Focal vertebral artery dissection causing Brown-Séquard's syndrome.
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Aortic Dissection↗
Biomedical subjects
R Jäger
Publications and source records attributed to R Jäger.
Differential expression and biological activity of the heparin-binding growth-associated molecule (HB-GAM) in lung cancer cell lines.
The growth of human lung cancer cells is regulated positively and negatively by a variety of growth factors through autocrine as well as paracrine mechanisms. In the present report, we studied the differential role and expression of a neuropolypeptide growth factor in 26 lung cancer cell lines. Expression of the heparin-binding growth-associated molecule (HB-GAM) in 12 small cell lung cancer (SCLC) cell lines was compared to that in 14 non-small cell lung cancer (NSCLC) cell lines. HB-GAM mRNA was expressed in 9 of 12 SCLC and 3 of 14 NSCLC cell lines as determined by RT-PCR analyses. Normal human bronchial epithelial cells were used as negative controls. All cell lines which expressed HB-GAM mRNA produced HB-GAM protein as well. Western blot analysis showed that the tumor cells secreted HB-GAM into the media. HB-GAM, purified from lung cancer cell lines, exerted biological activity on fibroblasts, endothelial cells and SW13 cells as determined by thymidine incorporation and soft agar cloning assays. In addition, the biological activity of HB-GAM was blocked by a specific antibody in a dose-dependent way. Our findings suggest that HB-GAM may serve as a marker for SCLC cell lines and that it may function as a paracrine growth factor in human lung cancer. HB-GAM may be a further member of the network of growth factors involved in proliferation, angiogenesis and metastasis of lung tumors.
Blotting, Western↗
Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice.
Expression of the apoptosis-inhibitory protein Bcl-2 has frequently been detected in human cancer including mammary carcinoma. The functional significance of its expression has been well established in experimental tumors of the lymphoid system, however, remains to be elucidated for epithelial tumors. In order to assess the role of Bcl-2 in mammary tumorigenesis we have generated WAP-bcl-2 transgenic mice. The strong overexpression of Bcl-2 in lactating mammary glands was preserved during early postlactational involution and apoptosis of alveolar epithelial cells was prevented without influencing the dedifferentiation of the milk-producing epithelium. Although Bcl-2 overexpression was not sufficient to induce spontaneous tumors it, however, led to an accelerated development of MMTV myc transgene-induced mammary tumors. In the mammary glands of MMTV myc transgenic mice, a high proportion of apoptotic cells was detected which was significantly reduced in the mammary glands of WAP-bcl-2/ MMTV myc double transgenic mice. Taken together, these results suggest that Bcl-2 contributes to mammary tumorigenesis by inhibiting apoptosis.
Animals↗
Control of proteinase expression by phorbol-ester- and Fos-dependent pathways in human non-small-cell lung-cancer cells.
Activation of protein kinase C- (PKC) and Fos/Jun-dependent signal transduction pathways are thought to be major effects of oncogene action in different tumor systems including human non-small-cell lung carcinoma (NSCLC). We have previously shown that the phorbol ester analogue phorbol-myristate-acetate (PMA), which is a potent activator of PKC, can induce squamous-type cellular differentiation and the expression of proteinases, such as plasminogen activators and pro-cathepsin L, in several NSCLC cell lines. To investigate the PMA-dependent effect on proteinase secretion in more detail, we have now analysed the role of a downstream transmitter of PKC activity in this process, namely Fos, which is part of the AP-1 transcription factor in the nucleus. We transfected a cell line derived from an undifferentiated squamous-cell lung carcinoma with different chimeric fos-estrogen receptor constructs (fos-ER) which makes selective activation of this transcription factor possible. The resulting clones were treated either with PMA as activator of PKC, or with diethylstilbestrol (DES), an estrogen analogue binding to and thereby activating preformed Fos-ER molecules. We show that cells treated with either substance undergo similar phenotypic changes (change from cuboidal to spindle-cell type) and decrease their doubling rates and cloning efficiencies. This is paralleled by the induction of several proteinase genes such as t-PA, urokinase, and pro-cathepsins B and L. Contrary to activated PKC, Fos in this system seems to be unable to initiate terminal squamous-cell differentiation, as assessed by the production of cornified envelopes. It is, however, efficient in the stimulation of neutral or lysosomal proteinase secretion as determined by Western-blot analysis and zymography. This Fos-ER expressing system thus seems to be a valuable tool in the molecular dissection of pathways that lead to the activation and secretion of proteinases in NSCLC cells.
