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Biomedical subjects

E Pfeifer

Publications and source records attributed to E Pfeifer.

18 recordsLinked to original sources
PubMed2001

Referral to autopsy: effect of antemortem cardiovascular disease: a population-based study in Olmsted County, Minnesota.

PURPOSE: Autopsy studies can provide insight into disease trends and their determinants, including data on the prevalence of atherosclerosis. However, such studies are subject to autopsy bias, which limits their generalizability to the source population. The impact of this bias on autopsy based estimates of time trends in heart disease prevalence is unknown. To report on the trends over time in autopsy rates in Olmsted County, MN, to examine the association between clinical diagnoses of cardiovascular diseases (CVDs) and referral to autopsy and how this association may have changed over time. METHODS: We examined the trends in autopsy rates between 1979 and 1994 in Olmsted County, and the association between antemortem characteristics including cardiovascular diagnoses and autopsy referral. RESULTS: From 1979 to 1994, a total of 9110 residents died in Olmsted County. The average annual autopsy rate was 30%. Autopsy rates declined from 36% in 1979 to 23% in 1994, corresponding to an average decline of 0.6%/year (p < 0.01). Referral to autopsy was positively associated with younger age, male sex, in-hospital place of death, antemortem diagnoses of myocardial infarction (MI) or peripheral vascular disease (PVD), and earlier calendar period. There was no evidence of an interaction between calendar period and any of these predictor variables. Antemortem diagnosis of heart failure was associated with a decrease in the odds of referral to autopsy over time as compared to persons without such diagnosis. CONCLUSIONS: In Olmsted County, autopsy rates, although declining over time, have remained on average approximately 30%. Antemortem diagnoses of MI or PVD are associated with autopsy referral but this association did not change over time. While the greater decline overtime in the use of autopsy observed among decedents with an antemortem diagnosis of congestive heart failure (CHF) deserves further studies, the present findings reduce the concern for bias of time trends in the prevalence of atherosclerosis by changes in the clinical characteristics of decedents referred to autopsy.

Adult↗
PubMed1999

Gamma responses and ERPs in a visual classification task.

OBJECTIVE: We examined event-related potentials (ERPs) and gamma range EEG activity in a visual classification task to assess which variables affect these responses. METHODS: Ten subjects silently counted the occurrence of rare Kanizsa squares (targets) among Kanizsa triangles and non-Kanizsa figures (standards). By applying a time-frequency analysis to the data and selectively calculating topographical maps of certain frequencies. RESULTS: We were able to find 3 different types of gamma responses to Kanizsa figures: an early phase-locked gamma response at 40 Hz in the N100 time range, late phase-locked gamma activity (200-300 ms) at 40 Hz and a continuous phase-locked gamma response at 80 Hz due to the monitor refresh frequency. The two 40 Hz responses were significantly higher for Kanizsa figures than for non-Kanizsa figures and within the Kanizsa figures were higher for the target figure than for the non-target. CONCLUSION: The phase-locking of these two responses, previously found also as non-phase-locked activity, could be synchronized due to the monitor flicker frequency. Also, our findings suggest that the gamma responses are not solely associated with the binding of stimulus features, but reflect some processes related to target processing.

Adult↗
PubMed1998

A MEG analysis of the P300 in visual discrimination tasks.

Based on recent research that indicated that P300 scalp topography varies as a function of task and/or information to be processed, this study examined scalp-recorded magnetic fields correlated with the P300 by means of whole-head magnetoencephalography. Subjects performed two discrimination tasks, in which targets, defined on either object or spatial characteristics of the same visual stimuli, had to be discriminated. Based on the across-subject root mean square (RMS) functions a sequence of 4 components could be identified in both tasks, N1m, P3m, and two later components, which, based on their estimated neuronal sources, were classified as representing motor processes during and following the manual responses to target stimuli. Reliable between-task differences in source localization were obtained for the P3m component, but not for the other components. Inferior-medial sources were found for the P3m evoked by both spatial and object targets, with these sources being located about 3.5 cm more anterior for object targets. These results suggest that different neuronal sources, possibly located in subcortical regions in the vicinity of the thalamus, contribute to the P3m evoked by target stimuli defined by either object or spatial stimulus characteristics.

