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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 307 records · Page 17Linked to original sources

Ablation of the slow-conduction area in chronic ventricular tachycardia.

The ablation techniques, which derive from surgical approach in the treatment of ventricular tachycardia, were originally based on the modification of conduction in the so-called site of origin of the arrhythmia. A reentrant tachycardia involves two areas of conduction, one which consists of normal tissue, and the other with slow-conduction properties isolated from the previous structure. We now think that a more appropriate place to deliver the shock should be the area of slow conduction. The purpose of this paper is to review the main electrophysiological characteristics of this tissue, which could be interesting markers to identify the site where the shock should be delivered.

Action Potentials↗

Mapping of functional domains in Fos and Jun proteins using epitope-specific antibodies.

A panel of epitope-specific antibodies, directed against c-Fos, c-Jun, and FosB derived oligopeptide sequences, was generated and used to study the interaction of Fos and Jun proteins and the binding of the Fos/Jun complex to the AP1-binding site (TRE). Our results strongly support results previously obtained by site-directed mutagenesis experiments. The leucine zipper is the major site of interaction between Fos and Jun. Antibodies directed against this domain of Fos bound free Fos protein efficiently, but were unable to recognize Fos within the Fos/Jun complex. In contrast, all other Fos epitope-specific antibodies showed similar reactivity with both free and complexed Fos. Antibodies directed against sequences adjacent to the leucine zipper inhibited formation of the complex. This may suggest that amino acids in the vicinity of the leucine zipper may also play some role in the formation of the protein complex. Binding of Fos/Jun to the TRE was inhibited only by antibodies directed against the basic regions in Fos or Jun previously suggested to represent the DNA binding sites. The fact that very similar results were obtained by two totally different strategies, i.e., mutagenesis experiments and domain mapping using epitope-specific antibodies, lends strong support to the proposed domain structure of Fos and Jun family members.

Amino Acid Sequence↗

[Electrophysiology in evaluating the treatment of sustained monomorphic ventricular tachycardia: criteria for efficacy].

The authors studied the influence on recurrence and mortality of induced ventricular arrhythmias during electrophysiological studies performed to assess the efficacy of treatment of sustained monomorphic ventricular tachycardia. One hundred and twenty-six consecutive patients investigated from 1981 to 1988 were included. The underlying pathology was chronic myocardial infarction (N = 56), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31) and there were 15 idiopathic cases. All these tachycardias could be induced during the control study. A second test was performed after instituting treatment. This was maintained whatever the result of the electrophysiological study except in patients in whom the tachycardia rate was over 130/mn and/or poorly tolerated. Recurrences were defined as the observation of tachycardia with the same morphology and/or the occurrence of sudden death. Follow-up averaged 29 +/- 21 months. The absence of recurrence and survival were assessed by the Kaplan-Meier method and Logrank's test. It was not possible to induce any arrhythmia after treatment in 52 patients (41%). The prevalence of absence of recurrence in this group was 0.863. If the induction of ventricular fibrillation, doublets or short runs of VT (N less than 6 with no recurrences) are included, the value increased to 0.877. These patients were considered to be non-inducible. The prevalence of absence of recurrence of arrhythmia in patients in whom it was possible to induce sustained ventricular tachycardia of the same morphology as the clinical arrhythmia was 0.512 (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Congenital and acquired right ventricular dysplasia].

Arrhythmogenic right ventricular dysplasia has been described as a developmental malformation occurring during foetal life. This explains a number of familial cases of this condition where dysplasia was the result of a genetic abnormality transmitted in an autosomal dominant mode with incomplete penetrance. Histological data of peroperative or post-mortem specimens of 27 cases showed a large number of grape-like lymphoplasmocytic infiltrations. These appearances suggest an inflammatory origin of the disease, most probably related to an infective etiology. The authors suggest that in addition to the congenital form there may also be a possibility of acquiring arrhythmogenic right ventricular dysplasia after an episode of myocarditis.

Adult↗

[Value and limitations of Holter monitoring and electrophysiologic testing in the evaluation of the treatment of sustained monomorphic ventricular tachycardia].

