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Biomedical subjects

P Jackson

Publications and source records attributed to P Jackson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Differentiation of common benign pigmented skin lesions from melanoma by high-resolution ultrasound.

BACKGROUND: There are potential clinical benefits if non-invasive methods can be used to diagnose or exclude melanoma. OBJECTIVES: We investigated high-resolution ultrasound (HRU) as a potential non-invasive diagnostic aid for pigmented skin lesions. METHODS: Using a 20-MHz ultrasound B-scan imaging system interfaced to a computer, we assessed acoustic shadowing and entry echo line enhancement (EEE) for 29 basal cell papillomas (BCPs) and 25 melanomas. Acoustic shadowing was estimated by the dermal echogenicity ratio (DER), comparing mean echogenicity below the lesion with that of adjacent dermis. Histological features were scored independently. RESULTS: DER < 3 correctly distinguished melanoma from BCP with 100% sensitivity and 79% specificity. Specificity increased to 93% if the presence of EEE was included as a discriminator. Shadowing correlated most significantly with histological extent of hyperkeratosis (P < 0.0001). Consequently, this method falsely identified non-keratotic acanthotic BCP (n = 3) as melanoma. Highly significant differences between benign naevi (n = 15) and melanomas (n = 24) were found. The SD of retrolesional echogenicity was higher for naevi than melanomas (P < 0.0001), but such an analysis was poorly specific for the diagnosis of melanoma (30%). CONCLUSIONS: Overall, HRU has considerable potential as a high-performance screening tool to assist in the discrimination between BCP, but not benign naevi, and melanoma. In particular, it may be possible to exclude melanoma with 100% certainty in the differentiation of BCP from melanoma.

Diagnosis, Differential↗
PubMed2000

Interleukin 6 induction in the canine myocardium after cardiopulmonary bypass.

OBJECTIVE: Interleukin 6 is a proinflammatory cytokine with a plasma concentration that has been noted to increase in response to cardiopulmonary bypass. The source of interleukin 6 after cardiopulmonary bypass is unknown. This study examined the myocardium as a potential source of interleukin 6 in this context. METHODS: Dogs underwent 90 minutes of hypothermic cardiopulmonary bypass with 60 minutes of cardioplegic arrest. After rewarming, they were reperfused with the chest open for either 3 (n = 4) or 6 (n = 4) hours, at the end of which myocardial samples were obtained. Four additional animals undergoing open thoracotomy without bypass served as time-matched controls. Northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridization were used to examine the myocardium for the induction of interleukin 6 and intercellular adhesion molecule-1. RESULTS: Northern blot analysis and reverse transcriptase-polymerase chain reaction demonstrated a marked increase in myocardial interleukin 6 messenger RNA in 3 of 4 dogs at 3 hours after bypass and 3 of 4 dogs at 6 hours after bypass, which was not present in sham-bypass control animals. Northern blots at 3 hours after cardiopulmonary bypass also demonstrated myocardial intercellular adhesion molecule-1 induction. In situ hybridization studies confirmed that cardiac myocytes were a principal source of interleukin 6 messenger RNA early after cardiopulmonary bypass. Northern blots of messenger RNA extracted from isolated neutrophils and mononuclear leukocytes obtained from blood samples before bypass, at the end of bypass, and 3 hours after bypass failed to demonstrate interleukin 6 induction. CONCLUSION: Despite protection with cold cardioplegic arrest, the myocardium was a significant source of interleukin 6 synthesis after cardiopulmonary bypass. Local production of interleukin 6 may play a pivotal role in postoperative myocardial function.

Animals↗
PubMed2000

Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man.

1. In the present study, nine cytochrome P450 enzyme activities in seven species were characterized to allow a practical means of comparing this important metabolic step between various test animals and man. 2. Enzyme activities and kinetic parameters were first determined towards marker substrates for human cytochrome P450 enzymes. Inhibition profiles were then determined with both antibodies directed against various cytochrome P450 enzymes and with chemical inhibitors. 3. Both the enzyme kinetic parameters/enzyme activities, and the inhibition profiles obtained for the animal species were compared with those obtained for human liver microsomes in order to postulate the animal species most similar to man with regard to each individual cytochrome P450 enzyme activity. 4. It was found that, as expected, none of the tested species was similar to man for all the measured P450 enzyme activities, but that in each species only some of the P450 enzyme activities could be considered as similar to man. 5. When it is known which human cytochrome P450 enzymes are involved in the metabolism of a compound, the comparative data presented here can be used for selecting the most suitable species for in vitro and in it no experiments.

