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Biomedical subjects

M J Jackson

Publications and source records attributed to M J Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1995

A stable isotope study of zinc kinetics in Irish setters with gluten-sensitive enteropathy.

The short-term kinetics of Zn turnover were studied in Irish setters with gluten-sensitive enteropathy and control dogs following intravenous injection of 0.25 mg 96.5% enriched 70ZnCl2. The 70Zn enrichment of serum was found closely to obey two-compartment kinetics and the derived two-compartment decay equation was used to calculate the size and turnover of the two initial rapidly exchanging pools of body Zn. In normal Irish setters isotopic Zn initially equilibrates with a pool (a) of size 1.27 (SD 0.46) mumol/kg and then with a second pool (b) of size 6.83 (SD 1.72) mumol/kg. The fractional turnover of pool (b) was approximately one eighth that of pool (a). Enteropathic dogs showed no reduction in the size of either rapidly exchangeable Zn pool, reduction in serum Zn concentration or abnormality in Zn balance and hence these results do not support the possibility of an underlying Zn deficiency in this disorder.

Animals↗
PubMed1995

Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients.

Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. Whilst recognition of these conditions is increasing, the need for sophisticated biochemical and molecular studies has tended to limit both their investigation and diagnosis to a few specialist centres. Using a group of 51 patients with histochemically, biochemically and/or genetically defined respiratory chain defects, we have examined both the clinical heterogeneity of these disorders and how they may be investigated most effectively in non-specialist centres. We evaluated the use of the following routinely available clinical investigations--fasting intermediary metabolites (lactate, pyruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum creatine kinase estimation, EMG, EEG, CT, MRI and histological/histochemical muscle biopsy analysis. Our studies show that, in addition to well-recognized syndromes (e.g. chronic progressive external ophthalmoplegia, mitochondrial encephalopathy lactic acidosis and stroke like episodes, and myoclonus epilepsy with ragged red-fibres, a significant number of patients present with non-specific encephalopathic disorders. Furthermore, even within those categories of respiratory chain disease which have been genetically defined, a wide variation of presenting symptoms and signs were found. Where there was initial doubt concerning the diagnosis, the following clinical features were helpful in suggesting respiratory chain disease: ophthalmoplegia; a maternal pattern of inheritance; the presence of myopathy or deafness in association with encephalopathy. Of the clinical investigations we assessed, elevated lactate in blood or cerebrospinal fluid and low density lesions in the basal ganglia were helpful in identifying patients with respiratory chain dysfunction. Histochemical analysis of muscle was, however, the single most useful investigation being diagnostic in patients with chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome and myopathy, and of significant importance in patients presenting primarily with central nervous system disease. The results of our study are used to discuss the most appropriate approach to diagnosis of this group of disorders.

Adolescent↗
PubMed1995

Failure of electron paramagnetic resonance spectroscopy studies to detect elevated free radical signals in liver biopsy specimens from patients with alcoholic liver disease.

Electron paramagnetic resonance spectroscopy (EPR) was used to study free radicals and transition metal complexes in liver tissue taken from patients with liver disease. Samples were frozen to 77K directly following biopsy to prevent deterioration. Our major aim was to compare signals from patients suffering from alcohol abuse with those from patients having liver damage not induced by alcohol. Samples were obtained from 19 chronic alcohol abusers and 7 non-alcoholic liver disease patients. Of the 19 alcoholic patients, 18 had an increased fat content, 6 had Mallory's hyaline, 12 had an acute inflammatory response, 9 had increased stainable iron and 4 had evidence of fibrosis. A signal derived from free radicals with a spectroscopic splitting factor of g = 2.0045 was found in all samples. This signal in the alcoholic patients had a mean amplitude of 2.96 cm (+/- 1.42 SD), and in patients with non-alcoholic liver disease 2.12 cm (+/- 0.82) (p = 0.10 NS), measured under identical instrument settings. The molar proportion of diene conjugated linoleic acid (DCLA), a free radical marker, in the sera of alcoholic patients was 2.68% (+/- 1.93), but did not correlate with the free radical signals obtained by EPR spectroscopy. Also, there was no correlation between the free radical derived EPR signal and fat content, Mallory's hyaline, inflammatory infiltrate, iron or fibrosis in the liver biopsy specimens. Similarly the concentrations of aspartate transaminase, albumin, and gamma-glutamyl transferase in serum samples showed no correlations with free radical concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Dantrolene sodium protects against experimental ischemia and reperfusion damage to skeletal muscle.

