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Biomedical subjects

M G Jones

Publications and source records attributed to M G Jones.

At least 19 recordsLinked to original sources
PubMed1992

Gene rescue in plants by direct gene transfer of total genomic DNA into protoplasts.

To study the possibility of gene rescue in plants by direct gene transfer we chose the Arabidopsis mutant GH50 as a source of donor DNA. GH50 is tolerant of chlorsulfuron, a herbicide of the sulfonylurea class. Tobacco protoplasts were cotransfected with genomic DNA and the plasmid pHP23 which confers kanamycin resistance. A high frequency of cointegration of the plasmid and the genomic DNA was expected, which would allow the tagging of the plant selectable trait with the plasmid DNA. After transfection by electroporation the protoplasts were cultivated on regeneration medium supplemented with either chlorsulfuron or kanamycin as a selective agent. Selection on kanamycin yielded resistant calluses at an absolute transformation frequency (ATF) of 0.8 x 10(-3). Selection on chlorsulfuron yielded resistant calluses at an ATF of 4.7 x 10(-6). When a selection on chlorsulfuron was subsequently applied to the kanamycin resistant calluses, 8% of them showed resistance to this herbicide. Southern analysis carried out on the herbicide resistant transformants detected the presence of the herbicide resistance gene of Arabidopsis into the genome of the transformed tobacco. Segregation analysis showed the presence of the resistance gene and the marker gene in the progeny of the five analysed transformants. 3 transformants showed evidence of genetic linkage between the two genes. In addition we show that using the same technique a kanamycin resistance gene from a transgenic tobacco could be transferred into sugar beet protoplasts at a frequency of 0.17% of the transformants.

Blotting, Southern↗
PubMed1991

Comparison of some arthropod toxins and toxin fragments as antagonists of excitatory amino acid-induced excitation of rat spinal neurones.

Wasp and spider venom toxins, which block glutamatergic transmission at invertebrate neuromuscular junctions, have recently been shown to block transmission at glutamate-operated synapses in mammalian central nervous system. Using the technique of iontophoresis on spinal neurones in anaesthetised rats, we have compared the action of five arthropod toxins and two toxin fragments, on responses to excitatory amino acids including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, kainate and N-methyl-D-aspartate (NMDA). All toxins caused greater than 70% mean reduction of non-NMDA responses. Only argiotoxin636 significantly reduced responses to NMDA. This blockade, like that induced by philanthotoxin-433 and -343, was readily reversible whereas blockade induced by Joro Spider toxin or Nephila Spider toxin was less readily reversible. Neither 2,4-dihydroxyphenylacetate nor 2,4-dihydroxyphenylacetylasparagine blocked NMDA or non-NMDA responses. It appears, therefore that small structural differences in the polyamine part of these toxin molecules give rise to different activity profiles with respect to selectivity and reversibility.

Action Potentials↗
PubMed1991

NMDA receptor antagonist effects of the stereoisomers of beta-cyclazocine in rats, in vivo and in vitro.

(+)- and (-)-beta-cyclazocine were examined as NMDA receptor antagonists following bath application to rat cortical wedges in vitro and i.v. administration to rat spinal cord neurones in vivo. Both isomers were found to be selective NMDA antagonists with little effect on excitations evoked by quisqualate. In vitro, IC50 values for (-)- and (+)-beta-cyclazocine against responses to 40 microM NMDA were estimated at 0.51 and greater than 100 microM, respectively. In vivo, (-)-beta-cyclazocine 0.25 mg.kg-1 reduced NMDA-evoked excitations by 70%, an effect substantially greater than that produced by (+)-beta-cyclazocine 2.5 mg.kg-1. (-)-beta-cyclazocine is the most potent NMDA antagonist benzomorphan tested to date, being about twice as potent as (-)-alpha-cyclazocine in this respect. In addition, the separation in potency exhibited by the beta-cyclazocine enantiomers as NMDA antagonists is much greater than that reported previously for the stereoisomers of the alpha-series.

Animals↗
PubMed1991

Performance of new criteria for right ventricular hypertrophy and myocardial infarction in patients with pulmonary hypertension due to cor pulmonale and mitral stenosis.

