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Biomedical subjects

C Blake

Publications and source records attributed to C Blake.

At least 37 records · Page 2Linked to original sources

Effects of macrophage colony-stimulating factor on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus.

The effects of recombinant human macrophage colony-stimulating factor (M-CSF) on antifungal activity of human monocytes (MNC), MNC-derived macrophages (MDM), and rabbit pulmonary alveolar macrophages (PAM) against Aspergillus fumigatus were studied. MNC-induced hyphal damage was augmented by incubation with M-CSF (P = .027); PAM-induced hyphal damage was moderately enhanced by M-CSF (P = .046). Phagocytosis of Aspergillus conidia by MDM and PAM was strongly enhanced by M-CSF (P < .01). MNC pretreated with M-CSF exhibited enhanced superoxide anion production in response to PMA (P = .026). This effect was not associated with increased levels of mRNA transcripts of the components of NADPH oxidase, the enzyme responsible for superoxide anion production. M-CSF augments antifungal activity of mononuclear phagocytes against both conidia and hyphae of Aspergillus fumigatus partly by enhancement of oxidation-dependent mechanisms and may have an important immunomodulatory role in prevention and treatment of invasive aspergillosis in leukopenic patients.

Animals↗

Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-gamma.

Human monocytes are important effector cells in host defenses against Aspergillus hyphae, and as elutriated monocytes (EHM) they may be transfused in large quantities to leukopenic patients with invasive aspergillosis. The antifungal activity of EHM against Aspergillus hyphae was compared with that of polymorphonuclear leukocytes (PMNL). The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on superoxide anion (O2-) release and on hyphal damage caused by EHM against unopsonized A. fumigatus hyphae was investigated. EHM had antihyphal activity comparable to that of PMNL. GM-CSF significantly augmented O2- release by EHM in response to PMA. Also, both GM-CSF and IFN-gamma significantly enhanced the antifungal activity of EHM compared with untreated controls. Thus, EHM have demonstrable antifungal activity against Aspergillus hyphae that may be increased by GM-CSF and IFN-gamma, suggesting their potential therapeutic role in immune reconstitution of effector cells.

Adult↗

Protective wear and instrument sterilisation/disinfection in UK general dental practice.

The 18,000 United Kingdom general dental practitioners registered for National Health Service (NHS) practice were surveyed in July 1991 to assess their current use of protective gloves, eyewear and masks, and instrument sterilisation. Nearly 7,000 (6,588) valid responses were obtained immediately; of these, 70% of practitioners wore gloves routinely for clinical work, but only 14.5% donned new gloves for each patient. About 60% wore protective eyewear routinely or all the time but 12% never wore eye protection, and only 36% of practitioners used masks. Autoclaves or chemical solutions were the most popular methods to disinfect handpieces, but less than half the respondents stated that handpieces were sterilised or disinfected after each patient use. Most respondents (81%) routinely used autoclaves for sterilisation of other instruments. Although the response rate to the questionnaire was low, the results indicate that, despite the risks of, and publicity about, cross-infection, a substantial number of NHS dental practitioners may not adequately disinfect or sterilise their equipment between patients.

Attitude of Health Personnel↗

The control of cross-infection in UK clinical dentistry in the 1990s: immunisation against hepatitis B.

Thirty thousand dentists and clinical ancillary staff in the UK were surveyed in July 1991 to assess the current state of immunisation against hepatitis B virus (HBV). About 11,000 responded immediately and nearly 94% of these had been, or were being, immunised against HBV. Nearly all dentists and therapists (94% in each group), 95% of hygienists, and 96% of dental surgery assistants had been immunised. However, one half of the respondents were at or approaching 5 years post-immunisation, the time when booster immunisation is recommended. About 53% of most responding clinical dental staff had been vaccinated 4 to 5 years before the survey, but, of these, nearly 81% had not had booster immunisation. Booster immunisation will now be indicated for most dental clinical personnel.

Dental Staff↗

Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus.

Human immunodeficiency virus (HIV)-infected patients may acquire invasive aspergillosis without previously recognized risk factors, such as neutropenia or corticosteroid therapy. Because neutrophils (PMNL) are an important component of host defense in aspergillosis, the antifungal activity of PMNL against hyphae of Aspergillus fumigatus in 31 HIV-infected children was assessed. Hyphal damage was unaffected in 15 HIV-infected children with age-adjusted CD4 cell counts > or = 25% of the normal median value; it was decreased in 16 with CD4 cell counts < 25% (both vs. 20 healthy controls, P = .001. Incubation with sera from 12 of 14 HIV-infected children but not with the recombinant HIV proteins gp120, gp41, and p24 suppressed antifungal activity of normal PMNL compared with normal serum (P = .002). Pretreatment of defective PMNL from 5 patients with granulocyte colony-stimulating factor (G-CSF) partially corrected the defect (P = .002). These findings suggest that impaired serum-mediated antifungal activity against Aspergillus hyphae exists in PMNL of HIV-infected patients with low CD4 cell counts; G-CSF may improve this activity.

