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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 325 records · Page 18Linked to original sources

[Treatment of ventricular tachycardia using endocavitary fulguration. 5 years' experience with 53 cases].

53 patients, between the ages of 14 and 76 years, presented a ventricular tachycardia which was treated by the fulguration method. 19 resulted from a complication of an old myocardial infarction, 15 from a right arrhythmogenic ventricular dysplasia, 8 from a dilated myocardiopathy. 10 patients presented idiopathic tachycardias: 3 originated in the infundibulum of the right ventricule and 7 from the left ventricle. One case originated from a surgical scar of the infundibulum. These tachycardias were continuous or occurred daily in half of the cases, or presented monthly recurrences. 1 to 17 shocks were delivered at each session, 143 on the right, 112 on the left and 2 transseptal. Four patients died from haemodynamic deterioration prior to the shock. The other 49 patients are considered as clinical successes. Three died within the first three months of low cardiac output without any recurrence of the tachycardia. 26 did not longer present any recurrent tachycardia and were not given any preventive anti-arrhythmic treatment. 19 developed recurrence or could be triggered off again, but the anti-arrhythmic medications which were ineffective, become effective. One female patient again developed slavos of ventricular tachycardia after a few months. Seven patients died 4 to 18 months after fulguration, and three presented a sudden death. They belong to the group with medically treated recurrences. This technique is a major factor in the therapeutic strategy of ventricular tachycardias, either used alone or associated with a pharmacological treatment.

Adolescent↗

Tissue distribution of beta 1- and beta 2-subunits of regulatory guanine nucleotide-binding proteins.

The beta-subunit of G-proteins occurs in two forms (beta 1 and beta 2), which differ in their primary structure as derived from cDNA clones and in their mobilities on SDS gels (36 and 35 kDa, respectively). To assess the tissue distribution of the two forms of beta-subunits, we synthesized peptides corresponding to defined regions of beta 1- and beta 2-subunits and injected them into rabbits; the antisera obtained reacted either with both beta-subunits or specifically with the beta 1- or the beta 2-subunit. They were used to identify the two beta-subunits in membranes prepared from various rat tissues and from human placenta. The concentration of total beta-subunits was high in rat brain and lung, human placenta, rat kidney, liver and spleen; it was much lower in rat erythrocytes, cardiac and skeletal muscle. In all tissues studied, both beta 1- and beta 2-subunits were detectable. In most tested tissues, the two forms were about equally distributed, whereas in the placenta, the beta 2-subunit was found to occur in approx. 2-fold excess over the beta 1-subunit. Our results demonstrate that both beta-subunits are widely distributed. In the majority of tissues, levels of beta 2-subunits are very similar to those of beta 1-subunits. Thus, the abundance of beta 2-subunits as compared to that of the beta 1-subunit is considerably higher than was previously estimated by measuring the respective mRNA levels.

Amino Acid Sequence↗

Homology of 54K protein of signal-recognition particle, docking protein and two E. coli proteins with putative GTP-binding domains.

Most proteins exported from mammalian cells contain a signal sequence which mediates targeting to and insertion into the membrane of the endoplasmic reticulum (ER). Involved in this process are the signal-recognition particle (SRP) and docking protein (DP), the receptor for SRP in the ER membrane. SRP interacts with the signal sequence on nascent polypeptide chains and retards their further elongation, which resumes only after interaction of the arrested ribosomal complex with the docking protein. SRP is a ribonucleoprotein particle comprising a 7S RNA and six polypeptides with relative molecular masses (Mr) of 9,000 (9K) 14K, 19K, 54K, 68K and 72K (ref. 1). The 9K and 14K proteins are essential for elongation arrest and the 68K-72K heterodimer is required for docking to the ER membrane. The 54K protein binds to the signal sequence when it emerges from the ribosome. Docking protein consists of two polypeptides, a 72K alpha-subunit (DP alpha) and a 30K beta-subunit (DP beta). No components structurally homologous to SRP and docking protein have yet been found in yeast or Escherichia coli. To understand the molecular nature of the interaction between the signal sequence and its receptor(s) we have characterized a complementary DNA coding for the 54K protein of SRP. Significant sequence homology was found to part of DP alpha and two E. coli proteins of unknown function. The homologous region includes a putative GTP-binding domain.

Amino Acid Sequence↗

The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH- and calcium-induced aggregation.