Carcinoma, Non-Small-Cell Lung↗
Uptake of various trace elements during germination of wheat, buckwheat and quinoa.
The practice of sprouting is widely used to improve the nutritional value of grain seeds. Several nutritive factors such as vitamin concentrations and bioavailability of trace elements and minerals increase during germination. The objective of this work was to study the enrichment of various essential trace elements during germination of wheat (Triticum aestivum), buckwheat (Fagopyrum esculentum), and quinoa (Chenopodium quinoa) seeds in order to improve their nutritional role as a source of bioavailable trace elements. Seeds were sprouted either in distilled- or tap-water and in five different electrolyte solutions to investigate the concentration-dependent uptake. The time-dependence was investigated by analyzing aliquots of the sprouts after certain germination periods. Samples were analyzed after freeze drying for their Li, V, Cr, Fe, Mn, Co, Cu, Zn, Sr, Mo, As and Se concentrations with inductively-coupled plasma mass-spectrometry (ICP-MS). As a control for possible changes in the biochemical metabolism of the sprouts, the biosynthesis of vitamin C was also determined by using reversed-phase ion-pair HPLC. It was shown that quinoa was the most resistant to the applied electrolyte solutions and had the highest uptake rates for almost all elements, followed by buckwheat and wheat. Greatest increases were observed for Co, Sr, and Li. No significant changes in vitamin C biosynthesis were observed between sprouts grown in different electrolyte solutions. The time-dependent uptake for most elements was characterized by a significant absorption during soaking of the seeds, followed by a lag phase during the first day of germination and an increased uptake during the second and third day. Se and As showed distinctly different uptake behaviors.
Ascorbic Acid↗
Separate channels for visuomotor transformations in the pigeon.
Since the discovery of two parallel visual systems in humans and primates there has been much speculation about their functions. One prominent current model, suggesting independent processing of visual information for perception and action, is supported by neuroanatomical, electrophysiological, neurobehavioral, and human clinical data. Furthermore, studies of visuomotor behavior in amphibians and non-primate mammals indicate that neural processing of action-related behavior is mediated by separate neuronal channels thus suggesting an evolutionary principle in the organization of visuomotor behavior. If such an evolutionary principle operates it should also apply to birds. I will present and discuss behavioral and behavioral physiological evidence that action-related behavior in pigeons like pecking, grasping and control of gaze is controlled via separate neuronal channels subserving visuomotor functions.
Amphibians↗
The human ubiquitin C promoter directs high ubiquitous expression of transgenes in mice.
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Animals↗
Can grapefruit juice influence ethinylestradiol bioavailability?
The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.
Administration, Oral↗
Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells.
