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Biomedical subjects

M A White

Publications and source records attributed to M A White.

At least 37 records · Page 2Linked to original sources
PubMed2000

Body image assessment for obesity (BIA-O): development of a new procedure.

OBJECTIVE: A new measure of body image, named the body image assessment for obesity (BIA-O) was developed and tested for reliability and validity in a sample of 1,209 adult men and women. Separate BIA-O procedures were developed for men and women. Current, ideal and reasonable body image estimates of Caucasian and African-American men and women were compared. METHOD: Figural stimuli of males and females were developed for body sizes ranging from very thin to very obese in 18 increments. Participants selected figures that represented estimates of current, ideal and reasonable (a body size that could be maintained over time) body size. Some participants (n=641) also completed two measures of body dissatisfaction in a test of the validity of the BIA-O as a measure of body dissatisfaction. A sample of 77 participants was administered the BIA-O on two occasions to test the test-retest reliability of the BIA-O. RESULTS: The reliability of the BIA-O was supported by test-retest reliability coefficients which ranged from 0.65 to 0.93. Concurrent validity of the discrepancy between current and ideal and current and reasonable body size estimates was supported by positive correlations with two measures of body dissatisfaction. The BIA-O body size estimates of Caucasians and African-Americans, controlled for age and BMI, were compared. As BMI increased, Caucasian men and women were found to select larger current body size estimates in comparison to African-Americans. DISCUSSION: The reliability and validity of the BIA-O were supported. Greater body size dissatisfaction in obese Caucasians, relative to African-Americans of the same size, may be a function of biased estimates of current body size.

Adolescent↗
PubMed2000

Family dynamics, parental-fetal attachment and infant temperament.

Family dynamics, parental-fetal attachment and infant temperament The purpose of this longitudinal study of families having their first or second baby was to explore relationships among family dynamics, paternal- and maternal-fetal attachment, and infant temperament. Data were collected from 156 women and 62 of their partners during the third trimester of pregnancy. One year later, when the infant was 8-9 months old, 75 of the women and 30 of their partners participated. In a hierarchical multiple regression analysis, after controlling for demographic variables, mutuality in the family was associated with greater maternal- and paternal-fetal attachment. Family dynamics were stable across the transition to parenthood except for an increase in role conflict reported by mothers. Sensitivity to specific family experiences by clinicians can provide assistance to families during these periods.

Adult↗
PubMed2000

Ral GTPases contribute to regulation of cyclin D1 through activation of NF-kappaB.

Ral GTPases have been implicated as mediators of Ras-induced signal transduction from observations that Ral-specific guanine nucleotide exchange factors associate with Ras and are activated by Ras. The cellular role of Ral family proteins is unclear, as is the contribution that Ral may make to Ras-dependent signaling. Here we show that expression of activated Ral in quiescent rodent fibroblasts is sufficient to induce activation of NF-kappaB-dependent gene expression and cyclin D1 transcription, two key convergence points for mitogenic and survival signaling. The regulation of cyclin D1 transcription by Ral is dependent on NF-kappaB activation and is mediated through an NF-kappaB binding site in the cyclin D1 promoter. Ral activation of these responses is likely through an as yet uncharacterized effector pathway, as we find activation of NF-kappaB and the cyclin D1 promoter by Ral is independent of association of Ral with active phospholipase D1 or Ral-binding protein 1, two proteins proposed to mediate Ral function in cells.

3T3 Cells↗
PubMed1999

Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control.

The activity of the catalytic domain of the orphan MAP kinase ERK5 is increased by Ras but not Raf-1 in cells, which suggests that ERK5 might mediate Raf-independent signaling by Ras. We found that Raf-1 does contribute to Ras activation of ERK5 but in a manner that does not correlate with Raf-1 catalytic activity. A clue to the mechanism of action of Raf-1 on ERK5 comes from the observation that endogenous Raf-1 binds to endogenous ERK5, suggesting the involvement of regulatory protein-protein interactions. This interaction is specific because Raf-1 binds only to ERK5 and not ERK2 or SAPK. Finally, we demonstrate the ERK5/MEK5 pathway is required for Raf-dependent cellular transformation and that a constitutively active form of MEK5, MEK5DD, synergizes with Raf to transform NIH 3T3 cells. These observations suggest that ERK5 plays a large role in Raf-1-mediated signal transduction.

Animals↗
PubMed1999

Functional requirement of p23 and Hsp90 in telomerase complexes.

