Biomedical subjects

G Burton

Publications and source records attributed to G Burton.

At least 19 recordsLinked to original sources

PubMed2006

Placental morphology: from molecule to mother -- a dedication to Peter Kaufmann -- a review.

Theories on the development of placental pathologies and insufficiencies are based on the assumption that the development of the placental villous trees, the invasion of extravillous trophoblast or the differentiation of the villous trophoblast is somehow dysregulated. One of the pioneers trying to answer these questions is Peter Kaufmann, who started research on the placenta nearly 40 years ago. In this review, we try to shed light on various aspects of placental development, and on how important morphology is in combination with other disciplines to elucidate the differences between a normal and a pathological placenta.

Female↗

PubMed2006

Regulation of placental efficiency for nutrient transport by imprinted genes.

Intrauterine growth and development can impact upon the long-term health of an individual. The fetus is dependent upon the placenta for its supply of nutrients and oxygen from the mother. In turn, the functional capacity of the placenta to supply that demand is under the control of the fetal and maternal genomes. Recent evidence suggests that imprinted genes, a class of genes found in placental mammals whose expression depends on their parental origin, have multiple roles in the placenta. The imprinted genes regulate the growth and transport capacity of the placenta, thereby controlling the supply of nutrients. They may also regulate the growth rate of fetal tissues directly, thereby controlling nutrient demand by the fetus. Recent studies using mice with deletions or disruption of imprinted genes with an altered balance between placental and fetal growth and changes in placental efficiency are indicative of feto-placental signalling of fetal nutrient demand. We propose that signalling mechanisms involving growth demand signals and nutrient transporters are likely to occur and are important for fine tuning normal fetal growth.

Animals↗

PubMed2005

The role of preimplantation genetic diagnosis in the management of severe rhesus alloimmunization: first unaffected pregnancy: case report.

Rhesus (Rh) D alloimmunization may cause haemolytic disease of the fetus and newborn if the fetal Rh blood type is positive. Although the incidence of severe RhD alloimmunization has decreased with prophylactic anti-D immunoglobulin administration during and after pregnancy, sensitization still occurs in a small group of women. In such women, Rh disease will continue to be significant problem and for their babies who may be affected. Preimplantation genetic diagnosis (PGD) may be utilized to avoid materno-fetal blood group incompatibility in an RhD-sensitized woman. Biopsy of a single cell from early cleavage-stage embryos screening for RhD-negative embryos allows the transfer of only RhD-negative embryo(s) into the uterus. This avoids any complications related to haemolytic disease of the fetus and newborn. This article describes the first reported case of an unaffected pregnancy using PGD for Rh disease. IVF and embryo transfer resulted in a clinical pregnancy and the birth of a healthy girl confirmed to be blood type RhD negative. PGD in couples with a heterozygous RhD-positive male partner provides an option for avoiding haemolytic disease of the newborn in RhD alloimmunized mothers.

Adult↗

PubMed2004

Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of pregnanesteroids.

The mineralocorticoid receptor (MR) is primarily localized in the cytoplasm of the cell in the absence of ligand. The first step in the genomic-dependent mechanism of action of mineralocorticoids is the binding of steroid to the MR, which in turn triggers MR nuclear translocation. The regulation of hormone-binding to MR is complex and involves a multifactorial mechanism, making it difficult to determine the optimal structure of a steroid for activating the MR and promoting its nuclear translocation. Here we review the structure-activity relationship for several pregnanesteroids that possess various functional groups, and suggest that a flat conformation of the ligand rather than the presence of particular chemical groups is a critical parameter for the final biological effect in vivo. We also discuss how the MR undergoes differential conformational changes according to the nature of the bound ligand, which in turn affects the dynein-dependent retrograde rate of movement for the steroid/receptor complex.

Active Transport, Cell Nucleus↗

PubMed2004

Efficacy of cyclosporin in the treatment of atopic dermatitis in dogs--combined results from two veterinary dermatology referral centres.