Adult↗
PubMed1997

The adenylation domain of tyrocidine synthetase 1--structural and functional role of the interdomain linker region and the (S/T)GT(T/S)GXPKG core sequence.

Sequence analysis of peptide synthetases revealed extensive structure similarity with firefly luciferase, whose crystal structure has recently become available, providing evidence for the localization of the active site at the interface between two subdomains separated by a distorted linker region [Conti, E., Franks, N. P. & Brick, P. (1996) Structure 4, 287-298]. The functional importance of two flexible loops, corresponding to the linker region of firefly luciferase and the highly conserved (S/T)GT(T/S)GXPKG core sequence, has been studied in view of the proposed conformational changes by the use of mutant analysis, limited proteolysis and chemical modification of tyrocidine synthetase 1. Substitution of the highly conserved Arg416, residing in the loop separating the subdomains of the adenylation domain, resulted in profound loss of activity. Limited proteolysis of the mutant suggested significant structural changes as manifested by lack of protection to degradation in the presence of substrates, revealing a probable disturbance of the induced-fit mechanism regulating the transformation from an open to a closed conformation. Mutants, obtained by replacement of the conserved Lys186 from the (S/T)GT(T/S)GXPKG core sequence, displayed only minor differences in substrate-binding affinity despite significant reduction of catalytic efficiency. Residue Lys186 appears to play an important role in either stabilization of the bound substrate through charge-charge-interactions, and/or fixing of the loop for maintainance of the active-site conformation.

Amino Acid Sequence↗
PubMed1996

An immunological and genetic study of patients with gestational diabetes mellitus.

The aim of the study was to evaluate the frequency of islet cell (ICA) and insulin (IAA) antibodies and of HLA antigen typing in a group of subjects diagnosed with gestational diabetes mellitus (GDM) in a screening-diagnostic program during pregnancy. ICA, complement-fixing (CF) ICA and other autoantibodies, absolute number and percentage of lymphocyte subpopulations, and HLA antigens were evaluated in 68 women with GDM and compared with those of matched controls. ICA were found in 2 (2.9%) and IAA in 1 (1.5%). Both ICA-positive women had CF-ICA; one of them was receiving insulin therapy. while the other was on a special diet. No correlations were found between ICA and IAA, nor between IAA and insulin treatment. As far as lymphocyte subsets were concerned, we found a significant increase in the absolute number of total and activated (CD3+HLA-DR+) T lymphocytes and a significant increase in the absolute number and percentage of suppressor/cytotoxic T lymphocytes (CD8) and NK lymphocytes (CD57) in GDM patients compared with normal pregnant controls. Concerning frequency for HLA A, B, C, DR antigens in the GDM population, only Cw7 was found to be significantly increased and A10 significantly decreased in comparison with controls. Our study suggests that GDM is a heterogeneous disorder in which few patients present with the immunologic and genetic markers of type 1 diabetes.

Adult↗
PubMed1996

Event-related potentials reveal topographical and temporal distinct neuronal activation patterns for spatial and object working memory.

This study examined whether working memory processes for object and spatial information are associated with different patterns of ERP activity. Subjects performed two versions of a delayed match-to-sample task in which either object forms or two-dimensional spatial configurations (S1) had to be encoded and retained in working memory for 6800 ms for comparison with a subsequent stimulus (S2). Event-related potentials (ERPs) were recorded from 29 electrode sites in the S1-S2 interval. Negative slow wave activity in the ERP varied with both, the type of memory task and the amount of materials held in working memory. When spatial information was maintained in working memory negative slow wave activity rapidly rose at recording sites overlying posterior parietal and occipital cortical areas. At these recording sites, slow wave increased in amplitude with increasing spatial memory load. For object information, load-sensitive negative slow wave activity was obtained approximately 2000 ms later than in the spatial task and it was focused to mid-frontal recording sites. Moreover, in the object memory task more pronounced negative slow wave activity was found at right inferior temporal recording sites indicating a larger involvement of the right temporal lobe in the processing of object as compared to spatial information. The results provide evidence for the notion that encoding and retention processes for object information and for spatial information can be functionally dissociated and involve differential patterns of neuronal activation rapidly shifting in time.

