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Biomedical subjects

J R Jenkins

Publications and source records attributed to J R Jenkins.

At least 73 records · Page 4Linked to original sources
PubMed1988

Atrioventricular nodal accommodation in isolated guinea pig hearts: physiological significance and role of adenosine.

The progressive prolongation of atrioventricular node (AVN) conduction time to a new steady-state value caused by sudden and maintained increases in atrial rate is the most common form of AV nodal accommodation. This study was undertaken to 1) characterize AV nodal accommodation in isolated perfused guinea pig hearts, 2) investigate the influence of potential modulators of this phenomenon such as acetylcholine and adenosine, and 3) determine the physiological significance of AV nodal accommodation on cardiac function. Beat-by-beat changes in AVN conduction time caused by single- or multiple-step increases in atrial pacing rate were measured during control conditions and in the presence of atropine (1 microM), propranolol (1 microM), and the adenosine antagonist BW-A1433 (1 microM). BW-A1433 was the only intervention that significantly reduced the cumulative and frequency-dependent prolongation of AVN conduction time but this was only observed at atrial cycle lengths less than or equal to 170 msec. In addition, BW-A1433 shortened the Wenckebach cycle length from 163 +/- 2 to 153 +/- 2 during normoxia and from 172 +/- 3 to 164 +/- 4 during mild hypoxia. In contrast, dipyridamole (1 microM), an adenosine uptake blocker, markedly accentuated the AVN conduction time prolongation, accentuated the AV block associated with fast atrial rates, and significantly increased the Wenckebach cycle length. These effects of dipyridamole were prevented and antagonized by BW-A1433 and adenosine deaminase. When O2 supply was limited and at the same time demand increased secondary to fast atrial pacing, the rate of adenosine release increased from a control of 125 +/- 27 to 580 +/- 54 pmol/min/g. This was accompanied by a significant prolongation in AVN conduction time that invariably progressed to AV block. Once AV block occurred, O2 consumption decreased, O2 supply-to-demand ratio improved and the rate of adenosine release dropped to 310 +/- 61 pmol/min/g. Reversal of the AV block with adenosine antagonists resulted in a decrease in O2 supply-to-demand ratio and a severalfold increase in the rate of adenosine release. In this feedback system, adenosine signals the imbalance between O2 supply and demand, causes AV block and, thus, reduces demand to compensate for the limited O2 supply. On the other hand, adenosine deaminase and antagonists act as "error signals" by attenuating the effect of adenosine, whereas dipyridamole enhances the "gain" of the system by potentiating the effects of adenosine.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1988

Mouse p53 blocks SV40 DNA replication in vitro and downregulates T antigen DNA helicase activity.

Immunopurified mouse p53 proteins were used to gain experimental access to the mechanisms underlying nonprimate p53 directed suppression of SV40 origin directed DNA replication in vivo. In replication competent HeLa cell extracts containing exogenous T antigen, mouse p53 blocks T antigen dependent DNA synthesis as in vivo. However, in transcription competent HeLa extracts, mouse p53 has no effect either on overall transcription or on the ability of immunopurified T antigen to downregulate SV40 early transcription. We show that although mouse p53 has no significant effect on T antigen encoded activities such as ATPase and DNA binding, helicase activity is somewhat reduced suggesting that the in vivo suppression by mouse p53 of SV40 replication may be due, at least in part, to direct modulation of T antigen function.

Adenosine Triphosphatases↗
PubMed1987

A microcomputer system for on-line study of atrioventricular node accommodation.

An automated on-line programmable stimulator and interval measurement system was developed to study atrioventricular node (AVN) accommodation. This dedicated microcomputer system measures and stores the stimulus-to-His bundle (S-H) interval from His bundle electrogram (HBE) recordings. Interval measurements for each beat are accurate to within 500 microsecond. This user-controlled system has been used to stimulate at any rate up to 6.5 Hz and to measure intervals up to 125 ms in isolated perfused guinea pig hearts. A built-in timer-reset mechanism prevents failure of the system in the absence of a His potential (i.e., 2:1 AV block). It may be modified for use in clinical studies or other experimental systems and has the ability to measure other physiological intervals. The system provides the precision in pacing and accuracy in the measurement of AVN conduction time that is necessary for meaningful analysis of AVN accommodation and has the simplicity of design and use that is not available in previously described systems. Furthermore, this computer system can be used not only in studies involving AV conduction, but also in any setting where programmed stimulation and interval measurement and recording need to be performed simultaneously.

Animals↗
PubMed1987

Mutant p53 proteins bind hsp 72/73 cellular heat shock-related proteins in SV40-transformed monkey cells.

