Biomedical subjects

S Schrader

Publications and source records attributed to S Schrader.

At least 19 recordsLinked to original sources

PubMed2006

Membrane-assisted liquid-liquid extraction coupled with gas chromatography-mass spectrometry for determination of selected polycyclic musk compounds and drugs in water samples.

Selected polycyclic musk compounds and drugs were extracted from water samples by membrane-assisted micro liquid-liquid extraction. The two-phase extraction system consisted of polyethylene membrane bags filled with an organic solvent. Chloroform proved to be most suited as acceptor phase to extract caffeine, Galaxolide, Tonalide, phenazone and carbamazepine from aqueous samples. The compounds were enriched from 50 mL sample into a volume of 500 microL of chloroform. Gas chromatography-mass spectrometry (GC-MS) was applied for analysis. The extraction procedure was optimised in regard to membrane material, extraction time and temperature. The evaluation of the entire analysis protocol found limits of detection that ranged from 20 to 200 ng/L. The linear range of calibration covered one magnitude with standard deviations between 4 and 12%. Method comparison with standard analysis techniques such as solid-phase extraction (SPE) combined with GC-MS as well as LC-MS-MS confirmed this method as an easy and reliable protocol, even for the monitoring of matrix-loaded wastewater. The analysis of real samples established the feasibility of the technique.

Calibration↗

PubMed2005

Nanoclusters in polymer matrices prepared by co-deposition from a gas phase.

This paper reviews the fabrication of organic and metal nanoclusters in polymer matrices by three co-deposition techniques. In particular, the structure and properties of polytetrafluoroethylene (PTFE), polychlortrifluoroethylene (PCTFE), polyparaphenylene sulphide (PPS), polystyrene (PS) and polyparaxylylene (PPX) films, containing gold (Au) and dye clusters are discussed. For the first time, dye-filled polymers and multi-component films, consisting of both Au nanoparticles and dye molecules, dispersed in the PTFE matrix were studied. A low temperature plasma was used for film structure modification. Cluster formation process was studied using optical spectroscopy in situ. Transmission electron microscopy (TEM), atomic force microscopy (AFM) and ellipsometry were used for characterisation of the grown films. During Au-PTFE film growth plasmon band shifted from 460-480 nm to 560 nm. Au cluster diameter was in the 3-7 nm range. Plasma treatment of the vapours led to formation of smaller, but more aggregated clusters. During Au-PPS film deposition a two-step growth mechanism was discovered. At the beginning of film growth the plasmon band at 540 nm appeared, but as thickness increased, the band at 430 nm dominated. Without plasma treatment a disordered mixture was deposited, while with plasma treatment large Au aggregates confined with PPS matrix having plasmon band at 620 nm were formed. Dye cluster formation depends on the dye ability to aggregate, its concentration and the properties of the polymer matrix. But cluster formation can also be tuned by varying the deposition conditions. Laser beam evaporation promoted cluster formation, while plasma treatment and dilution in a polymer matrix prevented cluster formation. In all cases both equilibrium and non-equilibrium film structure can be formed using kinetic factor. Asymmetric molecules with bulky substituents were oriented in polymer matrices by applying an electric field in situ or by corona poling. These molecules did not aggregate even at high dye load. The films exhibited second harmonic generation, which demonstrated chromophore orientation in the polymer matrices.

Coloring Agents↗

PubMed2005

Differential approach to the study of integral characteristics in polymer films.

The differential approach is based on the determination of dimensionless differential slope, for instance, of current-voltage characteristics (IVC), I=f(V). This slope (alpha) is given by formula alpha=d(lgI)/d(lgV). With such definition the ranges of constancy of the alpha(V) dependency correspond to the part of IVC characterized by the power behaviour (I approximately V(alpha)). The differential slope of alpha(V) dependency gamma=d(lgalpha)/dlgV determines the exponent behaviour of curve (I approximately exp(eV(gamma)/kT)). Processing by the differential approach of the investigated theoretical or experimental characteristics permits us to determine the peculiarity of charge flow mechanisms, temperature behaviour of conductivity, etc. The theoretical base and some applications of differential approach to the investigation of the current-voltage, temperature and degradation characteristics of the polyaniline and poly(p-phenilenevinilene) based structures have been shown.