Adolescent↗

Defective antifungal activity of monocyte-derived macrophages from human immunodeficiency virus-infected children against Aspergillus fumigatus.

Invasive aspergillosis recently has been encountered in adults and children with human immunodeficiency virus (HIV) infection even without known risk factors, such as neutropenia or corticosteroid therapy. Macrophages play a significant role in the host defenses against Aspergillus organisms by ingesting conidia and preventing their germination to hyphae. The antifungal activity of peripheral blood monocyte-derived macrophages (MDM) from 19 HIV-infected children was compared with that of 16 normal controls. The phagocytic activity of patients' MDM, measured as percentage of phagocytosis, was significantly decreased compared with normal donors (P = .014). In addition, the inhibitory activity of MDM on germination of intracellular A. fumigatus conidia was significantly impaired in patients compared with normal controls (P = .016). There was no significant difference in the defects between patients with lower or higher CD4 lymphocyte counts. Impairment of antifungal activity of macrophages may contribute to the susceptibility of HIV-infected patients to aspergillosis.

Adolescent↗

Synthesis and antitumor activity of novel 4-demethoxyanthracyclines.

A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity.

Animals↗

Synthesis and antitumor activity of 9-[(carbamoyloxy)alkyl]anthracyclines: a novel class of anthracycline derivatives.

A number of 4-demethoxyanthracyclines having hydroxylalkyl functions at the 9-position have previously been synthesized and shown to have potent antitumor activity. A series of carbamate derivatives of these (hydroxyalkyl)anthracyclines have now been prepared, many of which possess considerably greater efficacy in an L-1210 leukemia test system than do the parent alcohols or the known anthracyclines daunorubicin (1), doxorubicin (2), and 4-demethoxydaunorubicin (3). Phenylcarbamate 8a was more active than methyl analogue 8b, while the 4'-deoxy and 4'-epi phenylcarbamates 17 and 18 showed particularly high efficacy at optimal dose levels similar to that of doxorubicin. Secondary carbamates were more potent, with the 13R isomer 23 having significantly higher efficacy than 13S analogue 24.

Animals↗

Simultaneous enzyme immunoassay of two thyroid hormones.

We describe an enzyme immunoassay in which the two thyroid hormones, triiodothyronine and thyroxin, are measured simultaneously in a single tube. The method involves labeling the two with separate enzymes (beta-galactosidase and alkaline phosphatase, respectively), whose catalyzed reactions can easily be distinguished from each other by absorption spectrophotometry, with o-nitrophenyl-beta-galactoside and phenolphthalein monophosphate as substrates. Performance of this dual assay method compares well with that of conventional single-hapten enzyme-labeled assays, and results compare well with those by two single-hapten radioimmunoassays. The dual assay has certain advantages over single-hapten methods: smaller sample volume, lower reagent cost, and shorter overall assay time. As presented here, the use of enzyme labels to measure two (or more) haptens simultaneously represents a significant advance in the use of immunoassay techniques.

Humans↗

Effects of lucanthone on the sedimentation properties of DNA from HeLa cells.

Exposure of HeLa cells to lucanthone (3 microgram/ml) caused dissociation of a fast-sedimenting duplex DNA complex, as judged by lysis and sedimentation in alkaline sucrose gradients. The effect of lucanthone on the DNA complex resembled that of actinomycin D and ionizing radiation. Protein synthesis inhibitors such as cycloheximide or inhibitors of DNA synthesis such as hydroxyurea did not lead to dissociation of the complex. Lucanthone was more active than were hycanthone and five other closely related thiaxanthenones tested. Lucanthone promoted X-ray-induced denaturation of DNA in intact cells, as judged by their nuclear immunoreactivity to antinucleoside antibodies. Lucanthone did not inhibit repair of X-ray-induced DNA single-strand breaks.

Centrifugation, Density Gradient↗

Impact of litigation on quality of life outcomes in patients with chronic low back pain.

Low back pain progresses to chronic low back pain (CLBP) in 5-10 per cent of patients. A Multi-disciplinary Pain Management Programme was tested in 20 patients (m = 4, f = 16). This regime involved psychological and behaviour modification strategies, combined with intensive exercise. Treatment outcome in terms of impairment was assessed by lumbar flexibility, trunk muscle endurance and pain. The disability assessed was exercise fitness and handicap was assessed using the Sickness Impact Profile (SIP) to define the impact of the condition on the patient's life. Overall the patients showed significant improvement (p < 0.05) in all of the measured variables. Patients with on-going litigation however (n = 11) showed no significant improvement in the SIP quality of life score, although they shared the significant improvements attained by the whole group in the domains of impairment (lumbar flexibility, trunk muscle endurance and pain) and disability (exercise fitness).

Adult↗