Retinoids and vitamin D are important factors that regulate cellular growth and differentiation. An additive growth-inhibitory effect of retinoids and vitamin D analogues has been demonstrated for human myeloma, leukaemic and breast cancer cells. We set out to study the effects of the vitamin D analogue EB1089 and the retinoids all-trans- and 9-cis-retinoic acid on the human pancreatic adenocarcinoma cell lines Capan 1 and Capan 2 and the undifferentiated pancreatic carcinoma cell line Hs766T. The cell lines investigated expressed vitamin D receptor, retinoic acid receptor (RAR)-alpha and gamma as determined by polymerase chain reaction after reverse transcription. RAR-beta was expressed only in Hs766T cells. Addition of all-trans-retinoic acid increased the amount of RAR-alpha mRNA in the three cell lines and induced RAR-beta mRNA in Capan 1 and Capan 2 cells. All-trans-retinoic acid at a concentration of 10 nM inhibited the growth of Capan 1 and Capan 2 cells by 40% relative to controls. 9-cis-Retinoic acid was less effective. Neither all-trans-retinoic acid nor 9-cis-retinoic acid affected the growth of Hs766T cells. EB1089, if added alone to the cells, did not significantly inhibit growth. However, the combination of 1 nM EB1089 with 10 nM all-trans-retinoic acid exerted a growth-inhibitory effect of 90% in Capan 1 cells and of 70% in Capan 2 cells. Our data suggest that vitamin D analogues together with retinoids inhibit the growth of human pancreatic cancer cells. However, in vivo studies are necessary to examine the potential use of retinoids and vitamin D analogues on pancreatic cancer.
Animals↗
[Results of an open study for evaluating the effectiveness and tolerance of adjuvant administration of the ISF nutrient program in HIV positive patients].
HIV positive patients usually show a gradual deterioration of their general condition and the laboratory key values which are accompanied by the resulting negative effects on their subjective condition. This study showed a very good stabilization of HIV positive patients by using the complex ISF nutrient program over a period of ten or 15 months. Only a very low proportion of antiviral and antibiotic supply had been given. The ratio did not change over the entire testing period of 15 months. The mortality rates observed here were a fraction of the AIDS mortality rates that are otherwise published. The data of this study also show a very good benefit/risk relationship for the patients, which can be derived from the overall favorable statements on the tolerance.
Adolescent↗
Modulation of noradrenaline release in rat isolated stomach by prostanoids, but not by histaminergic mechanisms.
Several gastric functions are modulated by the sympathetic nervous system, but local mechanisms involved in the control of noradrenaline release are largely unknown. Overflow of endogenous noradrenaline was studied from isolated rat stomach incubated in Ussing chambers allowing the separate determination of mucosal and serosal overflow. Spontaneous noradrenaline overflow was similar at the mucosal and serosal side, but electrical field stimulation caused a frequency-dependent increase in noradrenaline overflow selectively at the serosal side. Evoked noradrenaline overflow was blocked by tetrodotoxin, not affected by indometacin and markedly enhanced (by about 250%) by yohimbine. In the presence of indometacin and yohimbine, sulprostone (an agonist at EP1/EP3 receptors) and misoprostol (an agonist at EP2/EP3 receptors) reduced the noradrenaline overflow evoked by stimulation at 3 Hz maximally by about 80% (EC50: 6 nmol/l and 11 nmol/l, respectively). The EP1 receptor selective antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) did not antagonize the inhibition by sulprostone. Noradrenaline overflow evoked by stimulation at 1 Hz and 3 Hz was increased by scopolamine by about 50% and almost completely inhibited by oxotremorine. Neither, histamine nor the H3 receptor selective agonist (R)-alpha-methyl-histamine, nor the H1, H2 and H3 selective receptor antagonists mepyramine, cimetidine and thioperamide significantly affected noradrenaline overflow evoked by stimulation at 1 Hz or 3 Hz. In conclusion, impulse-induced noradrenaline release in the rat stomach is controlled by multiple presynaptic mechanisms involving alpha 2-adrenergic autoreceptors, EP3 prostanoid and muscarine heteroreceptors, whereas histaminergic mechanisms do not appear to be significant.
Abortifacient Agents, Nonsteroidal↗
Blood eosinophils, eosinophil-derived proteins, and leukotriene C4 generation in relation to bronchial hyperreactivity in children with atopic dermatitis.
