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Biomedical subjects

R Meister

Publications and source records attributed to R Meister.

At least 19 recordsLinked to original sources
PubMed2005

Testing differential gene expression in functional groups. Goeman's global test versus an ANCOVA approach.

OBJECTIVES: Single genes are not, in general, the primary focus of gene expression experiments. The researcher might be more interested in relevant pathways, functional sets, or genomic regions consisting of several genes. Efficient statistical tools to handle this task are of interest to research of biology and medicine. METHODS: A simultaneous test on phenotype main effect and gene-phenotype interaction in a two-way layout linear model is introduced as a global test on differential expression for gene groups. Its statistical properties are compared with those of the global test for groups of genes by Goeman et al. in a preliminary simulation study. The procedure presented also allows adjusting for covariates. RESULTS: The proposed ANCOVA global test is equivalent to Goeman's global test in a setting of independent genes. In our simulation setting for correlated genes, both tests lose power, however with a stronger loss for Goeman's test. Especially in cases where the asymptotic distribution cannot be used, the stratified use of the ANCOVA global test shows a better performance than Goeman's test. CONCLUSIONS: Our ANCOVA-based approach is a competitive alternative to Goeman's global test in assessing differential gene expression between groups. It can be extended and generalized in several ways by a modification of the projection matrix.

Algorithms↗
PubMed2003

Poling of liquid crystals in thin films.

We examine the effect of a strong DC electric field on the molecular orientational order and the nonlinear optical response of liquid crystals in thin films. We compare the results of second-harmonic generation measurements with the predictions of two models, one assuming that the dipoles carried by the molecules have no interactions (the isotropic model), and the other assuming that the dipoles evolve in a Maier-Saupe orienting field responsible for the liquid-crystalline order (the Maier-Saupe model). In both cases, we take into account the effect of surfaces and confinement on the behavior of the molecules. We find that the molecular dipoles behave as predicted by the isotropic model, but that their reorientation is correlated in such a way that the apparent dipole moment of the reorienting units is one order of magnitude larger than the molecular dipole moment.

Journal Article↗
PubMed2002

Increased lipogenesis in isolated hepatocytes from cold-acclimated ducklings.

Thermogenic endurance and development of metabolic cold adaptation in birds may critically depend on their ability to synthesize and use fatty acids (FA) as fuel substrates. Hepatic lipogenesis and the capacity to oxidize FA in thermogenic tissues were measured in cold-acclimated (CA) ducklings (Cairina moschata) showing original mechanisms of metabolic cold adaptation in the absence of brown adipose tissue, the specialized thermogenic tissue of rodents. The rate of FA synthesis from [U-(14)C]glucose and from [1-(14)C]acetate, measured in incubated hepatocytes isolated from 5-wk-old thermoneutral (TN; 25 degrees C) or CA (4 degrees C) fed ducklings, was higher than in other species. Hepatic de novo lipogenesis was further increased by cold acclimation with both glucose (+194%) and acetate (+111%) as precursor. Insulin slightly increased (+11-14%) hepatic lipogenesis from both precursors in CA ducklings, whereas glucagon was clearly inhibitory (-29 to -51%). Enhanced de novo lipogenesis was associated with higher (+171%) hepatocyte activity of glucose oxidation and larger capacity (+50 to +100%) of key lipogenic enzymes. The potential for FA oxidation was higher in liver (+61%) and skeletal muscle (+29 to +81%) homogenates from CA than from TN ducklings, suggesting that the higher hepatic lipogenesis may fuel oxidation in thermogenic tissues. Present data underline the high capacity to synthesize lipids from glucose in species like muscovy ducks susceptible to hepatic steatosis. Lipogenic capacity can be further increased in the cold and may represent an important step in the metabolic adaptation to cold of growing ducklings.

Acclimatization↗
PubMed2000

Cold acclimation or grapeseed oil feeding affects phospholipid composition and mitochondrial function in duckling skeletal muscle.

