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Biomedical subjects

M Cartwright

Publications and source records attributed to M Cartwright.

At least 19 recordsLinked to original sources
PubMed2006

Investigation of the lipid component of neuromelanin.

OBJECTIVE: Neuromelanin (NM) is different to other melanins in that its ultrastructure includes a lipid component. The objectives of this study were to identify and quantify lipids associated with NM. RESULTS: Quantification of the lipid component associated with the pigment on electron micrographs demonstrated that this component comprises 35% of the NM granule volume in the normal brain. The irregular ultrastructural appearance of the NM granules was quite different to the round regular boundary of melanin granules. Using reversed phase high performance liquid chromatography (HPLC) coupled with atmospheric pressure chemical ionization (APCI) mass spectrometry we demonstrated that the isoprenoid dolichol accounted for approximately 12% of total NM pigment mass. Low levels of other lipids were detectable (cholesterol, ubiquinone-10 and alpha-tocopherol) and account for <0.05% of NM lipid, in contrast to cholesterol accounting for 35% of total brain lipids. CONCLUSION: Unlike other melanins, a substantial proportion of NM volume is comprised of lipid and the major type of lipid associated with NM granules is the isoprenoid dolichol.

Adult↗
PubMed2006

alpha2-adrenoceptor agonists as nasal decongestants.

Nasal congestion, one of the major disease features of rhinitis, is induced by the filling of venous sinusoids causing mucosal engorgement with resultant obstruction of nasal airflow. The only available drugs that directly target the underlying vascular features driving nasal obstruction are the sympathomimetic alpha-adrenoceptor agonists due to their vasoconstrictor action. However, standard decongestants are nonselective alpha-adrenoceptor agonists, which have the potential for side-effects liabilities such as hypertension, stroke, insomnia and nervousness. In the present study, the effects of nonsubtype selective alpha(2)-adrenoceptor agonists BHT-920 and PGE-6201204 were evaluated in several isolated nasal mucosa contractile bioassays including dog, pig and monkey, and in a real-time tissue contractility assay using isolated pig nasal explants for BHT-920. The decongestant activity of PGE-6201204 was evaluated in vivo in a cat model of experimental congestion. Our results showed that alpha(2)-adrenoceptor agonists (1) contract nasal mucosa of different species, (2) exert a preferential vasoconstrictor effect on the capacitance vessels (veins and sinusoids), and (3) elicit decongestion. In conclusion, a selective alpha(2)-adrenoceptor agonist causing constriction preferentially in the large venous sinusoids and veins of nasal mucosa and producing nasal decongestion is expected to show efficacy in the treatment of nasal congestion without the characteristic arterio-constrictor action of the standard nonselective sympathomimetic decongestants.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2003

Socioeconomic disparities in cancer-risk behaviors in adolescence: baseline results from the Health and Behaviour in Teenagers Study (HABITS).

BACKGROUND: This study explores the association between socioeconomic deprivation and five factors associated with long-term risk of cancer, in adolescents. METHODS: BMI, fat intake, fruit and vegetable intake, smoking, and exercise were assessed in 4320 students ages 11 to 12, from 36 schools, in the first year of a 5-year longitudinal study of the development of health behaviors (HABITS study). Neighborhood socioeconomic deprivation for each student's area of residence was matched to their postcode (zip code). We used multiple logistic regression analyses to investigate the relationship between risky behaviors and socioeconomic circumstances. RESULTS: Univariate analyses showed boys and girls from more deprived neighborhoods were more likely to have tried smoking, to eat a high fat diet, and to be overweight. Girls living in more deprived areas were also less likely to eat five servings of fruit and vegetables or to exercise at the weekend. Most differences persisted after controlling for ethnicity. A clear deprivation gradient emerged for each risk factor, indicating the linear nature of the relationship. CONCLUSIONS: This study demonstrates the influence of deprivation on engaging in cancer-risk health behaviors. These patterns may set young people from more socioeconomically deprived social environments on a trajectory leading to increased cancer mortality in adult life.

Adolescent↗
PubMed2003

Examining the relationship between pubertal stage, adolescent health behaviours and stress.

BACKGROUND: This paper examines the associations between puberty and three important health behaviours (smoking, food intake and exercise) and explores whether these associations are mediated by puberty's relationship to stress and psychological difficulties. METHOD: Data were taken from the first year of the ongoing, 5-year, Health and Behaviours in Teenagers Study (HABITS). This is a school-based study set in 36 schools in London. In the first year of the study, 4320 students (2578 boys, 1742 girls) in their first year of secondary education took part. RESULTS: Among girls, being more pubertally advanced was associated with a greater likelihood of having tried smoking. Among boys, being more pubertally advanced was associated with a greater likelihood of having tried smoking, a higher intake of high-fat food and higher levels of exercise. More pubertally advanced girls experienced more stress but not more psychological difficulties. There were no associations between puberty and either stress or psychological difficulties in boys. Stress and psychological difficulties were associated with health behaviours in girls and boys, but neither of these factors mediated the relationship between pubertal stage and health behaviours found in girls. CONCLUSIONS: These results suggest that the onset of puberty has a marked effect on the development of health behaviours. Puberty was related to an acceleration of the development of unhealthy behaviours, except for exercise behaviour in boys, where advanced puberty was associated with more exercise. These changes were unrelated to adolescent issues of stress and a causal explanation for these associations must be sought elsewhere.

