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Biomedical subjects

W Block

Publications and source records attributed to W Block.

At least 73 records · Page 4Linked to original sources
PubMed1990

Chronic animal testing of new cardiac pacing electrodes.

To evaluate the electrical performance of new electrode technologies, 24 leads containing either carbon coated porous titanium (BIOPORE, (Intermedics, Inc., Freeport, TX], iridium oxide (IROX), or iridium oxide coated with polyethylene glycol (IROX-PEG) electrodes (eight of each) were implanted into the ventricles of 12 canines. Stimulation threshold data was measured at regular intervals for 24 weeks. Low acute values were observed for all leads (0.32 +/- .13 V at 0.6 msec pulse width), but the IROX-PEG electrode demonstrated lower subchronic, peak, and chronic values. Compared to implant, the IROX-PEG electrodes' stimulation thresholds rose only 0.23 V when chronic conditions occurred. There were no significant differences between the electrodes in pacing impedance or R wave amplitude measurements. We conclude that both IROX and IROX-PEG technologies represent a promising approach to the design of more efficient cardiac pacing leads.

Animals↗
PubMed1985

Tumorigenic poxviruses: genomic organization of malignant rabbit virus, a recombinant between Shope fibroma virus and myxoma virus.

The genome of malignant rabbit virus (MRV), a newly discovered tumorigenic poxvirus of rabbits, has been analyzed using cloned DNA probes from Shope fibroma virus (SFV) and myxoma virus. Under high stringency conditions for Southern blotting such that SFV probes do not cross-hybridize with myxoma virus DNA, it is demonstrated that greater than 90% of the MRV genome has been derived from myxoma virus, and that approximately 10 kb of SFV-derived sequences have substituted for a similar amount of myxoma sequences. Mapping of the MRV genome indicates that the SFV sequences are present in two regions of the genome, one in each copy of the MRV terminal inverted repeat sequence. Furthermore, fine mapping studies of the integration sites for SFV into the myxoma background show that these SFV sequences are not symmetrical with respect to the left and right genomic termini. At the left end, 4 kb of SFV-derived DNA maps between 6 and 10 kb from the terminus, while at the right end about 5.5 kb of SFV sequences are found to extend at least 1 kb further toward the unique internal sequences. Based on this asymmetrical bipartite distribution of SFV sequences in MRV, a two-stage model to rationalize the origin of MRV is proposed. This model postulates an initial recombination event similar to gene conversion between myxoma and SFV at the right terminus of myxoma, followed by an incomplete transposition of only part of these SFV sequences to the left terminus.

Animals↗
PubMed1984

Tumorigenic poxviruses: construction of the composite physical map of the Shope fibroma virus genome.

The sites for the restriction enzymes BamHI, Bg/I, HindIII, PstI, PvuII, and SstI on the linear DNA genome of Shope fibroma virus, a tumorigenic poxvirus of rabbits, have been determined by digestions of the cloned BamHI and HindIII restriction fragments and by hybridization of 32P-labeled cloned fragments to Southern blots of Shope fibroma virus DNA cleaved partially or completely with the various enzymes. The linear genome is shown to be 160 kilobases in length and to possess terminal inverted repeat sequences of between 12.2 and 12.5 kilobases extending inwards from the cross-linked DNA telomeres. The fine map of the Shope fibroma virus terminal inverted repeats has been constructed and shown to be distinctly different from that of members of the orthopoxvirus group, such as vaccinia, by the absence of detectable tandemly repeated sequences near the termini and by the lack of detectable sequence homology with vaccinia termini.

Animals↗
PubMed1983

The elongation factor Tu from Escherichia coli, aminoacyl-tRNA, and guanosine tetraphosphate form a ternary complex which is bound by programmed ribosomes.

The interaction of the Escherichia coli elongation factor Tu guanosine tetraphosphate complex (EF-Tu ppGpp) with aminoacyl-tRNAs(aa-tRNA) was reinvestigated by gel filtration and hydrolysis protection experiments. These experiments show that EF-Tu X ppGpp like EF-Tu X GDP (Pingoud, A., Block, W., Wittinghofer, A., Wolf, H. & Fischer, E. (1982) J. Biol. Chem. 257, 11261-11267) forms a fairly stable complex with Phe-tRNAPhe, KAss being 0.6 X 10(5) M-1 at 25 degrees C. The binding of the EF-Tu X ppGpp X aa-tRNA complex to programmed ribosomes was investigated by a centrifugation technique. It is shown that this complex is bound codon-specific with KAss = 3 X 10(7) M-1 at 0 degrees C and that it stimulates peptidyl transfer. A numerical estimation of the intracellular concentration of EF-Tu X GTP X aa-tRNA and EF-Tu X ppGpp X aa-tRNA during normal growth and under the stringent response indicates that ppGpp accumulation does affect the EF-Tu X GTP X aa-tRNA concentration but does not lead to major depletion of this pool. Furthermore, due to the higher affinity of EF-Tu X GTP to aa-tRNA and of the ternary complex EF-Tu X GTP X aa-tRNA to the ribosome, EF-Tu X ppGpp X aa-tRNA binding to the ribosome is not significant. According to our measurements and calculations, therefore, a direct participation of EF-Tu in slowing down the rate of protein biosynthesis and improving its accuracy during amino acid starvation is not obvious.

Escherichia coli↗
PubMed1982

The elongation factor Tu binds aminoacyl-tRNA in the presence of GDP.

