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1.
Subst Use Misuse ; 44(13): 1926-40, 2009.
Article in English | MEDLINE | ID: mdl-20001289

ABSTRACT

The purpose of this study was to examine the relationship of spirituality, religiosity and self-efficacy with drug and/or alcohol cravings. A cross-sectional survey was completed by 77 male participants at an Australian Salvation Army residential rehabilitation service in 2007. The survey included questions relating to the participants' drug and/or alcohol use and also measures for spirituality, religiosity, cravings, and self-efficacy. The sample included participants aged between 19 and 74 years, with more than 57% reporting a diagnosis for a mental disorder and 78% reporting polysubstance misuse with alcohol most frequently endorsed as the primary drug of concern (71%). Seventy-five percent of the clients reported that spirituality and religious faith were useful components of the treatment program. A multivariate multiple regression analysis identified that spirituality and self-efficacy have significant relationships with cravings. Self-efficacy mediated the relationship between spirituality and drug and/or alcohol cravings. The limitations of this study included its cross-sectional design and a sample that was drawn from a faith-based program. Future research would benefit from the longitudinal examination of the relationship between spirituality, self-efficacy, and cravings; the exploration of a broader range of client-specific and interpersonal variables; and the inclusion of a control group from a secular treatment facility.


Subject(s)
Behavior, Addictive/psychology , Religion , Spirituality , Substance-Related Disorders/psychology , Adult , Aged , Humans , Male , Middle Aged , Pilot Projects , Psychotherapy , Self Efficacy , Substance-Related Disorders/therapy
2.
Biotechnol Annu Rev ; 11: 101-25, 2005.
Article in English | MEDLINE | ID: mdl-16216775

ABSTRACT

The nuclear receptor (NR) superfamily represents a major class of drug targets for the pharmaceutical industry. Strategies for the development of novel, more selective and safer compounds aimed at these receptors are now emerging. Reporter assays have been used routinely for the identification and characterisation of NR ligands. As the NR drug development process evolves, the increase in screening demand in terms of both capacity and complexity has necessitated the development of novel assay formats with increased throughput and flexibility. BacMam technology, a modified baculovirus system for over-expressing genes of interest in mammalian cells has helped answer this requirement. BacMam has many advantages over traditional gene delivery systems including high transduction efficiencies, broad cell host range, speed, cost and ease of generation and use. As outlined in this review, the technology has shown itself to be robust and efficient in various NR assay formats including transactivation (ER alpha/beta, MR, PR and PXR) and transrepression (GR-NFkappaB). In addition, the flexibility of this system will allow greater multiplexing of receptor, reporter, and cell host combinations as NR assays become more complex in order to relate better to relevant cellular and biological systems.


Subject(s)
Baculoviridae/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Technology, Pharmaceutical/methods , Transfection/methods , Animals , Gene Expression Regulation/genetics , Genetic Vectors/genetics , Humans , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Receptors, Steroid/antagonists & inhibitors , Receptors, Steroid/genetics
3.
J Biomol Screen ; 10(7): 715-24, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16129777

ABSTRACT

The authors describe the use of modified baculoviruses containing mammalian expression cassettes (BacMam technology) in steroid nuclear receptor reporter assays designed for screening and profiling agonist and antagonist compounds. Baculo-viruses were constructed that express full-length human genes for mineralocorticoid receptor (MR), glucocorticoid receptor (GR), progesterone receptor A (PR-A), and progesterone receptor B (PR-B) from the cytomegalovirus immediate early promoter. A virus carrying the mouse mammary tumor virus-firefly luciferase (MMTV-Luc) cassette was generated to provide a suitable reporter construct. Feasibility studies with BacMam-MR in single-dose tests of 1000 compounds showed high correlation to the standard transfection-based assay results. Likewise, in dose-response experiments, BacMam-based assays for GR and PR-B produced potency and efficacy values similar to transfection assay results. At various receptor/reporter ratios, the BacMam assays showed good flexibility, demonstrating consistent signal-to-background (S/B) ratios and compound potencies. Increasing transduction time from 24 to 48 h provided no benefit, actually reducing overall assay performance as measured by S/B and Z' values. The BacMam technology was applied in studies of isoforms PR-A and PR-B, which showed similar responses to a series of agonists. Taken together, the results demonstrate the utility of steroid nuclear receptor BacMam constructs for compound screening procedures with high reproducibility, reduced turnaround time, and lower cost.