The phospholipid fatty acid (FA) composition and functional properties of skeletal muscle and liver mitochondria were examined in cold-acclimated (CA, 4 degrees C) ducklings. Phospholipid FA of isolated muscle mitochondria from CA birds were longer and more unsaturated than those from thermoneutral (TN, 25 degrees C) reared ducklings. The rise in long-chain and polyunsaturated FA (PUFA, mainly 20:4n-6) was associated with a higher State 4 respiration rate and a lower respiratory control ratio (RCR). Hepatic mitochondria, by contrast, were much less affected by cold acclimation. The cold-induced changes in phospholipid FA profile and functional properties of muscle mitochondria were reproduced by giving TN ducklings a diet enriched in grapeseed oil (GO, rich in n-6 FA), suggesting a causal relationship between the membrane structure and mitochondrial functional parameters. However, hepatic mitochondria from ducklings fed the GO diet also showed an enrichment in long-chain PUFA but opposite changes in their biochemical characteristics (lower State 4, higher RCR). It is suggested that the differential modulation of mitochondrial functional properties by membrane lipid composition between skeletal muscle and liver may depend on muscle-specific factors possibly interacting with long-chain PUFA and affecting the proton leakiness of mitochondrial membranes.

Animals↗
PubMed1999

White adipose tissue fatty acids of Alpine marmots during their yearly cycle.

Alpine marmots (Marmota marmota) were maintained on a laboratory diet, and the fatty acid composition of gonadal and subcutaneous white adipose tissues (WAT) was studied during a yearly cycle. Fatty acids (FA) released from isolated adipocytes were also identified after stimulation of in vitro lipolysis. Analysis of the FA composition of WAT depots showed that marmot WAT mainly contained monounsaturated FA (65%, mostly oleic acid, 18:1n-9) although laboratory food contained 45% of linoleic acid (18:2n-6) and only 21% of 18:1n-9. During stimulated lipolysis, saturated FA were preferentially released from isolated adipocytes whereas unsaturated FAs were retained. Despite this selective release of FA from isolated WAT cells in vitro, and despite the FA composition of the food, marmots maintained a constant FA composition in both WAT depots throughout the year. Six months of hibernation and fasting as well as an intense feeding period did not affect this composition. The potential adaptive benefit of such regulation of WAT composition, based on a high level of monounsaturated FA, might be to maintain fat with appropriate physical properties allowing animals to accommodate to and survive the wide range of body temperatures experienced during hibernation.

Adipose Tissue↗
PubMed1999

Regional variation of white adipocyte lipolysis during the annual cycle of the alpine marmot.

During winter, hibernating animals rely on their lipid stores for survival. In vitro lipolytic activity of isolated adipocytes from gonadal and subcutaneous white adipose tissue (WAT) was studied in captive alpine marmots (Marmota marmota) at two different times of their yearly cycle. During the summer, when marmots were eating, adipocyte responsiveness and sensitivity to isoprenaline and noradrenaline were higher in gonadal than in subcutaneous WAT. During hibernation, when marmots were spontaneously fasting. both the response and sensitivity to catecholamines decreased in gonadal WAT to the level of subcutaneous WAT. A similar pattern of response was also observed when lipolysis was stimulated with glucagon but the lipolytic rate was three times lower than with catecholamines. Adenosine deaminase (ADA) had a marked stimulatory effect on lipolysis, especially during the 'feeding' period, suggesting that adenosine may be a potent lipolytic modulator in marmot adipocytes. It is concluded that in marmots, lipolysis could be differentially regulated between fat depots during the annual cycle possibly to optimize either the building-up or the use of fat reserves.

Adenosine Deaminase↗
PubMed1999

Efficacy and tolerability of myrtol standardized in long-term treatment of chronic bronchitis. A double-blind, placebo-controlled study. Study Group Investigators.

