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Biomedical subjects

V Braun

Publications and source records attributed to V Braun.

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

Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note.

OBJECTIVE: This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. METHODS: In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. CONCLUSION: Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip).

Brain↗
PubMed2001

Control of the ferric citrate transport system of Escherichia coli: mutations in region 2.1 of the FecI extracytoplasmic-function sigma factor suppress mutations in the FecR transmembrane regulatory protein.

Transcription of the ferric citrate transport genes is initiated by binding of ferric citrate to the FecA protein in the outer membrane of Escherichia coli K-12. Bound ferric citrate does not have to be transported but initiates a signal that is transmitted by FecA across the outer membrane and by FecR across the cytoplasmic membrane into the cytoplasm, where the FecI extracytoplasmic-function (ECF) sigma factor becomes active. In this study, we isolated transcription initiation-negative missense mutants in the cytoplasmic region of FecR that were located at four sites, L13Q, W19R, W39R, and W50R, which are highly conserved in FecR-like open reading frames of the Pseudomonas aeruginosa, Pseudomonas putida, Bordetella pertussis, Bordetella bronchiseptica, and Caulobacter crescentus genomes. The cytoplasmic portion of the FecR mutant proteins, FecR(1-85), did not interact with wild-type FecI, in contrast to wild-type FecR(1-85), which induced FecI-mediated fecB transport gene transcription. Two missense mutations in region 2.1 of FecI, S15A and H20E, partially restored induction of ferric citrate transport gene induction of the fecR mutants by ferric citrate. Region 2.1 of sigma(70) is thought to bind RNA polymerase core enzyme; the residual activity of mutated FecI in the absence of FecR, however, was not higher than that of wild-type FecI. In addition, missense mutations in the fecI promoter region resulted in a twofold increased transcription in fecR wild-type cells and a partial restoration of fec transport gene transcription in the fecR mutants. The mutations reduced binding of the Fe(2+) Fur repressor and as a consequence enhanced fecI transcription. The data reveal properties of the FecI ECF factor distinct from those of sigma(70) and further support the novel transcription initiation model in which the cytoplasmic portion of FecR is important for FecI activity.

Amino Acid Sequence↗
PubMed2001

FhuA barrel-cork hybrids are active transporters and receptors.

The crystal structure of Escherichia coli FhuA reveals a beta-barrel domain that is closed by a globular cork domain. It has been assumed that the proton motive force of the cytoplasmic membrane through the interaction of the TonB protein with the TonB box of the cork opens the FhuA channel. Yet, deletion of the cork results in an FhuA derivative, FhuADelta5-160, that still displays TonB-dependent substrate transport and phage receptor activity. To investigate this unexpected finding further, we constructed FhuADelta5-160 derivatives of FhuA proteins from Salmonella paratyphi B, Salmonella enterica serovar Typhimurium, and Pantoea agglomerans. The FhuADelta5-160 proteins inserted correctly into the outer membrane, and with the exception of the P. agglomerans protein, transported ferrichrome and albomycin. FhuA hybrids consisting of the beta-barrel of one strain and the cork of another strain were active and showed higher TonB-dependent ferrichrome transport rates than the corkless derivatives. Exceptions were the E. coli beta-barrel/Salmonella serovar Typhimurium cork hybrid protein and the Salmonella serovar Typhimurium beta-barrel/P. agglomerans cork hybrid protein, both of which were less active than the beta-barrels alone. Each of the FhuA mutant proteins displayed activity for each of their ligands, except for phage T5, only when coupled to TonB. The hybrid FhuA proteins displayed a similar activity with the E. coli TonB protein as with their cognate TonB proteins. Sensitivity to phages T1, T5, and phi80, rifamycin CGP 4832, and colicin M was determined by the beta-barrel, whereas sensitivity to phage ES18 and microcin J25 required both the beta-barrel and cork domains. These results demonstrate that the beta-barrel domain of FhuA confers activity and specificity and responds to TonB and that the cork domains of various FhuA proteins can be interchanged and contribute to the activities of the FhuA hybrids.

Bacterial Outer Membrane Proteins↗
PubMed2001

In vivo synthesis of the periplasmic domain of TonB inhibits transport through the FecA and FhuA iron siderophore transporters of Escherichia coli.

