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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 37 records · Page 2Linked to original sources
PubMed2001

Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia.

BACKGROUND: Colesevelam hydrochloride is a novel, lipid-lowering agent that binds bile acids with high affinity. A multicenter, randomized, double-blind, placebo-controlled, parallel-design study was conducted to assess the efficacy and tolerability of combination low-dose colesevelam and lovastatin treatment in patients with primary hypercholesterolemia. HYPOTHESIS: Combination therapy with low doses of colesevelam and lovastatin decreases low density (LDL) cholesterol with minimal adverse events. METHODS: Following a 4- to 6-week dietary lead in, 135 patients were randomized into five groups for a 4-week treatment period: placebo, colesevelam 2.3 g at dinner, lovastatin 10 mg at dinner, the combination of colesevelam and lovastatin given at dinner (dosed together), and combination treatment with colesevelam given at dinner and lovastatin administered at bedtime (dosed apart). RESULTS: Combination colesevelam and lovastatin treatment decreased LDL cholesterol by 34% (60 mg/dl, p < 0.0001) and 32% (53 mg/dl, p < 0.0001) when colesevelam and lovastatin were dosed together or dosed apart, respectively. Both combination therapies were superior to either agent alone (p < 0.05). Decreases in LDL cholesterol exceeded the combined decreases observed for colesevelam alone (13 mg/dl, 7%) and lovastatin alone (39 mg/dl, 22%). Both combination treatments reduced total cholesterol by 21% (p < 0.0001) and apolipoprotein B by 24% (p < 0.0001). Neither combination treatment significantly altered high-density lipoprotein cholesterol or triglycerides. Adverse side effects were not significantly different among randomized groups. CONCLUSIONS: Combination colesevelam and lovastatin was efficacious and well tolerated, resulting in additive decreases in LDL cholesterol levels whether or not both agents were administered simultaneously.

Allylamine↗
PubMed2001

Projection reconstruction balanced fast field echo for interactive real-time cardiac imaging.

A balanced fast field echo (FFE) sequence (also referred to as true fast imaging with steady precession (true FISP)), based on projection reconstruction (PR) is evaluated in combination with real-time reconstruction and interactive scanning capabilities for cardiac function studies. Cardiac image sequences obtained with the balanced PR-FFE method are compared with images obtained with a spin-warp (2D Fourier transform (2DFT)) technique. In particular, the representation of motion artifacts in both techniques is investigated. Balanced PR-FFE provides a similar contrast to spin-warp-related techniques, but is less sensitive to motion artifacts. The use of angular undersampling within balanced PR-FFE is examined as a means to increase temporal resolution while causing only minor artifacts. Furthermore, a modification of the profile order allows the reconstruction of PR images at different spatial and temporal resolution levels from the same data. This study shows that balanced PR-FFE is a robust tool for cardiac function studies.

Artifacts↗
PubMed2001

Ultrahigh-resolution colocalization of spectrally separable point-like fluorescent probes.

An ultrahigh-resolution colocalization method based on the simultaneous acquisition and analysis of spectrally separated images of the excitation point-spread function of point-like fluorescent probes is reviewed. It is shown that molecular distances can be measured with accuracy better than 10 nm using conventional far-field optics. A detailed account of the methodology, theoretical considerations, signal processing, and data fitting algorithms is given.

Fluorescent Dyes↗
PubMed2001

[Subretinal microphotodiode array as replacement for degenerated photoreceptors?].

A survey is given on the status of developments, concerning a subretinal electronic microphotodiode array that aims at replacing degenerated photoreceptors. Various prototypes have been developed, tested, and implanted in various experimental animals up to 18 months. The fact that electrical responses were recorded from the visual cortex of pigs after electrical stimulation by subretinal electrodes and the fact that responses are also recorded in-vitro in degenerated rat retinae, shows the feasibility of this approach. However, there are a number of open questions concerning the biocompatibility, the long-time stability, and the type of transmitted image to be solved before application in patients can be considered.

