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Biomedical subjects

H Keller

Publications and source records attributed to H Keller.

At least 91 records · Page 5Linked to original sources

RNase activity prevents the growth of a fungal pathogen in tobacco leaves and increases upon induction of systemic acquired resistance with elicitin.

The hypersensitive response and systemic acquired resistance (SAR) can be induced in tobacco (Nicotiana tabacum L.) plants by cryptogein, an elicitin secreted by Phytophthora cryptogea. Stem application of cryptogein leads to the establishment of acquired resistance to subsequent leaf infection with Phytophthora parasitica var nicotianae, the agent of the tobacco black shank disease. We have studied early events that occur after the infection and show here that a tobacco gene encoding the extracellular S-like RNase NE is expressed in response to inoculation with the pathogenic fungus. Upon induction of SAR with cryptogein, the accumulation of NE transcripts coincided with a rapid induction of RNase activity and with the increase in the activity of at least two different extracellular RNases. Moreover, exogenous application of RNase activity in the extracellular space of leaves led to a reduction of the fungus development by up to 90%, independently of any cryptogein treatment and in the absence of apparent necrosis. These results indicate that the up-regulation of apoplastic RNase activity after inoculation could contribute to the control of fungal invasion in plants induced to SAR with cryptogein.

Algal Proteins↗

PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents.

The nuclear receptor PPAR alpha is a key regulatory transcription factor in lipid homeostasis, some liver detoxification processes and the control of inflammation. Recent findings suggest that many hypolipidemic drugs and anti-inflammatory agents can potentially act by binding to PPAR alpha and inducing its activity. Here, we identify some structure-function relationships in PPAR alpha, by using the species-specific responsiveness to the two hypolipidemic agents, Wy 14,643 and 5,8,11,14-eicosatetraynoic acid (ETYA). We first show that the species-specific differences are mediated primarily via the ligand binding domain of the receptor and that these two drugs are indeed ligands of PPAR alpha. By mutagenesis analyses we identify amino acid residues in the ligand binding domains of Xenopus, mouse and human PPAR alpha, that confer preferential responsiveness to ETYA and Wy 14,643. These findings will aid in the development of new synthetic PPAR alpha ligands as effective therapeutics for lipid-related diseases and inflammatory disorders.

5,8,11,14-Eicosatetraynoic Acid↗

The prevalence of lung lesions in pigs at slaughter in Switzerland.

A survey of the prevalence of lung lesions in randomly selected slaughtered swine representative of the Swiss fattening pig population was carried out from May to September 1992 in six large abattoirs. In total 8921 lungs out of 561 herds were examined. Histological investigations were completed in every herd. No gross lesions could be found in 56% of the pigs. The most frequent lesions in individuals were bronchopneumonia (21%) and diffuse pleuritis (21%). Linear scars (9%), focal pleural fibrosis without any pneumonic lesion (2%), pleuropneumonia (1%) and abscesses (1%) were less prevalent. The prevalence of lesions at the herd level was completely different. The lungs of only 14% of the herds were free of any lesions. The main finding at the herd level was a diffuse pleuritis (75%), followed by bronchopneumonia (64%), linear scars (60%), focal pleural fibrosis (20%), abscesses (14%) and pleuropneumonia (9%). In 94% of the herd samples with macroscopically diagnosed bronchopneumonia, the histological lesions were consistent with enzootic pneumonia of pigs.

Abattoirs↗

Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX.

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.

Aged↗

The PPARalpha-leukotriene B4 pathway to inflammation control.

Inflammation is a local immune response to 'foreign' molecules, infection and injury. Leukotriene B4, a potent chemotactic agent that initiates, coordinates, sustains and amplifies the inflammatory response, is shown to be an activating ligand for the transcription factor PPARalpha. Because PPARalpha regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mechanism is proposed that controls the duration of an inflammatory response and the clearance of leukotriene B4 in the liver. Thus PPARalpha offers a new route to the development of anti- or pro-inflammatory reagents.

Adaptation, Physiological↗

[Cerebral insult in heart surgery].

The aim of the study was to identify causes for perioperative stroke in cardiac surgery in order to reduce its occurrence. From 1989 to 1994, 3593 open heart operations were performed in adult patients. In 59 patients carotid endarterectomy for high grade stenosis was combined with the cardiac operation. There were a total of 68 (2%) focal strokes, 41 of which were considered minor and 14 major; 13 were lethal. The etiology of the 27 major and lethal events was most probably an embolus from the ascending aorta (6), from the ascending aorta or a cardiac valve (5), a thrombus in the left heart (6), air (1), cardiac arrest and resuscitation (4), cerebral hemorrhage (1), preoperatively unknown but high grade internal carotid stenosis (3), and a 50% stenosis of both internal carotid arteries preoperatively known but not operated on (1). There were 2 minor but no major neurologic complications in patients undergoing a combined carotid and cardiac procedure. A wide indication for preoperative neuroangiologic examination, echocardiography and careful intraoperative management may help to identify sources of possible emboli. Endarterectomy of high grade carotid stenosis is recommended simultaneously with the cardiac procedure.