This multicenter, placebo-controlled, double-blind, randomized parallel-group trial was conducted to investigate the efficacy and tolerability of myrtol standardized (MYS, Gelomyrtol forte, 3 x 300 mg) in the long-term treatment of patients with chronic bronchitis during the winter. 246 patients received the investigational treatments (MYS: 122, placebo: 124) for at least 1 month; 215 subjects (110 under MYS and 105 under placebo) were evaluable in terms of efficacy (exacerbation rate, the need for antibiotics, symptom scores and general well-being) for the protocol-defined 6 months of treatment. Statistically significantly (p < 0.01) more patients remained without acute exacerbation in the myrtol standardized group (72%) compared to the placebo group (53%). In the placebo group, there was an evident peak in the incidence of exacerbations during the third month of treatment, which was not observed in the active treatment group. In the MYS group, 51.6% of the patients with an acute exacerbation required antibiotics vs. 61.2% under placebo. 62.5% of the patients treated with antibiotics in the MYS group required them for < or = 7 days, whereas 76.7% of the patients in the placebo group treated with antibiotics for exacerbation needed antibiotics for > 7 days. Well-being (assessed in terms of general health and health impairment by cough and expectoration) was significantly better under treatment with MYS. The overall therapeutic efficacy evaluation scored higher for MYS. Therefore, it is concluded that long-term treatment with MYS is equally well tolerated as placebo but is clearly superior in efficacy in terms of protecting against acute exacerbations in patients with chronic bronchitis: it reduces the frequency and intensity of acute exacerbations, the need of antibiotics for them and the health impairment by cough and expectoration.

Aged↗
PubMed1997

Bioeffects induced by exposure to microwaves are mitigated by superposition of ELF noise.

We have previously demonstrated that microwave fields, amplitude modulated (AM) by an extremely low-frequency (ELF) sine wave, can induce a nearly twofold enhancement in the activity of ornithine decarboxylase (ODC) in L929 cells at SAR levels of the order of 2.5 W/kg. Similar, although less pronounced, effects were also observed from exposure to a typical digital cellular phone test signal of the same power level, burst modulated at 50 Hz. We have also shown that ODC enhancement in L929 cells produced by exposure to ELF fields can be inhibited by superposition of ELF noise. In the present study, we explore the possibility that similar inhibition techniques can be used to suppress the microwave response. We concurrently exposed L929 cells to 60 Hz AM microwave fields or a 50 Hz burst-modulated DAMPS (Digital Advanced Mobile Phone System) digital cellular phone field at levels known to produce ODC enhancement, together with band-limited 30-100 Hz ELF noise with root mean square amplitude of up to 10 microT. All exposures were carried out for 8 h, which was previously found to yield the peak microwave response. In both cases, the ODC enhancement was found to decrease exponentially as a function of the noise root mean square amplitude. With 60 Hz AM microwaves, complete inhibition was obtained with noise levels at or above 2 microT. With the DAMPS digital cellular phone signal, complete inhibition occurred with noise levels at or above 5 microT. These results suggest a possible practical means to inhibit biological effects from exposure to both ELF and microwave fields.

Animals↗
PubMed1995

Embryotoxicity induced by alkylating agents: 9. Low dose prenatal-toxic risk estimation of ethylmethanesulfonate based on no-observed-adverse-effect-level risk factor approach, dose-response relationships, and molecular dosimetry.

