Search PubMed⌕ Search

Biomedical subjects

D Braun

Publications and source records attributed to D Braun.

At least 19 recordsLinked to original sources
PubMed2002

Disabling disturbance of olfaction in a dental technician following exposure to methyl methacrylate.

It is often difficult to diagnose dysosmia due to occupational olfactotoxic substances. The authors present a case of disabling disturbance of olfaction in a dental technician. This is very likely to have been caused by exposure to methyl methacrylate. From 1988-1992, the dental technician had very extensive and sustained contact with a self-polymerizing acrylic resin based on methyl methacrylate. Her perception of smell was still normal in 1988, but it deteriorated up to 1992. The olfactory disorders have persisted and impede social life and occupational rehabilitation.

Dental Technicians↗
PubMed2001

The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.

Autosomal dominant polycystic kidney disease (ADPKD) strikes 1 in 1000 individuals and often results in end-stage renal failure. Mutations in either PKD1 or PKD2 account for 95% of all cases [1-3]. It has recently been demonstrated that polycystin-1 and polycystin-2 (encoded by PKD1 and PKD2, respectively) assemble to form a cation channel in vitro [4]. Here we determine that the Caenorhabditis elegans PKD1 and PKD2 homologs, lov-1 [5] and pkd-2, act in the same pathway in vivo. Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects. Also, pkd-2;lov-1 double mutants are no more severe than either of the single mutants, indicating that lov-1 and pkd-2 act together. LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies. Cytoplasmic, nonnuclear staining in cell bodies is punctate, suggesting that one pool of PKD-2 is localized to intracellular membranes while another is found in sensory cilia. In contrast to defects in the C. elegans autosomal recessive PKD gene osm-5 [6-8], the cilia of lov-1 and pkd-2 single mutants and of lov-1;pkd-2 double mutants are normal as judged by electron microscopy, demonstrating that lov-1 and pkd-2 are not required for ultrastructural development of male-specific sensory cilia.

Animals↗
PubMed2001

Universality of decoherence.

We consider environment induced decoherence of quantum superpositions to mixtures in the limit in which that process is much faster than any competing one generated by the Hamiltonian H(sys) of the isolated system. While the golden rule then does not apply we can discard H(sys). By allowing for couplings to different reservoirs, we reveal decoherence as a universal short-time phenomenon independent of the character of the system as well as the bath and of the basis the superimposed states are taken from. We discuss consequences for the classical behavior of the macroworld and quantum measurement: For decoherence of superpositions of macroscopically distinct states H(sys) is always negligible.

Journal Article↗
PubMed2001

Fast voltage transients in capacitive silicon-to-cell stimulation detected with a luminescent molecular electronic probe.

The capacitive stimulation of nerve cells from semiconductor chips is a prerequisite for the development of neuroelectronic devices. We report on the primary response of a cell membrane to a voltage step applied to oxidized silicon. It is observed with a luminescent voltage-sensitive dye. We find exponential voltage transients with a time constant of 1-5 micros. We assign the short response to an electrical decoupling by a thin film of electrolyte between oxide and membrane. The high-pass filtering of stimulation is a crucial constraint for the development of silicon-to-neuron interfaces.

Journal Article↗
PubMed2001

NMR structure of the calreticulin P-domain.

The NMR structure of the rat calreticulin P-domain, comprising residues 189-288, CRT(189-288), shows a hairpin fold that involves the entire polypeptide chain, has the two chain ends in close spatial proximity, and does not fold back on itself. This globally extended structure is stabilized by three antiparallel beta-sheets, with the beta-strands comprising the residues 189-192 and 276-279, 206-209 and 262-265, and 223-226 and 248-251, respectively. The hairpin loop of residues 227-247 and the two connecting regions between the beta-sheets contain a hydrophobic cluster, where each of the three clusters includes two highly conserved tryptophyl residues, one from each strand of the hairpin. The three beta-sheets and the three hydrophobic clusters form a repeating pattern of interactions across the hairpin that reflects the periodicity of the amino acid sequence, which consists of three 17-residue repeats followed by three 14-residue repeats. Within the global hairpin fold there are two well-ordered subdomains comprising the residues 219-258, and 189-209 and 262-284, respectively. These are separated by a poorly ordered linker region, so that the relative orientation of the two subdomains cannot be precisely described. The structure type observed for CRT(189-288) provides an additional basis for functional studies of the abundant endoplasmic reticulum chaperone calreticulin.

Amino Acid Sequence↗
PubMed2001

Adhesion proteins for a tight neuron-electrode contact.