The authors studied the value and limitations of Holter monitoring and electrophysiological investigation in the evaluation of treatment of sustained monomorphic ventricular tachycardia (VT). One hundred and twenty-four consecutive patients were included in the study from January 1981 to February 1988. The etiologies were chronic myocardial infarction (N = 54), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31), and idiopathic VT (N = 15). All the tachycardias could be induced during baseline electrophysiological investigations and presented as complex ventricular arrhythmias on the Holter recordings. The investigations were repeated after treatment which was maintained irrespective of the results, unless the tachycardia which was induced or recorded was over 130 cycles/min and/or poorly tolerated. Recurrence was defined as the recording of VT in the absence of a change of treatment and/or the occurrence of sudden death. The follow-up period averaged 29 +/- 21 months. The Kaplan-Meier method was used to study the prevalence of absence of recurrence and survival rates. We observed 28 recurrences of VT and there were 21 deaths. Eighty-five per cent of patients had normal Holter monitoring after treatment. The prevalence of absence of recurrence was 0.751 when the Holter was normal and 0.485 when an arrhythmia was recorded (p = 0.03). The sensitivity was 25 per cent and the specificity 88 per cent. The survival rates were 0.66 and 0.585 respectively (p = 0.008). Fifty-three per cent of patients remained inducible after treatment with a prevalence of absence of recurrence of 0.572. This value rose to 0.877 when VT could not be induced (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

[Case report: aneurysm of the arteria lusoria--CT and MRI].

CT and MR were used to evaluate a right paramediastinal and retrotracheal mass in a 77-year old woman. An aneurysm of an aberrant right subclavian artery with a lumen partially occluded by parietal clots was clearly diagnosed by both methods. The value of CT and MRI is discussed with regard to planning surgical intervention.

Aged↗

[Retinoid-induced changes of the bones and ligaments].

Bone and ligament lesions induced by systemic retinoids (premature epiphyseal closure, osteophytes, calcification of ligaments, osteoporosis, etc.) are radiologically nonspecific. We assessed the incidence of "possibly retinoid-induced bone and ligament lesions" (MRKBV) in 46 patients (aged 24-82 years) who had been treated with various systemic retinoids for a variety of chronic dermatoses for an average of 4.5 years and compared the data with observations in a similarly structured group of control patients. All types of MRKBV were found more frequently in the retinoid group (41.3% vs 30.2%) and were more severe. Differences were only slight, however, being statistically significant only for moderate and severe MRKBV and for calcification of ligaments. Within the retinoid group, MRKBV were strikingly correlated with age, whereas no correlation was found with duration of treatment, mean daily and cumulative retinoid dose, underlying dermatosis, type of retinoid used or presence of other retinoid side-effects. Within the control group, MRKBV were also correlated with age, although to a lesser degree. We conclude that retinoids amplify and accelerate physiological and pathophysiological remodelling of the bones, thereby producing a varied range of lesions, which are characteristic for the age and the individual constitution of the patient treated. Retinoid-induced bone and ligament lesions, as a rule, do not cause subjective symptoms and are not associated with predictive or accompanying laboratory values. Also, MRKBV are not paralleled by other retinoid-induced side-effects (hyperlipidaemia, elevation of liver transaminases). In 16 cases in which bone X-ray had been performed prior to retinoid treatment, no indication of reversibility of MRKBV was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Termination of health benefits for Pittston mine workers: impact on the health and security of miners and their families.

Mine workers represented by the United Mine Workers of America (UMWA) have had comprehensive medical care coverage since 1950. On February 1, 1988, UMWA employees of the Pittston Coal Group had their health care benefits abruptly terminated. Renewal of these benefits became a major reason for the subsequent UMWA strike against Pittston. In December, 1989, physician interviewers were organized to document the human experience of this termination of health care benefits. This report summarizes these interviews, and concludes that the UMWA experience in the Pittston coal fields is one example of the barriers to health care experienced by an increasing proportion of the United States population.

Adolescent↗

[Revision of criteria for locating the accessory pathway by electrocardiogram in Wolff-Parkinson-White syndrome. A new algorithm].

