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Biomedical subjects

S Mills

Publications and source records attributed to S Mills.

At least 19 recordsLinked to original sources
PubMed2002

Use of lacticin 481 to facilitate delivery of the bacteriophage resistance plasmid, pCBG104 to cheese starters.

AIMS: Use of lacticin 481 to facilitate the conjugal transfer of the bacteriophage resistance plasmid pCBG104 to various starter cultures. METHODS AND RESULTS: A raw milk isolate of Lactococcus was found to harbour determinants for lacticin 481 production and immunity and phage resistance on a plasmid designated pCBG104. The lacticin 481 was successfully used to mobilize the phage resistance determinant to a variety of cheese starters enabling the formation of highly phage resistant starters. In addition, it facilitated the stacking of a number of phage resistance genes, namely a type I restriction modification system, a phage abortive infection system and a phage adsorption blocking system in a single Lactococcus strain without the use of recombinant techniques. The transconjugants were all shown to produce lacticin 481 and to contain the entire 481 operon. Subsequently one transconjugant was selected and successfully used for large-scale cheddar cheese manufacture. CONCLUSIONS: Lacticin 481 could be used as a food-grade selectable marker to facilitate the introduction of advantageous traits to starter cultures for industrial food fermentations. SIGNIFICANCE AND IMPACT OF THE STUDY: Food-grade selectable markers greatly facilitate the introduction of various advantageous traits to starter cultures for industrial food fermentation. Indeed self-cloning which is becoming increasingly important for strain improvement has a requirement for the identification and demonstration of the utility of tools such as lacticin 481.

Bacterial Proteins↗
PubMed2001

The use of cadmium resistance on the phage-resistance plasmid pNP40 facilitates selection for its horizontal transfer to industrial dairy starter lactococci.

AIMS: To facilitate the horizontal transfer and selection of phage-resistance plasmids in industrial lactococci. METHODS AND RESULTS: Cadmium-resistance properties similar to those previously identified in Lactococcus were linked to the well-known phage-resistance plasmid pNP40. This finding was exploited to facilitate delivery of the plasmid to an industrial cheese starter Lactococcus lactis DPC4268. Additionally, 25 different cadmium-sensitive cheese starter lactococci were also identified as potential recipients for the phage-resistance plasmid pNP40, and also the plasmids pAH90/pAH82 which also encode cadmium resistance. All three plasmids were successfully conjugated to strain DPC4268. Cheddar cheese was manufactured in industry with the pNP40 phage-resistant transconjugant. SIGNIFICANCE AND IMPACT OF THE STUDY: Food-grade enhancement of phage resistance in industrial starter strains has been made simpler by the use of this selection, especially since the majority of potential recipient starter strains analysed were cadmium sensitive.

Bacteriophages↗
PubMed2001

Profile of ligand binding to the porcine beta2-adrenergic receptor.

Chinese hamster ovary cells expressing the porcine beta2-adrenergic receptor (betaAR) were used to determine the binding kinetics of agonists and antagonists by competitive displacement of the radioligand [125I]iodocyanopindolol. Several purported agonists, including isoproterenol, epinephrine, norepinephine, dobutamine, salbutamol, and terbutaline, exhibited dual-affinity displacement curves, which is characteristic of agonist binding to betaAR. In each case, the addition of guanosine triphosphate (GTP) eliminated the high-affinity state and resulted in a one-site displacement curve. All of the antagonists modeled to only one site in the presence or absence of GTP. Several ligands, including ones used to promote animal growth (clenbuterol, L-644,969, and ractopamine) and the beta3AR-selective agonist BRL 37344 modeled to only one site, suggesting that these ligands would not be full agonists at the porcine beta2AR (pbeta2AR). Most of the tested ligands exhibited binding affinities that were similar to published values for the beta2AR from other species. However, several exceptions were observed. The BRL 37344 ligand bound the pbeta2AR with a 10-fold higher affinity than the human beta2AR, and the Kd of this was similar to Kd values reported for the human and rat beta3AR. The Kd of the pbeta2AR for ICI 118,551 was 50-fold higher than that for the beta2AR from rats and humans. For both BRL 37344 and ICI 118,551 the subtype-selective character of these ligands was different in the pig compared with the human and rat. These data demonstrate the value of using species-specific betaAR for selection of agonists and antagonists. Further, these data support the growing evidence that few ligands are full agonists for pbetaAR and that binding data may be useful for identifying ligands with full agonist potential.