OBJECTIVE: To evaluate the efficacy of cyclosporin in controlling the clinical signs associated with atopic dermatitis in dogs under Australian field conditions. DESIGN: A multicentre prospective clinical investigation of the use of cyclosporin in 41 dogs with atopic dermatitis. PROCEDURE: Dogs were treated with cyclosporin (5 mg/kg orally once daily with food) for 6 weeks. Four clinical parameters of severity of atopic dermatitis were measured on Day 0 and on Day 42 using a 0 to 4 scoring system. Individual variables were then combined to form a Global Score. Both client and clinician observed pruritus scores were combined to form a Pruritus Score. Pre- and post-treatment scores were statistically analysed. The difference in results between the two investigators was also recorded and analysed. RESULTS: All dogs showed a marked reduction in pruritus and erythema during the 6-week treatment period. All dogs showed a significant (P < 0.001) improvement in clinical lesion scores and Global Score (P < 0.001). The mean percentage improvement in Global Score from Day 0 to Day 42 was 83.9%. The mean percentage improvement in Pruritus Score from Day 0 to Day 42 was 83%. The medication was well tolerated. Side effects such as vomiting, diarrhoea and soft stools were observed in four dogs. Another four dogs developed bacterial pyoderma during the trial period. There was no significant difference in results between the two centres. CONCLUSION: Cyclosporin was well tolerated and efficacious in the symptomatic treatment of atopic dermatitis in dogs attending two veterinary dermatology referral centres in Australia, under Australian field conditions, when administered at 5 mg/kg/day for 6 weeks.

Administration, Oral↗

PubMed2003

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy.

PURPOSE: This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant ('Faslodex'). PATIENTS AND METHODS: A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting > or = 24 weeks, or disease progression. RESULTS: Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in > 80% of patients. CONCLUSIONS: After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required.

Adult↗

PubMed2002

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment. PATIENTS AND METHODS: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability. RESULTS: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P =.43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease > or = 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%; P =.26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole; the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated. CONCLUSION: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.

Adult↗

PubMed2001

Preparation and cytotoxicity toward cancer cells of mono(arylimino) derivatives of beta-lapachone.

A regio- and stereospecific synthesis of monoarylimino o-quinones derived from beta-lapachone (1) was achieved by treatment of the quinone with a slight excess of an arylamine in the presence of an excess of triethylamine/titanium tetrachloride 4:1. Imine formation occurred exclusively at position 6, giving the Z diastereomer, as determined by single-crystal X-ray analysis. In vitro tests for cytotoxicity in 55 human cancer cell cultures showed a substantial loss in activity for the p-nitrophenylimine (5), whereas the phenylimine (2), p-methylphenylimine (3), and p-methoxyphenylimine (4) retained (or bettered) most of the cytotoxicity and selectivity of the parent quinone. Preliminary in vivo testing in hollow fiber assays against a standard panel of 12 human tumor cell lines showed that although beta-lapachone failed, compounds 2 and 3 had good scores with net cell kills.

Antineoplastic Agents↗

PubMed2001

Withanolides from Salpichroa origanifolia.

Five new withanolides, 5 alpha,6 alpha:22,26:24,25-triepoxy-16 alpha,26-dihydroxy-18(13-->17)-abeo-ergosta-2,13-dien-1-one (salpichrolide N, 1), 5 alpha,6 alpha:22,26:24,25-triepoxi-15 alpha,26-dihydroxyergosta-2,16-dien-1-one (salpichrolide L, 2), 5 alpha,6 alpha:22,26-diepoxi-24,25,26-trihydroxy-17(13-->18)-abeo-ergosta-2,13,15,17-tetraen-1-one (salpichrolide M, 3a), 5 alpha,6 alpha:22,25:22,26-triepoxy-24-hydroxy-17(13-->18)-abeo-ergosta-2,13,15,17-tetraen-1-one (salpichrolide J, 4), and 5 alpha,6 alpha:22,26-diepoxy-22,24,25-trihydroxy-17(13-->18)-abeo-ergosta-2,13,15,17-tetraen-1-one (salpichrolide K, 5), were isolated from the leaves of Salpichroa origanifolia and characterized by a combination of spectroscopic (1D and 2D NMR, MS) and chemical methods.

Argentina↗

PubMed2001

Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks' gestation.