The effect of 4 hours of ischemia followed by reperfusion for 1 hour has been studied in fully anesthetized rabbits. Muscles from the limb subjected to ischemia and reperfusion showed considerable ultrastructural damage, although the distribution of damage between muscles was not uniform (anterior tibialis > soleus > quadriceps). Damage to the muscle was associated with a significant increase in the concentration of some indicators of free radical-mediated processes (thiobarbituric acid-reactive substances and diene conjugates), although others (glutathione and protein sulfhydryl groups) were unchanged. Reperfused muscles also showed considerable changes in their calcium and sodium contents. Treatment of animals with dantrolene sodium (4 mg/hr) throughout the periods of ischemia and reperfusion was found to preserve the ultrastructural appearance of quadriceps, soleus and anterior tibialis muscles. No effect of dantrolene sodium on indicators of free radical activity or muscle cation content was seen.

Animals↗
PubMed1994

Molecular cloning and characterization of a murine LPS-inducible cDNA.

Murine macrophages respond to endotoxins by inducing a vast array of genes that play a major role in the host's response to infection and tumor growth. We have isolated and characterized a 1.8-kb cDNA, designated IRG2, from a cDNA library prepared from RNA isolated from the murine cell line, RAW 264.7, after bacterial LPS stimulation. The cDNA encodes a protein of 47 kDa that is the murine homologue of a small family of proteins described from IFN-induced human cells. The IRG2 message does not appear until 3 h after LPS exposure and its induction is dependent on new protein synthesis. IRG2 induction by LPS is slightly inhibited by the anti-inflammatory steroid, dexamethasone. Increasing cytosolic cAMP with either forskolin, dibutyryl cAMP, or 8-(4-chlorophenylthio)-cAMP caused marked inhibition of the LPS induction of IRG2. In contrast, activation of PKC with phorbol ester potentiated the LPS response. Removing extracellular Ca2+ with EGTA inhibited IRG2 induction; increasing intracellular calcium with the calcium ionophore A23187 led to enhanced levels of the IRG2 transcript. These data suggest that the induction of IRG2 occurs via a PKC pathway.

Amino Acid Sequence↗
PubMed1994

Serum octadeca-9,11 dienoic acid--an assay of free radical activity or a result of bacterial production?

The diene conjugated linoleic acid isomer is currently used as an assay of free radical activity, but recent studies have cast doubt on the specificity of the assay. Therefore, 180 strains of common bacterial lung pathogens were studied to determine whether they could produce the diene conjugated isomer of linoleic acid in vitro. The various strains were grown in tissue culture fluid spiked with linoleic acid. Concentrations of the diene conjugated 18:2 [9,11] linoleic acid isomer and the parent compound, 18:2 [9,12] linoleic acid were then determined using a high performance liquid chromatography method. The percentage molar ratio of these two isomers was found to be significantly elevated in 12.8% of all bacterial strains examined. In contrast the thiobarbituric acid reactivity, a non-specific measure of lipid peroxidation, was not elevated in any of the strains incubated in an identical fashion. These results suggest that the diene conjugated linoleic assay may not be a reliable marker of the free radical processes in the lung in the presence of certain bacterial infections.

Bacteria↗
PubMed1994

Time course of changes in plasma membrane permeability in the dystrophin-deficient mdx mouse.

