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Biomedical subjects

J Russell

Publications and source records attributed to J Russell.

At least 127 records · Page 7Linked to original sources

The chemokine interleukin-8 regulates parathyroid secretion.

Interleukin-8 (IL-8) is a chemokine important in inflammatory processes. Homology cloning experiments performed using bovine parathyroid cDNA and degenerate primers encoding transmembrane regions III and VI of peptide and protein hormone G-protein coupled receptors identified a set of known receptors not previously identified in the parathyroid. Among these was the IL-8 type B receptor. Incubation of freshly isolated bovine parathyroid cells with recombinant IL-8 for 6-48 h produced an increase in the levels of mRNA for parathyroid hormone (PTH). The levels of PTH secreted in response to nanomolar amounts of IL-8 were also elevated in cells incubated for 1 h with IL-8. Differential display analysis of mRNA from parathyroid cells, incubated in the presence and absence of IL-8, permitted the identification of cDNA clones for RNA species whose expression was either elevated or suppressed. These experiments suggest that IL-8 and inflammatory events play a role in bone homeostasis through actions on the parathyroid gland.

Animals↗

Differential expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) in murine tissues.

OBJECTIVE: To characterize and compare the expression of PECAM-1 in unstimulated and tumor necrosis factor alpha-(TNF-alpha)-stimulated tissues of mice. METHODS: Binding and non-binding monoclonal antibodies (mAb) were radiolabeled and injected into wild-type mice and mice deficient of P-selectin, CD18, or ICAM-1. The relative accumulation of binding mAb (PECAM-1 mAb) was determined in wild-type mice following a 25 micrograms/kg i.p. injection of TNF-alpha and in mutant mice under basal conditions. RESULTS: Under unstimulated conditions, PECAM-1 was significantly expressed in all tissues examined, with no changes occurring after TNF-alpha stimulation. An equivalence of PECAM-1 expression was observed in unstimulated tissues among wild-type mice and mice that are genetically deficient in either CD18, ICAM-1, or P-selectin. The level of PECAM-1 expression in different vascular beds was highly correlated to published values of endothelial surface area. Normalization of previously published values of ICAM-1, VCAM-1, E- and P-selectin expression relative to PECAM-1 expression in the same tissues revealed a diminished organ-to-organ variability in expression of the different adhesion molecules. Estimates of adhesion molecule expression in lung and brain were most profoundly affected by normalization to PECAM-1 expression. CONCLUSIONS: These findings support the use of PECAM-1 expression in regional vascular beds as an indicator of endothelial cell surface area.

Animals↗

A community outbreak of Vero cytotoxin producing Escherichia coli O157 infection linked to a small farm dairy.

A community outbreak of infection with Vero cytotoxin producing Escherichia coli O157 (VTEC 0157) occurred in a small area of north west England in 1996. An outbreak control team was established to investigate the outbreak and implement control measures. Nine people developed symptomatic infections with VTEC O157, and a further three were found to be excreting the bacteria. All were infected with the same genotype of VTEC O157. Three children under 5 years of age and one adult were admitted to hospital. One child developed haemolytic uraemic syndrome. All cases recovered. All primary cases had consumed milk from a particular farm dairy. No other common foods were identified. The farm dairy had a faulty pasteuriser and the potential for post pasteurisation contamination existed. VTEC O157 was isolated from a milk sock specimen and from two cows, but these strains differed from that infecting the cases. All local doctors and the public were alerted and advised about preventative measures. Distribution of unpasteurised milk from the farm was discontinued as was the sale of pasteurised milk when the faulty pasteuriser was discovered. A replacement pasteuriser was installed and checked before milk was released for human consumption. No conclusive evidence of the origin of this outbreak was found, but the farm was the most probable source. The investigations raised concerns about the distribution of VTEC O157 colonised dairy cattle, the natural history of such colonisation, the effectiveness of pasteurisation with respect to the elimination of VTEC O157, and the effectiveness of current legislation for the prevention and control of milkborne infection.