Animals↗
PubMed2001

Conscientious metabolic monitoring on a patient with hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome undergoing anaesthesia.

Currently we know not more than 50 patients who show an interesting combination of increased plasma ornithine concentrations, postprandial hyperammonemia, and homocitrullinuria (HHH-syndrome). Since exact knowledge of this severe, although rare syndrome is important for any perioperative or intensive medical treatment concerning therapy and progression of the disease, we report a comprehensive study on a 32-year old woman with this rare multifaceted disorder who had to undergo general anaesthesia. For the first time amino acid status in plasma, urine, cerebrospinal fluid and especially polymorphonuclear leucocytes, which in the investigation showed to be valuable tool for evaluating amino acid metabolism in nucleated cells in HHH-syndrome, and further important pathophysiologic indicators of cellular and metabolic function have been conscientiously investigated and compared. The pathophysiological repercussions of our results as well as the recommendations for conscientious therapeutical management are discussed.

Adult↗
PubMed2001

Germ-line transcripts of the immunoglobulin lambda J-C clusters in the mouse: characterization of the initiation sites and regulatory elements.

Transcription of unrearranged immunoglobulin gene segments strongly correlates with their accessibility to the V(D)J recombination machinery. The regulatory mechanisms governing this germ-line transcription are still poorly defined. In order to identify new regulatory elements, we first carried out a detailed characterization of the transcription initiation sites for the J-C germ-line transcripts, using rapid amplification of 5' cDNA ends, assisted by a template switching mechanism at the 5'-end of the RNA. Transcripts were observed that initiated heterogeneously, starting up to 293 (lambda1), 116 bp (lambda2) and 79 bp (lambda3) upstream from the respective Jlambda gene segment. Additional RT-PCR analysis revealed the existence of germ-line transcripts of lambda and also of kappa that initiate even more upstream of these transcription initiation sites, although their frequencies were low. Promoter activity was detected in vitro 5' of Jlambda2, with the minimal promoter activity mapping to the region between positions -35 and -120. In addition, computer analysis allowed the prediction of a nuclear scaffold/matrix attachment (S/MAR) region between the two J-C gene clusters at each hemi-locus. This region between the lambda1/lambda3 clusters binds to the nuclear matrix in vitro, and J-C lambda1 germ-line transcription initiates a short distance downstream from this S/MAR element.

Animals↗
PubMed2001

Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-L-glutamine supplementation.

The objective of this study was to determine the effects of diazepam, L-alanyl-L-glutamine (ala-gln) or diazepam combined with ala-gln on polymorphonuclear leukocyte (PMN) free amino acid profiles. In a parallel study the effects on PMN immune functions were also documented for the first time. The incubation of whole blood with diazepam led to significant changes in PMN free glutamine, aspartate, glutamate, ornithine, arginine, citrulline, taurine and methionine as well as branched chain and neutral amino acid concentrations. Ala-gln caused significant increases in PMN glutamine and alanine and asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine profiles. Regarding PMN immune functions, diazepam significantly decreased superoxide anion (O(2)(-)) and hydrogen peroxide production (H(2)O(2)) and myeloperoxidase activity (MPO) while ala-gln significantly increased PMN immune functions. Ala-gln supplemented to diazepam largely reversed the changes in PMN amino acid profiles and PMN immune functions brought about by diazepam. Overall, diazepam or ala-gln lead to significant changes in PMN free amino acids. Important PMN immune functions also seem to be affected. In regards to the results, there is significant relevance to the pharmacological regimens which enhance the supply of diazepam or ala-gln in whole blood suggesting that considerable changes in PMN "labile free amino acid pool" occur. These regimens often follow beneficial nutritional therapy or maleficent pharmacological stress and may be one of the determinants in cell nutrition which influence PMN function. It is partially through its effect on PMN labile free amino acid pool that ala-gln supplemented to diazepam may maintain PMN immune functions in vitro.

