Search PubMed⌕ Search

Biomedical subjects

S Gauthier

Publications and source records attributed to S Gauthier.

At least 235 records · Page 13Linked to original sources
PubMed1977

Purification and properties of a 3'-phosphoryl former endodeoxyribonuclease from eggs of Asterias forbesi.

A DNA endonuclease has been purified from eggs of Asterias forbesi by a simple four-step-purification procedure. The purified enzyme is at least 96% pure and is free of phosphatase, phosphodiesterase, and RNase. It has a pH optimum of 6.5 and does not require divalent cations. The enzyme produces 3'-phosphoryl and 5'-hydroxyl end groups. The products of exhaustive hydrolysis can be grouped in two fractions. The first fraction, 40%, contains a small amount of mononucleotides and di-, tri-, tetra-, penta-, and hexanucleo-tides. The second fraction, 60%, contains oligonucleotides larger than hexanucleotides.

Animals↗
PubMedDate not supplied

Distribution of label after intrathecal administration of 125I-substance P in the rat.

Despite the widespread use of the intrathecal route for the administration of neuroactive agents, little is known about the penetration of these agents into the spinal cord. In the present study, 125I-substance P was injected via a spinal catheter to the thoracic or sacro-coccygeal spinal cord in the rat (350-400 g) anesthetized with urethane (2.5 g/kg). Spinal cords were removed rapidly at 1 or 10 min after injection and immediately frozen in CCl2F2. Frozen sections, 20 micron thick, were cut and mounted for autoradiography. Autoradiographs of transverse sections demonstrated that the label penetrated 700 to 1800 micron from the surface of the spinal cord at both levels. In longitudinal sections, this penetration extended about 0.5 cm rostrally and caudally from the site of injection. Serial autoradiographs of transverse sections showed a similar penetration rostro-caudally. In addition, venous blood samples were taken at 1, 6, 11 and 16 min after injection of the labelled peptide. Quantification of the radioactivity in the samples revealed that 0.8 to 3.5% of the total CPM injected had passed into the general circulation at these times. These data indicate that after intrathecal administration of radiolabelled substance P, the label penetrates into the grey matter of the spinal cord to presumed sites of action. They also suggest that the rostro-caudal extent of penetration is more localized than suggested from earlier studies which looked only at levels of radioactivity in pieces of whole spinal cord. Finally, our study has indicated that passage of label into the circulation is negligible at least for substance P.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Growth hormone response to apomorphine, a dopamine receptor agonist, in normal aging and in dementia of the Alzheimer type.

The growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg SC) was studied in young and elderly normal subjects as well as in patients with dementia of the Alzheimer type (DAT) and controls matched for age, gender and Quetelet index. The GH response was significantly decreased in normal elderly men (mean age 67.3 years; N = 16) compared with young men (mean age 21.2 years; N = 12) and in elderly women (mean age 65.4 years; N = 9) compared with young women (mean age 25.5 years; N = 6) in the luteal phase but not in the early follicular phase. Young men had a significantly greater GH response than young women in either phase of the menstrual cycle. The decline in GH response with normal aging may be related to a decrease in sex steroid activity. There was no significant difference in GH response between DAT patients (N = 15) and paired controls. This suggests that hypothalamic D2 receptor function regulating GH secretion is not altered in DAT.

Adult↗
PubMedDate not supplied

Regional spectral analysis of the REM sleep EEG in mild to moderate Alzheimer's disease.

Regional spectral analyses of the EEG during wakefulness and REM sleep was performed in eight patients with mild to moderate Alzheimer's disease and compared to that of healthy age-matched controls. Alzheimer patients presented some EEG slowing in frontal, parieto-occipital and temporal regions in the waking state. However, this EEG slowing was much better revealed in REM sleep, whether expressed by the ratio of slow to fast frequencies or by changes in each of the frequency bands. Moreover, regional differences in EEG slowing, relatively nonexistent in the awake EEG, were a prominent feature of the REM sleep EEG. Importance of cholinergic basal forebrain in the desynchronization of the REM sleep EEG might explain these results because this structure is affected in early Alzheimer's disease.

Aged↗
PubMedDate not supplied

Alteration of nitric oxide synthase activity in young and aged apolipoprotein E-deficient mice.

Impairments in cognitive performance have been observed in aged apolipoprotein E (apoE)-deficient mice, and apoE epsilon 4 allele is a risk factor in Alzheimer's disease (AD). The absence of apoE correlates with diminished antioxidative capacity in animals, and elevated cerebral oxidative stress has been observed in AD individuals carrying the epsilon 4 alleles. Nitric oxide (NO) is a neurosignaling molecule that has significant roles in cognition. NO has also been implicated in neurodegenerative diseases due to its oxidative properties. The current study examined the possible relationship between apoE and nitric oxide synthase (NOS) by comparing hippocampal and cortical NOS activities in wild-type and apoE-knockout mice. Our results showed that apoE deficiency had no effect on NOS activity in these animals; however, aged animals uniformly exhibited significantly higher NOS activity levels. These findings suggest that increased NOS activity may contribute to cognitive impairments in aged wild-type and apoE-knockout mice due to excess accumulation of oxidative damages in areas involved in learning and memory.

