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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 325 records · Page 18Linked to original sources
PubMed1997

Factors influencing views of patients with gynecologic cancer about end-of-life decisions.

OBJECTIVE: This study was undertaken to assess the life views, practices, values, and aspirations of women with various stages of gynecologic cancer. STUDY DESIGN: A self-administered questionnaire was completed by 108 women with various stages of cancer and 39 women with benign gynecologic disease. The questionnaire included items on demographics in addition to 16 multiple choice and 4 true-false items. The four questions related to criteria of good care, degree of involvement in decision making, psychosocial well-being, religious experience, and aspirations form the basis of this study. The data were analyzed with the Pearson chi 2 test (Systat, version 5.1) with significance set at p < 0.05. RESULTS: The women in this study placed greatest emphasis on receiving "straight talk" (96%) and compassion (64%) from their physicians. The newly diagnosed group put significantly less emphasis on compassion (33%, p = 0.037). Less than half expected their physicians to cure (43%, 56% for newly diagnosed) or contain (49%) the disease. For these women fear was the most dominant psychosocial consequence of having cancer, with difficulty communicating or feeling abandoned, isolated, or embarrassed less common. Those who specified their ears were afraid of pain (63% vs 39% for patients with benign disease, p = 0.019), dying (56%), losing control (48%), or becoming totally dependent (46%). Seventy-six percent indicated that religion had a serious place in their lives, with 49% becoming more religious since their cancer diagnosis, whereas no one became less religious. Ninety-three percent believed that the religious commitment helped sustain their hopes. CONCLUSIONS: These data suggest that (1) physicians should aim to educate their patients sufficiently for them to exercise control over their experience, to allay their fears, and to make personal decisions that further their aspirations, (2) patients in different stages of disease varied in their perceptions of themselves and their aspirations, (3) patients are dealing with fear as a primary problem, and (4) women with gynecologic cancer depend on their religious convictions and experiences as they cope with the disease.

Adult↗
PubMed1997

Prostaglandin F2alpha-induced nest-building in pseudopregnant pigs. II. Space restriction stress does not influence secretion of oxytocin, prolactin, oestradiol or progesterone.

We have previously shown that prostaglandin F2alpha (PG) is capable of inducing nest-building behaviour in pseudopregnant gilts and established a protocol. This experiment examined which reproductive endocrine systems might mediate these behavioural responses, in the presence or absence of a space restriction stress. Pseudopregnancy was induced with 5 mg/day i.m. (intramuscular) injections of oestradiol valerate (OV) on Days 11-15 of the oestrous cycle, jugular vein catheters were placed on Day 39 of pseudopregnancy, and blood samples were collected daily from Day 40 to Day 48. On Day 42, gilts were either space restricted to farrowing crates 1.6 x 0.6 m (C: n = 11) or left in pens 2.8 x 1.74 m (P: n = 11). On Day 47, blood samples were collected from all animals every 15 min from 90 min prior to a single i.m. injection of 15 mg of prostaglandin F2alpha (PG: Lutalyse, Upjohn, Crowley, West Sussex) to 120 min post-PG and then hourly for 4 h and assayed for oxytocin, prolactin, progesterone, and oestradiol. Results showed that mean daily concentrations of prolactin and progesterone were significantly lower (p < 0.05 respectively) in C than P gilts from Day 42 to Day 46 of pseudopregnancy. There were no significant differences in mean daily concentrations of oxytocin and oestradiol between C and P gilts during this time. For both groups, oxytocin, prolactin, and progesterone concentrations increased significantly (p < 0.05) post-PG when compared to their respective pre-PG values. However, for both groups, oestradiol concentrations were unaffected by PG injection. The prostaglandin-induced increases in oxytocin, prolactin, and progesterone concentrations did not differ between groups. We conclude that coincident changes in oestradiol secretion does not influence nesting behaviour and that space restriction stress associated with nest-building does not influence secretion of oxytocin, prolactin, oestradiol, or progesterone.

Animals↗
PubMed1997

Prostaglandin F2alpha-induced nest-building in pseudopregnant pigs. I. Effects of environment on behaviour and cortisol secretion.