Electric Conductivity↗

PubMed2005

Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV potency.

The goal of this study was to optimize the hydroxyurea dosage in HIV-infected patients, and to minimize the toxicity and maximize the antiviral efficacy of the hydroxyurea-didanosine combination. In a randomized, open-label study (RIGHT 702, a multicenter trial performed in private and institutional practices), three daily doses (600 microg, 800-900 microg, and 1200 microg) of hydroxyurea were administered in combination with didanosine and stavudine to 115 chronically HIV-infected patients, one-third antiretroviral drug naive, with viremia between 5000 and 200,000 copies/ml regardless of CD4+ cell count. The primary efficacy end point was the proportion of patients with plasma HIV-1 RNA levels below 400 copies/ml after 24 weeks of therapy. In the RIGHT 702 intent-to-treat population the lowest (600 mg) dose of hydroxyurea was better tolerated, associated with fewer adverse events, and more potent by all efficacy parameters, including the primary end point (76 versus 60% patients with viremia<400 copies/ml at week 24 for the 600-mg and 800- to 900-mg dose groups, respectively; p=0.027), the mean area under the curve (60.3 versus 65.8; p=0.016), and the mean log10 decrease (-1.95 versus -0.77; p=0.001). Patients receiving 600 mg of hydroxyurea daily also had the highest CD4+ cell count, CD4+/CD8+ cell ratio, and lowest CD8+ cell count and percentage (p=0.035). The RIGHT 702 trial provides an explanation for the increased toxicity and decreased efficacy of hydroxyurea when it was used at high dosage (1200 mg daily). At the optimal dosage of 600 mg daily, hydroxyurea, in combination with didanosine, deserves reevaluation for the long-term management of HIV/AIDS worldwide, because of its excellent resistance profile, durability, and affordability.

Anti-HIV Agents↗

PubMed2004

Using new structurally related additive schemes in the precalculation of gas chromatographic retention indices of polychlorinated hydroxybiphenyls on HP-5 stationary phase.

A new additive scheme is proposed for the precalculation of gas chromatographic retention indices of complex organic compounds. The principal feature of this approach is the absence of previously calculated I increments for any structural fragments or functional groups in the molecule. Instead, arithmetical operations involving I values of simpler structural analogues of target compounds are used directly. I precalculation for polychlorinated hydroxybiphenyls (839 congeners) on the HP-5 stationary phase was chosen as one of the most important applications of the method under discussion. Such a large number of congeners cannot be obtained as reference samples and their gas chromatographic (GC)-mass spectrometric (MS) identification should therefore be based currently on precalculated I values.

Chromatography, Gas↗

PubMed2003

Sequential fractionation procedure for the identification of potentially cytochrome P4501A-inducing compounds.

A multistep fractionation procedure for the separation of nonpolar aromatic compounds with respect to cytochrome P4501A induction is presented. Normal-phase HPLC on nitrophenylpropyl silica and cyanopropyl silica was tested for group-specific separation as a first fractionation step. Subsequent individual compound-specific PAH fractionation was done by means of reversed-phase HPLC. Electron-donor-acceptor HPLC and size-exclusion chromatography were applied to separate PAHs, PCBs, PCNs and PCDD/Fs according to their number of aromatic carbon atoms, their hydrophobicity, their degree of chlorination, their planarity and their molecular size. The method was validated for complex environmental mixtures on the basis of two sediment extracts.

Chromatography, Gel↗

PubMed2002

Directional sensitivity of wind-sensitive giant interneurons in the cave cricket Troglophilus neglectus.