Secretogranin II (previously also called chromogranin C) is a tyrosine-sulfated secretory protein found in secretory granules in a wide variety of endocrine cells and neurons. Here, we have determined the primary structure of human secretogranin II from a full length cDNA clone and have investigated its properties, predicted from the sequence, by studying the behavior of purified secretogranin II under conditions characteristic of the milieu of secretory granules. Analysis of a 2.35-kilobase cDNA clone isolated from a human pituitary library and identified as secretogranin II by various criteria showed that human presecretogranin II is a 617-residue polypeptide containing an NH2-terminal located signal peptide. Secretogranin II lacks the disulfide-bonded loop structure near the NH2 terminus which is conserved in chromogranin A and chromogranin B (secretogranin I), two other widespread constituents of neuroendocrine secretory granules, but like the latter two proteins contains (i) an -E-N/S-L-X-A/D-X-D/E-X-E-L- motif and (ii) multiple potential dibasic cleavage sites for the generation of smaller, perhaps biologically active peptides. Another structural feature that secretogranin II shares with chromogranin A and chromogranin B (secretogranin I) is the abundance of acidic residues all along the polypeptide chain whose negative charge must somehow be neutralized to allow condensation and packaging of the protein into secretory granules. Experiments with purified secretogranin II showed that in the presence of 10 mM calcium at pH 5.2, conditions characteristic of the milieu of neuroendocrine secretory granules, this protein formed aggregates. Immunoglobulin G, a secretory protein that in vivo is not packaged into secretory granules, did not form aggregates under these in vitro conditions and was excluded from the secretogranin II aggregates. Very little aggregation of secretogranin II was observed in the absence of calcium at pH 5.2 or in the presence of calcium at neutral pH. In vivo, ammonium chloride, which is known to neutralize the pH of acidic intracellular compartments, inhibited the packaging of newly synthesized secretogranin II into secretory granules. Our results suggest that the low pH- and calcium-induced aggregation of secretogranin II may be important for the organization of the secretory granule matrix and raise the possibility that aggregation of secretogranin II may be involved in its sorting to secretory granules.

Amino Acid Sequence↗

Expression of human parathyroid hormone in Escherichia coli.

Human parathyroid hormone (PTH) has been expressed in Escherichia coli as a cro-beta-galactosidase-hPTH fusion protein under temperature-sensitive control of the lambda phage PR promoter. The lacZ gene has been truncated to a different extent revealing an optimal length of the prokaryotic peptide portion between 199 and 407 amino acid residues. Up to 250 mg of pure fusion protein have been obtained from 1-liter E. coli culture by stepwise solubilization with urea. The linkage between the prokaryotic and the eukaryotic protein moiety consists of an Asp-Pro peptide bond and therefore is easily cleavable by acid treatment. A simple procedure for the purification of the hormone is described. The resulting recombinant hormone reacts with anti-PTH antibodies and stimulates renal adenylate cyclase identically to bovine or human PTH.

Adenylyl Cyclases↗

[Therapeutic management of the Wolff-Parkinson-White syndrome].

Reentry tachycardia and atrial fibrillation occur in 12 to 36 per cent of patients with Wolff-Parkinson-White (WPW) syndrome. The severity of the arrhythmia depends on the frequency of attacks, on the heart rate in tachycardia and on the condition of the underlying myocardium. Moreover, ventricular fibrillation has been observed in some cases of atrial fibrillation with a fast ventricular response due to accessory pathways with very short refractory periods. This is the mechanism of sudden death in WPW syndrome. The prognosis can be assessed by atrial pacing, now often performed by the transoesophageal method. pacing makes it possible to measure the atrial vulnerability and the value of the shortest interval conducted through the accessory pathway. Indirect methods, such as exercise electrocardiogram or ajmaline injection, are less specific in predicting the characteristics of the accessory pathway. The therapeutic approach depends on the symptoms. Asymptomatic patients or those who present with only rare episodes of reciprocal tachycardia can be left untreated, but a preventive medical treatment is necessary in patients with atrial fibrillation or frequent attacks of tachycardia. When this treatment is ineffective or complicated by side-effects, a more radical therapy must be proposed. For the last 20 years this has been surgery, but nowadays catheter ablation of the accessory pathway gives similar results in skilled hands and tends to replace surgery.

Electrosurgery↗

Molecular cloning of the chicken myelomonocytic growth factor (cMGF) reveals relationship to interleukin 6 and granulocyte colony stimulating factor.

Normal as well as retrovirally transformed avian myeloid precursor cells require the colony stimulating factor cMGF for their survival, proliferation and colony formation in vitro. cMGF has been shown to be a glycoprotein which is active in the picomolar concentration range. Co-expression of kinase type oncogenes in v-myb or v-myc transformed myeloid cells induces cMGF expression and confers factor independence via an autocrine mechanism. Here we describe the molecular cloning of cMGF from a myeloblast cDNA library and show that it is a 201 amino acid residue secretory protein which is modified by signal peptide cleavage and glycosylation during translocation into the lumen of membrane vesicles. A bacterially expressed trpE-cMGF fusion protein induces proliferation of E26 transformed myeloblasts in a cMGF bioassay suggesting that glycosylation is not absolutely necessary for biological activity. Sequence comparison reveals that cMGF is distantly related to G-CSF and IL-6.

Amino Acid Sequence↗

Identification of a cDNA clone specific for the neural cell adhesion molecule AMOG.

A cDNA clone of the neural cell adhesion molecule AMOG was isolated from a lambda gt10 library constructed from 8-day-old mouse brain poly(A) + RNA with a 17mer oligonucleotide probe designed from a nonapeptide sequence obtained from tryptic peptides of AMOG. The cDNA clone expressed as a fusion protein that is recognized by polyclonal AMOG antibodies; conversely, polyclonal antibodies prepared against the fusion protein react with AMOG. The clone contains the full sequence derived from the nonapeptide. Of all tissues tested, only brain expresses detectable levels of AMOG by ELISA and Northern blot analyses, indicating a high correlation in expression at the protein and mRNA levels. Both brain and astrocytes express a 3 kb long mRNA, which appears to be encoded by a single gene.

