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Biomedical subjects

M A White

Publications and source records attributed to M A White.

At least 19 recordsLinked to original sources
PubMed2006

Evolutionary divergence of LFY function in the mustards Arabidopsis thaliana and Leavenworthia crassa.

LEAFY (LFY), a transcription factor involved in the regulation of flower development in Arabidopsis thaliana, has been identified as a candidate gene in the diversification of plant architecture in Brassicaceae. Previous research with Leavenworthia crassa, which produces solitary flowers in the axils of rosette leaves, has shown that the L. crassa LFY ortholog, LcrLFY, rescues most aspects of flower development in A. thaliana but showed two novel traits: flowers produced additional petals and inflorescences produced terminal flowers. In this paper, we explore the molecular mechanisms responsible for these novel phenotypes. We used microarray hybridizations to identify 32 genes differentially expressed between a transgenic LcrLFY line and a control transgenic LFY line. Of particular interest, TERMINAL FLOWER 1 (TFL1) transcripts were found at elevated levels in LcrLFY lines. To distinguish regulatory versus functional changes within the LcrLFY locus, reciprocal chimeric transgenes between LcrLFY and LFY were constructed. These lines implicate divergence of LcrLFY cis-regulation as the primary cause of both novel transgenic phenotypes but implicate divergence of LcrLFY protein function as the primary cause of elevated TFL1 levels. Taken together these results show that LcrLFY has diverged from A. thaliana in both the cis-regulatory and protein-coding regions and imply that molecular coevolution of LcrLFY and the L. crassa TFL1 ortholog, LcrTFL1, contributed to the evolution of rosette flowering.

Arabidopsis↗
PubMed2006

Extreme heat reduces and shifts United States premium wine production in the 21st century.

Premium wine production is limited to regions climatically conducive to growing grapes with balanced composition and varietal typicity. Three central climatic conditions are required: (i) adequate heat accumulation; (ii) low risk of severe frost damage; and (iii) the absence of extreme heat. Although wine production is possible in an extensive climatic range, the highest-quality wines require a delicate balance among these three conditions. Although historical and projected average temperature changes are known to influence global wine quality, the potential future response of wine-producing regions to spatially heterogeneous changes in extreme events is largely unknown. Here, by using a high-resolution regional climate model forced by the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios A2 greenhouse gas emission scenario, we estimate that potential premium winegrape production area in the conterminous United States could decline by up to 81% by the late 21st century. While increases in heat accumulation will shift wine production to warmer climate varieties and/or lower-quality wines, and frost constraints will be reduced, increases in the frequency of extreme hot days (>35 degrees C) in the growing season are projected to eliminate winegrape production in many areas of the United States. Furthermore, grape and wine production will likely be restricted to a narrow West Coast region and the Northwest and Northeast, areas currently facing challenges related to excess moisture. Our results not only imply large changes for the premium wine industry, but also highlight the importance of incorporating fine-scale processes and extreme events in climate-change impact studies.

Agriculture↗
PubMed2005

Association of body size estimation and age in African-American females.

This cross-sectional research study tested the hypothesis that body image estimates of African-American females differ as a function of age. To test this hypothesis, body image estimates of 379 African-American females, ranging in age from 16 to 96 years, were contrasted as a function of age group, while statistically controlling body mass index. Three body size estimates, current body size, ideal body size, and reasonable body size were measured using the Body Image Assessment for Obesity. The discrepancies between current and ideal body size estimates and between current and reasonable body size estimates were also analyzed to assess for differences in body size dissatisfaction. The study found that younger African-American women (16 to 35 years) differed from older African-American women (>35 years) on measures of body size dissatisfaction. Women in the age range of 26 to 35 years reported higher estimates of current body size in comparison to women older than 35 years. The youngest age group (16 to 25 years) reported thinner ideal body size goals in comparison to women who were slightly older (26 to 35 years) and women who were older than 75 years. The pattern of body image estimates across a large age range suggests that younger African-American women, in comparison to older African-American women, may have body images that may make them more susceptible to eating disorders.

Adolescent↗
PubMed2005

Efficacy of an internet-based behavioral weight loss program for overweight adolescent African-American girls.

