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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 73 records · Page 4Linked to original sources
PubMed2000

Low chronic pacing thresholds of steroid-eluting active-fixation ventricular pacemaker leads: a useful alternative to passive-fixation leads.

Active-fixation pacemaker leads enable pacing at various sites, have a low dislodgment rate, and are easier to extract than passive-fixation leads, though are usually not routinely implanted in the ventricle because of their higher pacing threshold. The long-term pacing threshold associated with an active-fixation steroid-eluting lead was prospectively measured in 18 women and 20 men. At a mean follow-up of 14 months (range 3-25 months), pacing threshold increased from 0.71 +/- 0.29 V to 0.96 +/- 0.28 V (P = 0.01) between implant and the first month of follow-up, then remained stable over time, consistently allowing the long-term programming of the ventricular output at 2.5 V, while lead impedance remained stable (from 647 +/- 161 omega at implant to 666 +/- 122 omega at last follow-up). If the long-term performance of this type of lead is confirmed, the routine implantation of ventricular steroid-eluting active-fixation leads should be considered since lead extraction has become a major concern.

Adult↗
PubMed2000

Identification of immunodominant antigens from Helicobacter pylori and evaluation of their reactivities with sera from patients with different gastroduodenal pathologies.

Colonization of the gastric mucosa by Helicobacter pylori is the major cause of gastroduodenal pathologies in humans. Studying the outcome of the humoral immune response directed against this gastric pathogen may contribute substantially to vaccine development and to the improvement of diagnostic techniques based on serology. By using two-dimensional gel electrophoresis, 29 proteins from H. pylori G27 were identified which strongly react with sera derived from H. pylori-infected patients suffering from different gastroduodenal pathologies. These antigens were characterized by mass spectrometry and proved to correspond to products of open reading frames predicted by the H. pylori genome sequence. The comparison of the antigenic patterns recognized by these sera revealed no association of specific H. pylori antigens with antibodies in patients with particular gastroduodenal pathologies.

Antibodies, Bacterial↗
PubMed2000

Molecular characterization of two-component systems of Helicobacter pylori.

Two-component systems are frequently involved in the adaptation of bacteria to changing environmental conditions at the level of transcriptional regulation. Here we report the characterization of members of the two-component systems of the gastric pathogen Helicobacter pylori deduced from the genome sequence of strain 26695. We demonstrate that the response regulators HP166, HP1043, and HP1021 have essential functions, as disruption of the corresponding genes is lethal for the bacteria, irrespective of the fact that HP1043 and HP1021 have nonconserved substitutions in crucial amino acids of their receiver domains. An analysis of the in vitro phosphorylation properties of the two-component proteins demonstrates that HP244-HP703 and HP165-HP166 are cognate histidine kinase-response regulator pairs. Furthermore, we provide evidence that the variability of the histidine kinase HP165 caused by a poly(C) tract of variable length close to the 3' end of open reading frame 165/164 does not interfere with the kinase activity of the transmitter domain of HP165.

Adaptation, Biological↗
PubMed2000

[Burst of idiopathic ventricular tachycardia complicated by arrhythmia-induced cardiomyopathy].

The authors report the case of a young man with idiopathic ventricular tachycardia occurring in bursts and arising from the pulmonary infundibulum. During follow-up, progressive, severe, dilated cardiomyopathy was observed. Radiofrequency ablation of the site of origin of this very active arrhythmia resulted in total regression of the cardiomyopathy. Contrary to generally accepted concepts, paroxystic ventricular tachycardia, usually qualified as benign, may be complicated by cardiomyopathy when the ventricular extrasystole is incessant and repetitive.

Adult↗
PubMed2000

[Etiopathogenesis of arrhythmogenic right ventricular dysplasia].

Arhythmogenic right ventricular dysplasia (ARVD) is a genetically determined cardiomyopathy with a dominant transmission mode and variable penetrance. Transdifferenciation of cardiomyocytes into adipocytes is likely to explain massive replacement of right ventricular and to a lesser extent left ventricular myocardium by adipose tissue. This phenomenon starts in the mediomural layers and extends into the epicardium. It can occur in the fetus, however youth and young adults are more frequently involved. Apoptosis defined as a programmed cell death, is likely to enhance adipogenesis and tiny fibrosis production. Inflammation can be superimposed on the genetically determined substrate and usually involves both ventricles. Myocarditis can be acute or chronic with interstitial or scar fibrosis, or active chronic. In some cases, left ventricular involvement can be as important as right ventricle, characterizing biventricular dysplasia. In Naxos disease, ARVD is associated with an ectodermic dysplasia. The transmission mode is recessive.