Unlike the situation in most cockroach and cricket species studied so far, the wind-sensitive cerci of the cave cricket Troglophilus neglectus Krauss (Rhaphidophoridae, Orthoptera) are not oriented parallel to the body axis but perpendicular to it. The effects of this difference on the morphology, and directional sensitivity of cercal giant interneurons (GIs), were investigated. In order to test the hypothesis that the 90 degrees change in cercal orientation causes a corresponding shift in directional sensitivity of GIs, their responses in both the horizontal and vertical planes were tested. One ventral and four dorsal GIs (corresponding to GIs 9-1a and 9-2a, 9-3a, 10-2a, 10-3a of gryllid crickets) were identified. The ventral GI 9-1a of Troglophilus differed somewhat from its cricket homologue in its dendritic arborisation and its directional sensitivity in the horizontal plane. The morphology and horizontal directionality of the dorsal GIs closely resembled that of their counterparts in gryllids. In the vertical plane, the directionality of all GIs tested was similar. They were all excited mainly by wind puffs from the axon-ipsilateral quadrant. The results suggest that directional sensitivity to air currents in the horizontal plane is maintained despite the altered orientation of the cerci. This is presumably due to compensatory modifications in the directional pReferences of the filiform hairs.

Animals↗

PubMed2001

Rapid, ATP-dependent degradation of a truncated D1 protein in the chloroplast.

The D1 protein constitutes one of the reaction center subunits of photosystem II and turns over rapidly due to photooxidative damage. Here, we studied the degradation of a truncated D1 protein. A plasmid with a precise deletion in the reading frame of the psbA gene encoding D1 was introduced into the chloroplast of Chlamydomonas reinhardtii. A homoplasmic mutant containing the desired gene was able to synthesize the truncated form of the polypeptide, but could not accumulate significant levels of it. As a consequence, other central photosystem II subunits did not assemble within the thylakoid membrane. In vivo pulse-chase experiments showed that the abnormal D1 protein is rapidly degraded in the light. Degradation was delayed in the light in the presence of an uncoupler, or when cells were incubated in the dark. Pulse-chase experiments performed in vitro indicate that an ATP and metal-dependent protease is responsible for the breakdown process. The paper describes the first in vivo and in vitro functional test for ATP-dependent degradation of a defect polypeptide in chloroplasts. The possible involvement of proteases similar to those removing abnormal proteins in prokaryotic organisms is discussed on the basis of proteases recently identified in chloroplasts.

Adenosine Triphosphate↗

PubMed2000

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Amino Acid Sequence↗

PubMed2000

Central projections of Drosophila sensory neurons in the transition from embryo to larva.

Sensory axons of different sensory modalities project into typical domains within insect ganglia. Tactile and gustatory axons project into a ventral layer of neuropil and proprioceptive afferents, including chordotonal axons, into an intermediate or dorsal layer. Here, we describe the central projections of sensory neurons in the first instar Drosophila larva, relating them to the projection of the same sensory afferents in the embryo and to sensory afferents of similar type in other insects. Several neurons show marked morphologic changes in their axon terminals in the transition between the embryo and larva. During a short morphogenetic period late in embryogenesis, the axon terminals of the dorsal bipolar dendrite stretch receptor change their shape and their distribution within the neuromere. In the larva, external sense organ neurons (es) project their axons into a ventral layer of neuropil. Chordotonal sensory neurons (ch) project into a slightly more dorsal region that is comparable to their projection in adults. The multiple dendrite (md) neurons show two distinctive classes of projection. One group of md neurons projects into the ventral-most neuropil region, the same region into which es neurons project. Members of this group are related by lineage to es neurons or share a requirement for expression of the same proneural gene during development. Other md neurons project into a more dorsal region. Sensory receptors projecting into dorsal neuropil possibly provide proprioceptive feedback from the periphery to central motorneurons and are candidates for future genetic and cellular analysis of simple neural circuitry.

Animals↗

PubMed2000

Sequence of the two operons encoding the four core subunits of the cytochrome b(6)f complex from the thermophilic Cyanobacterium synechococcus elongatus.

The genes encoding cytochrome f (petA), cytochrome b(6) (petB), the Rieske FeS-protein (petC), and subunit IV (petD) of the cytochrome b(6)f complex from the thermophilic cyanobacterium Synechococcus elongatus were cloned and sequenced. Similar to other cyanobacteria, the structural genes are arranged in two short, single-copy operons, petC/petA and petB/petD, respectively. In addition, five open reading frames with homology to known orfs from the cyanobacterium Synechocystis PCC 6803 were identified in the immediate vicinity of these two operons.