OBJECTIVE: This randomized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for weight management in African-American girls. DESIGN: African-American girls were randomly assigned to an interactive behavioral internet program or an internet health education program, the control condition. The behavioral intervention included internet counseling and was highly interactive. The control intervention was a passive (non-interactive) educational program. Parents were also participants in the study. Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention. SUBJECTS: The study enrolled 57 African-American adolescent girls (ages 11 to 15 years) who were overweight or obese and had at least one biological parent who was obese [body mass index (BMI) >30 kg/m2]. Of the 57 participants, 50 (88%) completed the 6-month trial. MEASUREMENTS: Outcome data, including BMI, body weight, body composition, dietary intake, and weight loss behaviors were collected at baseline and 6-months later. A computer server tracked utilization of the websites. Participation in the program was measured by number of "hits" on the website. RESULTS: Compared to the control condition, adolescents in the behavioral treatment lost more body fat (group difference =1.6% body fat) and parents lost significantly more body weight (group difference =2.1 kg). Utilization of the behavioral website by adolescents and parents was associated with positive outcome. Dietary fat intake was lowered for adolescents and parents in the behavioral treatment group. CONCLUSION: An internet-based behavioral intervention was superior to internet-based health education and yielded decreased body fat for adolescent girls and decreased body weight for parents.

Absorptiometry, Photon↗
PubMed2005

Percent body fat measured by BIA and DEXA in obese, African-American adolescent girls.

OBJECTIVE: To compare the estimation of body fat between bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DEXA) in overweight, African-American female adolescents. SUBJECTS: In total, 54 African-American adolescent female subjects were recruited for Study 1. Each adolescent's body mass index was greater than the 85th percentile and their average body fat was 45% according to DEXA. A total of 26 African-American adolescent female subjects were available for Study 2, and had an average body fat of 26% according to DEXA. MEASUREMENTS: Percent body fat was measured by DEXA and BIA. Seven different BIA equations were tested. Both sets of data were analyzed using Bland-Altman regression analyses, utilizing percent body fat measured by DEXA as the criterion. RESULTS: The Kushner equation provided estimates that were unaffected by body fat in both studies. Estimates were unbiased when applied to the exclusively overweight sample and biased when utilized with the separate sample of normal weight and obese girls. The remaining equations were biased, provided inconsistent estimates across body weight, or were biased and provided inconsistent estimates. Ethnicity-specific and ethnicity-combined equations performed similarly in the obese sample, but became more disparate when applied to a sample encompassing a wider body weight range. The limits of agreement between all BIA equations and the DEXA estimates ranged from 6 to 9%. CONCLUSION: The study suggests that the Kushner BIA equation is appropriate for use with African-American female adolescents across the weight spectrum, while the majority of BIA equations underestimated percent body fat as body fat increased.

Absorptiometry, Photon↗
PubMed2003

Racial/ethnic differences in weight concerns: protective and risk factors for the development of eating disorders and obesity among adolescent females.

OBJECTIVE: This study compared African American and Caucasian adolescent girls on measures of appearance concerns, body-contingent self-esteem, pressures for thinness, and dieting behaviour. Also, correlations among these measures were contrasted across the two ethnic groups. METHOD: African American (n = 32) and Caucasian (n = 29) adolescent girls completed a series of self-report measures concerning dieting behaviour, perceived pressures for thinness, self-esteem, and perceptions of physical appearance. RESULTS: Across all measures, Caucasian girls endorsed more disturbed eating behaviors and beliefs about body shape and weight. Dieting among Caucasian girls was correlated with preoccupation with body shape. Among African American girls dieting behaviour was unrelated to concerns about body shape. DISCUSSION: These findings support the hypothesis that in comparison to Caucasian girls, African American girls may be at lessened risk for developing eating disorders but may be at greater risk for developing obesity. This conclusion is based upon the findings of higher levels of eating disorder symptoms among Caucasian girls and the relative absence of significant correlations between dieting and body shape and appearance concerns among African American girls.

Adolescent↗
PubMed2002

Determination of cadmium and zinc in Alzheimer's brain tissue using inductively coupled plasma mass spectrometry.