Adipose Tissue↗
PubMed2000

[Behavior of 20 pacemakers as patients pass through 2 models of theft-detection doors].

Episodic interference between the magnetic field of anti thief devices in stores (Electronic Article Surveillance, EAS) and pacemaker function have been reported, but no systematic in vivo study. 20 implanted pacemakers from ten different companies, 1 VVIR, 1 VDD and 18 DDD, were tested with two different EAS systems. #1 uses a 7.5 and 5 kHz field of 670 microTesla and #2 a 72.3 Hz magnetic field, of 1.10 microTesla. Under continuous ECG monitoring, patients had to walk through, and then stay between the doors while moving, and finally to lay against each wall. This was done with their usual pacemaker setting, and then set at their highest sensitivity in the unipolar atrial and ventricular mode. No abnormal PM behavior was observed with standard settings (V sensitivity 1.4 to 5 mV, A sensitivity 0.25 to 1 mV, bipolar (14) or unipolar (6). When programmed at the highest sensitivity, the magnetic field was detected by 5 models, but only with ventricular sensing set at less than 1.2 mV. moreover this only occurred in #2 EAS and not in #1. This resulted in short inhibitions < 1.2 s, and in one safety zone pacing. All occurred in devices conceived before 1993 (6/14) and none after (0/6). EAS devices should not inhibit implanted PM with standard settings, especially in recent models. Ventricular sensitivity should not be programmed in the unipolar mode at 1.2 mV or less.

Adult↗
PubMed2000

[Effect of external electrical interference on pacemakers].

Cardiac pacemaker are sensitive to many kind of electromagnetic interference (EMI). However the low rate of reported effects is due to many protective features. Risks are minimal in everyday life conditions as airport detectors, electronic anti-thief systems, domestic electrical appliances and even mobile phones with the most recent models. Interference detection can be prevented by "medically correct" setting, with the use of bipolar sensing, and ventricular sensitivity above 2 mV. The effect of EMI from the industrial world are difficult to assess and need an individual study. The most important risks occur in the medical world, with the electrocutary, thransthoracic DC shocks, and magnetic resonance imaging.

Electromagnetic Fields↗
PubMed1999

Method for determining protein kinase substrate specificities by the phosphorylation of peptide libraries on beads, phosphate-specific staining, automated sorting, and sequencing.

A method is described for the elucidation of the peptide substrate phosphorylation specificity of a protein kinase. Peptide libraries with two to six degenerate positions and a length of seven or nine amino acids were generated directly on Sepharose beads by solid-phase peptide synthesis according to the split-and-mix procedure. The immobilized peptides were incubated with the catalytic subunit of the cyclic AMP-dependent protein kinase (PKA) as a model enzyme resulting in the phosphorylation of the beads that contain the recognition motif of the kinase. The beads were then stained with a new phosphate-monoester-specific fluorescent dye consisting of a complex of iron(III) with fluorescein-coupled iminodiacetic acid. A flow cytometer was used to analyze the phosphorylation efficiency and the beads with the highest phosphorylation degree were isolated by the use of a fluorescence-activated cell sorter. Pool sequencing of those beads revealed the preferred kinase motif. The results are in good agreement with data from the literature. The method lends itself to the rapid elucidation of the specificity of uncharacterized protein kinases.

Amino Acid Sequence↗
PubMed1999

Tubulin binding sites on gamma-tubulin: identification and molecular characterization.

gamma-Tubulin is essential to microtubule organization in eukaryotic cells. It is believed that gamma-tubulin interacts with tubulin to accomplish its cellular functions. However, such an interaction has been difficult to demonstrate and to characterize at the molecular level. gamma-Tubulin is a poorly soluble protein, not amenable to biochemical studies in a purified form as yet. Therefore basic questions concerning the existence and properties of tubulin binding sites on gamma-tubulin have been difficult to address. Here we have performed a systematic search for tubulin binding sites on gamma-tubulin using the SPOT peptide technique. We find a specific interaction of tubulin with six distinct domains on gamma-tubulin. These domains are clustered in the central part of the gamma-tubulin primary amino acid sequence. Synthetic peptides corresponding to the tubulin binding domains of gamma-tubulin bind with nanomolar K(d)s to tubulin dimers. These peptides do not interfere measurably with microtubule assembly in vitro and associate with microtubules along the polymer length. On the tertiary structure, the gamma-tubulin peptides cluster to surface regions on both sides of the molecule. Using SPOT analysis, we also find peptides interacting with gamma-tubulin in both the alpha- and beta-tubulin subunits. The tubulin peptides cluster to surface regions on both sides of the alpha- and beta- subunits. These data establish gamma-tubulin as a tubulin ligand with unique tubulin-binding properties and suggests that gamma-tubulin and tubulin dimers associate through lateral interactions.