Journal Article↗
PubMed2001

Transfer of eukaryotic expression plasmids to mammalian host cells by bacterial carriers.

The concept of transkingom transfer of DNA from bacteria to other organisms has recently been extended to include eukaryotic host cells. Intracellular bacteria have been shown to transfer eukaryotic expression plasmids to mammalian host cells in vitro and in vivo. This can be used to induce immune responses towards protein antigens encoded by the plasmid, to complement genetic defects or even to direct the production of proteins in appropriate organs. The ease of generating such vehicles makes this a highly attractive area for further research.

Animals↗
PubMed2001

An exploratory study of social support, distress, and life disruption among low-income Hispanic women under treatment for early stage breast cancer.

Relationships between distress and perceived availability of social support were examined in 51 Hispanic women being treated for early stage breast cancer. Distress and different types (emotional, instrumental) and sources (spouse, women family members, other family members, friends) of support were measured at presurgery, postsurgery, and at 3-, 6-, and 12-month follow-ups. Emotional support from friends and instrumental support from spouse at presurgery predicted lower distress postsurgery. No other prospective benefits of perceived support emerged. Distress at several time points predicted erosion of subsequent support, particularly instrumental support from women in the family. In contrast to the adverse effects of distress (and independent of them), illness-related disruption of recreational and social activities at 6 months elicited greater support at 12 months.

Adult↗
PubMed2001

Methohexital affects neutrophil (PMN) dynamic free amino acid pool and immune functions in vitro.

BACKGROUND AND OBJECTIVE: The objective of this study was to determine the dose as well as the duration of exposure-dependent effects of methohexital on neutrophil [polymorphonuclear leucocyte (PMN)] free amino acid profiles and, in a parallel study, on PMN immune functions. METHODS: Whole blood samples were taken from 20 volunteers and incubated with methohexital [0 (control), 3.6, 26, 130 and 260 microg mL-1] for 10, 30, 60 or 120 min. PMN amino acid profiles were documented using advanced PMN separation and high-performance liquid chromatography procedures. Superoxide anion (O2-) and hydrogen peroxide production (H2O2), and activity of released myeloperoxidase (MPO), were determined photometrically. RESULTS: After methohexital, significant dose (> or = 26 microg mL-1) as well as duration of exposure-dependent (> or = 30 min) increases in histidine, isoleucine, leucine, valine, methionine, serine, glycine, threonine, and decreases in glutamine, glutamate, aspartate, asparagine, arginine, ornithine, citrulline, alanine and taurine were observed (P < or = 0.05). Concerning PMN immune functions, methohexital significantly decreased O2-, H2O2 formation and MPO (> or = 26 microg mL-1, > or = 30 min, P < or = 0.05). CONCLUSIONS: Altogether, there is significant relevance to the pharmacological regimens which enhance the supply of methohexital in whole blood. In regards to our results, we suggest that considerable changes in PMN 'dynamic free amino acid pool', for example induced by methohexital, may be one of the determinants in cell nutrition adversely affecting PMN metabolism. It is partially through its effect on the PMN free amino acid pool that maleficent pharmacological stress may have an unintentional influence on PMN immune functions.

Adult↗
PubMed2001

EGF-responsive neural stem cells are a transient population in the developing mouse spinal cord.

The adult mouse forebrain, which exhibits substantial ongoing cell genesis, contains self-renewing multipotent neural stem cells that respond to epidermal growth factor (EGF), but the adult spinal cord, which exhibits limited cell genesis, does not. Spinal cord development is a process characterized by defined periods of cell histogenesis. Thus, in the present study we asked whether EGF-responsive neural stem cells are present within the spinal cord during development. At embryonic day (E) 11, subsequent to the onset of neurogenesis, only fibroblast growth factor (FGF) receptors and FGF-2 (requiring heparan sulphate)-responsive stem cells are present in the spinal cord. Between E12 and 14, at the peak of spinal cord neurogenesis and the onset of gliogenesis, EGF receptors appear along with clonally derived highly expandable EGF-responsive neural stem cells. Following the cessation of cell histogenesis, the adult spinal cord is largely devoid of both EGF receptors and EGF-responsive stem cells. On the other hand, the FGF receptor1c subtype and multipotent FGF-2-responsive neural stem cells are present in early development and in the adult. The order of appearance of spinal cord neural stem cells and in vitro lineage analysis suggests that a more primitive FGF-2-responsive stem cell produces the EGF-responsive stem cell. These findings suggest that EGF-responsive neural stem cells appear transiently in the spinal cord, during the peak period of cell histogenesis, but are no longer present in the relatively quiescent adult structure.

