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Biomedical subjects

J C Fowler

Publications and source records attributed to J C Fowler.

At least 55 records · Page 3Linked to original sources

Small marker chromosomes in man: origin from pericentric heterochromatin of chromosomes 1, 9, and 16.

Three patients with different marker chromosomes were screened by in situ hybridisation using biotinylated probes to chromosome specific pericentric repeats to determine the chromosomal origin of the marker. Each marker had a different origin, with one from each of chromosomes 1, 9, and 16. This is the first time that autosomal marker chromosomes consisting of a small ring have been shown to be derived from the pericentric heterochromatin of metacentric and submetacentric chromosomes. Evidence suggests that such markers are not associated with any significant risk of phenotypic abnormalities, but additional cases need to be studied.

Adolescent↗

Adenosine antagonists delay hypoxia-induced depression of neuronal activity in hippocampal brain slice.

Submerged rat hippocampal slices were exposed to hypoxic medium prepared with 95% N2/5% CO2. The population spikes recorded from CA1 cell layer were completely blocked within a range of 5-10 min. The adenosine antagonist theophylline (100 microM) delayed and partially prevented the hypoxia-induced depression. Increasing concentrations of the more potent adenosine antagonist 8-phenyltheophylline (8-PT; 0.1, 1, 10 microM) resulted in progressively less hypoxia-induced depression. The antidromically elicited afterpotentials recorded in the absence of synaptic transmission in low calcium, high magnesium medium were blocked within 8 min of hypoxia. Theophylline (100 microM) and 8-PT (10 microM) delayed to a similar extent the hypoxia-induced depression of the first afterpotential but did not prevent its complete depression.

Action Potentials↗

Human satellite III DNA: genomic location and sequence homogeneity of the TaqI-deficient polymorphic sequences.

Human Satellite III DNA is a major tandem repeat in the human genome and presents a TaqI-specific hypervariable restriction fragment length polymorphism when a Satellite III related sequence (228S) is used as a probe. In situ examination shows this sequence to be near specific for the region 9qh on chromosome 9 when it is used at low probe concentrations. However the region 9qh does not appear to be the only or even the primary source of the TaqI-deficient polymorphic sequences (TDPS). Rather, such sequences appear to be mostly present in chromosomes 20, 21, and 22, and these represent the largest regions of homogeneous Satellite III in the genome; they are also resistant to digestion with a range of other restriction endonucleases. The TDPS do not arise from either of the two currently recognized Satellite III-enriched genomic regions, namely autosomal 'K-domains', which form part of 15p in chromosome 15 or the heterochromatin of chromosome Y.

Base Sequence↗

Modulation of neuronal excitability by endogenous adenosine in the absence of synaptic transmission.

Rat hippocampal slices were superfused with low calcium, high magnesium medium. Reductions in flow rate were associated with a marked depression of antidromically elicited afterpotentials with little change in the initial antidromic population spike recorded from CA1 pyramidal neurons. The depression of the afterpotential at the lower flow rates was largely reversed by the adenosine antagonist, theophylline (100 microM), by adenosine deaminase (10 micrograms/ml) and was mimicked by the application of the adenosine reuptake blocker, dipyridamole (100 microM). Since synaptic transmission was blocked, it is concluded that sufficient endogenous adenosine exists in the absence of synaptic function to alter neuronal excitability.

Action Potentials↗

Antagonism of the responses to isoproterenol in the rat hippocampal slice with subtype-selective antagonists.

The electrophysiological and cAMP responses to the beta-adrenoceptor agonist isoproterenol were measured in the in vitro hippocampal slice preparation. Subtype-selective antagonists were used to evaluate the specificity of these responses. The beta 1-selective antagonist ICI 89,406 was 60-fold more potent than was the beta 2-selective antagonist ICI 118,551 at antagonizing the electrophysiological response. ICI 89,406 was 200 times more potent in its antagonism of the cAMP response. These results suggest that the electrophysiological and cAMP responses in this preparation are primarily mediated by beta 1-adrenoceptors.

Adrenergic beta-Antagonists↗

Prostaglandins block a Ca2+-dependent slow spike afterhyperpolarization independent of effects on Ca2+ influx in visceral afferent neurons.

