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Biomedical subjects

A Sinclair

Publications and source records attributed to A Sinclair.

At least 19 recordsLinked to original sources
PubMed2002

Repassivation of a high chromium stainless steel orthopaedic alloy.

The repassivation of Ortron90, a high chromium stainless steel alloy, was studied to assess the effect of passive layer removal on corrosion levels. Cathodic dissolution of the passive layer followed by potentiostatic experiments within the passive region were employed to study the repassivation process. The scratch method, carried out for comparison purposes, yielded current densities similar to those obtained by cathodic dissolution. The detailed analysis of the slopes of plots of log I/log t indicated that the repassivation did not follow any of the existing growth models. It also suggested that the slope depended on the extent of repassivation and reached a minimum when three to five monolayers of oxide were completed. The virtual potentiodynamic plots suggested the presence of some form of protective layer within 5-10 seconds and the change in open circuit potential vs time indicated that the passive layer present after 10 seconds of repassivation continued to evolve for about 1000 to 1500 seconds possibly representing a transition between two different forms such as oxide and a oxyhydroxides. Estimation of the effect of localized removal of passive layer on the corrosion indicated a dramatic increase in local corrosion density. These results show that a fast repassivation rate is an important requirement for biocompatibility of alloys used to manufacture dental and orthopaedic devices.

Biocompatible Materials↗
PubMed2001

Ageing: definitions, mechanisms and the magnitude of the problem.

All multi-cellular organisms undergo change with time. Conception heralds the onset of growth and development, leading to reproductive competence and propagation of the species. With time, organisms age, leading to death as a final end-point. Whilst our knowledge and definitions of growth and reproduction are firmly established, the concept of ageing remains less well understood. One of the reasons for the lack of a singular definition of ageing is that it can be considered in many different ways, according to social, behavioural, physiological, morphological, cellular and molecular changes. Research has led to a number of theories being proposed that may explain the ageing process. In this chapter, we will review some of these theories and address some of the following fundamental questions: What is ageing? How can ageing be measured? When does ageing begin? When is an organism defined as old?

Aged↗
PubMed2001

Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans.

Elderly humans are more susceptible to bacterial infections because of declining immune status. We have investigated the effect of aging on neutrophil bactericidal responses, comparing neutrophil function in healthy, young (23-35 years) and elderly (>65 years) volunteers. Superoxide generation in response to fMLP was slightly increased in neutrophils from elderly donors, and serum from the elderly was able to opsonize E. coli efficiently. In contrast, phagocytic index was significantly lower in neutrophils from the elderly, compared with young donors (P<0.005). CD11a and CD11b expression was not affected by age, but CD16 was significantly reduced in neutrophils from elderly donors (P<0.0001). CD16 expression and phagocytic index were measured in the same neutrophils using FITC-labeled E. coli, PE-conjugated anti-CD16 antibody, and CD16 expression correlated with phagocytic index (r=0.83; P<0.05). In elderly patients with bacterial infection, CD16 expression remained low. We propose that reduced neutrophil CD16 expression and phagocytosis contribute to human immunesenescence.

Adult↗
PubMed2000

ASW: a gene with conserved avian W-linkage and female specific expression in chick embryonic gonad.

Vertebrates exhibit a variety of sex determining mechanisms which fall broadly into two classes: environmental or genetic. In birds and mammals sex is determined by a genetic mechanism. In mammals males are the heterogametic sex (XY) with the Y chromosome acting as a dominant determiner of sex due to the action of the testis-determining factor, SRY. In birds females are the heterogametic sex (ZW); however, it is not known whether the W chromosome carries a dominant ovary-determining gene, or whether Z chromosome dosage determines sex. Using an experimental approach, which assumes only that the sex-determining event in birds is accompanied by sex-specific changes in gene expression, we have identified a novel gene, ASW (Avian Sex-specific W-linked). The putative protein for ASW is related to the HIT (histidine triad) family of proteins. ASW shows female-specific expression in genital ridges and maps to the chicken W chromosome. In addition, we show that, with the exception of ratites, ASW is linked to the W chromosome in each of 17 bird species from nine different families of the class Aves.

Amino Acid Sequence↗
PubMed2000

Polyunsaturated fatty acids reduce non-receptor-mediated transcellular permeation of protein across a model of intestinal epithelium in vitro.

BACKGROUND: Dietary polyunsaturated fatty acids influence the natural history of intestinal inflammatory diseases. Varying the types of long-chain fatty acids that are exposed to cells alters the physicochemical properties of cell membranes. This study aimed to determine whether such variations alter transcellular and paracellular permeability in intestinal epithelium. METHODS: Monolayers of Caco-2 cells, allowed to differentiate by culturing for 7 days following confluence, were used as the model for intestinal epithelium. Paracellular permeability was assessed by measurement of transepithelial resistance, while transcellular permeability was assessed by the transepithelial flux of horseradish peroxidase. RESULTS: Exposure of the cells to 100 micromol/L of palmitic acid, oleic acid, eicosapentaenoic acid, or linoleic acid, was not toxic to cells (measured by leakage of lactate dehydrogenase), and altered cell membrane fatty acid composition (as measured by gas chromatography). Flux of horseradish peroxidase was significantly affected by 24 h fatty acid exposure (P= 0.038, ANOVA), being decreased by 23 +/- 6% (mean +/- SEM) by eicosapentaenoic acid and 25 +/- 3% by linoleic acid. Oleic acid, palmitic acid and butyrate, had no effect. Transepithelial resistance also varied significantly across the treatment groups (P< 0.001) due to a 28 +/- 5% increase induced by butyrate. The long-chain fatty acids had no effect. CONCLUSIONS: Both omega-3 and omega-6 polyunsaturated fatty acids reduce transcellular, non-receptor-mediated permeation of proteins across differentiated Caco2 cell monolayers, without altering paracellular permeability. Alteration of intestinal barrier function should be considered as a possible mechanism of action of dietary polyunsaturated fatty acids.

