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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 235 records · Page 13Linked to original sources
PubMed1992

Definition of immunogenic determinants of the human papillomavirus type 16 nucleoprotein E7.

Specific T lymphocyte lines and T cell clones were established from peripheral blood mononuclear cells of asymptomatic seropositive individuals employing synthetic peptides which correspond to the sequence of the human papillomavirus (HPV) type 16 transforming protein E7. Specificity analysis of T cells as determined by means of [3H] thymidine incorporation after stimulation with individual peptides revealed three immunogenic determinants of E7 that are recognised in association with at least two different HLA haplotypes. One N-terminal region (aminoacids 5-18) was recognised by one T cell line. T cell clones and the corresponding T cell line established from another donor responded to a different N-terminal (17-38) and to a C-terminal region (69-86). The N-terminal sequence 5-18 and the C-terminal determinant contain a periodicity of hydrophilic and hydrophobic residues that have been found in many T cell epitopes. Phenotypic characterisation of T cell clones by indirect immunofluorescence revealed that the T cell clones expressed the CD4 surface glycoprotein suggesting that the specific E7 determinants were recognised in association with major histocompatibility complex (MHC) class II molecules. With regard to functional properties, at least three T cell clones exhibited specific cytotoxic activity towards autologous B lymphocytes transformed by Epstein-Barr virus in the presence of the relevant HPV16 E7 peptides. The implications of these results regarding the development of vaccination strategies and host-virus interaction are discussed.

Amino Acid Sequence↗
PubMed1992

Critical checking of the radiological diagnosis of "complete remission" and "partial remission" following induction chemotherapy of small-cell lung cancer in the light of postoperative histological examination.

A multimodal therapy concept for small-cell lung cancer, which for patients with established pretherapeutic homolateral lymph-node metastases (N2) prescribes induction chemotherapy with subsequent resection as well as supplemental chemo- and radiotherapy, provided the opportunity to evaluate histologically the radiological diagnoses "complete remission" and "partial remission" using resection specimens. In 17 patients a 75% to 100% reduction in tumor size was achieved according to radiological diagnosis. Predictions of "no evidence of disease" or "evidence of disease" were only correct in ten cases. In the remaining seven cases, histology showed the radiological findings to be incorrect. This gives a 77% sensitivity for radiological diagnosis with no specificity. Moreover, differentiation between therapy effect on the primary tumor and on the N2 metastases gives similar results: sensitivity 64% and 67% respectively, specificity 33% and 25% respectively. It is concluded that, particularly after the tumor responds well to therapy, radiological techniques are unsuitable for establishing a diagnosis of "no evidence of disease" or "evidence of disease" in small-cell lung cancer. This is because on the one hand the radiological methods available do not permit clear differentiation between vital tumor tissue and necrosis or fibrosis, while on the other hand groups of vital tumor cells beyond the resolution power of X-ray technology will escape detection.

Antineoplastic Agents↗
PubMed1992

Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily.

The chick axon-associated surface glycoprotein neurofascin is implicated in axonal growth and fasciculation as revealed by antibody perturbation experiments. Here we report the complete cDNA sequence of neurofascin. It is composed of four structural elements: At the NH2 terminus neurofascin contains six Ig-like motifs of the C2 subcategory followed by four fibronectin type III (FNIII)-related repeats. Between the FNIII-like repeats and the plasma membrane spanning region neurofascin contains a domain 75-amino acid residues-long rich in proline, alanine and threonine which might be the target of extensive O-linked glycosylation. A transmembrane segment is followed by a 113-amino acid residues-long cytoplasmic domain. Sequence comparisons indicate that neurofascin is most closely related to chick Nr-CAM and forms with L1 (Ng-CAM) and Nr-CAM a subgroup within the vertebrate Ig superfamily. Sequencing of several overlapping cDNA probes reveals interesting heterogeneities throughout the neurofascin polypeptide. Genomic Southern blots analyzed with neurofascin cDNA clones suggest that neurofascin is encoded by a single gene and its pre-mRNA might be therefore alternatively spliced. Northern blot analysis with domain specific probes showed that neurofascin mRNAs of about 8.5 kb are expressed throughout development in embryonic brain but not in liver. Isolation of neurofascin by immunoaffinity chromatography results in several molecular mass components. To analyze their origin the amino-terminal sequences of several neurofascin components were determined. The NH2-terminal sequences of the 185, 160, and 110-135 kD components are all the same as the NH2 termini predicted by the cDNA sequence, whereas the other neurofascin components start with a sequence found in a putative alternatively spliced segment between the Ig- and FNIII-like part indicating that they are derived by proteolytic cleavage. A combination of enzymatic and chemical deglycosylation procedures and the analysis of peanut lectin binding reveals O- and N-linked carbohydrates on neurofascin components which might generate additional heterogeneity.