Adult↗

Public health. Leading questions.

The arguments in favour of the public health director being a doctor remain powerful. It is difficult to imagine someone without a medical qualification being accepted by junior doctors, consultants and GPs. However, other disciplines may have a better understanding of social and economic determinants of health, and more skills in working with communities. Given current prevailing attitudes, it is unlikely that a professional other than a doctor could gain the confidence of the range of groups that a public health director must work with. But attitudes could and possibly should, change.

Attitude to Health↗

Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner.

Replication protein A (RPA) is required for both DNA replication and nucleotide excision repair. Previous studies have shown that RPA interacts with the tumor suppressor p53. Herein, we have mapped a 20-amino acid region in the N-terminal part of p53 that is essential for its binding to RPA. This region is distinct from the minimal activation domain of p53 previously identified. We also demonstrate that UV radiation of cells greatly reduces the ability of RPA to bind to p53. Interestingly, damage-induced hyperphosphorylated RPA does not associate with p53. Furthermore, down-regulation of the RPA/p53 interaction is dependent upon the capability of cells to perform global genome repair. On the basis of these data, we propose that RPA may participate in the coordination of DNA repair with the p53-dependent checkpoint control by sensing UV damage and releasing p53 to activate its downstream targets.

Animals↗

Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse.

The dual radiolabeled mAb technique was used to quantify the constitutive and induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the microvasculature of different organs of the mouse. The constitutive expression of both adhesion molecules varied significantly between tissues, with ICAM-1 levels consistently higher than VCAM-1 in all tissues studied. Following systemic administration of endotoxin (LPS), an increased surface expression of both adhesion molecules occurred in most organs, with the largest increases for ICAM-1 (2 to 3x increase) noted in the heart, small intestine, and brain, while heart and small intestine exhibited the largest increases in LPS-induced VCAM-1 expression (2 to 5x increase). These responses occurred in the face of an unaltered expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in all tissues. TNF-alpha also elicited an increased expression of both adhesion molecules, with initial increases noted at 2 to 5 h, peak levels at 5 to 9 h, and a sustained elevation above baseline at 24 h. The TNF-alpha-induced increases in both ICAM-1 and VCAM-1 were dose dependent, with significant up-regulation noted at 5 microg/kg and maximal increases occurring at 10 to 25 microg/kg. These studies indicate that while there are significant quantitative differences in constitutive and induced expression of murine ICAM-1 and VCAM-1, the kinetics and dose-response characteristics of the two adhesion molecules to TNF-alpha are qualitatively similar.

Animals↗

Obsessive compulsive comorbidity in the dieting disorders.

OBJECTIVE: This study investigated the comorbidity of obsessive compulsive disorder and obsessive compulsive personality disorder with the dieting disorders. A comorbid sample was examined in order to test the hypothesis that obsessive compulsive symptoms and personality are premorbid in these patients. METHOD: Sixty-eight inpatients (35 with anorexia nervosa and 33 with bulimia nervosa) were assessed for DSM-III-R Axis 1 and Axis 11 obsessive compulsive psychopathology using the Composite International Diagnostic Interview (CIDI) and the Personality Disorders Inventory (PDE), respectively. RESULTS: Twenty-one percent of the group met criteria for a diagnosis of obsessive compulsive disorder. Thirty-seven percent of anorexia nervosa patients were comorbid for obsessive compulsive disorder compared to only 3% of bulimia nervosa patients. In most, the obsessive compulsive disorder had predated the dieting disorder. Nineteen percent of patients were found to have premorbid obsessive compulsive personality disorder. DISCUSSION: This study supports the assumption of obsessive compulsive comorbidity within the dieting disorders and provides empirical support that this obsessionality is a premorbid characteristic.

Adolescent↗

A role for Edman degradation in proteome studies.

