Biomedical subjects

E Dudley

Publications and source records attributed to E Dudley.

At least 19 recordsLinked to original sources

PubMed2006

New insights from MALDI-ToF MS, NMR, and GC-MS: mass spectrometry techniques applied to palynology.

The present study for the first time describes the application of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-ToF MS) to palynology. With an accessible mass range of up to about 350,000 Da at subpicomolar range, this technique is ideal for the characterisation of bio-macromolecules, such as sporopollenin, found in fossil and extant pollen and spore walls, which often can only be isolated in very small quantities. At this stage, the limited solubility of sporopollenin allows for the identification of sections of this biopolymer, but with the optimisation of MALDI-ToF matrices, further structure elucidation will become possible. Furthermore, gas chromatography-mass spectrometry (GC-MS) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy data obtained from a number of experiments revealed that some previously reported data were misinterpreted. These results add support to the hypothesis that common plasticizers were wrongly described as sporopollenin compounds.

Butylated Hydroxytoluene↗

PubMed2002

Empty nest or revolving door? A prospective study of women's quality of life in midlife during the phase of children leaving and re-entering the home.

BACKGROUND: This study documents changes in household composition and effects on women's quality of life of children leaving and returning home. METHODS: A 9-year annual prospective study of a population-based sample of mid-aged Australian-born women who were premenopausal at baseline (N = 438) was conducted. Documentation was made of household composition and change, well-being, bothersome symptoms, daily hassles, feelings for partner and frequency of sexual activities. RESULTS: There was an increase in the number of women living alone, and a reduction in number of households in which there were children or parents. Each year > 25% of women reported a change in household composition. In the first year after the last child departed (N = 155), there was an improvement in women's positive mood and total well-being and a reduction in negative mood and the number of daily hassles. This improvement in mood was confined to those women who at baseline were not worried about children leaving home. In the first year after children return home there was a trend towards reduced frequency of sexual activities but no mood changes. CONCLUSIONS: For the majority of women, the departure of the last child from the household leads to positive changes in women's mood state and a reduced number of daily hassles. Return of offspring may have an adverse effect on sexual relating of the parents.

Adult↗

PubMed2001

Analysis of urinary nucleosides. II. Comparison of mass spectrometric methods for the analysis of urinary nucleosides.

Qualitative and quantitative analyses of urinary nucleosides have diagnostic potential as tumour markers. We have developed separation techniques linked to mass spectrometric detection in order to overcome the problems associated with past identification and quantitation methods. The three methods of analysis utilised were: gas chromatography/mass spectrometry (GC/MS), high-performance liquid chromatography/ion-trap mass spectrometry (HPLC/ITMS) and capillary liquid chromatography/triple quadrupole mass spectrometry (CapLC/TQMS). Here we compare the relative effectiveness of each of the techniques for subsequent application in the systematic study of urinary nucleoside profiles in cancer patients. All three methods proved to be valuable techniques for such urinary nucleoside analyses, and a combination rather than one single choice is concluded as the ideal.

Chromatography, High Pressure Liquid↗

PubMed2001

Are changes in sexual functioning during midlife due to aging or menopause?

OBJECTIVE: To determine whether changes in women's sexual functioning during midlife are due to aging or menopause. DESIGN: Prospective, observational study. SETTING: Population-based sample assessed in own homes. PATIENT(S): Four hundred thirty-eight Australian-born women aged 45-55 years and still menstruating at baseline. One hundred ninety-seven were studied for effects of the natural menopausal transition. Control group A (n = 44) remained premenopausal or early perimenopausal for 7 years. Control group B (n = 42) remained postmenopausal over 5 years. INTERVENTION(S): Nil; questionnaires and blood sampling annually. MAIN OUTCOME MEASURE(S): Shortened version of the Personal Experiences Questionnaire. RESULT(S): By the late perimenopause, there was a significant decline in the factors we had derived of sexual responsivity and total score, and there was an increase in the partner's problems factor. By the postmenopausal phase, there was a further decline in the factors sexual responsivity, frequency of sexual activities, libido, and in the total score, and a significant increase in vaginal dyspareunia and partner's problems. Sexual responsivity significantly declined in both control groups. CONCLUSION(S): Sexual responsivity is adversely affected by both aging and the menopausal transition. Other domains of female sexual functioning were significantly adversely affected when the women became postmenopausal. The relationship with the partner and his ability to perform sexually is adversely affected by the menopausal transition.

