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Biomedical subjects

B Jenkins

Publications and source records attributed to B Jenkins.

At least 37 records · Page 2Linked to original sources

Age-dependent striatal excitotoxic lesions produced by the endogenous mitochondrial inhibitor malonate.

Intrastriatal injection of malonate, a reversible inhibitor of succinate dehydrogenase (SDH), produced age-dependent striatal lesions, which were significantly greater in 4- and 12-month-old animals than in 1-month-old animals. Both histologic and neurochemical studies showed that the lesions were significantly attenuated by administration of the noncompetitive NMDA receptor antagonist MK-801. Water-suppressed chemical shift magnetic resonance imaging showed that malonate produces increased striatal lactate concentrations and striatal lesions on T2-weighted scans that were attenuated by MK-801. Neurochemical characterization of the lesions showed significant decreases in markers of medium-sized spiny neurons (GABA and substance P), whereas a marker of medium-sized aspiny neurons (somatostatin) was not different from control values, consistent with an NMDA receptor-mediated mechanism. The effects of intrastriatal injections of malonate on ATP concentrations were compared with those of the irreversible SDH inhibitor 3-nitropropionic acid (3-NP). The ATP depletions following an equimolar injection of malonate were less marked and more transient than those of 3-NP. These results show that the competitive SDH inhibitor malonate produces more transient and milder bioenergetic defects than 3-NP, which are associated with selective activation of NMDA receptors. The results strengthen the possibility that a subtle impairment of energy metabolism may play a role in the pathogenesis of Huntington's disease.

Adenosine Triphosphate↗

1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism.

The effects of 1-methyl-4-phenylpyridinium (MPP+) were studied in rat striatum. Using freeze-clamp, microwave, and water-suppressed proton chemical shift magnetic resonance imaging techniques, MPP+ resulted in marked increases in lactate and a depletion of ATP for up to 48 h after the injections. MPP+ produced dose-dependent depletions of dopamine, serotonin, gamma-aminobutyric acid, and substance P that were partially blocked at 1 week by prior decortication or completely blocked by MK-801 at 24 h. The lesions showed relative sparing of somatostatin-neuropeptide Y neurons, consistent with N-methyl-D-aspartate (NMDA) excitotoxicity. MPP+ produces impairment of oxidative phosphorylation in vivo, which may result in membrane depolarization with persistent activation of NMDA receptors and excitotoxic neuronal degeneration. An impairment of energy metabolism may therefore underlie slow excitotoxic neuronal death in neurodegenerative diseases.

1-Methyl-4-phenylpyridinium↗

Spatiotemporal isosensitivity fields in the human visual system.

The human visual system is capable of detecting correlations, manifested perceptually as global pattern, in mathematically constrained dynamic textures. This ability has given rise to speculation that correlative mechanisms in the human visual system exist and that they have a neural basis similar to the orientationally selective structures discovered in area 17 of the mammalian visual cortex. The limits to the detection of correlation were mapped, spatially and temporally, by means of a psychophysical technique. Evidence is presented that, at least in the spatial domain, the correlation mechanism may be served by a population of such neural units.

Humans↗

Effects of beta-adrenergic inhibition on scar formation after myocardial infarction.

In view of clinical interest in the efficacy of beta-adrenergic blockade during acute myocardial infarction (AMI), we have determined the long-term effect of therapy on scar formation after experimental myocardial ischemia. Intact anesthetized dogs underwent acute occlusion of the left anterior descending coronary artery, by means of a balloon catheter, which permitted monitoring of the aortic-peripheral coronary artery pressure gradient during the 4-hour period of balloon inflation. Practolol administration was begun 15 minutes after the onset of ischemia in group A. Control animals (group B) received procainamide to approximate the antiarrhythmic action of beta blockade. Only group A exhibited significant reduction in the ST segments during acute ischemia. Chronic therapy was maintained for 1 month and the mature scar formed in the myocardium was assessed after 4 months. The extent of subendocardial scar was similar in both groups but subepicardial scar formation was significantly less in group A. There was also a significant decrease in the percentage of total myocardium involved with scar in this treatment group. Although thinning of the left ventricular wall was similar for both groups in the central scar region, this process was significantly reduced at the lateral margin in group A. Thus, specific beta-receptor blockade during acute myocardial ischemia and sustained during the repair process can result in a reduced quantity and altered distribution of mature scar.