Animals↗
PubMed2001

Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex.

PURPOSE: To evaluate the effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the cytochrome oxidase blobs of V1 cortex in the macaque visual system. METHODS: Monocular experimental glaucoma was induced in adult monkeys (Macaca mulatta and Macaca fascicularis) by laser application to the trabecular meshwork, increasing the intraocular pressure. After other experiments, the primary visual cortices were analyzed for functional excitation from surviving ganglion cells, as indicated by cytochrome oxidase histochemistry. RESULTS: Cytochrome oxidase reactivity was uniformly reduced in blobs with input from the glaucomatous eye in a manner consistent with loss of known afferent inputs. The average size of glaucomatous blobs in layers 2 and 3 of V1 cortex was reduced by half. CONCLUSIONS: Experimental glaucoma in monkeys reduces retinal input to the central nervous system, thereby reducing the metabolic drive to downstream targets, as indicated by the reduction in the size of cytochrome oxidase blobs in layers 2 and 3 of V1 cortex. The pattern of cytochrome oxidase loss within the blob was uniform, suggesting that all sources of afferent input to the blobs were affected by experimental glaucoma.

Afferent Pathways↗
PubMed2000

Elevated levels of cognitive-perceptual deficits in individuals with a family history of schizophrenia spectrum disorders.

This study finds that the relatives of schizophrenics have elevated scores on the cognitive-perceptual factor of the schizotypal personality questionnaire (SPQ), particularly for the 'unusual perceptual experiences' and 'ideas of reference' subscales. These results support recent findings by Kremen et al. (1998) and suggest that previous failures to demonstrate elevated scores on 'positive' symptoms of schizotypy may be a function of instrumentation.

Adult↗
PubMed2000

Beta-adrenergic receptor subtypes mediating lipolysis in porcine adipocytes. Studies with BRL-37344, a putative beta3-adrenergic agonist.

The beta3-selective adrenergic receptor ligand BRL 37344 (BRL) was used to differentiate the presence and functional role of beta-adrenergic receptor (betaAR) subtypes in pig tissues. BRL did not stimulate adenylyl cyclase in membrane preparations or increase lipolysis from pig adipocytes. In contrast to some species, BRL appears to be a poor agonist for the pig betaAR and is not a useful betaAR ligand. Based on displacement of [3H]dihydroalprenolol binding, BRL exhibited a 100-fold selectivity for pig betaAR subtypes in adipose and skeletal muscle membranes. The high affinity site was proposed to be the beta2AR. When used as an antagonist, BRL blockade of the high affinity site did not interfere with isoproterenol-stimulated lipolysis but did inhibit adenylyl cyclase activation. Results indicate that the high affinity betaAR (betaAR) is not linked to lipolysis, possibly due to intracellular compartmentalization. Therefore, betaAR subtypes may have function-specific effects.

Adenylyl Cyclases↗
PubMed2000

Sexual bridging by Cambodian men: potential importance for general population spread of STD and HIV epidemics.

BACKGROUND: Linkages between sexual networks influence STD and HIV epidemics. GOAL: This study quantifies male sexual "bridging" and associated factors in Cambodia's 1997 behavioral surveillance survey. STUDY DESIGN: Among persons randomly selected from clusters of military, police, and motorcycle taxidrivers in five cities, associations between individual characteristics, behaviors, social context, and "active bridging" were tested using logistic regression analyses. RESULTS: The authors defined 20.5%, 15.7%, and 14.7% of military, police, and motorcycle taxidrivers as active bridgers (men who have unprotected sex with high and low risk partners). Among the military and police, logistic regression revealed that age (odds ratio [OR], 1.05), age of first sexual intercourse (OR, 0.89), having friends who frequent sex workers (OR, 3.31), and residence in the port city (OR, 3.34) were associated with active bridging. Among motorcycle taxidrivers, residence in the border city (OR, 2.23) or the port city (OR, 2.84) was associated with active bridging. Sexually transmitted disease symptoms during the past year were significantly associated with active bridging. CONCLUSIONS: Social characteristics influence sexual bridging more than individual ones. The pervasiveness of bridging and the association with sexually transmitted disease symptoms underscore the potential of men who are active bridgers to spread sexually transmitted disease and HIV in Cambodia beyond high-risk groups.

