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Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 19 recordsLinked to original sources
PubMed1995

[Age dependence of interleukin 6 and acute phase proteins].

In 59 healthy subjects of different age groups with no signs of inflammatory processes, the basal II-6 levels were measured. The II-6 concentrations were significantly higher in the oldest group (66-90 years) than in the two other age groups (24-40, 41-65 years). A positive correlation was found between age and II-6 concentration (r = 0.470). Otherwise, a statistically detectable relationship was found merely with alpha-2-macroglobulin and with total and LDL cholesterol.

Acute-Phase Proteins↗
PubMed1995

[Determination of Escherichia coli Shiga-like toxins by means of the MTT bioassay].

Tissue culture cells' metabolism and viability are measured by the mitochondrial reduction rate of a yellow tetrazolium salt (MTT) to blue formazan crystals in the MTT-bioassay. Thus the MTT-bioassay is a standardizable and reproducible bioassay for measuring cytotoxicity or cytostimulation. It is shown that the MTT-bioassay is also very suitable for determining bacterial cytotoxins using Escherichia coli's Shiga-like toxins as example. 177 strains of E. coli, isolated from carcasses and organs of cattle, are classified biochemically and tested for cytotoxin production by means of the MTT-bioassay. One of these strains is recognized as producer of Shiga-like toxin 2. 4 Enterohemolysin-producing strains of E. coli are cultivated from a feces sample of a diarrhoeic nubian ibex and identified as Shiga-like toxin 1 producers by help of the MTT-bioassay.

Animals↗
PubMed1995

A dynamic relationship between myopia and blur-driven accommodation in school-aged children.

Previously we reported that recently myopic children accommodated insufficiently to blur induced by negative lenses. The purpose of the present study was to relate changes in blur-driven accommodation to myopia development in children. Refractive errors and the accommodation response function (ARF) were measured in 23 myopic and 40 emmetropic children on two occasions separated by periods ranging from 6 to 12 months. Repeated measures of accommodation were made with a Canon R-1 autorefractor while negative lenses of increasing power were placed in front of the child's right eye viewing 20/100 letters at 4 m. Concomitant changes in refractive error and in accommodative function over periods of 6-12 months were found to be highly correlated in myopes (r = 0.77) but not in emmetropes (r = 0.09).

Accommodation, Ocular↗
PubMed1995

Endotoxin-induced appearance of immunoreactive interleukin-1 beta in ramified microglia in rat brain: a light and electron microscopic study.

Interleukin-1 plays an important role as mediator of endotoxin-induced responses in the brain such as fever, sleep, anorexia, behavioural and neuroendocrine changes. In the present study, interleukin-1 beta immunocytochemistry has been performed at the light and electron microscopic level to study the cellular and subcellular localization of interleukin-1 beta in the brains of rats given endotoxin or saline. Light microscopic analysis of rats killed 4, 8 or 24h after endotoxin (2.5 mg/kg) given intraperitoneally or intravenously revealed a region-specific localization of immunoreactive interleukin-1 beta in macrophages and microglial cells. After saline treatment, no induction of interleukin-1 beta immunoreactivity occurred in the brain. After administration of endotoxin, many interleukin-1 beta-positive cells were found in the meninges, choroid plexus, circumventricular organs, cerebral cortex and hypothalamus. The number of interleukin-1 beta-positive microglial cells reached a maximum 8 h after administration of endotoxin, irrespective of the route of administration. In general, more interleukin-1 beta-positive microglial cells were found after intravenous than after intraperitoneal administration of endotoxin. Interleukin-1 beta-positive microglial cells were often grouped in patches in the vicinity of blood vessels. At the surface of the cerebral cortex, in the meninges, intermediate cell forms between interleukin-1 beta-positive macrophages and microglial cells were found. interleukin-1 beta-positive perivascular microglia were localized at the brain side of the basal lamina. Immunoreactive interleukin-1 beta was found at the luminal side of the endothelial cells lining the venules. Furthermore, microglial cells that extended their processes into the ependymal layer of the third ventricle were observed. Results of the electron microscopic studies revealed immunoreactive interleukin-1 beta in many cells with the cellular characteristics of microglial cells, but also, in some cells, identified as astrocytes. In microglial cells, immunoreactive interleukin-1 beta was found in the cytoplasm but not in the endoplasmatic reticulum or Golgi apparatus. These results show that after peripheral administration of endotoxin, immunoreactive interleukin-1 beta is induced in macrophages in the meninges and in the choroid plexus, as well as in microglial cells in parenchyma. Interleukin-1 beta produced by these cells may serve as a signal for adjacent or more distant targets (neurons, endothelial cells, microglial cells) to play a role in the induction of non-specific symptoms of sickness.