A new algorithm has been developed for locating the anomalous conduction pathway from the ECG which is based on 62 cases of Wolff-Parkinson-White syndrome with a single anomalous conduction pathway, located by epicardial mapping, i.e. 28 on the free edge of the left ventricle (FL), 22 posterior septal, including 11 left (LPS) and 11 right (RPS), 8 right lateral (RL) and 4 right anterior septal (RAS). Criteria use the orientation of the delta wave and the QRS complex in the right precordial leads and the frontal plane, combined with the presence or absence of left or right ventricular hypertrophy. The algorithm is worked out in 15 steps, each criterion being applied only if the preceding criterion has not been observed. It identifies 100 per cent of the study population. This high specificity has been checked on independent series which include 55 FL pathways, 9 LPS, 17 RPS, 10 RL and 5 RAS. Only 2 LPS pathways were identified as FL and 1 RPS pathway as RL corresponding, perhaps, to "borderline" cases. The ECG thus remains the simplest non invasive examination for locating the ventricular origin of anomalous conduction pathways.

Algorithms↗

[Effect on atrioventricular conduction of a new calcium antagonist: lacidipine. Evaluation by the Holter method].

The modification of AV conduction induced by 4 mg b.i.d. of lacidipine (L), a new calcium antagonist, was assessed by studying the changes in ventricular rhythm in 10 patients with stable chronic atrial fibrillation (mean age 71 +/- 15) by daily Holter recordings. The study was single blind versus placebo (P), nifedipine (N) 10 mg b.i.d. and for five patients diltiazem (D) 120 mg b.i.d. Five or seven consecutive 24 hours Holter were recorded in the following order: P, P, N or L, P, N or L, D, D. For each hour, an RR histogram was drawn and the 10 per cent and 90 per cent values of the cumulative cycle length curve were computed, as were the total number of QRS, and the mean value of RR intervals. The correlation coefficient between the number of QRS from the same hour on different days, the Student t test between the mean hourly RR interval values and the comparison between the histograms did not demonstrate a significant difference between the placebo, the nifedipine and the lacidipine periods. The only significant changes were induced by diltiazem (p less than 0.01), with a significant prolongation of the RR intervals. This suggests that lacidipine, like nifedipine, has no effect on AV conduction.

Aged↗

Human leukocyte elastase inhibitors: designed variants of human pancreatic secretory trypsin inhibitor (hPSTI).

Variants of human secretory trypsin inhibitor were constructed with the aim of producing inhibitors specific for human leukocyte elastase. Models of the hPSTI/HLE and hPSTI/chymotrypsin complexes were generated by computer aided protein design and used to plan better HLE inhibitors. This resulted in the production of the strongest and most specific inhibitors of HLE known.

Animals↗

A yeast nucleolar protein related to mammalian fibrillarin is associated with small nucleolar RNA and is essential for viability.

In order to study the structural and functional organization of the eukaryotic nucleolus, we have started to isolate and characterize nucleolar components of the yeast Saccharomyces cerevisiae. We have identified a major 38 kd nucleolar protein (NOP1), which is located within nucleolar structures resembling the dense fibrillar region of mammalian nucleoli. This 38 kd protein is conserved in evolution since affinity-purified antibodies against the yeast protein stain the nucleolus of mammalian cells in indirect immunofluorescence microscopy and the yeast protein is decorated by antibodies directed against human fibrillarin. Affinity-purified antibodies against the yeast NOP1 efficiently precipitate at least seven small nuclear RNAs involved in rRNA maturation. We have cloned the gene encoding the yeast NOP1 protein. Haploid cells carrying a disrupted copy of the gene are not viable, showing that NOP1 is essential for cell growth. The gene codes for a 34.5 kd protein which contains glycine/arginine rich sequence repeats at the amino terminus similar to those found in other nucleolar proteins. This suggests that NOP1 is in association with small nucleolar RNAs, required for rRNA processing and likely to be the homologue of the mammalian fibrillarin.

Amino Acid Sequence↗

Treatment of rhythm disorders by endocardial fulguration.