Most normal human diploid cells have no detectable telomerase; however, expression of the catalytic subunit of telomerase is sufficient to induce telomerase activity and, in many cases, will bypass normal senescence. We and others have previously demonstrated in vitro assembly of active telomerase by combining the purified RNA component with the reverse transcriptase catalytic component synthesized in rabbit reticulocyte extract. Here we show that assembly of active telomerase from in vitro-synthesized components requires the contribution of proteins present in reticulocyte extracts. We have identified the molecular chaperones p23 and Hsp90 as proteins that bind to the catalytic subunit of telomerase. Blockade of this interaction inhibits assembly of active telomerase in vitro. Also, a significant fraction of active telomerase from cell extracts is associated with p23 and Hsp90. Consistent with in vitro results, inhibition of Hsp90 function in cells blocks assembly of active telomerase. To our knowledge, p23 and Hsp90 are the first telomerase-associated proteins demonstrated to contribute to telomerase activity.

Adenosine Triphosphate↗
PubMed1999

Determination of trace elements in porcine brain by inductively coupled plasma-mass spectrometry, electrothermal atomic absorption spectrometry, and instrumental neutron activation analysis.

Methods have been developed for the analyses of trace metals in various areas of porcine brains, (temporal, parietal, frontal cortex, both right and left hemispheres). Determinations were carried out using inductively coupled plasma-mass spectrometry (ICP-MS) and electrothermal atomic absorption spectrometry (ETAAS). The elements investigated were Li, Mn, Cu, Zn, Cd, Hg, and Pb by ICP-MS and Cu, Cd, and Mn by ETAAS. For determination by ICP-MS, a method of standard additions calibration coupled with internal standards was used, and for ETAAS, standard additions calibrations were prepared. The accuracy of all methods was determined using NIST and IAEA certified reference material. A small number of pig brains were analyzed by instrumental neutron activation analysis for Cr, Co, Cs, Fe, Rb, Se, Sc, Sb, and Zn using the comparator method of analysis. Four separate NIST standard reference materials have been used to examine the validity of the comparator method.

Animals↗
PubMed1999

A comparison of inductively coupled plasma mass spectrometry with electrothermal atomic absorption spectrophotometry for the determination of trace elements in blood and urine from non occupationally exposed populations.

Quadrupole Inductively coupled plasma mass spectrometric (QICP-MS) and electrothermal atomic absorption spectrophotometric (ETAAS) methods for the determination of Pb and Cd in whole blood and Al, Cd, Co and Ni in urine were compared. Simple sample pretreatments were used for both instrumental techniques. Urine samples were diluted with either Millipore water or dilute HNO3, while blood samples were diluted with a solution containing either 0.14M NH3 or 0.03 M NH3, 0.05% EDTA and 0.05% Triton X-100 in Millipore water. Scandium, yttrium and indium were used as internal standards for ICP-MS measurements and (NH4)2HPO4 as a chemical modifier for the determination of Pb and Cd by ETAAS. For ICP-MS analysis, pneumatic nebulization was used for introduction of urine samples and flow injection for introduction of blood samples. Matrix matched standards were used for all calibrations and methods were validated by analyzing reference materials and samples from external quality assurance programmes. Concentrations of the listed metals were determined in blood and urine samples obtained from a healthy non occupationally exposed population and reference samples, using both instrumental techniques. The study group (n = 90) was randomly selected from a study population (n = 220) recruited from three regions considered representative of the environment encountered by the majority of the United Kingdom population. Males and females were equally represented and ranged in age from 17-65 yrs. The correlation between results obtained by the two techniques was good for all elements measured, ranging from r = 0.88 for Co in urine to r = 0.99 for both Pb and Cd in blood.

Adolescent↗
PubMed1999

Absence of cancer-associated changes in human fibroblasts immortalized with telomerase.

The ectopic expression of telomerase in normal human cells results in an extended lifespan, indicating that telomere shortening regulates the timing of cellular senescence. As telomerase expression is a hallmark of cancer, we investigated the long-term effects of forced expression of human telomerase catalytic component (hTERT) in normal human fibroblasts. In vitro growth requirements, cell-cycle checkpoints and karyotypic stability in telomerase-expressing cells are similar to those of untransfected controls. In addition, co-expression of telomerase, the viral oncoproteins HPV16 E6/E7 (which inactivate p53 and pRB) and oncogenic HRAS does not result in growth in soft agar. Thus, although ectopic expression of telomerase in human fibroblasts is sufficient for immortalization, it does not result in changes typically associated with malignant transformation.

Catalytic Domain↗
PubMed1999

Cancer patients' expectations of the role of family physicians in communication about complementary therapies.