The siderophore transport activities of the two outer membrane proteins FhuA and FecA of Escherichia coli require the proton motive force of the cytoplasmic membrane. The energy of the proton motive force is postulated to be transduced to the transport proteins by a protein complex that consists of the TonB, ExbB, and ExbD proteins. In the present study, TonB fragments lacking the cytoplasmic membrane anchor were exported to the periplasm by fusing them to the cleavable signal sequence of FecA. Overexpressed TonB(33-239), TonB(103-239), and TonB(122-239) fragments inhibited transport of ferrichrome by FhuA and of ferric citrate by FecA, transcriptional induction of the fecABCDE transport genes by FecA, infection by phage phi80, and killing of cells by colicin M via FhuA. Transport of ferrichrome by FhuADelta5-160 was also inhibited by TonB(33-239), although FhuADelta5-160 lacks the TonB box which is involved in TonB binding. The results show that TonB fragments as small as the last 118 amino acids of the protein interfere with the function of wild-type TonB, presumably by competing for binding sites at the transporters or by forming mixed dimers with TonB that are nonfunctional. In addition, the interactions that are inhibited by the TonB fragments must include more than the TonB box, since transport through corkless FhuA was also inhibited. Since the periplasmic TonB fragments cannot assume an energized conformation, these in vivo studies also agree with previous cross-linking and in vitro results, suggesting that neither recognition nor binding to loaded siderophore receptors is the energy-requiring step in the TonB-receptor interactions.

Bacterial Outer Membrane Proteins↗
PubMed2001

Demonstration that the group II intron from the Clostridial Conjugative transposon Tn5397 undergoes splicing In vivo.

Previous work has identified the conjugative transposon Tn5397 from Clostridium difficile. This element was shown to contain a group II intron. Tn5397 can be conjugatively transferred from C. difficile to Bacillus subtilis. In this work we show that the intron is spliced in both these hosts and that nonspliced RNA is also present. We constructed a mutation in the open reading frame within the intron, and this prevented splicing but did not prevent the formation of the circular form of the conjugative transposon (the likely transposition intermediate) or decrease the frequency of intergeneric transfer of Tn5397. Therefore, the intron is spliced, but splicing is not required for conjugation of Tn5397.

Bacillus subtilis↗
PubMed2001

Evaluation of iatrogenic lesions in 722 surgically treated cases of peripheral nerve trauma.

OBJECT: The purpose of this study was to discover the number and types of iatrogenic nerve injuries that were surgically treated during a 9-year period at a relatively busy nerve center. The specific nerves involved, their sites of injury, and the mechanisms of injury were also documented. METHODS: The authors retrospectively evaluated the surgically treated iatrogenic lesions by reviewing case histories, operative reports, and follow-up notes in 722 cases of trauma. These cases were treated between January 1990 and December 1998 because of pain, dysesthesias, and sensory and/or motor deficits. latrogenic injury was a much larger category of trauma than predicted. One hundred twenty-six (17.4%) of the 722 surgically treated cases were iatrogenic in origin. Most of these injuries occurred during a previous operation. To a major extent, nerves of the extremities were affected, and a relatively large number of injuries occurred in the neck and groin. Incidence was highest in the spinal accessory nerve (14 cases), the common peroneal nerve (11 cases), the superficial radial nerve (10 cases), the genitofemoral nerve branches (10 cases), and the median nerve (nine cases). At least two thirds of the patients did not undergo surgery for the iatrogenic injury within an optimal time interval due to delayed referral. Follow-up data were available in 97 of the 126 patients. Surgical outcomes demonstrated improvement in 70% of patients. Operative results were especially favorable in patients suffering from iatrogenic injuries to the accessory and superficial sensory radial nerves. CONCLUSIONS: latrogenic injuries should be corrected in a timely fashion just like any other traumatic injury to nerve.

Extremities↗
PubMed2000

Two-step fast protein liquid chromatographic purification of the Serratia marcescens hemolysin and peptide mapping with mass spectrometry.

The pore forming toxin of Serratia marcescens (ShlA) is secreted and activated by an outer membrane protein (ShlB). Activation of inactive ShlA (termed ShlA*) by ShlB is dependent on phosphatidylethanolamine (PE). Activation may be a covalent modification of ShlA. To test this hypothesis, the responsible activation domain (in the N-terminal 255 amino acids of ShlA) was isolated from whole bacteria with 8 M urea in an inactive form (ShlA-255*) and from the culture supernatant in an active form (ShlA-255), followed by a two-step purification by anion-exchange chromatography and gel permeation chromatography. Comparison of a tryptic peptide map of both forms with subsequent electrospray mass spectrometry (ES-MS) and sequencing by tandem ES-MS revealed no modification. These data imply that ShlB presumably imposes a conformation on ShlA-255 that triggers activity.