Historically, electrocardiographic criteria for right ventricular (RV) hypertrophy has achieved high specificity but low sensitivity. Recently, however, Butler-Leggett et al. have introduced three criteria that attained a 66% sensitivity in a population with RV hypertrophy due to mitral stenosis while maintaining a 95% specificity in an extensive normal control group. Electrocardiographic diagnosis of RV hypertrophy is principally dependent on changes in the QRS complex that may be masked or mimicked by myocardial infarction (MI). This dilemma has been confirmed by documentation of the low specificity of both the Selvester QRS scoring system for MI size estimation (greater than 3 points) and its screening subset (greater than 0 points) in a pure mitral stenosis population. This study introduces the population characterized by RV hypertrophy due to cor pulmonale, which has a mean pulmonary arterial systolic pressure that is higher than the mean for the mitral stenosis population and consequently suggests more severe RV hypertrophy. When compared, the Butler-Leggett criteria for RV hypertrophy are more sensitive in the new population than in the mitral stenosis population (89% versus 60%) and the Selvester QRS scoring system is less specific (12% versus 60%). Three sequential steps are suggested for electrocardiographic analysis: (1) diagnosis of RV hypertrophy using the Butler-Leggett criteria, (2) diagnosis of MI using the Selvester screening criteria in those patients with step 1 negative, and (3) estimation of MI size using the complete Selvester scoring system in patients with step 1 negative and step 2 positive.

Cardiomegaly↗
PubMed1991

Epitope mapping.

The immune response to extrinsic and intrinsic antigens involves specific antigen receptors on T and B cells. The precise antigenic determinants, or epitopes, recognized by these receptors are discrete sequences within the native antigen. The ability to identify and manufacture key epitopes in the immune response has important implications for disease diagnosis and immunointervention. Consequently, increasingly sophisticated technologies are being applied to epitope mapping. This report from a recent workshop gives a balanced view of progress to date and the challenges ahead.

B-Lymphocytes↗
PubMed1991

Resistance in Solanum brevidens to both potato virus Y and potato virus X may be associated with slow cell-to-cell spread.

A series of experiments was carried out to investigate the nature of the resistance of the wild potato species, Solanum brevidens, to potato virus X (PVX) and potato virus Y (PVY). In vitro inoculation of leaf protoplasts of S. brevidens and the virus-susceptible dihaploid S. tuberosum genotype PDH40 with PVX or PVY using polyethylene glycol showed that protoplasts of both species were similar in susceptibility. However, examination of protoplasts prepared from the leaves of S. tuberosum and S. brevidens inoculated 2 to 5 weeks earlier showed that the percentage of PVX- and PVY-infected leaf cells of S. tuberosum were, respectively, 45- to 100-fold and about 1000-fold greater than the percentage of infected leaf cells of S. brevidens. These results suggest that resistance in S. brevidens to both PVX and PVY could be associated with slow cell-to-cell spread rather than with slow virus replication.

Disease Susceptibility↗
PubMed1991

Excitatory amino acids: new tools for old stories or pharmacological subtypes of glutamate receptors: electrophysiological studies.

Although the N-methyl-D-aspartate (NMDA) subtype of L-glutamate receptor is well characterized, the significance of non-NMDA glutamate-sensitive binding sites is not well documented. In this study, a new tricyclic quinoxalinedione (NBQX) and an arthropod toxin (philanthotoxin) were shown to block responses of spinal neurones in vivo to kainate, quisqualate, and AMPA in parallel but had little effect on responses to NMDA. Philanthotoxin appeared to be a use-dependent antagonist consistent with a channel-blocking mode of action. On cortical wedges in vitro, however, NBQX proved to be a more potent antagonist of AMPA and quisqualate than of kainate (pA2 values of 7.1, 7.0, and 5.6, respectively) with no effect at 10 microM on responses to NMDA. These studies provide evidence that on cortical neurones, but not on spinal neurones. AMPA and kainate depolarize by pharmacologically different mechanisms.

Amino Acids↗
PubMed1991

Rheumatoid factors and complex formation. The role of light-chain framework sequences and glycosylation.

New information regarding rheumatoid factors (RFs) indicates that the RFs synthesized in synovium and lymphoid tissues of patients with rheumatoid arthritis (RA) are different from monoclonal and nonspecific RFs associated with other inflammatory states. The characteristics of RF associated with RA are as follows. They are of all Ig isotypes (not just IgM), indicating T-cell participation in antibody maturation. They have higher avidity for human IgG than for rabbit IgG. They use the human germline heavy-chain variable region (VH) gene VHIII more frequently than other VH genes, and light chains from multiple families. (In contrast, monoclonal RFs use predominantly VH1 and very commonly the V kappa IIIb germline gene HUMkv325). RA IgG is somatically mutated. (In contrast, monoclonal RFs use unmutated germline Ig genes). This suggests they are matured by stimulation either with specific antigens or other activation signals such as cytokines. They are abnormally glycosylated. In general, during periods of disease activity in adult and juvenile RA, a galactose is missing from the Fc of the IgG molecule, leaving an empty "pocket" between the C gamma 2 domains of heavy chains. The IgG RFs self-associate. This may result at least in part when galactose on the F(ab')2 portion of one IgG molecule fills the empty pocket in the Fc of another Ig molecule. Self-association forms immune complexes capable of fixing complement and probably of causing joint damage and vasculitis.

