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C Heck

Publications and source records attributed to C Heck.

14 recordsLinked to original sources
PubMed2001

An mRNA degrading complex in Rhodobacter capsulatus.

An RNA degrading, high molecular weight complex was purified from Rhodobacter capsulatus. N-terminal sequencing, glycerol-gradient centrifugation, and immunoaffinity purification as well as functional assays were used to determine the physical and biochemical characteristics of the complex. The complex comprises RNase E and two DEAD-box RNA helicases of 74 and 65 kDa, respectively. Most surprisingly, the transcription termination factor Rho is a major, firmly associated component of the degradosome.

Amino Acid Sequence↗
PubMed2001

Vagus nerve stimulation: analysis of device parameters in 154 patients during the long-term XE5 study.

PURPOSE: To determine the effect of changes in device settings and duty cycle (on and off times) on the efficacy of vagus nerve stimulation (VNS) for refractory epilepsy. In the long-term XE5 study of VNS for intractable epilepsy, the median reduction in seizure frequency improved significantly after 1 year of follow-up. A central question is whether device changes improve efficacy. We analyzed the effects of device parameter changes on seizure frequency in 154 subjects who completed the study and who had complete data for analysis. METHODS: Retrospective analysis of device changes during the XE5 long-term study of VNS. During the XE5 long-term follow-up study, the subject's device settings were modified within a Food and Drug Administration (FDA)-approved range of output current, pulse duration, frequency, on time, and off time. Significant changes in device settings occurred after 3 months. We investigated the relationship between percentage reduction in seizures and changes in device parameters between the 3- and 12-month visits. Within-group comparisons were performed for those who continued on standard on/off cycle of 30 s on and 5 min off, and those with the most common off times of 3, 1.8, and < 1.1 min. RESULTS: Output current, pulse duration, frequency, and off time changed significantly between the 3- and 12-month long-term follow-ups. For the group as a whole, changes in device settings were not correlated with an improvement in efficacy. However, a significant improvement in efficacy occurred in a subgroup whose off time was reduced to < or = 1.1 min. In this group, the median reduction in seizures improved from 21% before the change in off time, to 39% after the change in off time (Wilcoxon Signed-Rank, p = 0.011). The responder rate (> 50% reduction in seizures) also significantly improved from 19 to 35% (McNemar's test, p = 0.046). CONCLUSIONS: The data from this retrospective analysis indicate that device changes were not the primary determinant of increased efficacy at 12 months of long-term follow-up. In general, patients who remained on the original settings of 30 s on and 5 min off continued to respond or improve in their response over the 1-year period. However, some patients may benefit from reductions in off time (increases in duty cycle). In a subgroup initially resistant to VNS, a change in off time to < or = 1.1 min off did result in significant improvements in efficacy.

Double-Blind Method↗
PubMed2000

Initial events in the degradation of the polycistronic puf mRNA in Rhodobacter capsulatus and consequences for further processing steps.

Individual segments of the polycistronic puf mRNA of Rhodobacter capsulatus exhibit extremely different half-lives contributing to the stoichiometry of light-harvesting and reaction centre complexes of this facultative phototrophic bacterium. While earlier investigations shed light on the processes leading to the degradation of the 2.7 kb pufBALMX mRNA and, consequently, to the formation of the highly stable 0.5 kb pufBA mRNA processing product, we have now investigated the initial events in the degradation of the highly unstable 3.2 kb pufQBALMX primary transcript. Sequence modifications of two putative RNase E recognition sites within the pufQ coding region provide strong evidence that RNase E-mediated cleavage of a sequence at the 3' end of pufQ is involved in rate-limiting cleavage of the primary pufQBALMX transcript in vivo. The putative RNase E recognition sequence at the 5' end of pufQ is cleaved in vitro but does not contribute to rate-limiting cleavage in vivo. Analysis of the decay of puf mRNA segments transcribed from wild-type and mutated puf DNA sequences in R. capsulatus and Escherichia coli reveal that RNase E-mediated cleavage within the pufQ mRNA sequence also affects the stability of the 0.5 kb pufBA processing product. These findings demonstrate that the stability of a certain mRNA segment depends on the pathway of processing of its precursor molecule.