Adult↗
PubMed1995

Characterization of tyrocidine synthetase 1 (TY1): requirement of posttranslational modification for peptide biosynthesis.

Tyrocidine synthetase 1 (TY1), produced by Bacillus brevis ATCC 8185, consists of a single multifunctional polypeptide chain catalyzing the activation, thioesterification, and epimerization of phenylalanine. Because we were concerned about possible posttranslational issues, a comparative study between the wild-type isolate and the in Escherichia coli overexpressed protein was performed. Analysis by matrix assisted laser desorption mass spectrometry (MALDI) provided a molecular mass of 122,516 +/- 120 Da for the recombinant protein, which is in agreement with the value of 122,590 Da calculated from the gene sequence. MALDI analysis of the tryptic fragments revealed that in the recombinant TY1 the putative 4'-phosphopantetheine binding site (562Ser) is not modified by the cofactor. The substrate specificity profiles of the amino acid dependent ATP[32P]PPi exchange reactions were identical, including activation of L-phenylserine, L-tyrosine, and L-methionine. However, the rates of the reverse adenylation reaction for the recombinant protein were only 22% relative to those of the wild-type enzyme. The aminoacylation levels of about 60% for TY1 from Bacillus brevis reduced to 1.4% in the overexpressed protein. A similar distribution of the D- and the L-isomer was detected at the thioester attachment site. The pI values of the wild-type and expressed TY1 are 4.9 and 5.0, respectively. In conclusion, it could be established that apo- and holo-TY1 differ in their amino acid activating properties. Posttranslational modification by 4'-phosphopantetheine is an essential requirement for aminoacylation, epimerization, and thus the functioning of the multienzyme in peptide synthesis.

Adenosine Triphosphate↗
PubMed1994

Identification of the ATP binding site in tyrocidine synthetase 1 by selective modification with fluorescein 5'-isothiocyanate.

Identification of the nucleotide binding site in peptide synthetases has been approached by affinity labeling of tyrocidine synthetase 1 with fluorescein 5'-isothiocyanate. Binding was accompanied by irreversible inhibition of the ATP-dependent phenylalanine activation reaction and was prevented in the presence of MgATP2-. The reaction obeyed pseudo first-order rate kinetics and was accelerated by Mg2+. Complete inhibition corresponded to incorporation of 2.3 mol of fluorescein 5'-isothiocyanate (FITC)/mol of protein. Upon protection by MgATP2-, about 1 mol of FITC is still incorporated; however, this does not affect activity. The modified synthetase was extensively fragmented by tryptic digestion and the labeled fragments isolated by reverse-phase high performance liquid chromatography. Two peptides, DHQVKIR and LDKMPLTPNDKIDR, have been identified by sequencing, and the FITC conjugate of the former peptide has been detected by laser desorption mass spectrometry. The labeled residues, Lys-422 and Lys-505, are located within highly conserved segments of this new class of synthetases.

Adenosine Triphosphate↗
PubMed1994

ATP binding in peptide synthetases: determination of contact sites of the adenine moiety by photoaffinity labeling of tyrocidine synthetase 1 with 2-azidoadenosine triphosphate.

Characterization of the nucleotide binding domain in peptide synthetases was approached by photoaffinity labeling of tyrocidine synthetase 1 (TY1) with 2-azidoadenosine triphosphate (2-azido-ATP). Exposure of TY1 in the presence of photolabel to irradiation with ultraviolet light resulted in a time-dependent covalent modification of the enzyme with a concomitant loss of catalytic activity. Inactivation was not observed if incubation was performed in the absence of either light or the nucleotide analogue. Specificity of labeling was indicated by the ability of 2-azido-ATP to serve as a substrate in the amino acid activation reaction. The modified protein was subjected to tryptic digestion, and the fragments labeled by the nucleotide analogue were purified by reverse-phase high-performance liquid chromatography. Sequence analysis identified three tryptic peptides corresponding to residues G373-K384, W405-R416, and L483-K494, derived from the N-terminal half of the TY1 sequence. As this region shows similarity to strongly conserved regions in other peptide synthetases and acyl-CoA synthetases, it is considered to be the region catalyzing aminoacyl adenylate formation. The identified sequences appear to define components of the nucleotide binding domain found in close proximity to the adenine ring in ATP. Conservation of primary structure and homology to other carboxyl-activating enzymes of this superfamily, including peptide synthetases, insect luciferases, and acyl-CoA synthetases, is discussed.

