Biomedical subjects

R Vogel

Publications and source records attributed to R Vogel.

At least 37 records · Page 2Linked to original sources

PubMed2001

Should all patients with cardiovascular disease receive statin therapy?

With the strong correlation between the development of coronary heart disease and elevated levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C), therapies that significantly lower lipid levels will be widely prescribed. Within the past 15 years, major studies have shown the statins to be very effective in lowering LDL-C levels. Are the effects of statin therapy powerful enough to justify administering one of these drugs to every patient with cardiovascular disease? Among the arguments favoring its general usage are its safety record, its high rate of patient compliance (especially in comparison to alternative therapies such as diet and exercise), and its cost effectiveness. On the other hand, elevated levels of LDL-C are not the only cause of atherosclerosis, so simply lowering the LDL-C level is not the sole answer to reducing the risk of mortality and morbidity from coronary heart disease.

Anticholesteremic Agents↗

PubMed2001

Delayed vaccination does not improve antibody responses in splenectomized rats experiencing hypovolemic shock.

Delayed vaccination after splenectomy has been shown to increase the antibody response in normotensive rats. The purpose of this experiment was to study the effect of timing of vaccination on antibody responses in rats undergoing splenectomy and experiencing hypovolemic shock. Sixty male Sprague-Dawley rats weighing 250 to 400 g underwent either a sham abdominal surgery or splenectomy after a 30-minute period of controlled hypovolemic shock. All rats then received pneumococcal vaccinations one day, 7 days, or 28 days postoperatively. Antibody levels were determined by enzyme-linked immunosorbent assay 3 weeks after vaccination. Results were compared by analysis of variance. Animals vaccinated one day postoperatively had similar or higher antibody responses than did rats receiving delayed vaccinations after 7 or 28 days. These results were similar for immunoglobulins G and M and more importantly were consistent for animals undergoing splenectomy and sham operations. Delayed vaccinations failed to improve antibody responses when hypovolemic shock preceded splenectomy. We propose that this is the result of complex cytokine responses to hypovolemic shock. These responses have been studied extensively in the setting of septic shock but not in the setting of hypovolemic or hemorrhagic shock.

Animals↗

PubMed2000

The molecular origin of the inhibition of transducin activation in rhodopsin lacking the 9-methyl group of the retinal chromophore: a UV-Vis and FTIR spectroscopic study.

The formation of the active rhodopsin state metarhodopsin II (MII) is believed to be partially governed by specific steric constraints imposed onto the protein by the 9-methyl group of the retinal chromophore. We studied the properties of the synthetic pigment 9-demethyl rhodopsin (9dm-Rho), consisting of the rhodopsin apoprotein regenerated with synthetic retinal lacking the 9-methyl group, by UV-vis and Fourier transform infrared difference spectroscopy. Low activation rates of the visual G-protein transducin by the modified pigment reported in previous studies are shown to not be caused by the reduced activity of its MII state, but to be due to a dramatic equilibrium shift from MII to its immediate precursor, MI. The MII state of 9dm-Rho displays only a partial deprotonation of the retinal Schiff base, leading to the formation of two MII subspecies absorbing at 380 and 470 nm, both of which seem to be involved in transducin activation. The rate of MII formation is slowed by 2 orders of magnitude compared to rhodopsin. The dark state and the MI state of 9dm-Rho are distinctly different from their respective states in the native pigment, pointing to a more relaxed fit of the retinal chromophore in its binding pocket. The shifted equilibrium between MI and MII is therefore discussed in terms of an increased entropy of the 9dm-Rho MI state due to changed steric interactions.

Animals↗

PubMed2000

Requirement for beta-catenin in anterior-posterior axis formation in mice.

The anterior-posterior axis of the mouse embryo is defined before formation of the primitive streak, and axis specification and subsequent anterior development involves signaling from both embryonic ectoderm and visceral endoderm. Tauhe Wnt signaling pathway is essential for various developmental processes, but a role in anterior-posterior axis formation in the mouse has not been previously established. Beta-catenin is a central player in the Wnt pathway and in cadherin-mediated cell adhesion. We generated beta-catenin-deficient mouse embryos and observed a defect in anterior-posterior axis formation at embryonic day 5.5, as visualized by the absence of Hex and Hesx1 and the mislocation of cerberus-like and Lim1 expression. Subsequently, no mesoderm and head structures are generated. Intercellular adhesion is maintained since plakoglobin substitutes for beta-catenin. Our data demonstrate that beta-catenin function is essential in anterior-posterior axis formation in the mouse, and experiments with chimeric embryos show that this function is required in the embryonic ectoderm.

