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Biomedical subjects

C M Murray

Publications and source records attributed to C M Murray.

15 recordsLinked to original sources
PubMed2007

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma.

BACKGROUND: Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory-tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. OBJECTIVE: To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. METHODS: Sputum cells were induced from steroid-naïve, allergen-challenged and allergen-naïve subjects (atopic asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. RESULTS: hRTDC stained HLA-DR(+) (negative for markers of other cell lineages) were predominantly myeloid and comprised approximately 0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4(+) naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC-dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05-P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c(-)CD123(high) hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. CONCLUSION: Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.

Administration, Inhalation↗
PubMed2005

Validation of a 21-locus autosomal SNP multiplex for forensic identification purposes.

A single nucleotide polymorphism (SNP) multiplex has been developed to analyse highly degraded and low copy number (LCN) DNA template, i.e. <100 pg, for scenarios including mass disaster identification. The multiplex consists of 20 autosomal non-coding loci plus Amelogenin for sex determination, amplified in a single tube PCR reaction and visualised on the Applied Biosystems 3100 capillary electrophoresis (CE) system. Allele-specific primers tailed with shared universal tag sequences were designed to speed multiplex design and balance the amplification efficiencies of all loci through the use of a single reverse and two differentially labelled allele denoting forward universal primers. As the multiplex is intended for use with samples too degraded for conventional profiling, a computer program was specifically developed to aid interpretation. Critical factors taken into account by the software include empirically determined extremes of heterozygous imbalance (Hb) and the drop-out threshold (Ht) defined as the maximum peak height of a surviving heterozygous allele, where its partner may have dropped out. The discrimination power of the system is estimated at 1 in 4.5 million, using a White Caucasian population database. Comparisons using artificially degraded samples profiled with both the SNP multiplex and AMPFISTR SGM plus (Applied Biosystems) demonstrated a greater likelihood of obtaining a profile using SNPs for certain sample types. Saliva stains degraded for 147 days generated an 81% complete SNP profile whilst short tandem repeats (STRs) were only 18% complete; similarly blood degraded for 243 days produced full SNP profiles but only 9% with STRs. Reproducibility studies showed concordance between SNP profiles for different sample types, such as blood, saliva, semen and hairs, for the same individual, both within and between different DNA extracts.

Amelogenin↗
PubMed2001

Structure-based focusing using pharmacophores derived from the active site of 17beta-hydroxysteroid dehydrogenase.

Structure-based focusing constitutes a powerful approach to design libraries of compounds with a given biological profile. Computers with special software can be used to analyse the large amount of data usually available for the compounds. Pharmacophores can be used to identify new compounds that present a specific arrangement of features responsible for a certain type of activity. When available, information about the 3D structure of a biological target can also be included in the building of pharmacophore models. These pharmacophores can then be used as queries to search and/or focus large compound libraries. Multiple pharmacophores were generated from the 3D structure 17beta-hydroxystreoid dehydrogenase type1 complexed with different inhibitors. The validity of these pharmacophores was assessed against a test database containing known active and inactive 17beta-hydroxystreoid dehydrogenase type1 inhibitors. The most selective models were then used to search commercial databases for new structural lead molecules. This approach has allowed us to identify a few new compounds possessing structural features common to flavonoids, a structural class of compounds known to contain good inhibitors of 17beta-hydroxystreoid dehydrogenase type1 enzyme. A structure-based focusing approach is demonstrated to be a meaningful and powerful technique for identifying new lead candidates, which can be taken into the lead optimization process.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

Interpersonal problem-solving skills training in the treatment of self-poisoning patients.