The neural cell adhesion molecules axonin-1 and NgCAM have been genetically engineered and covalently immobilized on glass and silicon oxide surfaces in their correct orientation. Surfaces treated with these adhesion molecules were used as substrates for culturing dorsal root ganglion neurons. The cleft between the neuron cell membrane and the surface was determined using fluorescence interference contrast (FLIC) microscopy. For comparison, cell--material distances on laminin, RGDC, polylysine and amino-terminated surfaces were measured. When the neurons grow on axonin-1 the cell--surface distance is at a minimum (37 nm) probably because the glycocalyx hinders a closer contact. A selective treatment of extracellular electrodes with axonin-1 could be used to improve the cell-material contact and thus increase extracellularly recorded signals.

Animals↗
PubMed2001

Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment.

Calreticulin (CRT) is an abundant molecular chaperone of the endoplasmic reticulum. Its central, proline-rich P-domain, comprising residues 189-288, contains three copies of each of two repeat sequences (types 1 and 2), which are arranged in a characteristic '111222' pattern. Here we show that the three-dimensional structure of CRT(189-288) contains a single hairpin fold formed by the entire polypeptide chain. The loop at the bottom of the hairpin consists of residues 227-247, and is closed by an anti-parallel beta-sheet of residues 224-226 and 248-250. Two additional beta-sheets contain residues 207-209 and 262-264, and 190-192 and 276-278. The 17-residue spacing of the beta-strands in the N-terminal part of the hairpin and the 14-residue spacing in the C-terminal part reflect the length of the type 1 and type 2 sequence repeats. As a consequence of this topology the peptide segments separating the beta-strands in the N-terminal part of the hairpin are likely to form bulges to accommodate the extra residues. These results are based on nearly complete sequence-specific NMR assignments for CRT(189-288), which were obtained using standard NMR techniques with the (13)C/(15)N-labeled protein, and collection of nuclear Overhauser enhancement upper distance constraints.

Amino Acid Sequence↗
PubMed2001

No correlation of focal contacts and close adhesion by comparing GFP-vinculin and fluorescence interference of Dil.

In regions of focal adhesion, cells adhere to a substrate through the interaction of extracellular matrix proteins and transmembrane integrins which are coupled to the cell skeleton. It is generally assumed that the plasma membrane is brought to close proximity to the substrate there. We used the novel method of fluorescence interference contrast (FLIC) microscopy to measure the distance of the plasma membrane of GD25 fibroblasts on silica coated with fibronectin. We correlated the distance map with the distribution of vinculin tagged with green fluorescent protein. We found that the major part of the membrane was separated by 50 nm from the substrate. With respect to this plateau, we found spots of upward deformation and of close adhesion as well as a general ruffling of the membrane. There was no correlation between the areas of close adhesion and the distribution of vinculin. We conclude that focal adhesion does not imply a close attachment of membrane and substrate.

Animals↗
PubMed2001

Sociodemographic and clinical factors associated with low quality of life one year after coronary bypass operations: the Israeli coronary artery bypass study (ISCAB).

OBJECTIVES: We sought to examine the effect of sociodemographic characteristics and perioperative clinical factors 1 year after coronary bypass operations on low health-related quality of life. We also sought to assess the usefulness of an additional single question on overall health for identifying patients with low health-related quality of life. METHODS: This report is part of the Israeli coronary artery bypass study of 1994, in which every patient undergoing isolated coronary bypass grafting in Israel was included. The target population for this report comprised all survivors beyond 1 year who were 45 to 65 years of age. Patients were interviewed before the operations. Self-administered questionnaires regarding health-related quality of life (SF-36) were sent to 1724 patients who were successfully located 1 year postoperatively, and 1270 questionnaires were completed. Low health-related quality of life was defined as the lowest tertile of the distribution of scores for the 2 summary components of the SF-36 and the single question on overall health. Logistic models were constructed for each of the 3 outcomes. RESULTS: Female sex and low socioeconomic background were associated with low health-related quality of life in the logistic models. Other significant factors were symptoms of angina, sleep disturbances, hypertension, high severity of illness scores, hospital readmission, no rehabilitation, and hospitals with high perioperative mortality. Of the 3 study outcomes, the model for the single question on overall health was the most discriminating (C statistic = 0.76 vs 0.70 and 0.70, respectively). CONCLUSIONS: The study identifies patients who would most benefit from posthospitalization community support after bypass operations. Under circumstances of limited resources, these disadvantaged groups should be targeted as a priority. Encouraging participation in existing rehabilitation programs or introducing telephone hotlines could improve health-related quality of life after coronary bypass grafting without large investments.

