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Biomedical subjects

C B Andersen

Publications and source records attributed to C B Andersen.

At least 19 recordsLinked to original sources
PubMed1995

Insulin resistance: interactions between obesity and a common variant of insulin receptor substrate-1.

We previously discovered two aminoacid polymorphisms in codons 513 and 972 of the protein insulin receptor substrate-1 (IRS-1), which is important in cellular insulin action. We have investigated whether these polymorphisms are associated with changes in insulin sensitivity in a random sample of young healthy adults. Insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test in 380 unrelated white subjects aged 18-32. IRS-1 polymorphisms were examined by single-strand conformation polymorphism and verified by restriction-enzyme digestion. No homozygous carrier of the codon-513 variant was identified, but one non-obese man had the codon-972 mutation on both alleles. He had low fasting-serum insulin and C-peptide concentrations and low insulin sensitivity and glucose effectiveness. During a 24 h dexamethasone test, he developed transient diabetes. In their heterozygous forms the codon-513 and codon-972 variants of IRS-1 were found in 3% and 9% of the subjects. Non-obese carriers of either polymorphism had similar insulin sensitivity and pancreatic beta-cell function to non-obese wild-type subjects (no known variants of IRS-1). Analysis of variance showed, however, a significant interaction between obesity (body-mass index > or = 25 kg/m2) and the heterozygous form of the codon-972 variant (p < 0.003); obese polymorphism carriers had lower insulin sensitivity than obese non-carriers (mean 6.0 [SD 3.3] vs 12.3 [9.5] x 10(-5) L min-1 pmol-1). The obese carriers of the codon-972 variant were also characterised by a clustering of metabolic cardiovascular risk factors, with raised fasting concentrations of plasma glucose, serum triglyceride, and plasma tissue-plasminogen-activator and its fast-acting inhibitor. With adjustment for known modulators of insulin sensitivity, multivariate analyses showed that the combination of obesity and the codon-972 variant was associated with a 50% reduction in insulin sensitivity (p = 0.0008). Our results suggest that the codon-972 IRS-1 gene variant may interact with obesity in the pathogenesis of common insulin-resistant disorders.

Adolescent↗
PubMed1995

Morphological, stereological, and biochemical analysis of the mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction.

Chronic partial bladder outlet obstruction was created in nine mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days, the ring was removed and after a recovery period of median 60 days the animals were sacrificed. Changes in muscle and connective tissue were assessed by unbiased, modern morphometry and biochemical analysis. After obstruction the results were as follows: (1) a 6-fold increase in bladder weight, (2) a 2.5-fold increase in smooth muscle cell size, (3) a 3-fold increase in smooth muscle cell number, (4) unchanged proportions between muscle and connective tissue, (5) unchanged hydroxyproline concentrations, (6) an 8-fold increase in total collagen content, (7) an increase in the ratio of type I/III collagen, and (8) a 7-8-fold increase in total content of type I and III collagen. All changes were markedly, though incompletely, reversed after recovery, except smooth muscle cell number and the ratio of type I/III collagen.

Animals↗
PubMed1995

Length density and total length of acetylcholinesterase positive nerves related to cystometry and in vitro studies of muscle strips in mini-pig urinary bladder after chronic outflow obstruction and recovery from obstruction.

Chronic partial bladder outlet obstruction was created in mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days, the ring was removed and after a median recovery period of 60 days the animals were sacrificed. At each occasion stepwise cystometry, measurement of residual urine, muscle strips studies with electrical and carbachol stimulation, and stereological estimations of length density and total length of acetylcholinesterase positive nerves were performed. The results can be summarized as follows: (1) unchanged sensitivity of muscle strips to carbachol, but markedly decreased contractility and rate of contraction to carbachol, (2) no evidence of detrusor instability, but severely decompensated bladders in two pigs, (3) a significant increase in residual volume, (4) a pronounced decrease in length density and total length of acetylcholinesterase positive nerves, and (5) at field stimulation strips from some pigs showed increased sensitivity and contractility with high atropine and TTX resistance, while strips from the other pigs revealed decreased sensitivity and markedly decreased contractility to electrical stimulation. In general, most of the changes were markedly, though incompletely, reversed after recovery. Light and electron microscopy of muscle strips showed no histological or ultrastructural changes during the experiments or after storing 1 day at 4 degrees C.

Acetylcholinesterase↗
PubMed1995

The etiology of hypertension in nonrenovascular unilateral renal disease--two cases of renin induced hypertension in congenital renal dysplasia.

We report two cases of severe hypertension and unilateral renal dysplasia. No renal artery stenosis and no other urogenital malformations were found. In both cases we found substantially enhanced secretion of renin from the dysplastic kidney. After nephrectomy both patients obtained a distinctive and permanent reduction or normalization of blood pressure. In the two cases reported, regional renin release induced by ischemia is a very likely etiological factor.

