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Biomedical subjects

C B Andersen

Publications and source records attributed to C B Andersen.

At least 73 records · Page 4Linked to original sources
PubMed1994

Acute kidney graft rejection. A morphological and immunohistological study on "zero-hour" and follow-up biopsies with special emphasis on cellular infiltrates and adhesion molecules.

Serial biopsies from 41 consecutive renal allotransplanted patients were evaluated in order to obtain pretransplant data as well as information on well-functioning and acutely rejecting grafts. Each patient served as his own control. Thirty-five patients were followed according to the schedule which included biopsy prior to transplantation, shortly after opening of reanastomosis, at least once postoperatively (days 7-10), and furthermore whenever clinically indicated. The morphological evaluation was in each case combined with immunofluorescence (to detect immunoglobulins and complement fractions) and immunohistochemistry with a wide panel of monoclonal antibodies for T cells (CD2, CD3, CD4, CD8, gamma delta), B cells (CD20, CD22), macrophages (CD68, MAC387) NK cells (leu-7, CD16), activation markers (IL-2-R, Ki-67, transferrin-R), MHC antigens (HLA-ABC, HLA-DR), adhesion molecules (ICAM-1, VCAM-1, ELAM-1, PADGEM, VLA-4, LFA-1 alpha/beta), and growth factors (EGF, TGF-alpha, EGF-R). When 132 biopsies and 10 failed allografts were examined, no specific morphological or immunohistological parameter predictive of rejection or graft outcome could be found. Morphology in follow-up biopsies from non-rejecting and rejecting patients revealed a continuum of inflammatory changes, and several non-rejecting cases demonstrated cellular inflammatory infiltrates which could not be discriminated from those seen in acute rejection. Of the patients 44% had acute rejection accompanied by increased infiltration of T cells and macrophages showing enhanced IL-2-R expression, increased tubular and endothelial staining for MHC class II, ICAM-1, and VCAM-1, and strong leukocytic expression of VLA-4 and LFA-1 alpha/beta.

Adolescent↗
PubMed1994

Calcium channel blockers in kidney transplantation.

PURPOSE: To review the question as to whether treatment with a calcium channel blocker (CCB) influences the course and outcome of cadaveric renal transplantation in recipients treated with cyclosporin A. METHODS: Computer-assisted search (Medline) and manual search of the literature. Odds ratio, Mantel-Haenszel test, Fischer's test and Chi 2 test. RESULTS: Two Randomised, placebo-controlled studies, 12 randomised, open studies, 3 retrospective studies, 1 study using a historic control group and 3 studies only reported in abstract form were identified. In the randomised, open studies treatment with CCB reduced the rate of delayed graft function but had no effect on the rate of rejection and graft survival. The effect on graft function was equivocal. In the blind, placebo-controlled studies no beneficial effects of treatment with CCB were found. Treatment with CCB reduced the dose of CyA needed to reach target whole blood level of CyA in nearly all studies. CONCLUSION: Results are conflicting. Further studies are needed.

Cadaver↗
PubMed1993

[Electron microscopy of needle biopsies from cancer patients with unknown primary tumors].

The aim of the present study was to evaluate the diagnostic value of electron microscopy (EM) performed on Surecut biopsies from patients without known primary tumour. The material consisted of 108 consecutive biopsies, obtained over a period of two years, from patients with tumour(s) in the liver or lymph nodes (on the neck, in the axilla or retroperitoneum). From each patient fine needle aspirations and Surecut biopsies for light microscopy and electron microscopy were taken. Only biopsies in which material for both electron microscopy and light microscopy was sufficient were included (60%). Immunohistochemical reactions were performed on paraffin sections when indicated. Final diagnoses were confirmed on surgically removed specimens and/or autopsies. Electron microscopy was necessary for obtaining the final histological diagnosis in 15% of the cases. It is therefore recommended to obtain additional ultrasound guided biopsies for EM from cancer patients with tumours in the liver or lymph nodes in cases where the primary origin of the tumour is unknown.

Biopsy, Needle↗
PubMed1993

Acute effects of FK506 and cyclosporine A on cultured human proximal tubular cells.