Australia↗

PubMed2001

Factors contributing to positive mood during the menopausal transition.

This study determined which variables affect women's positive mood state during the menopausal transition using nine prospective annual assessments of a population based sample of 267 Australian mid-aged women. Longitudinal data analysis carried out by analysis of covariance on Summary Statistics found that positive mood scores remained stable over time and were not related to natural menopausal transition, age, or education. In the early phase of the menopausal transition, positive mood was adversely influenced by baseline interpersonal stress (p = .009) and negative attitudes to aging (p = .026). The most important predictor of positive mood at the phase of late peri-/ postmenopause was positive mood in the premenopause (p = .000). Other factors affecting positive mood in the late peri-/postmenopause were changes in dysphoric symptoms (p = .000), major life events (p = .041), daily hassles (p = .014), marital status (p = .007), and work satisfaction (p = .001). Structural equation modelling found a goodness of fit index of .821.

Affect↗

PubMed2001

Lactococcus lactis LM0230 contains a single aminotransferase involved in aspartate biosynthesis, which is essential for growth in milk.

Amino acid aminotransferases (ATases), which catalyse the last biosynthetic step of many amino acids, may have important physiological functions in Lactococcus lactis during growth in milk. In this study, the aspartate ATase gene (aspC) from L. lactis LM0230 was cloned by complementation into Escherichia coli DL39. One chromosomal fragment putatively encoding aspC was partially sequenced. A 1179 bp ORF was identified which could encode for a 393 aa, 43.2 kDa protein. The deduced amino acid sequence had high identity to other AspC sequences in GenBank and is a member of the Igamma family of ATases. Substrate-specificity studies suggested that the lactococcal AspC has ATase activity only with aspartic acid (Asp). An internal deletion was introduced into the L. lactis chromosomal copy of aspC by homologous recombination. The wild-type and mutant strain grew similarly in defined media containing all 20 amino acids and did not grow in minimal media unless supplemented with asparagine (Asn). The mutant strain was also unable to grow in or significantly acidify milk unless supplemented with Asp or Asn. These results suggest that only one lactococcal ATase is involved in the conversion of oxaloacetate to Asp, and Asp biosynthesis is required for the growth of L. lactis LM0230 in milk.

Animals↗

PubMed2000

Analysis of urinary nucleosides. I. Optimisation of high performance liquid chromatography/electrospray mass spectrometry.

In order to optimise the analysis of urinary nucleosides by high performance liquid chromatography/mass spectrometry (HPLC/MS), the HPLC separation of these compounds was performed at different 'flow rates' and 0.2mL/min was found to give both a better separation and ionisation. The ionisation conditions were optimised to give the best intensity of the molecules quasi-molecular ions. The ion distribution profile and ionisation in both positive and negative mode were examined and the detection of the protonated molecule in positive mode chosen for further analysis. The limits of detection of the method developed are reported and representative LC/MS and LC/MS/MS spectra shown. Typical urinary nucleoside chromatograms are presented.

Chromatography, High Pressure Liquid↗

PubMed2000

Development of a purification procedure for the isolation of nucleosides from urine prior to mass spectrometric analysis.

A chromatographic separation of nucleosides from urine has been developed in order to facilitate their mass spectrometric analysis for clinical diagnosis. A number of chromatographic resins were studied in order to develop an effective and efficient purification procedure. The optimized sequential protocol comprises a centrifugation, acidification and neutralization step, followed by application of an affinity chromatographic column and finally further separation on an acidic cation exchange column and a basic anion exchanger. This scheme shows effective clean-up of a standard radiolabelled nucleoside with a recovery of 92.5%, and recovery of nucleosides added to urine samples before extraction showed recoveries of 72-82%.

