Placebo-controlled trials in palliative care: the argument against.
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Ethics, Medical↗
Biomedical subjects
J Abel
Publications and source records attributed to J Abel.
Random-network simulation of an ultracapacitor based on metal-solid-electrolyte composite.
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Journal Article↗
Aryl hydrocarbon receptor mRNA levels in different tissues of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-responsive and nonresponsive mice.
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Animals↗
Dose-response relationship of cytochrome P4501b1 mRNA induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin in livers of C57BL/6J and DBA/2J mice.
The dose-response relationship of cytochrome P4501b1 (Cyp1b1) and Cyp1a1 induction in livers of TCDD-treated female C57BL/6J and DBA/2J mice are described. The animals were treated i.p. with 0.001, 0.01, 0.1, 1, 10 and 50 micrograms TCDD/kg for 24 h, and Cyp1b1 and Cyp1a1 mRNA expression was analyzed by RT-PCR. In the livers of both mouse strains, the Cyp1b1 and Cyp1a1 mRNA content was increased after TCDD exposure in a dose-dependent manner. These effects were more pronounced in TCDD-responsive C57BL/6J mice than in the less responsive DBA/2J mice, although Cyp1a1 was more responsive to TCDD than Cyp1b1 in both strains. The calculated ED50 values for Cyp1b1 and Cyp1a1 induction in livers of TCDD-treated C57BL/6J mice were 1.3 and 0.08 micrograms TCDD/kg, respectively. The corresponding values for half-maximal induction response in livers of DBA/2J mice were 3.4 micrograms TCDD/kg for Cyp1b1 and 1.5 micrograms TCDD/kg for Cyp1a1. These results show that Cyp1b1 mRNA expression is less inducible by TCDD than Cyp1a1. Both genes are highly inducible in TCDD-responsive C57BL/6J mice expressing the high affinity arylhydrocarbon receptor (Ah receptor), suggesting that Cyp1b1, like Cyp1a1, is a potential Ah receptor-regulated gene.
Animals↗
Serum erythropoietin levels in patients with sepsis and septic shock.
The role of the immune system in the control of the production of erythropoietin is still poorly understood. Herein, the levels of circulating immunoreactive erythropoietin, tumour necrosis factor alpha, interleukin-1 beta and interleukin-6 were determined in 10 septic patients for up to 4 d following the admission to an internal intensive care unit. The data show that the production of erythropoietin was not suppressed despite an increase in the levels of proinflammatory cytokines. Circulating erythropoietin and interleukin-6 greatly increased in the 6 nonsurviving patients. The pattern of the serum erythropoietin level in the nonsurvivors resembled that of acute phase proteins and was independent of the blood haemoglobin concentration. Similar to interleukin 6, abnormally high serum erythropoietin levels appear to be a negative prognostic indicator in patients suffering from septic shock.
Adult↗
Different response of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive genes in human breast cancer MCF-7 and MDA-MB 231 cells.
Human breast cancer cell lines are widely used to study the antiestrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vitro. Like other groups we found that 10 nM TCDD inhibits cell growth and induces cytochrome P450 1A1 (CYP1A1)-associated 7-ethoxyresorufin-O-deethylase (EROD) activity in MCF-7 cells expressing the estradiol receptor (ER). Neither cell growth nor EROD activity was affected in ER-negative MDA-MB 231 cells. Results of reverse transcription-polymerase chain reaction (RT-PCR) revealed a strong induction of CYP1A1 mRNA in MCF-7 but only a weak increase in MDA-MB 231 cells treated with 1, 10, or 100 nM TCDD. Transcripts of CYP1B1 were detected in both cell lines and mRNA content was enhanced 8- and 30-fold in MCF-7 and MDA-MB 231 cells treated with 1 nM TCDD, respectively. In gel mobility shift assay a stronger signal of DNA-binding aryl hydrocarbon receptor (AhR) was observed in MDA-MB 231 than in MCF-7 cells treated with 10 nM TCDD. These results were confirmed by RT-PCR analyses which showed an approximately 40-fold higher AhR mRNA content in untreated MDA-MB 231 than in MCF-7 cells. In contrast the mRNA of the AhR nuclear translocator was expressed in a similar range of magnitude. Treatment of the cells with TCDD did not change mRNA expression of both genes. Analysis of NADPH:quinone oxidoreductase (NMO-1) and plasminogen activator inhibitor-2 (PAI-2) mRNA expression revealed a dose-dependent induction of both genes in MDA-MB 231 cells after TCDD-treatment. From the results it was concluded that AhR-mediated transactivation is not impaired in ER-negative MDA-MB 231 cells. In addition, the results confirm reported data that expression of ER seems to be important for regulation of CYP1A1 induction after TCDD in human breast cancer cell lines but the present data show that ER does not appear to have a function in TCDD-induced mRNA expression of CYP1B1, NMO-1, and PAI-2 in MDA-MB 231 cells.