Adenine↗
PubMed1994

Nucleotide binding by multienzyme peptide synthetases.

Peptide synthetases consist of linearly arranged catalytic units, which by sequence alignment show equally spaced amino-acid-activating segments/modules of 600-700 amino acid residues. The consensus sequence comprises a new class of sequence motifs which are shared by some carboxyl-activating enzymes, but which do not occur in aminoacyl-tRNA synthetases. The catalytic properties of peptide synthetases with respect to the nucleotide substrate were investigated by enzyme kinetic studies. In the activation reaction ATP may be substituted by 2'-deoxy-ATP (dATP) and 7-deazaadenosine 5'-triphosphate, substrate analogues which are not recognised by many aminoacyl-tRNA synthetases, and may thus prove useful alternative substrates in the detection of peptide synthetases within complex protein mixtures. ATP derivatives substituted at C2 are substrates, while those substituted at C8 are not, indicating a preference for the anti-conformation in substrate binding. Kinetic studies revealed that coenzyme A is a non-competitive inhibitor of the activation reaction, suggesting the presence of a second nucleotide binding site which accommodates nucleotides with phosphate in the C2' or C3' position. This substrate and inhibition profile is markedly different from that of aminoacyl-tRNA synthetases and indicative of a separate homogeneous family of carboxyl-activating enzymes.

Adenosine Triphosphate↗
PubMed1994

Processing of surgical instruments for minimally invasive surgery.

Processing of surgical instruments for Minimally Invasive Surgery (MIS). General information on the development of Minimally Invasive Surgery and MIS instruments is given. The "MIS" scientific study group was formed to discuss and find solutions for design and hygienic problems in MIS. The article describes various groups of MIS instruments, i.e. disposable instruments, instruments with a cleaning channel, and instruments which can be dismantled. Aspects of how the instruments can be processed effectively will be discussed in detail, including an example of a survey carried out in a German hospital with a special monitoring method. Requirements are described for MIS instrumentation with regard to design, material, and surface conditions. Requirements for hygienic processing methods are listed. The article also describes the necessary control and confirmation of cleanliness, which proves to be a very particular problem. Conclusions on the present status of technology and the possibilities for future development with regard to the processing of MIS-instrumentation are given.

Disposable Equipment↗
PubMed1993

Event-related brain potentials during natural speech processing: effects of semantic, morphological and syntactic violations.

The present study investigated different aspects of auditory language comprehension. The sentences which were presented as connected speech were either correct or incorrect including a semantic error (selectional restriction), a morphological error (verb inflection), or a syntactic error (phrase structure). After each sentence, a probe word was presented auditorily, and subjects had to decide whether this word was part of the preceding sentence or not. Event-related brain potentials (ERPs) were recorded from 7 scalp electrodes. The ERPs evoked by incorrect sentences differed significantly from the correct ones as a function of error type. Semantic anomalies evoked a 'classical' N400 pattern. Morphological errors elicited a pronounced negativity between 300 and 600 ms followed by a late positivity. Syntactic errors, in contrast, evoked an early negativity peaking around 180 ms followed by a negativity around 400 ms. The early negativity was only significant over the left anterior electrode. The present data demonstrate that linguistic errors of different categories evoke different ERP patterns. They indicate that with using connected speech as input, different aspects of language comprehension processes cannot only be described with respect to their temporal structure, but eventually also with respect to possible brain systems subserving these processes.

Adult↗
PubMed1993

Strategic thinking and stress.