Adolescent↗
PubMed2000

Body piercing: what nurse practitioners need to know.

Body piercing is a growing trend among today's youth. Chances are, nurse practitioners will be in contact with someone who has a body piercing and/or complication relating to piercing. This article includes the history of body piercing, the environment of piercing parlors, the methods commonly used, site-specific explanations of select piercings, complications, treatment and practice implications. Nurse practitioners need to establish collaborative working relationships with their clients as well as those who do the piercings.

Cosmetic Techniques↗
PubMed1998

Recombinant E1-deleted adenovirus-mediated gene therapy for cancer: efficacy studies with p53 tumor suppressor gene and liver histology in tumor xenograft models.

Type 5 adenoviral (Ad) vectors have been the "vector-of-choice" for preclinical studies on p53 tumor suppressor gene therapy of cancer. Previous studies have examined the in vivo efficacy of p53 Ad when given intratumorally. However published information does little to guide clinicians in the design of intraperitoneal (i.p.) dosing trials for i.p. tumors, e.g., ovarian, or clinical trials using regional organ perfusion, e.g., for lung tumors. Therefore, we examined several parameters with special significance for these routes of administration. Lung metastases from p53mut MDA-MB-231 mammary xenografts were treated with therapeutic levels of intravenous buffer, beta-galactosidase (beta-Gal) Ad, or p53 Ad. Treatment with intravenous p53 Ad significantly reduced the number of metastases per lung and there was a dramatic reduction in the surface area occupied by these tumors as compared to control groups. Two types of i.p. tumor xenografts were used for preclinical modeling of i.p. gene therapy, the p53null SK-OV-3 ovarian and the p53mut DU-145 prostate human cancers. In a study examining the effect of different vehicle volumes on the efficacy of a constant drug dose, all mice treated with p53 Ad had reduced tumor burden compared to controls. Dosing volumes between 0.2 and 1 ml were equally effective and all were more effective than a dosing volume of 0.1 ml. However, reduced efficacy was observed when a volume of 1.5 ml was used. When the effect of dosing frequency on antitumor efficacy was examined, fractionated doses of p53 Ad had somewhat greater efficacy than fewer, bolus injections. One of the significant elements in the emerging toxicology associated with recombinant adenoviruses is the hepatocyte pathology caused by high systemic concentrations of adenovirus. For recombinant Ad used in this study, there was a pronounced dose-dependence for the liver response, with very high, repeated doses causing significant hepatocellular insult. Expression of cytoplasmic beta-Gal protein coincided with areas of greatest damage in mice treated with high doses of beta-Gal Ad. Ultrastructural examination of hepatocyte intranuclear inclusions revealed moderately electron-dense, tightly packed granular material interspersed with more electron-dense nuclear material. Human tumor xenografts, but not mouse tissues, expressed viral hexon protein. In summary, hepatic toxicity caused by high concentrations of recombinant adenovirus was observed in murine cancer models. However, therapeutic levels of p53 Ad could be achieved which had dramatic efficacy without significant pathology.

Adenoviridae↗
PubMed1996

Numeracy needs of the beginning registered nurse.

The literature indicates: Nursing students demonstrate serious numeracy skills deficits. Consensus that such skills are necessary, particularly for medication administration. Diagnostic testing and remediation are desirable, or basic mathematics is pre-requisite for entry into nursing courses. Calculation skills mastered at one point in time diminish if ongoing practise is not maintained. The frequency with which nurses perform drug calculation in the clinical setting is decreasing. This study aimed to identify and analyze numeracy skills required by beginning registered nurses to facilitate development of numeracy skills by nursing students. A convenience sample of metropolitan and rural health care facilities in New South Wales (NSW) was selected. Within each facility an area where nursing graduates customarily work was selected. Numeracy input required to complete patients' charts was identified. Additional counting, measuring or computation the nurses performed was also identified. Except for paediatric areas, the frequency with which a nurse has to perform other than a simple calculation in order to administer a medication, or calculate a per minute drip rate is low. However, the necessity to calculate drug doses does exist. Creative ideas are needed to enable nurses to do this accurately. Three general approaches are suggested. A number of recommendations are presented.

Clinical Competence↗
PubMed1996

Characterization of Prostaglandin G/H Synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts.