Animals↗
PubMed1990

Prognostic use of a QRS scoring system after hospital discharge for initial acute myocardial infarction in the Framingham cohort.

Myocardial infarct size is an important risk factor for survival after acute myocardial infarction (AMI). The purpose of this study was to determine the prognostic value of myocardial infarct size, as estimated by the Selvester 54-criteria/32-point QRS scoring system, in the Framingham cohort. During the first 30 years of the Framingham Heart Study, a total of 384 participants developed an AMI requiring hospitalization; from this group, 243 patients met the following inclusion criteria: (1) no electrocardiographic changes due to a previous infarction, (2) survival greater than 3 days after discharge from the AMI hospitalization and (3) no electrocardiographic evidence of conduction disturbances or ventricular hypertrophy at the time of their final in-hospital electrocardiogram. Univariate and multivariate analyses were performed to test the association of the QRS score, and other associated risk factors, with time until coronary heart disease-related death. QRS score was found to be significantly associated with outcome (p = 0.03), as was the systolic blood pressure before infarction (p greater than 0.001). Both univariate and multivariate analysis showed that a history of systolic hypertension was the variable most strongly associated with coronary heart disease-related death. Thus, identification of AMI survivors at high risk for subsequent mortality can be improved by routine blood pressure measurement before AMI, and QRS scoring of the electrocardiogram taken at hospital discharge.

Adult↗
PubMed1990

Sarcoidosis presenting as recurrent alcohol-induced pancreatitis.

A previously well 27-year-old Caucasian woman presented with five episodes of alcohol-induced abdominal pain over two years culminating in severe acute pancreatitis. Chest x-ray showed bilateral hilar lymphadenopathy and nodular pulmonary infiltrates. In hospital she developed a unilateral facial nerve palsy and other features of sarcoidosis, which was confirmed by biopsy of a pretracheal lymph node. No previous case is reported of sarcoidosis presenting with recurrent pancreatitis apparently induced on each occasion by moderate alcohol consumption and in the absence of other risk factors. Pancreatic involvement as part of sarcoidosis is uncommon but is treatable if recognized and has a good prognosis.

Adult↗
PubMed1990

Urinary levels of proteins and metabolites in workers exposed to toluene. A cross-sectional study.

We measured urinary excretion of albumin and retinol-binding proteins to investigate the occurrence of early renal dysfunction in 45 paint workers exposed principally to toluene, and in the same number of unexposed control subjects matched individually for sex and age. Two biological indicators of personal toluene absorption, namely urine hippuric acid and o-cresol, were also measured in the exposed subjects. A significantly higher level and increased prevalence of elevated retinol-binding protein in the urine of exposed workers was found, whereas no significant difference in urinary albumin concentration was seen between the two groups. Urinary concentrations of retinol-binding protein was correlated (r = 0.399, P less than 0.006) with that of o-cresol, but not with hippuric acid or employment duration. The results suggest a dose-dependent early tubular effect due to toluene exposure that might be useful for monitoring individuals exposed to toluene at work.

Adult↗
PubMed1990

Philanthotoxin blocks quisqualate-, AMPA- and kainate-, but not NMDA-, induced excitation of rat brainstem neurones in vivo.

1. The effect of electrophoretic ejection of philanthotoxin (the polyamine toxin, from the Egyptian digger wasp) was tested on responses of brainstem and spinal neurones in the pentobarbitone-anaesthetized rat to excitatory amino acids. 2. Philanthotoxin caused a dose-dependent reduction of responses to quisqualate, alpha-amino-3-hydroxy-5-phenyl-4-isoxazolepropionate (AMPA) and kainate with little effect on those to N-methyl-D-aspartate (NMDA). 3. The time-course of this antagonist action was slow. In particular the rate of recovery was dependent on frequency of ejection of the agonist. This agonist-dependent recovery suggests that philanthotoxin has a channel blocking mode of action on mammalian central neurones.

Action Potentials↗
PubMed1990

Specificity of rheumatoid factors in relation to the disease state in rheumatoid arthritis.