Animals↗
PubMed2000

Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake.

Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (-120 to -20 min), a control (-20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 microg. kg(-1). min(-1)) was infused along with intraportal insulin (1.2 mU. kg(-1). min(-1)) and glucagon (0.5 ng. kg(-1). min(-1)). Hepatic sinusoidal insulin was four times basal (73 +/- 7 microU/ml) and glucagon was basal (55 +/- 7 pg/ml). Glucose was infused peripherally (0-300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 microg and 0.1 microg. kg(-1). min(-1) from 120 min on. ACh was infused intraportally at 3 microg. kg(-1). min(-1) from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg. kg(-1). min(-1)) from output (2.1 +/- 0.3 and 1.1 +/- 0.2) to uptake (2.8 +/- 0.9 and 2.6 +/- 0.6) and lactate balance (micromol. kg(-1). min(-1)) from uptake (7.5 +/- 2.2 and 6.7 +/- 1.6) to output (3.7 +/- 2.6 and 3.9 +/- 1.6) by 120 min in the control and test protocols, respectively. Thereafter, in the control protocol, NHGU tended to increase slightly (3.0 +/- 0.6 mg. kg(-1). min(-1) by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 +/- 0.6 and 4.6 +/- 0.6 mg. kg(-1). min(-1) by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery.

Acetylcholine↗
PubMed1999

Magma flow instability and cyclic activity at soufriere hills volcano, montserrat, british west indies

Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.

Journal Article↗
PubMed1999

Sequence, assembly and analysis of pX01 and pX02.

Bacillus anthracis plasmids pX01 and pX02, harboured by the Sterne and Pasteur strains, respectively, have been sequenced by random 'shotgun' cloning and high throughout sequence analysis. These sequences have been assembled (Sequencher) to generate a circulate pX01 plasmid containing 181 656 bp and a single linear (gapped) pX02 contig containing at least 93.479 bp. Initial annotation suggests that the two plasmids combined contain at least 200 potential open reading frames (ORFs) with < 40% having significant similarity to sequences registered in open databases. Collectively, only 118 566 bp of the pX01 DNA (65%) represent predicted coding regions. This value is similar to published gene densities for other plasmids and is indicative of the larger intergenic spaces in plasmids vs those found in the chromosomes of the parental microbes (85-93% gene density). A 70 kbp region including the toxin genes (cya, lef and pag) is distinct from the remainder of the pX01 sequence: (1) it has a lower gene density (58 vs 70%) than the remaining 111 kbp; (2) it contains all but one of the co-regulated transcriptional fusions identified by transposon mutagenesis (Hoffmaster & Koehler 1997) and (3) it contains a significantly higher proportion of positive BLAST scores (62 vs 20%) for putative ORFs. These data suggest different origins for the two regions of pX01.

Bacillus anthracis↗
PubMed1999

Caffeine-increased radiosensitivity is not dependent on a loss of G2/M arrest or apoptosis in bladder cancer cell lines.

PURPOSE: Bladder cancer cell lines UCRU-BL-13, UCRU-BL-17/2 and UCRU-BL-28, with differing p53 status and molecular responses to irradiation, were used to investigate possible mechanisms for caffeine-induced radiosensitization. MATERIALS AND METHODS: After treatment with caffeine and exposure to X-radiation, radiosensitivity was determined by clonogenic assay. Cell-cycle arrest and apoptosis were measured by flow cytometry. RESULTS: Both BL-13 and BL-28 cells (each expressing p53 with a wild-type sequence) fail to arrest at the G2 checkpoint after radiation, but nevertheless caffeine did induce radiosensitization. In contrast, in BL-17/2 cells (expressing p53 with a point mutation in codon 280), caffeine treatment abrogated the radiation-induced G2 arrest but was not accompanied by radiosensitization. No effects on radiosensitivity were seen in RT112 cells (expressing a functionally defective p53) at low caffeine doses (2 mM), but at higher doses (4 mM and 10 mM) caffeine caused both abrogation of radiation-induced G2 arrest and radiosensitization. In none of the cell lines examined did caffeine treatment and/or irradiation result in apoptosis. CONCLUSIONS: In contrast with previous studies, the data suggest that radiosensitization induced by caffeine is not dependent on abrogation of G2 arrest or the induction of apoptosis, and is not selective for cells expressing p53 proteins with mutations.