Acrylic Resins↗

PubMed2000

Tubal ligation, hysterectomy and D&C: evidence from the Melbourne Women's Midlife Health Project.

The question of whether tubal ligation (TL) is associated with increased risk of hysterectomy or dilatation and curettage (D&C) is examined using data from a population-based study. Retrospective information on TL, D&C and hysterectomy was gathered from 1,810 Australian-born women aged 45-55 who were randomly selected from the population of Melbourne, Australia. Odds ratios for the outcomes were adjusted via logistic regression for age, years of education, smoking status, alcohol consumption, history of premenopausal complaints, number of lost pregnancies, and whether women have discussed menstruation or menopause with their doctor. With these variables taken into account, TL does not emerge as a risk factor for hysterectomy. Though there was a significant association between TL and the probability of ever experiencing a D&C, related extraneous variables which appear to link these events are identified.

Alcohol Drinking↗

PubMed2000

Early follicular phase serum FSH as a function of age: the roles of inhibin B, inhibin A and estradiol.

OBJECTIVE: Reproductive aging in regularly cycling normal women is characterized by a gradual decline in ovarian follicle number and a progressive increase in serum follicle stimulating hormone (FSH), particularly over the age of 40 years. The lack of any consistent decrease in circulating estradiol and progesterone has led to the hypothesis that the FSH increase results from decreasing ovarian inhibin production. The aim of this study was to investigate the relationship between serum inhibins A and B, FSH and estradiol in normal women between the ages of 20 and 50 years. DESIGN AND PATIENTS: Serum from 66 regularly cycling subjects, aged 20-50 years, was collected on days 3-5 of the menstrual cycle for this cross-sectional study. MEASUREMENTS: Serum inhibin A and inhibin B levels were measured by specific enzyme-linked immunosorbent assays (ELISAs). Alpha subunit forms were determined by an immunofluorometric assay which detects all known monomeric and dimeric forms of inhibin A and inhibin B and free alpha subunit. FSH and estradiol levels were measured by immunoassay. Data were log transformed before analysis. RESULTS: Serum FSH, inhibin A and estradiol, but not inhibin B, were positively correlated (p < 0.05-p < 0.001) with age between years 20 and 50. Between 40 and 50 years, serum FSH was negatively correlated with inhibin B (r = -0.61, p < 0.001) and alpha subunit forms (r = -0.47, p < 0.05) and with estradiol (r = -0.39, p < 0.05), but not with inhibin A (r = -0.21, not significant). When log(FSH) was modelled as a function of log(inhibin B) and log(estradiol) with age fitted as a covariate, inhibin B only was a significant independent predictor of FSH (beta = -0.30, p < 0.01). Using purified inhibin A and B standards for the three assays, which were calibrated in terms of their alpha subunit content, serum inhibin A levels were 10-15% of those of inhibin B, with inhibin A + B levels being 22% of total alpha subunit levels. No significant correlation was observed between total inhibin alpha subunit and its dimers. The free alpha subunit, as determined from the difference in levels of total alpha subunit and inhibin A + B, remained relatively unchanged with age, suggesting that it is not differentially regulated. CONCLUSIONS: This study shows that, during the early follicular phase, FSH, inhibin A and estradiol but not inhibin B increase with age. Some of the increase in inhibin A and estradiol may be the result of accelerated follicular development with increasing age. Serum inhibin B and estradiol but not inhibin A are inversely correlated with FSH between ages 40 and 50, but only inhibin B is a significant independent predictor of FSH. This supports the postulate that inhibin B is the main form of inhibin regulating FSH at this stage of the menstrual cycle. During the early follicular phase, serum levels of inhibin A are presumably too low to play a significant physiological role or are less active.

Adult↗

PubMed1999

NF-kappaB regulates Fas/APO-1/CD95- and TCR- mediated apoptosis of T lymphocytes.

