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Biomedical subjects

C Harding

Publications and source records attributed to C Harding.

At least 19 recordsLinked to original sources
PubMed2001

Water modulation of stratum corneum chymotryptic enzyme activity and desquamation.

Exposure to a dry environment leads to depletion of water from the peripheral stratum corneum layers in a process dependent on the relative humidity (RH) and the intrinsic properties of the tissue. We hypothesized that by modulating the water content of the stratum corneum in the surface layers, RH effects the rate of desquamation by modulating the activity of the desquamatory enzymes, and specifically stratum corneum chymotryptic enzyme (SCCE). Using a novel air interface in vitro desquamatory model, we demonstrated RH-dependent corneocyte release with desquamatory rates decreasing below 80% RH. Application of 10% glycerol or a glycerol-containing moisturizing lotion further increased desquamation, even in humid conditions, demonstrating that water was the rate-limiting factor in the final stages of desquamation. Furthermore, even in humid conditions desquamation was sub-maximal. In situ stratum corneum SCCE activity showed a dependence on RH: activity was significantly higher at 100% than at 44% RH. Further increases in SCCE activity were induced by applying a 10% glycerol solution. Since SCCE, a water-requiring enzyme, must function in the water-depleted outer stratum corneum, we sought to determine whether this enzyme has a tolerance to lowered water activity. Using concentrated sucrose solutions to lower water activity, we analysed the activity of recombinant SCCE and compared it to that of trypsin and chymotrypsin. SCCE activity demonstrated a tolerance to water restriction, and this may be an adaptation to maintain enzyme activity even within the water-depleted stratum corneum intercellular space. Overall these findings support the concept that in the upper stratum corneum, RH modulates desquamation by its effect upon SCCE activity, and possibly other desquamatory hydrolases. In addition, SCCE may be adapted to function in the water-restricted stratum corneum intercellular space.

Animals↗
PubMed2001

The urgent postoperative CT scan: a critical appraisal of its impact.

Urgent CT scanning of critically ill neurosurgical patients is costly, labour intensive and associated with some risk. A study of urgent postoperative CT scans was carried out to assess the proportion that changed patient management. A further study evaluated the accuracy of predicting a haematoma. A retrospective analysis was carried out over a 6-month period of all scans performed within 48 h of craniotomy. This was followed by a prospective comparison between the surgeon's estimate of the chance of a haematoma on the scan and the scan result. Of 184 patient undergoing craniotomy, 40 patients (22%) were scanned within 48 h. Five patients were re-operated for haematoma formation. Prospective assessment showed that surgeons consistently over-estimated the risk at haematoma (mean prescan estimate 63%, actual risk 8%, p = 2.5 x 10(-12)). Less than 1 in 10 postoperative scans show a neurosurgical target. Other changes in management following scanning were slight.

Costs and Cost Analysis↗
PubMed2000

Hormonally-regulated proteins in breast secretions are markers of target organ sensitivity.

Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate end points of the effect of tamoxifen on the normal breast are available. Therefore, the purpose of this study was to develop a physiological measure of oestrogen action on the breast. We measured oestrogen-stimulated and -inhibited proteins in breast secretions from women on and off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and cathepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease fluid protein 15; Apo,: apolipoprotein D) were measured. Premenopausal women had significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential nipple aspirates from women treated with the luteinizing hormone releasing hormone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, median nipple secretion levels of pS2 fell (P < 0.02) and Apo D and CP15 rose significantly (P < 0.03 and P < 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment with HRT resulted in a rise of pS2 (P < 0.001) and a fall in Apo D (P < 0.05). Measurement of pS2 and Apo D in nipple aspirates may prove useful intermediate end point of breast responsiveness to anti-oestrogens.

Adult↗
PubMed1999

Dietary management of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). A case report and survey.

Current dietary management of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD; long-chain-(S)-3-hydroxyacyl-CoA:NAD+ oxido-reductase, EC 1.1.1.211) deficiency (LCHADD) is based on avoiding fasting, and minimizing energy production from long-chain fatty acids. We report the effects of various dietary manipulations on plasma and urinary laboratory values in a child with LCHADD. In our patient, a diet restricted to 9% of total energy from long-chain fatty acids and administration of 1.5 g medium-chain triglyceride oil per kg body weight normalized plasma acylcarnitine and lactate levels, but dicarboxylic acid excretion remained approximately ten times normal. Plasma docosahexaenoic acid (DHA, 22:6n-3) was consistently low over a 2-year period; DHA deficiency may be related to the development of pigmentary retinopathy seen in this patient population. We also conducted a survey of metabolic physicians who treat children with LCHADD to determine current dietary interventions employed and the effects of these interventions on symptoms of this disease. Survey results indicate that a diet low in long-chain fatty acids, supplemented with medium-chain triclyceride oil, decreased the incidence of hypoketotic hypoglycaemia, and improved hypotonia, hepatomegaly, cardiomyopathy, and lactic acidosis. However, dietary treatment did not appear to effect peripheral neuropathy, pigmentary retinopathy or myoglobinuria.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1999

The value of program certification for performance contracting.