The effects were studied of FK506 and cyclosporine A on human proximal tubular cells. An in vitro assay was used with cultured renal cells which displayed characteristics of proximal tubular cells. Cell growth was measured by [3H]thymidine uptake. FK506 inhibited cell growth by about 50% at 1 micrograms/ml but cells were not killed as shown by the dye exclusion test. The growth rate of cells recovered to control levels after removal of FK506 from the cultures. FK506 and cyclosporine A showed an additive effect on tubular cell growth reduction. This effect was similar at equivalent doses of FK506 and cyclosporine A, whereas in cultures of leukocytes, the half maximal response to mitogen was obtained at 0.01 micrograms/ml FK506 and 0.5 micrograms/ml cyclosporine A, respectively. Immunocytochemistry demonstrated that FK506 reduced the expression of interferon-gamma induced major histocompatibility complex (MHC) class I on the proximal tubular cells, but had no effect on the expression of the MHC class II antigens or the intercellular adhesion molecule (ICAM-1) on the cultured cells.

Cell Adhesion Molecules↗
PubMed1993

Comparison of the effects of tumour necrosis factor alpha stimulation and phorbol ester treatment on the immunocytochemical staining of intercellular adhesion molecule 1 in human renal carcinoma cell cultures.

Incubation of the human renal carcinoma cell line CaKi-1 with tumour necrosis factor alpha (TNF alpha) or the phorbol ester phorbol-12-myristate 13 acetate (PMA) strongly enhanced the immunocytochemical staining of the intercellular adhesion molecule ICAM-1, in a non-linear manner. Since PMA is capable of activating Ca2+/phospholipid-dependent protein kinase C (PKC), we investigated the role of this kinase during TNF alpha signal transduction. Calcium ionophore A23187 significantly enhanced PMA, but not TNF alpha-induced ICAM-1 staining. The PKC inhibitors H7, staurosporine and sphingosine abrogated the action of PMA, while TNF alpha was unaffected. Simultaneous incubation with TNF alpha and PMA resulted in maximal ICAM-1 staining significantly above values obtained when cultures were treated with either agent alone. Finally, chronic PMA treatment with subsequent TNF alpha stimulation enhanced ICAM-1 staining above values from cultures where TNF alpha was omitted. Our findings suggest that the immunocytochemical staining of ICAM-1 in CaKi-1 cells can be induced by TNF alpha through mainly PKC-independent mechanisms or by PMA through PKC-dependent mechanisms. The two agents may work synergistically in this respect.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Effects of pertussis and cholera toxin on the interferon-gamma stimulated immunocytochemical staining of ICAM-1 and inositol phosphate formation in a human renal carcinoma cell line.

We have recently shown that interferon-gamma (IFN-gamma) stimulated immunocytochemical staining of the intercellular adhesion molecule ICAM-1 may be dependent on inositol phosphate formation in the human renal carcinoma cell line CaKi-1. In the present study we investigated the possible role of GTP-binding proteins (G-proteins) during IFN-gamma signalling. Preincubation of CaKi-1 cells for 24 h with increasing amounts of pertussis toxin (PT) or cholera toxin (CT), two regulators of G-protein activity, inhibited IFN-gamma induced ICAM-1 staining. Preincubation with PT or CT for 24 h also inhibited IFN-gamma induced inositol 1-monophosphate (Ins 1-P), inositol 1,4 bisphosphate (Ins 1,4-P2) and inositol 1,4,5 trisphosphate (Ins 1,4,5-P3) formation. Our findings suggest that IFN-gamma induced ICAM-1 staining and inositol phosphate formation in CaKi-1 cells is dependent on a PT and CT sensitive signalling pathway. This may reflect a role for G-proteins in the coupling of IFN-gamma receptor activation and phospholipase C catalyzed phosphoinositide hydrolysis.

Carcinoma, Renal Cell↗
PubMed1993

Role of protein kinase C during interferon-gamma- and phorbol ester-stimulated immunocytochemical expression of ICAM-1 in human renal carcinoma cells.