Amino Acid Sequence↗
PubMed2000

Sequence and organization analyses of a Zygosaccharomyces rouxii DNA fragment containing the HIS3 gene.

The nucleotide sequence of a 3.4 kb fragment containing the HIS3 gene of the osmotolerant yeast Zygosaccharomyces rouxii has been determined. The fragment was cloned from a Z. rouxii genomic DNA library by complementation of a Saccharomyces cerevisiae his3 mutant strain. The sequenced DNA fragment contained three open reading frames; the middle one (678 bp long, predicting a protein of 226 amino acids) shared a high degree of similarity with HIS3 genes of other yeast species. In the promoter region of the putative ZrHIS3 gene, a T(c) element required for constitutive transcription was found. The GenBank Accession No. of the sequenced DNA region is Y18561.

Amino Acid Sequence↗
PubMed2000

Organization of specific genomic regions of Zygosaccharomyces rouxii and Pichia sorbitophila: comparison with Saccharomyces cerevisiae.

The genomes of Zygosaccharomyces rouxii and Pichia sorbitophila were partially explored. The genome of Z. rouxii CBS 732 consists of seven chromosomes with an approximate size of 1.0-2.75 Mb, 12.8 Mb in total. Five of the chromosomes were labelled with specific probes. Three Z. rouxii genomic DNA fragments were sequenced; all 10 ORFs found were without introns and they have homologues in S. cerevisiae. Gene order comparison revealed that the organization is partially conserved in both species. The genome of P. sorbitophila CBS 7064 consists of seven chromosomes with an approximate size of 1.0-2.9 Mb, 13.9 Mb in total. Three of the chromosomes were labelled with specific probes. The sequencing of a 5.2 kb genomic DNA fragment revealed three ORFs, but no conservation of their organization was found, although all of them have their respective homologues in S. cerevisiae. According to our results, the presence of two overlapping ORFs in S. cerevisiae (YJL107c-YJL108c) could be interpreted as the result of a frameshift mutation.

Base Sequence↗
PubMed2000

[Effect of microneurosurgical operation in acoustic neurinoma on symptoms of vertigo and tinnitus].

After exstirpation of an acoustic neuroma one trends to concentrated on the preservation of hearing and facial function. But how does the surgical removal for an acoustic neuroma, influence the symptoms of tinnitus and vertigo? Our report follows a retrospective evaluation of 78 patients. Based on these results we will also discuss aspects of the origin of these symptoms. Our patients suffered from tinnitus at a rate of 73% preoperatively and 59% postoperatively. With increasing tumor size tinnitus occurred less often, therefore we considered the size of the tumor exclusively. Also, an intraoperative dissection of the cochlear nerve often did not result in an improvement of the symptoms. Vertigo was stated prooperatively in 44% of the cases, postoperatively in 22%. Again as with tinnitus, there was an inverse relationship between the size of the tumor and the severity of the symptoms. In conclusion a deafferention-like syndrome has to be considered as the major causative factor for the tinnitus in patients with acoustic neuromas. However, in the vertigo cases, the symptoms seem to be caused vestibularily due to the increasing tumor and then after a temporary compensation a cerebellar ataxia occurred which the patients often perceive as vertigo.

Adolescent↗
PubMed2000

ShlB mutants of Serratia marcescens allow uncoupling of activation and secretion of the ShlA hemolysin.

The ShlB protein in the outer membrane of Serratia marcescens secretes hemolytic ShlA protein into the culture medium. In the absence of ShlB, nonhemolytic ShlA remains in the periplasm. ShlB mutants were isolated in which secretion was uncoupled from activation. Mutants with a tetrapeptide insertion after residues 136 or 224 of mature ShlB and a mutant with an insertion after residue 154 and a deletion secreted inactive ShlA. In vitro, secreted nonhemolytic ShlA was converted into hemolytic ShlA by isolated wild-type ShlB and by complementation with an N-terminal ShlA fragment of 255 residues (ShlA-255). The isolation of secretion-competent, but activation-negative mutants indicates that secretion alone is not sufficient for activation of ShlA. Rather, ShlB is required for activation and secretion, and the mutants define sites in ShlB which are involved in activation. According to a predicted transmembrane model of ShlB, the mutations that retain secretion competence but abolish activation competence are located in the most prominent surface loop and the following transmembrane loop. In one tetrapeptide insertion mutant, ShlB-332, most of the ShlA remained cell-associated in an inactive form and low amounts (6%) were hemolytic. Secreted inactive ShlA(o) was completely degraded by trypsin, in contrast to hemolytic ShlA, which was cleaved into two fragments of 60 and 100 kDa. This result indicates that the conformational change from a highly trypsin-sensitive to a highly trypsin-resistant protein with only a single cleavage site in a polypeptide of 1,578 residues occurs upon activation of ShlA and not during secretion.