Aged↗
PubMed2000

Sequential logistic models for 30 days mortality after CABG: pre-operative, intra-operative and post-operative experience--The Israeli CABG study (ISCAB). Three models for early mortality after CABG.

OBJECTIVES: The goal of this paper was to examine the added effect of operative and post-operative variables on 30 days mortality, in addition to patients' case-mix factors. SETTING AND DESIGN: A prospective study of 4835 patients, 95% of all Israeli patients who underwent coronary artery bypass grafting (CABG) in 1994. Information related to risk of death was collected at admission to hospital (preceding the operation), at time of the operation and in the immediate post-operative period. Deaths were independently ascertained. METHOD: Data collectors followed every patient from admission to discharge. Sequential logistic models were constructed for the 'case-mix', 'operative' and the 'post-operative' periods in chronological order. Each model incorporated and adjusted for the risk estimated at the previous point in time, by forcing individual risk scores. RESULTS: Significant pre-operative risk factors for 30 days mortality, in the case-mix model included mainly severity of illness characteristics, such as, left ventricular dysfunction and emergency admission, (c-statistic 78.8%). Model 2 (the 'operation' model) included in addition to the case-mix score, excessive duration of the operation per graft, bleeding, etc. (c-statistic 85.3%). The post-operative model showed the added effect of the post-operative factors such as low haemoglobin, additional surgery, and excessive time on respirator, (c-statistic 92.4%). CONCLUSIONS: The sequential analysis was an efficient method for updating patients' risk over time, where the number of events was small, relative to the number of risk factors. The addition of peri-operative factors increased significantly the predictive power of the model, adding clinical insights to the role of the hospital experience on 30 days mortality.

Adult↗
PubMed2000

Sequence-specific NMR assignment of proteins by global fragment mapping with the program MAPPER.

A new program, MAPPER, for semiautomatic sequence-specific NMR assignment in proteins is introduced. The program uses an input of short fragments of sequentially neighboring residues, which have been assembled based on sequential NMR connectivities and for which either the 13C(alpha) and 13C(beta) chemical shifts or data on the amino acid type from other sources are known. MAPPER then performs an exhaustive search for self-consistent simultaneous mappings of all these fragments onto the protein sequence. Compared to using only the individual mappings of the spectroscopically connected fragments, the global mapping adds a powerful new constraint, which results in resolving many otherwise intractable ambiguities. In an initial application, virtually complete sequence-specific assignments were obtained for a 110 kDa homooctameric protein, 7,8-dihydroneopterin aldolase from Staphylococcus aureus.

Aldehyde-Lyases↗
PubMed2000

[15N,1H]/[13C,1H]-TROSY for simultaneous detection of backbone 15N-1H, aromatic 13C-1H and side-chain 15N-1H2 correlations in large proteins.

This paper describes a [15N,1H]/[13C,1H]-TROSY experiment for the simultaneous acquisition of the heteronuclear chemical shift correlations of backbone amide 15N-1H groups, side chain 15N-1H2 groups and aromatic 13C-1H groups in otherwise highly deuterated proteins. The 15N-1H and 13C-1H correlations are extracted from two subspectra of the same data set, thus preventing possible spectral overlap of aromatic and amide protons in the 1H dimension. The side-chain 15N-1H2 groups, which are suppressed in conventional [15N,1H)-TROSY, are observed with high sensitivity in the 15N-1H subspectrum. [15N,1H]/[13C,1H]-TROSY was used as the heteronuclear correlation block in a 3D [1H,1H]-NOESY-[15N,1H]/[13C,1H]-TROSY experiment with the membrane protein OmpA reconstituted in detergent micelles of molecular weight 80000 Da, which enabled the detection of numerous NOEs between backbone amide protons and both aromatic protons and side chain 15N-1H2 groups.

Bacterial Outer Membrane Proteins↗
PubMed2000

The influence of intrapartum antibiotics on the clinical spectrum of early-onset group B streptococcal infection in term infants.