The maintenance of lymphocyte homeostasis by apoptosis is a critical regulatory mechanism in the normal immune system. The transcription factor NF-kappaB has been shown to play a role in protecting cells against death mediated by TNF We show here that NF-kappaB also has a role in regulating Fas/APO-1/CD95-mediated death, a major pathway of peripheral T cell death. Transfection of Jurkat cells with the NF-kappaB subunits p50 and p65 confers resistance against Fas-mediated apoptosis. Reciprocally, inhibition of NF-kappaB activation by a soluble peptide inhibitor or a dominant form of the NF-kappaB inhibitor, IkappaB, makes the cells more susceptible to Fas-mediated apoptosis. Furthermore, inhibition of NF-kappaB activation by a soluble peptide inhibitor rendered a T cell hybridoma more susceptible to TCR-mediated apoptosis. Correspondingly, transfection of p50 and p65 provided considerable protection from TCR-mediated apoptosis. These observations were corroborated by studies on Fas-mediated death in primary T cells. Concanavalin A-activated cycling T cell blasts from mice that are transgenic for the dominant IkappaB molecule have increased sensitivity to Fas-mediated apoptosis, associated with a down-regulation of NF-kappaB complexes in the nucleus. In addition, blocking TNF, itself a positive regulator of NF-kappaB, with neutralizing antibodies renders the cells more susceptible to anti-Fas-mediated apoptosis. In summary, our results provide compelling evidence that NF-kappaB protects against Fas-mediated death and is likely to be an important regulator of T cell homeostasis and tolerance.

Animals↗

PubMed1999

Mood and the menopausal transition.

This study determined which variables affect women's mood state during the menopausal transition by using six prospective annual assessments of a community-based sample of 354 Australian mid-aged women. Repeated measures multivariate analysis of covariance found that negative mood scores decreased significantly over time and were not related to natural menopausal transition, follicle-stimulating hormone, estradiol, inhibin, age, or education. The magnitude of negative mood was significantly predicted by baseline reporting of premenstrual complaints, negative attitudes to ageing and menopause, and parity of one. During follow-up, the magnitude of negative mood was significantly adversely affected by: prior experience of negative mood, experience of bothersome symptoms, poor self-rated health, negative feelings for partner, no partner, current smoking, low exercise, daily hassles, and high stress. Negative mood was reduced by decreasing symptoms, improving health, positive feelings for partner, gaining a partner, and reducing stress. The menopausal transition had an indirect effect in amplifying the effect of reducing paid work, poor health, and daily hassles.

Adult↗

PubMed1999

Factors affecting sexual functioning of women in the mid-life years.

OBJECTIVE: To model the interaction of hormones, symptoms and psychosocial factors on women's sexuality during the menopausal transition. DESIGN AND METHODS: A prospective, observational study was carried out of a community-based sample of 438 Australian-born women aged 45-55 years at baseline. The study comprised six annual assessments in the women's own homes utilizing a core questionnaire, with rating scales for well-being and daily hassles, and a Personal Experiences Questionnaire as a measure of sexual functioning. Levels of follicle stimulating hormone (FSH), estradiol and inhibin were measured annually. Statistical analysis was performed by structural equation modelling. RESULTS: The retention rate was 90% (final sample size after exclusions, n = 354). The normal fit index for the global model obtained was 0.92. There is a significant direct effect of menopausal status on vaginal dryness/dyspareunia, and an indirect effect on sexual responsivity via a direct effect of menopausal status on symptoms, which then affect well-being. Menopausal status reflects hormonal status. Feelings for the partner and the partner's sexual problems have direct effects on different aspects of sexual functioning. Other social variables such as paid work, interpersonal stress, daily hassles and educational level affect sexual functioning indirectly via effects on symptoms and well-being. CONCLUSIONS: Psychosocial factors, symptoms and the menopausal transition affect women's sexual functioning during the mid-life years.

Aging↗

PubMed1998

Relationship of endogenous sex hormones to lipids and blood pressure in mid-aged women.