Alkaline Phosphatase↗
PubMed2000

A chimeric ribozyme in clostridium difficile combines features of group I introns and insertion elements.

CdlSt1, a DNA insertion of 1975 bp, was identified within tcdA-C34, the enterotoxin gene of the Clostridium difficile isolate C34. Located in the catalytic domain A1-C34, Cd/St1 combines features of two genetic elements. Within the first 434 nt structures characteristic for group I introns were found; encoding the two transposase-like proteins tlpA and tlpB nucleotides 435-1975 represent the remainder of a IS605-like insertion element. We show that the entire CdlSt1 is accurately spliced from tcdA-C34 primary transcripts and that purified TcdA-C34 toxin is of regular size and catalytic activity. A search for CdlSt1-related sequences demonstrates that the element is widespread in toxinogenic and non-toxinogenic C. difficile strains, indicating the mobility of CdlSt1. In strain C34, we characterize 10 CdlSt1 variants; all are highly homologous to CdlSt1 (> 93% identity), integrated in bacterial open reading frames (ORFs), show the typical composite structure of CdlSt1 and are precisely spliced from their primary transcripts. CdlSt1-like chimeric ribozymes appear to combine the invasiveness of an insertion element with the splicing ability of a group I intron, rendering transposition harmless for the interrupted gene.

Amino Acid Sequence↗
PubMed2000

Neurosurgery without shaving: indications and results.

The objective of the investigation was to prevent the stigmatizing effect of a totally or partially shaved head with openly visible signs of a head operation, easing the reintegration of the patient into his daily life. After extended surface cleaning with a colourless, regular skin disinfection liquid (undyed isopropanol/dibrom/propylenglycol solution) the hair was combed apart from the incision line before draping. Wound closure was performed as usual, taking care to remove meticulously hair from the wound. To aid closure we made use of a 20% chlorhexidine jelly that holds the hair away from the incision. A neomycin ointment served for sealing the wound surface, no further dressing being used. After 215 cranial neurosurgical operations, among them 63 for tumours, 33 stereotactic procedures 18 shunt, 55 for torticollis and 46 other operations performed without shaving the hair, we saw one wound infection (0.5%). This percentage corresponds very well to our general infection rate of 0.6%. All patients very much appreciated the offered opportunity and the result. If the objective is to give patients a psychological advantage by preventing a partially bald head we think one can safely refrain from the shaving procedure without risking a higher infection rate.

Brain↗
PubMed2000

Disposition of haloperidol pyridinium and reduced haloperidol pyridinium in schizophrenic patients: no relationship with clinical variables during short-term treatment.

In an open clinical trial, serum concentrations of haloperidol pyridinium (C(HP+)) and reduced haloperidol pyridinium (C(RHP+)), as well as haloperidol (CH) and reduced haloperidol (C(RH)), were measured in 57 schizophrenic and schizoaffective inpatients during 6 weeks of short-term treatment. Psychopathology was monitored with the Brief Psychiatric Rating Scale (BPRS), and extrapyramidal adverse effects were assessed with the Extrapyramidal Symptom Rating Scale (EPS). Significantly linear relationships were found between haloperidol dose (D) and pyridinium metabolite serum concentrations, as well as between C(H) and the pyridinium metabolite serum concentrations. C(HP+) (range, 0.2-4.9 ng/mL) and C(RHP+) (range, 0.03-6.23 ng/mL) were low compared with C(H) and C(RH), being as mean values approximately 7% and 14% of C(H) and C(RH), respectively. Additionally, the values of C(RHP+) and the slope of the correlation of C(H) with the C(RHP+)/C(HP+) ratio were considerably lower than in a previous report of long-term treatment with haloperidol. This is explained by the shorter time of treatment of the present study. Carbamazepine comedication was found to not influence relative pyridinium metabolite serum concentrations C(HP+)/D and C(RHP+)/D. However, the aromatization ratios of haloperidol (C(HP+)/C(H)) and reduced haloperidol (C(RHP+)/C(RH)) were increased by concomitant carbamazepine. As the main result, no relationships between the pyridinium metabolite serum concentrations and clinical variables (BPRS change, EPS, dose of biperiden) were detected. For instance, the aromatization ratios C(HP+)/C(H) and C(RHP+)/C(RH) did not predict clinical improvement or extrapyramidal adverse effects. Therefore, no confirmation of the "pyridinium hypothesis," which suggests haloperidol pyridinium metabolites to be the origin of adverse effects and decreased therapeutic effect, can be derived from this study. However, the authors emphasize that pyridinium metabolites cannot be excluded as the origin of decreased therapeutic effect in long-term treatment and of adverse effects not investigated in the present study, such as tardive dyskinesia. Finally, it is concluded that the serum concentration of the parent drug remains the main variable of interest in the therapeutic drug monitoring of haloperidol during short-term treatment.