3T3 Cells↗
PubMed1992

Comparison of DDD and 'VVI-R like' pacing during moderate exercise: echo-Doppler study.

The non-invasive haemodynamic comparisons of DDD and 'VVI-R like' pacing at rest and during moderate exercise by echo Doppler are reported. Twelve patients (six males, six females, mean age 48.2 years) with a dual chamber pacemaker were submitted to a series of two exercise tests in a semi-supine position, the first test in DDD mode and the second test in a 'VVI-R like' mode: VVT mode, during which pacing rate was externally increased by chest wall stimulation. During the second test, the workload profile was matched to that of the first test (66 watts and same exercise stages) and ventricular pacing rate was incremented via chest wall stimulation and reproduced exactly the heart rate profile of the first test in DDD mode. The heart rate averaged 81 beats.min-1 at rest and reached 116 beats.min-1 during exercise. At rest and throughout exercise tests, aortic blood flow velocity spectra were continuously recorded on video tape and analysed with the calculation program of the echocardiograph. At rest, ejection time, flow velocity integral, flow acceleration and stroke volume differed between DDD and 'VVI-R like' mode while other parameters did not. During exercise all but two parameters differed. DDD mode especially was associated with a larger stroke volume (81.9 vs 70.9 ml; P less than 0.001) and cardiac output (9.24 vs 8.011.min-1; P less than 0.001) than VVI-R mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Proteinase-catalyzed conversion of a substance P-precursor peptide.

The protease-catalyzed conversion of peptides and proteins produced by recombinant DNA technology is a promising method for large-scale production of peptides including those with non-proteinogenic structural elements. As a model system we have investigated the proteinase-catalyzed modification of a chemically synthesized substance P-precursor. In the precursor peptide the residues of substance P(1-8) were flanked by tripeptide linkers on both sides. In the first step the C-terminal tripeptide amide was replaced by the authentic C-terminal tripeptide amide of substance P via alpha-chymotrypsin-catalyzed transpeptidation. The enzyme simultaneously attacks two peptide bonds in the precursor molecule leading to the formation of several side-products. The desired peptide was obtained with 25% yield. In the second step the other tripeptide linker was selectively and almost quantitatively removed from the N-terminus of the precursor via trypsin-catalyzed hydrolysis. This study demonstrates that substance P can be obtained from an engineered protein by proteinase-catalyzed processing.

Amino Acid Sequence↗
PubMed1992

Factors predicting success in DC catheter ablation of accessory pathways.

In a series of 33 patients with accessory pathways, 26 had successful catheter ablation (fulguration [23 patients] or modification [3 patients]) of their accessory pathway conduction, and could be considered as a clinical success. One hundred thirteen single discharge or double discharge shocks were delivered, and each shock was studied to reveal which parameters were important to predict the success or failure of catheter ablation. Double discharge shocks resulted in successful accessory pathway modification or ablation twice as often as single discharge shocks (32% vs 16%). This effect was more pronounced in left lateral accessory pathways (48% vs 4%). Shocks in the electrophysiologically defined ventricular zone were more likely to be successful (33%) than shocks delivered in the atrial zone (14%), irrespective of accessory pathway location. The presence of a probable Kent potential was the parameter most strongly associated with success. The parameter most strongly associated with failure, with a 100% negative predictive value, was the absence of earliest activation recorded on the ablating catheter prior to shock delivery. An AV interval of < 60 msec significantly divided the successful from the unsuccessful shocks (P = 0.01). The VA interval during orthodromic reciprocating tachycardia or right ventricular stimulation did not allow for significant division into successful and unsuccessful attempts in this relatively short series. VA intervals, when longer, were predictive of failure but, when shorter, had low positive predictive value. Mean follow-up in 25 successful patients was 15 +/- 6 months. All patients did well in the follow-up period. Neither those patients with ablation nor modification of the accessory pathway had recurrent episodes of tachycardia or required pharmacological treatment for control of arrhythmias.