Incubation of the human renal carcinoma cell line CaKi-1 with interferon-gamma (IFN-gamma) or the phorbol ester, phorbol-12-myristate 13-acetate (PMA) strongly stimulated the immunocytochemical expression of the intercellular adhesion molecule-1 (ICAM-1) in a dose-dependent manner. Since PMA is capable of activating the Ca2+/phospholipid-dependent protein kinase C (PKC), we investigated the role of this kinase during IFN-gamma signal transduction. Calcium ionophore A23187 significantly enhanced IFN-gamma- and PMA-induced ICAM-1 staining. While staurosporine, H7 and sphingosine, three known PKC inhibitors, blocked the PMA effect, only staurosporine abrogated the action of IFN-gamma. Finally, 24 h of PMA pretreatment with subsequent IFN-gamma stimulation enhanced ICAM-1 staining above values from cultures where IFN-gamma was omitted. This occurred despite the fact that 24 h of PMA pretreatment abolished the effect of IFN-gamma on PKC activation, as determined by acetylated myelin basic protein 4-14 phosphorylation. In conclusion, these results suggest that additional events other than PKC activation are required for complete regulation of ICAM-1 antigen by IFN-gamma in the whole cell population. Hence, other Ca(2+)-dependent signalling pathway(s) mediated by IFN-gamma receptors must act. Further studies are needed to elucidate these specific pathway(s) activated during IFN-gamma stimulation in our model.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

[Transfusion-associated graft-vs-host disease in a patient with Hodgkin's disease].

Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood transfusion which is caused by immunocompetent donor lymphocytes reacting against recipient antigens. We report a case of TA-GVHD in a male patient with Hodgkin's disease who had received several units of non-irradiated blood components. TA-GVHD was diagnosed by histological examination of affected skin and demonstration of engrafted lymphocytes of female phenotype by in situ hybridization using a Y-chromosome specific probe. The need to irradiate blood components given to patients in defined risk-groups is stressed.

Adult↗
PubMed1992

[Extracardiac rhabdomyomas].

Two cases of extracardial rhabdomyomata are described. One case was discovered incidentally at autopsy while the other was primarily examined by needle aspiration biopsy. As far as the authors are aware, this is the first case to be reported.

Aged↗
PubMed1992

Transfusion-associated graft-versus-graft and potential graft-versus-host disease in a renal allotransplanted patient.

Transfusion-associated graft-versus-host disease (GVHD) is a rare but often fatal condition. We report on a case in which a 54-year-old man with polycystic kidneys shortly after receiving a male cadaver donor kidney developed severe intractable rejection and symptoms of GVHD. In situ hybridization with a Y chromosome- "specific" DNA probe and combined in situ hybridization and immunohistochemistry with monoclonal antibodies defining cellular phenotypes were performed on biopsy and tissue specimens taken at rejection episodes and from the lost allograft. The vast majority of infiltrating leukocytes in the morphologically rejecting kidney parenchyma were of female origin and consisted mainly of T lymphocytes and macrophages. This could only be explained by engraftment of leukocytes received in connection with transfusion of female whole blood in association with the transplantation. The patient developed symptoms of GVHD, and graftectomy was performed due to life-threatening cytomegalovirus infection. This case of combined "graft"-versus-graft disease and GVHD indicates that precautions in the administration of blood transfusion to severely immunosuppressed patients should be taken. We recommend the use of gamma-irradiated and lymphocyte-depleted blood products.

Graft Rejection↗
PubMed1992

Expression of the intercellular adhesion molecule-1 (ICAM-1) in human renal allografts and cultured human tubular cells.

The in vivo distribution of the intercellular adhesion molecule ICAM-1 was investigated in renal tissue specimens obtained from 17 renal allotransplanted patients, nine normal kidneys (controls), seven native kidneys, nine patients with mesangioproliferative glomerulonephritis, and nine patients with active extracapillary glomerulonephritis. Biopsies from patients with signs of acute rejection showed a significant increase in ICAM-1 expression in the tubular epithelium (P less than 0.05). In normal kidneys (controls) ICAM-1 expression was found in endothelial cells; additional expression in the tubular epithelial cells was induced in patients with extracapillary glomerulonephritis. The in vitro expression of ICAM-1 was examined in cultured human tubular cells after stimulation with gamma-interferon and interleukin-1, treatment with cyclosporin and/or verapamil and coculture with allogenic mononuclear cells. An increased ICAM-1 expression was demonstrated by coculture with allogenic mononuclear cells and after stimulation with gamma-interferon and/or interleukin-1. Cyclosporin or verapamil induced no changes. Our results give support to the hypothesis that ICAM-1 upregulation is important in immune interactions such as allograft rejection. Furthermore, the in vitro model indicates that ICAM-1 expression is regulated by gamma-interferon and interleukin-1 produced by activated T lymphocytes and macrophages.

Adult↗
PubMed1992

Single and combined effects of the vitamin D analogue KH1060 and cyclosporin A on mercuric-chloride-induced autoimmune disease in the BN rat.