In this work, brain tissue was taken from Alzheimer's Disease (AD) subjects (n=11), 'normal' subjects (n=10) and from subjects with senile involutive cortical changes (SICC) (n=6). Concentrations of Cd and Zn were determined in all samples, using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The brain tissue was selected and obtained from the Netherlands Brain Bank. Samples were taken in each case, from both hemispheres of the superior frontal gyrus, the superior parietal gyrus, the medial temporal gyrus, the hippocampus and the thalamus of the same brain.Cd which is known to have no essential role in the brain was found to follow, as expected, a lognormal distribution of concentrations in 'normal' subjects (Shapiro-Wilk's test (0.98) (p<0.18)). For the Alzheimer's Disease subjects and SICC subjects, the data tends to follow a lognormal distribution, rather than a normal distribution, but is still significantly different from it (Shapiro-Wilk's test (0.97) (p<0.03); (0.93) (p<0.0067), respectively)). In the case of Zn concentrations, the data tends to follow a normal distribution for the 'normal' subject group, even though the data is significantly different from it (Shapiro-Wilk's test (0.95) (p<0.001)). Whereas in the Alzheimer's Disease and SICC subject groups, the data follows a normal distribution (Shapiro-Wilk's test (0.98) (p<0.21); (0.97) (p<0.2002), respectively)). When comparing age-matched groups, for all regions and both hemispheres, no significant differences (p>0.1) for Cd were found between 'normals' and Alzheimer's Disease subjects and Alzheimer's Disease subjects and SICC but at a low level of significance, lower concentrations of Cd were found in the SICC group compared to the 'normals'. For all regions and both hemispheres, Zn was found to be significantly decreased in the Alzheimer's Disease group, compared to the 'normal' and SICC groups. Zn concentrations were also found to be significantly decreased in the 'normals' compared to the SICC group. It is also of interest that Cd negatively correlates with the scale of tangles in both 'normals' (p<0.001) and Alzheimer's Disease subjects (p<0.01). In the SICC subjects Cd correlates negatively with the tangles but not significantly so (p>0.1).

Aging↗
PubMed2001

Structural and functional linkages between subunit interfaces in mammalian pyruvate kinase.

Mammalian pyruvate kinase (PK) is a four-domain enzyme that is active as a homo-tetramer. Tissue-specific isozymes of PK exhibit distinct levels of allosteric regulation. PK expressed in muscle tissue (M1-PK) shows hyperbolic steady-state kinetics, whereas PK expressed in kidney tissue (M2-PK) displays sigmoidal kinetics. Rabbit M1 and M2-PK are isozymes whose sequences differ in only 22 out of 530 residues per subunit, and these changes are localized in an inter-subunit interface. Previous studies have shown that a single amino acid mutation to M1-PK at either the Y (S402P) or Z (T340 M) subunit interface can confer a level of allosteric regulation that is intermediate to M1-PK and M2-PK. In an effort to elucidate the roles of the inter-subunit interaction in signal transmission and the functional/structural connectivity between these interfaces, the S402P mutant of M1-PK was crystallized and its structure resolved to 2.8 A. Although the overall S402P M1-PK structure is nearly identical with the wild-type structure within experimental error, significant differences in the conformation of the backbone are found at the site of mutation along the Y interface. In addition, there is a significant change along the Z interface, namely, a loss of an inter-subunit salt-bridge between Asp177 of domain B and Arg341 of domain A of the opposing subunit. Concurrent with the loss of the salt-bridge is an increase in the degree of rotational flexibility of domain B that constitutes the active site. Comparison of previous PK structures shows a correlation between an increase in this domain movement with the loss of the Asp177: Arg341 salt-bridge. These results identify the structural linkages between the Y and Z interfaces in regulating the interconversion of conformational states of rabbit M1-PK.

Allosteric Regulation↗
PubMed2001

Raf-induced transformation requires an interleukin 1 autocrine loop.

The c-Raf-1 serine/threonine protein kinase plays a critical role in the proliferation of most cell types that have been examined. As such, the Raf proto-oncogene is thought to play a central role in the development of human tumors. Although the c-raf-1 gene itself rarely appears to be mutated in human tumors, the kinase activity of Raf is frequently found to be more active in tumor cells, likely through constitutive activation of upstream activators of Raf. The downstream events triggered by Raf that are involved in transformation have been studied less extensively. We show in this study that Raf-induced transformation of NIH 3T3 cells requires the activation of the ubiquitously expressed transcription factor, nuclear factor-kappaB, by Raf. Furthermore, through the use of CrmA, interleukin 1 (IL-1) receptor antagonist, and a dominant-negative form of TRAF6, we demonstrate a requirement for IL-1 production and signaling from the IL-1 receptor as necessary components of Raf-induced transformation. These results indicate that IL-1 may be used as an autocrine growth factor by a number of tumors in which activation of Raf plays an important role in transformation and suggest that blockade of IL-1 signaling may be an approach to limiting the growth of certain tumors.

3T3 Cells↗
PubMed2001

Isolation of effector-selective Ras mutants by yeast two-hybrid screening.