Amino Acid Sequence↗
PubMed1999

Vaccine candidate MSP-1 from Plasmodium falciparum: a redesigned 4917 bp polynucleotide enables synthesis and isolation of full-length protein from Escherichia coli and mammalian cells.

The Plasmodium falciparum malaria parasite is the causative agent of malaria tropica. Merozoites, one of the extracellular developmental stages of this parasite, expose at their surface the merozoite surface protein-1 complex (MSP-1), which results from the proteolytic processing of a 190-200 kDa precursor. MSP-1 is highly immunogenic in humans and numerous studies suggest that this protein is an effective target for a protective immune response. Although its function is unknown, there are indications that it may play a role during invasion of erythrocytes by merozoites. The parasite-derived msp-1 gene, which is approximately 5000 bp long, contains 74% AT. This high AT content has prevented stable cloning of the full-size gene in Escherichia coli and consequently its expression in heterologous systems. Here, we describe the synthesis of a 4917 bp gene encoding MSP-1 from the FCB-1 strain of P. falciparum adjusted for human codon preferences. The synthetic msp-1 gene (55% AT) was cloned, maintained and expressed in its entirety in E.coli as well as in CHO and HeLa cells. The purified protein is soluble and appears to possess native conformation because it reacts with a panel of mAbs specific for conformational epitopes. The strategy we used for synthesizing the full-length msp-1 gene was toassemble it from DNA fragments encoding all of the major proteolytic fragments normally generated at the parasite's surface. Thus, after subcloning we also obtained each of these MSP-1 processing products as hexahistidine fusion proteins in E.coli and isolated them by affinity chromatography on Ni2+agarose. The availability of defined preparations of MSP-1 and its major processing products open up new possibilities for in-depth studies at the structural and functional level of this important protein, including the exploration of MSP-1-based experimental vaccines.

Animals↗
PubMed1999

Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter.

A cytogenetically cryptic (12;21) translocation is the most common molecular abnormality identified in childhood acute lymphoblastic leukemia (ALL), and it generates a chimeric TEL-AML1 protein. Fusion of the Helix-Loop-Helix (HLH) (also called the pointed) domain of TEL to AML1 has been suggested to convert AML1 from a transcriptional activator to a repressor. To define the structural features of this chimeric protein required for repression, we analysed the transcriptional activity of a series of TEL-AML1 mutants on the AML1-responsive interleukin-3 (IL-3) promoter, a potentially relevant gene target. Our results demonstrate that TEL-AML1 represses basal IL-3 promoter activity in lymphoid cells, and deletion mutant analysis identified three distinct domains of TEL-AML1 that are required for repression; the HLH (pointed) motif contained in the TEL portion of TEL-AML1, and both the runt homology domain (Rhd) and the 74 amino acids downstream of the Rhd that are present in the AML1 portion of the fusion protein. Although AML1B (and a shorter AML1 isoform, AML1A) have transcriptional activating activity on the IL-3 promoter, fusion of the AML1 gene to the TEL gene generates a repressor of IL-3 expression. Consistent with this activity, freshly isolated human ALL cells that contain TEL-AML1 do not express IL-3.

Child↗
PubMed1999

Virtual reality of the lower urinary tract in women.