Mercuric chloride induces in BN rats a self-limiting systemic autoimmune disease characterized by proliferation of autoreactive CD4+ T lymphocytes, polyclonal activation of B lymphocytes, and the development of an anti-glomerular basement membrane (GBM) nephritis with concomitant nephrotic range proteinuria. We have used this model of autoimmune disease to test the immunosuppressive ability of a novel vitamin D3 analogue KH1060. This compound prevents autoimmune manifestations including proteinuria, serum IgE, and serum anti-laminin antibodies in a dose-dependent manner, as does cyclosporin A (CyA). When dosages of KH1060 capable of partial reduction of proteinuria without causing significant hypercalcaemia are combined with small dosages of CyA also capable of partial prevention of proteinuria, an additive effect is seen, leading to complete prevention of proteinuria and substantial reductions in serum IgE and anti-laminin levels. Possible mechanisms of action are discussed and it is suggested that KH1060 could prove useful as an immunosuppressive agent in the treatment of autoimmune diseases.

Animals↗
PubMed1992

Stereological estimation of nucleolar organizer regions in prostatic tissue with an optical disector.

Silver-stained nucleolar organizer regions (AgNORs) were studied in 10 hyperplastic, 10 inflamed, nine prostatic intraepithelial neoplastic (PIN) and 20 malignant prostatic lesions. Optical disector measurement on 15 micron sections showed that upper frequency limits for 1.5 microns and 2.0 microns AgNOR particles were 10% and 2% in benign lesions and 18% and 9% in PIN. Using these cut-off values for diagnosis we found a low sensitivity and high specificity in distinguishing benign lesions from PIN and PIN from carcinoma. A high sensitivity and high specificity were obtained in separating benign lesions from carcinoma. AgNOR typing on routine "two-dimensional" sections showed that upper frequency limits for types B2, B3 and C2 were 25%, 3% and 0% in benign lesions and 38%, 23% and 11% in PIN. Using these cut-off values for diagnosis we found lower sensitivity and specificity values among all the differential diagnostic categories. We conclude that although both methods may contribute to the differential diagnosis between benign and malignant prostatic lesions, stereological estimation was a technically simple method, ensuring unbiased sampling and resulting in higher sensitivity and specificity. It may thus prove helpful in the differentiation of borderline cases in routine diagnostic pathology.

Diagnosis, Differential↗
PubMed1992

Human proximal tubular cells modulate allogen responses of leukocytes in vitro.

The interaction between proximal tubular cells and leukocytes was examined. In co-cultures of tubular cells and allogenic leukocytes, tubular cells expressed MHC antigens and ICAM-1. A small number of leukocytes adhered to tubular cells and induced cytotoxic damage. Thus, 65% of the tubular cells were viable after co-culturing with allogenic leukocytes. These cells had low alloreactive capacity, which was not due to lack of interleukin-1 or interferon-gamma. The presence of tubular cells modulated the immune response of leukocytes by reducing the effect of mitogen by 80%, allogens by 65% and interleukin-2 by 40%. A soluble factor released in the co-cultures was a likely mediator, since addition of supernatants from co-cultures suppressed mitogen responses by 27% compared to leukocytes cultured alone. This mediator might be prostaglandin, because addition of indomethacin to co-cultures increased the growth response of leukocytes.

Cell Adhesion Molecules↗
PubMed1992

Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease.

Concentrations of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and soluble IL-2 receptors (sIL-2R) were determined by enzyme linked immunosorbent assays (ELISA) in supernatants of sonicated endoscopical mucosal biopsy specimens from 31 patients with inflammatory bowel disease and 19 controls. IL-1 beta was detected in 53% of the patient supernatants (p = 0.0001), IL-2 in 35% (p = 0.0031), compared with none of the controls. Soluble IL-2R was present in 55% and 26% of the specimens, respectively (p = 0.07). The concentrations of IL-1 beta (p = 0.00015), IL-2 (p = 0.0019), and sIL-2R (p = 0.0073) were highest in the most inflamed biopsy specimens, compared with less inflamed specimens and controls. There were no significant differences in IL-1 beta, IL-2, and sIL-2R concentrations between ulcerative colitis (16) and Crohn's disease patients (15). The results suggest that enhanced cellular immunity operates in vivo at the mucosal level in active inflammatory bowel disease.

Aged↗