Search PubMedSearch

Biomedical subjects

E Beck

Publications and source records attributed to E Beck.

At least 19 recordsLinked to original sources

Cardiac effects of R 79595 and its isomers (R 80122 and R 80123) in an acute heart failure model. A new class of cardiotonic agents with highly selective phosphodiesterase III inhibitory properties.

R 79595 (N-cyclohexyl-N-methyl-2-[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1-b]-quinazolin-7-yl) methylene] amin] oxy] acetamide) and its isomers represent a novel class of compounds with phosphodiesterase (PDE) inhibitory and cardiotonic (positive inotropic) actions. The cardiac effects of this class of compounds were investigated in the hexobarbital-depressed heart-lung preparation of the guinea-pig. After induction of heart failure (reduction of cardiac output to 25% of the initial value) cumulative addition of R 79595 or its isomers R 80122 (E-isomer) and R 80123 (Z-isomer) concentration-dependently reversed the cardiac depressant effects of hexobarbitone-Na. With regard to reconstitution of contractility and cardiac function R 80122 (E-isomer) was 10 fold more potent than R 79595 (1:1 mixture of the isomers) and nearly 100 fold more potent than R 80123 (Z-isomer). Furthermore, the cardiotonic action of the most potent isomer (R 80122) was compared to the effects of several positive inotropic reference compounds. The order of cardiotonic potency was as follows: (-)-adrenaline > R 80122 = adibendan > digitoxin > milrinone = enoximone > theophylline. Adibendan (EC50 value: 6.7 +/- 1.8 x 10.-8 mol/l), which showed cardiotonic effects in the same concentration range as R 80122 (EC50 value: 6.1 +/- 1.3 x 10(-8) mol/l), was significantly (p < 0.01) less effective than R 80122 with respect to the maximally induceable increase in cardiac output (CO). The cardiotonic effects of R 80122 could be observed in the low concentration range of 3 x 10(-8) to 1 x 10(-6) mol/l, whereas enoximone (EC50 value: 1.2 +/- 0.1 x 10(-5) mol/l) and milrinone (EC50 value: 8.9 +/- 3.5 x 10(-6) mol/l) elicited positive inotropic effects at 100 fold higher concentrations. Digitoxin was 10 fold less and theophylline was 300 fold less potent than R 80122 with regard to reconstitution of heart function. The cardiotonic effects of R 80122 were not accompanied by an increase in heart rate as found with milrinone, theophylline or (-)-adrenaline in this model. Furthermore, the PDE inhibitory effect of R 79595 and its E-isomer R 80122 were investigated in partially purified isoenzymes from guinea-pig ventricles. The IC50 values of R 79595 and R 80122 on PDE I-IV were compared to the IC50 values of adibendan, milrinone, enoximone and theophylline. The selectivity of an inhibitor for PDE III was evaluated by division of its IC50 values on PDE I, II and IV by the IC50 value on PDE III. R 80122 was the most potent and selective PDE III inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The effects of alcohol and benzodiazepines on the severity of ski accidents.

Urine samples from 402 victims of ski accidents were analyzed for the presence of benzodiazepines (BZD) and alcohol. Eighty-one (20%) samples were positive for alcohol; BZD were detected in 34 (8.5%) cases. Ten of the samples (2.5%) were found to be positive for both alcohol and BZD. Subjects who were positive for either alcohol or BZD or both were older than the other persons examined. The prevalence of alcohol was significantly higher among male accident victims. BZD intake could be demonstrated to have a significant influence on the severity of injuries. Besides an increased awareness of the need for skier education regarding drug use, heightened attention of medical caregivers is warranted to inform their patients about potential accident hazards in sport activities when BZD are prescribed.

Adolescent

VPg gene amplification correlates with infective particle formation in foot-and-mouth disease virus.

In order to analyze the function of VPg amplification in aphthoviruses, we have undertaken the first mutational analysis of the repetitive VPg-coding region using an improved foot-and-mouth disease virus (FMDV) cDNA clone from which infective viral RNA was synthesized. A set of VPg mutants was constructed by site-directed mutagenesis which includes different VPg deletion mutations, a VPg insertion mutation, and amino acid residue replacement mutations that interfere with binding of the VPg protein to the viral RNA and with its proteolytic processing. Our results revealed that an amazing flexibility in the number of VPgs is tolerated in FMDV. Optimal viability is given when three VPgs are encoded. Deletion as well as insertion of one VPg gene still resulted in infective particle production. Infective particle formation was observed as long as one VPg remained intact. No obvious differences in the individual VPg molecules with regard to their promoting viral RNA synthesis were observed, indicating that all three VPgs can act equally in FMDV replication. Mutant polyprotein processing was comparable to that of the wild-type virus. However, VPg mutants showed reduced viral RNA synthesis levels after infection. The levels of viral RNA synthesis and infective particle formation were found to correlate with the number of functional VPgs left in the mutant virus. These findings suggest a direct VPg gene dosage effect on viral RNA synthesis, with a secondary effect on infective particle formation.