Apoptosis↗
PubMed1999

Molecular aspects of cell wall modifications during fruit ripening.

Fruit ripening is associated with cell wall modifications. The present review focuses on cell wall components and the nature of noncovalent and covalent interactions in the primary cell wall. The role of structural protein cross-links are evaluated within the context of cell wall-mediated changes in texture during fruit ripening. The article discusses molecular approaches in fruit cell wall interactions to regulate processes in fruit ripening in order to improve post-harvest textural characteristics.

Biotechnology↗
PubMed1999

Ontogeny of hepatitis C virus (HCV) hypervariable region 1 (HVR1) heterogeneity and HVR1 antibody responses over a 3 year period in a patient infected with HCV type 2b.

Hypervariable region 1 (HVR1) sequences of 96 clones at six time-points representing 27 variants in two major and one minor group were identified in a patient with chronic hepatitis C virus (HCV) infection over 3 years. Major and selected minor variants were used to design synthetic peptides corresponding to the HVR1 C terminus. Peptide ELISA reactivity with IgG was plotted against the corresponding clone frequency, and three patterns emerged: (1) three peptides were unreactive; (2) antibodies against two peptides followed emergence of the corresponding variant, suggesting isolate-specificity; (3) antibodies against four peptides preceded the appearance of the corresponding variant, indicating cross-reactivity or previous exposure. Cross-reactivity was investigated further: sera from six time-points were tested against 11 unrelated HVR1 peptides, seven of which (63.6%) showed cross-reactivity at all time-points. Cross-reactivity of nine patient-specific peptides tested against a panel of 45 heterologous sera from chronic HCV carriers ranged between 0 and 20%. Only three of 27 variants appeared at more than one time-point and in two cases specific and/or cross-reactive HVR1 antibodies coexisted with the corresponding variant, consistent with emergence of escape mutants. In addition, analysis of HVR1 IgG reactivity within a group of closely related patient-specific peptides revealed a loss of reactivity in one peptide attributable to a single amino acid substitution. Interferon-alpha treatment considerably reduced viral RNA but, paradoxically, heterogeneity increased.

Adult↗
PubMed1999

Blockade of NAALADase: a novel neuroprotective strategy based on limiting glutamate and elevating NAAG.

Excessive glutamate receptor activation is thought to be involved in the neuronal injury caused by stroke. Based on the hypothesis that N-acetyl-aspartyl-glutamate (NAAG) is a modulatory neurotransmitter or storage form of glutamate, we have pursued a novel strategy of therapeutic intervention, blockade of N-acetylated alpha-linked acidic dipeptidase (NAALADase), the enzyme that hydrolyzes NAAG to liberate glutamate. Using the suture model of transient middle cerebral artery occlusion (MCAO) in rats, the prototype NAALADase inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) dramatically reduced extracellular glutamate accumulation measured by microdialysis both during a 2-hour occlusion and during reperfusion, consistent with an effect on glutamate supply. During reperfusion, the decrease in glutamate was accompanied by an equimolar, reciprocal rise in extracellular NAAG. NAALADase inhibition may prove to be a well tolerated therapy for cerebral ischemia. In addition, NAALADase inhibitors should prove to be important tools in understanding the physiological role of NAAG in the brain.

Animals↗
PubMed1999

Correlation between epithelial cell proliferation and histological grading in gastric mucosa.

AIM: To determine if there is a correlation between the histological findings in the gastric mucosa and the degree of cell proliferation in gastric antral biopsies. METHODS: Cell proliferation in gastric antral biopsies was determined by in vitro bromodeoxyuridine labelling. Histological sections were assessed using the Sydney System. RESULTS: There was a positive correlation between antral mucosal cell proliferation and the acute inflammatory cell infiltrate (r = 0.29; p = 0.03). There was a stronger correlation with the chronic inflammatory cell infiltrate (r = 0.53; p < 0.0001) and the density of H pylori colonisation (r = 0.54; p < 0.0001). There was no correlation between gastric epithelial proliferation and the degree of atrophy. Stepwise multiple regression indicates that the only independent predictor of epithelial cell proliferation is the density of H pylori colonisation (p < 0.0001). CONCLUSIONS: H pylori increases gastric epithelial cell proliferation through the mucosal inflammatory response and probably by other means. The strong correlation between epithelial proliferation, the chronic inflammatory cell infiltrate, and the density of H pylori colonization may have implications for gastric carcinogenesis.