Rheumatoid factors found in patients with rheumatoid arthritis react with human IgG and with IgG from some other species. The levels of rheumatoid factor give some indication of prognosis, albeit a rather poor one in this highly variable disease. The high degree of variability may, in part, be due to differences in the fine specificity of the rheumatoid factor in each individual patient, leading to differences in the types of immune complex formed. To study this hypothesis the fine specificity of rheumatoid factors of the IgM, IgA, and IgG classes for IgG from human, baboon, orangutan, macaque, owl monkey, gorilla, marmoset, cow, pig, sheep, goat, horse, mouse, and chicken was examined. Differential reactivity for these species was found and associations between the presence of rheumatoid factor and the development of moderate or severe erosions.

Animals↗
PubMed1989

Transient gene expression in electroporated Solanum protoplasts.

Electroporation was used to evaluate parameters important in transient gene expression in potato protoplasts. The protoplasts were from leaves of wild potato Solanum brevidens, and from leaves, tubers and suspension cells of cultivated Solanum tuberosum cv. Désirée. Reporter enzyme activity, chloramphenicol acetyl transferase (CAT) under the control of the cauliflower mosaic virus (CaMV) 35S promoter, depended on the field strength and the pulse duration used for electroporation. Using field pulses of 85 ms duration, the optimum field strengths for maximum CAT activity were: S. brevidens mesophyll protoplasts--250 V/cm; Désirée mesophyll protoplasts--225 V/cm; Désirée suspension culture protoplasts--225 V/cm; and Désirée tuber protoplasts--150 V/cm. The optimum field strengths correlated inversely with the size of the protoplasts electroporated; this is consistent with biophysical theory. In time courses, maximum CAT activity (in Désirée mesophyll protoplasts) occurred 36-48 h after electroporation. Examination at optimised conditions of a chimaeric gene consisting of a class II patatin promoter linked to the beta-glucuronidase (gus) gene, showed expression (at DNA concentrations between 0-10 pmol/ml) comparable to the CaMV 35S promoter in both tuber and mesophyll protoplasts. At higher DNA concentrations (20-30 pmol/ml) the patatin promoter directed 4-5 times higher levels of gus expression. Implications and potential contributions towards studying gene expression, in particular of homologous genes in potato, are discussed.

Chloramphenicol O-Acetyltransferase↗
PubMed1989

Transient gene expression in aleurone protoplasts isolated from developing caryopses of barley and wheat.

Methods have been developed for the isolation of aleurone protoplasts from developing caryopses of Hordeum vulgare and Triticum aestivum in order to study transient expression of introduced genes. Chimaeric gene constructs were introduced into aleurone protoplasts by polyethylene glycol (PEG). Transient expression directed by the 35S promoter from cauliflower mosaic virus (CaMV) of the reporter gene encoding chloramphenicol acetyl transferase (CAT) was detected in aleurone protoplasts from developing barley and wheat grains. Using a similar construct, CAT activity increased when the alcohol dehydrogenase intron 1 fragment from maize was ligated between the 35S promoter and the CAT coding region. The demonstration of transient expression in protoplasts from developing aleurone layers indicates that they may be useful for investigating tissue and developmental control of genes coding for cereal seed proteins.

Brassica↗
PubMed1989

A system for accelerated provision of hearing aids to residents of homes for the elderly.

A study was undertaken to detect undiagnosed deafness in elderly people, living in Part III Residential Homes in North Tees, South Tees and Hartlepool Health Districts, to provide hearing aids and to estimate the subsequent success in rehabilitation. The residents were referred by the senior staff in the homes and assessed by a doctor and audiology technician in a domiciliary setting. Those found to have a significant hearing impairment were prescribed hearing aids without formal pure tone audiometry. A pilot study compared the method of hearing evaluation employed with such conventional testing. Six months after fitting, the degree of compliance with aiding was assessed. The results show a significant level of undiagnosed deafness in the community and, with this method of provision, an acceptance rate of 41.2 per cent of those recommended for aiding at six months which is higher than suggested by previous similar studies of this population.

Aged↗
PubMed1989

The evolution of a simplified method for interpretation of EEG in the preterm neonate.

We describe the evolution of a simplified method for the interpretation of serial EEG in preterm neonates which was tested in a first sample and revised and improved in a second sample of preterm neonates. There were 185 EEGs in the first sample and 206 EEGs in the second sample. The interpretation of the EEGs was related to mental, motor and neurological outcome in late infancy. Serial EEG is an excellent indicator of brain function in the preterm neonate.

Brain↗