Control C57Bl/10 and mutant, dystrophin-deficient mdx mice of different ages were used to study the permeability of the plasma membrane to cytosolic components, to a vital stain (procion orange) and to extracellular 45calcium. Prenecrotic, 14 +/- 2-day-old mdx mice had normal serum activities of creatine kinase (CK) and pyruvate kinase (PK). Muscles from these animals also had no increased permeability to procion orange or extracellular 45calcium. Serum activities of CK and PK had risen acutely in the 21-day-old mdx mouse compared with control and remained elevated up to 6 months of age. The influx of procion orange and 45calcium content were abnormally elevated in the 40 +/- 4-day-old mdx mouse. These data provide no evidence for an increase in muscle plasma membrane permeability as a primary pathogenic effect of a lack of dystrophin, but results suggest that some factor expressed or de-expressed during mouse development may be necessary for the full expression of the dystrophic process.

Aging↗
PubMed1994

Free-radical activity after primary coronary angioplasty in acute myocardial infarction.

Free-radical activity in coronary venous outflow was assessed before and after reperfusion in nine patients with acute infarction who had undergone successful recanalization of the infarct-related artery by primary coronary angioplasty. Free-radical activity was measured in serum samples from coronary venous outflow over a timed period of 24 hours by using (1) the percentage molar ratio (PMR) of the diene conjugate 9,11-linoleic acid, and (2) malonaldehyde concentration. Preangioplasty PMR means lay within the normal range, but showed a marked increase soon after successful recanalization. Relative to baseline, the changes over time reached statistical significance between 2 and 60 minutes. No statistically significant changes in malonaldehyde occurred over the study period. We conclude that successful recanalization of the infarct artery is associated with significantly elevated free-radical activity, as measured by the PMR of conjugated diene, in coronary venous outflow. Such patients may be at risk from free radical mediated reperfusion injury.

Adult↗
PubMed1994

Circulating markers of free radical activity in patients with pulmonary tuberculosis.

SETTING: Toxic free radicals have been implicated in the development of lung fibrosis which may be a long-term sequela of pulmonary tuberculosis. OBJECTIVE: To measure circulating indicators of free radical activity in patients with pulmonary tuberculosis in order to determine whether patients with active pulmonary TB have elevated levels of circulating free radical activity, and whether these levels correlated with disease activity as determined by other blood markers of inflammation. DESIGN: 17 patients with active pulmonary tuberculosis were studied. Serial serum levels of 3 assays of free radical activity were measured at diagnosis (17 patients), and over a 2-7 month period on chemotherapy (8 patients). 3 patients with active lymph node tuberculosis were also studied and 4 patients with old lung scarring from previously treated tuberculosis had their serum markers analysed. RESULTS: All 3 serum markers of free radical activity were elevated in patients with active pulmonary tuberculosis. During serial measurement in 8 patients the % molar ratio of 9,11 linoleic acid/9,12 linoleic acid fell progressively with treatment. Thiobarbituric acid reactive substances (TBARS) were initially elevated in 6/8 patients and remained elevated despite treatment. In 2 patients TBARS were in the normal range at presentation but subsequently rose with treatment. Desferrioxamine-chelatable iron was initially normal in all but 1 patient, remained normal in 2 patients, rose in 4 patients and fell in 1 patient. CONCLUSIONS: These results suggest that increased circulating levels of free radical activity are found in active pulmonary tuberculosis and hence may play a role in the resultant fibrosis. It also reinforces the belief that a range of free radical activity (FRA) indicators are produced in any inflammatory process with fibrogenic potential and that these indicators may be measuring different stages of the disease process.

Adolescent↗
PubMed1994

Interleukin-1 beta stimulates nitrite production in the rat ovary: evidence for heterologous cell-cell interaction and for insulin-mediated regulation of the inducible isoform of nitric oxide synthase.