Adolescent↗
PubMed1998

Individual promoter and intron p53-binding motifs from the rat Cyclin G1 promoter region support transcriptional activation by p53 but do not show co-operative activation.

The rat Cyclin G1 gene promoter contains one p53-binding motif upstream of the transcription start site, and a second motif downstream in the first intron. We have investigated the possibility that these motifs co-operate to permit high level promoter activation by p53. Although individual motifs supported p53-dependent, orientation-independent transcriptional activation, using reporter plasmids containing both motifs, we found no evidence for co-operative promoter activation either after co-transfection with human p53 expression plasmids, or after exposure of transfected cells to cisplatin and UV-radiation.

Animals↗
PubMed1998

Synergistic transcriptional activation of the MCK promoter by p53: tetramers link separated DNA response elements by DNA looping.

The WAF1, Cyclin G and muscle creatine kinase (MCK) genes, all contain multiple copies of the consensus p53-binding element within their regulatory regions. We examined the role of these elements in transactivation of the muscle creatine kinase (MCK) gene by p53. The MCK promoter possesses distal (-3182 to -3133) and proximal (-177 to -81) p53-binding elements within which residues -3182 to -3151 (distal) and -176 to -149 (proximal) show homology to the consensus p53-binding site. Using promoter deletion studies, we find that both proximal and distal elements are required for high level, synergistic transcriptional activation in vivo. Electron microscopy indicates that p53-p53 interactions link proximal and distal p53-binding elements and cause looping out of intervening DNA, suggesting that this DNA sequence may be dispensable for synergy. This idea was confirmed by progressive deletion of the DNA between p53-binding elements. Synergism persisted with spacing reduced to only 150 bp. Tetramerization-deficient p53 mutants were defective for transcriptional activation but still capable of synergy. Our results provide evidence for a model by which high level transcriptional activation of promoters with multiple p53 response elements is achieved.

Animals↗
PubMed1998

Intercellular adhesion molecule-1 regulation in the canine lung after cardiopulmonary bypass.

OBJECTIVE(S): Neutrophil sequestration in the lung after cardiopulmonary bypass has been shown to be dependent on the adhesion molecule CD18. Thus we sought to determine whether endothelial expression of intercellular adhesion molecule-1 (a ligand for CD18) in pulmonary capillaries mediates neutrophil adhesion in this setting. METHODS: Seven adult mongrel dogs underwent 90 minutes of hypothermic cardiopulmonary bypass with 60 minutes of cardioplegic arrest. After warming, dogs were reperfused for up to 9 hours and lung biopsy specimens were obtained. Lung tissue was examined by Northern and Western blot analysis and by immunohistologic methods. Three sham-operated dogs served as time-matched controls. RESULTS: Northern blots demonstrated increased expression of intercellular adhesion molecule-1 messenger ribonucleic acid within 5 minutes of cessation of bypass (or approximately 30 minutes after aortic crossclamp release), which persisted at 9 hours of recovery and was not present in controls. Western blots showed intercellular adhesion molecule-1 protein expression before bypass but a measurable increase in intercellular adhesion molecule-1 protein in four of seven dogs in the bypass group by the ninth hour of recovery. Pulmonary neutrophil accumulation 9 hours after cardiopulmonary bypass was greater in those dogs with an increased intercellular adhesion molecule-1 protein expression. Immunoelectron microscopy demonstrated the pulmonary capillary endothelium capable of increased intercellular adhesion molecule-1 protein expression at the 9-hour time point. CONCLUSIONS: Cardiopulmonary bypass resulted in intercellular adhesion molecule-1 induction in the canine lung during recovery. An increased expression of intercellular adhesion molecule-1 protein in the lung was associated with an increased accumulation of neutrophils in affected animals. Thus intercellular adhesion molecule-1 expression may serve as a mechanism that predisposes the lungs to inflammatory cell-mediated injury postoperatively.