Advances in protein database design and the software used to access the sequence data has led to progress in using protein attributes such as amino acid composition and peptide masses to identify proteins separated by two-dimensional electrophoresis. However, Edman degradation remains the principal technique for protein identification and it presents a significant bottleneck in the progress towards rapid protein identification. Simple modifications to the sequencing hardware, which automate the delivery of protein spots into the sequencer, and parallel sequencing of the protein spots represent a significant advance in the use of Edman degradation to rapidly generate the powerful protein attribute, an N-terminal sequence tag.

Amino Acid Sequence↗

Role of Kupffer cells in gut ischemia/reperfusion-induced hepatic microvascular dysfunction in mice.

Kupffer cells (KCs) have been implicated in the leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs in the leukocyte adhesion and oxidative stress elicited in the liver by gut ischemia/reperfusion (I/R). The accumulation of rhodamine-6G-labeled leukocytes and the number of nonperfused sinusoids (NPS) were monitored (by intravital microscopy) in mouse liver for 1 hour after a 15-minute period of normothermic intestinal ischemia. Autofluorescence of pyridine nucleotide [NAD(P)H] was measured as an index of mitochondrial O2 consumption and redox status. Leukostasis, as well as increases in NPS and NAD(P)H autofluorescence (indicating hypoxia), were observed in the liver at 60 minutes after gut I/R. Pretreatment with gadolinium chloride (GdCl3), which reduces KC function, attenuated the liver leukostasis and NPS elicited by gut I/R. The platelet activating factor (PAF) antagonist, WEB2086, and a tumor necrosis factor (TNF)-alpha-specific antibody were also effective in attenuating the gut I/R-induced leukostasis and NAD(P)H autofluorescence. The findings of this study suggest that KCs play an important role in mediating the leukocyte recruitment, impaired sinusoidal perfusion, and tissue hypoxia elicited in the liver after gut I/R. These KC-mediated responses appear to involve the participation of both PAF and TNF-alpha.

Alanine Transaminase↗

The development of recency and frequency memory: is there a developmental shift from reliance on trace-strength to episodic recall?

Recency and frequency judgements can be made either on the basis of the familiarity of items or by retrieving item-specific contextual information. Although normal adults seem to use the latter basis, several studies have shown that adults with memory impairments rely on trace-strength information. We report the results of a study examining the basis of 4-, 6-, and 8-year-old children's recency and frequency judgements. Both the frequency and the recency of presentation of items were manipulated such that reliance on trace-strength would lead to a characteristic pattern of performance, as shown by amnesic patients. Although the accuracy of both recency and frequency judgements improved between 4 and 6 years of age, there was no evidence that children in any age-group based their recency judgements on trace-strength, although there was some indication that 4-year-olds may have used this basis for judgements of frequency.

Child↗

HPLC determination of biologically active thiols using pre-column derivatisation with 5,5'-dithio-(bis-2-nitrobenzoic acid).

5,5'-Dithio-(bis-2-nitrobenzoic acid), Ellmans reagent (ESSE), is used as a pre-column derivatisation reagent for the determination of biologically active thiols by HPLC. D-penicillamine, N-acetyl-d-penicillamine, N-acetylcysteine, cysteine, captopril and thiomalic acid all give well resolved derivatives. The calibration graph and reproducibility (%R.S.D. +/- 1.3%) for the analysis of glutathione indicates that the method could be used for quantitative analysis. ESSE is widely used as a reagent in thiol determinations by electronic spectroscopy via the detection of the Ellmans anion (ES-) generated without any prior separation procedures. However, there are considerable reservations over its use for the spectrophotometric determination of thiols because of the possibility of side reactions which generate another Ellmans based species (ESO2-). The assay described determines the thiol as a derivatised mixed disulphide (ESSR) and since speciation between the anion ES- and the oxidation product ESO2- occurs it enables the process of oxidation to be monitored simultaneously.

Chromatography, High Pressure Liquid↗

Quantitation of the cell surface level of Ld resulting in positive versus negative selection of the 2C transgenic T cell receptor in vivo.