The fulguration procedure was originally introduced for the treatment of supraventricular arrhythmias by a pervenous interruption of His bundle conduction. This procedure has been extended to the treatment of almost any cardiac arrhythmia resistant to antiarrhythmic drug therapy. Recent results suggest that ablation could be selectively applied to the site of abnormal conduction. Overall results obtained at the Jean Rostand Hospital are reported for a series of 104 patients ranging in age from 14 to 83 years with atrial, junctional and ventricular tachycardias. The follow-up extends up to 65 months. Clinical efficacy, defined as a control of the arrhythmias by fulguration used alone or in association with drug therapy that was previously ineffective, lead to a success rate ranging from 80 to 85%. Mortality was less than 10% in the worst situation (chronic resistant ventricular tachycardia). Mortality was always related to inappropriate protocols. Therefore, fulguration, which was originally reserved to treat the most difficult cases, is now considered for non-life-threatening but incapacitating arrhythmias. Despite these results the technique is not simple. Fulguration should be performed by groups knowledgeable in electrophysiology and with expertise in high voltage electricity and biophysics.

Arrhythmias, Cardiac↗

Cloning, sequencing and expression of the L-2-hydroxyisocaproate dehydrogenase-encoding gene of Lactobacillus confusus in Escherichia coli.

The gene (L-HicDH) encoding L-2-hydroxyisocaproate dehydrogenase (L-HicDH) from Lactobacillus confusus was cloned in Escherichia coli. A 69-mer oligodeoxyribonucleotide probe, derived to be complementary to the N-terminal amino acid (aa) coding sequence, was used for screening. The complete nucleotide (nt) sequence of the L-HicDH gene was determined. The 5'-end of the mRNA was mapped by primer extension and the promoter identified. Downstream from the L-HicDH gene is a typical Rho-independent terminator. The aa sequence of L-HicDH, deduced from the nt sequence, has an overall similarity of 30% to the aa sequence of L-lactate dehydrogenase (L-LDH) from Lactobacillus casei. The aa residues involved in binding of coenzyme and substrate are highly conserved in L-HicDH with respect to prokaryotic and eukaryotic L-LDHs. The L-HicDH gene could be expressed under control of phage lambda 'Leftward' and 'rightward' promoters in E. coli up to 35% of total cell protein. The enzyme produced under these conditions exhibits full specific activity and is found exclusively in soluble form.

Alcohol Oxidoreductases↗

Probing hairpin structures of small DNAs by nondenaturing polyacrylamide gel electrophoresis.

The influence of temperature on the electrophoretic mobility of small DNAs, capable of forming hairpin structures, is investigated under nondenaturing conditions. Three series of hairpin-forming DNAs containing different numbers of thymidine, deoxyadenosine, and deoxyguanosine residues in their loop, and an identical sequence in the helical region, are analyzed. All show enhanced electrophoretic mobility if they adopt the hairpin conformation. The same quantitative relationship between hairpin formation and increase in electrophoretic mobility is observed for all of the three series. The constancy of this increase suggests a dependence of electrophoretic acceleration on the length of the helical region. A possible application of nondenaturing electrophoresis is monitoring the hairpin/coil transition. Another possible application is the detection of dimers formed by partially self-complementary sequences. This dimer formation is detected for completely complementary DNAs, whereas sequences which might form imperfect double helices, especially those with three bulged-out nucleotides, prefer hairpin formation. The possible applications are experimentally approached and discussed.

DNA↗

The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain.

The nuclear protein LF-B1 (also referred to as HNF-1) is a transcription activator required for the expression of several liver-specific genes. LF-B1 has been purified to homogeneity from rat liver nuclear extracts. The sequence of the protein has been partially determined and, subsequently, overlapping cDNA clones containing the entire open reading frame of LF-B1 were isolated. The full-length cDNA encodes a 628 amino acid protein and directs the synthesis in vitro of a protein capable of binding DNA with the same specificity as LF-B1. The cDNA was recombined into a vaccinia virus vector and active LF-B1 was obtained from infected HeLa cells. Addition of the vaccinia recombinant protein to rat spleen extracts results in activation of transcription of an LF-B1-dependent promoter. The DNA binding domain of LF-B1 is located in the amino-terminal part of the protein and displays distant structural similarity to the homeobox domain. The distribution of LF-B1 mRNA is restricted to liver, which correlates with the tissue-specific expression of its target genes.

Amino Acid Sequence↗