OBJECTIVE: Our purpose was to evaluate the changes in intrauterine gases and acid-base gradients inside the human fetoplacental unit at 7 to 16 weeks' gestation. STUDY DESIGN: Respiratory gases and acid-base values were recorded by means of a multiparameter sensor and samples from inside the exocoelomic or amniotic cavity, placental tissue, decidua, and fetal blood of 30 early pregnancies. RESULTS: Before 11 weeks' gestation, placental PO(2) was 2.5 times lower than decidual PO(2). The PO(2) increased independently at both sites during gestation, but a PO(2) gradient of 13.3 mm Hg persisted during the fourth month. At 13 to 16 weeks, PO(2), oxygen saturation, and oxygen content gradients were observed between the fetal blood and the placenta and between the placenta and underlying decidual tissue. There was no fetoplacental gradient for pH and PCO(2) between 7 and 16 weeks, but fetal blood pH values were much lower and fetal PCO(2) values were much higher than those reported in older fetuses. CONCLUSIONS: Early human placental tissue develops in a physiologically low-oxygen environment compared with uterine tissue. This may be necessary to allow specific placental metabolic activities and to protect both placental and fetal tissues against toxic oxygen metabolites.

Acid-Base Equilibrium↗

PubMed2001

Breast cancer: a socioeconomic and racial comparison in northwest Louisiana.

A tumor registry data review on breast cancer populations seen at two hospitals in North Louisiana was completed in order to determine if race is independent of socioeconomic status (SES) factors related to breast cancer stage at diagnosis. The North Louisiana tumor registry identified 1183 patients diagnosed with breast cancer between 1987 and 1991, 304 patients from Louisiana State University Health Science Center (LSUHSC), a state supported hospital providing predominantly indigent care, and 879 patients from a private hospital (PH) serving predominantly insured patients. Hospital site was used as a proxy for SES (LSUHSC low, PH high). The patient populations differed significantly by age, racial makeup, and stage at presentation. Both white and African-American patients seen at PH had more stage 0 disease compared with LSUHSC (9.2% and 2.7%). White patients seen at PH had more stage I cancer as compared to white patients at LSUHSC (31.3% and 19.2%) or African-American patients at either PH or LSUHSC (19.4% and 19.9%). The frequency of stage III/IV cancer was higher in African-American patients at both LSUHSC (30.1%) and PH (29.0%) and white patients at LSUHSC (24.0%) as compared to white patients at PH (14.7%). Two hundred and nine patients were available for individual interview and specific definition of SES. LSUHSC patients were predominantly indigent (83% indigent and without insurance), while only 10% of PH patients lacked insurance. This study provides further support that the SES of white patients influences breast cancer stage at presentation. African-American patients, however, presented with more advanced breast cancer stages regardless of SES. Factors influencing African-American patient's disease stage are not limited to defined SES factors. Further studies are needed to define barriers and develop intervention strategies.

Breast Neoplasms↗

PubMed2000

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group.

PURPOSE: The efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women. PATIENTS AND METHODS: The randomized, double-blind, multicenter study was designed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor-positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy. Primary end points were objective response (OR), defined as complete (CR) or partial (PR) response, time to progression (TTP), and tolerability. RESULTS: Anastrozole was as effective as tamoxifen in terms of OR (21% v 17% of patients, respectively), with clinical benefit (CR + PR + stabilization > or = 24 weeks) observed in 59% of patients on anastrozole and 46% on tamoxifen (two-sided P =.0098, retrospective analysis). Anastrozole had a significant advantage over tamoxifen in terms of TTP (median TTP of 11.1 and 5.6 months for anastrozole and tamoxifen, respectively; two-sided P =.005). The tamoxifen:anastrozole hazards ratio was 1.44 (lower one-sided 95% confidence limit, 1.16). Both treatments were well tolerated. However, thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen (4.1% v 8.2% [thromboembolic events] and 1.2% v 3.8% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer.

Adult↗

PubMed2000

Metal mediated protease inhibition: design and synthesis of inhibitors of the human cytomegalovirus (hCMV) protease.

A versatile synthetic route to a novel series of bis-imidazolemethanes designed to inhibit the hCMV protease has been developed and a series of potential metal binding inhibitors has been identified. In selectivity assays, the compounds were highly specific for CMV protease and showed no inhibition (IC50 > 100 microM) of other prototypical serine proteases such as trypsin, elastase, and chymotrypsin. Although the presence of free zinc ions was found to be an absolute requirement for the in vitro biological activity of this class of inhibitor, the potency of the inhibitors could not be improved beyond the micromolar level.