The 2C transgenic TCR is positively selected on Kb and is alloreactive for and negatively selected on Ld. To test an avidity model for positive selection, mice were bred to express different levels of surface Ld by varying the number of gene copies encoding beta 2-microglobulin (beta 2m) or Ld heavy chain. Whereas mice expressing 35% Ld (beta 2m+/- Ld+/-) negatively selected the 2C TCR, mice expressing 2% Ld (beta 2m-/- Ld+/-) positively selected the 2C TCR. Furthermore, 2C cytotoxic T lymphocytes selected on 2% Ld showed peptide-specific cytolytic activity against Ld/p2Ca targets. These findings provide clear in vivo evidence that positive selection can occur on very low levels of the same class I antigen capable of negative selection when expressed at higher levels.

Animals↗

Counting abilities in autism: possible implications for central coherence theory.

We examined the claim that children with autism have a "weak drive for central coherence" which biases them towards processing information at an analytic rather than global level. This was done by investigating whether children with autism would rapidly and automatically enumerate a number of dots presented in a canonical form, or count each dot individually to obtain the total. The time taken to count stimuli was compared across three participant groups: children with autism, children with moderate learning difficulties, and normally developing children. There were 22 children in each group, and individuals were matched across groups on the basis of verbal mental age. Results implied that children with autism did show a tendency towards an analytic level of processing. However, though the groups differed on measures of counting speeds, the number or children showing patterns of global or analytic processing did not differ significantly across the groups. Whether these results implicate a weak drive for central coherence in autism, which is both specific to, and pervasive in the disorder, is discussed.

Adolescent↗

How to use an article on therapy or prevention: pneumonia prevention using subglottic secretion drainage.

Evidence based critical care medicine involves integrating clinical experience, expertise, and patient preferences with explicit, systematic, and judicious use of current best evidence in making medical decisions. Published evidence has many sources: research from the basic sciences of medicine, and from patient-centered clinical research on the accuracy of diagnostic tests, the power of prognostic markers, and the effectiveness and safety of preventive, therapeutic, rehabilitative, and palliative interventions. When critically appraising a clinical article for potential use in intensive care unit (ICU) practice, the first question we ask ourselves is: Is this study valid? If examination of the study methods reveals that the design is rigorous, we can turn to the two other key questions: What are the results? and, Will the results help me care for my patients? This approach may aid in the interpretation of an article on therapy or prevention; in it we discuss a strategy designed to prevent ventilator associated pneumonia in critically ill patients.

Critical Care↗

Error rate for HLA-B antigen assignment by serology: implications for proficiency testing and utilization of DNA-based typing methods.

Until recently, the majority of HLA class I typing has been performed by serology. Expensive commercial typing trays are frequently used for testing non-Caucasian subjects and new strategies using DNA-based methods have been adopted for improving clinical histocompatibility testing results and adapted as supplements in proficiency testing. A double-blind comparison of the typing of HLA-B specificities in 40 samples was carried out between serology and two polymerase chain reaction (PCR) methods, PCR amplification with sequence-specific primers (PCR-SSP) and PCR amplification and subsequent hybridization with sequence-specific oligonucleotide probes (PCR-SSOP). The results demonstrated 22.5% misassignments of HLA-B antigens by serology. There was complete concordance between the results obtained with the two PCR based typing methods. A second panel of 20 donor samples with incomplete or ambiguous serologic results was analyzed by PCR-SSP and SSOP Both PCR methods identified correctly the HLA-B antigens. Our results suggest that more accurate typing results can be achieved by complementing serologic testing with DNA-based typing techniques. The level of resolution for HLA-B antigen assignment can be obtained by this combination of serology and limited DNA-based typing is equivalent to the HLA-B specificities defined by the WHO-HLA Committee. This level of resolution cannot routinely be achieved in clinical histocompatibility testing or in proficiency testing using serologic reagents only.