Animals↗

PubMed2000

Electrospray and chemical ionization mass spectrometry of di-n-butyl sulfate. Unimolecular chemistry of its protonated form and quantification method by liquid chromatography/electrospray ionization tandem mass spectrometry

Di-n-butyl sulfate (DNBS) has been studied by electrospray (ESI) and chemical (CI) ionization mass spectrometry. The use of methanol as solvent in electrospray ionization allows observation of relatively abundant [DNBS + CH(3)OH + H](+) ions (m/z 243) which upon collision dissociate to [DNBS + H](+) ions (m/z 211). In both ESI and CI experiments, it is found that [DNBS + H](+) ions lead to m/z 113 daughter ions. The composition of this m/z 113 fragment ion and its mechanism of formation have been established by high resolution measurements and CID-MIKE experiments. An 'internal substitution' reaction involving an ion-neutral intermediate is proposed to explain the formation of a [C(8)H(17)](+) ion (m/z 113) by loss of a H(2)SO(4) molecule. Finally, a LC/ESI-MS/MS quantification method is proposed in which a detection limit of di-n-butyl sulfate in the ppm range is obtained. It is suggested that the quantification method might be extended to higher dialkyl sulfates. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2000

The kinetics of gap junction currents are sensitive to the ionic composition of the pipette solution.

Myocytes were isolated from neonatal rat hearts using an enzymatic procedure. Cell pairs were used to control the junctional voltage, V(j), and to measure the transjunctional current, I(j), using the dual voltage-clamp method. V(j) gradients provoked I(j) signals with voltage-dependent inactivation. During voltage pulses, I(j) remained virtually constant at ¿V(j)¿ <40 mV. At ¿V(j)¿>40 mV, it inactivated with time to a residual level. The inactivation followed a single exponential. The time constant of I(j) inactivation, taui, and the size of I(j) at steady state, I(j,ss), were both sensitive to the ions in the pipette solution. I(j,ss) was smaller in the presence of tetraethylammonium aspartate (TEA+ aspartate-) than KC1, while taui was smaller in the presence of KC1 than TEA+ aspartate-. The modification of I(j,ss) is readily explained by a change in the residual conductance of the gap junction channels, gammaj,residual x The alterations in taui are correlated with a change in beta, the rate constant that describes the transition of the channel from the main state to the residual state. Pipette solutions may affect the kinetics of gap junction currents by altering the conductive and/or kinetic parameters. Computer simulations revealed a substantial influence of the latter, but only a marginal effect of the former. Conceivably, ions of the pipette solution may affect the kinetics of gap junction channels by screening surface charges of the channel wall.

Animals↗

PubMed2000

Polyphasic identification of wild yeast strains isolated from Greek sourdoughs.

A total of forty-five wild yeast strains were isolated from five traditional Greek wheat sourdoughs. Strains were identified using the classical identification technique along with the sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole cell proteins (SDS-PAGE), Fourier transform-infrared spectroscopy (FT-IR) and the randomly amplified polymorphic DNA-polymerase chain reaction analysis (RAPD-PCR). The latter methods confirmed the classical identification. According to the results obtained, fourteen strains were identified as Saccharomyces cerevisiae strains, twenty-five as Pichia membranaefaciens strains and six as Yarrowia lipolytica.

Bread↗

PubMed2000

Vibrational spectroscopy as a tool for probing protein function.

Vibrational spectroscopy has become increasingly important as a tool for understanding the mechanisms of photosystem II, phytochrome and terminal oxidases. More general enzymatic or receptor systems have been studied, opening a new field of applications. Femtosecond infrared pump/probe studies of the important amide-I band seem to provide a basis for its molecular and structural interpretation.

Light↗

PubMed2000

In vitro germ cell models for the detection of fertility impairment.

Pluripotent embryonic carcinoma cells and pluripotent embryonic stem cells established from undifferentiated cells of an early mouse embryo were investigated for induction of proliferation inhibition, sister chromatid exchanges (SCE) and single-strand breaks by treatment with various germ cell mutagens. The comparison of malignant cells with nonmalignant cells showed an increased sensitivity of nonmalignant cells independent of their state of differentiation. Mitomycin C (MMC) inhibited the proliferation of nonmalignant cells at a concentration of 10(-6) M but did not affect growth of the teratocarcinoma cell line P19. There were no differences between the investigated cell lines at a lower MMC concentration. At the concentration of 10(-6) M MMC the sister chromatid exchanges of P19 were enhanced up to 41 SCE per metaphase. Testing of another germ cell mutagen, ethylnitrosourea (ENU), gave similar results: a decreasing generation time of nonmalignant cell lines after treatment with 1 mM ENU and no effect on the teratocarcinoma cells. This concentration also induced a high number of SCE. Single-strand breaks could be produced by exposure to methanmethylsulphonate (MMS). 56.3% of embryonic stem cell DNA was passing through the filter after MMS treatment. In contrast to the embryonic stem cells, only 35.6% of teratocarcinoma DNA was affected.

