Apmis

Rygaard, Jørgen

doi: 10.1111/j.1699-0463.1996.tb00678.xpmid: N/A

KALLAN, ARAM A.; VRIES, RENÉ R. P.; ROEP, BART O.

doi: 10.1111/j.1699-0463.1996.tb00679.xpmid: 8645454

Autoimmune T cells reactive to β‐cell autoantigens are generally believed to play an essential role in the immune‐mediated selective pancreatic islet β‐cell destruction process leading to insulin‐dependent diabetes mellitus (IDDM). Many of the supportive data have been obtained from animal models of this disease, but often these data remain to be validated in human IDDM, including the nature of the responsible autoreactive T cells and their targets on the β cells. In the last few years, however, considerable progress has been made, and several candidate autoantigens have been identified. Diabetogenic T‐cell clones have been isolated and characterized in animal models, but for the majority of these clones, the target autoantigen is unknown. In humans, the first islet autoantigens recognized by autoreactive T cells have been defined. This opens the way to designing immunointerventive strategies selective for these T cells and their candidate target antigens, in an attempt to prevent the onset of IDDM. In this review, we described the significance of T lymphocytes for the pathogenic process leading to type 1 diabetes and our studies showing (auto)immune responses by β‐cell‐reactive T lymphocytes of newly diagnosed patients.

CLARK, A.; CHARGE, S. B. P.; BADMAN, M. K.; KONING, E. J. P.

doi: 10.1111/j.1699-0463.1996.tb00680.xpmid: 8645452

Amyloid deposits are found in pancreatic islets of 90% of type 2 (non‐insulin‐dependent) diabetic subjects at postmortem. Islet amyloid is formed from islet amyloid polypeptide (IAPP). IAPP is a 37 amino acid peptide which is a normal constituent of β cells and is co‐secreted with insulin in animals and in man. The causative factors for fibrillogenesis of IAPP are unclear, but could be related to the sequence of IAPP and abnormal production of the peptide. The lack of islet amyloid in rodent models of diabetes is due to proline substitutions in the amyloidogenic region of IAPP. Amyloid fibrils are deposited between β cells and islet capillaries: fibrils in invaginations of the plasma membrane may interfere with membrane signalling and insulin release. Amyloid fibrils are formed within 2 days in culture in islets isolated from transgenic mice expressing the gene for human IAPP, but not in vivo. Overexpression and decreased clearance of human IAPP from islet spaces may be important factors. Progressive deposition of IAPP fibrils combined with the associated reduction in the insulin‐secreting β cells is likely to contribute to deterioration of islet function in the course of type 2 diabetes.

NAKAJIMA, SHIGEMI; ARIZONO, NAOKI; HATTORI, TAKANORI; BAMBA, TADAO

doi: 10.1111/j.1699-0463.1996.tb00681.xpmid: 8645453

Gastric ulcers were induced in rats by acetic acid treatment, and the mast cell kinetics in the lesions were studied. Within 24 h, mast cells had disappeared from the treated site and from the marginal zone, corresponding to the area of severe tissue injury. Regenerating epithelium appeared at day 10, and the lesion had healed by day 30. In this healing process, the number of mast cells was significantly increased, and their density in the regenerating mucosa, marginal mucosa, and marginal muscularis propria was 3.2 1.8, and 7.5‐fold the control level, respectively. The increase in the number of mast cells was preceded by an increase in the percentage of S‐phase mast cells. Mast cells in the mucosa were Alcian blue (AB)+/safranin (S)− and rat mast cell protease (RMCP) I−/II+, consistent with the features of mucosal mast cells throughout the observation period. On the other hand, most mast cells in the muscularis propria exhibited AB+/S+ and RMCP I+/II+ in the early period of ulcer healing. The latter feature was changed to RMCP I+/II− on day 30, indicating that immature CTMC appeared and then developed into mature CTMC during the ulcer healing. The significant change in the number of mast cells suggests that mast cells play an important role in the development and healing of gastric ulcers.

JENKINS, ANDREW; KRISTIANSEN, EWY; ASK, EIRIK; SERVOLD, TRULS; CHRISTENSEN, ARNE; KRISTIANSEN, BJØRN‐ERIK

doi: 10.1111/j.1699-0463.1996.tb00682.xpmid: 8645455

Polymerase chain reaction (PCR) and Southern blotting were used to assess the prevalence of HPV in cervical biopsies of 100 women who were treated at the gynecology department of Telemark Central Hospital for non‐cancerous conditions. Nine (9%) of the biopsies were HPV positive. Four (4%) were of HPV type 18, one (1%) was HPV11 positive, and four contained different unrecognized HPV types (HPVX). HPV16 was not detected.

SUN, XIAO‐FENG; CARSTENSEN, JOHN M.; STÅL, OLLE; ZHANG, HONG; BOERYD, BERNT; NORDENSKJÖLD, BO

doi: 10.1111/j.1699-0463.1996.tb00683.xpmid: 8645456

We analyzed the interrelations of sex, age, tumor site, Dukes' stage, growth pattern and differentiation, and their prognostic value in 293 patients with primary colorectal adenocarcinoma. Simultaneously, growth pattern, differentiation, DNA and S‐phase fraction (SPF) in paired primary tumors and lymph node metastases from 97 colorectal cancer patients were compared. The results revealed that poorly differentiated and mucinous tumors, as against well/moderately differentiated tumors, were frequently located in the proximal colon, and their frequencis were increased as Dukes' stage advanced (p=0.03). Tumor differentiation was usually identical in primaries and corresponding metastases (p=0.002), but this was not true of tumor growth pattern, DNA ploidy or SPF. In multivariate survival analyses, Dukes' stage provided strongly prognostic information (p<0.001) and mucinous tumors tended to predict worse survival (p=0.08).