Base Sequence↗
Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on growth factor expression in the human breast cancer cell line MCF-7.
The aim of this study was to examine whether changes in growth factor or cytokine expression could be responsible for the growth inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the human breast cancer MCF-7 cell line. Treatment of MCF-7 cells with 10 nM TCDD for 7 days reduced the cell growth to 60% of control; this effect was partly abolished by cotreatment of the cells with 100 nM 17 beta-estradiol (E2). The inhibition of cell growth by TCDD was accompanied by an enhanced secretion of transforming growth factor-beta (TGF-beta) and the TGF-beta content in cell culture supernatants was 2-fold higher than in controls. Using reverse transcription polymerase chain reaction (RT-PCR), the effect of TCDD on the expression of TGF-beta isoforms, transforming growth factor-alpha (TGF-alpha), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) was investigated. It was demonstrated that incubation with 1, 10 and 100 nM TCDD for 24 h increased mRNA levels of TGF-alpha, TNF-alpha and IL-1 beta. The strongest effect was found on IL-1 beta, the mRNA level of which was dose-dependently increased. TCDD had a minor effect on TGF-alpha and TNF-alpha mRNA. The mRNA levels were significantly increased after treatment with 10 and 100 nM TCDD. The mRNA expression of TGF-beta 1 and TGF-beta 2 was unchanged, whereas the TGF-beta 3 mRNA level was enhanced 2 to 3-fold after TCDD treatment. From the results, we suggest that TCDD-induced growth inhibition in MCF-7 cells is related to the growth inhibitory action of a set of growth factors and cytokines which have a contextual action on MCF-7 cell proliferation.
Analysis of Variance↗
Ah receptor in different tissues of C57BL/6J and DBA/2J mice: use of competitive polymerase chain reaction to measure Ah-receptor mRNA expression.
A competitive polymerase chain reaction (PCR) method was used to determine the Ah-receptor mRNA content in several tissues of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6J and less susceptible DBA/2J mice. Total RNA from liver, lung, thymus, spleen, heart, kidney, brain, muscle, and placenta was isolated and reverse-transcribed. Each cDNA was coamplified with a known amount of homologous competitor fragment, and PCR products were quantified by extrapolating against a standard curve. The Ah-receptor mRNA was expressed in all tissues examined. The highest mRNA level was found in lung, yielding concentrations of 31.7 +/- 11.0 X 10(3) molecules/100 ng RNA and 20.3 +/- 8.9 X 10(3) molecules/100 ng RNA in C57BL/6J and DBA/2J mice, respectively. In heart, liver, thymus, brain, and placenta the Ah-receptor mRNA content was about 5-10 times lower than in lung. Low levels were found in spleen, kidney, and muscle. Statistical analysis of the data revealed no significant differences regarding the Ah-receptor mRNA expression between C57BL/6J and DBA/2J mice. From these results it is suggested that factors other than differences in Ah-receptor mRNA content may be responsible for different susceptibility of C57BL/6J and DBA/2J mice toward TCDD.
Animals↗
Transforming growth factor-beta 1 inhibits TCDD-induced cytochrome P450IA1 expression in human lung cancer A549 cells.
The effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of cytochrome P450IA1 (CYPIA1) was examined in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human lung cancer A549 cells. Using the reverse transcription-polymerase chain reaction (RT-PCR) it was demonstrated that TGF-beta 1 inhibits CYPIA1 expression in a dose dependent manner. Based on the inhibitory concentration 50 (IC50) of about 5 pM it is suggested that TGF-beta 1 has a physiological function in downregulation of this cytochrome. In the presence of cycloheximide, the effect of TGF-beta 1 on CYPIA1 mRNA disappeared. This finding indicates that protein synthesis may be required for the TGF-beta 1 mediated response of CYPIA1. The possible mechanisms by which TGF-beta 1 interacts with TCDD-responsive drug metabolizing enzymes are discussed.
Cycloheximide↗
Modulation of growth factor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant, which causes a variety of toxic effects including alterations in cell growth and differentiation. In the last years it became increasingly evident that growth factors and their corresponding receptors are involved in toxic responses of this compound. The interference of TCDD with growth factor expression has been studied in several in vitro and in vivo systems. Here, we give a short summary of the published data about interactions between TCDD and growth factors.
Animals↗
Metallothionein in isolated pancreatic islets of mice: induction by zinc and streptozotocin, a naturally occurring diabetogen.