Aphthovirus

[Russe surgical procedures in treatment of scaphoid pseudarthrosis (Russe I, Russe II)].

In scaphoid nonunion, Russe's modification of the Matti procedure with cancellous bone grafting, using a cortico-cancellous graft is very useful. In small proximal scaphoid fragments with avascular necrosis, resection and interspacing of bone graft of the iliac crest leads to good results. In old cases of nonunion and avascular necrosis of proximal fragment, the use of a bone block from the iliac crest with microvascular anastomosis of the vessels leads to better results.

Bone Transplantation

Expression of the aphthovirus RNA polymerase gene in Escherichia coli and its use together with other bioengineered nonstructural antigens in detection of late persistent infections.

A plasmid has been constructed containing the DNA sequences that direct the expression of the aphthovirus RNA-dependent RNA polymerase (virus infection-associated antigen, VIAA) in its native form. The aphthovirus polypeptide was designed to contain only a single additional amino acid, the N-terminal methionine. The recombinant protein has been purified and used in enzyme-linked immunoelectrotransfer blots to detect aphthovirus-specific antibodies in the sera of persistently infected animals. Furthermore, studies were carried out to test the hypothesis that antibodies against other nonstructural antigens appear in the sera of these animals. It was established that antibodies against polypeptides 3A and 3B can serve as complementary markers for late aphthovirus-carrier state detection. The considerable potential of this approach to detect aphthovirus-specific antibodies, when the isolation of infectious virus is not possible, was demonstrated. Negative results were obtained in animals from virus-free areas and in vaccinated cattle. This assay has the added advantage that no infectious or noninfectious virus is involved during antigen production.

Animals

[Effect of alcohol and benzodiazepines on the severity of ski accidents].

Urine samples from 402 victims of ski accidents were analyzed for the presence of alcohol and benzodiazepines. In a second stage of the investigation, patients were asked to fill in a questionnaire evaluating among other things the consumption of alcohol and the use of benzodiazepines during the last 24 hours before the accident. 81 (20.1%) samples were found to be positive for alcohol, in 34 cases (8.5%) benzodiazepines were detected by urinalysis. 10 samples were positive for both alcohol and benzodiazepines. Subjects positive for alcohol and benzodiazepines presented with significantly more severe injuries than the negative controls. Native accident victims were significantly less frequently positive for alcohol than were subjects from foreign countries. Accidents most commonly occurred early in the afternoon, the positive urine samples, however, were evenly distributed over the whole day. The questionnaire was answered and returned by 76.6% of the study population. 80% of the patients with urine samples positive for alcohol reported having consumed alcohol before the accident, whereas none of those who had been positive for benzodiazepines admitted having ingested tranquilizers.

Adolescent

[Disseminated intraperitoneal trophoblast tissue after laparoscopic treatment of extrauterine pregnancy].

We report on the atypical course of a 31-year old primigravida, who underwent conservative treatment for a tubal pregnancy. After confirmation of the diagnosis by means of laparoscopy, a linear salpingotomy and removal of the products of gestation were performed through the laparoscope. Routine measurements of the serum HCG levels postoperatively showed, after a short period of decreasing HCG levels, a new rapid increase of HCG values. At relaparoscopy, evidence for an intraperitoneal dissemination of trophoblastic tissue was found and confirmed by histology. After treatment with 20 mg methotrexate q.i.d. per os for 5 days, HCG levels returned to normal within a short time. Apart from a minor degree of an aphthosal stomatitis, the patient did not experience any major side effects from the treatment.

Adult

Comparison of the 5' and 3' untranslated genomic regions of virulent and attenuated foot-and-mouth disease viruses (strains O1 Campos and C3 Resende).

The complete 5' and 3' non-coding regions of two attenuated South American foot-and-mouth disease virus (FMDV) vaccine strains, O1C-O/E and C3R-O/E, and their corresponding virulent parental strains, O1 Campos and C3 Resende, have been cloned from polymerase chain reaction-amplified primary cDNA. Differences observed in the derived nucleotide sequences between attenuated and virulent viruses seem not to affect regulatory signal structures, supporting the theory that genetic variations, primarily in the 3' halves of the viral genomes, contribute to the attenuation phenotype of the vaccine strains. In addition, this is the first report on the complete sequence of the 5' untranslated region of a C-type aphthovirus. Approximately 10% of the nucleotides differ from the corresponding known sequences of serotypes A or O.

Aphthovirus

Interaction of a cellular 57-kilodalton protein with the internal translation initiation site of foot-and-mouth disease virus.

