

The major leukocyte protein L1 as an indicator of inflammatory joint disease.

L1 is a major protein in granulocytes and monocytes. It is released during activation of these cells, and the plasma level of L1 is therefore thought to reflect the turnover of leukocytes. Peripheral blood from 96 patients hospitalized in a rheumatological department, was analysed for L1, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The total patient material was divided into groups depending on diagnosis: 47 patients with rheumatoid arthritis, 27 patients with arthritis of different etiologies, 15 patients with non-inflammatory diseases and 7 patients with arteritis. Correlation analysis were made between the different laboratory parameters. A high positive correlation was found between L1 and CRP in all the groups, and with a correlation coefficient of the total patient material of 0.68 (p less than 0.001). The correlation coefficient between L1 and ESR was 0.54 (p less than 0.001) in the total patient material, and between CRP and ESR it was 0.66 (p less than 0.001). The results indicate that the L1 protein could be a new laboratory marker of inflammation in rheumatic diseases.

Antigens, Surface↗
PubMed1988

L1, a major granulocyte protein: antigenic properties of its subunits.

L1, a major granulocyte protein, was purified and analysed by use of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Three subunits were visualized, and they were found to have molecular weights of 12.5 kDa, 13.3 kDa and 8.3 kDa. They were extracted from 2D-gels, and different combinations of subunits and two L1 antisera were analysed by immunodiffusion in agarose gel. The 8.3 kDa polypeptide in combination with one or both of the other polypeptides, gave immunoprecipitation with one of the L1 antisera, while no precipitation occurred when the three polypeptides were tested separately. Neither was there any precipitation when the two heavier polypeptides were tested in combination. By use of another L1 antiserum, all the L1 polypeptides were found to be antigenic and give immunoprecipitations. The L1 protein has a great affinity for calcium, and calcium was necessary for immunoprecipitation with the L1 subunits to occur. Autoradiographs of 2D-PAGE gels with labelled leucocytes visualized the L1 subunits in the same position as the subunits from purified, cold L1, indicating no significant alteration of the L1 protein during the purification procedure.

Blood Proteins↗
PubMed1987

Distribution of a formalin-resistant myelomonocytic antigen (L1) in human tissues. I. Comparison with other leukocyte markers by paired immunofluorescence and immunoenzyme staining.

L1 is an approximately 36-kd protein recently identified as a cytoplasmic and surface marker antigen of virtually all resting peripheral blood neutrophils and monocytes. This study of its tissue distribution showed that L1 is particularly well preserved in formalin-fixed and paraffin-embedded routine material. It had a restricted distribution within the monocyte-derived cell lineage, being mainly confined to reactive histiocytes (infiltrating macrophages). L1 was a much more reliable marker for such cells than lysozyme, except that the latter was better expressed by epithelioid and giant cells. L1 was lacking in HLA-DR-positive interdigitating, Langerhans', and most intestinal histiocytic cells. The same was true for Kupffer cells in normal livers; but in livers of three patients with malignant histiocytosis or histiocytic medullary reticulosis infiltrating histiocytes and putative Kupffer cells stained positively. Follicular dendritic cells and tangible body macrophages were always questionably L1 positive.

Antigens, Surface↗