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Biomedical subjects

D Braun

Publications and source records attributed to D Braun.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1999

Prediction of readmissions after CABG using detailed follow-up data: the Israeli CABG Study (ISCAB)

OBJECTIVE: To use detailed pre-discharge follow-up data to predict readmissions within 3 months after Coronary Artery Bypass Grafting (CABG). SETTINGS AND DESIGN: A prospective nationwide study (ISCAB) of 4,835 patients undergoing isolated CABG in Israel in 1994. Survivors of the initial hospitalization were candidates for the readmission study. METHODS: Patient information was prospectively collected from preoperative interviews and hospital follow-up. Readmissions' data were obtained from the National Hospital Admission Registry. Logistic and multinomial models were constructed for total and cause-specific readmissions, respectively. RESULTS: Of CABG survivors, 1,094 (24.1%) were rehospitalized within 3 months of the original surgery. Significant multivariate predictors of total readmissions included the following: preoperative co-morbidities; operative factors; immediate post-operative complications and socio-demographic characteristics as well as provider characteristics. However, the logistic model had low predictive power (c-statistic = 0.65). The heterogeneous reasons for readmissions were classified into specific serious cardiac diagnoses (19.0%), other cardiac reasons (35.4%), specific infections at the site of the operation (10.2%), other infections (7.3%), and various other reasons (23.0%). The multinomial model for cause-specific readmissions caused by either serious cardiac reasons or wound infection had a higher predictive value (c-statistics of 0.75, 0.72, respectively). CONCLUSIONS: Total readmissions after CABG in Israel were difficult to predict, even with an extensive pre-discharge follow-up data. We propose that reasons for readmission vary from true emergencies to nonspecific causes, with the latter related to a lack of support services in the community. We suggest that cause-specific rehospitalizations could be a better outcome for evaluating quality of care.

Aged↗
PubMed1999

Possible precipitants of psychiatric hospitalization in patients with major depression: results from the Jerusalem Collaborative Depression Project.

In spite of substantial advances in the treatment of major depression by pharmacotherapy and other means, a significant number of depressed patients require hospitalization. In the context of the Jerusalem Collaborative Depression Project, possible precipitants of psychiatric hospitalization were sought in a cohort of patients (n = 107) who were admitted to hospitals in the Jerusalem area during a 14-month period because of a depressive episode. The patients fulfilled DSM III-R criteria for major depression, single or recurrent; bipolar 1 disorder, depressed or mixed; bipolar 2, depressed. The cohort encompassed more than two thirds of potential subjects admitted during this period with the ICD-9 equivalents of the specified diagnoses (as reported to the Israel Ministry of Health National Psychiatric Case Register) and were similar to the entire potential population in terms of their diagnostic breakdown. The patients underwent extensive socio-demographic and clinical evaluation that included detailed documentation of treatment received prior to hospitalization. Notwithstanding the absence of a comparison group of depressed patients who were not hospitalized, a number of potential precipitants were identified. These included older age (55.2% > 60 years, 20.6% > 70 years), immigration to Israel during the preceding 5 years (34.7%), concomitant physical illness (60%) which was associated with moderate to severe disability in 41% and poor quality of antidepressant pharmacotherapy prior to hospitalisation (only 24.3% received an adequate trial of antidepressant medication). Further evaluation of these and other potential factors could facilitate targeting of patient groups at particular risk for hospitalization and reduce the need for it.

Adult↗
PubMed1998

Role for Bcl-xL in delayed eosinophil apoptosis mediated by granulocyte-macrophage colony-stimulating factor and interleukin-5.

Eosinophils are potent inflammatory cells involved in allergic reactions. Inhibition of apoptosis of purified eosinophils by certain cytokines has been previously shown to be an important mechanism causing tissue eosinophilia. To elucidate the role of Bcl-2 family members in the inhibition of eosinophil apoptosis, we examined the expression of the known anti-apoptotic genes Bcl-2, Bcl-xL, and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human eosinophils express significant amounts of Bcl-xL and Bax, but only little or no Bcl-2, Bcl-xS, or A1. As assessed by reverse transcription-polymerase chain reaction, immunoblotting, flow cytometry, and immunocytochemistry, we show that spontaneous eosinophil apoptosis is associated with a decrease in Bcl-xL mRNA and protein levels. In contrast, stimulation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-5 (IL-5) results in maintenance or upregulation of Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is also not expressed in tissue eosinophils as assessed by immunohistochemistry using two different eosinophilic tissue models. Furthermore, Bcl-xL antisense but not scrambled phosphorothioate oligodeoxynucleotides can partially block the cytokine-mediated rescue of apoptotic death in these cells. These data suggest that Bcl-xL acts as an anti-apoptotic molecule in eosinophils.