Analogously to an earlier study using methylnitrosourea (MNU) the prenatal-toxic risk of low doses of ethylmethanesulfonate (EMS) was estimated using different procedures, comparatively. First, the risk of low doses was estimated using linear extrapolation to zero. When using the variable "all gross structural abnormalities" the lowest effective dose in the experiment was 150 mg/kg body wt (5.6% incidence), the additional risk over background was calculated to be 5.0%, and the hypothetical incidence 0.1% was associated with the dose 3 mg/kg EMS. When evaluating "gross structural limb abnormalities," which are not observed in controls, the dose associated with the hypothetical incidence 0.1% was 17.4 mg/kg EMS. Furthermore, derived from a dose-response study of teratogenicity extrapolation to the possible risk of low doses was performed using nonlinear mathematical models. In this case, the results obtained are dependent on the dose response variable as well as from the statistical approach which was chosen. As an example, the values obtained from one evaluation are given: all gross structural abnormalities, Weibull transformation, jackknife approach: ED0.1% = 72 mg/kg EMS. For comparison a "virtually safe dose" was calculated by use of the no-observed-adverse-effect-level (NOAEL) risk factor approach. The NOAEL under our experimental conditions was 100 mg per kg body wt. By using an arbitrarily chosen risk factor of 100 a "safe dose" of 1 mg EMS per kg body wt was obtained. In addition, molecular dosimetry of the DNA adduct rate of O6-ethylguanine in the 11-day-old embryos was used. Based on the assumption that a linear correlation exists between this specific adduct rate and the incidence of teratogenic effects, the hypothetical incidence of 0.1% was associated with a dose of 99 mg/kg EMS. This value is quite similar to that obtained by extrapolation using probit analysis which is in contrast to the results obtained with MNU.

Alkylating Agents↗
PubMed1995

[Endoscopic dissection of perforating veins].

Endoscopic subfascial sectioning (ESDP) is an effective method for the interruption of incompetent perforating veins. From March 1993 to April 1994 27 patients underwent ESDP in 35 legs. ESDP was performed in combination with Babcock's operation in 31 cases. Most patients demonstrated chronic venous insufficiency stage II or III (n = 25). A venous ulcer was found in 9 patients. Intraoperative complications were not seen. Postoperative complications were delayed wound healing (n = 1) and subfascial hematoma (n = 1). At follow-up examination after a mean interval of 8 months persistent insufficient perforating veins were seen in 3 of 88 Cockett veins (4%). A local dysesthesia of the saphenous nerve was found in 6 legs. Prior active venous ulcers had healed in 8 of 9 cases.

Adult↗
PubMed1993

Determination of the induced ELF electric field distribution in a two layer in vitro system simulating biological cells in nutrient solution.

In-vitro studies of biological effects of electromagnetic fields are often conducted with cultured cells either in suspension or grown in a monolayer. In the former case, the exposed medium can be assumed to be homogeneous; however, eventually the cells settle to the bottom of the container forming a two layer system with different dielectric and conductive properties. In the present work the effect of this separation on the electric field distribution is calculated and experimentally measured at selected positions for a commonly used exposure configuration. The settled cell suspension is modeled by a well-defined two layer system placed in a rectangular container with the base of the container parallel to the direction of the magnetic field. Theoretical calculations based on numerical techniques are done for various two layer systems with different conductivities in each layer. The agreement between the theoretical calculations and the experimental measurements is within +/- 1.5 mV/m, or 10% of the maximum induced field when the conductivity of the lower layer is ten times that of the upper layer. This result is well within experimental error. When the thickness of one of the layers is small compared to the thickness of the other layer, it is found that the electric field distribution is essentially that of the homogeneous case. The latter situation corresponds to a typical cell exposure condition.

Cells, Cultured↗
PubMed1993

Embryotoxicity induced by alkylating agents: 7. Low dose prenatal-toxic risk estimation based on NOAEL risk factor approach, dose-response relationships, and DNA adducts using methylnitrosourea as a model compound.