Animals↗
PubMed1995

Intensification of chemotherapy for the treatment of solid tumours: feasibility of a 3-fold increase in dose intensity with peripheral blood progenitor cells and granulocyte colony-stimulating factor.

Dose intensity may be an important determinant of the outcome in cancer chemotherapy, but is often limited by cumulative haematological toxicity. The availability of haematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and of peripheral blood progenitor cell (PBPC) transplantation has allowed the development of a new treatment strategy in which several courses of high-dose combination chemotherapy are administered for the treatment of solid tumours. PBPCs were mobilised before chemotherapy using 12 or 30 micrograms kg-1 day-1 G-CSF (Filgrastim) for 10 days, and were collected by 2-5 leucaphereses. The yields of mononuclear cells, colony-forming units and CD34-positive cells were similar at the two dose levels of Filgrastim, and the numbers of PBPCs were sufficient for rescue following multiple cycles of chemotherapy. High-dose chemotherapy (cyclophosphamide 2.5 g m-2 for 2 days, etoposide 300 mg m-2 for 3 days and cisplatin 50 mg m-2 for 3 days) was administered sequentially for a median of three cycles (range 1-4) to ten patients. Following the 30 evaluable cycles, the median duration of leucopenia < or = 0.5 x 10(9) l-1 and < or = 1.0 x 10(9) l-1 was 7 and 8 days respectively. The median time of thrombopenia < or = 20 x 10(9) l-1 was 6 days. There was no cumulative haematological toxicity. The duration of leucopenia, but not of thrombopenia, was inversely related to the number of reinfused CFU-GM (granulocyte-macrophage colony-forming units). In the majority of patients, neurotoxicity and ototoxicity became dose limiting after three cycles of therapy. However, the average dose intensity delivered was about three times higher than in a standard regimen. The complete response rate in patients with small-cell lung cancers was 66% (95% CI 30-92%) and the median progression-free survival and overall survival were 13 months and 17 months respectively. These results are encouraging and should be compared, in a randomised fashion, with standard dose chemotherapy.

Adult↗
PubMed1995

Human follicular and papillary thyroid carcinoma cells interact differently with human venous endothelial cells.

Follicular thyroid carcinomas (FTC) characteristically spread via blood vessels, while papillary thyroid carcinomas (PTC) predominantly metastasize to lymph nodes. This different behavior of cancer cells originating from one organ was investigated by layering multicellular tumor spheroids (MCTS) consisting of various kinds of human thyroid cells onto confluent monolayers of human venous endothelial cells (HEC). The MCTS and HEC were cocultured in an incubation chamber fixed under a microscope, and the behavior of the cells was investigated. In this way significant differences between FTC, PTC, and follicular adenoma cells (FTA) were observed regarding their in vitro behavior upon interaction with HEC. FTC cells required 20 min for adhesion and another hour until they migrated out of a spheroid, whereas PTC- and FTA-MCTS were adhesive after 2 h or later, and their cells did not start migration until 5 h of incubation. Furthermore, one FTC-spheroid triggered about 100 endothelial cells to enter the replication cycle, while no spheroid consisting of either PTC or FTA cells induced more than 20 endothelial cells to start proliferation. During these processes, the cells of the MCTS and the endothelial cells contacted each other directly and remained viable. The results show that FTC cells interact faster and more intensively with human endothelial cells than PTC and FTA cells. Thus the study suggests that an enhanced capability of the FTC cells to interact with venous endothelial cells might favor the clinically observed hematogenous spreading of follicular thyroid carcinomas.

Adenocarcinoma, Follicular↗
PubMed1995

Basic research.

Basic research is currently investigating the molecular cascade associated with bladder cancer development. Many new findings are potential leads towards the improvement of the diagnosis and prognosis of this disease. Special care, however, should be taken in the design of protocols for clinical evaluation of the value of these markers. Some initial guidelines have been put forward in this report.

Alleles↗
PubMed1995

[Post-traumatic os odontoideum].

This is a report about a 20-month-old child with acquired os odontoideum caused by a fall. Diagnosis of atlanto-axial instability was eventually made 29 months later after repeated trauma and transitory tetraparesis. Dorsal C1/2 fusion with an autogenic rib graft and plaster fixation for 8 weeks failed; an autogenic iliac bone graft plus external fixation for 12 weeks finally resulted in solid fusion.

Aged↗
PubMed1995

[Catamenial seizures--an analysis].