Apoptosis↗
PubMed1998

Disruption of fas receptor signaling by nitric oxide in eosinophils.

It has been suggested that Fas ligand-Fas receptor interactions are involved in the regulation of eosinophil apoptosis and that dysfunctions in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases. Here, we demonstrate that nitric oxide (NO) specifically prevents Fas receptor-mediated apoptosis in freshly isolated human eosinophils. In contrast, rapid acceleration of eosinophil apoptosis by activation of the Fas receptor occurs in the presence of eosinophil hematopoietins. Analysis of the intracellular mechanisms revealed that NO disrupts Fas receptor-mediated signaling events at the level of, or proximal to, Jun kinase (JNK), but distal to sphingomyelinase (SMase) activation and ceramide generation. In addition, activation of SMase occurs downstream of an interleukin 1 converting enzyme-like (ICE-like) protease(s) that is not blocked by NO. However, NO prevents activation of a protease that targets lamin B1. These findings suggest a role for an additional NO-sensitive apoptotic signaling pathway that amplifies the proteolytic cascade initialized by activation of the Fas receptor. Therefore, NO concentrations within allergic inflammatory sites may be important in determining whether an eosinophil survives or undergoes apoptosis upon Fas ligand stimulation.

Apoptosis↗
PubMed1998

Antisocial patients: a comparison of those with and those without childhood conduct disorder.

The purpose of this study was to compare persons with antisocial personality disorder (ASP) with those who meet the adult criteria for ASP but fail to meet the criteria for childhood conduct disorder. Sociodemographic data, medical history, and psychiatric symptoms exhibited during a recent hospital admission were compared in the two groups by chart review. The two groups were virtually indistinguishable, except that patients without childhood conduct disorder were less likely to smoke or consume alcohol, were less likely to have spent time in a training school/boot camp as a child or adolescent, were less likely to have been admitted for a recent suicide attempt, and were less likely to have conned others. We conclude that persons meeting the adult criteria for ASP but not the childhood conduct disorder criteria essentially suffer the same disorder as those who meet full ASP criteria but are less severely affected.

Adult↗
PubMed1998

Deficits and recovery of first- and second-order motion perception in patients with unilateral cortical lesions.

Unilateral lesions in the posterior parietal cortex can degrade motion perception in the contralesional visual hemifield. Our aim was to investigate whether deficits caused by cortical lesions may be different for first- and second-order motion perception, and to study the time scale of any potential recovery. In nine patients with circumscribed lesions mainly in the parietal and fronto-parietal cortex, thresholds for direction discrimination were measured for stimuli presented peripherally in their ipsi- and contralesional hemifield. Subjects had to identify the direction of a vertically moving object embedded in a background of dynamic random dot noise. The object consisted of various proportions of signal and noise dots. Signal dots were either (a) coherently moving in the same direction as the object (first-order), (b) stationary (second-order: drift-balanced), or (c) coherently moving in the opposite direction (second-order: theta). Noise dots were flickering. Two patients showed significant threshold elevations for all three types of motion stimuli presented in their contralesional hemifield, while thresholds for ipsilesional targets were unaffected. Neither showed any selective deficit of first- versus second-order motion perception, but second-order motion was more impaired. Their lesions probably included the motion area V5-MT, which was spared in the other seven patients. One of the patients, who was retested several times during a 27-month postlesional period, showed complete recovery for first- and second-order motion direction discrimination, as well as for the detection of speed differences.

Adult↗
PubMed1998

Complex motion stimuli localize higher-order visual processing in normal observers and in patients with parietal lesions.

The present paper illustrates how modern techniques applied in neuroscience can help us to understand the processing of visual information in the human brain and, in turn, how they can be helpful to characterize functional deficits in patients with cortical lesions. Based on theoretical considerations, motion stimuli are developed that require very specific operations to be performed by the visual system. Computational models explaining the processing of these 'Fourier' and 'second-order' motion stimuli are characterized by increasing complexity. The same types of stimuli are used to map the distribution of cortical activity during motion perception by measuring the magnetic and electrical fields on the head surface. Clinical investigations of patients with lesions in the parietal cortex indicate specific deficits in the perception of such stimuli that can be related to the lesion sites.

Action Potentials↗