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Biomedical subjects

P G Williams

Publications and source records attributed to P G Williams.

18 recordsLinked to original sources

Coping processes as mediators of the relationship between hardiness and health.

Hardiness has been hypothesized to moderate the impact of stress on health by influencing coping responses, but little attention has been focused upon these associations. This study examined the relationship among hardiness, coping, and illness while attending to recent criticisms of the hardiness literature including the potential overlap with neuroticism, whether hardiness is a unitary construct, and the predominant use of male samples. Hardiness was found to be positively related to adaptive coping variables and negatively related to maladaptive coping variables. Problem-focused, support-seeking, and avoidant coping were found to mediate the hardiness-illness relationship. Although these hardiness-coping relationships were partially independent of the influence of neuroticism, the relationship of both coping and hardiness with self-reported illness appeared to result from the common influence of neuroticism. Consistent with previous research, the commitment and control components correlated most consistently with coping variables, and predicted hardiness effects were most consistently demonstrated for males.

Adaptation, Psychological

Personality and health: advantages and limitations of the five-factor model.

Interest in the association between personality characteristics and physical health has been renewed in recent years. Theory and research in this area has also been complicated by conceptual and methodological limitations. The present article briefly reviews this literature and discusses the advantages and limitations of the five-factor model of personality as an integrating framework for studies of personality and health. The model has already been fruitfully applied in several contexts, and more possibilities exist. Although it has some potential limitations, the application of the five-factor model--as well as other aspects of current personality theory and research--is likely to facilitate progress in the study of how personality influences health.

Humans

Tritium NMR spectroscopy of ligand binding to maltose-binding protein.

Tritium-labeled alpha- and beta-maltodextrins have been used to study their complexes with maltose-binding protein (MBP), a 40-kDa bacterial protein. Five substrates, from maltose to maltohexaose, were labeled at their reducing ends and their binding studied. Tritium NMR spectroscopy of the labeled sugars showed large upfield chemical shift changes upon binding and strong anomeric specificity. At 10 degrees C, MBP bound alpha-maltose with 2.7 +/- 0.5-fold higher affinity than beta-maltose, and, for longer maltodextrins, the ratio of affinities (KD beta/KD alpha) was even larger (between 10 and 30). The maximum chemical shift change was 2.2 ppm, suggesting that the reducing end of bound alpha-maltodextrin makes close contact with an aromatic residue in the MBP-binding site. Experiments with maltotriose (and longer maltodextrins) also revealed the presence of two bound beta-maltotriose resonances in rapid exchange. We interpret these two resonances as arising from two distinct sugar-protein complexes. In one complex, the beta-maltodextrin is bound by its reducing end, and, in the other complex, the beta-maltodextrin is bound by the middle glucose residue(s). This interpretation also suggests how MBP is able to bind both linear and circular maltodextrins.

ATP-Binding Cassette Transporters

Relationship of the children's form of the Rosenzweig Picture-Frustration Study to children's behavior, gender, and fantasies.

To examine the validity of the Children's Form of the Picture-Frustration (P-F) Study, the instrument was administered to 245 children in Grades 1 through 6. Children were also administered the Make A Picture Story (MAPS) and the Response Hierarchy Measure. Teachers rated children's aggression on the Conners Teacher Rating Scale. Hostile responses on the P-F Study were related to self-reported verbal and physical aggression in conflict situations but were unrelated to teachers' ratings of aggressive behavior. Hostile responses were exhibited more often by boys than girls. Responses on the measure were related to children's fantasy patterns. Results supported the validity of the P-F Study as a measure of children's thought content in response to frustration.

Aggression

3H nuclear magnetic resonance study of anaerobic glycolysis in packed erythrocytes.

The utility and power of 3H NMR spectroscopy as a technique for monitoring biological systems in vivo is illustrated with glucose metabolism in erythrocytes. Use of C-1-tritiated glucose allowed us to monitor the disappearance of the alpha and beta tritons, with the production of lactate and 1H3HO (HTO), as well as some intermediates. Spin lattice relaxation times (T1) were measured to avoid T1 distortion of the spectral intensities. Detection of the formation of 1 mM tritiated water in the presence of 110 M H2O protons and deuterons allows the eventual fate of the label in the pentose shunt to be observed in vivo.

Anaerobiosis

Vinblastine sensitivity of leukaemic lymphoblasts modulated by serum lipid.

The high-resolution proton magnetic resonance spectrum of leukaemic lymphoblasts is characteristic of neutral lipid in an isotropic environment. When such lymphoblasts are selected for resistance to the anticancer drug vinblastine, the intensity of this spectrum increases with increasing drug resistance. A reversal of this trend can be achieved by growing cells in delipidated serum, whereby lipid spectrum and drug resistance are diminished. However, both can be restored by subsequent regrowth in normal medium. Thus, although detectable genetic changes accompany the development of vinblastine resistance, the expression of these changes can be modulated by environmental lipid.

Cholesterol

Variability of responses within the aggression categories on the Rosenzweig Picture-Frustration Study, Children's Form.

This study examined whether the procedure for combining scores to make aggression categories on the Children's Form of the Picture-Frustration Study is psychometrically sound. Subjects were 245 children from Grades 1 through 6. Their responses were rated according to the 11 kinds of responses defined in the manual (Rosenzweig, 1978c). Results indicated that most of the scores did not correlate with their corresponding categories. Thus, the way scores are combined into aggression categories may be invalid, because they seem to be combinations of very dissimilar kinds of responses to frustration. Until psychometrically sound and empirically validated ways of combining the 11 scores are determined, it is recommended that the 11 scores themselves be used for clinical and research purposes.

Aggression

Inhibition of metastatic potential by fucosidase: an NMR study identifies a cell surface metastasis marker.