PURPOSE: The relationship between endogenous sex hormones and blood lipids was examined in a representative sample of 438 Australian-born women 45 to 56 years of age taking part in a longitudinal study of the menopausal transition. Data from 363 women who were taking neither exogenous hormones nor lipid-altering medications, were not diabetic, and who had provided blood samples were available for analysis. METHODS: Multiple linear regression was used to examine the relationship between sex hormones and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides, and diastolic blood pressure (DBP), taking account of the effects of age, body mass index (BMI), smoking, alcohol intake, and exercise. RESULTS: There was no significant relationship between estradiol and HDL, LDL, triglyceride, or DBP levels. Free androgen index was positively associated with LDL. However, BMI was an important predictor of all three lipid measures and DBP. HDL was positively associated with age and was highest among women with lowest BMI, high alcohol intake, and in nonsmokers. LDL increased with BMI, free androgen index, and age, but was lower amongst women who exercised more than two or three times per week. Triglyceride also increased with BMI, and was higher among smokers. DBP increased with BMI only. CONCLUSIONS: The results do not support the view that endogenous sex hormones are strongly associated with cardiovascular risk factors around the time of menopause.

Androgens↗

PubMed1998

Serum inhibins A and B fall differentially as FSH rises in perimenopausal women.

BACKGROUND: Serum FSH levels rise with increasing age in normal women, particularly as they enter the menopausal transition and progress to the postmenopausal state. The contributions of decreasing levels of inhibin-A (INH-A) and inhibin-B (INH-B) to this rise are presently unclear, as there are no reports of dimeric INH levels in relation to menopausal status. The present study was undertaken in order to provide preliminary data on relationships amongst the dimeric inhibins, oestradiol (E2) and FSH in normal subjects of defined menopausal status. METHODS: Single serum samples were obtained between cycle days 3 and 8 in regularly cycling women, or at random in those with irregular cycles or amenorrhoea, in 110 women, aged 48-59 years, in the third year of a prospective longitudinal study of the menopausal transition, 'The Melbourne Women's Mid-Life Health Project'. Samples were assayed for FSH, E2, INH-A, INH-B and immunoreactive inhibin (IR-INH) and results were analysed following logarithmic transformation. Undetectable values were assigned the limit of sensitivity of the respective assays. The relationships between hormones were evaluated as a function of menopausal stage. The latter was assigned as Stage 1, premenopausal (no reported change in menstrual cycle pattern), Stage 2, early peri-menopausal (reported change in menstrual cycle frequency in the preceding year with a bleed in the preceding 3 months), Stage 3, late peri-menopausal (no menses in the preceding 3-11 months) and Stage 4, postmenopausal (no menses in the preceding 12 months). RESULTS: The hormone concentrations in premenopausal subjects (geometric means, FSH 13.5 IU/l, E2 306 pmol/l, IR-INH 217 U/l, INH-A 96 ng/l, and INH-B 48 ng/l) were used as reference points for the other stages of menopausal status. Early peri-menopausal subjects had significantly lower levels of IR-INH (147 U/l) and INH-B (13.5 ng/l) in the presence of a small, statistically nonsignificant rise in FSH (to 21.4 U/l) and no significant change in E2 or INH-A. In late peri-menopausal subjects, IR-INH fell to 76 U/l, INH-A fell to 4.2 ng/l, whilst INH-B was not significantly different at 14 ng/l. FSH had risen significantly to 72.21 U/l. Oestradiol also fell significantly to 89 pmol/l. In the postmenopausal subjects there were no further significant changes in the peptide hormones or FSH, but E2 fell further to 41 pmol/l. There was a significant (P < 0.05) inverse correlation between FSH and E2 (R = -0.78), FSH and IR-INH (R = -0.66), FSH and INH-A (R = -0.53), FSH and INH-B (R = -0.29) while IR-INH and either INH-A or INH-B were positively correlated (R = +0.57 and +0.35, respectively). The data are consistent with negative feedback roles for both dimeric inhibins and E2 as contributors to the regulation of FSH secretion as menopausal status changes. CONCLUSIONS: The major significant endocrine event in women in the early peri-menopausal phase of the menopausal transition is a substantial fall in the circulating levels of inhibin-B with no significant change in inhibin-A or oestradiol. Progression to late peri-menopausal status is accompanied by a marked fall in inhibin-A and oestradiol and a rise in FSH without further change in inhibin-B. Inhibin-B, a marker of follicle number, is a significant factor in the endocrinology of the menopausal transition.