OBJECTIVE: To explore cancer patients' experiences with and expectations of the role of family physicians in communication about complementary therapies. DESIGN: Focus group interviews. SETTING: British Columbia Cancer Agency and the University of Calgary. PARTICIPANTS: Sample of 14 cancer patients using complementary therapies comprising 3 focus groups (2 in BC and 1 in Alberta). RESULTS: The role of family physicians in discussing complementary therapies varied from being extraneous to patients' decision making to being a partner in making decisions about cancer treatments. Patients expected their physicians to be supportive, caring, kind and to show an interest in them. They also expected their physicians to be accepting and nonjudgmental regarding complementary therapy use and to reinforce a sense of hope. Most patients did not expect their doctors to have extensive knowledge about these therapies. All patients strongly felt the need to seek information themselves. In addition, they felt that believing in the type of therapies they were using was very important. CONCLUSION: Family physicians can play an important role in exploring and discussing complementary therapies with their patients. It is important that they are made aware of their patients' needs in this area.

Aged↗
PubMed1999

The Swedish family: transition to parenthood.

Family interaction during pregnancy and the transition to parenthood creates the social environment in which the fetus becomes part of the family, family relationships and roles are reorganized, and the infant's temperament appears. The purpose of this study was to examine the relationships among family dynamics, parental-fetal attachment, and infant temperament across the transition to parenthood. A sample of 91 families in Helsingborg, Sweden completed the Family Dynamics Measure and the Maternal/Paternal Fetal Attachment Scale during the third trimester of pregnancy. When the infant was 8-9 months old, mothers (n = 62) and fathers (n = 54) again completed the Family Dynamics Measure. The mother completed the Revised Infant Temperament Questionnaire as well. Overall, we found small changes in family dynamics, with an increase in perceived role conflict and mutuality reported by mothers. Fathers reported greater fetal attachment than their partners. Greater paternal- and maternal fetal attachment was related to more positive family dynamics, and maternal-fetal attachment was positively related to infant mood at 8 months. The stability of family dynamics across the transition to parenthood is a sign that most families negotiate this transition without difficulty.

Demography↗
PubMed1998

Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation.

PAKs are serine/threonine protein kinases that are activated by binding to Rac or Cdc42hs. Different forms of activated PAK1 have been reported to either promote membrane ruffling and focal adhesion assembly or cause focal adhesion disassembly and stress fiber dissolution. To understand the basis for these distinct morphological effects, we have examined the mechanism of mutational activation of PAK1, and characterized the effects of different active PAK1 proteins on cytoskeletal structure in vivo. We find that PAK1 contains an autoinhibitory domain that overlaps with its small G protein binding domain and that two separate activating mutations within this regulatory region each decrease autoinhibitory activity. Because only one of these mutations affects Cdc42hs binding activity, this indicates that activation of PAK1 by these mutations results from interference with the function of the autoinhibitory domain and not with small G protein binding activity. When we examined the morphological effects of these different forms of PAK1 in vivo, we found that PAK1 kinase activity was associated with disassembly of focal adhesions and actin stress fibers and that this may require interaction with potential SH3 domain-containing proteins. Lamellipodia formation and membrane ruffling caused by active PAK1 expression, however, was independent of PAK1 catalytic activity and likely requires interaction among multiple proteins binding to the PAK1 regulatory domain.

Cell Adhesion↗
PubMed1998

A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation.

BACKGROUND: Mitogen-activated protein (MAP) kinases are ubiquitous components of many signal transduction pathways. Constitutively active variants have been isolated for every component of the extracellular-signal-regulated kinase 1 (ERK1) and ERK2 MAP kinase pathway except for the ERK itself. RESULTS: To create an activated ERK2 variant, we fused ERK2 to the low activity form of its upstream regulator, the MAP kinase kinase MEK1. The ERK2 in this fusion protein was active in the absence of extracellular signals. Expression of the fusion protein in mammalian cells did not activate endogenous ERK1 or ERK2. It was sufficient, however, to induce activation of the transcription factors Elk-1 and AP-1, neurite extension in PC12 cells in the absence of nerve growth factor, and foci of morphologically and growth-transformed NIH3T3 cells, if the fusion protein was localized to the nucleus. A cytoplasmic fusion protein was without effect. CONCLUSIONS: Activation of ERK2 is sufficient to cause several transcriptional and phenotypic responses in mammalian cells. Nuclear localization of activated ERK2 is required to induce these events.

3T3 Cells↗
PubMed1998

A role for RalGDS and a novel Ras effector in the Ras-mediated inhibition of skeletal myogenesis.