Escherichia coli elongation factor (EF-Tu) binds aminoacyl-tRNAs (aa-tRNA) not only in the presence of GTP but also in the presence of GDP. Complex formation leads to a protection of the aa-tRNA against nonenzymatic deacylation and digestion by pancreatic ribonuclease, as well as to a protection of EF-Tu against proteolysis by trypsin. The equilibrium constant for the binding of Phe-tRNAPheyeast for example to EF-Tu.GDP has been determined to be 0.7 X 10(5) M-1 which is 2 orders of magnitude lower than the equilibrium constant for Phe-tRNAPheyeast binding to EF-Tu.GTP. In the presence of kirromycin, aminoacyl-tRNA binding to EF-Tu.GDP is not affected as much: Phe-tRNAPheyeast is bound with an equilibrium constant of 3 X 10(5) M-1. While there is also a measurable interaction between EF-Tu.GTP and tRNA, such an interaction cannot be detected with EF-Tu.GDP and tRNA, not even at millimolar concentrations. A so far undetected complex formation between aminoacyl-tRNA and EF-Tu.GTP in the presence of pulvomycin, however, could be detected. The results are discussed in terms of the structural requirements of ternary complex formation and in the light of proofreading schemes involving A-site binding on the E. coli ribosome.

Escherichia coli↗
PubMed1982

The antibiotics kirromycin and pulvomycin bind to different sites on the elongation factor Tu from Escherichia coli.

Pulvomycin and kirromycin, two antibiotics which inhibit protein biosynthesis in Escherichia coli by complex formation with the elongation factor Tu (EF-Tu), bind to different sites on the protein. While only one molecule of kirromycin can be bound to one molecule of EF-Tu, more than one molecule of pulvomycin interacts with a molecule of EF-Tu. This has been deduced from experiments in which the aminoacyl-tRNA binding and the GTPase activity of EF-Tu were measured in the presence of varying amounts of both antibiotics. These experiments are interpreted to mean that pulvomycin but not kirromycin can replace the other antibiotic in its respective site. Our conclusions are supported by circular dichroism spectroscopy.

Aminoglycosides↗
PubMed1981

The elongation factor Tu . guanosine tetraphosphate complex.

The elongation factor Tu (EF-Tu) isolated from Escherichia coli cells that have undergone the stringent response is predominantly complexed with guanosine 5'-diphosphate 3'-diphosphate. This complex can be separated by anion-exchange chromatography from Ef-Tu . GDP. Unlike EF-Tu complexed with guanosine 5'-triphosphate 3'-diphosphate, the complex with guanosine 5'-diphosphate 3'-diphosphate cannot form a ternary complex with aminoacyl-tRNAs as can be shown directly by hydrolysis protection experiments.

Bacterial Proteins↗
PubMed1981

The pharmacokinetics, bioequivalence and bioavailability of different formulations of metoclopramide in man.

The pharmacokinetics of 4-amino-5-chloro-N-(2-diethylaminoethyl)-2-methoxybenzamide (metoclopramide, Paspertin) after a single dose of the drug in five different dosage forms: ampoules, tablets, drops, dragées and suppositories, were studied. The clinical investigations were carried out on 10 healthy subjects under carefully controlled conditions. The analysis of metoclopramide in plasma was carried out using reverse-phase high-pressure liquid chromatography. Bioavailabilities between 76 and 79% were determined for the oral application forms and 53% for the rectal application form. Significant differences between maximum plasma levels were found for different individuals. The initial distribution of the drug is very rapid, and the elimination half-lives are comparable for all formulations and ranged from 3.9 and 5.3 h. The apparent volume of distribution is 3.1 l/kg body weight and the total body clearance is 38.4 l/h.

Adolescent↗
PubMed1978

Chromatographic study on the specificity of bis-p-nitrophenylphosphate in vivo. Identification of labelled proteins of rat liver after intravenous injection of bis-p-nitro[14C]phenylphosphate as carboxylesterases and amidases.

The procedure established to isolate the carboxylesterases E1, E2 and EA from rat liver (Arndt, R. and Krisch, K. (1972) Hoppe-Seyler's Z. Physiol. Chem. 353, 589-598) was applied to characterize in vivo bis-p-nitro[14C]-phenyl-P-labelled proteins. The peaks of radioactivity and of residual enzyme activities (hydrolysing methylbutyrate, p-nitrophenylacetate and acetanilide) were found in the same peaks after column chromatography and could be related to the well-defined esterases E1, E2 and EA. There is no indication of a nonspecific binding of bis-p-nitrophenyl-P or of one of its metabolites. The relative quantitative amounts of E1, E2 and EA were calculated to represent 40, 14 and 46%, respectively, of the total carboxylesterase content of rat liver. The relative amount of bound (not dialysable) radioactivity in rat liver depended on the survival time. During purification, the yield of enzyme activities corresponded to that of bound radioactivity, confirming the specificity of bis-p-nitrophenyl-P in vivo. Hence the radioactive metabolites of the inhibitor obviously do not possess binding affinities of quantitative importance to the rat liver proteins.

Amidohydrolases↗
PubMed1977

Glucose tolerance and physical fitness: an epidemiologic study in an entire community.

A modification of the Harvard Step Test was administered to approximately 4700 males and females, age 10-69 in Tecumseh, Michigan. Heart rate response to this standardized exercise test is an estimate of capacity for muscular work. A blood sample was drawn 1 h after a glucose challenge on the same day the exercise test was given. Four skinfolds were measured as an index of body fatnes. It was the purpose of this analysis to study the relationship of glucose tolerance to heart rate response to exercise. All analyses were done in age and sex-specific sub-groups. The correlation coefficients are low but positive in all but one sub-group and half of the coefficients are statistically significant. This suggests that poor fitness for work (high heart rate in response to exercise) was related, albeit weakly, to lowered glucose tolerance. However, there is a positive relationship between body fatness on the one hand and serum glucose and heart rate response to exercise on the other. When the effect of body fatness was eliminated the relationship of heart rate response to exercise ahd glucose tolerance remained about the same; low but statistically significant in some age groups.

Adolescent↗