Recent studies suggest that endogenously generated nitric oxide (NO) may mediate the effects of cytokines in a variety of tissues. In an effort to determine whether NO generation mediates any of the intraovarian actions of interleukin-1 beta (IL-1 beta), we have looked for and characterized the accumulation of nitrite by IL-1 beta-treated, cultured whole ovarian dispersates. Application of IL-1 beta significantly enhanced basal nitrite release in a dose-, cell density- and time-dependent manner, the latter characterized by a lag time of about 20 h, suggestive of induction of NO synthase (NOS). Cellular NOS activity was also elevated by IL-1 beta. Sustained nitrite accumulation required continuous application of IL-1 beta. The maximally stimulating dose of IL-1 beta (50 ng/ml) produced a 10-fold increase in nitrite accumulation by 96 h of culture, an effect reduced 23% when cells were cultured in substrate (i.e., arginine)-free media. IL-1 beta-stimulated nitrite accumulation was reduced to control levels by the simultaneous application of an IL-1 beta receptor antagonist, thereby suggesting a specific receptor-mediated effect. Both the control and IL-1 beta-stimulated levels of nitrite accumulation were attenuated in a dose-dependent manner by inhibitors that favor the inducible form of NOS. In contrast, selective inhibitors of the constitutive form of NOS were significantly less potent. No inhibition was noted after application of an inactive stereoisomeric analogue. IL-1 beta-induced nitrite accumulation was shown to require cell-cell interaction between granulosa and theca-interstitial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Dietary fish-oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation.

Ultraviolet radiation (UVR)-induced erythema may be mediated in part by free radical-generated tissue damage, including lipid peroxidation. We have examined the effect of dietary fish oil rich in omega-3 fatty acids upon susceptibility to UVB-induced erythema and epidermal lipid peroxidation. Fifteen volunteers took 10 g fish oil, containing 18% eicosapentaenoic acid and 12% docosahexaenoic acid, daily for 3 or 6 months. Sensitivity to UVB was assessed at intervals on fish oil, and 2.5 months after stopping treatment. Paired skin shave biopsies were taken from six subjects, at baseline and 3 months, from both irradiated and control skin. Fatty acid composition was analyzed and thiobarbituric acid-reactive substances measured as an index of lipid peroxidation. With increasing time on fish oil the minimal erythema dose rose progressively, from 18.9 +/- 13.9 mJ/cm2 (mean +/- SD) at baseline to 41.1 +/- 16.6 mJ/cm2 at 6 months, p < 0.01. Ten weeks after stopping fish oil the minimal erythema dose fell to 23.1 +/- 4.9 mJ/cm2, p < 0.05. Epidermal total omega-3 fatty acids rose from 1.8 +/- 0.4% total fatty acids (mean +/- SEM) to 24.2 +/- 3.9% at 3 months, p < 0.01. This was accompanied by a rise in thiobarbituric acid-reactive substances in irradiated skin from 6 +/- 0.3 (mean +/- SEM) to 18.5 +/- 2.6 A532/g skin, p < 0.01. Hence dietary omega-3 fatty acids produce a pronounced reduction in UVB-erythemal sensitivity, although susceptibility of skin to lipid peroxidation is increased. Thus, omega-3 fatty acids may act as an oxidizable buffer, protecting more vital structures from free radical damage.

Adolescent↗
PubMed1994

Release of creatine kinase and prostaglandin E2 from regenerating skeletal muscle fibers.

To study the effect of regeneration on the release of creatine kinase (CK) and prostaglandin E2 from muscle, extensor digitorum longus muscles of mice were injected with 50 microliters of BaCl2 solution in saline (1.2% wt/vol). Injected muscles showed almost complete degeneration at 3 days postinjection but had regenerated to approximately the same fiber cross-sectional area as contralateral control muscles by 12 days postinjection. These muscles released reduced amounts of intracellular CK compared with contralateral control muscles in response to excessive isometric contractile activity or treatment with the calcium ionophore A-23187 (20 microM) in vitro. However, regenerating muscles contained a lower total CK activity than contralateral control muscles, which accounted for the reduced CK efflux after experimental damage. Regenerating muscles released an increased amount of prostaglandin E2 compared with control muscles after both damaging stimuli. We conclude that regenerated muscles show no reduced susceptibility to contraction-induced damage (as assessed by CK release) but show an elevated release of prostaglandin E2 in response to contractile activity or an increase in intracellular calcium.

Animals↗