The blockade of a slow Ca2+-activated K+-dependent afterhyperpolarization (AHPs) in rabbit visceral sensory neurons by the prostaglandins, PGE1 and PGD2, was investigated to determine whether the blockade was indirectly due to a reduction in Ca2+ influx. The prostaglandins (PGs) could block the AHPs in the absence of any change in Ca2+-dependent spikes elicited in the presence of tetrodotoxin and tetraethylammonium bromide. A PG-induced decrease in Ca2+-dependent spike width observed in some neurons was temporally dissociated from the PG-induced block of the AHPs. In addition, a slow afterhyperpolarization produced by the application of the Ca2+ ionophore, A23187, was blocked by the PGs. It is concluded that a reduction in Ca2+ influx is not responsible for the PG-induced blockade of the AHPs.

Action Potentials↗

Two calcium-sensitive spike after-hyperpolarizations in visceral sensory neurones of the rabbit.

Intracellular recordings were made from rabbit nodose neurones in vitro. Two temporally distinct spike after-hyperpolarizations (a.h.p.s) were identified in a subpopulation of C-type neurones. The fast a.h.p. after a single spike lasted no longer than 500 ms, while the slow a.h.p. persisted for seconds. Both a.h.p.s. were increased in amplitude in low K+ (0.56 mM) solutions and decreased in amplitude in high K+ (11.2 mM) solutions, and both were reversed at hyperpolarized membrane potentials. The slow a.h.p. was reduced in low Ca2+ (0.22 mM), in the presence of Ca2+ antagonists (Ni2+, 1 mM; Cd2+, 100 microM; or Co2+, 1 mM) and was enhanced in tetraethylammonium (5 mM). In approximately half of the cells tested, the fast a.h.p. was reduced in low Ca2+ and in the presence of the Ca2+ antagonists. In the remaining cells the fast a.h.p. was insensitive to these procedures. Prostaglandin (PGE1, 1-10 micrograms/ml) reduced the slow a.h.p. in all cells tested. Neither the Ca2+-sensitive nor the Ca2+-insensitive fast a.h.p. was affected by the prostaglandin. It is concluded that there is a subpopulation of C-type nodose neurones possessing a slow a.h.p. which is due to a Ca2+-dependent K+ current. This subpopulation of neurones can further be divided on the basis of the presence of a Ca2+-sensitive fast a.h.p. Furthermore, PGE1 pharmacologically separates the fast and slow a.h.p.s by selectively blocking the slow one. The blockage by the PGE1 is most probably not due to a reduction in Ca2+ influx.

Action Potentials↗

Examination of the correlation of groupings in blood and semen.

The grouping of blood/saliva samples from a male so as to predict his semen groups is only justified if there is a strict correlation between the groupings in these body fluids. This correlation has been examined in the ABO, phosphoglucomutase (PGM1) and glyoxalase I (GLO) grouping systems in blood and semen samples collected from more than 250 individuals. Though no results proved inconsistent with this correlation, a number of semen gave inconclusive grouping results. Reasons for this are discussed as well as the relevance of the results to semen stain analysis. Semen amylase activities are also reported.

ABO Blood-Group System↗

The effect of pentylenetetrazol on inward currents of non-bursting neurons and its role in plateau formation.

The epileptogenic drug, pentylenetetrazol (PTZ) produces paroxysmal depolarization shifts in molluscan neurons that are similar to PDSs seen at a mammalian epileptic focus. Most research on molluscan neurons indicates that PTZ acts by altering ionic somatic conductances. This study was carried out to investigate the effect of PTZ on inward currents in isolated neurons of the pond snail, Lymnaea stagnalis, and to investigate how these altered currents might lead to the production of PDSs. In concentrations from 10 to 60 mM, PTZ decreased maximum inward current conductance and shifted the inactivation and activation curves to the left with the former shift being consistently greater. There was no change in reversal potential or time constants for activation and inactivation of inward currents. The effects of the PTZ-induced alterations in the inward currents were studied by incorporating them along with alterations of outward currents seen in this and other studies in a computer model for molluscan neuronal firing. The composite model reproduced in large part the intermediate changes in electrical activity seen before the development of the PDS as well as the PDS.

Animals↗

Noncholinesterase actions of an irreversible acetylcholinesterase inhibitor on synaptic transmission and membrane properties in autonomic ganglia.