To assess the relation among eosinophil-related variables in the peripheral blood, bronchial hyperreactivity, and the presence of atopic dermatitis in children aged 5-14 years, we studied 11 patients with atopic dermatitis alone, six with asthma and atopic dermatitis, 12 with asthma alone, and 12 healthy controls. Eosinophil counts, levels of eosinophil cationic protein, and the capacity of eosinophils to generate leukotriene (LT) C4, as well as bronchial hyperreactivity and a severity score for atopic dermatitis, were determined. Eosinophil variables were significantly higher in both patient groups with atopic dermatitis than in normal controls. In particular, ionophore A 23187 LTC4 generation was higher in patients with atopic dermatitis alone (median 82, range 25-273 ng/10(6) cells) and patients with combined asthma and atopic dermatitis (median 68, range 32-583 ng/10(6) cells) than in normal controls (median 9, range 1-67 ng/10(6) cells). However, there was no difference between the group of atopic dermatitis patients with asthma and without asthma. We conclude that eosinophil variables in the peripheral blood are mainly influenced by the presence of atopic dermatitis, and not the presence and the severity of asthma in patients with both asthma and atopic dermatitis.
Adolescent↗
Is cranial computerized tomography useful in the diagnosis of multiple system atrophy?
Cranial computer tomographic (CT) images of 33 patients with multiple system atrophy (MSA) and of 40 age-matched controls were blindly analyzed by two neuroradiologists. All patients had autonomic dysfunction, all but one had parkinsonism, and 13 had cerebellar signs. The scans were judged entirely normal in 21%. Moderate or severe infratentorial atrophy was found in 42%. Cerebellar atrophy was present in 39%, and pontine atrophy was present in 18%. Of the 13 patients with cerebellar signs, only eight had cerebellar atrophy. Of the 20 patients without cerebellar signs, five had cerebellar atrophy. Supratentorial involvement was much less common and less severe. Thus, CT demonstrated system involvement that was not evident clinically in five of 33 cases (15%). However, in all five the clinical diagnosis was already evident from the presence of both autonomic and pyramidal signs in addition to parkinsonism. We conclude that CT imaging is of limited diagnostic use in individual patients with MSA.
Adult↗
Blood eosinophils, leukotriene C4 generation, and bronchial hyperreactivity in formerly preterm infants.
Infants born prematurely are known to display longstanding bronchial hyperreactivity. The mechanism responsible for this is still unclear. Eosinophils are thought to play a central part in the development of bronchial hyperreactivity in asthma. It was the aim of this study to assess the relation of bronchial hyperresponsiveness to potential markers of eosinophilic inflammation in peripheral blood. Eosinophil count, the concentration of serum eosinophilic cationic protein, the capacity of purified eosinophils to generate leukotriene C4, and bronchial reactivity was studied in 24 non-atopic children born prematurely, 12 healthy controls, and 12 children with asthma aged 6 to 9 years. There was no difference in serum concentrations on eosinophil cationic protein and eosinophil counts. However, eosinophils from the 15 formerly preterm infants with significant bronchial hyperreactivity generated significantly higher amounts of leukotriene C4 than normal controls and prematurely born children without bronchial hyperreactivity. Levels of leukotriene C4 in this group were comparable with those obtained with eosinophils from patients with asthma. In contrast with cells from the other groups, eosinophils from the children with bronchial hyperreactivity born prematurely show no enhancement of leukotriene C4 generation on prestimulation with platelet activating factor. It is concluded that bronchial hyperreactivity of children born prematurely is accompanied by the prestimulation of eosinophils.
Asthma↗
Effect of granulocyte/macrophage colony-stimulating factor on human monocytes infected with influenza A virus. Enhancement of virus replication, cytokine release, and cytotoxicity.
The activating properties of granulocyte/macrophage (GM)-CSF were studied in vitro with human monocytes infected by influenza A virus. When monocytes were pretreated for 8 h with GM-CSF (100 U/ml) and then exposed to influenza A virus, de novo virus protein synthesis was enhanced, more virus particles were released, and cells were killed at a higher rate. In virus-infected monocytes, GM-CSF induced a more rapid IFN-alpha release and potentiated production of TNF-alpha, IL-1 beta, and IL-6. Although GM-CSF or influenza A virus were each capable of independently activating TNF-alpha, IL-1 beta, and IL-6 gene transcription, a combination of both induced a massive cytokine mRNA accumulation which was readily translated into bioactive protein. Thus, GM-CSF may display a Janus-like action by accelerating virus infection but also by priming monocytes for elevated cytokine production. Whether the facilitated influenza A virus replication caused by GM-CSF may be counterbalanced by an improved cytokine response remains to be studied under more complex in vivo conditions.