Advances in computerized and imaging technology permit both students and doctors to depict the anatomy of the human pelvis more realistically than with previous methods. Further refinements outline fine pelvic structures, such as the nerve plexus, which may as a result be spared during major pelvic surgery, thus preserving the function of the bladder neck and urethra. Dynamic computerized tomography or magnetic resonance imaging, coupled with three-dimensional depiction of the lower urinary tract and its adjacent structures, enable visualization of the whole lower urinary tract and the pelvic floor musculature in both continent and incontinent women. In patients with a reconstructed lower urinary tract computer-assisted image processing shows the postoperatively altered topographical anatomy. This may be clinically useful for interpretation of unexpected findings with conventional imaging modalities, postoperative morbidity, and surgical planning of a lower abdominal reoperation. Examples of our own work regarding the innervation of female pelvic organs, dynamic depiction of the bladder and pelvic floor musculature during straining in normal and incontinent women, and the situation of female patients after undergoing an anterior pelvic exenteration with subsequent orthotopic neobladder procedure, are given. In addition, the data of these patients have been compiled for virtual reality endoscopy, which is useful for patient consent and for teaching residents, students and nurses.

Female↗
PubMed1999

Vitamin E treatment of focal segmental glomerulosclerosis: results of an open-label study.

Experimental data indicate that excessive production of reactive oxygen molecules contributes to progressive renal injury and that treatment with antioxidants attenuates this damage. Therefore, we investigated whether vitamin E supplementation could ameliorate renal disease and reduce proteinuria in children with a variety of kidney disorders. Vitamin E, 200 IU twice daily, was administered orally to 11 children with focal segmental glomerulosclerosis (FSGS) (group A) and 9 patients with miscellaneous kidney diseases (group B) [Henoch-Schönlein purpura nephritis (n=3), urinary tract anomalies (n=2), non-specific immune complex glomerulonephritis (n=2), IgA nephropathy (n=1), and reflux nephropathy (n=1)]. The duration of vitamin E treatment, when no other therapy was introduced, was 2.9+/-0.4 months. Proteinuria was determined by measuring the protein:creatinine ratio (mg/mg) in an early morning urine specimen. In children with FSGS, administration of vitamin E lowered the protein:creatinine ratio in 10 of 11 patients from 9. 7+/-5.1 to 4.1+/-1.1 (P<0.005). In contrast, among children with miscellaneous renal diseases, vitamin E had no beneficial impact on urinary protein excretion-protein:creatinine ratio 2.5+/-1.0 pre versus 2.4+/-1.2 post antioxidant. Vitamin E supplementation had no effect on glomerular filtration rate, serum albumin, or cholesterol concentration in either group of patients. These findings suggest that reactive oxygen molecules may play a more-prominent role in causing renal injury in patients with FSGS than in other kidney disorders. Antioxidant therapy may be a useful adjunct in the treatment of children with FSGS and proteinuria that is refractory to standard medical management.

Adolescent↗
PubMed1999

Radiofrequency catheter ablation of common atrial flutter: role of the eustachian valve.

INTRODUCTION: During radiofrequency catheter ablation of a common atrial flutter between the tricuspid annulus and the Eustachian valve "septal isthmus", double potentials were recorded along the Eustachian valve, previously described as an anatomical line of conduction block between the coronary sinus ostium and the inferior vena cava. RESULTS: Just before flutter termination, lengthening and beat to beat delay variations between the 2 components of the double potentials were correlated with simultaneous modifications of the flutter cycle length. CONCLUSION: The "septal isthmus" is a common pathway for the flutter wavefront and the impulse generating the second component of the double potential. It is also a good target for flutter ablation.

Adult↗
PubMed1999

[Behavioral pattern and behavioral characteristics of children in two pediatric clinics].

OBJECTIVES: To describe systematically patterns of behavior of children and parents in pediatric hospitals. METHODS: A questionnaire to systematically rate behavior of children and parents was administered by nurses to two independent samples in two different pediatric hospitals. At the von Haunersches Kinderspital, Klinikum Innenstadt of the Ludwig-Maximilian-University of Munich, 659 children were rated, at the Pediatric Hospital of the University of Freiburg, 484 children. Latent class analysis grouped children/parents according to similar patterns of behavior. RESULTS: In Munich a five-class model is most appropriate to classify children/parent behavior, in Freiburg a six-class model best first the data. Four classes in Munich and in Freiburg display nearly identical profiles. Three of them describe inconspicuous behavior of children in different age groups, whereas the fourth group describes disturbed children. These four groups classify 87% of the children in Munich and 73% of those in Freiburg. In Munich 25% of the children are rated as disturbed, as opposed to 39% in Freiburg. CONCLUSIONS: The questionnaire is suitable for everyday clinical practice. Results of both samples mostly correspond. Remaining differences are caused by type of hospital (pediatrics vs. pediatric surgery) and by the differing depth of nurses' rater training.

Child↗