Animals↗
PubMed1998

An ultrastructural and systemic analysis of glycosaminoglycans in thyroid-associated ophthalmopathy.

PURPOSE: To determine the ultrastructural localisation of glycosaminoglycans (GAGs) in the extraocular muscles (EOMs) of patients with thyroid-associated ophthalmopathy (TAO) and to see whether the quantity and type of GAGs present in blood and urine are markers of the disease. METHODS: Biopsies of affected EOMs were taken and studied by transmission electron microscopy (TEM). These were either fixed conventional for TEM, or in 0.5% tannic acid and others for immunogold staining. Serum hyaluronan (HA) was measured using a radioimmunoassay in patients with TAO as well as control subjects, and urinary GAG levels assessed by photometric quantitation of hexuronic acid after reaction with carbazole. The excretion pattern of the urinary GAGs was determined by discontinuous electrophoresis. RESULTS: TEM showed that there is a marked expansion of the endomysial space in TAO EOM biopsies as compared with non-TAO strabismus specimens. This is caused by an increased number of collagen fibres, interspersed with a granular amorphous material surrounding striated collagen fibres shown to be hyaluronan by immunogold staining. In contrast, serum hyaluronan concentrations were similar in TAO and control patients, although there was a statistically significant difference in the urinary GAG excretion between the two groups of patients examined. By discontinuous electrophoresis, chondroitin sulphate and heparan sulphate were present in both patients and controls. CONCLUSION: GAGs and in particularly HA are present at the EOM level in patients with recently inactive TAO. However, serum levels of HA and urinary GAGs are not sensitive indicators for their presence within the EOMs.

Adult↗
PubMed1998

A community survey of children with severe intellectual disability and their families: psychological adjustment, carer distress and the effect of respite care.

The present paper describes a cross-sectional study of the psychosocial adjustment of 143 children with severe disability and their families identified from a regional case register for children with special needs. Thirty-eight per cent of the children had significant psychiatric morbidity. By contrast, the overall level of distress in carers was not that different from probable community prevalence figures. Nevertheless, distress among carers was consistently associated with increased disability in the child. Although respite care is a valuable resource for many carers, its use is indicative of underlying distress in the carer.

Adaptation, Psychological↗
PubMed1998

Acute lithium administration impairs the action of parathyroid hormone on rat renal calcium, magnesium and phosphate transport.

1. Chronic lithium (Li+) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown. 2. The present study evaluated the acute effect of Li+ on renal electrolyte transport, particularly Ca2+ and Mg2+ in thyroparathyroidectomized (TPTX) and intact rats. 3. The acute administration of Li+ significantly increased water, sodium, potassium and phosphate excretion in both TPTX and intact animals; however, Ca2+ and Mg2+ excretion was only increased in the intact group. Fractional excretion (FE) of Ca2+ and Mg2+ increased from 2.2 +/- 0.2 to 3.5 +/- 0.3% and 12 +/- 2 to 18 +/- 2%, respectively (P < 0.01). 4. In further experiments in TPTX rats, Li+ administration inhibited the usual reduction in urine Ca2+ and Mg2+ excretion following parathyroid hormone (PTH) administration and inhibited the phosphaturia. However, supramaximal concentrations of PTH overcame this inhibitory effect. For example, an FECa of 3.8 +/- 0.2% was reduced to 1.4 +/- 0.2% and 1.7 +/- 0.2% with maximal and supramaximal PTH concentrations, respectively, while in the presence of Li+ an FECa of 4.0 +/- 0.2 was decreased to 2.8 +/- 0.2 and then 1.9 +/- 0.3% with the same PTH concentrations. 5. The inhibitory effect of Li+ was reduced with a lower plasma Li+ concentration (0.7 +/- 0.2 vs 1.6-1.8 mmol/L). The FEMg results were comparable. 6. These results demonstrate that Li+ directly inhibits PTH-mediated renal reabsorption of Ca2+ and Mg2+ and also blunts PTH-mediated phosphaturia. Therefore, the hyperparathyroidism in humans following Li+ treatment may be a consequence of reduced renal Ca2+ reabsorption.

Animals↗