Metallothionein (MT) concentrations were determined in the cytosol of isolated pancreatic islets of mice, using both the cadmium (Cd)-heme and the Cd-Chelex assay. Both constitutive MT levels and significant MT induction were detected in islet cells. For MT induction, mice were injected intraperitoneally (i.p.) with either zinc sulfate (Zn) or the diabetogen streptozotocin (STZ). Following an i.p. injection of 15 mg Zn.kg-1 body weight (body wt), the mean index of MT induction found in islets was comparable to that found in liver tissue, which was used as control. After i.p. injection of 30 mg Zn.kg-1 or a single high dose of STZ (100 or 200 mg.kg-1), the indices of MT induction in islets exceeded those in liver by a factor of 1.3, 2.5, or 1.5. After multiple low doses of STZ (3 or 5 x 40 mg.kg-1 given on consecutive days), in contrast, the MT induction indices in islets exceeded those in liver by a factor of 3.5 and 3.9 for 3 x 40 respectively 5 x 40 mg STZ.kg-1. In conclusion, our results demonstrate constitutive MT levels in isolated pancreatic islets and significant MT induction after i.p. injection with Zn or STZ, in particular after repeated low doses of STZ.
Animals↗
Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.
Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.
Amyloid beta-Protein Precursor↗
[Spastic hemiparesis after apoplexy in renal hypertension due to mesangioproliferative glomerulonephritis (with immunosuppressive treatment) and primary hypothyroidism--which vaccinations are permitted?].
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Cerebrovascular Disorders↗
Comparative study on metallothionein induction in whole testicular tissue and isolated Leydig cells.
The present study aimed at investigating whether previously reported interstrain differences of mice in testicular susceptibility to cadmium toxicity can be attributed to different metallothionein expression in the testes and other organs. Furthermore, purified Leydig cell systems were employed to identify a testicular compartment capable to respond specifically to exogenous cadmium by increased metallothionein expression. It was shown that species differences in testicular damage after cadmium administration can not be explained by differences in cadmium-induced stimulation of hepatic and renal metallothionein. In contrast to these organs, no metallothionein response to cadmium was observed in testicular homogenates. However, both freshly isolated and purified rat Leydig cells and a murine tumor Leydig cell line are not only able to synthesize metallothionein under basal conditions, but also respond to exogenous cadmium by increased synthesis of metallothionein (35S-cysteine incorporation) and an increased Mt-mRNA content. Extracts from freshly isolated and purified rat Leydig cells contained a cadmium-binding component which eluted in gel chromatography with the same properties as metallothionein. It was concluded that the use of purified cell systems is a valuable tool to investigate possible targets of cadmium toxicity.
Animals↗
Technique and pitfalls of retrograde continuous warm blood cardioplegia.
The recent development of normothermic myocardial preservation and systemic perfusion during bypass has questioned the fundamental need for hypothermia during cardiac operations. The antegrade technique of almost continuous perfusion by the aortic root and vein grafts has been supplemented by continuous normothermic blood cardioplegia through the coronary sinus. Recently, great interest has been shown in this technique. It is important to describe the method in detail along with its potential shortcomings and dangers. This communication describes the technical details, pitfalls, and shortcomings of retrograde continuous warm blood cardioplegia.
Blood↗
Serum prolactin concentration and hypothalamic-pituitary hormone release in CF-children.
Some experimental data from animals suggest that prolactin (PROL) is involved in sweat production and modulates the chloride concentration of sweat. We determined the serum PROL level by RIA in 38 CF-patients (age: 3-24 years) and 48 patients with bronchial asthma (age: 2-18 years) and found no concentration differences between the two groups each taken as a whole; the TSH level was increased in CF (p less than 0.05). Separate analysis showed a significantly higher PROL level in CF-females and in CF-children (male and female) under 12 years old (p less than 0.05). To assess the hypothalamic-pituitary system we performed the metoclopramide test (by Cerucal) on 30 children suffering from CF (n = 10), bronchial asthma (n = 10) or pyelonephritis (n = 10) for PROL, LH, FSH, TSH and HGH. The hormone release was normal for all kinds checked in all groups of patients. Hence it follows that the neurohormonal system of prolactin is normal in CF-patients and the increased serum PROL and TSH concentrations in CF should be seen as a regulatory phenomenon but not as a mechanism associated with the basic defect of the CF-disease.
Adolescent↗
[Acute poisoning caused by the herbicide dichlorprop (preparation SYS 67 PROP)].
We report on the acute poisoning of a 5-year-old boy by the herbicide "dichlorprop". This preparation is described as an effective means of plant protection. The effects of the intoxication were established by changes observed in almost all of the child's organs. The predominant effect was haemolytic anemia. All the pathological parameters regressed as a result of symptomatic therapy. General conclusions are drawn about intoxication, especially by means of plant protection agents.
2,4-Dichlorophenoxyacetic Acid↗
[Urodynamics of urethral valve resection].
Basing on the cases of 8 children with urethral valves who were diagnosed and treated during the first year of life we report on the urodynamic results. It is concluded that after valve resection enhanced pressure levels may still exist during micturition for some time even if the flow of urine has become normal. A morphologically and functionally satisfactory treatment result (separate lasix clearance on both sides) can be expected only after the pressure has dropped, a phenomenon that often occurs spontaneously.
Follow-Up Studies↗