Oncogenic Ras inhibits the differentiation of skeletal muscle cells through the activation of multiple downstream signaling pathways, including a Raf-dependent, mitogen-activated or extracellular signal-regulated kinase kinase/mitogen-activated protein kinase (MEK/MAPK)-independent pathway. Here we report that a non-Raf binding Ras effector-loop variant (H-Ras G12V,E37G), which retains interaction with the Ral guanine nucleotide dissociation stimulator (RalGDS), inhibits the conversion of MyoD-expressing C3H10T1/2 mouse fibroblasts to skeletal muscle. We show that H-Ras G12V,E37G, RalGDS, and the membrane-localized RalGDS CAAX protein inhibit the activity of alpha-actin-Luc, a muscle-specific reporter gene containing a necessary E-box and serum response factor (SRF) binding site, while a RalGDS protein defective for Ras interaction has no effect on alpha-actin-Luc transcription. H-Ras G12V,E37G does not activate endogenous MAPK, but does increase SRF-dependent transcription. Interestingly, RalGDS, RalGDS CAAX, and RalA G23V inhibit H-Ras G12V, E37G-induced expression of an SRF-regulated reporter gene, demonstrating that signaling through RalGDS does not duplicate the action of H-Ras G12V,E37G in this system. As additional evidence for this, we show that H-Ras G12V,E37G inhibits the expression of troponin I-Luc, an SRF-independent muscle-specific reporter gene, whereas RalGDS and RalGDS CAAX do not. Although our studies show that signaling through RalGDS can interfere with the expression of reporter genes dependent on SRF activity (including alpha-actin-Luc), our studies also provide strong evidence that an additional signaling molecule(s) activated by H-Ras G12V,E37G is required to achieve the complete inhibition of the myogenic differentiation program.

Actins↗
PubMed1998

Trace element reference values in tissues from inhabitants of the European Union. X. A study of 13 elements in blood and urine of a United Kingdom population.

Electrothermal atomic absorption spectrophotometry (ETAAS), inductively coupled plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA) were used for the quantitative determination of 13 trace elements in urine and seven trace elements in whole blood of healthy unexposed British subjects living in three regions of the United Kingdom. Careful control of pre-analytical and analytical factors have enabled the results obtained from more than 200 individuals to be used in proposing reference intervals for the following elements; Al, As, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Se, Tl in urine, and Cd, Cr, Hg, Mn, Pb, Se and Tl in blood.

Adolescent↗
PubMed1998

Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav.

Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.

Amino Acid Sequence↗
PubMed1998

Inductively coupled plasma mass spectrometric determination of molybdenum in urine from a Danish population.

Molybdenum creatinine levels in urine were measured in 128 Danish inhabitants by ICP-MS in order to establish reference intervals of molybdenum in urine for the Danish population as a part of the EURO-TERVIHT project (Trace Element Reference Values in Human Tissues). The Mo concentration was determined using the isotopes 95Mo and 98Mo. The values measured based on 98Mo were about 2% lower than those calculated using 95Mo, a negligible difference in the context of reference values. The limit of detection was 0.2 microgram l-1, the precision was 8.6% and the recovery of added NIST 1643c certified reference material was 94%. The distribution of the data, with and without correction for creatinine concentration, was long-normal. The mean concentration measured was 42.5 micrograms l-1, (3.89 micrograms Mo mmol-1 creatinine) using 95Mo and 41.5 micrograms l-1 (3.81 micrograms Mo mmol-1 creatinine) using 98Mo, with the 95% parametric reference intervals 10.0-124.0 micrograms l-1 (0.89-11.50 micrograms Mo mmol-1 creatinine) and 9.6-122.6 micrograms l-1 (0.84-11.47 micrograms Mo mmol-1 creatinine), respectively. The difference between men and women reached the level of significance only after the values were corrected for the creatinine concentration. There was no influence of age on the Mo concentration. Specific effects of different food and beverage intakes could not be demonstrated, with the exception of a positive correlation between butter consumption and Mo concentration.

Adult↗
PubMed1998

Arabian Peninsula men tend to insulin resistance and cardiovascular risk seen in South Asians.

OBJECTIVE: To test the hypothesis that peninsular Arabs and South Asians share a tendency to insulin resistance, differing from other ethnic groups living in the United Arab Emirates (UAE). METHODS: A representative sample of 358 apparently healthy men aged 35-49 years drawn from a multiethnic office-based workforce in the UAE was tested. The sample included a reference group of expatriate South Asians, in whom insulin resistance has already been described as the cause of high coronary heart disease (CHD) mortality. All subjects were screened for CHD risk factors, including glucose tolerance and 2-h serum insulin determinations. RESULTS: There was a high prevalence of previously undiagnosed cases of diabetes (10.1%) and hypertension (14.2%). South Asian and peninsular Arab men shared the tendency to significantly higher 2-h glucose and insulin levels, lower HDL cholesterol concentrations and abdominal obesity especially compared to Europeans, who were five times less likely to be glucose-intolerant (OR 5.40, P = 0.015). Three other Arab groups were intermediate in most trends. CONCLUSION: Susceptibility to insulin resistance in Arabian peninsula men is strongly supported, suggesting that control of obesity and promotion of exercise are the best approach to CHD prevention.

Adult↗