Validation of the inflammatory bowel disease questionnaire in Swedish patients with ulcerative colitis.

BACKGROUND: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease-specific health-related quality of life (HRQOL) questionnaire including four dimensions and a sum score. The aim of this study was to assess the internal and external validity, reliability, and sensitivity of a Swedish version of the IBDQ. METHODS: Three hundred consecutive patients with ulcerative colitis completed the IBDQ and three other health-related quality of life questionnaires (the Rating Form of IBD Patient Concerns (RFIPC), the Short Form-36 (SF-36) and the Psychological General Well-Being (PGWB) index). Disease activity was evaluated using a 1-week symptom diary, blood tests and rigid sigmoidoscopy. One hundred and fourteen patients filled in the questionnaire a second time, of whom 75 had been in stable remission for over 6 months and 39 had a significant clinical change in disease activity. RESULTS: Factor analysis of the 32 IBDQ items did not support the four dimensional scores. The dimensional scores had sufficient convergent validity, but low discriminative validity and homogeneity. The homogeneity was also low for the sum score. The inter-dimensional correlations were high. The concurrent validity was supported by correlations between the dimensional scores and other measures of disease activity and HRQOL. Patients in relapse scored significantly less on the sum score and the four dimensions compared to patients in remission. The test-retest correlations for the dimensional scores were 0.40-0.76. Patients with a change in disease activity during the 6-month follow-up period had a significant change in IBDQ scores not found in those who remained in remission. CONCLUSIONS: The Swedish version of the IBDQ had external validity and was shown to be a reliable and sensitive measure of HRQOL in ulcerative colitis, though there are some concerns regarding the internal validity. The use of a sum score was not supported and the questionnaire may benefit from a redivision of items into dimensions with better homogeneity and discriminative validity.

Surface properties, connective tissue protein binding and Shiga-like toxin production of Escherichia coli isolated from patients with ulcerative colitis.

Escherichia coli strains isolated from intestinal biopsies of patients with ulcerative colitis (n 146), Crohn's disease and colonic polyposis (n 41) were analysed for binding of collagen I, collagen IV, fibronectin and laminin. Strains expressed varying degrees of binding of one or more of the four connective tissue proteins. Only 32 strains did not express binding of any of the proteins. The strains expressed low or moderate cell surface hydrophobicity. There was no correlation between protein binding and expression of cell surface hydrophobicity. E. coli isolated from inflamed rectal mucosa were slightly less negatively charged than strains isolated from healthy intestinal mucosa. Shiga-like toxins I and II were detected in 32 strains from 28 patients. Of these, 5 strains had been isolated from normal or healed tissue. In patients with inflammatory bowel disease, connective tissue proteins are exposed in intestinal ulcerations. Strains expressing binding of one or several of these proteins may have a selective advantage to colonize these lesions.

Type 2 diabetes. Primary vascular disorder with metabolic symptoms?

It is postulated that in the resting state insulin-dependent tissue uptake of glucose is limited by the rate of blood flow, capillary permeability, and the number of perfused capillaries in the skeletal muscles. A mathematical model, simulating these relations, is developed. According to this model, changes in the indicated parameters might cause type 2 diabetes.

Polar differences of delayed and implanting mouse blastocysts in binding of Alcian Blue and concanavalin A.

Mouse blastocysts in delay of implantation and after an 18-hour activation for implantation by estrogen were recovered by flushing with glutaraldehyde containing Alcian Blue or by flushing with cold Dulbecco's PBS containing 0.1% sodium azide for further processing according to an Alcian Blue technique and a ConA-latex technique, respectively. Blastocysts in delay of implantation showed no or only faint staining with Alcian Blue, while blastocysts activated for 18 hours displayed a marked staining of the abembryonic pole. Binding of ConA-latex spheres demonstrated a markedly higher density at the abembryonic end of both delayed and implanting blastocysts. It is concluded that, as demonstrated by the Alcian Blue technique, the abembryonic trophoblast, which is the first one to attach and invade at implantation, has changed the properties of the extracellular coat, probably in a way that favors increase of adhesiveness and invasiveness. The similarity in pattern of ConA binding of both delayed and implanting blastocysts, however, suggests that this property is related more to preimplantational differences in proliferative activity of the two poles than to implantatory changes.

On the mode of incorporation of human transplantation antigens into lipid vesicles.

