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Biomedical subjects

R H Osborne

Publications and source records attributed to R H Osborne.

At least 19 recordsLinked to original sources

The value of the Hospital Anxiety and Depression Scale (HADS) for comparing women with early onset breast cancer with population-based reference women.

BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is frequently used in cancer studies, yet its utility for comparing people with cancer with people in the community is uncertain. METHODS: HADS scores were obtained from population-based samples of women with (n = 731) and without (n = 158) early-onset breast cancer. Psychometric properties were examined using differential item functioning (DIF) which is the presence of systematic group differences in certain response items independent of the trait being measured. RESULTS: Women with breast cancer scored lower than reference women on anxiety (mean (SD) 7.5 (4.3) vs. 8.2 (4.0); p = 0.06) and depression (3.3 (3.2) vs. 4.2 (3.0); p = 0.003). Group differences remained following adjustment for demographics. Time since diagnosis was not related to anxiety or depression scores. DIF was present in two anxiety and five depression items. Adjustment for DIF did not substantially change the anxiety or depression group differences. CONCLUSION: Specific sampling or DIF effects do not explain the observation that women with breast cancer have lower levels of anxiety and depression than population controls. The psychometric properties of the HADS appear to be acceptable in these groups.

Adult↗

The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine.

Anthraquinone stimulant cathartics, such as emodin, are believed to increase the rate of contraction of ileum tissue in vitro via multiple mechanisms. The aim of this study was to probe the effects of emodin on acetylcholine (ACh)-induced contraction of the rat isolated ileum preparation. 2 Ileal sections were incubated in Tyrode's solution and responses to methacholine, ACh and emodin obtained in the absence and presence of the muscarinic antagonist atropine and the choline uptake inhibitor hemicholinium (HC-3). Depletion of endogenous ACh in the presence of HC-3 was achieved by construction of an ACh dose-response curve, using exogenous ACh, prior to re-testing the effects of emodin in the presence of HC-3. 3 Emodin caused dose-dependent tissue contraction that was abolished by inclusion of atropine (1 microM) in the buffer. Atropine (1 microM) antagonized the response caused by methacholine. Incubation of tissues with HC-3 (1 and 10 microM) reduced the maximum response caused by emodin by 45% and 71% respectively, but had no effect on ACh-induced tissue contraction. These data suggest that, emodin causes contraction of the ileum by triggering the release of endogenous ACh which acts on muscarinic receptors to cause contraction of the rat isolated ileum preparation.

Acetylcholine↗

Age-specific norms and determinants of anxiety and depression in 731 women with breast cancer recruited through a population-based cancer registry.

The aim of this study was to determine population norms and determinants of anxiety and depression in a population-based sample of 731 women with breast cancer (aged 23-60 years) with the Hospital Anxiety and Depression scale (HADS). The prevalence of 'probable' psychological morbidity due to anxiety was 23% and due to depression was 3%. When the women identified as 'possible' cases were included, the respective proportions were 45 and 12%. Higher anxiety was present in younger, less educated women not born in Australia. There was no clear pattern of risk factors for depression. These population-based findings highlight the need for clinicians to be aware that age, education and country of birth may identify a particularly vulnerable subgroup. While brief scales such as the HADS are limited in their ability to accurately predict a clinical diagnosis, high scores identify those who may warrant referral for clinical evaluation.

Adaptation, Psychological↗

The genetic epidemiology of glioma.

With traditional epidemiologic research designs, few environmental risk factors for malignant brain tumors have been revealed, and although syndromes exist where brain tumors occur frequently, these explain a small proportion of the overall incidence. In a similar way, the search for genetic causes has been thwarted by the rarity of families with multiple affected relatives, inhibiting genetic linkage, sib-pair, or even population-based association studies. Molecular genetic studies generally involve searching for candidate proto-oncogenes and tumor suppressor genes by comparing DNA from tumor material with constitutional (germline) DNA. However, it remains difficult to distinguish causative genetic aberrations from chaotic neoplastic processes, and studies so far have not yielded consistent information on the location of such causative genetic lesions. The current literature covering the molecular genetics of glioma is discussed herein and alternative approaches that can be used to identify genetic causes of glioma described.

Adult↗

Tooth eruption symmetry in functional lateralities.