The present study evaluated the effectiveness of interpersonal problem-solving skills training (IPSST) for the treatment of self-poisoning patients. Thirty-nine self-poisoning patients were assigned randomly either to IPSST or to a control treatment condition (a brief problem-oriented approach). Both conditions were equally effective in reducing the number of presenting problems and in reducing hopelessness levels. However, the IPSST condition was significantly more effective than the control condition as determined by other outcome measures (measures of interpersonal cognitive problem solving, self-rated personal problem-solving ability, perceived ability to cope with ongoing problems, and self-perception). Follow-up studies showed maintenance of IPSST treatment gains at 6 months and a greater reduction of repetition of self-poisoning in the IPSST group at 1 year posttreatment.

Adolescent↗
PubMed1993

A single photon emission computerised tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia.

The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.

Age of Onset↗
PubMed1990

Prevalence of gastric lesions in foals without signs of gastric disease: an endoscopic survey.

Gastroendoscopic examinations were conducted on 75 Thoroughbred foals aged two to 85 days on seven breeding farms in England and Ireland. The foals showed no signs of gastric disease. There was no significant difference between lesion prevalence in foals in England (16 of 28 foals; 57 per cent) or Ireland (22 of 47 foals; 47 per cent). Neither was there any sex predilection (18 of 36 males; 20 of 39 females). Lesions were most prevalent in foals under 10 days old (8 of 9) and least prevalent in foals older than 70 days (3 of 10). Lesions occurred most frequently in the squamous mucosa immediately adjacent to the margo plicatus along the greater curvature (34 foals), whereas lesions in the squamous fundus, the glandular fundus, and the lesser curvature were observed in 11, six and three foals, respectively. Lesions were not observed in the squamous mucosa surrounding the cardia. Gastric lesions were more prevalent in foals with a previous disorder than in those without (68 vs 43 per cent) and particularly with a history of recent or concurrent diarrhoea (9 of 14).

Age Factors↗
PubMed1989

Delayed response of the mouse uterus to progesterone and oestradiol.

The delayed response of the uterus of the ovariectomized mouse to progesterone (P) required the presence of a low dose of oestradiol-17 beta (E2) and was associated with a maintained level of uterine DNA, an increase in RNA:DNA ratio and in total tissue protein and a decreased level of uterine P. This last parameter was associated with an increased level of in vitro metabolism of P by the uterus. Changes in the level of receptors for P and E2 were temporally unrelated to the delayed response. Omission of oestradiol every second, third or fourth day inhibited development of the delayed response, which could also be obtained with the long acting progestogen, medroxy progesterone acetate, and E2 or oestradiol benzoate.

Animals↗
PubMed1987

Interpersonal problem-solving deficits in self-poisoning patients.

Self-poisoning patients (n = 40) were compared with psychiatric patients (n = 40) and nonpatient controls (n = 20) on measures of interpersonal problem-solving skills and locus of control in an effort to determine the importance of these cognitive and personality variables in self-poisoning behavior. The psychiatric and self-poisoning groups showed deficits on measures assessing interpersonal problem solving when compared with nonpatient controls. The self-poisoning group performed below the level of the psychiatric patients on all except one test, on which they performed at the level of the psychiatric group. Locus of control did not differentiate self-poisoning patients from nonpatient controls, and it was concluded that this variable is not an important factor in self-poisoning behavior.

Adolescent↗
PubMed1986

Evaluation of leukapheresis and thrombocytapheresis in the horse.