Adult↗

Inhibition of protein kinase C-dependent protein phosphorylation correlates with increased polarity and locomotion in Walker 256 carcinosarcoma cells.

Signal transduction pathways controlling tumor cell locomotion are not yet well understood. We have studied the role of protein kinase C (PKC)-dependent protein phosphorylation associated with changes in cell shape and locomotor activity of Walker carcinosarcoma cells in culture. We show that the inhibitory effect of phorbol-12-myristate-13-acetate (PMA), an activator of PKC, on cell polarity and locomotion can be suppressed by the PKC-selective inhibitor Ro 31-8220. PMA induces increased phosphorylation of at least 2 proteins, of 65 and 80 kDa, in intact Walker carcinosarcoma cells. These bands are enriched in cytosolic fractions isolated from cells incubated with 32PO4. Pre-incubation with Ro 31-8220 inhibits the PMA-induced phosphorylation of both bands in a concentration-dependent manner. This effect is very likely not due to inhibition of translocation of PKC to the membrane as Ro 31-8220 enhances, rather than inhibits, PMA-induced transfer of PKC beta(II) to the particulate fraction. We have carried out a quantitative analysis of phosphorylation of the 80-kDa band. Ro 31-8220 reverses both PMA-induced phosphorylation of this band and PMA-induced suppression of cell polarity in parallel. Increased phosphorylation of proteins via PKC may thus be a stop signal for locomoting Walker carcinosarcoma cells.

Animals↗

Estimation of the lower limits of manual and automated platelet counting.

Most evaluators of automated or manual methods for platelet counting focus on characteristics such as imprecision, linearity, and carry over. The limits of the analytical procedure are usually not assessed. The limits of the different techniques are neither discussed in the literature nor do manufacturers of analytical systems supply these data. A new procedure is presented to assess the performance of the manual as well as the automated platelet count. This procedure allows, with defined statistical confidence (eg, 95%), the determination of (1) the limit of platelet detection (LD) at which signals of platelets can be discriminated from the system noise; (2) the lower limit of quantification (LLQ), at which a certain imprecision is not surpassed; and (3) the power of definition (PD) that defines the number of values that can be discriminated in a certain interval. For each value, the PD allows calculation of the two adjacent (lower and higher) values that are significantly (P > or = 0.95) different. For the manual count, LD was found to be 1.6 x 10(9) plt/L and the LLQ 6.9 x 10(9) plt/L. For the automated count with the Technicon H1, LD was 4.3 x 10(9) plt/L and LLQ 13.8 x 10(9) plt/L (CVmax = 15%). The PD in the range 20 to 100 x 10(9) plt/L is 8 for the automated and 7 for the manual count.

Analysis of Variance↗

Micronutrient status in elderly people. Geriatrie/Min. Vit. Aux Network.

A biochemical assessment of the vitamin and trace element status of 756 institutionalized elderly men and women, 66-103 years old (average 83.5 +/- 7.6 y), was conducted in 26 nursing homes in different areas of France. Serum concentrations of beta- and alpha-carotene, beta-cryptoxanthin, lycopene, retinol, alpha- and gamma-tocopherol, vitamin C, zinc and selenium were measured. A difference in biochemical markers according to sex was observed for vitamins E and C: elderly women had higher levels of alpha-tocopherol and vitamin C than elderly men. When expressed as a ratio of cholesterol, the difference between sexes for alpha-tocopherol disappeared. Simple regression analysis showed that most vitamins and trace elements were significantly negatively correlated with age. A high prevalence of low concentrations of vitamin C, zinc and selenium was revealed.

Aged↗

[The concentration changes of different phenylbutazone formulations in horse plasma].

In a study in the horse, the disposition, the pharmacokinetic parameters and the absorption rates of 3 formulations of phenylbutazone (injection solution, powder and paste suspension) have been determined. After i.v. injection, the half-life time of phenylbutazone has been determined to be 6.6-6.7 h. After oral administration, the absorption of phenylbutazone was found to be faster after administration via stomach tube than after direct application into the mouth. The absorption rat constant of the paste suspension was found to be higher than that of the powder (1.797-2.304 h-1 vs. 0.656-1.197 h-1). The maximal plasma concentrations were attained within 0.5-3 hours with all formulations and were dose-dependent. The elimination of phenylbutazone was not dependent on the dose and formulation applied. The bioavailability of the studied powder and paste formulation was calculated to be 55.1-96.7%. Generally, the bioavailability was higher following administration of the drug via stomach tube. In some horses, the disposition pattern was atypical and delayed absorption was found. This may be due to adsorption of phenylbutazone on the food with subsequent release in the large intestine. The minimal therapeutic level of 5 micrograms/ml was attained 0.2-0.8 hours after administration of the drug and lasted 8.2-22 hours depending on the dose applied. The paste suspension of phenylbutazone may provide a good therapeutic tool for horses, which normally refuse to take powder supplemented food. At the end the authors report on their good clinical results in using Butasan-Paste with 30 ill horses.

Absorption↗