Adult↗
PubMed1992

[Gene amplification with PCR and sequence specific HLA oligonucleotide typing].

Genetic polymorphism in the HLA class II region has been identified by the analysis of the polymerase chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant typing kit enables HLA typing independent of gene expression and quality of lymphocytes. One of the advantages of this technique is that the definition of splits is much better than typing by serology.

Base Sequence↗
PubMed1992

[Right ventricular dysplasia].

Arrhythmogenic right ventricular dysplasia is responsible for ventricular tachycardia affecting an apparently healthy heart. It can sometimes lead to sudden death, which may be the presenting symptomatology of the disease. It results from fibro-adipose infiltration of the free wall of the right ventricle, and sometimes of the septum, possibly secondary to myocarditis. The prognosis depends upon the quality of the left ventricle. If it is healthy, the only risk is that of arrhythmia. Treatment using anti-arrhythmic drugs is most often effective and, with proper management, the prognosis is good and the risk of sudden death eliminated. If the left ventricle is abnormal, there is the risk that dysplasia associated with arrhythmia will progress to right then congestive cardiac failure in the context of a dilated idiopathic cardiomyopathy with ventricular tachycardias originating on the right side. Arrhythmogenic right ventricular dysplasia is a notable cause of sudden death in athletes. Routine screening of such individuals is justified, as is that of those with high risk occupations (locomotive and vehicle drivers, etc.).

Adolescent↗
PubMed1992

[VVI mode cardiac pacing: cause or risk factor of cerebral embolism?].

Epidemiological studies suggest that VVI pacing is associated with a higher risk of embolic complications than atrial or dual chamber pacing. However, no studies have been performed on pacemaker patients admitted to a neurological department with a cerebral embolism. The authors report the cases of 8 patients (6 men and 2 women) with an average age of 74 years and having the following characteristics: 1) a cerebral embolism, 2) a permanent cardiac pacemaker (7 VVI and 1 DDD mode). The average delay between implantation of the pacemaker and the neurological complication was 31 months. Cardiological investigations at the time of admission showed: a clinically evident cause of cardiac embolism in 3 cases (2 with VVI and 1 with DDD pacing); paroxysmal or permanent atrial fibrillation in 4 cases with VVI pacing at the time of the embolic event (in only one case at the time of implantation); various echocardiographic abnormalities in 6 of the 7 patients who underwent this examination, mainly left atrial dilatation (6/7), septal wall motion abnormalities in all related to ventricular pacing and unexplained left ventricular dilatation in 2 patients with VVI pacemakers. These results suggest that although the etiology of cerebral embolism was probably multifactorial in some patients, VVI packing probably a predisposing role, though not the only cause, and could be considered to be an embolic risk factor as suggested by previous epidemiological studies. These preliminary retrospective data should be interpreted cautiously taking into account the small population size. Prospective studies on pacemaker patients with cerebral embolism are required.

Aged↗
PubMed1992

[Ventricular tachycardia in a patient with rate-responsive cardiac pacemaker].

The authors report a case of syncopal ventricular tachycardia in a patient with a respiratory-dependent rate responsive pacemaker, followed-up for valvular heart disease with severe left ventricular dysfunction and sustained atrial and ventricular arrhythmias. The introduction of low dose betablocker therapy with reinforcement of the treatment of cardiac failure controlled the ventricular arrhythmia, after suppression of the data responsive function had been shown to be ineffective. The authors discuss the role of the rate responsive function in the triggering of the ventricular tachycardias.

Aged↗
PubMed1992

[Ventricular anti-arrhythmic treatments during postinfarction].

Antiarrhythmic agents may be prescribed in the post-infarction period either as systematic therapy to prevent sudden death or as prophylactic treatment against recurrences of documented life-threatening arrhythmias. Systematic therapy or even the treatment of symptomatic ventricular extrasystoles by Class IC anti-arrhythmics is associated with an increased risk, especially in patients with a low risk of sudden death at the outset. Betablockers are effective on symptoms: they are not always effective on the arrhythmia but at least they do not aggravate the mortality of these patients. However, for high risk patients with post-infarction left ventricular dysfunction, betablockers are the only drugs which have a proven efficacy: they should therefore be prescribed, especially those whose efficacy has been demonstrated, at the same dosages as those used in clinical trials. Preventive treatment of sustained ventricular tachycardia should be chosen with respect to the patient's hemodynamic status. When the ejection fraction is under 40%, amiodarone and betablockers are the drugs of first intention, with controls of their efficacy by the inability to induce or the slowing of the tachycardia rhythm during endocavitary electrophysiological studies.