A survey of clubhouses listed in the 1996 ICCD Clubhouse Directory provided a research sample of 80 ICCD-certified clubhouses and 88 non-certified clubhouses with which to test the discriminant validity of ICCD certification. A statistically significant logistic regression model revealed that ICCD certification status could be clearly predicted for 78% of the clubhouses in the survey sample on the basis of director-reported compliance with representative measures of the Standards for Clubhouse Programs. The predictive power of compliance with the Standards was obtained even while controlling for other organizational variables, including clubhouse age, total staff salaries, and receipt of Medicaid funding. These findings provide support for the practical utility of adopting program certification as a performance indicator in an era of managed care, as well as the specific value of relying on ICCD certification as a quality assurance indicator.

Certification↗
PubMed1999

Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast.

An association has been reported between consumption of a high soy diet and a low incidence of breast cancer within populations of Southeast Asia. Phytoestrogens present in soy act as partial estrogen agonists or antagonists and can inhibit breast cancer cell proliferation in vitro. The effect of 14-day dietary soy supplementation with 60 g (45 mg isoflavones) on the normal breast of 84 premenopausal patients was determined. Serum concentrations of the isoflavanoids, genistein, daidzein, and equol, were raised in patients after soy supplementation (P < or = 0.025). Nipple aspirate (NA) levels of genistein and daidzein were higher than paired serum levels, both before (P < 0.001 and P = 0.001, respectively) and after soy supplementation (P < 0.001 and P = 0.049, respectively); however, there was no significant increase in NA isoflavone levels in response to soy. NA levels of apolipoprotein D were significantly lowered and pS2 levels raised in response to soy supplementation (P < or = 0.002), indicative of an estrogenic stimulus. No effect of soy supplementation on breast epithelial cell proliferation, estrogen and progesterone receptor status, apoptosis, mitosis, or Bcl-2 expression was detected. In conclusion, short term dietary soy has a weak estrogenic response on the breast, as measured by nipple aspirate apolipoprotein D and pS2 expression. No antiestrogenic effect of soy on the breast was detected.

Adult↗
PubMed1998

Aluminum toxicity.

Explore the source record for details and available documents.

Abnormalities, Drug-Induced↗
PubMed1998

Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast.

A high dietary intake of soy products (eg, as in Japan and Singapore) has been associated with a reduction in the incidence of breast cancer in premenopausal women. Phytoestrogens present in soybeans inhibit human breast cancer cell proliferation in vitro and breast cancer development in animal models, but no data exist on the effects of phytoestrogens on histologically normal human breasts. This study examines the effects of dietary soy supplementation on the proliferation rate of premenopausal, histologically normal breast epithelium and the expression of progesterone receptor. Women (n = 48) with benign or malignant breast disease were randomly assigned to receive their normal diet either alone or with a 60-g soy supplement (containing 45 mg isoflavones) taken daily for 14 d. Biopsy samples of normal breasts were labeled with [3H]thymidine to detect the number of cells in S phase and were immunocytochemically stained for the proliferation antigen Ki67. The phytoestrogens genistein, daidzein, equol, enterolactone, and enterodiol were measured in serum samples obtained before and after supplementation. Serum concentrations of the isoflavones genistein and daidzein increased in the soy group at 14 d. Results showed a strong correlation between Ki67 and the thymidine labeling index (r = 0.868, P < or = 0.001). The proliferation rate of breast lobular epithelium significantly increased after 14 d of soy supplementation when both the day of menstrual cycle and the age of patient were accounted for. Progesterone receptor expression increased significantly in the soy group. Short-term dietary soy stimulates breast proliferation; further studies are required to determine whether this is due to estrogen agonist activity and to examine the long-term effects of soy supplementation on the pituitary gland and breast.

Adult↗
PubMed1996

Stratum corneum lipids: the effect of ageing and the seasons.

Stratum corneum lipids play a predominant role in maintaining the water barrier of the skin. In order to understand the biological variation in the levels and composition of ceramides, ceramide 1 subtypes, cholesterol and fatty acids, stratum corneum lipids collected from tape strippings from three body sites (face, hand, leg) of female Caucasians of different age groups were analysed. In addition, we studied the influence of seasonal variation on the lipid composition of stratum corneum from the same body sites. The main lipid species were quantified using high-performance thin-layer chromatography and individual fatty acids using gas chromatography. Our findings demonstrated significantly decreased levels of all major lipid species, in particular ceramides, with increasing age. Similarly, the stratum corneum lipid levels of all the body sites examined were dramatically depleted in winter compared with spring and summer. The relative levels of ceramide 1 linoleate were also depleted in winter and in aged skin whereas ceramide 1 oleate levels increased. The other fatty acid levels remained fairly constant with both season and age, apart from lignoceric and heptadecanoic acid which showed a decrease in winter compared with summer. The decrease in the mass levels of intercellular lipids and the altered ratios of fatty acids esterified to ceramide 1, are likely to contribute to the increased susceptibility of aged skin to perturbation of barrier function and xerosis, particularly during the winter months.