Highly purified HLA (A and B) antigens in octylglucoside were quantitatively incorporated into egg lecithin vesicles, and it was demonstrated that vesicles of different densities could be prepared by varying the ratio of lipid to protein. The HLA antigens were bound to the vesicles by the hydrophobic stretch of amino acids normally integrated into the plasma membrane, and most if not all HLA antigens in the lipid vesicles occurred in the right-side-out orientation, as demonstrated by pronase digestion and by quantitative radioimmunoassay determinations on intact HLA antigen-containing vesicles. Both the lipid and the HLA antigens aggregated at octylglucoside concentrations below the critical micelle concentration. The protein aggregates appeared stable and could be incorporated into preformed lipid vesicles. It is suggested that vesicle formation preceeds the incorporation of protein into the lipid vesicles.

Chemical, physical-chemical, and immunological properties of papain-solubilized human transplatation antigens.

Papain-solubilized HLA-A, -B, and -C antigens have been isolated from cadaveric spleens. The isolated material was homogeneous and comprised subunits with the apparent molecular weights 33,000 and 12,000. Amino acid analyses of a mixture of HLA antigen heavy chains obtained from a great number of spleens with different HLA antigen phenotypes revealed a composition that is very similar to that of individual HLA-A and -B antigens. Likewise, the NH2-terminal 30 residues of the HLA-antigen heavy chain mixture were virtually identical with that recorded for individual specificities. The circular dichroism spectra for the isolated HLA antigens and for free beta2-microglobulin revealed similarities with spectra recorded for immunoglobulin chains and domains. The HLA-antigen heavy chain may contain an appreciable amount of beta structure. Antibodies raised against free beta2-microglobulin react better with beta2-microglobulin in free form than when bound to the HLA-A, -B, and -C antigen heavy chains. This is due to the fact that free beta2-microglobulin can bind a maximum of four Fab fragments simultaneously, whereas the HLA-antigen-associated beta2-microglobulin can bind only two Fab fragments without dissociating from the heavy HLA-antigen subunit.

Demonstration of HLA-DR-like antigens on milk fat globule membranes.

Milk fat globules (MFG), which are formed by exocytosis of lipid from epithelial cells of the mammary gland, are enveloped by plasma membrane from the epithelial cells. Highly purified, detergent-solubilized MFG membranes have been shown to contain molecules reactive with a rabbit antiserum against HLA-DR antigens. Indirect immunoprecipitation combined with polyacrylamide gel electrophoresis in sodium dodecyl sulfate demonstrated that the MFG membrane material reactive with the antiserum comprised molecules which under denaturing conditions displayed molecular weights of 28,000 and 35,000. The two types of polypeptide chains, which were both glycosylated, were held together by noncovalent forces under nondenaturing conditions. Various types of chemical and physicochemical analyses failed to reveal any significant differences between the HLA-DR-like antigens from MFG and from spleen cells. Since the HLA-DR-like antigens bound detergent in micellar form and were expressed on the outside of intact MFG, as revealed by indirect immunofluorescence, it is concluded that these antigens are embedded in the hydrocarbon matrix of the MFG and not merely passively adsorbed onto the MFG.

Isolation and properties of detergent-solubilized HLA antigens obtained from platelets.

Deoxycholate-solubilized HLA antigens have been isolated from platelets and comprised a mixture of 43,000- and 39,000-dalton polypeptide chains associated with beta2-microglobulin. Limited proteolysis experiments suggested that the 39,000-dalton chain is a fragment of the intact 43,000-dalton chain. Further proteolysis of the 39,000-dalton fragment yields a 33,000-dalton component. The 39,000-dalton molecule is more acidic than both the 43,000- and the 33,000-dalton chains. Differences in the amino acid compositions of the 43,000- and 39,000-dalton species demonstrate that the peptide(s) released on generation of the 39,000-dalton component are charged. The proteolytic split most probably occurs in the COOH-terminal end, which, owing to its content of charged amino acids, most probably is not integrated into the hydrocarbon matrix of the membrane. The 39,000- and 43,000-dalton components bind detergent in micellar form and can be incorporated into liposomes. The 33,000-dalton fragment has lost the ability to bind detergent micelles and is not incorporated into liposomes.

Presence of alloreactive Ia antigens on murine intestine epithelial cells.

Purified intestine epithelial cells express Ia antigens as determined by immunoprecipitation and sodium dodecyl sulphate polyacrylamide-gel electrophoresis. The intestinal Ia antigens react at least with alloantisera directed against the H-2 I-A subregion.