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Biomedical subjects

S Coleman

Publications and source records attributed to S Coleman.

At least 19 recordsLinked to original sources
PubMed2005

The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer.

A clinical trial employing an immunotherapeutic approach based on the use of a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes carrying tumour-associated antigens is planned in advanced ovarian cancer in conjunction with conventional first line chemotherapy. Most patients with ovarian cancer present with advanced disease and despite high initial response rate to chemotherapy the majority will relapse within 2 years with poor overall survival. Tumour antigen-specific T cells are naturally occurring in ovarian cancer patients and T cell infiltration of the tumour is highly prognostic. Novel immunotherapy to expand and activate tumour antigen-specific T cells combined with adjuvant treatment to overcome tumour-induced immunosuppression is considered to be therapeutically beneficial. The rationale for adopting such a combined approach is discussed here.

Animals↗
PubMed2005

How evidence based is the management of two common sports injuries in a sports injury clinic?

OBJECTIVES: To examine the diagnosis and management of adults attending a sports injury clinic, to establish to what extent the management of the two most common injuries treated at this clinic is evidence based, and to explore factors that affect management. METHODS: A retrospective examination of 100 random case notes extracted age, sex, sport, type and site of injury, treatment, and outcome. Systematic literature reviews examined the extent and quality of scientific evidence for the management of the two most commonly presenting injuries. A clinical attachment period and practitioner interviews allowed recognition of factors impinging on management decisions. RESULTS: Patellofemoral pain syndrome (PFPS; 10% of all injuries) and Achilles tendinopathy (6% of all injuries) were the most commonly presenting injuries. The mean (SD) number of treatments used for PFPS was 2.8 (0.9). The mean number of treatments used for Achilles tendinopathy was 3.7 (1.0). Clinicians reported that personal experience formed the basis of management plans in 44% of PFPS cases and 59% of Achilles tendinopathy cases, and that primary research evidence only accounted for 24% of management plans in PFPS and 14% in Achilles tendinopathy. Practitioners were unaware of literature supporting over 50% of the treatment modalities they used. However, clinicians were often using evidence based treatments, unaware of the supporting research data. CONCLUSIONS: This study highlights a lack of evidence base, a lack of knowledge of the research evidence, and a lack of management based on the current evidence that is available for these conditions. Practitioners practised evidence based medicine in under 50% of cases.

Achilles Tendon↗
PubMed2002

Characterisation, mutation detection, and association analysis of alternative promoters and 5' UTRs of the human dopamine D3 receptor gene in schizophrenia.

The dopamine D(3) receptor gene (DRD3) is a candidate for a number of psychiatric conditions including schizophrenia, bipolar disorder and alcohol and drug abuse. Previous studies have reported associations between polymorphisms in DRD3 and these disorders, but these findings may have reflected linkage disequilibrium with pathogenic variants that are further upstream. We have isolated and sequenced approximately 9 kb of genomic sequence upstream of the human DRD3 translational start site. Using 5' RACE, we have identified within this region three additional exons and two putative promoter regions which show promoter activity in three different cell lines. A 5' UTR identified only in lymphoblasts is spread over three exons and is 353 bp long. A second 5' UTR, found in adult and fetal brain, lymphocytes, kidney and placenta is spread over two exons and is 516 bp long. A 260-bp sequence within this 9 kb corresponds to a previously reported EST, but corresponding mRNA could not be found in the tissues above. The EST, 5' UTRs and putative promoter regions have been analysed for polymorphisms, revealing 10 single nucleotide polymorphisms, seven of which were tested for association in a large sample of unrelated patients with schizophrenia and matched controls. No associations were observed with schizophrenia. In addition we failed to replicate previous findings of association with homozygosity of the Ser9Gly variant. The results from this study imply that neither the coding nor the regulatory region of DRD3 plays a major role in predisposition to schizophrenia.

5' Untranslated Regions↗
PubMed2002

A hydrogel material for plastic and reconstructive applications injected into the subcutaneous space of a sheep.

Soft tissue reconstruction using tissue-engineered constructs requires the development of materials that are biocompatible and support cell adhesion and growth. The objective of this study was to evaluate the use of macroporous hydrogel fragments that were formed using either unmodified alginate or alginate covalently linked with the fibronectin cell adhesion peptide RGD (alginate-RGD). These materials were injected into the subcutaneous space of adult, domesticated female sheep and harvested for histological comparisons at 1 and 3 months. In addition, the alginate-RGD porous fragments were seeded with autologous sheep preadipocytes isolated from the omentum, and these cell-based constructs were also implanted. The results from this study indicate that both the alginate and alginate-RGD subcutaneous implants supported tissue and vascular ingrowth. Furthermore, at all time points of the experiment, a minimal inflammatory response and capsule formation surrounding the implant were observed. The implanted materials also maintained their sizes over the 3-month study period. In addition, the alginate-RGD fragments supported the adhesion and proliferation of sheep preadipocytes, and adipose tissue was present within the transplant site of these cellular constructs, which was not present within the biomaterial control sites.