Bacterial Proteins↗
PubMed2000

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Electric Stimulation Therapy↗
PubMed1999

RNase E enzymes from rhodobacter capsulatus and Escherichia coli differ in context- and sequence-dependent in vivo cleavage within the polycistronic puf mRNA.

The 5' pufQ mRNA segment and the pufLMX mRNA segment of Rhodobacter capsulatus exhibit different stabilities. Degradation of both mRNA segments is initiated by RNase E-mediated endonucleolytic cleavage. While Rhodobacter RNase E does not discriminate between the different sequences present around the cleavage sites within pufQ and pufL, Escherichia coli RNase E shows preference for the sequence harboring more A and U residues.

Bacterial Proteins↗
PubMed1997

Identification, sequence analysis, and expression of the lepB gene for a leader peptidase in Rhodobacter capsulatus.

The leader peptidase (signal peptidase I) gene, lepB, of Rhodobacter capsulatus has been cloned and sequenced. The amino acid sequence of the predicted protein exhibits similarity to other known bacterial leader peptidases. R. capsulatus belongs to the alpha-subdivision of purple bacteria and thus is a relative of mitochondria in eukaryotes. Like the yeast mitochondrial inner membrane proteases IMP1 and IMP2, the leader peptidase from Rhodobacter has only one membrane-spanning segment. Sequence comparison of the Rhodobacter Lep protein with IMP1 and IMP2 did not reveal a higher overall similarity than between other prokaryotic signal peptidases and the mitochondrial enzymes. Expression studies using lacZ fusions in combination with primer extension analysis provide evidence for a weak promoter located a short distance from the transcription start of the lepB gene. Failure to establish a Rhodobacter strain with a disrupted lepB gene indicates that this gene is essential.

Amino Acid Sequence↗
PubMed1996

Cloning, nucleotide sequence and characterization of the rpoD gene encoding the primary sigma factor of Rhodobacter capsulatus.

A synthetic oligodeoxynucleotide probe based on a highly conserved region of the sigma factors was used to identify and clone the rpoD gene encoding the principal sigma factor of R. capsulatus. The deduced polypeptide contains 674 amino acids and has a predicted molecular mass of 75,942 Da. The deduced amino acid sequence of R. capsulatus RpoD protein exhibits 46.2% and 45.7% identity with housekeeping sigma factors of Pseudomonas and E. coli, respectively. Unsuccessful attempts to inactivate the single chromosomal rpoD gene of R. capsulatus by gene replacement technique indicate that this gene is essential for cell survival, as expected for the primary sigma factor. The rpoD transcript 5'-end was mapped by primer extension analysis, 74 bp upstream of the initiation codon and DNA sequence analysis has identified a motif resembling the delta 70 E. coli consensus promoter sequences at the expected distance from this proposed transcription start site. rpoD gene expression, as measured by the activity of the phi (rpoD'-lacZ+) translational fusion, was found to be constant throughout exponential and early plateau phases, but significantly increased at later times of the stationary phase.

Amino Acid Sequence↗
PubMed1996

Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging.

OBJECTIVE: To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS: We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS: The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS: VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Adult↗
PubMed1996

Effect of the pufQ-pufB intercistronic region on puf mRNA stability in Rhodobacter capsulatus.