Chymotrypsin↗

PubMed2000

Sesquiterpene lactone variability in Parthenium hysterophorus L.

A population of Parthenium hysterophorus collected in Salta Argentina afforded two ambrosanolides, 2beta-hydroxycoronopilin and 1alpha,2beta,4beta-trihydroxypseudoguaian-6beta,12-olide, as well as five known others. Plants of the fructification from those transplanted from the Puna Argentina at 1200 m over the sea level produced hymenin.

Asteraceae↗

PubMed2000

Synthesis and GABA(A) receptor activity of 6-oxa-analogs of neurosteroids.

The 6-oxasteroids 3alpha-hydroxy-6-oxa-5alpha-pregnan-20-one (3) and 3alpha-hydroxy-6-oxa-5beta-pregnan-20-one (4) were obtained from pregnenolone acetate via the corresponding (5alpha or 5beta) 3beta, 20beta-diacetoxy-6-oxa-pregnane. Both steroids showed ca. 100-fold reduced potency for modulating [(3)H]flunitrazepam, [(3)H]muscimol or [(35)S]TBPS binding to the GABA(A) receptor when compared to their natural carbon analogs 3alpha-hydroxy-5alpha-pregnan-20-one (1) and 3alpha-hydroxy-5beta-pregnan-20-one (2).

Animals↗

PubMed2000

Withanolides from Vassobia lorentzii.

Eight new withanolides were isolated from the aerial parts of Vassobia lorentzii and characterized by spectroscopic methods and with the aid of molecular modeling. The compounds were identified as (17S,20R,22R)-5beta,6beta:18,20-diepoxy-18-hydro xy-1-oxowitha-2,5, 24-trienolide (1); (17S,20R,22R)-18,20-epoxy-4beta, 18-dihydroxy-1-oxowitha-2,5,24-trienolide (2); (17S,18R,20R, 22R)-4beta-hydroxy-18,20-epoxy-18-methoxy-1-oxowitha-2,5, 24-trienolide (3); (17S,18S,20R,22R)-4beta-hydroxy-18, 20-epoxy-18-methoxy-1-oxowitha-2,5,24-trienolide (4); (17S,20R, 22R)-4beta-hydroxy-18,20-epoxy-1,18-dioxowitha-2,5,24-tri enolide (5); (17S,18R,20R,22R)-18,20-epoxy-18-methoxy-1,4-dioxowitha++ +-2,5, 24-trienolide (6); (17S,18S,20R,22R)-18,20-epoxy-18-methoxy-1, 4-dioxowitha-2,5,24-trienolide (7); and (17S,20R,22R)-5beta, 6beta-epoxy-4beta,18,20-trihydroxy-1-oxowitha-2,24-die nolide (8). Compounds 1 and 2 were obtained as epimeric mixtures at C-18.

Animals↗

PubMed2000

Antifeedant activity of withanolides from Salpichroa origanifolia on Musca domestica.

The antifeedant effect of several salpichrolides on larvae of Musca domestica was investigated. Three naturally occurring compounds, salpichrolide A (1), salpichrolide C (2), and salpichrolide G (3), previously isolated from Salpichroa origanifolia, and two known (4, 6) and three new (5, 7, 8) synthetic analogues were tested. The maximal effect on development was observed for salpichrolide A (1), while salpichrolide G (3) was the most toxic. The content of the salpichrolides in S. origanifolia was monitored by HPLC during plant development, reaching a maximum during summer.

Animals↗

PubMed2000

The role of the sound of tapping for nonvisual judgment of gap crossability.

The author investigated the possibility that nonvisual locomotion with a cane depends on the sound of the cane tapping. Blindfolded participants were asked to judge whether a gap in front of them could be crossed by walking. An acoustic analysis suggested that sound could, in theory, distinguish the gaps. Blindfolded sighted participants in Experiments 1 and 2 judged crossability under conditions in which only the sound of tapping was available and in which the sound was minimized; the third and fourth experiments included experienced cane users. Both inexperienced observers and experienced cane users were unaffected by sound reduction and were less able to discriminate gaps when using sound only than when using reduced sound. A fifth experiment indicated that active-passive differences were not responsible for these effects. Results indicate that sound is not necessary or sufficient for judging nonvisible crossability with a probe.

Auditory Perception↗