In this study we investigate the behaviour and the performance of experimental subjects, who had to solve a series of tasks of 'strategic thinking' under a stress and a non-stress condition. No significant differences between the conditions could be found with respect to performance and improvement of performance within the series of tasks, but the experimental subjects exhibited under the different conditions different forms of behaviour. Unexpectedly the Ss working under the stress-condition exhibited a more 'analytical' behaviour and increased their workload, instead of decreasing it. Additionally they exhibited a tendency for measures with salient effects and proved to be better in finding the right points of main effort. The results are discussed with respect to a general theory of action regulation.

Humans↗
PubMed1991

Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Aspergillus nidulans. Molecular characterization of the acvA gene encoding the first enzyme of the penicillin biosynthetic pathway.

The Aspergillus nidulans gene (acvA) encoding the first catalytic steps of penicillin biosynthesis that result in the formation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), has been positively identified by matching a 15-amino acid segment of sequence obtained from an internal CNBr fragment of the purified amino-terminally blocked protein with that predicted from the DNA sequence. acvA is transcribed in the opposite orientation to ipnA (encoding isopenicillin N synthetase), with an intergenic region of 872 nucleotides. The gene has been completely sequenced at the nucleotide level and found to encode a protein of 3,770 amino acids (molecular mass, 422,486 Da). Both fast protein liquid chromatography and native gel estimates of molecular mass are consistent with this predicted molecular weight. The enzyme was identified as a glycoprotein by means of affinity blotting with concanavalin A. No evidence for the presence of introns within the acvA gene has been found. The derived amino acid sequence of ACV synthetase (ACVS) contains three homologous regions of about 585 residues, each of which displays areas of similarity with (i) adenylate-forming enzymes such as parsley 4-coumarate-CoA ligase and firefly luciferase and (ii) several multienzyme peptide synthetases, including bacterial gramicidin S synthetase 1 and tyrocidine synthetase 1. Despite these similarities, conserved cysteine residues found in the latter synthetases and thought to be essential for the thiotemplate mechanism of peptide biosynthesis have not been detected in the ACVS sequence. These observations, together with the occurrence of putative 4'-phosphopantetheine-attachment sites and a putative thioesterase site, are discussed with reference to the reaction sequence leading to production of the ACV tripeptide. We speculate that each of the homologous regions corresponds to a functional domain that recognizes one of the three substrate amino acids.

Amino Acid Sequence↗
PubMed1991

Principles of the molecular construction of multienzyme templates for peptide biosynthesis in integrated reaction sequences.

The amino acid sequences of the genes coding for four multienzyme peptide synthetases, operating by the thiotemplate mechanism are compared, to show underlying principles in the biosynthetic mechanism. Alignment with other carboxylic acid activating enzymes shows the sequences. LAY(V/I)I(Y/F)TSGT(T/S)GxPKGV and GELx(L/I)GGxG(V/I) to be involved in MgATP2-binding and adenylate formation, and two other sequences, one containing the element FxLGG(H/D)S(I/L) to be involved in covalent binding of the amino acid. As a general rule, 1000 amino acid building blocks are responsible for the incorporation of one amino acid into the nascent peptide.

Amino Acid Sequence↗
PubMedDate not supplied

Preoperative renal tumor embolization. A useful procedure?

The medical reports of 113 patients operated upon for renal tumors were retrospectively reviewed to assess the value of preoperative embolization. Coils or ethanol were used preoperatively in 55 patients while 58 patients underwent nephrectomy without embolization. The tumors were staged according to the TNM and the Robson staging classification. T1 and T2 tumors as well as T3 and T4 tumors were grouped together for statistical evaluation. There was no significant difference in intraoperative blood loss, operation time and survival rate between patients undergoing preoperative embolization and those who had only nephrectomy. Duration of hospital stay was always longer in the preoperatively embolized group. Preoperative embolization of renal tumors neither improved the patients' outcome nor reduced the surgical risk. Robson's classification, stage III/IV, did not show any significant differences for embolized patients or for those nephrectomized without embolization.

Adult↗