Cloning, Molecular↗

PubMed2000

Solid-phase microextraction-gas chromatography-mass spectrometry of biologically active substances in water samples.

A solid-phase microextraction (SPME) method for determining trace amounts of polar, biologically active substances in water systems was developed and compared with solid-phase extraction followed by derivatization and GC-MS. SPME was examined with respect to the simultaneous determination of pharmaceuticals such as ibuprofen, paracetamol, phenazone, carbamazepine, and nonylphenols known to be xenoestrogens. The extraction performance of different SPME fibre coatings was studied. Coatings like polyacrylate and Carbowax-divinylbenzene proved to be the best suited. The optimum extraction time was found to be 30 min and the detection limits were between 0.2 and 50 microg/l. Low concentrations of accompanying organic matter did not impair these limits. One of the main pharmaceutical contaminants found in ground and river water around Leipzig (Germany) was ibuprofen, with a concentration in the ng/l range. The enantioselective metabolism of ibuprofen was investigated.

Estrogens↗

PubMed2000

Deuterium labelled nonylphenols in an in-vitro model of percutaneous absorption of environmental xenoestrogens.

A technical mixture of isomeric nonylphenols NP is formed as rather persistent degradation product of nonionic surfactants and has become widespread in the environment, e.g., in surface waters. Information about possible pathways for incorporation is needed for risk assessments, as NP has estrogenic properties. NP uptake after skin contact was determined using isolated and perfused bovine udders as models for human skin. NP-d2 labelled in the positions ortho to the OH-group was prepared by an exchange procedure which did not measurably change the relative amount of isomers. Samples of udder perfusate, milk equivalent produced during the experiments and skin tissue were taken immediately before administration of 500 mg or 50 mg NP-d2 on an udder skin area of 200 cm2 and then for 5 h. They were analyzed by GC-MS for NP and NP-d2 after cleanup by steam distillation and final extraction with SPME fibres. The results are an unambiguous proof of the penetration of NP into the capillary system of living mammals after skin contact.

Administration, Cutaneous↗

PubMed2000

A randomized study of the safety and antiretroviral activity of hydroxyurea combined with didanosine in persons infected with human immunodeficiency virus type 1. American Foundation for AIDS Research Community-Based Clinical Trials Network.

This randomized open-label trial of human immunodeficiency virus type 1-infected persons compared safety and efficacy for 38 patients receiving hydroxyurea/didanosine combination therapy with findings in 42 persons given didanosine monotherapy for 12 weeks, followed by 12 weeks of hydroxyurea/didanosine combination therapy for all patients. Week 12 on-treatment group comparisons showed a mean decrease in virus load between hydroxyurea/didanosine versus didanosine groups of -0.93 versus -0.74 log10 copies/mL (P=.20); a higher percentage of the hydroxyurea/didanosine group below the assay's detection limit (500 copies/mL), 29% versus 7% (P=.017); and median change in CD4 cells for the hydroxyurea/didanosine versus didanosine group of 0 versus 43 cells/mm3 (P=.045), although median change in CD4 percentage was similar (0.9% vs. 1.2%, P=.64). Week 24 virus load reductions and CD4 cell changes were similar in both groups. Intent-to-treat and on-treatment analyses showed similar results. The hydroxyurea/didanosine combination was well tolerated.

Adult↗

PubMed2000

Identification of INSL6, a new member of the insulin family that is expressed in the testis of the human and rat.