Adenosine Triphosphatases↗

Neural cell recognition molecule F11: homology with fibronectin type III and immunoglobulin type C domains.

We report here the complete cDNA sequence of F11 130 kd polypeptide, a chick neural cell surface-associated glycoprotein implicated in neurite fasciculation and elongation. The predicted protein sequence of 1010 amino acids includes an amino-terminal signal peptide and a carboxy-terminal hydrophobic stretch, which is compatible with the consensus motif for covalent attachment of glycosyl-phosphatidylinositol. Accordingly, F11 lacks an intracellular domain, which is consistent with evidence obtained from protease protection experiments on isolated microsomes. In addition, the molecule comprises six domains related to the immunoglobulin domain type C and four resembling fibronectin repeat type III. Both types of repeats resemble those present in neural cell adhesion molecules L1 and N-CAM. The possible identity of F11 with the chick neural glycoprotein contactin is discussed.

Amino Acid Sequence↗

[The importance of quantitative grey-scale analysis of the sonogram in "diffuse" thyroid diseases].

A sonographic grey scale (gs) analysis of the thyroid gland was retrospectively (1985-1986) performed in 248 patients with normal sized thyroid glands or "diffuse" thyroid diseases. During the examination the physical parameters for gain, far and near gain were constant. The normal value (means +/- 2 s) in 95 patients with normal sized and euthyroid thyroid glands was lower in females (gs: 14 +/- 4) than in males (gs: 16 +/- 6), children had obviously lower patterns (gs: 7.1), adolescents had low normal patterns (gs: 11). The echogenicity increased with increasing thyroid volumes. In patients with autoimmune thyroid diseases an obvious low echogenicity could be demonstrated (Hashimoto's thyroiditis, gs-SEM: 8.3 +/- 1.5; Grave's disease, gs-SEM: 6.7 +/- 1.2) (SEM = standard error of the mean). Euthyroid patients with microsomal antibody titers showed low normal grey scale patterns (gs: 10.9 +/- 3). In patients after subtotal thyroidectomy the grey scale pattern decreased with decreasing volume of the residual thyroid gland. The grey scale pattern increased years after surgery. The subjective grading of the grey scale pattern was different from the quantitatively measured pattern in 18% of the patients with glands of normal size.

Adolescent↗

Long-term follow-up in patients with arrhythmogenic right ventricular disease.

Follow-up was obtained in 33 of 35 patients with arrhythmogenic right ventricular disease (ARVD) from three centers, one in France, and two in the United States. The majority of patients are living but require antiarrhythmic drug therapy. Analysis of syncope as a prognostic factor for arrhythmic death in this series, as well as in patients with ARVD reported in the literature, suggests a more favourable long-term prognosis in those patients who did not have a history of syncope. ARVD may be due to a variety of pathological entities and the prognosis of patients who have different aetiologies may well be distinct from one another.

Adult↗

Electrode catheter ablation of resistant ventricular tachycardia in arrhythmogenic right ventricular dysplasia: experience of 13 patients with a mean follow-up of 45 months.

Electrode catheter ablation (fulguration) is a new technique for the treatment of ventricular tachycardia resistant to medical treatment. It proved effective in our hands in a series of 65 cases of ventricular tachycardia of varied origin. This paper reports the early results in a subgroup of 13 patients suffering from arrhythmogenic right ventricular dysplasia in whom shocks ranging from 160 to 280J, single or multiple, in one or up to three sessions were delivered. In the 11 patients surviving the DC ablation procedure single or multiple monomorphic sustained VT was brought under control. However, four patients (36%) required therapeutic antiarrhythmic treatment following the fulguration therapy. During the learning phase one case of death was related to poor catheter selection and the other to poor protocol. The post-mortem study of the effect of shocks depends on the anatomical structure to which the shocks have been delivered.

Adult↗

Assessment of the optimal atrio-ventricular delay in DDD paced patients by impedance plethysmography.

The beneficial haemodynamic effects of sequential atrioventricular (AV) pacing have been clearly established and are dependent on the AV delay and pacing rate. However, the optimal AV delay is difficult to determine in each particular patient. We used a modified impedance plethysmographic method to assess variations in stroke volume for different AV delay and pacing rate settings. Impedance measurements showed a good correlation with CO2 rebreathing stroke volume measurements in VVI patients. Impedance variations were then used to set the optimal AV delay at different pacing rates in DDD patients. The inverse relationship between the optimal AV delay and the pacing rate has been accurately identified in most of the patients but is not predictable. In all cases, the cardiac output was higher in DDD mode at the optimal AV delay than in VVI mode. In some patients with a damaged myocardium, the stroke volume appeared to be highly sensitive to multiple AV delay settings. Impedance plethysmography can permit such repetitive non-invasive quick measurements, increasing the accuracy of optimal AV delay determination and is well suited for routine examination of patients with cardiac dual chamber pacemakers.

Atrioventricular Node↗