NMR spectroscopy is able to detect subtle changes to the surface chemistry of cells. We have previously shown that high-resolution 1H NMR methods can identify tumor cells with the capacity to metastasize, and we now report that the long T2 relaxation value (500-800 ms) observed in metastatic rat mammary adenocarcinoma cells is removed by treatment with fucosidase. Two-dimensional scalar-correlated NMR (COSY) spectra of fucosidase-treated cells show that a cross peak, consistent with scalar coupling between the methyl and methine groups on fucose and usually associated with malignancy and metastatic ability, is absent. Metastases were observed in only two out of ten rats injected subcutaneously with enzyme-treated cells compared to eight out of ten with untreated cells. NMR studies on isolated cellular lipids identified the long T2 relaxation value only in the ganglioside fraction. This fraction accounts for 51% of the total 14C-labelled fucose incorporated into the cells. We propose that fucogangliosides are an indicator of metastatic potential in rats. The observation that a cell surface metastasis marker has an NMR signal with a characteristically long relaxation value has important consequences for the future use of magnetic resonance imaging and spectroscopy in the cancer clinic.

Adenocarcinoma

Application of a T2-filtered COSY experiment to identify the origin of slowly relaxing species in normal and malignant tissue.

The 1H NMR spectrum of whole cells consists of many overlapping resonances which are difficult to resolve into individual components. We have developed a modification of the COSY pulse sequence which filters out resonances on the basis of their T2 relaxation rate. When applied to malignant cells, this technique has helped to identify fucose as the origin of the slowly relaxing species associated with their metastatic capacity. The technique can also be used to obtain T2 relaxation rates for individual resonances in a broad envelope of lines.

Adipose Tissue

A comparison of the chemical analyses of cell lipids with their complete proton NMR spectrum.

Whole cells are made up of molecules in different environments to which NMR spectroscopy is sensitive. In particular, malignant and transformed cells contain lipids not only in bilayers but in isotropically tumbling domains which give rise to high-resolution spectra. We have recently developed a technique for simultaneously analyzing broadline and high-resolution signals (M. Bloom, K. T. Holmes, C. E. Mountford, and P. G. Williams, J. Magn. Reson., in press) and we report here its application to a range of rat, mouse, and human cell lines. Some selected features of the NMR spectra were compared with the chemical analysis of the whole-cell lipid. We found that in general the proportion of protons in the narrow methylene resonance at 1.3 ppm increased with the neutral lipid content of the cells. This peak was chosen because its T2 relaxation behavior correlates with metastatic potential in a rat model system. This new technique could be applied to other high-resolution components both in healthy and in diseased states.

Animals

Cell surface involvement in cancer metastasis: an NMR study.

NMR spectroscopy is one of the few techniques which has the sensitivity to detect subtle changes to the surface chemistry of cells. It has previously been demonstrated that high resolution 1H NMR methods can distinguish tumour cells with the capacity to metastasis and this information appears to arise from a type of proteolipid in or attached to the plasma membrane. Here we report that the 1H NMR signal, which we have used to identify metastatic cells in rat tumours, is significantly reduced in intensity after cultured cells are treated with trypsin/EDTA. The long T2 relaxation value (greater than 350 ms) observed in metastatic cells is absent after enzyme treatment. 2D scalar correlated NMR (COSY) spectra of these treated cells show that a cross peak normally associated with malignancy and metastatic disease is markedly reduced. These findings indicate that the plasma membrane lipid particle which generates the high resolution spectrum is directly affected by trypsin/EDTA. Alterations to the cell surface properties were also demonstrated in vivo since reduced numbers of metastases were observed in animals injected with enzyme-treated cells. The correlation between the absence of a long T2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic PROCESS.

Adenocarcinoma

Classification of human tumours by high-resolution magnetic resonance spectroscopy.

Malignant tumours yield a high-resolution proton magnetic resonance (MR) spectrum. Fifty-one tumour biopsy specimens from patients with cancer of the ovary or colon were examined by magnetic resonance spectroscopy (MRS) to determine whether it was possible to identify tumour subtypes with metastatic potential. Relaxation parameters (T2) for visible lipid methylene protons were within the range of those measured for three animal metastasis models. Primary carcinomas with metastases gave T2 values greater than 350 ms, whereas carcinomas not associated with known metastases at the time of tumour excision gave a range of values from 150 to 1500 ms. All but two carcinomas gave a long T2 (greater than 350 ms) indicating metastatic potential. The MRS method designated five of six histologically borderline epithelial ovarian tumours as malignant with metastatic potential. MRS may be sensitive enough to detect malignant cells in a tumour which is of intermediate or borderline malignancy by light microscopy. Malignancy without a potential for metastasis is uncommon.

Colonic Neoplasms

The intramitochondrial location of cytochrome c peroxidase in wild-type and petite Saccharomyces cerevisiae.

Cytochemical and ultrastructural analysis of wild-type cells of Saccharomyces cerevisiae, grown aerobically in a glucose-limited chemostat, shows that cytochrome c peroxidase is localized between the membranes of the cristae, that is, in the intracristal space. This enzyme is thus positioned appropriately within the organelle to act as an alternate terminal oxidase for the respiratory chain. The proximity of the peroxidase to major sites of generation of its two substrates may account for the small leakage of hydrogen peroxide from yeast mitochondria, as compared with the larger outflow from mammalian mitochondria. In the cytoplasmic petite mutant, gross distortion of promitochondrial membrane arrangement is evident. Nevertheless, cytochrome c perioxidase activity is present in the same amounts as is found in wild-type cells, and is localized predominantly within annuli of membrane which constitute the promitochondria in these cells. No unequivocal evidence was obtained for the localization of catalase in microbodies or other organelles in either wild-type or petite cells.

Amitrole