Absorbable Implants↗
PubMed2001

Process capability measurement of frequent replacement toric soft contact lenses.

PURPOSE: Frequent replacement soft contact lenses, and particularly toric soft lenses, require good reproducibility in order to avoid clinical problems arising from manufacturing variations in their parameters. This study assessed the actual and potential process capability of six frequent replacement toric soft lenses in relation to sphere power, cylinder power, cylinder axis, total diameter, back optic zone radius and centre thickness. METHOD: In total, 1260 lenses consisting of three sphere powers (plano, -3.00 and -6.00 D) were measured for six lens types. Three cylinder powers and six cylinder axes were assessed for each sphere power, except for one lens type where only two cylinder powers were available. RESULTS: Significant differences in reproducibility were found between the lens types tested. Process capability and optical quality decreased with increasing sphere power for all lenses. Cylinder power process capability tended to be better than that for sphere power. In general, lenses showed adequate reproducibility with those dimensions likely to affect lens fit, namely total diameter, back optic zone radius and centre thickness. CONCLUSIONS: Process capability was shown to be a useful measure of contact lens reproducibility for comparing toric soft lenses and assessing their potential for use on a frequent replacement basis. The results suggest some need for improvement in manufacturing accuracy and precision.

Journal Article↗
PubMed2001

Poorly fitting soft lenses affect ocular integrity.

PURPOSE: The purpose of this study was to determine whether borderline fitting soft lenses have a greater effect on ocular physiology than well fitting lenses. METHOD: The study was a retrospective analysis of data from seven soft lens clinical studies. The results of 63 eyes wearing borderline fitting lenses (31 tight and 32 loose fittings) were evaluated and compared with control eyes wearing optimally fitting lenses. Tight and loose lens fittings were defined as those showing tightness on push-up of > or =65% and < or =35%, respectively. An optimally fitting lens was defined as one showing tightness on push-up in the range 45-50% and decentration less than 0.7 mm. Slit lamp findings at the 1-month follow-up visit were compared. RESULTS: There was a significantly greater level of corneal staining among the tight lens wearing group than the controls (P=0.001); 68% of eyes wearing tight lenses showed staining as compared with 42% of eyes wearing well fitting lenses. There was also a greater level of conjunctival staining among tight lens wearing eyes but no significant difference in bulbar or limbal hyperemia. The loose lens wearing eyes showed a higher level of corneal staining: 69% vs 39% (P=0.04). In addition, the loose lens wearing eyes showed a higher level of bulbar (P=0.03) and limbal hyperemia (P=0.006). From supplementary analysis of 408 lens fittings, the incidence of corneal staining was found to increase with increasing tightness or looseness of fit. CONCLUSION: The results show that corneal staining and other physiological effects of soft lens wear vary with the quality of lens fit suggesting that practitioners should be less tolerant of sub-optimal fitting soft lenses.

Conjunctiva↗
PubMed2000

Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes.

Acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methyl-phenyl)-acetamide], alachlor [N-(methoxymethyl)-2-chloro-N-(2, 6-diethyl-phenyl)acetamide], butachlor [N-(butoxymethyl)-2-chloro-N-(2,6-diethyl-phenyl)acetamide], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] are pre-emergent herbicides used in the production of agricultural crops. These herbicides are carcinogenic in rats: acetochlor and alachlor cause tumors in the nasal turbinates, butachlor causes stomach tumors, and metolachlor causes liver tumors. It has been suggested that the carcinogenicity of these compounds involves a complex metabolic activation pathway leading to a DNA-reactive dialkylbenzoquinone imine. Important intermediates in this pathway are 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) produced from alachlor and butachlor and 2-chloro-N-(2-methyl-6-ethylphenyl)acetamide (CMEPA) produced from acetochlor and metolachlor. Subsequent metabolism of CDEPA and CMEPA produces 2,6-diethylaniline (DEA) and 2-methyl-6-ethylaniline (MEA), which are bioactivated through para-hydroxylation and subsequent oxidation to the proposed carcinogenic product dialkylbenzoquinone imine. The current study extends our earlier studies with alachlor and demonstrates that rat liver microsomes metabolize acetochlor and metolachlor to CMEPA (0.065 nmol/min/mg and 0.0133 nmol/min/mg, respectively), whereas human liver microsomes can metabolize only acetochlor to CMEPA (0.023 nmol/min/mg). Butachlor is metabolized to CDEPA to a much greater extent by rat liver microsomes (0.045 nmol/min/mg) than by human liver microsomes (< 0.001 nmol/min/mg). We have determined that both rat and human livers metabolize both CMEPA to MEA (0.308 nmol/min/mg and 0.541 nmol/min/mg, respectively) and CDEPA to DEA (0.350 nmol/min/mg and 0.841 nmol/min/mg, respectively). We have shown that both rat and human liver microsomes metabolize MEA (0.035 nmol/min/mg and 0.069 nmol/min/mg, respectively) and DEA (0.041 nmol/min/mg and 0.040 nmol/min/mg, respectively). We have also shown that the cytochrome P450 isoforms responsible for human metabolism of acetochlor, butachlor, and metolachlor are CYP3A4 and CYP2B6.