Dental casts and oral photographs from a cross-sectional sample of 2092 young North Americans with detailed information on functional lateralities (eyedness, handedness and footedness) were examined to compare the proportions of symmetrical and asymmetrical eruption of the antimeric (left-right, contralateral pair) permanent teeth using a four-grade eruption scale. The proportion of symmetrically erupting antimeric teeth was higher for some teeth in those with non-right-sidedness of the feet and eyes, but not significantly so in the case of handedness. Left-footedness was significantly (95% confidence interval) associated with an increased proportion of symmetrical pairs of the maxillary first molar and mandibular lateral incisor, and non-right-eyedness with an increased proportion of symmetrical eruption and left/right non-balanced proportions of asymmetrical eruption in maxillary central incisors. True right-sidedness (hand, foot and eye) was significantly (P< or =0.05) associated with advanced eruption of the left mandibular first molar. It is suggested that while the timing of antimeric tooth emergence and clinical eruption is primarily programmed before crown mineralization, starting approximately at the 30th gestational week in the case of first permanent molars, symmetrical/asymmetrical tooth emergence and eruption may provide information a posteriori on prenatal and early postnatal growth and development.

Body Patterning↗

Permanent tooth crown dimensions in prematurely born children.

AIM: The aim was to examine the effect of preterm birth on permanent tooth crown dimensions. MATERIALS AND METHODS: The data consisted of 328 prematurely born white and black children and 1804 control children who participated in the cross-sectional study of the Collaborative Perinatal Project (USA) in the early 1960s and 1970s. The dental examinations were carried out in a standardized fashion at ages varying from 6 to 12 years in 95% of cases. Tooth crown size measurements were performed on the dental casts with an electronic measuring device and readout by two experienced observers according to precise definitions generally quoted in the anthropological and genetic literature. The preterm and control groups were divided by sex and race. RESULTS: The results show both increased and decreased tooth crown dimensions in the prematurely born children. Significantly increased dimensions were found in the means of the intercuspal distances of the first permanent molars in the white boys and in the mesiodistal dimensions (MD) of the lower lateral incisors and the upper left first molar in the black girls. By contrast, there were decreased intercuspal distances, MD and labiolingual (LL) tooth crown dimensions in the white girls and black boys. The statistical method used was the Mann-Whitney's U-test (Willcoxon Rank-Sums test). CONCLUSIONS: The findings partly support previous reports of decreased tooth crown dimensions in preterm infants, but the increased dimensions found in the preterm white boys and black girls differ from earlier reports. Our results indicate the importance of environmental factors including neonatal factors in determining permanent tooth crown dimensions. Growth patterns, the buffering capacity and the timing of sensitive moments in tooth crown volume gain may vary between the sexes and ethnic groups and the possible effect of the accelerated growth period in preterm infants (catch-up growth) may influence the determination of permanent tooth crown dimensions.

Adolescent↗

The relationship of handedness to asymmetry in the occlusal morphology of first permanent molars.

Handedness has been shown to be related to a number of systematic asymmetries in body dimensions, dermatoglyphic patterns and cerebral morphology. The aim here was to compare linear and angular tooth crown asymmetries of the permanent molars in healthy right-handed and left-handed subjects. The material comprised 27 children with recorded concordant left-side dominance of hand, eye and foot. The controls were an age- and sex-matched group with right side dominance. The material is based on the Collaborative Perinatal Project where detailed medical records and the dentitions, including accurate dental impressions, of over two thousand American children were examined in the USA in the sixties. Machine vision technique was used to obtain accurate three-dimensional information from the occlusal surfaces of the first permanent upper and lower molars. The directional asymmetry values of angular measurements of mandibular first molars showed evidence of asymmetry of opposite direction between the two examined groups. The results indicate that occlusal morphology of first permanent molars may be affected by handedness, and this tendency is most evident in the angular measurements of the mandibular molars. Fluctuating asymmetry did not differ significantly between the examined groups.

Child↗

Conformationally-restricted ligands for the histamine H1 receptor.

Potent H1-antagonistic activity in a series of novel indeno[2,1-c]pyridines and their 4-arylpiperidinol precursors is reported; one compound shows an in vitro activity four times that of the standard mepyramine that it was screened against. Their failure to translate this protection to in vivo tests is discussed.

Animals↗

Proctolin antagonists bind to [(3)H]proctolin binding sites in the locust hindgut.

Proctolin caused dose-dependent (1-200 nM) contraction of the isolated hindgut of S. gregaria which was abolished by [alpha-methyl-L-tyrosine(2)]-proctolin (1 microM). In comparison, cycloproctolin (5 microM) reduced the proctolin maximum response by 41%. Hindgut homogenates contained [(3)H]proctolin binding sites with a K(d) value of 660 nM, a B(max) value of 23.8 pmol/mg protein and a Hill coefficient of 0.934. Cycloproctolin (IC(50,) 220 nM; K(i), 204 nM), unlabeled proctolin (IC(50) 680 nM) and [alpha-methyl-L-tryosine(2)]-proctolin (IC(50) 3.1 microM, K(i), 2.9 microM) but not SchistoFLRFamide (1 nM-10 microM) were capable of displacing bound [(3)H]proctolin.

Animals↗

The Mental Adjustment to Cancer (MAC) scale: replication and refinement in 632 breast cancer patients.