Adrenergic beta-Antagonists↗

Patients' evaluation of a post-myocardial infarction teaching programme administered by nurses.

Two-hundred and twenty-eight patients admitted to a District General Hospital Coronary Care Unit with a confirmed myocardial infarction were given a detailed information session by nurses. Information included a detailed programme of exercise during convalescence and attitudes toward diet, smoking and sexual intercourse. Patients were asked to assess the value of these sessions using questionnaires administered during convalescence. Between 76% and 91% of patients considered the presentation necessary and there was a significant improvement in their understanding of what an infarction was. More than 80% of patients found a booklet entitled Recovering from your Heart Attack particularly helpful. The great majority of patients believed that more health education should be given at school and that members of the general public should be taught the techniques of cardio-pulmonary resuscitation. The teaching programme appears to have reduced the admitted smoking habits of patients. On admission 56% of patients were smokers. This fell to 7% at the end of 3 weeks, but had risen to 17% at 6 months.

Attitude to Health↗

Expression plasmid vectors containing Escherichia coli tryptophan promoter transcriptional units lacking the attenuator.

Two DNA fragments which contain the Escherichia coli tryptophan promoter operator region but lack the attenuator have been used in the construction of a series of pAT153 based plasmids suitable for the regulated expression of foreign genes in E. coli. The first, a 139-bp HhaI fragment includes 59 bp of the trp leader sequence, ending within the "attenuator peptide" coding sequence, eleven codons from the N-terminus. A fusion-type expression plasmid incorporating this fragment has been constructed. The second, a 99-bp HaeIII-TaqI fragment contains no coding sequence but includes the "attenuator peptide" SD site situated 4 bp upstream of the TaqI site. This fragment has been incorporated in expression vectors which result in the direct expression of cloned gene sequences. To further maximise expression, plasmids with directly repeating trp promoter HaeIII-TaqI units have been constructed.

Escherichia coli↗

Spatial limits to the detection of transpositional symmetry in dynamic dot textures.

If a set of random dots is translated along a uniform axis and superimposed on itself, then the resulting texture is seen to have three possible perceptual outcomes depending on the degree of translation: pairedness, striation, and randomness. Similar perceptual effects are obtained by plotting identical point-pairs randomly in space and uniformly over time. The threshold between striation and randomness in dynamic dot textures was investigated, since it represents a spatial limit to the detection of transpositional symmetry. This limit was found to vary as a function of three factors: stimulus field diameter, retinal eccentricity, and high frequency attenuation. The limit was found to be invariant over a fourfold range of texture density. It is proposed that the ability of the human visual system to detect correlations in dynamic transpositionally symmetric textures is the result of the activation of populations of orientationally selective cells identified in the mammalian visual cortex. It is also proposed that the limits to this ability could be related to the average size of the receptive fields of such cells within a given region of the retina.

Adult↗

Synthesis of calf prochymosin (prorennin) in Escherichia coli.

A gene for calf prochymosin (prorennin) has been reconstructed from chemically synthesized oligodeoxyribonucleotides and cloned DNA copies of preprochymosin mRNA. This gene has been inserted into a bacterial expression plasmid containing the Escherichia coli tryptophan promoter and a bacterial ribosome binding site. Induction of transcription from the tryptophan promoter results in prochymosin synthesis at a level of up to 5% of total protein. The enzyme has been purified from bacteria by extraction with urea and chromatography on DEAE-cellulose and converted to enzymatically active chymosin by acidification and neutralization. Bacterially produced chymosin is as effective in clotting milk as the natural enzyme isolated from calf stomach.

Animals↗

Construction of a genetic map for Caulobacter crescentus.

RP4-mediated conjugation has been used to transfer large fragments of chromosomal material in Caulobacter crescentus. In this system, conjugation proceeds from multiple origins, and haploid recombinants are recovered at frequencies of 10(-6) and 10(-7) per donor cell. The data from five-factor crosses were subjected to computer-assisted crossover analyses as a rapid method to determine marker order. Using this information and data from additional two- and three-factor crosses mediated by RP4 or the generalized transducing bacteriophage phi Cr30, we constructed the first genetic map for C. crescentus.

Bacteria↗