Continuous-flow centrifugation leukapheresis techniques were used to collect 300-ml volumes of leukocyte-rich plasma from 5 nonmedicated horses and from 5 corticosteroid-stimulated horses. White blood cell counts and differential counts were performed on the horses before (base line) and up to 48 hours after leukapheresis. Systemic administration of hydrocortisone increased numbers of total WBC and neutrophils and improved harvest of these cells. Nonmedicated horses had a mean yield of 3.38 X 10(10) leukocytes in the 300-ml volume. Stimulated horses yielded a mean of 6.88 X 10(10) leukocytes. After leukapheresis, WBC counts decreased a mean of 38% in nonstimulated horses and decreased a mean of 30% in stimulated horses. By 6 hours after leukapheresis, circulating WBC counts of horses in both groups had returned to preleukapheresis values. The relationship between neutrophil yield and the 4 variables (preleukapheresis WBC count, preleukapheresis neutrophil count, preleukapheresis lymphocyte count, and the PCV of the leukocyte-rich plasma) were examined, using simple (pair-wise) correlation and multiple linear regression. A significant positive correlation was found between neutrophil yield and preleukapheresis WBC and neutrophil counts. Because sodium citrate was used in the collection system to prevent extracorporeal blood coagulation, ionized and total serum calcium concentrations were monitored before and after leukapheresis. Although total serum calcium concentrations remained unchanged, ionized calcium concentrations decreased approximately 33% from base-line values during the 2-hour leukapheresis procedures. Occasional mild muscle fasciculations were the only adverse clinical signs of citrate toxicity exhibited by the horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Continuous-flow centrifugation hemapheresis in the horse.

In a continuous-flow centrifugation apheresis technique adapted for blood-component separation and collection in horses, hydroxyethyl starch was not required for erythrocyte sedimentation. The efficacy and separation characteristics of whole blood from 10 horses were evaluated at various gravitational forces (700 to 1,500 rpm), using a constant withdrawal rate (100 ml/min). Maximum leukocyte collection occurred at 700 rpm (P less than 0.01), and optimal neutrophil collection occurred at 700 to 750 rpm (P less than 0.01). Although neutrophil counts decreased and lymphocyte counts remained constant at higher rpm settings, an optimal rpm range could not be determined for lymphocyte collection. Peak platelet collection occurred at 1,500 rpm. The response of whole blood from 5 horses was evaluated at lower (500 to 700 rpm) and higher (1,400 to 2,200 rpm) centrifuge speeds. A constant whole blood withdrawal rate of 100 ml/min and a leukocyte collection rate of 3 ml/min were maintained. The optimal rpm settings were determined and compared with values obtained from the 10 horses. Significant differences (P less than 0.01) did not exist between maximum numbers of leukocytes collected at low and high speeds. There was a significant (P less than 0.01) decrease in neutrophils and a concomitant increase in the numbers of lymphocytes recovered at the higher rpm. Platelet yields increased as rpm was increased to 2,000.

Animals↗
PubMed1978

Community-acquired bacteremic Achromobacter xylosoxidans type IIIa pneumonia in a patient with idiopathic IgM deficiency.

A man was hospitalized with bacteremic Achromobacter xylosoxidans type IIIa pneumonia. The authors are aware of no previously reported similar infections caused by this bacterium. A clinical cure was achieved with a combination of carbenicillin and kanamycin therapy. Microtiter susceptibility testing revealed that carbenicillin was the antibiotic to which A. xylosoxidans IIIa was most sensitive (minimal inhibitory concentration, 1.6 microgram/ml) and that synergy between carbenicillin and kanamycin existed. During the patient's hospitalization, deficiency of IgM (21 mg/dl) was found. Specific serum activity against A. xylosoxidans IIIa was detected by the agglutination method. Specific anti-A. xylosoxidans IIIa IgG, but not IgM, was detected by indirect immunofluorescence. It appears that a defect in immunologic recognition of A. xylosoxidans IIIa as an invasive bacterium, a defect in synthesis of specific IgM, or both, contributed to this patient's infection.

Agglutination Tests↗
PubMedDate not supplied

Design of libraries to explore receptor sites.

Despite rapid progress in both combinatorial chemistry and high-throughput screening, the number of molecules that could potentially be made and tested for biological activity still far exceeds the capacity for synthesis or screening. Consequently, it is potentially valuable to select and synthesize sublibraries that contain rationally selected subsets. When the structure of the protein receptor site is known, this may be used to impose restrictions of the selection on molecules. This paper describes a method for rapid analysis of large virtual libraries to select a subset that can exhibit at least one conformer which wil interact strongly with the receptor and fit within the receptor site.

Binding Sites↗