Animals↗

PubMed2000

Changes of interstitial fluid volume in superficial tissues detected by a miniature ultrasound device.

We evaluated the changes of tissue layer thickness in circumscribed superficial tissue areas with a 10-MHz A-mode and a 20-MHz B-mode ultrasound device under alterations in body posture and plasma volume to detect fluid shifts between the different compartments. In 20 male volunteers, we measured tissue thickness by A mode and corium and subcutis thickness by B mode at the forehead before and 30 min after three procedures: change from upright to supine position (P1); change from upright to 30 degrees head-down-tilt position (P2); infusion of 10 ml/kg body wt of Ringer solution (P3). We found a significant correlation between baseline tissue thickness and the sum of corium and subcutis thicknesses (r = 0.75, P < 0.01). The changes of body posture and plasma volume resulted in significant increases of tissue thickness (P1, 2.9%; P2, 11.6%; P3, 5.8%) and corium thickness (P1, 4.7%; P2, 8.1%; P3, 9.1%) but not of the sum of chorium and subcutis thicknesses. We conclude that fluid shifts from the intravascular to the extravascular compartment are detectable by evaluating corium thickness with a B-mode, or more easily tissue thickness with an A-mode, ultrasound device.

Adult↗

PubMed2000

[Substance dependence and suicide in hospitalized patients. A description].

OBJECTIVE: The research group "Suicide and Psychiatric Hospital" has studied inpatient suicides in psychiatric hospitals in Baden-Württemberg and Bavaria (Germany) from 1970-1996. Whereas suicides in depression and schizophrenia are described very well, a description of addicted inpatients who committed suicide is still missing. PATIENTS AND METHODS: We studied the data of substance dependent patients of the collective of 726 inpatient suicides. RESULTS AND CONCLUSIONS: Among the generally rare suicides of addicted inpatiens--33 of 726--about 81% were alcohol dependent. The frequency of suicide in this group of patients decreased from 6.7% in the years 1970-1984 to 1.4% between 1990 and 1996. Whereas the age remained more or less stable in the middle of the fifth decade, the time from hospitalisation until suicide shortened from 192 days (mean) to 52 days. Suicide of alcohol dependent and poly-drug-abusing patients today almost exclusively takes place during treatment on an open station and among patients being in treatment on a voluntary basis. Suicide attempts in the anamnesis are extraordinarily rare in alcohol dependent suiciders.

Adult↗

PubMed2000

Bacterial expression of G-protein-coupled receptors: prediction of expression levels from sequence.

Eleven G-protein-coupled receptors were expressed in Escherichia coli as fusion proteins with N-terminal glutathione-S-transferase and a C-terminal (His)6 tag. Expression levels varied between 0.1% and 10% of the total cellular protein. Low expression levels, as quantified by analytical nickel chelating chromatography, coincided with a toxic effect of protein expression. Multiple linear regression analysis was used to establish a correlation between the occurrence of positively charged amino acid residues in the loop regions and the expression level. Indeed, 44% of the variation in expression levels could be attributed to the positive charge content. Consequently, this sequence feature is the major determinant of expression level. Our results were supported by two mutations where positive charges were introduced into loop regions of two low-expressing receptors: As predicted, these mutations led to a considerably higher expression. A similar mutation of an olfactory receptor described previously increased expression approximately 100-fold and further supports our model. The data are discussed in the context of the "positive inside rule".

Amino Acid Sequence↗

PubMed1999

The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required.