SEDGLEY, CHRISTINE M.; SAMARANAYAKE, LAKSHMAN P.; DARVELL, BRIAN W.

doi: 10.1111/j.1699-0463.1996.tb00684.xpmid: N/A

An in vitro model and an image analysis were designed to improve on existing quantification methods in the assessment of the adherence of Enterobacteriaceae to human epithelial cell monolayers. Adherence to HeLa cell monolayers of three oral isolates and one type strain from each of four species of Enterobacteriaceae over two incubation time periods was examined. Correction for actual cell area and a cube root transformation of the data to stabilize variance were applied. While behaviour varied between strains within species, E. cloacae was the most, and K. pneumoniae the least, adherent species irrespective of the incubation period. Increasing the incubation period from 30 min to 60 min resulted in greater adherence for E. cloacae, E. coli, and C. freundii, but not K. pneumoniae strains. The method permits the reliable measurement and valid analysis of the adherence of Enterobacteriaceae to cultured epithelial cell monolayers.

ÖGMUNDSDÓTTIR, HELGA M.; GU?LAUGSDÓTTIR, SIGFRÍ?UR; BJÖRNSSON, JÓHANNES; JÓNASDÓTTIR, SIGURRÓS

doi: 10.1111/j.1699-0463.1996.tb00685.xpmid: N/A

CA‐125 is a high molecular weight glycoprotein that is best known as a tumour marker for ovarian carcinoma but has been found to be present on various epithelial surfaces including normal tissues. Elevated serum levels of CA‐125 have been described in malignancies other than ovarian carcinoma as well as in inflammatory conditions. The expression of CA‐125 was studied in paraffin‐embedded tissue from 48 mammary carcinomas and 11 samples of normal mammary gland using two monoclonal antibodies, M2 and M11. CA‐125 was detected in all normal tissue samples and 64% of the breast carcinomas. Eight of the thirty CA‐125‐positive carcinomas reacted with only one of the antibodies, indicating molecular change. In normal mammary tissue, CA‐125 was seen on apical surfaces and in ductal contents, whilst the majority of the carcinomas (90%) expressed CA‐125 in cytoplasmic granules, often showing membranous staining as well. In 16 samples of lymph node metastases CA‐125 expression was similar to that seen in the primary tumour. Elevated serum levels of CA‐125 were detected in only 3 out of 41 samples available from this patient group. No significant associations were detected with various clinical parameters. We conclude that CA‐125 is normally expressed in the mammary gland and that the expression is frequently altered and sometimes absent in mammary carcinoma, possibly reflecting the loss of cellular polarity. Measuring serum levels of CA‐125 is not relevant in breast carcinoma patients since one third of breast carcinomas were CA‐125 negative and even patients with strongly CA‐125‐positive tumors had undetectable CA‐125 serum levels.

JENSEN, THOMAS JON; KHARAZMI, ARSALAN; SHAND, GEOFFREY; NIELSEN, HENRIK; TVEDE, MICHAEL

doi: 10.1111/j.1699-0463.1996.tb00686.xpmid: 8645459

The aim of the study was to measure and compare the oxidative burst, chemotaxis and cytokine production of human white blood cells, stimulated with meningococcal lipopolysaccharides (LPS) extracted from three different serogroups (A, B and C) of Neisseria meningitidis, and to evaluate whether convalescent sera from patients with meningococcal disease could modify cell stimulation of LPS. All three preparations of LPS from groups A, B and C were tested using the Limulus amoebocyte lysate assay (LAL), and the KDO concentrations of the LPS extracts were measured. Equivalent amounts of biologically active LPS, judged by LAL, and LPS with the same KDO concentration were assayed. IL‐1α, IL‐1β, 1L‐6 and TNF‐α production was stimulated by all three LPS preparations. All three preparations stimulated oxidative burst in monocytes (MNC). Only group A LPS stimulated neutrophil chemotaxis, while none of the three LPS stimulated superoxide production. Pooled convalescent sera from five patients with meningococcal disease suppressed the activity of neutrophils stimulated with LPS from groups B and C (p<0.05, Mann‐Whitney U‐test).

KJÆRGÅRD, L. L.; LARSEN, F. O.; NORN, S.; CLEMENTSEN, P.; SKOV, P. STAHL; PERMIN, H.

doi: 10.1111/j.1699-0463.1996.tb00687.xpmid: N/A

The investigation includes 12 patients hospitalized with acute exacerbations of chronic bronchitis (CB) and infected in the lower respiratory tract with Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP). Eight patients were infected with HI, three with SP, and one patient with both species. Basophil‐bound IgE and serum IgE directed against these species were examined using the patients' own bacterial isolates. All patients showed IgE‐mediated histamine release when their peripheral leukocytes were incubated in vitro with the infecting species, indicating basophil‐bound IgE directed against their own bacterium. No IgE‐mediated response was obtained in the control group of 12 healthy individuals. Bacteria‐specific IgE in serum was demonstrated by immunofluorescence assay and further verified by passive sensitization. There was a positive serum titre in seven of nine patients housing HI and in all SP‐infected patients but not in the control group. No synchronism was found between a positive response in the histamine release test and the immunofluorescence assay by parallel testing during the test period. This may be due to a time delay between production of serum IgE and its fixation to the cell surface. The results indicate a potential for a bacteria‐specific IgE‐mediated immune response in CB. Thus, by triggering mediator release, bacteria may be involved in the pathogenesis of exacerbations in CB.