BACKGROUND: Assessment of adjustment of patients in cancer treatment trials is becoming more common and increasingly regarded as a useful outcome measure. The widely used Mental Adjustment to Cancer (MAC) Scale was designed to measure Fighting Spirit (FS), Anxious Preoccupation (AP), Helpless-hopelessness (HH) and Fatalism. METHODS: Questionnaire responses from 632 breast cancer patients were randomly divided into two groups, one for exploratory analyses and possible scale refinement, and the other for validation purposes. RESULTS: Estimates of reliability (Cronbach's alpha) were satisfactory for two scales, FS (alpha = 0.85) and HH (alpha = 0.81), but lower for AP (alpha = 0.65) and Fatalism (alpha = 0.64). Exploratory factor analysis suggested that the MAC Scale might be measuring six independent constructs including two related to Fighting Spirit (Positive Orientation to the Illness, Minimizing the Illness), two related to Fatalism (Fatalism-revised, Loss of Control), a construct we have named Angst, and an unchanged HH construct. Scales developed to measure these constructs were satisfactorily replicated in confirmatory analyses but some reliabilities were lower than desirable. The general structure of the MAC Scale remained little changed despite the division of two scales and the suggested removal of six items. The refined scales correlated with the Hospital Anxiety and Depression scale and the Medical Coping Modes Questionnaire, indicating good concurrent validity. CONCLUSIONS: While reasonable reliability of the original scales persists through analyses of the MAC Scale, the original factor structure could not be reproduced. Six refined constructs with strong construct validity were identified within the overall domain of mental adjustment to cancer.

Adaptation, Psychological↗

BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer.

The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% CI 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence.

Adult↗

Characterization of actions of Leucophaea tachykinin-related peptides (LemTRPs) and proctolin on cockroach hindgut contractions.

The nine Leucophaea Tachykinin-Related Peptides (LemTRP 1-9) isolated from the midgut and brain of the cockroach, Leucophaea maderae, all induced increases in spontaneous contractions of the L. maderae hindgut. Synthetic LemTRP 1 and 3-9, were equally potent in inducing contractions of the hindgut. More than seven of the nine C-terminal residues of the closely related locust peptide locustatachykinin I (LomTK I) are required for full activity of the peptide on the L. maderae hindgut. Proctolin, a well characterized myostimulatory neuropeptide, was shown to be more potent than LemTRPs. LemTRP 1 and proctolin did not have synergistic actions in potentiating the amplitude and tonus of contractions of the L. maderae hindgut. Several differences could be seen in actions of LemTRP 1 and proctolin. In contrast to proctolin, LemTRP 1 could not override the inhibitory action of 10(-9) M of the myoinhibitory peptide leucomyosuppressin. Spantide I, an antagonist of the mammalian tachykinin receptors, at a concentration of 5 microM, blocked the response to LemTRP 1, but not to proctolin. The competitive proctolin receptor antagonist [alpha-methyl-L-tyrosine2]-proctolin blocked the action of both proctolin and LemTRP 1 when applied at 1 microM, whereas cycloproctolin had no antagonist action on either peptide. Verapamil, a blocker of voltage gated Ca2+-channels, and the less specific Ca2+-channel blocker Mn2+, abolished the action of LemTRP 1, but not of proctolin. The results obtained indicate that LemTRPs act on receptors distinct from those of proctolin. Double label immunocytochemistry revealed that all LomTK-like immunoreactive fibers impinge on the proctolinergic fibers in the hindgut. This finding and the inhibitory actions of Ca2+-channel blockers on TRP responses and of the proctolin receptor antagonist on both peptides, may suggest that the LemTRP receptors are not on the hindgut muscle fibers but on the terminals of the proctolinergic neurons. Thus, LemTRPs may induce release of proctolin on the hindgut. An alternative is that LemTRPs act by mechanisms clearly distinct from those of proctolin.

Amino Acid Sequence↗

Maternal smoking and tooth formation in the foetus. III. Thin mandibular incisors and delayed motor development at 1 year of age.

Dental casts from 2159 black and white Americans with detailed neurological data available from the Collaborative Perinatal Study were examined to investigate the relationship of maternal smoking during pregnancy and delayed motor development at 1 year of age to morphological traits in the dentition. Earlier results have indicated that maternal smoking during pregnancy may cause selected tooth size metric reductions in the deciduous dentition and at least in some of the permanent teeth with prenatal crown formation, these features being influenced by sex and race differences. The present results suggest that a thinning of the incisal parts of the permanent mandibular incisors is associated with heavy maternal smoking during pregnancy, and those white girls, in whom this dental variant is found, have probably experienced more severe central damage during the smoking sensitive gestational months, as is also seen in a delayed motor development at the age of 1 year.

