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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 145 records · Page 8Linked to original sources
PubMed1993

A brief mental fatigue questionnaire.

A brief mental fatigue questionnaire was administered to normal subjects and muscle-diseased, Chronic Fatigue Syndrome (CFS), recovered CFS and depressed patients. The questionnaire was found to have excellent internal consistency and discriminated effectively between CFS and depressed patients on the one hand and recovered CFS, normal and muscle-diseased patients on the other. However, the scale failed to discriminate between CFS and depressed subjects, who were found to experience qualitatively and quantitatively similar mental fatigue symptoms.

Adult↗
PubMed1993

Exercise performance and fatiguability in patients with chronic fatigue syndrome.

To examine the role of delay in recovery of peripheral muscle function following exercise in the fatigue experienced by patients with the chronic fatigue syndrome (CFS) and to examine the influence of effort perception in limiting exercise performance in these patients, a study was carried out on a group of twelve patients with chronic fatigue syndrome and 12 sex and age-matched sedentary control subjects. Symptom limited incremental cycle exercise tests including measurements of perceived exertion were performed followed by examination of the contractile properties of the quadriceps muscle group for up to 48 hours. Muscle function was assessed by percutaneous electrical stimulation and maximum voluntary contractions. Muscle function at rest and during recovery was normal in CFS patients as assessed by maximum isometric voluntary contraction, 20:50 Hz tetanic force ratio and maximum relaxation rate. Exercise duration and the relationship between heart rate and work rate during exercise were similar in both groups. CFS patients had higher perceived exertion scores in relation to heart rate during exercise representing a reduced effort sensation threshold of 3.2 units on an unmodified Borg scale in CFS patients. Patients with chronic fatigue syndrome show normal muscle physiology before and after exercise. Raised perceived exertion scores during exercise suggest that central factors are limiting exercise capacity in these patients.

Adolescent↗
PubMed1993

Ethanol increases delta-opioid receptor gene expression in neuronal cell lines.

Long-term treatment with ethanol increases delta-opioid receptor (DOR) expression in the NG108-15 neuroblastoma x glioma hybrid cell line. To determine the underlying mechanism, we studied the effects of ethanol on [3H]diprenorphine binding to intact cells and DOR gene expression in four related clonal neural cell lines. Incubation with 200 mM ethanol for 48 hr increased [3H]diprenorphine binding by 1.4- (N18TG2), 1.8- (NG108-15), 1.9- (N4TG1), and 3.0-fold (N1E-115). Treatment with 25, 50, or 100 mM ethanol for 1 week caused a dose-dependent increase in receptor expression. Receptor up-regulation was associated with an increase in the potency of etorphine for inhibiting prostaglandin E1-stimulated cAMP accumulation. Constitutive DOR expression differed more than 3-fold among the different cell lines and correlated positively with basal cAMP levels. Long-term ethanol treatment increased basal cAMP levels in three of the four cell lines, but did not induce cellular differentiation. Northern blot analysis demonstrated an identical pattern of multiple transcripts in the four cell lines. Ethanol increased the abundance of DOR mRNA by approximately 3-fold in N18TG2 cells and by approximately 5-fold in the remaining cell lines. These findings indicate that clinically relevant concentrations of ethanol regulate DOR expression by increasing the abundance of DOR mRNA. The disparity between the increase in gene expression and ligand binding suggests that ethanol may also modify mRNA translation or receptor processing.

Animals↗
PubMed1993

Ileal perforation in typhoid: bacteriological and immunological findings.

In typhoid perforation patients, Salmonella typhi was isolated from blood in 4%, ileal contents in 23%, peritoneal pus in 13% and from mesenteric lymph nodes in 71%. While isolation of S. typhi was made from patients with less than 4 days of chloramphenicol therapy, cultures were negative from these sites after 5 days of therapy; however, S. typhi appeared to remain viable in the lymph nodes even after such therapy. All isolates of S. typhi were sensitive to chloramphenicol. Significant SAT titers (0 > or = 1/240) were obtained in only 7/21 (33%) of patients. The perforated group had lower geometric mean titers (0-1/138; H-1/46), when compared to matched patients with uncomplicated typhoid fever (0-1/476; H-1/148). This difference was significant (0- p < 0.005; H- p < 0.0025). The two groups (uncomplicated and perforated) showed no significant difference in total serum IgG, IgM and IgA or isohemagglutinin levels, indicating that the apparent hyporeactivity was not due to a generalized humoral immunodeficiency. Mesenteric lymph node histology showed hyporeactivity in both the T cell and B cell zones. These findings are discussed with the suggestion that S. typhi-specific host immunological hyporeactivity could be an explanation for these observations and a basis for the pathogenesis of perforation. Aerobic cultures of the peritoneal pus gave 39 isolates from 25 patients; the predominant isolates were Escherichia coli (24) and Klebsiella pneumoniae (12). On no occasion was S. typhi the predominant isolate. Gentamicin and kanamycin were the only two antibiotics which were consistently effective in vitro against the aerobic isolates from peritoneal pus.