Ras mutants displaying selective target interactions will often display partial loss of function phenotypes when expressed in cells. Thus the isolation of mutations in Ras and Ras family members has proved to be a productive approach for testing the requirement of specific target interactions to mediate downstream responses. The procedures outlined here greatly simplify the isolation of such mutants, and it is hoped will contribute to a better understanding of Ras effector function.

Genes, ras↗
PubMed2001

Current research activity in the measurement of thorium and the identification of future research needs.

A pre-requisite in the setting and enforcement of regulatory limits for exposure to thorium in the workplace is that thorium and its progeny can be accurately measured. Literature surveys have shown that the majority of thorium measurements were performed using either a radiochemical technique, such as alpha or gamma spectroscopy, or ICP-MS. For many methods. there was a separation step to isolate and pre-concentrate thorium from the sample matrix. Thorium was most commonly measured in geological matrices and industrial materials. A survey of current research activity was performed through distribution of a questionnaire to laboratories and national centres. From the rcsponses, four areas of current activity were identified: (i) development of methods for low level thorium determination, (ii) biological monitoring and metabolism of thorium, (iii) environmental monitoring for thorium, and (iv) health risks from X ray contract media. Two key areas for priority research were identified by the thorium Thematic Network: namely sample preparation methods and for traceable standards and reference materials for thorium analysis.

Environmental Exposure↗
PubMed2000

ERK5 and ERK2 cooperate to regulate NF-kappaB and cell transformation.

We have previously demonstrated an involvement of MEK5 and ERK5 in RafBXB-stimulated focus formation in NIH3T3 cells. We find here that MEK5 and ERK5 cooperate with the RafBXB effectors MEK1/2 and ERK1/2 to induce foci. To further understand MEK5-ERK5-dependent signaling, we examined potential MEK5-ERK5 effectors that might influence focus-forming activity. Consistent with results from our focus-formation assays, constitutively active variants of MEK5 and MEK1 synergize to activate NF-kappaB, and MEK5 and ERK5 are required for activation of NF-kappaB by RafBXB. The MEK5-ERK5 pathway is also sufficient to activate both NF-kappaB and p90 ribosomal S6 kinase. Our results support the hypothesis that NF-kappaB and p90 ribosomal S6 kinase are involved in MEK5-ERK5-dependent focus formation and may serve as integration points for ERK5 and ERK1/2 signaling.

3T3 Cells↗
PubMed2000

Uncoupling Raf1 from MEK1/2 impairs only a subset of cellular responses to Raf activation.

The Raf family of serine/threonine protein kinases is intimately involved in the transmission of cell regulatory signals controlling proliferation and differentiation. The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins. However, accumulating evidence suggests that there are additional Raf substrates and that subsets of Raf-induced regulatory events are mediated independently of Raf activation of MEK1/2. To examine the possibility that there is bifurcation at the level of Raf in activation of MEK1/2-dependent and MEK1/2-independent cell regulatory events, we engineered a kinase-active Raf1 variant (RafBXB(T481A)) with an amino acid substitution that disrupts MEK1 binding. We find that disruption of MEK1/2 association uncouples Raf from activation of ERK1/2, induction of serum-response element-dependent gene expression, and induction of growth and morphological transformation. However, activation of NF-kappaB-dependent gene expression and induction of neurite differentiation were unimpaired. In addition, Raf-dependent activation of p90 ribosomal S6 kinase was only slightly impaired. These results support the hypothesis that Raf kinases utilize multiple downstream effectors to regulate distinct cellular activities.

3T3 Cells↗
PubMed2000

A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis.

OBJECTIVES: To determine patient preferences and cost differences between home-based and hospital-based chemotherapy. DESIGN: Randomised crossover trial. SETTING: A tertiary cancer hospital in Melbourne, Victoria. PARTICIPANTS: 20 patients who required chemotherapy suitable for administration at home. INTERVENTIONS: Patients were assigned at random to receive their first chemotherapy treatment in either the home or the hospital and the second treatment in the alternative setting. MAIN OUTCOME MEASURES: Patient preference, costs. RESULTS: There was universal agreement by the 20 patients in the randomised trial that home-based chemotherapy was the preferred option (P < 0.0001). No problems were nominated by the patients as being associated with home-based chemotherapy. Home-based treatment was estimated to result in an increased cost of $83 (P = 0.0002) for each chemotherapy treatment compared with hospital-based treatment. Reported advantages for chemotherapy in the home included the elimination of travel, reduction in treatment-associated anxiety, reduction in the burden on carers and family, and the ability to continue other duties. There were no significant complications associated with administration of chemotherapy in the home. CONCLUSIONS: Patients prefer home-based chemotherapy to hospital-based treatment. The future of chemotherapy-in-the-home programs in Australia will depend on whether patient preferences are deemed to offset any potential increase in costs.