Black People↗

Proctolin analogues and a proctolin metabolite as antagonist of the peptide proctolin.

The locust oviduct bioassay was used to assess a variety of proctolin analogues as possible agonists and antagonists of the peptide proctolin. Both [alpha-methyl-L-tyrosine2]proctolin and [N-methyl-L-tyrosine2] proctolin were antagonists of proctolin with thresholds of 5 x 10(-9) M. Interestingly, at these threshold doses the analogues were antagonists when applied along with proctolin, being capable of shifting the dose-response curve for proctolin an order of magnitude to the right. Of the three tripeptides tested Tyr-Arg-Thr and Arg-Tyr-Thr showed no agonistic effects and were incapable of antagonizing proctolin-induced contractions. The third tripeptide, Leu-Pro-Thr, showed minimal agonistic effects and when applied with proctolin, significantly decreased the maximum response and increased the ED50 values of the parent compound. Interestingly, this tripeptide is a degradation product of proctolin. Cycloproctolin possessed no agonistic activity up to 10(-5) M but did antagonize proctolin's response in a dose-dependent manner with 2 x 10(-5) M cycloproctolin shifting the proctolin curve nearly two orders of magnitude to the right. Simultaneous application of 10(-9) M [alpha-methyl-L-tyrosine2]proctolin and 10(-5) M cycloproctolin showed some synergistic effect as the maximum response to the peptide was decreased by 21.6% and the dose-response curve shifted further to the right. These proctolin antagonist will be useful tools for examining the physiological importance of proctolin in insects as well as helping to identify receptor subtypes.

Animals↗

Insect neurotransmission: neurotransmitters and their receptors.

The roles of acetylcholine, dopamine, octopamine, tyramine, 5-hydroxytryptamine, histamine, glutamate, 4-aminobutanoic acid (gamma-aminobutyric acid) and a range of peptides as insect neurotransmitters are evaluated in terms of the criteria used to identify transmitters. Of the biogenic amines considered, there is good evidence that acetylcholine, dopamine, octopamine, 5-hydroxytryptamine, and histamine should be considered to be neurotransmitters, but the case for tyramine is less convincing at the moment. The evidence supporting neurotransmitter roles for glutamate and gamma-aminobutyric acid at specific insect synapses is overwhelming, but much work remains to be undertaken before the full significance of these molecules in the insect nervous system is appreciated. Attempts to characterise biogenic amine and amino acid receptors using pharmacological and molecular biological techniques have revealed considerable differences between mammalian and insect receptors. The number of insect neuropeptides isolated and identified has increased spectacularly in recent years, but genuine physiological or biochemical functions can be assigned to very few of these molecules. Of these, only proctolin fulfills the criteria expected of a neurotransmitter, and the recent discovery of proctolin receptor antagonists should enable the biology of this pentapeptide to be explored fully.

Animals↗

Selective activity of a proctolin analogue reveals the existence of two receptor subtypes.

1. The neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) both potentiates neurally evoked contractions and causes contractures of insect skeletal muscle. In the hindleg extensor tibiae muscle of the locust, Schistocerca gregaria, the proctolin analogue [Afb (p-NO2)2]-proctolin is also able to potentiate neurally evoked contractions but is approximately 1,000-fold less effective in evoking contractures. 2. Proctolin and [Afb (p-NO2)2]-proctolin are equipotent in their ability to elevate the second-messenger inositol trisphosphate in isolated extensor tibiae muscle fiber membranes. 3. [Afb (p-NO2)2]-proctolin is approximately 1,000-fold less effective than proctolin in reducing the resting potassium conductance (GK) in extensor tibiae fibers. 4. We conclude that the action of proctolin on the extensor tibiae muscle is mediated by at least two receptor subtypes and that [Afb (p-NO2)2]-proctolin acts selectively on the receptor that potentiates neurally evoked contractions.

Animals↗

Maternal smoking and tooth formation in the foetus. II. Tooth crown size in the permanent dentition.

Altogether 2159 pregnancies among black and white Americans in the Collaborative Perinatal Study and dental casts from their children at the age of 6-12 years were studied to determine the effect of maternal smoking on permanent tooth crown dimensions. A trend of reduction, similar to that observed in the deciduous second molars, was found in the permanent first molars and also in the mesio-distal dimension of permanent incisors in relation to sex and race of the children and smoking habits of the mother. In terms of peak in their mitotic growth, the results can be interpreted to indicate a sensitive period of intra uterine development from the 24th to 28th gestational weeks. Comparisons of postnatal body size and differential correlation patterns in affected tooth dimensions with early postnatal body and head size between smokers and non-smokers, suggests that maternal smoking during pregnancy may have an effect on basic growth of the head and body and/or the developmental process that impacts tooth development at some specific sensitive period also during the postnatal formation of these tooth crowns.

Birth Weight↗