Adult↗
PubMed2000

Cytochalasin B modulation of Caco-2 tight junction barrier: role of myosin light chain kinase.

The intracellular mechanisms that mediate cytochalasin-induced increase in intestinal epithelial tight junction (TJ) permeability are unclear. In this study, we examined the involvement of myosin light chain kinase (MLCK) in this process, using the filter-grown Caco-2 intestinal epithelial monolayers. Cytochalasin B (Cyto B) (5 microg/ml) produced an increase in Caco-2 MLCK activity, which correlated with the increase in Caco-2 TJ permeability. The inhibition of Cyto B-induced MLCK activation prevented the increase in Caco-2 TJ permeability. Additionally, myosin-Mg(2+)-ATPase inhibitor and metabolic inhibitors (which inhibit MLCK induced actin-myosin contraction) also prevented the Cyto B-induced increase in Caco-2 TJ permeability. Cyto B caused a late-phase (15-30 min) aggregation of actin fragments into large actin clumps, which was also inhibited by MLCK inhibitors. Cyto B produced a morphological disturbance of the ZO-1 TJ proteins, visually correlating with the functional increase in Caco-2 TJ permeability. The MLCK and myosin-Mg(2+)-ATPase inhibitors prevented both the functional increase in TJ permeability and disruption of ZO-1 proteins. These findings suggested that Cyto B-induced increase in Caco-2 TJ permeability is regulated by MLCK activation.

Actin Cytoskeleton↗
PubMed1999

Challenges and future directions for tailored communication research.

As informatics technology advances, a growing number of research trials on tailored communications provide an accumulation of promising evidence to support their efficacy. These trials also reveal gaps and opportunities for future research. The scope and boundaries of tailoring must be redefined in terms of both new technology and the trade-offs between complexity, demand burden on participants, and the minimal information required for effective and efficient tailoring. Basic and methods research is needed to broaden theory, develop a common language, standardize measures, and isolate the key mediating mechanisms that facilitate tailored communications. Applied research must consider more rigorous research designs for efficacy trials and conduct more effectiveness trials to investigate the mechanisms of technology transfer to enhance large-scale diffusion of tailored communications. The role of contextual variables needs to be examined, as well as their interaction with different population groups, and also the channels, modes, and methods of tailored message delivery. Research is also needed on the feasibility of tailoring across clusters of multiple risk factors to identify the commonalities, differences, and interrelations among diverse behaviors. The potential cost-effectiveness of tailored communications must also be examined. No matter how efficacious, tailored communications delivered to large populations (i.e. mass-customization) will not make a public health impact unless proven to be practical and cost-efficient.

Cost-Benefit Analysis↗
PubMed1999

Efficacy and tolerability of the specific cyclooxygenase-2 inhibitor DFP compared with naproxen sodium in patients with postoperative dental pain.

DFP [3-(2-propyloxy)-(4-methyl-sulfonylphenyl)-(5,5-dimethyl)-fu ranone] is a highly specific cyclooxygenase-2 inhibitor (>2500-fold selective in transfected Chinese hamster ovary cell assays) that has demonstrated efficacy in preclinical models of pain and inflammation. The present single-dose, randomized, double-masked, double-dummy, placebo-controlled, parallel-group study was undertaken to compare DFP 5, 25, and 50 mg with naproxen sodium 550 mg and with placebo in 196 patients (mean age, 25.8 years; 187 [95.4%] males) who experienced moderate-to-severe pain after surgical removal of > or =2 third molars. Overall analgesic effect, duration of effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. Both DFP 25 and 50 mg, as well as the active comparator, naproxen sodium 550 mg, were significantly more effective than placebo. The onset of analgesic effect in the DFP 25-mg, DFP 50-mg, and naproxen sodium 550-mg groups did not differ significantly. DFP was generally well tolerated in single doses up to 50 mg. DFP 50 mg was efficacious in the treatment of postoperative dental pain and was indistinguishable from the active comparator, naproxen sodium 550 mg.

Adult↗