Base Sequence↗
Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition.
Total body water, body fat, body cell mass (BCM), extracellular mass (ECM), and the ECM-BCM ratio by impedance analysis were determined in 193 human immunodeficiency virus (HIV)-infected patients and 340 control subjects. Walter Reed (WR) classification was WR 2 in 26, WR 3-5 in 85, and WR 6 in 82 patients. Whereas resistance was increased, reactance and the phase angle were significantly reduced in all patient groups. Neither body weight nor body mass index (BMI) was affected in WR 2 patients, but BCM was reduced (31.9 +/- 4.3 vs 35.8 +/- 7.3 kg, P < 0.007) and ECM (31.2 +/- 4.4 vs 28.8 +/- 3.8 kg) as well as ECM-BCM ratio increased (0.99 +/- 0.14 vs 0.83 +/- 0.16, P < 0.001). In contrast to WR classification, diarrhea did not correspond with malnutrition. A loss of BCM (malnutrition) occurred already in otherwise symptomless HIV-infected patients (WR 2). This effect can be measured by tetrapolar impedence analysis but not by body weight or BMI.
Adult↗
Pharmacokinetics of ethinylestradiol and levonorgestrel after administration of two oral contraceptive preparations.
Serum concentration profiles and pharmacokinetic parameters (cmax, tmax, AUC24, AUC0-00, MRT) of ethinylestradiol (EE2) and levonorgestrel (LNG) were obtained following administration of two combined oral contraceptives. The constituents of the preparations were as follows: Gravistat (0.05 mg EE2, 0.125 mg LNG); Minisiston (0.03 mg EE2, 0.125 mg LNG). In 20 of the volunteers blood samples were taken before and up to 36 hours following the intake of a single table. In 11 women the investigation was carried out at day 21 of a treatment cycle (steady-state condition). In spite of pronounced interindividual variations of the pharmacokinetic data, a clear dependency of EE2 concentration curves on the estrogen dose of the respective preparation could be demonstrated. Under the condition of steady-state (21st day of administration) there was a slight but significant rise of the EE2 peak serum concentrations and a pronounced increase of the LNG levels, closely reflected by elevation of the AUC values. SHBG serum concentration was significantly increased by the 10th day of treatment in all subjects receiving Gravistat, whereas the mean value in the Minisiston-group did not remarkably change. Although LNG is known to be bound to SHBG with high affinity, the missing parallelism between LNG- and SHBG-concentrations suggests other (additional?) mechanisms for the elevated LNG-binding capacity in women taking combined EE2-LNG preparations.
Administration, Oral↗
Enhanced production of platelet activating factor by peripheral granulocytes from children with asthma.
Granulocytes from 23 asthmatic children aged 4-15 years and 32 age-matched healthy children were studied. Cells were purified by Dextran sedimentation and Percoll gradient centrifugation from heparinized blood. After in vitro stimulation by ionophore A23187 the amount of newly synthesized PAF and LTC4 was assessed by radio receptor assay or radioimmunoassay respectively. Eight patients had symptoms of asthma within the last 3 weeks before examination. Granulocytes from the symptomatic patients showed a significantly higher PAF generation (median 125 ng/10(6) cells, range 7-189 ng/10(6) cells) when compared to asymptomatic patients (p less than 0.001, median 14 ng/10(6) cells, range 6-33 ng/10(6) cells) or controls (p less than 0.001, median 11 ng/10(6) cells, range 3-26 ng/10(6) cells). In contrast, LTC4 generation was increased in both patient groups. The results suggest a regulatory role of PAF in the exacerbation of asthma.
Adolescent↗