Adult↗
PubMed1995

A comparison between the effects of paraffin and plastic embedding of the normal and obstructed minipig detrusor muscle using the optical dissector.

PURPOSE: The purpose of this study was to estimate the relative shrinkage of the normal, obstructed and recovery minipig urinary bladder by comparing tissues from the same bladders embedded in paraffin or plastic. MATERIALS AND METHODS: Optical dissectors were used to make nucleus numerical density estimates in thick paraffin and plastic sections from the same bladder. The ratio of the 2 numerical densities depends only on differences in tissue shrinkage. In 9 minipigs a partial bladder outlet obstruction was created by implanting a 6 to 7 mm. Teflon ring around the proximal urethra. After an obstruction period (median 63 days) the ring was removed and after a recovery period (median 60 days) the animals were sacrificed. Biopsies were taken prior to obstruction, at removal of obstruction, and after recovery and were processed for paraffin and plastic sections to evaluate relative shrinkage. Two control pigs were sham-operated and biopsies taken at the same 3 time points. RESULTS: The optical dissector method was found to be an easy way to estimate the relative shrinkage of paraffin-embedded bladder tissue in proportion to plastic-embedded tissue. Both in human and minipig bladders, paraffin embedding caused a relative shrinkage of about 30% in proportion to plastic embedding. Both the obstructed and recovery detrusor muscles responded to embedding by either method in a manner indistinguishable from the normal bladder. CONCLUSION: When dealing with stereological evaluation of the detrusor muscle, the relative shrinkage of the embedded normal, obstructed and recovery bladder tissue can be ignored.

Animals↗
PubMed1994

Role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in peripheral blood mononuclear cell activation by human renal carcinoma cells.

We examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) during the activation of peripheral blood mononuclear cells (PBMCs) by the human renal carcinoma cell line CaKi-1. ICAM-1 antigen expression was induced on CaKi-1 cells by incubation with either phorbol-12-myristate 13 acetate (PMA) or interferon-gamma (IFN-gamma). Following a thorough washout of PMA and IFN-gamma and subsequent paraformaldehyde fixation, CaKi-1 cell monolayers were cocultered with allogenic PBMCs. While PMA-treated CaKi-1 cells induced PBMC proliferation and interleukin-2 receptor antigen expression, this was not the case for control or IFN-gamma-treated CaKi-1 cells. Furthermore, the induced PBMC proliferation was inhibited by specific monoclonal antibodies against ICAM-1 and LFA-1. Finally, although PMA induced human leukocyte antigen (HL)-A, B, C antigen expression on CaKi-1 cells, a monoclonal antibody against this antigen did not inhibit PBMC proliferation. We conclude that PMA can modulate CaKi-1 cells to stimulate allogenic PBMC proliferation in an ICAM-1/LFA-1 dependent, but HLA-A, B, C-independent, fashion. This stimulation might reside in the long-term activation of protein kinase C, induced by PMA.

Antibodies, Monoclonal↗
PubMed1994

Stimulation of intercellular adhesion molecule-1 (ICAM-1) antigen expression and shedding by interferon-gamma and phorbol ester in human renal carcinoma cell cultures: relation to peripheral blood mononuclear cell adhesion.

In the present study we investigated the effect of interferon-gamma (IFN-gamma) and phorbol-12-myristate 13 acetate (PMA) on intercellular adhesion molecule-1 (ICAM-1) antigen expression and shedding in human renal carcinoma cell cultures. We also examined the functional consequences of ICAM-1 antigen expression and soluble ICAM-1 molecules on the adhesion of peripheral blood mononuclear cells (PBMC). Incubation of the human renal carcinoma cell line CaKi-1 with IFN-gamma or PMA enhanced ICAM-1 antigen expression. The calcium ionophore, 4-bromo-calcium ionophore A23187 (Bromo-A23187) significantly enhanced the IFN-gamma and PMA effect. Soluble ICAM-1 (sICAM-1) was detected in the supernatants of stimulated but not unstimulated cultures, and correlated significantly with cellular expression. Using 51Cr-labelled peripheral blood mononuclear cells in a cell adhesion assay, we demonstrated increased adhesion in IFN-gamma-treated CaKi-1 cultures, which was augmented by Bromo-A23187. This adhesion was blocked by preincubation of CaKi-1 cells with monoclonal antibody against ICAM-1 or by preincubation of PBMC with either monoclonal antibody against leucocyte function associated antigen-1 alpha (LFA-1 alpha), a major receptor for ICAM-1, supernatants from treated cultures or purified sICAM-1 molecules. Thus, shedding of ICAM-1 may play a role during the escape from immunosurveillance by renal carcinoma cells.