Acetamides↗
PubMed2000

Selective enhancement of beta-adrenergic receptor signaling by overexpression of adenylyl cyclase type 6: colocalization of receptor and adenylyl cyclase in caveolae of cardiac myocytes.

We investigated the effect of adenovirally mediated overexpression of adenylyl cyclase type 6 (AC6), a major form of AC expressed in mammalian heart, on G protein-coupled receptor regulation of cAMP production in neonatal rat ventricular myocytes. Following gene transfer of AC6, isoproterenol- and forskolin-stimulated increases in cAMP were markedly enhanced, whereas basal levels of cAMP and responses to several other agonists that stimulate cAMP formation, e. g., prostaglandin E(2) (PGE(2)), H(2) agonist, glucagon, and A(2) agonist were not increased. Studies to test whether the selective enhancement in beta-adrenergic receptor (AR) response might result from inhibition of AC6 by Galpha(i) and Gbetagamma indicated that pertussis toxin-sensitive inhibition by the muscarinic cholinergic agonist carbachol was unaltered in myocytes overexpressing AC6. Pertussis toxin treatment failed to reveal an enhancement by AC6 overexpression of basal or PGE(2)-stimulated cAMP. Immunoblot analysis of membrane fractions indicated that beta(1)-AR and AC6 are expressed in fractions enriched in caveolin-3 and morphologic caveolae. The data suggest that loss of G(i)-mediated inhibition is not the mechanism for enhancement of beta-AR-stimulated cAMP formation and that key components of beta-AR-mediated activation of AC exist in caveolae of cardiac myocytes, providing a means by which beta-AR response is selectively enhanced by increasing AC6 expression.

Adenylyl Cyclases↗
PubMed1999

In vitro metabolism of alachlor by human liver microsomes and human cytochrome P450 isoforms.

Alachlor (2-chloro-N-methoxymethyl-N-(2,6-diethylphenyl)acetamide) is a widely used pre-emergent chloroacetanilide herbicide which has been classified by the USEPA as a probable human carcinogen. The putative carcinogenic metabolite, 2,6-diethylbenzoquinone imine (DEBQI), is formed through a complex series of oxidative and non-oxidative steps which have been characterized in rats, mice, and monkeys but not in humans. A key metabolite leading to the formation of DEBQI is 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA). This study demonstrates that male human liver microsomes are able to metabolize alachlor to CDEPA. The rate of CDEPA formation for human liver microsomes (0.0031 +/- 0.0007 nmol/min per mg) is significantly less than the rates of CDEPA formation for rat liver microsomes (0.0353+/-0.0036 nmol/min per mg) or mouse liver microsomes (0.0106 +/- 0.0007). Further, we have screened human cytochrome P450 isoforms 1A1, 1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4 and determined that human CYP 3A4 is responsible for metabolism of alachlor to CDEPA. Further work is necessary to determine the extent to which humans are able to metabolize CDEPA through subsequent metabolic steps leading to the formation of DEBQI.

Acetamides↗
PubMed1999

Brugia pahangi: quantitative analysis of infection in several inbred rat strains.

We report a comprehensive study of the infectivity of Brugia pahangi in male and female rats of eight different inbred strains. A single infection of any inbred rat strain will produce rats that become microfilaremic, have occult infection, or clear the primary infection. The proportion belonging to any category is determined by the basic susceptibility level of that strain. Patency rates (blood microfilaria+) ranged from 24% (AO rats) to 73% (WKA rats). The period for which microfilaria were in the circulation was directly related to microfilarial burden, with rats carrying less than 50 mf/ml of blood patent for 11.8 weeks +/- 12.2; for 50-499 mf/ml it was 37.6 +/- 14.8 and for 500+ mf/ml it was 63.3 +/- 34.2 weeks. Suckling rats were resistant to infection (0 patent) and weanlings were intermediate in resistance between suckling and adult rats. Female rats were highly resistant to infection. Approximately half of amicrofilaremic rats have occult infections. A high proportion of patent infections involve the testes or testicular lymphatics. In the most susceptible rat strains, more than 95% of the administered L3 or developing L4 parasites were killed within 28 days. During the course of the first 6 months, the ratio of males to females fell significantly, suggesting a shorter life span in male worms. The features of the infectivity/patency patterns in rats are compared with recognized patterns obtaining in human populations. We conclude that rats provide a valuable and underutilized model for the experimental analysis of filarial infections.