A cellular 57-kDa protein (p57) that binds specifically to the internal translation initiation site in the 5' untranslated region of foot-and-mouth disease virus RNA was detected in cell extracts of different mammalian species by UV cross-linking. The protein binds to two distinct sites of the translation control region which have as the only common sequence a UUUC motif. The first binding site consists of a conserved hairpin structure, whereas the second binding site contains an essential pyrimidine-rich region without obvious secondary structure. Competition experiments indicate that the complexes with the two binding sites were formed by a single p57 species. The protein binds also to the 5' untranslated region of other picornaviruses. Results from footprint analyses with foot-and-mouth disease RNA suggest the participation of additional cellular factors in the translation initiation complex.

Animals

Immunological analysis of cloned Schistosoma mansoni antigens Sm31 and Sm32 with sera of schistosomiasis patients.

Two immunogenic proteins, Sm31 and Sm32, originating from the gut of Schistosoma mansoni were evaluated for their potential as recombinant immunodiagnostic reagents. Sm31 and Sm32 cDNA fragments were cloned and expressed in Escherichia coli as polypeptides fused to RNA polymerase of bacteriophage MS2. The recombinant proteins were tested in enzyme-linked immunosorbent assays (ELISA) with paired sera of 182 persons from Mali with S. mansoni and S. haematobium infections collected before and one year after treatment with praziquantel. Pretreatment sera of the study population gave a strong antibody response to Sm31 and Sm32 in immunoblots of total worm extract with the sera. The sensitivities of both western blotting (86%) and ELISA (75%) using Sm31 and Sm32 fusion proteins compared well with a single egg count (84%). Chemotherapy resulted in an overall decline of egg counts. Posttreatment sera gave significantly lower reactivities than the pretreatment sera. Our results demonstrate the feasibility of detecting circulating antibodies with recombinant antigens in schistosomiasis.

Adolescent

[Fractures of the talus].

Peripheral fractures of the talus, such as fractures of the posterior and lateral process, need no special therapy. Larger fragments with dislocation require open reduction and screw fixation. Small flake fractures with stability of the joint can be removed arthroscopically, but larger fractures should be repositioned with K-wires, small screws. Ethipin or fibrin sealant. Dislocated fractures of the head of the talus should be reduced and fixed by screws or K-wires. Fractures of the neck of the talus with anteromedial or lateral dislocation can be treated by closed reduction and external fixation, irreducible fractures by open reduction and screw fixation. Fractures of the neck and body of the talus with dorsal dislocation or subluxation in the talonavicular joint require osteotomy of the internal malleolus, open reduction and screw fixation. Comminuted and open fractures of the body of the talus are treated by minimal osteosynthesis with K-wires or external fixation. In necrosis of the talus, revascularization using iliac crest bone with vascular pedicle seems to be successful. In arthrosis cases, triple arthrodesis is the best solution.

Bone Screws

A cellular 57 kDa protein binds to two regions of the internal translation initiation site of foot-and-mouth disease virus.

A ribosome-associated 57 kDa protein from rabbit reticulocytes was linked to the internal translation initiation site of foot-and-mouth disease virus by mild UV-irradiation. Binding studies with different RNA fragments revealed that this protein interacts with two distinct sites within the translational control region. One site is located approximately 400 nucleotides upstream from the translational start codon and the second binding site could be confined to 60 nucleotides preceding this codon. Both sequences coincide with hairpin structures at the two opposite ends of a secondary structure model of the internal ribosomal entry site proposed by Pilipenko et al. [(1989) Nucleic Acids Res. 17, 5701-5711].

Animals

Identification of a nucleotide deletion in parts of polypeptide 3A in two independent attenuated aphthovirus strains.

A set of antisera specific for each viral polypeptide of foot-and-mouth disease virus was used to provide a full comparison of polypeptides of two strains attenuated for cattle with respect to their parental virulent strains. Both attenuated strains, belonging to serotypes O1 Campos and C3 Resende, were obtained through serial passages of the corresponding virulent strains in chicken embryos. Although mutations were scattered throughout the genome, both attenuated strains showed an electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of viral polypeptide 3A faster than that of their respective wild-type strains. To determine the nature of this alteration, the nucleotide sequences of the genomic region encoding this polypeptide were determined. Comparative sequence analysis of wild-type and attenuated strains revealed 57 and 60 nucleotide deletions in the attenuated strains O1 Campos and C3 Resende, respectively. These studies, in conjunction with our previous analysis of recombinant viruses between wild-type and attenuated strains, which concluded that the major determinants of attenuation are located in the 3' half of the viral genome, strongly suggest that the alteration in polypeptide 3A of the attenuated strains is important for their reduced virulence in cattle.

Animals