Pigs may be susceptible to stress when they are strongly motivated to nest-build in a space-restricted environment. This study aimed to explore whether nest-building behaviour could be induced by prostaglandin F2alpha (PG) administration to pseudopregnant gilts and to determine whether induced behaviour and cortisol output differed between animals chronically placed in either farrowing crates or pens. Jugular vein catheters were placed on Day 39 of pseudopregnancy and blood samples collected daily from Day 40 to Day 48. On Day 42, gilts were either restricted to farrowing crates 1.6 x 0.6 m with no straw (C: n = 11) or left in pens 2.8 x 1.74 m with straw (P: n = 11). On Day 47, blood and behaviour sampling was from 90 min pre-PG (Dinoprost; Lutalyse, Upjohn, Kalamazoo, MI) to 6 h post-PG. PG injection successfully induced nest-building behaviour in P gilts within 15 min of injection. Penned gilts engaged in more straw/floor-directed behaviour than C gilts (p < 0.01), whereas attempts in C gilts seemed partial or incomplete. Conversely, C gilts showed increased (p < 0.05) amounts of fixture-directed behaviour, whereas P gilts did not post-PG. For both groups, cortisol increased significantly (p < 0.05) post-PG compared to pre-PG values. Cortisol concentrations in C gilts were significantly greater than in P gilts prior to and after PG (p < 0.05) on Day 47, whereas there were no significant differences in concentrations of cortisol between C and P on other days. These results demonstrate that PG can induce nest-building behaviour in the absence of foetal signals. Whereas the pseudopregnant gilt seemed to chronically adapt to the imposition of a farrowing crate, gilts subsequently attempting to nest-build showed increases in cortisol output when compared to their penned counterparts, suggesting that a stress was imposed by the space-restricted environment.

Animals↗
PubMed1997

Mixed D2/5-HT2 antagonism differentially affects apomorphine- and amphetamine-induced stereotyped behavior.

Evidence supports the hypothesis that psychostimulant stereotypy is mediated through postsynaptic dopamine receptors. Given the recent findings of behavioral, neurochemical and electrophysiological studies showing 5-HT2 modulation of dopamine systems, a series of experiments were undertaken to assess the ability of D2 and 5-HT2 antagonists to reverse apomorphine and amphetamine stereotypy in the rat. Haloperidol reduced stereotyped behavior induced by d-amphetamine (50% reduction with 0.162 mg/kg) and apomorphine (50% reduction with 0.112 mg/kg) MDL 28,133A, a mixed D2/5-HT2 antagonist, also reduced stereotypy in the apomorphine group (50% reduction with 3.89 mg/kg) but was much less effective in antagonizing the effects of d-amphetamine (not even a 25% reduction with 9.0 mg/kg). MDL 100,907, a selective 5-HT2 antagonist, was ineffective at reducing stereotyped behavior induced by either stimulant. Thus, 5-HT2 modulation of dopaminergic activity was not demonstrated in the case of psychostimulant stereotypy. Furthermore, 5-HT2 antagonism did not induce stereotypy, as has been proposed in some models. These findings provide further support for the hypothesis that antipsychotic medications with high affinity for 5-HT2 receptors do not interfere with the regulation of the nigrostriatal dopaminergic system and, therefore, would be less likely to produce extrapyramidal side effects.

Amphetamine↗
PubMed1997

Long-chain polyunsaturated fatty acid transport across the perfused human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentae (n = 9) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids and ratio of fatty acid to human albumin. There was no evidence of chain elongation and desaturation of the essential fatty acids. Relative to the value for oleic acid, the rate of transfer to the fetal circulation was: 1.30 +/- 0.02 (P < 0.001) for linoleic acid, 1.61 +/- 0.09 (P = 0.002) for alpha-linolenic acid, 0.67 +/- 0.10 (P = 0.033) for arachidonic acid and 2.10 +/- 0.16 (P = 0.003) for docosahexaenoic acid. For tissue accumulation the values were 1.47 +/- 0.39 (P < 0.001) for linoleic acid, 2.24 +/- 0.37 (P = 0.027) for alpha-linolenic acid, 9.84 +/- 1.03 (P = 0.001) for arachidonic acid, and 3.01 +/- 0.79 (P = 0.064) for docosahexaenoic acid. The order of selectivity for transfer from the maternal to the fetal circulation was docosahexaenoic > alpha-linolenic > linoleic > oleic > arachidonic acid. Such a mechanism would allow the preferential transfer of docosahexaenoic acid and the essential fatty acids to the fetal circulation, thereby protecting the polyunsaturated fatty acid supply to the fetus during a critical period of development.