Subject(s)
Baculoviridae/genetics , DNA, Recombinant/genetics , Receptors, Progesterone/analysis , Receptors, Progesterone/genetics , Animals , Cell Line , Cell Line, Tumor , Chlorocebus aethiops , Humans , Protein Isoforms/analysis , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptors, Progesterone/metabolism , Transduction, Genetic , Transfection
4.
Dysphagia ; 20(1): 46-61, 2005.
Article in English | MEDLINE | ID: mdl-15886967

ABSTRACT

Tube feeding is commonly used as a method of giving children nutrition while they are being treated for disease. While this is an effective way of ensuring a child thrives and grows, research studies and clinical experience have shown that long-term oral feeding difficulties often arise when the child no longer requires tube feeding. This article gives a critical review of the literature on tube feeding and its effect on normal eating and drinking skills. While few studies have followed a rigorous research design, there is enough literature to identify a number of factors which may be implicated in later feeding difficulties and which therefore need further exploration in research studies. These factors include age at which oral feeding commences, medical complications, exposure to taste and textures during sensitive periods, aversive experiences, and different methods of delivering tube feeds.


Subject(s)
Deglutition Disorders/diagnosis , Drinking , Eating , Enteral Nutrition , Infant Care , Deglutition Disorders/etiology , Enteral Nutrition/adverse effects , Gastrostomy , Humans , Infant
5.
J Vis Impair Blind ; 99(12): 741-754, 2005.
Article in English | MEDLINE | ID: mdl-20198108

ABSTRACT

The variability of the length and frequency of steps was measured in sighted and visually impaired walkers at three different paces. The variability was low, especially at the preferred pace, and similar for both groups. A model incorporating step counts and step frequency provides good estimates of the distance traveled. Applications to wayfinding technology are discussed.

6.
Mol Cell Biol ; 23(13): 4728-37, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12808110

ABSTRACT

Drugs that produce covalent interstrand cross-links (ICLs) in DNA remain central to the treatment of cancer, but the cell cycle checkpoints activated by ICLs have received little attention. We have used the fission yeast, Schizosaccharomyces pombe, to elucidate the checkpoint responses to the ICL-inducing anticancer drugs nitrogen mustard and mitomycin C. First we confirmed that the repair pathways acting on ICLs in this yeast are similar to those in the main organisms studied to date (Escherichia coli, budding yeast, and mammalian cells), principally nucleotide excision repair and homologous recombination. We also identified and disrupted the S. pombe homologue of the Saccharomyces cerevisiae SNM1/PSO2 ICL repair gene and found that this activity is required for normal resistance to cross-linking agents, but not other forms of DNA damage. Survival and biochemical analysis indicated a key role for the "checkpoint Rad" family acting through the chk1-dependent DNA damage checkpoint in the ICL response. Rhp9-dependent phosphorylation of Chk1 correlates with G(2) arrest following ICL induction. In cells able to bypass the G(2) block, a second-cycle (S-phase) arrest was observed. Only a transient activation of the Cds1 DNA replication checkpoint factor occurs following ICL formation in wild-type cells, but this is increased and persists in G(2) arrest-deficient mutants. This likely reflects the fraction of cells escaping the G(2) damage checkpoint and arresting in the subsequent S phase due to ICL replication blocks. Disruption of cds1 confers increased resistance to ICLs, suggesting that this second-cycle S-phase arrest might be a lethal event.


Subject(s)
Cross-Linking Reagents/pharmacology , Protein Serine-Threonine Kinases , Schizosaccharomyces/genetics , Schizosaccharomyces/metabolism , Camptothecin/pharmacology , Cell Survival , Checkpoint Kinase 2 , Cisplatin/pharmacology , DNA/drug effects , DNA/radiation effects , DNA Damage , DNA Repair , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Enzyme Inhibitors/pharmacology , G2 Phase , Hydroxyurea/pharmacology , Mitomycin/pharmacology , Nucleic Acid Synthesis Inhibitors/pharmacology , Phosphorylation , Protein Kinases/metabolism , Radiation-Sensitizing Agents/pharmacology , Recombination, Genetic , S Phase , Schizosaccharomyces pombe Proteins , Temperature , Time Factors
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