Humans↗
PubMed1992

Cloning of a delta opioid receptor by functional expression.

Opiate drugs have potent analgesic and addictive properties. These drugs interact with receptors that also mediate the response to endogenous opioid peptide ligands. However, the receptors for opioids have eluded definitive molecular characterization. By transient expression in COS cells and screening with an iodinated analog of the opioid peptide enkephalin, a complementary DNA clone encoding a functional delta opioid receptor has been identified. The sequence shows homology to G protein-coupled receptors, in particular the receptors for somatostatin, angiotensin, and interleukin-8.

Amino Acid Sequence↗
PubMed1992

Application of gas chromatography-mass spectrometry with selected ion monitoring to the urinanalysis of 4-pyridoxic acid.

An analytical protocol has been developed for the analysis of urinary 4-pyridoxic acid (4-PA) by gas chromatography-mass spectrometry (GC-MS) for use in metabolic studies. Aliquots of urine were deproteinised and fractionated by isocratic reversed-phase high-performance liquid chromatography. The eluent fraction containing the 4-PA was collected, freeze-dried and silylated using N-methyl-N-(tert.-butyldimethylsilyl)trifluoroacetamide. Derivatisation produced the mono-tert.-butyldimethylsilyl derivative of 4-PA lactone. This derivative was readily amenable to GC-MS analysis in the electron ionisation (70 eV) mode, yielding a prominent fragment ion at m/z 222 ([M-57]+; base peak). A heavy isotope-labelled derivative of pyridoxine [dideuteriated pyridoxine; 3-hydroxy-4-(hydroxymethyl)-5-[hydroxymethyl-2H2]-2-methylpyridine] has been synthesised and is being employed to determine the kinetics of labelling of the body pools of vitamin B6. Kinetic measurements are based on the determination of the relative proportions of metabolically produced deuterium-labelled and non-labelled 4-PA in urine, obtained from stable isotope ratios determined by low-resolution selected ion monitoring using a bench-top quadrupole GC-MS system.

Animals↗
PubMed1992

Gene transfer of a reserpine-sensitive mechanism of resistance to N-methyl-4-phenylpyridinium.

The toxin N-methyl-1,2,3,6-tetrahydropyridine produces a model of neural degeneration very similar to idiopathic Parkinson disease. To understand the cellular mechanisms that modulate susceptibility to its active metabolite N-methyl-4-phenylpyridinium (MPP+), we have transfected a cDNA expression library from the relatively MPP(+)-resistant rat pheochromocytoma PC12 cells into MPP(+)-sensitive Chinese hamster ovary (CHO) fibroblasts. Selection of the stable transformants in high concentrations of MPP+ has yielded a clone extremely resistant to the toxin. Reserpine reverses the resistance to MPP+, suggesting that a transport activity protects against this form of toxicity, perhaps by sequestering the toxin within an intracellular compartment. In support of this hypothesis, dopamine loaded into the CHO transformant shows a localized distribution that is distinct from the pattern observed in wild-type cells and is also reversed by reserpine.

1-Methyl-4-phenylpyridinium↗
PubMed1992

The synaptic vesicle protein SV2 is a novel type of transmembrane transporter.

The primary function of synaptic vesicles is to store and release neurotransmitter. Synaptic vesicles are locally recycled following exocytosis and rapidly refilled with neurotransmitter from the cytoplasm by a process that depends on the electrochemical gradient generated by a proton pump. Little is known about the molecules that import neurotransmitter into synaptic vesicles. We report here that the sequence of the synaptic vesicle protein SV2 identifies this protein as a novel type of transmembrane transporter. The deduced amino acid sequence of SV2 contains two sets of six predicted transmembrane domains: the six most N-terminal transmembrane domains are highly homologous to a subfamily of transporters that includes the human glucose transporter, while the six most C-terminal domains are homologous to the plasma membrane transporters for neurotransmitters. We propose that SV2 mediates transport of neurotransmitters into synaptic vesicles.

Amino Acid Sequence↗
PubMed1992

A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter.

Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Organization of central cholinergic neurons revealed by combined in situ hybridization histochemistry and choline-O-acetyltransferase immunocytochemistry.

Digoxigenin-labeled riboprobes and in situ hybridization of choline-O-acetyltransferase mRNA, both alone and in combination with immunohistochemical procedures for the synthetic enzyme of acetylcholine, were used to map the topography of putative cholinergic neurons in the rat central nervous system. Only the anti-sense riboprobe yielded specific labeling, which was absent in brain sections processed with sense riboprobe. Telencephalic neurons demonstrating the mRNA for choline-O-acetyltransferase and choline-O-acetyltransferase-like immunoreactivity were found in the caudate-putamen nucleus, nucleus accumbens, olfactory tubercule, Islands of Calleja complex, medial septal nucleus, vertical and horizontal limbs of the diagonal band, substantia innominata, nucleus basalis, and nucleus of the ansa lenticularis, as well as occasionally in the amygdala. Neurons in the cerebral cortex, hippocampus, and primary olfactory structures did not demonstrate hybridization signal, even though some cells in those areas were observed to exhibit choline-O-acetyltransferase-like immunopositivity. Thalamic cells were devoid of hybrido- and immunoreactivity, with the exception of several neurons located primarily in the ventral two-thirds of the medial habenula. A few cell bodies labeled with riboprobe and co-localizing choline-O-acetyltransferase-like immunopositivity were found in the lateral hypothalamus, caudal extension of the internal capsule, and zona incerta. Neurons in the pedunculopontine and laterodorsal tegmental nuclei evinced moderate hybridization signal, whereas cells of the parabigeminal nucleus were very weakly reactive. In contrast, motor neurons of the cranial nerve nuclei demonstrated high levels of choline-O-acetyltransferase mRNA and choline-O-acetyltransferase-like immunoreactivity. Putative cholinergic somata in the ventral horns and intermediolateral cell columns of the spinal cord and around the central canal were also labeled with riboprobe. It is concluded that hybridocytochemistry with digoxigenin-labeled riboprobes confirms the existence of cholinergic neurons in most of the neural regions believed to contain them on the basis of acetylcholinesterase pharmacohistochemistry and choline-O-acetyltransferase immunocytochemistry, with the prominent exceptions of the cerebral cortex, hippocampus, olfactory bulb, anterior olfactory nucleus, and caudal raphe nuclei, which apparently do not possess neurons expressing detectable levels of the mRNA for the synthetic enzyme of acetylcholine.

Animals↗
PubMed1992

Cholinergic neurons in the rat central nervous system demonstrated by in situ hybridization of choline acetyltransferase mRNA.

Digoxigenin-labeled RNA probes and in situ hybridization histochemistry were used to examine choline acetyltransferase gene expression in the rat central nervous system. Hybridization signal was present only in brain sections processed with the antisense riboprobe. The sense probe did not yield labeling, further validating the specificity of tissue reactivity. Telencephalic neurons containing the mRNA for the cholinergic synthetic enzyme were found in the caudate-putamen nucleus, nucleus accumbens, olfactory tubercule, islands of Calleja complex, medial septal nucleus, vertical and horizontal limbs of the diagonal band, substantia innominata, nucleus basalis, and nucleus of the ansa lenticularis. Some somata evincing hybridization signal were observed in the anterior amygdalar area, and an occasional such cell was seen in the basolateral and central amygdalar nuclei. Neurons in the cerebral cortex, hippocampus, and primary olfactory structures did not demonstrate hybridocytochemically detectable amounts of choline acetyltransferase mRNA. Thalamic cells were devoid of reactivity, with the exception of several neurons located primarily in the ventral two-thirds of the medial habenula. A few somata labeled with riboprobe were found in the lateral hypothalamus, caudal extension of the internal capsule, and zona incerta. Neurons in the pedunculopontine and laterodorsal tegmental nuclei were moderately reactive, whereas cells of the parabigeminal nucleus exhibited a very weak hybridization signal. No somata in the brainstem raphe nuclei, including raphe obscurus and raphe magnus, were observed to bind riboprobe. In contrast, motor neurons of the cranial nerve nuclei demonstrated relatively large amounts of choline acetyltransferase mRNA. Putative cholinergic somata in the ventral horns and intermediolateral cell columns of the spinal cord were also labeled with riboprobe, as were a few cells around the central canal. We conclude that hybridocytochemistry with digoxigenin-labeled riboprobes confirms the existence of cholinergic neurons (i.e. those that synthesize and use acetylcholine as a neurotransmitter) in most of the neural regions deduced to contain them on the basis of previous histochemical and immunocytochemical data. Notable exceptions are the cerebral cortex and hippocampus, which do not possess neurons expressing detectable levels of choline acetyltransferase mRNA.