Adult↗
PubMed1997

Localization of pH regulating proteins H+ATPase and Cl-/HCO3- exchanger in the guinea pig inner ear.

Mechanisms that regulate endolymphatic pH are unknown. It has long been recognized that, because of the large positive endolymphatic potential in the cochlea, a passive movement of protons would be directed out of endolymph leading to endolymphatic alkalization. However, endolymphatic pH is close to that of blood, suggesting that H+ is being secreted into endolymph. Since the kidney and the inner ear are both actively engaged in fluid and electrolyte regulation, we attempted to determine whether proteins responsible for acid secretion in the kidney also exist in the guinea pig inner ear. To that end, a monoclonal antibody against a 31 kDa subunit of a vacuolar vH+ATPase and a polyclonal, affinity purified antibody against the AE2 Cl-/HCO3- exchanger (which can also recognize AE1 under some conditions) were used. In the cochlea, the strongest immunoreactivity for the vH+ATPase was found in apical plasma membranes and apical cytoplasm of strial marginal cells. These cells were negative for the Cl-/HCO3- exchanger. Certain cells of the inner ear demonstrated both apical staining for vH+ATPase and basolateral staining for the Cl-/HCO3- exchanger; these included interdental cells and epithelial cells of the endolymphatic sac. Cochlear cell types with diffuse cytoplasmic staining for vH+ATPase and a basolaterally localized Cl-/HCO3- exchanger included inner hair cells, root cells and a subset of supporting cells in the organ of Corti. Hair cells of the utricle, saccule and cristae ampullaris also expressed both vH+ATPase and the Cl-/HCO3- exchanger, but immunostaining for the vH+ATPase was less intense and less polarized than in the cochlea. These immunocytochemical results support a role for the vH+ATPase and Cl-/HCO3- exchanger in the regulation of endolymphatic pH and suggest that certain cells (including strial marginal cells and epithelial cells of the endolymphatic sac) may be specialized for this regulation.

Animals↗
PubMed1997

The in vivo and in vitro characterisation of an engineered human antibody to E-selectin.

BACKGROUND: E-selectin is an endothelial cell specific adhesion molecule that is believed to play an important role in the early stages of leukocyte extravasation. OBJECTIVES: Here we describe the construction and evaluation of an engineered human monoclonal antibody that blocks E-selectin function. RESULTS: SPLAT-1 is an engineered human monoclonal antibody that has a very similar affinity for E-selectin as its murine parent antibody. In vitro SPLAT-1 blocks the binding of human leukocytes to E-selectin and does not mediate antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated lysis of endothelial cells. In vivo, SPLAT-1 inhibits the recruitment of leukocytes to cytokine-inflamed human skin grafted on to SCID mice and has a long circulating half-life in primates. It does not appear to provoke an immune response in primates even on repeat administration. CONCLUSIONS: SPLAT-1 has the characteristics of a antibody suitable for human therapy studies.

Animals↗
PubMed1997

Regulation of AE1 anion exchanger and H(+)-ATPase in rat cortex by acute metabolic acidosis and alkalosis.