DNA↗

Discriminating between barley genotypes using microsatellite markers.

Eleven microsatellite loci were used to survey 24 barley genotypes representing 23 cultivars and a breeding line in official trials. Three separate combinations of four microsatellites had overall probabilities of identity of less than 1 in 1000 and could distinguish between all 24 barley genotypes. It is shown that the microsatellites could distinguish genotypes with the same pedigree and also that patterns of discrimination were different from those obtained from botanical descriptors. The stability of microsatellites across different generations was demonstrated by a retrospective analysis of the pedigree of Golden Promise. One of the parents of Maythorpe, the immediate ancestor of Golden Promise, was shown to be Irish Goldthorpe rather than Goldthorpe, thereby resolving conflicting published pedigrees.

DNA, Plant↗

Modulation of P-selectin expression in the postischemic intestinal microvasculature.

The dual radiolabeled monoclonal antibody technique was used to 1) define the magnitude and kinetics of P-selectin expression in murine small intestine exposed to ischemia-reperfusion (I/R), and 2) determine the factor(s) responsible for initiating this response. Within 10 min after release of a 20-min arterial occlusion, intestinal P-selectin expression increased two- to threefold compared with control values. Peak (4-fold) expression of P-selectin was noted at 5 h after reperfusion, returning to the control value at 24 h. The early (10-30 min) I/R-induced upregulation of P-selectin appears to reflect mobilization of a performed pool of the adhesion molecule, whereas the later (5 h) rise appears to be transcription dependent. The early increase in P-selectin expression was not inhibited by pretreatment with either oxypurinol (inhibits xanthine oxidase), diphenhydramine (H1-receptor antagonist), or MK-571 (leukotriene C4/D4 antagonist), nor was it blunted in transgenic mice expressing three times the normal level of copper-zinc superoxide dismutase or in mast cell-deficient mice. However, significant inhibition was noted after treatment with either MK-886 (5-lipoxygenase inhibitor) or a nitric oxide (NO) donor (diethylenetriamine/NO). These findings indicate that the early I/R-induced increase in intestinal P-selectin expression is mediated by a 5-lipoxygenase-dependent NO-inhibitable mechanism.

Animals↗

Endothelial cell adhesion molecule expression in gene-targeted mice.

Gene-targeted mice are now routinely employed as tools for defining the contribution of different leukocyte and endothelial cell adhesion molecules to the leukocyte recruitment and tissue injury associated with acute and chronic inflammation. The objective of this study was to determine whether gene-targeted mice that are deficient in CD11/CD18, intracellular adhesion molecule-1 (ICAM-1), or P-selectin exhibit an altered constitutive or induced expression of the endothelial cell adhesion molecules E- and P-selectin. The gene-targeted mice were all developed in the 129Sv mouse strain and backcrossed into C57B1/6J mice. The number of backcrosses ranged between 8 (P-selectin) and 10 (CD18 and ICAM-1) generations. The dual-radiolabeled monoclonal antibody technique was used to quantify E- and P-selectin expression in different vascular beds. In the unstimulated state, E-selectin expression was significantly elevated (relative to wild-type mice) in the stomach, large intestine, and brain of mutants deficient in ICAM-1. In general, constitutive expression of P-selectin did not differ between wild-type, ICAM-1-deficient, and CD11/CD18-deficient mutants. In CD11/CD18-deficient mice, tumor necrosis factor-alpha (TNF-alpha) administration elicited a more profound upregulation of P-selectin in several vascular beds, compared with wild-type and ICAM-1-deficient mice. E-selectin expression in brain of TNF-alpha-stimulated, ICAM-1-deficient, and P-selectin-deficient mice was attenuated compared with wild-type mice. These findings indicate that chronic deficiency of some of the adhesion glycoproteins that mediate leukocyte recruitment alters basal and induced surface expression of other adhesion molecules on endothelial cells.

Animals↗