Butyrates↗
PubMed1999

Kallmann syndrome gene (KAL-X) is not mutated in schizophrenia.

Kallmann syndrome and schizophrenia share several clinical features, including dysfunctional olfactory ability, hypogonadotrophic hypogonadism, an excess of affected males, and psychiatric presentation. Because of this congruence, it has been proposed that up to 70% of male schizophrenics might have mutations affecting the function or expression of the gene mutated in Kallmann syndrome, KAL-X. We identified and studied 9 unrelated males with schizophrenia (as defined by DSM-IIIR criteria) who also have severe anosmia (first percentile of normal range) and low sex drive (seventh percentile of the normal range), and we sequenced the exons and the intron-exon junctions of the KAL-X gene for each. We found no mutations, and conclude that schizophrenia is rarely, if ever, due to a mutation in the coding sequence or splice junctions of KAL-X.

Extracellular Matrix Proteins↗
PubMed1999

Long-chain polyunsaturated fatty acids in diets for infants: choices for recommending and regulating bodies and for manufacturers of dietary products.

While the scientific evaluation of the physiologic effects, potential benefits, and risks of dietary preformed long-chain polyunsaturated fatty acids (LCPUFA) for infants have been discussed elsewhere, this manuscript addresses some of the resulting consequences and challenges of interpreting the available knowledge from the perspective of recommending and regulating bodies, and of manufacturers of dietary products and their ingredient materials. Traditionally human milk composition has served as a reference point for infant formula design. With respect to the use of LCPUFA in infant formula, much more emphasis than ever before invested for any other group of micronutrients has been put on clinical studies investigating the potential advantages and disadvantages of LCPUFA in infant foods, including growth, safety aspects, and a variety of other outcome measures.

Evaluation Studies as Topic↗
PubMed1999

The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters.

OBJECTIVE: The aim of this study was to assess thrombosis tendency in subjects who were habitual meat-eaters compared with those who were habitual vegetarians. DESIGN: Cross-sectional comparison of habitual meat-eaters and habitual vegetarians. SETTING: Free living subjects. SUBJECTS: One hundred and thirty-nine healthy male subjects (vegans n = 18, ovolacto vegetarians n = 43, moderate-meat-eaters n = 60 and high-meat-eaters n = 18) aged 20-55 y who were recruited in Melbourne. OUTCOME MEASURES: Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. The parameters of thrombosis were measured by standard methods. RESULTS: Saturated fat and cholesterol intakes were significantly higher and polyunsaturated fat (PUFA) was significantly lower in the meat-eaters compared with vegetarians. In the meat-eaters, the platelet phospholipids AA levels were significantly higher than in the vegetarians, but there was no increase in ex vivo platelet aggregation and plasma 11-dehydro thromboxane B2 levels. Vegetarians, especially the vegans, had a significantly increased mean collagen and ADP stimulated ex vivo whole blood platelet aggregation compared with meat-eaters. The vegan group had a significantly higher mean platelet volume than the other three dietary groups. However, meat-eaters had a significantly higher cluster of cardiovascular risk factors compared with vegetarians, including increased body mass index, waist to hip ratio, plasma total cholesterol (TC), triacylglycerol and LDL-C levels, ratio of TC/HDL-C and LDL-C/HDL-C and plasma factor VII activity. CONCLUSIONS: Consumption of meat is not associated with an increased platelet aggregation compared with vegetarian subjects.

Adult↗
PubMed1999

Spatial codes and the hardness of string folding problems.

We present a general technique for proving NP-hardness (under randomized polynomial time reductions) of string folding problems over a finite alphabet. All previous such intractability results have required an unbounded alphabet size. These problems correspond to the protein folding problem in variants of the hydrophobic-hydrophilic (or HP) model with a fixed number of monomer types. Our proof also establishes the MAX SNP-hardness of these problems (again under randomized polynomial time reductions). This means that obtaining even an approximate solution to the protein folding problem, to within some fixed constant factor, is NP-hard. Our technique involves replacing the symbols of an unbounded alphabet by code-words over a fixed alphabet, and has two novel aspects. The first is the essential use of the approximation hardness of the source problem in the reduction, even for the proof of NP-hardness. The second is the concept of spatial codes, a variant of classical error-correcting codes in which different codewords are required to have large "distance" from one another even when they are arbitrarily embedded in three-dimensional space.

Computational Biology↗
PubMed1999

Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men.

BACKGROUND: Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. OBJECTIVE: We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. DESIGN: During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. RESULTS: Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. CONCLUSION: ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males.

Adult↗