The cortical collecting duct (CCD) mediates net secretion or reabsorption of protons according to systemic acid/base status. Using indirect immunofluorescence, we examined the localization and abundance of the vacuolar H(+)-ATPase and the AE1 anion exchanger in intercalated cells (IC) of rat kidney connecting segment (CNT) and CCD during acute (6 hr) metabolic (NH4Cl) acidosis and respiratory (NaHCO3) alkalosis. AE1 immunostaining intensity quantified by confocal microscopy was elevated in metabolic acidosis and substantially reduced in metabolic alkalosis. AE1 immunostaining was restricted to Type A IC in all conditions, and the fraction of AE1+IC was unchanged in CNT and CCd. Metabolic acidosis was accompanied by redistribution of H(+)-ATPase immunostaining towards the apical surface of IC, and metabolic alkalosis was accompanied by H(+)-ATPase redistribution towards the basal surface of IC. Therefore, acute metabolic acidosis produced changes consistent with increased activity of Type A IC and decreased activity of Type B IC, whereas acute metabolic alkalosis produced changes corresponding to increased activity of Type B IC and decreased activity of Type A IC. These data demonstrate that acute systemic acidosis and alkalosis modulate the cellular distribution of two key transporters involved in proton secretion in the distal nephron.

Acid-Base Equilibrium↗
PubMed1997

Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND.

dHAND and eHAND are related basic helix-loop-helix (bHLH) transcription factors that are expressed in mesodermal and neural crest-derived structures of the developing heart. In contrast to their homogeneous expression during avian cardiogenesis, during mouse heart development we show that dHAND and eHAND are expressed in a complementary fashion and are restricted to segments of the heart tube fated to form the right and left ventricles, respectively. dHAND and eHAND represent the earliest cardiac chamber-specific transcription factors yet identified. Targeted gene deletion of dHAND in mouse embryos resulted in embryonic lethality at embryonic day 10.5 from heart failure. Our description of the cardiac phenotype of dHAND mutant embryos is the first demonstration of a single gene controlling the formation of the mesodermally derived right ventricle and the neural crest-derived aortic arches and reveals a novel cardiogenic subprogramme for right ventricular development.

Animals↗
PubMed1997

Labour force participation and employment among a sample of Australian patients with a spinal cord injury.

This study examined the employment achievements of 219 spinal cord injured people and attempted to identify predictors which, individually and in combination, (a) discriminated between those who were in the labour force or not, and (b) correlated with the amount of time in employment post injury. Results indicated that at the time of the survey 26% were in full-time work, 11% were in part-time work, 4% were unemployed and 59% were not actively seeking work. Multivariate analyses identified three variables (impairment type, study since injury, level of pre-injury secondary schooling) which were related to both labour force participation and the amount of work undertaken post-injury. These results are discussed with reference to post-injury services that could be offered to spinal cord injury people who wish to return to work or gain employment.

Adolescent↗
PubMed1997

The origins and significance of pulsatility in hormone secretion from the pituitary.

In this review we first consider what information is carried by the activity of oxytocin cells. For these, as for many neuroendocrine neurones, synchronized bursting activity leading to pulsatile secretion is particularly important, and we consider possible mechanisms by which bursting may arise, and the role of intrinsic cell properties. Vasopressin cells also show a type of bursting behaviour, but their activity is not synchronized. We show how the behaviour of vasopressin cells fits a very simple dynamical systems model. Even structurally simple dynamical systems models can be computationally complex, with a rich repertoire of behaviour, and we show how the vasopressin cell model can be adapted and expanded to model the LHRH pulse generator network, and how the pituitary responsiveness to hypothalamic releasing factors may also be modelled with a different class of dynamical systems model.

Animals↗
PubMed1997

Absence of anti-envelope antibodies and clearance of hepatitis C virus in a cohort of Irish women infected in 1977.

The presence or absence of antibodies to the second envelope protein (anti-E2) of hepatitis C virus (HCV) was determined in stored sera taken from a cohort of 87 Irish women with antibodies to HCV (anti-HCV) who were all infected by HCV genotype 1b from contaminated anti-D immunoglobulin given in 1977. Anti-E2 was found in 16 patients (100%) who were HCV RNA positive but only in 31 of 50 patients (62%) who were HCV antibody positive by recombinant immunoblot assay (RIBA) but HCV RNA negative. In the remaining 21 sera taken from women who had indeterminate recombinant immunoblot assays and who were repeatedly negative on testing for HCV RNA, anti-E2 was found in only three cases (14%). This suggests that loss or absence of anti-E2 may be useful in confirming clearance of HCV.