Catamenial seizures are defined as epileptic seizures occurring during distinct phases of the menstrual cycle (i.e., periovulatory, premenstrually and during menstruation). The cyclic changes of the gonadotropic hormones are thought to be the main cause of the seizures. This hypothesis is supported by results of animal experiments, which have shown oestrogens to increase neuronal excitability whereas progesterone lowered it. We investigated 21 women with epilepsy who reported a catamenial increase in seizure frequency. Only 24% of these women actually exhibited a catamenial manifestation in more than 75% of seizures. The incidence of catamenial seizures is reported in the literature to be between 10% and 72%. Catamenial seizures are treated with anticonvulsant drugs. However, when anticonvulsants have failed to suppress seizures, progesterone or progesterone-derivates have been administered with success. We treated 16 patients with a synthetic GnRH-analogue to suppress the hormonal release of gonadotropins. Four of the six patients with only catamenial seizure manifestations and no other seizures became seizure free. Ten patients had catamenial seizures as well as seizures not related to the menstrual cycle. A decrease in seizure frequency by more than 50% was achieved in 7 of these 10 patients.

Adult↗
PubMed1995

[Anticonvulsive drug therapy. Historical and current aspects].

The development of new antiepileptic drugs in recent years has enlarged the number of anticonvulsant compounds for the treatment of intractable focal epilepsies. The anticonvulsant potency of these drugs is usually compared by the number of patients who achieve a reduction in seizure frequency of more than 50%. Such an effect can be observed in approximately 20-30% of patients with pharmacoresistant focal epilepsies and is about the same with all the new compounds. In addition to the influence on focal seizures some of the novel anticonvulsant drugs exhibit efficacy in generalized seizures or in Lennox-Gastaut syndrome. In general there are fewer side effects in newly developed drugs than in standard anticonvulsants. However, in some cases characteristic side effects may occur: weight gain, depression or psychosis from vigabatrin; lamotrigine may provoke allergic rashes and felbamate may cause gastrointestinal side effects and sleeplessness. Apart from felbamate, there are no interactions with an antiepileptic comedication or they are of little importance. The development of the new anticonvulsants follows a rational design based on pathophysiological aspects: the main aim is to influence synaptic transmission, resulting in an increase in inhibitory and a decrease in excitatory transmitters. Thus, vigabatrin and tiagabine enhance the endogenous GABA amount, whereas felbamate and remacemide interact with the NMDA-receptor complex. Because it is not possible to draw sufficient conclusions from add-on studies in clinical testing it is necessary to establish new forms of trial design. Monotherapy designs are favored because they lack possible interactions with comedication and make the anticonvulsant efficacy of the compound better comparable to those of established anticonvulsants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Expression of an outwardly rectifying K+ channel in rat microglia cultivated on teflon.

Membrane currents of cultured human monocytes and rat microglia were recorded with the whole-cell patch clamp technique. Freshly isolated monocytes or resting (proliferating) microglia express only inwardly rectifying K+ channels. However, incubation in teflon bags leads to the expression of additional, outwardly rectifying K+ channels. The outward K+ conductance of microglial cells was inhibited by intracellular Cs+ and extracellular 4-aminopyridine or tetraethylammonium. Functional similarities with the microglial outwardly rectifying K+ channel were found in the Kn-channel of lymphocytes which has recently been cloned (RGK5). The polymerase chain reaction (PCR) was used to demonstrate the presence of RGK5-like mRNA in microglia.

Animals↗
PubMed1992

The human hepatoma Hep3B cell line as an experimental model in the study of the long-term regulation of acute-phase proteins by cytokines.

The regulation of the synthesis by the cytokines interleukin-1 (IL-1) and IL-6 of the positive acute-phase protein alpha 1-acid glycoprotein (AGP) and of the negative acute-phase protein alpha 2-HS glycoprotein (AHSG) has been studied in a long-term culture system of the human hepatoma cell line Hep3B. The culture system contained 30 nM-sodium selenite as the only supplement. This allowed maintenance of the synthesis of the proteins under study at a near steady state for over 3 months. An increase in AGP mRNA and a decrease in AHSG mRNA were observed when cells were treated for two successive 48 h-periods with monocyte-conditioned medium. A return to basal levels was obtained after cessation of the cytokine addition. Two further additions of cytokines led to alterations in mRNA levels similar to those observed following the first cytokine treatment. The amounts of AGP and AHSG secreted were altered in accordance with the mRNA modifications. These results suggest that new cytokine receptors were being constantly synthesized during cell culture. When cytokines were present in the culture medium for 10 days, maximum alterations in AGP and AHSG synthesis were obtained following 2 and 4 days of treatment respectively, but further alterations in protein levels could not be observed afterwards. Expression of IL-6 receptor mRNA was not up-regulated by cytokines, but only by 1 microM-dexamethasone. Our results show that, in this long-term culture system, cytokines induce a response in hepatoma cells similar to that observed in vivo during human inflammatory states. This model could be used to evaluate the effects of agonists or antagonists of cytokines responsible for the hepatic acute-phase protein response.