Adrenergic beta-Antagonists↗
PubMed1992

[Gene amplification with PCR and sequence-specific HLA oligotyping].

Genetic polymorphism in the HLA-class II region has been identified by the analysis of the polymerase-chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant-typing kit [2] enables HLA-typing independent of gene expression and lymphocytes quality. One of the advantages of this technique is that the definition of subtypes is much better than is typing by serology.

Amino Acid Sequence↗
PubMed1991

Cloned neuronal IK(A) channels reopen during recovery from inactivation.

The kinetic behaviour and functional role of potassium ion (K+) channels mediating a fast-inactivating K+ current (IK(A)) has been widely discussed. Activating in the subthreshold range of excitation, IK(A) channels are assumed to reduce the excitatory effect of depolarizing membrane currents in a time-dependent manner. Here we report that IK(A) channels not only open in response to a depolarization but open again after repolarization of the membrane. Although the current in response to the depolarization is rapidly inactivating, the current elicited by repolarization declines slowly and produces long-lasting afterhyperpolarizations under current-clamp conditions. This implies an additional physiological role for IK(A) channels, particularly those that activate positive to the threshold of excitation. The underlying biophysical mechanism was studied by fast-application of peptides corresponding to the N-terminal end of the IK(A) channel proteins. It was found to be a voltage-dependent release of the inactivation gate.

Amino Acid Sequence↗
PubMed1991

Involvement of pertussis toxin-sensitive G-proteins in the hormonal inhibition of dihydropyridine-sensitive Ca2+ currents in an insulin-secreting cell line (RINm5F).

Adrenaline inhibits insulin secretion via pertussis toxin-sensitive mechanisms. Since voltage-dependent Ca2+ currents play a key role in insulin secretion, we examined whether adrenaline modulates voltage-dependent Ca2+ currents of the rat insulinoma cell line, RINm5F. In the whole-cell configuration of the patch-clamp technique, dihydropyridine- but not omega-conotoxin-sensitive Ca2+ currents were identified. Adrenaline via alpha 2-adrenoceptors inhibited the Ca2+ currents by about 50%. Somatostatin which also inhibits insulin secretion was less efficient (inhibition by 20%). The hormonal inhibition of Ca2+ currents was not affected by intracellularly applied cAMP but blocked by the intracellularly applied GDP analog guanosine 5'-O-(2-thiodiphosphate) and by pretreatment of cells with pertussis toxin. In contrast to adrenaline and somatostatin, galanin, another inhibitor of insulin secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner. Immunoblot experiments performed with antibodies generated against synthetic peptides revealed that membranes of RINm5F cells possess four pertussis toxin-sensitive G-proteins including Gi1, Gi2, Go2, and another Go subtype, most likely representing Go1. In membranes of control but not of pertussis toxin-treated cells, adrenaline via alpha 2-adrenoceptors stimulated incorporation of the photo-reactive GTP analog [alpha-32P]GTP azidoanilide into pertussis toxin substrates comigrating with the alpha-subunits of Gi2, Go2, and the not further identified Go subtype. The present findings indicate that activated alpha 2-adrenoceptors of RINm5F cells interact with multiple G-proteins, i.e. two forms of Go and with Gi2. These G-proteins are likely to be involved in the adrenaline-induced inhibition of dihydropyridine-sensitive Ca2+ currents and in other signal transduction pathways contributing to the adrenaline-induced inhibition of insulin secretion.

Animals↗
PubMed1991

Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.

Modulation of neuronal excitability by regulation of K+ channels potentially plays a part in short-term memory but has not yet been studied at the molecular level. Regulation of K+ channels by protein phosphorylation and oxygen has been described for various tissues and cell types; regulation of fast-inactivating K+ channels mediating IK(A) currents has not yet been described. Functional expression of cloned mammalian K+ channels has provided a tool for studying their regulation at the molecular level. We report here that fast-inactivating K+ currents mediated by cloned K+ channel subunits derived from mammalian brain expressed in Xenopus oocytes are regulated by the reducing agent glutathione. This type of regulation may have a role in vivo to link metabolism to excitability and to regulate excitability in specific membrane areas of mammalian neurons.

Amino Acid Sequence↗