Adult↗
PubMed1995

The effect of glycerol and humidity on desmosome degradation in stratum corneum.

Moisturizers are known to have occlusive, emollient and humectant properties, all of which help to alleviate the symptoms of skin xerosis. Although the biological mode of action of moisturizers is poorly understood, the recent observation that skin xerosis is associated with incomplete desmosome digestion suggests that moisturizers improve the desquamation process in such conditions. To examine the possibility that certain moisturizers act by facilitating desmosomal digestion, we investigated the ability of glycerol, a common humectant, to influence this process in stratum corneum in vitro. Examining desmosome morphology in isolated stratum corneum by electron microscopy, it was observed that the desmosomes were in more advanced stages of degradation in glycerol-treated tissue compared with control tissue. This enhanced desmosomal degradation in glycerol-treated tissue was confirmed by significant decreases in the levels of immunoreactive desmoglein 1, a marker of desmosome integrity. Desmosomal degradation was also shown to be a humidity-dependent event, being significantly reduced at low relative humidity. The effect of glycerol on desmosome digestion was emphasized further in two in vitro model systems. Firstly, glycerol increased the rate of corneocyte loss from the superficial surface of human skin biopsies in a simple desquamation assay. Secondly, measurement of the mechanical strength of sheets of stratum corneum, using an extensiometer, indicated a dramatic reduction in the intercorneocyte forces following glycerol treatment. These studies demonstrated the ability of glycerol to facilitate desmosome digestion in vitro. Extrapolating from these results, we believe that one of the major actions of moisturizers in vivo is to aid the digestion of desmosomes which are abnormally retained in the superficial layers of xerotic stratum corneum.

Cytoskeletal Proteins↗
PubMed1995

Mother-firstborn attachment and the birth of a sibling.

Stability of the firstborn's quality of attachment to the mother was examined during the period from the last trimester of the mother's second pregnancy through the early postpartum period, as assessed by the Strange Situation. A second pregnancy and the birth of a sibling were significantly associated with instability in the mother-firstborn attachment.

Birth Order↗
PubMed1994

Issues of accountability in the assessment of practice.

The nature of nursing work makes the Code of Professional Conduct's moral and professional emphasis appropriate. However this is to the detriment of practitioners' moral, professional and contractual accountability towards learners. Practitioners may fail to make the paradigmatic shift necessary for them to be accountable for the teaching, supervision and assessment of learners. This is a direct consequence of the paucity of assessor preparation and the utilization of assessors with limited professional experience. They have been invested with an authority of which they are unaware and for which they are unprepared.

Clinical Competence↗
PubMed1990

The role of the father in the development of stranger sociability during the second year.

The relationship between quality of infant attachment to parents and sociability toward a strange adult was investigated, and level of stranger sociability with father present was compared to that with mother present. Results suggest that during the child's second year, and particularly for boys, the presence of the father represents a distinct social context for the child.

Child, Preschool↗
PubMed1985

Morphological analysis of ligand uptake and processing: the role of multivesicular endosomes and CURL in receptor-ligand processing.

The receptor-mediated endocytosis and intracellular processing of transferrin and mannose receptor ligands were investigated in bone marrow-derived macrophages, fibroblasts and reticulocytes. Mannosylated bovine serum albumin (BSA) conjugated to colloidal gold (Au-man-BSA) or colloidal gold-transferrin (AuTf) were used to trace ligand processing in these cells. These ligands appeared to be processed by mechanisms similar to those observed previously with other mannose receptor and galactose receptor ligand probes. After uptake via coated pits and coated vesicles, Au-man-BSA appeared in small uncoated vesicles and tubular structures and was transferred to large, sometimes multivesicular endosomes (MVEs), which sometimes had arm-like protrusions reminiscent of CURL (compartment of uncoupling of receptor and ligand) [10, 11]. Initially these structures became increasingly multivesicular, but during longer incubations the inclusion vesicles appeared to disintegrate to leave a denser, amorphous lumen. Inclusion vesicle disintegration may result from the introduction of lysosomal enzymes into these structures. These results suggest a model for differential receptor-ligand and ligand-ligand sorting. As suggested [10, 11] membrane constituents may be recycled to the plasma membrane from the arms of CURL. Receptor-bound ligands, such as transferrin, would also recycle. The luminal contents, including dissociated ligands, other soluble proteins and inclusion vesicles (containing some membrane proteins), would target to lysosomes. This would result in the lysosomal degradation of any membrane proteins that were incorporated in the inclusion vesicle membranes.

Animals↗