Acute-Phase Proteins↗
PubMed1992

Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells.

The gene for the beta A4-amyloid precursor protein (APP) consists of 19 exons which code for a typical N- and O-glycosylated transmembrane protein with four extracellular domains followed by the transmembrane domain and a short cytoplasmic domain. The beta A4-amyloid sequence is part of exons 16 and 17. Several APP isoforms can be generated by alternative splicing of exons 7 and 8, encoding domains with homologies to Kunitz-type protease inhibitors and the MRC OX-2 antigen, respectively. The mechanism by which the pathological beta A4 is generated is unknown, it is however a critical event in Alzheimer's disease and is distinct from the normally occurring cleavage and secretion of APPs within the beta A4 sequence. We report here for the first time considerable APP mRNA expression by rat brain microglial cells. In addition we showed by S1 nuclease protection and polymerase chain reaction analysis of reverse transcribed RNA (RT-PCR) that T-lymphocytes, macrophages, and microglial cells expressed a new APP isoform by selection of a novel alternative splice site and exclusion of exon 15 of the APP gene. This leads to a transmembrane, beta A4 sequence containing APP variant, lacking 18 amino acid residues close to the amyloidogenic region. The use of this novel alternative splice site alters the structure of APP in close proximity to the beta A4 region and thus may determine a variant, potentially pathogenic processing of leukocyte-derived APP in brain.

Amyloid beta-Protein Precursor↗
PubMed1992

Pharmacokinetics of pamidronate in patients with bone metastases.

BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.

Aged↗
PubMed1992

In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression, G-proteins, and integrins.

The EA hy926 cell line is a continuous, clonable, human cell line that displays a number of features characteristic of vascular endothelial cells (Edgell et al., 1983). Here we report that when EA hy926 cells (EA cells) are plated on an extracellular matrix material [Matrigel], they undergo a process of morphological re-organization leading to the formation of a complex network of cord or tubelike structures. These events seem to resemble, in some respects, an in vitro process of angiogenesis. The morphological re-arrangement occurs within a 12-16 hr period and seems to require expression of new messenger RNA and protein, since it is completely blocked when actinomycin D or cycloheximide are present at the time the cells are plated on Matrigel. This is not due to overt toxicity of the drugs, since exposure of cells to actinomycin D at 2 hr or more after plating on Matrigel has little effect on the formation of the tubelike structures. The process of Matrigel-induced tube formation also apparently involves a G-protein mediated signal. Treatment of the EA cells with pertussis toxin completely blocks the process and causes the ADP-ribosylation of a 42 kD protein that is recognized by an antibody to Gi-alpha subunits. In contrast, concentrations of pertussis toxin sufficient to block tube formation have only modest effects on the adhesion or motility of EA cells on purified matrix components such as laminin or collagen IV. The process of Matrigel-induced tube formation also involves integrins since monoclonal antibodies to integrin alpha 6 or beta 1 subunits can completely block the process. The concentrations of anti-integrin antibodies needed to block tube formation are much lower than those required to block cell adhesion on purified matrix components and are sufficient to occupy less than 10% of the alpha 6 or beta 1 subunits available at the cell surface. These results suggest that integrins may be involved in this potential model of angiogenesis in processes beyond their usual role in cell adhesion. Based on these results, it seems likely that the EA hy 926 cell line will prove to be a useful model for in vitro study of angiogenic processes.

Antibodies↗
PubMed1992

The effect of a synthetic GnRH analogue on catamenial epilepsy: a study in ten patients.

Ten female patients suffering from catamenial epilepsy were treated with a synthetic analogue of the gonadotrophin releasing hormone (GnRH) in addition to antiepileptic drugs. Three of the patients became seizure free, in four patients seizure frequency decreased and in one patient seizures were of shorter duration. In only two of the patients was there no therapeutic effect. Adverse effects, including hot flushes, headache and increase in weight, were noticed in eight patients. These results support the hypothesis that treatment with a synthetic GnRH analogue might be helpful in patients with intractable catamenial epilepsies.

Adult↗