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M K Larsen

Publications and source records attributed to M K Larsen.

4 recordsLinked to original sources
PubMed1997

Modified cytokeratins expressed on the surface of carcinoma cells undergo endocytosis upon binding of human monoclonal antibody and its recombinant Fab fragment.

Previously, we have reported on successful imaging of colon, rectal, and pancreatic carcinomas in patients by using a radiolabeled all-human monoclonal antibody, COU-1, directed against modified cytokeratin. To further develop this antibody for use as an immunoconjugate, COU-1 was cloned by phage display selection and the human Fab fragment was expressed in bacteria. Analysis by confocal laser scanning microscopy demonstrated that COU-1 bound in a uniform punctate pattern to the surface of viable carcinoma cells stained at 4 degrees C, and binding increased significantly when cells were cultured on fibronectin, laminin, or collagen IV. In the case of fibronectin, COU-1 staining was particularly enhanced at intercellular junctions. When carcinoma cells were cultured with COU-1 at 37 degrees C for 6 hr, the antibody was found in large perinuclear vesicles and the punctate surface staining was significantly reduced. Similar results were obtained using intact IgM COU-1 and the recombinant Fab fragment. Immunohistological studies indicated that COU-1, in contrast to murine monoclonal antibodies against normal cytokeratin 8 and 18, could differentiate between malignant and normal colon epithelia, and between colon cancer metastasis in the liver and surrounding normal hepatocytes. Within biopsies of malignant tissue, COU-1 exhibited membrane-associated staining of proliferating cells, while resting cells had a filamentous pattern. Thus, modified cytokeratin at the surface of carcinoma cells may represent a new target for immunoconjugates and may explain the promising results of the phase I/II clinical study.

Amino Acid Sequence↗
PubMed1997

The day-to-day variation in insulin sensitivity in non-insulin-dependent diabetes mellitus patients assessed by the hyperinsulinemic-euglycemic clamp method.

The objective was to study the day-to-day variation in insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) and to analyze within- and between-person variances in the glucose infusion rate during steady state (M value). Ten NIDDM patients attending the outpatient clinic at Aarhus Amtssygehus were studied three times under standardized conditions. Each time, a 120-minute hyperinsulinemic-euglycemic clamp was performed. Similar M values were found on the 3 study days, with difference between M values on the 3 days of (mean +/- SD) 0.3 +/- 1.8 mg glucose/kg lean body mass (LBM)/min. The total coefficient of variation (CV) for M values was 57% after the first clamp, 55% after the second, and 53% after the third. Ninety percent of the total day-to-day variation in M values could be ascribed to between-person variation and 10% to within-person variation. Within-person components of variance included all sources of variation other than between-person variation. The within-person CV for M values was 11.9% +/- 7.2% after two clamp studies and 12.1% +/- 7.3% after three (P < .55). In conclusion, under standardized conditions, a valid estimate of insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp in NIDDM patients is obtained after a single measurement. Because of large between-person variation, paired data should be used when comparing insulin sensitivity in NIDDM patients.

Blood Glucose↗