Animals↗
PubMed1992

The transport of neurotransmitters into synaptic vesicles.

As investigations identify additional plasma membrane neurotransmitter transporters, attention has focused on the molecular basis of neurotransmitter transport into synaptic vesicles. The transport of biogenic amines into chromaffin granules has served as the paradigm for understanding vesicular transport. Recent work now describes the vesicular transport of other classical neurotransmitters, which occur by distinct but related mechanisms. To determine their biochemical basis, several of the transporters have been functionally reconstituted in liposomes. The ability of vesicular amine transport to protect against the neurotoxin MPP+ has permitted the isolation of the first cDNA clone for a member of this family, and the sequence establishes a relationship with drug-resistance transporters in bacteria.

Animals↗
PubMed1992

Detection of bone marrow abnormalities in patients with Hodgkin's disease by T1 mapping of MR images of lumbar vertebral bone marrow.

Pixel by pixel T1 mapping of MR images has been used in conjunction with image analysis techniques to study the lumbar vertebral bone marrow of 20 patients with refractory or relapsed Hodgkin's disease prior to salvage chemotherapy, or high dose chemotherapy with autologous bone marrow rescue. Compared to 18 age matched controls, seven patients had significantly abnormal lumbar vertebral marrow T1 histograms with median, 5% and 95% centile T1 values that lay outside a three dimensional 95% probability region obtained for the normals. Six of these patients had increased areas of high T1 consistent with bone marrow involvement with lymphoma; although, only in two of them had Hodgkin's disease been detected by bilateral iliac crest bone marrow biopsy. Post-treatment studies were performed in four patients who had abnormal areas of high T1 in the lumbar vertebral bone marrow. All showed normalisation of the T1 histogram, with a reduction of T1 values to within the normal range as defined by the studies of age matched controls. T1 mapping of bone marrow offers potential for detecting bone marrow infiltrates in patients with lymphoma, and also for the assessment of treatment response.

Adult↗
PubMed1992

Accumulation of calcium by normal and dystrophin-deficient mouse muscle during contractile activity in vitro.

1. Accumulation of calcium by extensor digitorum longus muscles from dystrophin-deficient mdx and control C57BL/10 mice has been studied in vitro by measurements of total muscle calcium and by following the retention of 45Ca resulting from the incubation of muscles with the isotope for up to 2 h. 2. The rate of influx of calcium, calculated from the retention of 45Ca, was linear over 2 h in muscles at rest with no significant difference between mdx and control muscles. 3. Repetitive tetanic stimuli caused a substantial increase in 45Ca flux into both mdx and control muscles. This elevated rate of influx was maintained by control muscle, but not by mdx muscle after stimulation resulting in a significantly smaller total calcium flux into mdx muscle compared with control muscle by 1 h after stimulation. Similar changes were also seen in the total muscle calcium content of mdx and control muscles. Comparison of these results with those for loss of cytosolic creatine kinase previously reported (McArdle, A., Edwards, R.H.T. & Jackson, M.J. Clin. Sci. 1991; 80, 367-71) [1] indicate that control and dystrophin-deficient muscles release equivalent amounts of intracellular creatine kinase in response to the same accumulation of intracellular calcium. 4. These results therefore do not support the hypotheses that dystrophin deficiency in muscle leads to increased calcium influx during contractile activity, or that dystrophin-deficient muscle shows any inherent increased permeability to cytosolic proteins.

Animals↗
PubMed1992

Magnetic resonance spectroscopy and imaging of muscle--a physiological approach.

Magnetic resonance spectroscopy (MRS) and imaging (MRI) are now well established techniques for the study of cellular metabolism and gross structure of muscle. Using non-ferrous materials, we have constructed a system for the measurement of isometric force of quadriceps in response to percutaneous electrical stimulation and voluntary effort within the bore of a 48 cm diameter 1.5 T General Electric SIGNA whole body MR system. Using this system we have been able to study the relationship between electromechanical coupling and chemistry of muscle, with 31P MRS for the measurement of high-energy phosphates and pH, during electrically stimulated activity. Image analysis using the Context Vision system enables a distinction to be made, in 1H MRI by T1/T2 mapping, of muscle, fat and connective tissue to give force per unit cross sectional area of muscle. The combination of MR and functional measurements provide a valuable tool for further detailed analysis of human muscle weakness and fatigue.

Electric Stimulation↗