Metabolic pathways underlying the regeneration of reduced glutathione were investigated in acutely isolated metabolically active mitochondria from rat forebrain. The application of hydrogen peroxide to the organelles was accompanied by a transient increase in glutathione disulfide. The recovery of reduced glutathione was significantly improved in the presence of alternatively succinate, malate, citrate, isocitrate, or beta-hydroxybutyrate. Inhibition of succinate dehydrogenase by malonate abolished the beneficial effect of succinate on the reduction of glutathione disulfide but did not influence the effect of isocitrate. Fluorocitrate, an inhibitor of aconitase, blocked the effect exerted by citrate but did not inhibit the effects of malate or beta-hydroxybutyrate. Uncoupling of the respiratory chain by carbonyl cyanide m-chlorophenylhydrazone prevented the beneficial effect of beta-hydroxybutyrate but did not abolish the improved reduction of mitochondrial glutathione disulfide in the presence of malate and isocitrate. These results suggest that NADP+-dependent isocitrate dehydrogenase as well as malic enzyme and nicotinamide nucleotide transhydrogenase contribute to the regeneration of NADPH required for the reduction of glutathione disulfide in brain mitochondria.

Animals↗

PubMed1999

Extensive transmission of Mycobacterium tuberculosis from a child.

BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.

Adult↗

PubMed1999

Biophysical properties of mouse connexin30 gap junction channels studied in transfected human HeLa cells.

1. Human HeLa cells expressing mouse connexin30 (Cx30) were used to study the electrical properties of Cx30 gap junction channels. Experiments were performed on cell pairs with the dual voltage-clamp method. 2. The gap junction conductance (gj) at steady state showed a bell-shaped dependence on junctional voltage (Vj; Boltzmann fit: Vj,0 = 27 mV, gj,min = 0.15, z = 4). The instantaneous gj decreased slightly with increasing Vj. 3. The gap junction currents (Ij) declined with time following a single exponential. The time constants of Ij inactivation (taui) decreased with increasing Vj. 4. Single channels exhibited a main state, a residual state and a closed state. The conductances gammaj,main and gammaj,residual were 179 and 48 pS, respectively (pipette solution, potassium aspartate; temperature, 36-37 degrees C; extrapolated to Vj = 0 mV). 5. The conductances gammaj,residual and gammaj,main showed a slight Vj dependence and were sensitive to temperature (Q10 values of 1.28 and 1.16, respectively). 6. Current transitions between open states (i.e. main state, substates, residual state) were fast (< 2 ms), while those between an open state and the closed state were slow (12 ms). 7. The open channel probability (Po) at steady state decreased from 1 to 0 with increasing Vj (Boltzmann fit: Vj,0 = 37 mV; z = 3). 8. Histograms of channel open times implied the presence of a single main state; histograms of channel closed times suggested the existence of two closed states (i.e. residual states). 9. We conclude that Cx30 channels are controlled by two types of gates, a fast one responsible for Vj gating involving transitions between open states (i.e. residual state, main state), and a slow one correlated with chemical gating involving transitions between the closed state and an open state.

Animals↗

PubMed1999

Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

Animals↗

PubMed1999

Pluripotent stem cells of the mouse as a potential in vitro model for mammalian germ cells. Sister chromatid exchanges induced by MMC and ENU in undifferentiated cell lines compared to differentiated cell lines.

We tried to develop an in-vitro test system which could serve as a model for mammalian germ cells in vivo. Two pluripotent cell types were used, because they express some germ cell specific immunological and biochemical markers: (1) Embryonal carcinoma cells (ECC) of the line P19 had been isolated from a teratocarcinoma of murine primordial germ cells (PGC). (2) Embryonal stem cells (ESC) are obtained from the inner cell mass of mouse blastocysts. Sister chromatid exchanges (SCE) induced by mitomycin C and ethylnitrosourea (ENU) were analysed in the two undifferentiated cell lines, ECC and ESC, to detect differences in their sensitivity compared with differentiated cell lines of the mouse. Neither of the model cell lines have shown a greater sensibility after exposure to MMC and ENU. In contrary, the carcinoma cell line was able to tolerate higher concentrations of these genotoxicants. Therefore, SCE analysis in the ECC and ESC lines used does not provide a suitable model for genotoxicity testing on mammalian germ cells.

Animals↗

PubMed1999

A model for the generation of low level chemiluminescence from microbiological growth media and its depletion by bacterial cells.

We present a model for the development of chemiluminescence (CL) in autoclaved liquid growth media, as they are used in microbiology for the culturing of microorganisms, or in other related Maillard systems. The model distinguishes between four different stages consisting of sugar fragmentation during heating, autooxidation of highly reducing fragmentation products, radical chain reactions leading to a peroxidation of the media, and finally the formation of excited states, energy transfer reactions and CL emission. The proposed model is also discussed in regard of a recently reported elimination of this CL in growing cultures of microorganisms and possible pathways for this interference are suggested.

Bacteria↗