OBJECTIVE: The use of intrapartum antibiotics to prevent early-onset group B streptococcal (EOGBS) infection has left pediatricians in a quandary about the appropriate evaluation and treatment of infants at risk for this infection. The aim of this study was to determine whether intrapartum antibiotic prophylaxis changed the constellation and timing of onset of clinical signs of group B streptococcal (GBS) infection in term infants. METHODOLOGY: We conducted a retrospective chart review of infants who had EOGBS infection and were born in Southern California Kaiser Permanente Hospitals from 1988 through 1996. Objective criteria were used to ascertain maternal risk of infection, intrapartum antibiotic prophylaxis, and onset of clinical signs of infection. RESULTS: Three hundred nineteen infants with EOGBS sepsis, bacteremia, or clinically suspected infection were identified from a population of 277 912 live births. Of the 172 term infants with culture-positive infection who had clinical signs of infection, 95% exhibited them in the first 24 hours of life. All of the infants exposed to intrapartum antibiotics became ill within the first 24 hours of life. CONCLUSIONS: Exposure to antibiotics during labor did not change the clinical spectrum of disease or the onset of clinical signs of infection within 24 hours of birth for term infants with EOGBS infection. A 48-hour stay is not required to monitor asymptomatic term infants exposed to intrapartum antibiotics for onset of GBS infection.

Antibiotic Prophylaxis↗
PubMed1999

Lactose-derived oligosaccharides in the milk of elephants: comparison with human milk.

Human milk is commonly considered to be unique when compared with the milk of other species with regard to its high content of complex fucosylated and sialylated lactose-derived oligosaccharides. We describe the application of high-pH anion-exchange chromatography with pulsed amperometric detection and TLC to characterize and quantitate neutral and sialylated lactose-derived oligosaccharides in milk from three Asian elephants and human milk. The lactose contents of elephant and human milks were 25-30 g/l and about 66 g/l respectively, whereas total oligosaccharide concentration was about three times higher in elephant milk and comprised up to 40% (10% in human milk) of the carbohydrate content. The ratio neutral: acidic components was different in the milk of the two species; in elephant milk, the N-acetylneuraminic acid-containing oligosaccharides made up almost half of the total amount v. 30% in human milk. Most oligosaccharides in elephant milk were more fucosylated and/or sialylated compared with human milk components. By mild acid hydrolysis, fucose and N-acetylneuraminic acid were cleaved off from complex components, and this resulted in increased amounts of fucose, galactose, N-acetylneuraminic acid, lactose and lacto-N-neo-tetraose. Unique to elephant milk are the high levels of 3'-galactosyllactose (up to 4 g/l) and lacto-N-neo-tetraose which are present in human milk only in trace amounts. Elephant and human milks have high levels and unique patterns of oligosaccharides which may reflect the relative importance of these components in neonatal host defence, in endothelial leucocyte interactions or in brain development.

Animals↗
PubMed1999

NMR studies of subunit c of the ATP synthase from Propionigenium modestum in dodecylsulphate micelles.

The structure of the Na+, Li+ or H+-binding c subunit of the ATP synthase from Propionigenium modestum was studied by NMR. Subunit c in dodecylsulphate micelles consists of four alpha-helical segments, I-IV, that are connected by short linker peptides with non-regular secondary structures. We propose that helices I (V4-I26) and IV (I69-V85) are membrane-spanning structures, and that helices II and III and the intervening hydrophilic loop are located in the cytoplasm. The Na+-binding residues Q32, E65 and S66 are located in the I-->II and III-->IV helix connections, probably near the membrane surface on the cytoplasmic side.

Amino Acid Sequence↗
PubMed1999

Type I IFN sets the stringency of B cell repertoire selection in the bone marrow.

Locally produced type I interferon (IFN-I) enhances the sensitivity of bone marrow B cell to IgM receptor ligation. The establishment of B cell repertoires, on the other hand, seems to involve selective processes that are critically dependent on B cell receptor (BCR) ligation. In order to assess the importance of BCR triggering thresholds on the selection of polyclonal unmanipulated B cell populations, we compared VH gene expression and reactivity repertoires in various B cell compartments of wild-type and IFN-I receptor-deficient mice (IFN-I-R-/-). These analyses demonstrate that increased B cell sensitivity to BCR ligation mediated by IFN-I in the bone marrow (BM) has consequences on the stringency of B cell repertoire selection. Thus, the normal counter-selection of both VH7183 gene family expression and multireactivity was impaired among immature BM B cells from mutant mice. Furthermore, as a result of reduced efficiency of BCR ligation-dependent inhibition of terminal differentiation, IFN-I-R-/- animals produce, in BM and thymus, higher numbers of plasma cells secreting antibodies that are more multireactive than wild-type animals. Finally, mutant serum IgM natural antibodies display a more reactive repertoire than controls, a likely reflection of the BM resident plasma cell repertoire. The present observations demonstrate, therefore, that local modulation of BCR triggering thresholds leads to important modifications in the generation and/or selection of normal B cell populations.

Animals↗