Antigens, Neoplasm↗
PubMed1994

Interferon-gamma increases cellular calcium ion concentration and inositol 1,4,5-trisphosphate formation in human renal carcinoma cells: relation to ICAM-1 antigen expression.

In the present study, we investigated the effect of interferon-gamma (IFN-gamma) on cellular calcium ion concentration [Ca2+]i and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) formation in the human renal carcinoma cell line CaKi-1. We also examined the possible role of a Ca(2+)-dependent mechanism during IFN-gamma-induced intercellular adhesion molecule 1 (ICAM-1) antigen expression. IFN-gamma caused a rapid concentration-dependent rise in [Ca2+]i, which was partly inhibited by diltiazem, a calcium channel blocker, TMB-8, an inhibitor of intracellular calcium redistribution, and in calcium-free medium. IFN-gamma caused a fourfold increase in Ins 1,4,5-P3 formation. The induction of ICAM-1 antigen expression was synergistically enhanced by 4-bromocalcium ionophore A23187. Finally, the calcium antagonists diltiazem. TMB-8 and EGTA, as well as two potent inhibitors of Ca(2+)-dependent kinases, calmidazolium (R24571) and W7, had no or only a minor inhibitory effect on IFN-gamma induction. Our data suggest that IFN-gamma increases [Ca2+]i in CaKi-1 cells by stimulating influx of Ca2+ and release of Ca2+ from intracellular stores, probably via Ins 1,4,5-P3 formation. IFN-gamma signal transduction in our model may not be limited to an increase in [Ca2+]i and Ins 1,4,5-P3, since IFN-gamma-induced ICAM-1 antigen expression was abrogated to a minor degree by calcium antagonists and not coupled to Ins 1,4,5-P3 formation.

Antigens↗
PubMed1994

Influence of diltiazem on renal function and rejection in renal allograft recipients receiving triple-drug immunosuppression: a randomized, double-blind, placebo-controlled study.

In a prospective, randomized and placebo-controlled study we evaluated the influence of treatment with the calcium-channel blocker diltiazem on the course and results of cadaveric kidney transplantation in 39 graft recipients. The grafts were reperfused with Euro-Collins solution containing diltiazem 20 mg/l. All recipients except those in chronic treatment with a calcium-channel blocker received preoperatively a bolus of diltiazem or placebo 0.3 mg/kg and in all an infusion of diltiazem or placebo 3 mg/kg/24 h was started preoperatively. After that, diltiazem or placebo was given orally for 3 months. Donors were not treated. Immunosuppressive therapy consisted of prednisone, azathioprine and CsA. There were no significant differences between the groups concerning donor or recipient characteristics, HLA-mismatching, and ischaemic time. Thrombosis leading to graft loss occurred in 3 recipients (diltiazem:2, placebo:1) and one graft was lost due to septicaemia (diltiazem). For the remaining 35 grafts no beneficial effect of treatment with diltiazem was found for the rate of delayed graft function, the rate of rejections, time to first rejection, whole blood CsA concentration, or graft function. The CsA dose needed to reach target whole blood concentration was significantly less in the diltiazem group. In conclusion, our results do not indicate any beneficial effects of treatment with diltiazem in cadaveric kidney transplantation, except a reduction of costs because of a significant reduction of the CsA dosage.

Adult↗
PubMed1994

Polymerase chain reaction as a rapid diagnostic assay for cytomegalovirus infection in renal transplant patients.

The aim of this study was to apply a polymerase chain reaction for diagnosis of CMV infection and determine its clinical value in renal transplant recipients. We have applied the PCR to urine and blood specimens collected from 27 renal transplant recipients as well as blood from 49 normal blood donors. Ten of twenty-seven patients, compared to 3 of 49 normal blood donors, had CMV-DNA present in one or more samples. Six of the ten CMV-DNA-positive patients had positive CMV serology, and 3 of the 10 had severe clinical symptoms of active CMV infection. In four additional patients with positive CMV serology - but without clinical signs of active CMV infection - no CMV-DNA could be detected by the PCR. In the three patients with severe symptoms, PCR could detect CMV-DNA before serology became positive, and in one of these three patients, serology remained negative despite the patient's death from clinically obvious CMV pneumonia. PCR thus appears capable of detecting active CMV infection at a time when CMV serology is inconclusive, but cannot substitute for serology as the only routine analysis since a transient viraemia might be missed. However, in immunosuppressed patients with severe CMV infection, PCR could provide an early diagnosis, enabling the clinician to implement early specific treatment.

Antibodies, Viral↗
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↗