Aged↗
PubMed2000

Recovery from stroke: does rehabilitation counselling have a role to play?

AIMS AND OBJECTIVES: The aim of this paper is to explore the stroke literature, with particular emphasis on the management of psycho-social issues during and in the aftermath of stroke rehabilitation. Within the literature, there are a number of studies that indicate that the present 'medical/physical' approach to stroke rehabilitation may not be achieving desirable long-term psycho-social outcomes and these are considered. The studies highlight the potential effect of the human emotional and social aspects of having a stroke upon the physical and mental well-being of the person. For the person living with stroke, the ability to maintain a positive sense of direction in life as well as hold onto their, or develop a new, identity is crucial in terms of adapting to change. Holding onto one's self-worth and unity with the past and anticipating the future enhances the ability to cope and adapt in the aftermath of stroke rehabilitation. This links with the investigation into rehabilitation counselling as a potential strategy for the management of long-term psycho-social functional status following stroke. CONCLUSION: It is suggested that the medical model of stroke rehabilitation places undue emphasis on clinical diagnosis and treatment. By default, measurement of physical independence or disability that is compressed into standardized scales has arguably led to the neglect of the emotional and social consequences of stroke and a partial or inhibited view of the person. It is proposed that there is a need to develop and evaluate the effectiveness of rehabilitation counselling from short-term stroke rehabilitation through to long-term psychosocial adaptation, for this client group to provide clear evidence for service provision.

Counseling↗
PubMed2000

The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst injured drivers and their role in driver culpability: part ii: the relationship between drug prevalence and drug concentration, and driver culpability.

Blood samples from 2,500 injured drivers were analysed for alcohol, cannabinoids (measured by the presence of THC), benzodiazepines and stimulants. The relationship between the prevalence and concentration of drugs and the culpability of the driver was examined using an objective method for assessing culpability. There were no significant differences between males and females with respect to culpability. However, there was a relationship between age and culpability: drivers under 26 years and over 60 years were more likely to be culpable. Drivers who tested positive for alcohol only, benzodiazepines only and the combinations of alcohol and THC and alcohol and benzodiazepines were significantly more likely to be culpable for the crash compared with the drug-free group. Conversely, a lower percentage of drivers who only tested positive for THC were culpable for the crash compared with drug-free drivers. This difference was not statistically significant. For car drivers in single-vehicle crashes, the majority of drivers were judged culpable irrespective of drug use. In multiple-vehicle crashes, car drivers testing positive for alcohol only or benzodiazepines only were more likely to be culpable for the crash compared with drug-free drivers. For motorcycle riders in both single- and multiple-vehicle crashes, there were no significant differences between the drug-positive and drug-free groups. A higher percentage of drug-free riders in multiple-vehicle crashes were culpable compared with riders who only tested positive for THC, but this difference was not statistically significant. There was a significant concentration-dependent relationship between alcohol and culpability: as blood alcohol concentration increased, so did the percentage of culpable drivers. When THC was used alone, there was no significant increase in culpability. For those drivers with benzodiazepines at therapeutic concentrations and above, there was a significant increase in culpability. The relationship between stimulants and culpability was not significant, although a higher proportion of stimulant-positive drivers were culpable compared with drug-free drivers. The combinations of alcohol and THC, and alcohol and benzodiazepines also produced a significant increase in culpability, but this increase was not significantly greater than that produced by alcohol alone.

Accidents, Traffic↗
PubMed2000

The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst injured drivers and their role in driver culpability: part i: the prevalence of drug use in drive the drug-positive group.

Blood samples from 2,500 injured drivers were analysed for alcohol, cannabinnoids, benzodiazepines and stimulants. Overall, three-quarters of drivers tested negative for drugs. Alcohol was the most frequently detected drug. Cannabinoids were also detected at high rates, but the majority of drivers tested positive for THC-acid, the inactive metabolite of THC. Benzodiazepines and stimulants were detected at low rates, and detection rates for combinations of drugs were also low. Males were more likely to test positive for drugs, especially alcohol and THC, whereas females were more likely to test positive for benzodiazepines. A similar proportion of car drivers and motorcycle riders tested positive for drugs, although riders were more likely to test positive for THC. Single-vehicle crashes were particularly associated with alcohol for both car driver and riders, and for riders, multiple-vehicle crashes were particularly associated with THC.

Accidents, Traffic↗