Differential expression of genes localized within the polycistronic puf operon of Rhodobacter capsulatus is partly due to altered stabilities of individual mRNA segments. We show that the 5' untranslated region (UTR) of pufB contributes to the unusual longevity of the 0.5 kb light-harvesting (LH) I specific pufBA mRNA and of the 2.7 kb pufBALMX mRNA. Three stem-loop structures have been identified within the pufQ-pufB intercistronic region by means of RNA secondary-structure analysis in vitro and in vivo. Deletion analysis of the pufB 5' UTR indicates that the complete set of secondary structures is required to maintain wild-type levels of pufBA mRNA stability. A phylogenetic comparison of pufB 5' UTRs of other photosynthetic bacteria reveals an evolutionary conservation of the base-pairing potential despite sequence divergence. Comparison of puf mRNA decay in Escherichia coli strains with or without endoribonuclease E (RNase E) activity suggests that the pufB 5' secondary structures protect the downstream mRNA segment against degradation by RNase E. Removal of the 117-nucleotide pufQ-pufB intercistronic region results in loss of stability for the pufBA and pufBALMX mRNAs with concomitant stabilization of the full-length puf primary transcript (QBALMX). We therefore conclude that the deleted sequence functions both as a stabilizing element for pufBALMX and pufBA segments and as a target site for initial rate-limiting decay of the unstable pufQBALMX mRNA.

Bacterial Proteins↗
PubMed1993

[Improvement in myocardial function and perfusion after recanalizing a chronic coronary artery occlusion].

The purpose of the study was to evaluate the improvement of the left ventricular ejection fraction and myocardial perfusion after recanalization of chronic coronary artery occlusions. The patients were investigated by rest and exercise radionuclide ventriculography (25/31) and rest and exercise myocardial scintigraphy (22/31). The examinations were performed 3 +/- 1 days before and within 7 days and 4 months after recanalization. Exercise-induced chest pain was present in 77% (24/31) of the patients before, in 10% (3/31) after recanalization and in 23% (7/31) during follow-up. Six of the 7 patients with exercise-induced chest pain after 4 months developed restenosis in the former reopened coronary artery. The results of the exercise-ECG present that 71% (22/31) of the patients had ST-segment-depression before, 19% (6/31) after catheter-intervention and 26% (8/31) during follow-up. Six of the 8 patients with exercise-induced ST-depression after 4 months had a restenosis in the former reopened coronary artery. Reopening resulted in an increase of global rest ejection fraction (EF) from 51 +/- 11% to 54 +/- 13% (p < 0.05) and sectorial EF from 56 +/- 17% to 61 +/- 21% (p < 0.01) after recanalization. After 4 months patients with excellent angiographic results still had an increased global and sectorial EF at rest (global: 54 +/- 9%, sectorial: 59 +/- 17%; n.s.). Patients with restenosis (note: no reocclusion) developed a decrease of global and sectorial rest EF (global: 49 +/- 14%, sectorial: 57 +/- 19%; n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1987

Prophylactic antiarrhythmic therapy of high-risk survivors of myocardial infarction: lower mortality at 1 month but not at 1 year.

To determine whether prophylactic antiarrhythmic therapy influences mortality in high-risk patients after acute myocardial infarction, 143 such patients were randomized in a double-blind individually dose-adjusted, placebo-controlled trial an average of 14 +/- 7 days after myocardial infarction and followed for 1 year. Patients were judged to be at high risk on the basis of (1) ejection fraction less than 40% (n = 60), (2) arrhythmias of Lown class 3 or higher (n = 26), or (3) both (n = 57). Aprindine was chosen because of its long half-life, few side effects, and antiarrhythmic efficacy. Baseline characteristics in the treatment arms did not differ. Holter-detected arrhythmias were reduced in aprindine-treated patients at 3 months (p less than .001) and at 1 year (p less than .001). One patient was lost to follow-up; in the remaining patients 1 year mortality was 20% (28/142; 12 aprindine and 16 placebo). There was no significant difference between the two study arms in overall mortality and sudden death. However, among those who died, median duration of survival was longer in aprindine-treated patients (86 vs 21.5 days) (p = .04). Although antiarrhythmic treatment with aprindine of high-risk patients after myocardial infarction does not affect 1 year survival, mortality appears to be delayed; thus there may be a role for short-term treatment before more definitive therapy such as surgery.

Aprindine↗