BACKGROUND & AIMS: In the gastrointestinal tract, prostaglandins are implicated as important mediators of normal physiological processes. Prostaglandin G/H synthase (PGHS) is the first enzyme leading to the formation of prostaglandins. Two forms exist: the constitutive PGHS-1 and the inducible PGHS-2 isoforms. The purpose of this study was to examine the expression of PGHS-1 and -2 in gastrointestinal tissues. METHODS: PGHS-1 and -2 expression and activity were examined in rat, dog, monkey, and human gastrointestinal tracts by immunoblot and biochemical assays. RESULTS: PGHS-1 but not PGHS-2 protein was identified in all gastrointestinal tissues. PGHS-1 protein varied throughout the gastrointestinal tracts; interspecies differences were also noted. Immunohistochemical studies showed PGHS-1 staining of rat endothelial cells in all gastrointestinal regions; PGHS-2-specific staining was noted in a subset of macrophages in 3 of 22 rats examined. Elevated activity was shown in tissues expressing greater concentrations of PGHS-1 protein. Indomethacin, a nonsteroidal anti-inflammatory drug that inhibits both isoforms, inhibited prostaglandin synthesis, whereas NS-398, a selective PGHS-2 inhibitor, showed little or no inhibition of prostaglandin synthesis in gastrointestinal tissues. CONCLUSIONS: These results indicate that prostaglandins produced in normal gastrointestinal tissue and required for normal physiological functioning are derived from the PGHS-1 isoform.

Amino Acid Sequence↗
PubMed1994

Expression of neurotrophin genes in human fibroblasts: differential regulation of the brain-derived neurotrophic factor gene.

Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) are structurally related survival and differentiation factors for distinct sets of peripheral and central neurons. We previously reported that BDNF and NGF gene expression are differentially regulated in mouse L929 fibroblasts. Here we examine expression of these three neurotrophins in human fibroblasts. Northern blots detected BDNF and NT-3 mRNAs in fibroblasts derived from lung (WI-38), calvarium and foreskin. WI-38 cells and foreskin fibroblasts expressed 1.6 kb as well as 4 kb BDNF mRNAs whereas only the smaller BDNF mRNA was detected in calvarium fibroblasts. NGF mRNA was present in foreskin and calvarium but not lung fibroblasts. In WI-38 cells serum treatment increased levels of BDNF mRNA within 2 hr. Cycloheximide did not inhibit the increase. Treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) transiently suppressed BDNF mRNA. Treatment with both serum and TPA first stimulated and then transiently suppressed BDNF mRNA. TPA and/or serum did not significantly affect BDNF mRNA in calvarium fibroblasts. These results show that human fibroblasts derived from different tissues express and regulate neurotrophin genes differentially.

Blotting, Northern↗
PubMed1992

The human nerve growth factor gene: structure of the promoter region and expression in L929 fibroblasts.

We previously studied the transcriptional mechanisms involved in expression of the murine nerve growth factor (NGF) gene. To investigate the regulation of transcription of the human NGF gene, the promoter region was cloned. The nucleotide sequences of the human and mouse genes are greater than 90% similar near their promoters. The cloned human promoter was transcriptionally active in mouse L929 fibroblasts. 5' Deletion analyses indicated that the -85 to -45 region stimulates basal transcription 6-fold. This segment is greater than 80% identical in human and mouse genes except for an AP-1 consensus sequence found only in the human gene. A second AP-1 consensus sequence at +34, previously shown to function as a regulatory element in the mouse gene, is identical in both genes. Gel shift analyses of L929 cell extracts revealed binding of protein to oligonucleotide probes spanning each of the two AP-1 consensus sequences of the human gene. The gel shift patterns differed, suggesting interaction of different proteins with the two probes. Our results demonstrate that the human NGF gene promoter is transcriptionally active in mouse fibroblasts, and implicate an upstream region in basal transcription.

Animals↗
PubMed1989

Comparison of renal biopsy techniques in dogs.

To evaluate adequacy of biopsy specimens obtained and safety to the patient, the standard keyhole biopsy technique (using digital immobilization of the right kidney and placement of the biopsy needle up to the capsule before obtaining a tissue sample) was compared with 9 technical modifications. Adequacy was judged by the number of intact glomeruli observed in the specimen. Detection of transected blood vessels and renal pelvis was presumed to have predictive value for postbiopsy complications of hemorrhage and hydronephrosis. Needle biopsy specimens were also obtained from left and right kidneys by use of laparoscopic visualization and were compared with those obtained by use of the standard keyhole technique. Although the standard keyhole technique yielded the highest percentage of adequate biopsy specimens, there was no statistical difference between specimens obtained by this technique and those obtained by the modified technique or by laparoscope-guided biopsy. Also, significant difference in percentage of biopsy specimens with renal pelvis was not found between specimens obtained by the standard and modified techniques. For each technique, the biopsy core length was measured and the mean value was calculated. In this study, core length did not correlate with adequacy of the biopsy specimen.

Animals↗
PubMed1986

A model for the control of testosterone secretion.

We produce here a model to explain the control of testosterone secretion. In this model the hypothalamic secretion of the hormone LHRH (luteinizing hormone releasing hormone) is controlled by a combination of local testosterone concentration and of the local concentration of the pituitary hormone LH (luteinizing hormone). Since LHRH stimulates the release of LH, and LH in turn stimulates the release of testosterone, the three hormones constitute a three-component "feedback" network. We show how this model is able to account for the pulsatility of the release of these three hormones. Furthermore, the model is consistent with results obtained from a wide range of experimental manipulations of the system. For example, it accounts for the changes observed in hormone release patterns after castration. In particular, it follows that no "neural clock", or "neural pulse-generator", is required to force the system into pulsatile behaviour.

Gonadotropin-Releasing Hormone↗