Cross-Sectional Studies↗

PubMed1998

Menopausal status: subjectively and objectively defined.

This study aims to assess the relationship between self-rated and menstrually defined menopausal status, assesses criteria women use in perceiving their own menopausal status and compares symptom reporting and hormonal levels for self-rated and menstrually defined menopausal status. Women in the third year of the longitudinal phase of the Melbourne Women's Midlife Health Project (n = 332) were asked to assess their own menopausal status and the basis for this assessment. They were also specifically questioned on current menstrual cycle characteristics and levels of follicle-stimulating hormone (FSH), estradiol and inhibin were measured. For 67% of the women, the two definitions of menopausal status were in agreement. In women menstrually defined as premenopausal, self-rated menopausal status of peri- or postmenopausal appeared to be based on the occurrence of symptoms. In women menstrually defined as postmenopausal, persistence of hot flushes was taken to mean that 'the menopause was still in progress' despite absence of menses for more than 12 months. In women menstrually defined as perimenopausal yet who self-rated as premenopausal, FSH was lower (p < 0.01) and inhibin higher (p = 0.05) than women who self-rated as peri- or postmenopausal. Women's perceptions of the menopause are based on symptoms. Self-rated menopausal status appears to relate more closely to a women's endocrine status than definitions based on purely menstrual cycle characteristics.

Attitude to Health↗

PubMed1998

Relationships between premenstrual complaints and perimenopausal experiences.

This study evaluates whether a history of menstrually-related problems, termed premenstrual complaints (PMCs), is a significant predictive marker for a more symptomatic perimenopausal experience. Two hundred and ninety-one randomly selected urban women, aged between 45 and 55 years were interviewed yearly for three consecutive years to record their individual experiences and changes as they progressed through the menopause transition. Repeated measures were obtained on a range of physical, psychological and social indicators. The experiences of women who reported a self-defined history of premenstrual complaints (n = 104) were compared with those women with no prior premenstrual problems (n = 187) and predictors of perimenopausal symptoms were assessed. Relationships were found between a prior history of both physical and psychological premenstrual complaints and a more symptomatic perimenopause characterised by dysphoria, skeletal, digestive and respiratory symptoms (all ps < 0.05). The more symptomatic women also reported pronounced interpersonal stress (p < 0.001), significant 'hassles', current smoking and low exercise (ps < 0.05). The findings support predictive relationships between a prior history of premenstrual problems and a more problematic menopause transition. The issues of vulnerability and help-seeking behaviors are discussed.

Cross-Sectional Studies↗

PubMed1997

Determinants of self rated menopause status.

This study, based on a population survey, examines the self ratings of progress through the menopausal transition of women in natural menopause, women using hormone therapy and women who have undergone hysterectomy. The latter two groups are usually excluded from discussions of menopausal transition, since the accepted menstrually defined criteria do not apply to them. Hysterectomised women do not differ in their self rating profile from non-hysterectomised women, after hormone therapy status is taken into account. This is surprising, since they may have been expected to see themselves as in the main postmenopausal. Use of hormone therapy is tantamount to self perception as at least perimenopausal. Among women in natural menopause there is 29% disagreement between self ratings and menstrually defined categories. On the basis of these observations it is hypothesised that experience of symptoms associated with menopause is important in determining self ratings. The good fit of logistic regression predictions of self ratings from hysterectomy status, hormone therapy status and experience of hot flushes is consistent with this hypothesis. This research indicates that it is important to take women's subjective evaluations into account in assessing progress through the menopausal transition.

Attitude to Health↗