Animals↗
PubMed1999

Process capability measurement of frequent replacement spherical soft contact lenses.

Frequent replacement soft contact lenses must have good reproducibility in order to avoid clinical problems arising from manufacturing variations in lens parameters. This study assessed the actual and potential process capability of eight frequent replacement lenses (monthly or 2-weekly replacement) in relation to back vertex power, back optic zone radius, total diameter and centre thickness. Twenty-four lenses in three powers (-1.00, -3.00, -6.00 D) were measured for eight frequent replacement lenses: Acuvue, Acuvue 2, Biomedics 55, Encore, Focus, Optima FW, Soflens 66, Surevue. In general, the lenses showed adequate reproducibility in respect of those parameters likely to affect lens fit, namely back optic zone radius, total diameter and centre thickness. The process capability results showed some variation in reproducibility of BVP between lens types and between lens powers. Process capability was found to be a useful measure of contact lens reproducibility.

Journal Article↗
PubMed1999

Teaching fractional factorial experiments via course delegate designed experiments.

Industrial experiments are fundamental in enhancing the understanding and knowledge of a process and product behavior. Designed industrial experiments assist people in understanding, investigating, and improving their processes. The purpose of a designed experiment is to understand which factors might influence the process output and then to determine those factor settings that optimize the process output. Teaching "design of experiments" using textbook examples does not fully shed light on how to identify and formulate the problem, identify factors, and determine the performance of the physical experiment. Presented here is an example of how to teach fractional factorial experiments in a course on designed experiments. Also presented is a practical, hands-on experiment that has been found to be extremely successful in instilling confidence and motivation in course delegates. The experiment provides a great stimulus to the delegates for the application of experimental design in their own work environment.

Analysis of Variance↗
PubMed1999

Manual handling in the operating theatre.

Safer transfer practices are needed in operating theatres. An observational study on manual handling in an operating department led to improvements in transfer practice. Staff should have easy access to the appropriate handling aids.

Humans↗
PubMed1999

The on-eye dehydration of proclear compatibles lenses.

PURPOSE: The purpose of the study was to evaluate the on-eye dehydration over time, of molded omafilcon A lenses (Proclear Compatibles) compared to a range of frequent replacement lenses. METHODS: Ten subjects wore a Proclear Compatibles lens in one eye and a control lens in the other eye for 4-, 8- and 12-hours. The control lenses were Acuvue, Soflens 66 and Optima frequent replacement lenses. Each subject wore three different pairs of lenses for each time period in a masked, randomized fashion. A gravimetric technique was used to determine lens water content. RESULTS: The Proclear Compatibles lenses showed significantly less relative dehydration than the Acuvue and Soflens 66 lenses. The Acuvue and Soflens 66 lenses showed a significant increase in relative dehydration with increasing wearing time. Subjective comfort was graded higher with the Proclear Compatibles than with the Acuvue lenses. There was a significant negative correlation between Acuvue dehydration and subjective ratings of comfort. CONCLUSIONS: The study showed that Proclear Compatibles lenses dehydrate significantly less than the other frequent replacement high-water content lenses. The Acuvue and Soflens 66 lenses showed increasing dehydration during the 4-12 hour wearing period.

Contact Lenses, Hydrophilic↗
PubMed1998

In vitro cytokine-primed leukaemia cells induce in vivo T cell responsiveness in chronic myeloid leukaemia.

We previously showed that in chronic myeloid leukaemia (CML), it is possible to induce costimulatory molecules, CD80/CD86, on leukaemia cells by culturing adherent peripheral blood mononuclear cells from these patients with IL-4 and GM-CSF. In addition to the expression of CD80/CD86 molecules, some of the leukaemia cells also expressed the dendritic cell marker, CD1a. When these leukaemia cells were used in mixed lymphocyte leukaemia reactions, they mediated autologous T cell proliferation not seen when fresh leukaemia cells were used as the stimulator cells. In this study, we showed that reinfusion of these immunogenic leukaemia cells to the autologous hosts resulted in priming in vivo of T cells so that they could respond to subsequent rechallenge in vitro with fresh autologous leukaemia cells. Although cytotoxic T cells against leukaemia cells were not demonstrated, these T cells could proliferate and produce interferon-y when cocultured in vitro with the leukaemia cells. Our findings therefore provide further evidence for the immunogenicity of these cultured leukaemia cells in CML.

Adoptive Transfer↗