Cohort Studies↗
PubMed1997

Long-term evolution of the 5'UTR and a region of NS4 containing a CTL epitope of hepatitis C virus in two haemophilic patients.

Haemophilic patients exposed to unsterilized clotting factor concentrates prior to 1985 have become infected with hepatitis C virus (HCV). We have studied the sequence evolution of the 5'UTR and a region of NS4 over 12 years in one human immunodeficiency virus (HIV) positive haemophilic patient and 14 years for one HIV negative haemophilic patient. One sample each year from the date of HCV infection to 1994 was analysed for genotype, virus load and nucleotide sequence of the two genetic loci. Both patients were infected with HCV genotype 1 throughout the study period. The virus load profiles were similar except that the profile for the HIV infected patient was displaced 4 years earlier relative to the other patient. Mean divergence of the quasispecies at both the 5'UTR and NS4 loci was higher in the HIV coinfected patient. Phylogenetic analysis indicated that evolution of the 5'UTR was host independent, whereas the NS4 region containing a CD8 restricted CTL epitope evolved in a host specific fashion.

Amino Acid Sequence↗
PubMed1997

Reduced naphthylphthalamic acid binding in the tir3 mutant of Arabidopsis is associated with a reduction in polar auxin transport and diverse morphological defects.

Polar auxin transport plays a key role in the regulation of plant growth and development. To identify genes involved in this process, we have developed a genetic procedure to screen for mutants of Arabidopsis that are altered in their response to auxin transport inhibitors. We recovered a total of 16 independent mutants that defined seven genes, called TRANSPORT INHIBITOR RESPONSE (TIR) genes. Recessive mutations in one of these genes, TIR3, result in altered responses to transport inhibitors, a reduction in polar auxin transport, and a variety of morphological defects that can be ascribed to changes in indole-3-acetic acid distribution. Most dramatically, tir3 seedlings are strongly deficient in lateral root production, a process that is known to depend on polar auxin transport from the shoot into the root. In addition, tir3 plants display a reduction in apical dominance as well as decreased elongation of siliques, pedicels, roots, and the inflorescence. Biochemical studies indicate that tir3 plants have a reduced number of N-1-naphthylphthalamic (NPA) binding sites, suggesting that the TIR3 gene is required for expression, localization, or stabilization of the NPA binding protein (NBP). Alternatively, the TIR3 gene may encode the NBP. Because the tir3 mutants have a substantial defect in NPA binding, their phenotype provides genetic evidence for a role for the NBP in plant growth and development.

Arabidopsis↗
PubMed1997

Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes.

AIMS/BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours, but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to determine whether telomerase expression is useful for the detection of occult malignant cells in lymph nodes. METHODS: Telomerase activity was compared with histological findings in 123 surgically removed lymph nodes submitted for routine or frozen section diagnosis. Telomerase activity was measured using a modified, semi-quantitative PCR-based telomeric repeat amplification protocol (TRAP). The assay was adapted for single 5 microns OCT embedded cryostat sections. In either fresh tissues or cryostat sections, normalised activity was linear when compared with protein concentration. Furthermore, using an in situ hybridisation method, the human telomerase RNA (hTR) component was measured in a subset of negative and positive nodes. RESULTS: Most (96%) of the 97 histologically negative nodes expressed low levels of activity (mean value of positive samples = 3.0 units/microgram protein) which may be derived from activated lymphocytes that express telomerase activity. All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean value = 17.8 units/microgram protein). The rank order levels between the two groups differed significantly (p = 0.0002). In situ results showed clearly that the hTR was expressed relatively highly in metastatic cancer cells and at lower levels in germinal centres of secondary follicles. CONCLUSIONS: Although expression of telomerase by activated lymphocytes may limit its usefulness, measurement of enzyme activity combined with detection of hTR using in situ hybridisation may assist in the histopathological diagnosis of lymph nodes.

Frozen Sections↗
PubMed1997

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos.

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.

Adult↗