A new member of the insulin gene family (INSL6) was identified from an Expressed Sequence Tag database through a search for proteins containing the insulin family B-chain cysteine motif. Human and rat INSL6 encoded polypeptides of 213 and 188 amino acids, respectively. These orthologous sequences contained the B-chain, C-peptide, and A-chain motif found in other members of the insulin family. Human INSL6 was 43% identical to human relaxin H2 in the B- and A-chain regions. As with other family members, human and rat INSL6 had predicted dibasic sequences at the junction of the C-peptide and A-chain. Human INSL6 sequence had an additional dibasic site near the C-terminus of the A-chain. The presence of a single basic residue at the predicted junction of the B-chain and C-peptide suggests that multiple prohormone convertases are required to produce the fully mature hormone. INSL6 was found to be expressed at high levels in the testis as determined by Northern blot analysis and specifically within the seminiferous tubules in spermatocytes and round spermatids as detected by in situ hybridization analysis. Radiation hybrid mapping placed the human INSL6 locus at chromosome 9p24 near the placenta insulin-like homologue INSL4 and the autosomal testis-determining factor (TDFA) locus.

Amino Acid Sequence↗

PubMed2000

The function of the cercal sensory system in escape behavior of the cave cricket Troglophilus neglectus Krauss.

Long cerci of cave crickets Troglophilus neglectus Krauss (Rhaphidophoridae, Orthoptera) are, in contrast to other investigated species, oriented perpendicularly to the ground. Behavioural experiments indicated that cave crickets detect wind direction and respond to stimulation by jumping away from the stimulus. Directed wind puffs deflect filiform sensory hairs on the cerci, trigger physiological responses of their sensory neurons and change activity of interneurons that control the escape direction. Two local interneuron pairs, one non-spiking and one spiking, were identified using intracellular recording and subsequent dye injection techniques. The non-spiking interneuron responds to the puffs from sides with a large depolarization and to the puffs from the front and back of the animal with a small depolarization. After stimulation from the ipsilateral side the spiking interneuron responds with a burst of spikes at the onset of stimulation and, after stimulation from the contralateral side, it responds with a burst of spikes at the onset and at the end of the stimulation.

Air↗

PubMed1999

Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine. AI454-143 Team.

OBJECTIVE: To compare the antiviral activity of once-daily didanosine (ddI) and twice-daily ddI in combination with stavudine (d4T). DESIGN: Randomized, double-blind, multicenter study. SETTING: Twenty-one sites in the United States. PATIENTS: Eighty-seven antiretroviral-naive, HIV-1-infected adults with baseline plasma HIV RNA counts of > or = 10,000 copies/ml and CD4 cell counts of > or = 100 cells/mm3 started study therapy. INTERVENTIONS: Patients received once-daily ddI or twice-daily ddI, each combined with twice-daily d4T. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels, CD4 cell counts, and adverse events were regularly monitored. The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens in change from baseline plasma HIV-1 RNA levels over the first 12 weeks of therapy. RESULTS: At week 12, median log10 HIV-1 RNA changes were -1.83 log10 copies/ml in the once-daily ddI/d4T group and -1.80 log10 copies/ml in the twice-daily ddI/d4T group, and 18 out of 44 patients (41%) and 17 out of 43 patients (40%), respectively, had HIV-1 RNA levels below 400 copies/ml. Similar results were seen at week 24. The TAD between the two treatment groups (once-daily ddI/d4T minus twice-daily ddI/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14 log10 copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm3. The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm3 (95% CI: -40, 45). CONCLUSION: Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.

Adult↗

PubMed1999

Application of deuterated compounds for investigations of percutaneous absorption of chemical substances.

The percutaneous absorption of the xenoestrogen 2,2-bis-(4-hydroxyphenyl)-propane (bisphenol A) 1 has been studied and compared with results on dibenzoyl peroxide 2, a component of drug formulations for topical application. Isolated perfused bovine udders from slaughtered cows were employed as models for human skin. The deuterium labelled compounds 1-d14 and 2-d10 were applied to enhance the reliability of GC-MS trace determinations by use of reverse isotope dilution analysis. 1-d14 was found in perfusate and milk equivalent samples obtained between 60 and 300 min after topical application with maximum concentrations between 120 and 180 min. 1-d14 was enriched in the milk samples by a factor of about 300 compared with the perfusate. The results confirm a possible penetration of 1 from the environment through the skin into the capillary system. 2 studied on the same model system penetrated faster than 1 by a factor of about three.

Animals↗