The effect of coenzyme Q10 on blood glucose and insulin requirement in patients with insulin dependent diabetes mellitus.
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Adult↗
Biomedical subjects
C B Andersen
Publications and source records attributed to C B Andersen.
CD44 expression is up-regulated in the deep zone of osteoarthritic cartilage from human femoral heads.
AIMS: The objective of this study was to detail the topographical and zonal distribution of the cell adhesion molecule CD44 in normal and osteoarthritic cartilage. METHODS AND RESULTS: Immunohistochemistry utilizing well characterized anti-CD44 antibodies (clones A3D8, Bric 235, 2C5) was performed on cryostat and paraffin sections of human articular cartilage from macroscopically normal (n = 18) and osteoarthritic (n = 11) femoral heads. Samples for cryostat sections were obtained from 12 topographically different sites. Sections were divided into zones (superficial, middle, deep) and the CD44 staining scored. Chondrocytes in normal articular cartilage and cartilage from osteoarthritic femoral heads stained positive for CD44 in both cryostat and paraffin sections. Normal cartilage showed a significant decrease in CD44 staining in the deep zone as compared to the superficial zone (P < 0.05). However, cryostat sections of residual cartilage from osteoarthritic femoral heads showed increased CD44 staining in the deep zone as compared to normal articular cartilage. The CD44 staining showed no topographical variation in either the normal cartilage or the osteoarthritic residual cartilage. CONCLUSIONS: CD44 expression displays a distinct zonal variation in normal articular cartilage which is lost in osteoarthritic cartilage due to an up-regulated expression in the deep zone. CD44 expression does not exhibit topographical variation.
Aged↗
Interaction between proximal tubular cells and allogenic leukocytes mediated by interleukin-1 and prostaglandin.
The present study investigates the interaction between proximal tubular cells (TC) and peripheral blood mononuclear cells (PBMC) with respect to interleukin-1 (Il-1) and prostaglandin E2 (PGE2) in co-culture experiments. Stimulator cells were proliferating human TC propagated in culture and characterized by expression of ICAM-1 and MHC-class II in response to cytokines. The presence of TC reduced spontaneous growth of PBMC by 42%, with a concomittant 50% reduction of Il-1 release and a 6-fold increase of PGE2 release in the growth medium. The growth reduction was partly counteracted by addition of II-1 and indomethacin. Addition of II-1 stimulated the PGE2 release from PBMC and TC by about 75% and 500%, respectively. Growth of TC cultured alone was inhibited by II-1 in a dose-dependent manner, with maximum effect at 10 U/ml, whereas PGE2 showed no effect. These results suggest that TC have the capacity to interact with PBMC, and this potentially tissue-protective mechanism induced by TC may have clinical implications.
Cell Division↗
Dynamic autoregulation and renal injury in Dahl rats.
The Dahl salt-sensitive (Dahl S) rat develops hypertension and renal injuries when challenged with a high salt diet and has been considered to be a model of chronic renal failure. Renal injuries appear very early in life compared with the spontaneously hypertensive rat (SHR). During the course of hypertension, a gradual impairment of autoregulatory control of renal blood flow might expose the glomerular circulation to periods of elevated pressure, resulting in renal injuries in Dahl S rats. Dynamic autoregulatory capacity was assessed in Dahl S and Dahl salt-resistant (Dahl R) rats, SHR, and Sprague-Dawley rats by inducing broad-band fluctuations in the arterial blood pressure and simultaneously measuring renal blood flow. Dynamic autoregulation was estimated by the transfer function using blood pressure as the input and renal blood flow as the output. Renal morphological injuries were evaluated in Dahl S rats and SHR and were scored semiquantitatively. Dynamic autoregulation was efficient and comparable in the low-frequency range (<0.015 Hz) in Dahl R rats, SHR, and Sprague-Dawley rats. The response in Dahl S rats depended strongly on the initiation time of the high salt diet. Autoregulation was preserved during a low salt diet and in rats exposed to a late-onset hypertension of short duration, only partly preserved if the late-onset hypertension was of a longer duration, and abolished in early-onset hypertension. All Dahl S rats on a high salt diet showed severe morphological changes in the kidney. In conclusion, autoregulatory capacity in the kidney of Dahl S rats is gradually impaired when rats are rendered hypertensive with a high salt diet. Renal morphological injuries develop before loss of dynamic autoregulation. Impaired autoregulation appears to be the result, not the cause, of the process that ultimately leads to renal failure in the Dahl S rat.
Animals↗
Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index.
Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool in addition to being an insulin signal for translocation of glucose transporters to the plasma membrane. The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI3-K, to look for an association between gene variants and NIDDM in a case-control study, and to relate identified variability to potential changes in whole-body insulin sensitivity and glucose turnover in a phenotype study. Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation at nucleotide position 1020 (G-->A), changing a Met to Ile at codon 326. Using allele-specific oligohybridization, we found a similar allelic frequency of the codon 326Met-->Ile variant in 404 NIDDM patients (0.15 [95% CI 0.13-0.17]) and 224 matched glucose tolerant control subjects (0.16 [0.13-0.19]). In a random sample of 380 unrelated healthy young Caucasians aged 18-32 years, in whom we have performed a tolbutamide modified intravenous glucose tolerance test, we identified 263 wildtype subjects, 109 heterozygous subjects, and 8 subjects homozygous for the codon 326 variant (allelic frequency = 0.16 [0.13-0.19]). No difference in glucose disappearance constant (KG), insulin sensitivity index (SI), and glucose effectiveness (SG) was observed between wildtype and heterozygous subjects. However, compared with the combined values for wildtype and heterozygous carriers, KG was reduced by 40% (P = 0.004) and SG by 23% (P = 0.03) in homozygous carriers of the p85alpha variant. Moreover, in homozygous carriers, a 32% reduction was found in SI (P = 0.08). In conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha regulatory subunit is found in 31% of a random sample of young healthy Caucasians. About 2% of the subjects in this population carry the gene variant in its homozygous form, and these carriers are characterized by significant reductions in whole-body glucose effectiveness and intravenous glucose disappearance constant. In itself, the gene variant does not confer an increased risk of diabetes.
Adolescent↗
Prevalence of a polymorphism of the phosphatidylinositol 3-kinase p85 alpha regulatory subunit (codon 326 Met-->Ile) in Japanese NIDDM patients.
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Base Sequence↗
Transitional cell carcinoma express vitamin D receptors.
Recently, vitamin D analogues have shown antineoplastic effect in several diseases. Vitamin D analogues exert its effect by interacting with the vitamin D receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been reported. The purpose of the present study was therefore to examine whether human bladder tumor cells express VDR. Tumor biopsies were obtained from 26 patients with TCC. Expression of VDR was examined by immunohistochemical experiments. All tumors expressed VDR. Biopsies from advanced disease contained more VDR positive cells than low stage disease (p < 0.05). Similarly, also tumor grade appeared to be related to the number of cells expressing the receptor. Normal urothlium also expressed VDR but only with low intensity. Our study shows that TCC cells possess the VDR receptor which may make them capable to respond to stimulation with vitamin D, but functional studies of vitamin D's effect on TCC cells in vitro are necessary before the efficacy of treatment with vitamin D analogues in TCC can be evaluated in patients.
Biopsy↗
Acute kidney graft rejection morphology and immunology.
Human kidney allo-transplantation is a successful treatment for end-stage renal failure. The main complication is acute rejection. Although much information has been accumulated on the genetic factors, the clinical and morphological features and the immunological mechanisms involved in acute rejection much remains to be learned. Histological evaluation of needle biopsies is considered one of the most valuable tools in monitoring the transplant. However, very few parameters specific for acute rejection exist and the histological evaluation is complicated by a limited knowledge of the morphology and immunology in well-functioning allografts. The study was undertaken to enlighten the morphological and immunological alterations in the renal allotransplant by biopsiing patients consecutively before and after transplantation. Special emphasis was by immunohistochemistry put on activated cellular infiltrates and adhesion molecules. Studies with cultured human tubular cells were performed to obtain information on mechanisms involved in the regulation of MHC molecules and the intercellular adhesion molecule-1 (ICAM-1). In situ hybridization formats were developed in order to investigate donor-recipient traffic of cellular components and to evaluate the possible influence of cytomegalovirus-infection. Finally, renal changes induced by cyclosporine was sought in a group of patients with chronic uveitis receiving long-term cyclosporine treatment. Arteritis and endocapillary glomerulitis was found to be the only reliable parameters specific to acute rejection. All other morphological parameters showed a continuum of changes from nonrejecting to rejecting patients. Thus, tubulitis and dense mononuclear cellular infiltrates were strongly indicative of acute rejection. Immunohistochemically, strong expression of ICAM-1, vascular cellular adhesion molecule-1 and MHC class II antigens on tubular and endothelial cells along with interleukin-2-receptor bearing infiltrates of T-lymphocytes and significant presence of macrophages were highly correlated with acute rejection. Contrarily, the phenotype of T-lymphocytes including the ratio of CD4+/CD8(+)-lymphocytes, the presence of B-cells or deposits of immunoglobulins and complement factors showed no significant correlation in patients with acute rejection. The in vitro studies confirmed that cytokines such as interleukin-1, tumor necrosis factor and gamma-interferon produced by inflammatory cells are involved in the regulation of ICAM-1 and MHC class II antigens on likely target cells such as tubular epithelial cells. Renal CMV-infection was rare. CMV was not found to induce any changes specifically associated with acute or chronic rejection. Cyclosporine induced tubular atrophy, interstitial fibrosis, glomerulosclerosis and hyaline arteriolar degeneration in kidneys from long-term treated uveitis patients but not in renal transplanted patients. Conclusively, the study confirms the value of pre- and postoperative renal biopsies for the monitoring of renal transplantation. It also stresses the importance of the implementation of molecular biological techniques to obtain more information on the immunological and inflammatory processes involved in acute rejection.
Acute Disease↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