Superfusion of the organophosphorous acetylcholinesterase inhibitor soman (pinacolyl methylphosphonofluoridate; 0.01-25 microM) produced a dose-dependent reduction of extracellularly and intracellularly recorded synaptic responses in the isolated rat superior cervical ganglia at frequencies of orthodromic stimulation that do not normally produce synaptic depression. The magnitude of depression was dependent upon the frequency of stimulation (0.02-1 Hz), was maintained after the removal of soman from the superfusion solution, and recovered by over 65% during periods of inactivity. The depression of synaptic transmission produced by soman was not dependent upon the inhibition of acetylcholinesterase (AChE) activity by this agent. Transmission was increasingly depressed by doses of soman greater than those needed to inactivate all measurable ganglionic AChE activity. Dose-dependent depression of synaptic transmission in soman also occurred after pretreatment with the irreversible AChE inhibitor diisopropylphosphofluoridate (DFP; 100 microM), which inhibited greater than 98% of the AChE activity in the ganglia. Soman produced a decline in the input resistance, resting potential, spike amplitude, and spike threshold and a reduction in the hyperpolarizing afterpotential. Soman-induced depression of synaptic transmission was not due primarily to a blockade of postsynaptic nicotinic receptors. At concentrations of soman which produced significant depression in transmission, ganglionic depolarization produced by bath-applied carbamylcholine (carbachol) was either slightly depressed or facilitated. In the presence of soman, repetitive focal application of acetylcholine or carbachol did not reveal use-dependent desensitization. Muscarinic antagonists, atropine and pirenzepine, protected against the use-dependent depression of synaptic transmission induced by soman. These results suggest that a principal site of action for soman is at the presynaptic terminal and that this site is sensitive to muscarinic receptor blockade.

Animals↗

The erythrocyte acid phosphatase isoenzyme distribution among the negroid population of Rhodesia.

The value of the erythrocyte acid phosphatase isoenzyme system as a method for blood typing in forensic science in Rhodesia has been evaluated. Three hundred and three blood samples from negroid people were examined. The high incidence of the B phenotype (72%) results in a poor division of the population using this system. The R allele which has been found in other negroid peoples also occurs in the Rhodesian population.

Acid Phosphatase↗

Electrophoretic typing of glyoxalase I (GLO I) isoenzymes using a mixed starch/agarose gel.

A technique was developed to type the glyoxalase I (GLO I) isoenzymes using a mixed agarose/starch gel. Over six hundred blood samples from Caucasoid people living in separate regions of South Australia were examined and the results compared with other Caucasoid population surveys. Paired blood and semen samples were also tested and the limitations of the technique with regard to blood and semen stains analysis was evaluated.

Australia↗

Cytokeratin immunophenotyping of an unusual cervical vertebral chordoma with extensive chondroid foci and perilaryngeal recurrence: a case report with review of the literature.

Chordomas are midline, slowly growing, and locally destructive tumors derived from vestigial remnants of the notochord. We present an unusual case of a cervical vertebral chordoma with extensive chondroid change that aggressively recurred in the anterior larynx and surrounding neck structures, and subsequently in the mediastinum, resulting in the death of the patient. Recent literature has investigated and debated the significance of chondroid elements in chordomas as a differential diagnostic and a prognostic indicator. In particular, the use of immunohistochemical stains for cytokeratin and mesenchymal markers in these areas as a means of distinguishing true from pseudocartilage has received much attention. In this study, we used a spectrum of cytokeratin subtypes (CK 7, 20, 5/6, AE1/3) to further characterize these chondroid areas, and observed that they were positive for the majority of the cytokeratin subtypes, suggesting pseudo, rather than true, cartilaginous change. Clinicopathologic features of this lesion and the recent literature are reviewed.

Aged↗

Current molecular methods for plant genome identification.

At least four molecular methods have been used for plant species and plant varietal identification. These include protein isoenzymes, restriction fragment length polymorphisms and more recently two alternate PCR-based procedures. One approach is based broadly on methods which amplify plant DNAs using short oligonucleotide primers to produce complex multibanded 'fingerprint' patterns. The method can be used on any plant, is relatively cheap and easy to set up, but has a number of technical limitations. A second approach is to isolate short tandem repeats (STRs) from a test plant, each example of which is locus-specific and may show length variation between individuals. Results from several STR loci will provide a genetic profile of plant variety. However, in comparison with random amplification methods STRs are costly to establish in both time and resources.

Biotechnology↗