Animals↗
PubMed2001

Haplotype (mtDNA) diversity of brown trout Salmo trutta in tributaries of the Austrian Danube: massive introgression of Atlantic basin fish--by man or nature?

Mitochondrial haplotype diversity in 27 populations of brown trout, Salmo trutta L., in Austria was investigated by sequencing the 5' end of the mitochondrial DNA (mtDNA) control region. Although all populations are within the Danube drainage, 44% of all individuals carried Atlantic basin haplotypes. It is argued that the presence of these haplotypes in Austria primarily reflects introgression stemming from the stocking of hatchery-reared fish. However, several lines of evidence suggest that some natural colonization from Atlantic lineages may have contributed to the present haplotype diversity. Nonetheless, the more diverse Danubian clade is represented by regionally distinct haplotype diversity that should be protected from the continued introduction of domesticated strains of exogenous fish

Animals↗
PubMed2001

Eukaryotic expression plasmid transfer from the intracellular bacterium Listeria monocytogenes to host cells.

The facultative intracellular, Gram-positive bacterium Listeria monocytogenes invades phagocytic and non-phagocytic cells from the tissues and organs of a wide variety of animals and humans. Here, we report the use of these bacteria as vehicles for gene transfer. Eukaryotic expression plasmids were introduced into the nucleus of host cells following lysis of the intracytosolic, plasmid-carrying bacteria with antibiotics. Cell lines of different tissues and species could be transfected in this way. We examined bacterial properties required for delivery of the expression plasmids and found that this was strictly dependent on the ability of these bacteria to both invade eukaryotic cells and egress from the vacuole into the cytosol of the infected host cells. Macrophage-like cell lines or primary, peritoneal macrophages proved to be almost refractory to Listeria-mediated gene transfer. Thus, attenuated L. monocytogenes represents a serious candidate for consideration as a DNA-transfer vehicle for in vivo somatic gene therapy. The potential for oral administration of L. monocytogenes and the ease in producing and cultivating recombinant strains are further attributes that make its use as a gene transfer vehicle attractive.

Animals↗
PubMed2001

Stationary distributions of microsatellite loci between divergent population groups of the European rabbit (Oryctolagus cuniculus).

Previous analysis of mitochondrial DNA polymorphism in the native range of the European rabbit (Oryctolagus cuniculus) demonstrated the occurrence of two highly divergent (2 Myr) maternal lineages with a well-defined geographical distribution. Analysis of both protein and immunoglobulin polymorphisms are highly concordant with this pattern of differentiation. However, the present analysis of nine polymorphic microsatellite loci (with a total of 169 alleles) in 24 wild populations reveals severe allele-size homoplasy which vastly underestimates divergence between the main groups of populations in Iberia. Nonetheless, when applied to more recent historical phenomena, this same data set not only confirms the occurrence of a strong bottleneck associated with the colonization of Mediterranean France but also suggests a two-step dispersal scenario that began with gene flow from northern Spain through the Pyrenean barrier and subsequent range expansion into northern France. The strength and appropriateness of applying microsatellites to more recent evolutionary questions is highlighted by the fact that both mtDNA and protein markers lacked the allelic diversity necessary to properly evaluate the colonization of France. The well-documented natural history of European rabbit populations provides an unusually comprehensive framework within which one can appraise the advantages and limitations of microsatellite markers in revealing patterns of genetic differentiation that have occurred across varying degrees of evolutionary time. The degree of size homoplasy presented in our data should serve as a warning to those drawing conclusions from microsatellite data sets which lack a set of complementary comparative markers, or involve long periods of evolutionary history, even within a single species.