We have examined the expression of a series of mouse mutant, as well as wild-type, p53 proteins in SV40-transformed monkey COS cells. Wild-type mouse p53 binds predominantly to SV40 large T antigen in these cells. However, several of the mutants co-precipitate exclusively with proteins of approximately 68 Kd relative molecular mass. We show by immunological and proteolytic mapping techniques that these proteins are identical to the hsp 72/73 heat shock proteins. p53 mutants in complex with hsp 72/73 have an altered subcellular location compared to the wild-type protein and the hsp 72/73 binding p53 mutants fail to exhibit an epitope recognized by monoclonal antibody PAb 246. The existence of at least two antigenically distinct subclasses of hsp 72/73 complexed to mutant p53 is shown.

Animals↗
PubMed1985

Precise epitope mapping of the murine transformation-associated protein, p53.

Murine p53 cDNA sequences were cloned into an in vitro expression vector, Protem Hind. Four deletion libraries were generated using Bal31 double-stranded exonuclease; two being made from constructs encoding a fusion protein constructed from SV40 small t sequences and the p53 clone, p27.la; and two from the full length p53 clone, pp53-5. Both 5'- and 3'-terminal deletions of the p53 gene were made. Transcription of these constructs using Escherichia coli RNA polymerase holoenzyme, followed by translation in mRNA-dependent rabbit reticulocyte lysate, gave in vitro, truncated protein products which were immunoprecipitated by a panel of anti-p53 monoclonal antibodies. This approach enabled us to map accurately the binding sites of seven different monoclonal antibodies, demonstrating four distinct antigenic sites on p53. A synthetic peptide was constructed corresponding to the predicted amino acid sequence of one of these epitopes. This peptide competes with the epitope on the full length p53 protein for the relevant monoclonal antibodies and dissociates the corresponding p53/antibody complexes.

Animals↗
PubMed1984

Cloning and expression analysis of full length mouse cDNA sequences encoding the transformation associated protein p53.

We have cloned and sequenced overlapping cDNA fragments which together encode the entire mouse protein p53. Using these cDNA's we have reconstructed the full length coding region for the protein, and have analysed its coding potential by expression in vitro, both as a full length sequence and as a subfragment contained in a fusion protein. The predicted amino acid sequence contains no obvious homologies to any known oncogenes but includes a possible tyrosine kinase acceptor site.

Amino Acid Sequence↗
PubMed1983

In vitro synthesis of laminin and entactin polypeptides.

Total RNA and poly(A+) RNA, isolated from 13.5-day-old mouse embryo parietal endoderm cells and from differentiated F9 teratocarcinoma cells that synthesize laminin and entactin, were translated in the reticulocyte lysate. Antiserum raised against purified and denatured laminin B chains specifically immunoprecipitated from the translation reaction polypeptides of Mr = 205,000, 200,000, and 185,000. Antiserum against the native complex of laminin and entactin also immunoprecipitated these polypeptides, although less efficiently. In addition, this antiserum immunoprecipitated polypeptides of Mr = 300,000, 270,000, and 140,000. Antiserum against purified and denatured entactin immunoprecipitated only the Mr = 140,000 polypeptide. In contrast, no polypeptides were immunoprecipitated from translation reactions programmed with RNA from undifferentiated F9 cells that produce only small amounts of laminin and entactin. The in vitro synthesized polypeptides migrate on NaDodSO4-polyacrylamide gel electrophoresis slower than the respective unglycosylated laminin and entactin chains isolated from cells treated with tunicamycin. Supplementing the reticulocyte lysate with dog pancreas microsomal membranes yields in vitro translation products which co-migrate with the respective glycosylated laminin and entactin chains of control cells. Taken together, these results suggest that the polypeptides described represent in vitro synthesized laminin and entactin chains.

Animals↗
PubMed1983

Comparison of sensory integrative therapy and motor programming.

The relative effects of individualized sensory integrative therapy vs. small group, gross-motor programs were examined with a group of preschool children with mild to moderate motor delays. Children in the sensory integrative therapy group received one-to-one treatment twice weekly. Children in the motor-programming group received intervention four times weekly in small groups of three to four. Both intervention programs were carried out simultaneously for 17 weeks. No significant between group differences were observed in gross-motor gains on the Peabody Developmental Motor Scales or in sensorimotor gains on the Assessment of Sensory Integration in Preschool Children. Results of this study compared to results of similar previous studies were discussed.

Child, Preschool↗
PubMed1979

Molecular cloning of three major sequence species from Rainbow trout protamine mRNA.

Double stranded cDNA molecules complementary to purified Rainbow trout protamine mRNA have been cloned in the bacterial plasmid pBR322. In order to circumvent the problems associated with a heterogeneous cDNA probe when identifying recombinants, a comparative hybridisation technique was used which can resolve between closely related cloned sequences. Using this technique, selected recombinants were shown to carry sequences corresponding to separate major fractions of protamine mRNA. Partial nucleotide sequences of the inserts in two clones confirms this conclusion.

Animals↗
PubMed1978

As others see us. The patient's view of the anaesthetist.

One hundred hospital patients were given a questionnaire, designed to assess their beliefs about the anaesthetist in relationship to other workers in the United Kingdon national health service. The results of this survey, and the comments passed at a simultaneous interview, are discussed.

Adolescent↗