Prenatal-toxic risk estimation for the alkylating model compound methylnitrosourea (MNU) was performed using different procedures. Risk of low doses was estimated using linear extrapolation to zero (estimated ED0.1%: 0.1 mg/kg body wt MNU) as well as extrapolation by probit analysis based on a dose-response study (estimated ED0.1%: 1.6 mg/kg body wt). Furthermore, a "virtually safe dose" was established by means of the NOAEL risk factor approach (e.g., factor 30:0.03 mg MNU per kg body wt). In previous studies in murine embryos using MNU, we combined dose-response data and DNA adduct rate measurements and deduced that O6-methylguanine is a suitable variable for molecular dosimetry. In a tentative approach, we estimated the teratogenic risk of low doses based on the adduct rates of O6-methylguanine in the DNA of the embryos. It is concluded that in the case of steep dose-response relationships, which are typical for the majority of teratogenic effects, the NOAEL risk factor approach is more conservative than extrapolation based on probit analysis. Risk estimation using dosimetry with this model compound yields estimated incidences similar to linear extrapolation.

Abnormalities, Drug-Induced↗
PubMed1992

ELF in vitro exposure systems for inducing uniform electric and magnetic fields in cell culture media.

Many in vitro experiments on the biological effects of extremely low frequency (ELF) electromagnetic fields utilize a uniform external magnetic flux density (B) to expose biological materials. A significant number of researchers do not measure or estimate the resulting electric field strength (E) or current density (J) in the sample medium. The magnitude and spatial distribution of the induced E field are highly dependent on the sample geometry and its relative orientation with respect to the magnetic field. We have studied the E fields induced in several of the most frequently used laboratory culture dishes and flasks under various exposure conditions. Measurements and calculations of the E field distributions in the aqueous sample volume in the containers were performed, and a set of simple, quantitative tables was developed. These tables allow a biological researcher to determine, in a straightforward fashion, the magnitudes and distributions of the electric fields that are induced in the aqueous sample when it is subjected to a uniform, sinusoidal magnetic field of known strength and frequency. In addition, we present a novel exposure technique based on a standard organ culture dish containing two circular, concentric annular rings. Exposure of the organ culture dish to a uniform magnetic field induces different average electric fields in the liquid medium in the inner and outer rings. Results of experiments with this system, which were reported in a separate paper, have shown the dominant role of the magnetically induced E field in producing specific biological effects on cells, in vitro. These results emphasize the need to report data about the induced E field in ELF in-vitro studies, involving magnetic field exposures. Our data tables on E and J in standard containers provide simple means to enable determination of these parameters.

Culture Media↗
PubMed1992

Citrate and recurrent idiopathic calcium urolithiasis. A longitudinal pilot study on the metabolic effects of oral potassium citrate administered over the short-, medium- and long-term medication of male stone patients.

In idiopathic recurrent calcium urolithiasis (RCU) in men (n = 37) the metabolic effects of oral tripotassium citrate (PC) were investigated in a longitudinal field study. The patients were either normo- (n = 22) or hypocitraturic (n = 15). Laboratory examinations were performed before, and after 3, 6, and more than 12 months of medication. Acceptance of PC was poor, mainly because of the salty taste of the tablet preparation chosen, and a number of participants dropped out of the study. In the remaining participants, compliance was acceptable when evaluated on the basis of urinary potassium and undesired side effects did not occur. In the short term (up to 3 months), PC evoked compensated metabolic alkalosis (pH and citrate in urine increased; blood gases remained normal), a drop in urinary calcium, together with increasing oxaluria, hydroxyapatite supersaturation, and calcium phosphate crystalluria. In the long term (greater than 12 months) PC urinary pH and citrate "dissociated", in that pH returned to pretreatment baseline values, whereas citrate stayed at high levels. In normocitraturics but not in hypocitraturics, urinary urea and sodium increased with PC. Hypocitraturics appeared to be less sensitive to the effects of PC, as reflected by the relatively small rise in urinary pH and citrate, and they maintained higher mean levels of indicators of bone metabolism (osteocalcin, alkaline phosphatase, hydroxyproline) despite continuous administration of PC. It was concluded that although the PC tablet preparation was effective it may not be an ideal anti-stone drug treatment in the long term and that, especially in hypocitraturics, the intrinsic metabolic defect of RCU may not be sufficiently well controlled.

Acid-Base Equilibrium↗