Adult↗
PubMed2000

Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA.

One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of gram-negative bacteria. These "Trojan Horse" antibiotics may prove useful as an efficient means to combat multi-drug-resistant bacterial infections. Here we present the crystallographic structures of the natural siderophore-antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli. To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter. Albomycins are broad-host range antibiotics that consist of a hydroxamate-type iron-chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety. As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom. Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron-chelating siderophores and offers a structural platform for the rational design of hydroxamate-type siderophore-antibiotic conjugates.

Anti-Bacterial Agents↗
PubMed2000

Surface signaling in ferric citrate transport gene induction: interaction of the FecA, FecR, and FecI regulatory proteins.

In Escherichia coli, transcription of the ferric citrate transport genes fecABCDE is controlled by a novel signal transduction mechanism that starts at the cell surface. Binding of ferric citrate to the outer membrane protein FecA initiates a signal that is transmitted by FecR across the cytoplasmic membrane into the cytoplasm where FecI, the sigma factor, is activated. Interaction between the signaling proteins was demonstrated by utilizing two methods. In in vitro binding assays, FecR that was His tagged at the N terminus [(His)(10)-FecR] and bound to a Ni-nitrilotriacetic acid agarose column was able to retain FecA, and FecR that was His tagged at the C terminus [FecR-(His)(6)] retained FecI on the column. An N-terminally truncated, induction-negative but transport-active FecA protein did not bind to (His)(10)-FecR. The in vivo assay involved the determination of the FecA, FecR, and FecI interacting domains with the bacterial two-hybrid Lex-based system. FecA(1-79) interacts with FecR(101-317) and FecR(1-85) interacts with FecI(1-173). These data clearly support a model that proposes interaction of the periplasmic N terminus of FecA with the periplasmic C-terminal portion of FecR and interaction of the cytoplasmic N terminus of FecR with FecI, which results in FecI activation.

Bacterial Proteins↗
PubMed2000

Functional cranial neuronavigation. Direct integration of fMRI and PET data.

OBJECTIVE: We report our first experiences with the direct integration of fMRI data into cranial neuronavigation. METHOD: For navigation we used the MKM system and thin-sliced T1 contrast enhanced images. As a first step 21 patients had fMRI for localization of the precentral gyrus, 2 patients for Broca area detection. By anatomical correlation, these functional data were indirectly compared to the intraoperative findings using cortical SSEP (n=20) or cortical stimulation (n=3). Encouraged by these preliminary results, we started the direct integration of fMRI into neuronavigation in June 1999, followed by PET in January 2000, enabling us to compare functional images with intraoperative findings directly. fMRI and PET data were integrated by landmark matching referring on skin fiducials. Meanwhile, fMRI data of 8 patients (6 motorcortex, 2 Broca) and PET images of 1 patient were directly integrated into neuronavigation. Six out of 8 patients had additional cortical monitoring, 2/8 were exclusively operated on by functional neuronavigation. RESULTS: Using indirect comparison between fMRI and intraoperative findings we observed a good correlation in every case for the motorcortex, but only in 1/2 for the speech area. In all 6 direct integrated fMRI cases, these findings corresponded well to the conventional ones. Both patients with sole functional navigation did not have any postoperative neurological deficit. The inaccuracy of the fMRI ifT1 matching was 2. 7 mm (sigma=0.9 mm) and 1.3 mm (sigma=0.4 mm) of the subsequent referenciation of the navigation. The tumor delinement shown by 11C-methionine PET could be proven by intraoperative biopsy outside its indicated tumor margin. The inaccuracy of the PET matching was 0. 8 mm. CONCLUSION: Functional neuronavigation enables to visualize and preserve relevant brain areas. Other functional areas like short-term memory, which solely can be detected by fMRI might also be monitored in the future. The integration of PET data expect to gain a better differentiation of tumor and edema.

Adult↗