Animals↗
PubMed2001

An automatic sequential recognition method for cortical auditory evoked potentials.

The detection of cortical auditory evoked potentials (CAEP), which are part of the electroencephalogram (EEG) in reaction to acoustic stimuli, has important applications such as determining objective audiograms. The detection is usually performed by a human operator, with support from often basic signal processing methods. This paper presents a novel mechanism for the detection of CAEPs, which is fully automatic and stops the measurement when a given confidence is reached. This proposed detector comprises of three stages. First, a feature extraction by a wavelet transform parameterizes the time domain EEG signal by only few transform coefficients. This feature vector is then classified by a neural network which yields a binary vote on every EEG segment. Finally, a sequential statistical test is performed on successive classifications; this stops the measurement if a specified decision confidence has been reached. The adjustment of the detector according to a clinical database is discussed. Thus adjusted, the proposed CAEP detection scheme is applied to a study, and compared with a human operator. The results demonstrate that this method can attain similar results, but outperforms the human expert for stimulation levels close to the hearing threshold.

Adult↗
PubMed2001

Survival of Chlamydia pneumoniae-infected Mono Mac 6 cells is dependent on NF-kappaB binding activity.

The respiratory tract pathogen Chlamydia pneumoniae has been associated with atherosclerosis. Monocytes are supposed to serve as a vehicle for systemic dissemination of intracellular C. pneumoniae from the lung to the artery vessel wall. We were therefore interested in pathogen-induced cellular events associated with NF-kappaB, a crucial transcription factor for both inflammatory cytokines and antiapoptotic molecules. In this study we demonstrate by electrophoretic mobility shift assay that C. pneumoniae infection of the human monocytic cell line Mono Mac 6 induces activation of NF-kappaB over 48 h, with a maximum level at 1 h postinfection. As shown by supershift assay, the activated NF-kappaB complex consists of the subunits RelA (p65) and NF-kappaB1 (p50). Apoptotic host cells were not detected during the early stages of the infection when maximal activation of NF-kappaB was detected. Pretreatment of Mono Mac 6 with the antioxidant and NF-kappaB inhibitor PDTC (pyrrolidine dithiocarbamate) induced activation of caspase-3 and led to apoptotic cell death. The C. pneumoniae-induced activation of the NF-kappaB complex was reduced by PDTC, which in parallel resulted in an increased apoptosis, as quantified by annexin V labeling and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling reaction. In the complete absence of activated NF-kappaB, when Mono Mac 6 cells were pretreated with the more potent NF-kappaB inhibitors MG-132 and parthenolide a C. pneumoniae-mediated rescue of cells from induced apoptosis could not be achieved. Our results indicate that activation of NF-kappaB in C. pneumoniae-infected Mono Mac 6 cells is associated with protection of Mono Mac 6 cells against apoptosis and might thereby contribute to systemic spread of the pathogen.

Apoptosis↗
PubMed2001

Ratiometric single-molecule studies of freely diffusing biomolecules.

We outline recent developments in biological single-molecule fluorescence detection with particular emphasis on observations by ratiometric fluorescence resonance energy transfer (FRET) of biomolecules freely diffusing in solution. Single-molecule-diffusion methodologies were developed to minimize perturbations introduced by interactions between molecules and surfaces. Confocal microscopy is used in combination with sensitive detectors to observe bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract ratiometric observables such as FRET efficiency and polarization anisotropy. We describe the development of single-molecule FRET methodology and its application to the observation of the Förster distance dependence and the study of protein folding and polymer physics problems. Finally, we discuss future advances in data acquisition and analysis techniques that can provide a more complete picture of the accessible molecular information.

Biopolymers↗