Aging↗
PubMedDate not supplied

Lymphocyte content of amyloid precursor protein is increased in Down's syndrome and aging.

We quantified cellular amyloid precursor protein (APP) in ethanol-permeabilized peripheral lymphocytes from 13 subjects with Alzheimer's disease (AD), 11 subjects with Down's syndrome (DS), and 13 healthy elderly and 31 healthy young controls. APP content was analyzed by indirect immunofluorescence and flow cytometry, using the 22C11 monoclonal antibody (mAb) directed against an N-terminal domain of APP. Authenticity of 22C11 APP signal was confirmed by immunoblotting and flow cytometry studies with the mAb 6E10, directed against the A beta domain of APP. Consistent with gene dosage, patients with DS had 1.51-fold higher lymphocyte APP signal than age-matched normal young subjects (corrected p < 0.05). Both AD patients and elderly control groups had significantly increased lymphocyte APP signal compared to young controls (either comparison corrected p < 0.01). Indeed, increasing age in non-DS subjects was significantly correlated with lymphocyte APP (r = 0.508, p < 0.0001), such that APP immunoreactivity more than doubled from 20 to 80 years. Lymphocyte APP was nonsignificantly higher in AD vs. aged controls in this small sample. Increased cellular APP content in DS and aging may correspond to generalized alterations in expression or processing of this molecule, and suggests a novel determinant for the timing of AD onset.

Adult↗
PubMedDate not supplied

Beta-amyloid precursor protein is detectable on monocytes and is increased in Alzheimer's disease.

Using the anti-beta-amyloid precursor protein (betaAPP) monoclonal antibodies 4G8, 6E10 and 22C11 and flow cytometry, we report that human circulating peripheral blood monocytes display surface immunoreactivity for betaAPP. In contrast, circulating lymphocytes do not possess cell surface betaAPP immunoreactivity, despite similar levels of betaAPP expression. Immunoblotting analysis showed that monocytes, but not lymphocytes, possess an 82 kDa C-terminal betaAPP fragment consistent with a processed transmembrane species. Monocyte surface betaAPP was upregulated approximately threefold by activation with lipopolysaccharide and interferon-gamma, activation did not produce detectable betaAPP on the cell surface of lymphocytes. Surface betaAPP immunoreactivity was reduced in a normal aged population compared to normal young controls (Young = 81.07 +/- 13.67 mean fluorescence units, Aged = 36.74 +/- 3.81, p < 0.01), but was significantly increased in AD subjects compared to age-matched healthy controls (AD = 60.31 +/- 7.42, p < 0.05). Our data suggest that a proportion of peripheral A beta may be derived from monocyte/macrophages, and that defects in brain cell processing of betaAPP in AD may be shared by this readily accessible peripheral cell.

Adult↗
PubMedDate not supplied

EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium.

Breast cancer is the most frequent cancer in women while it is the second cause of cancer death. Estrogens are well recognized to play the predominant role in breast cancer development and growth and much efforts have been devoted to the blockade of estrogen formation and action. The most widely used therapy of breast cancer which has shown benefits at all stages of the disease is the use of the antiestrogen Tamoxifen. This compound, however, possesses mixed agonist and antagonist activity and major efforts have been devoted to the development of compounds having pure antiestrogenic activity in the mammary gland and endometrium. Such a compound would avoid the problem of stimulation of the endometrium and the risk of endometrial carcinoma. We have thus synthesized an orally active non-steroidal antiestrogen, EM-652 (SCH 57068) and the prodrug EM-800 (SCH57050) which are the most potent of the known antiestrogens. EM-652 is the compound having the highest affinity for the estrogen receptor, including estradiol. It has higher affinity for the ER than ICI 182780, hydroxytamoxifen, raloxifene, droloxifene and hydroxytoremifene. EM-652 has the most potent inhibitory activity on both ER alpha and ER beta compared to any of the other antiestrogens tested. An important aspect of EM-652 is that it inhibits both the AF1 and AF2 functions of both ER alpha and ER beta while the inhibitory action of hydroxytamoxifen is limited to AF2, the ligand-dependent function of the estrogen receptors. AF1 activity is constitutive, ligand-independent and is responsible for mediation of the activity of growth factors and of the ras oncogene and MAP-kinase pathway. EM-652 inhibits Ras-induced transcriptional activity of ER alpha and ER beta and blocks SRC-1-stimulated activity of the two receptors. EM-652 was also found to block the recruitment of SRC-1 at AF1 of ER beta, this ligand-independent activation of AF1 being closely related to phosphorylation of the steroid receptors by protein kinase. Most importantly, the antiestrogen hydroxytamoxifen has no inhibitory effect on the SRC-1-induced ER beta activity while the pure antiestrogen EM-652 completely abolishes this effect, thus strengthening the need to use pure antiestrogens in breast cancer therapy in order to control all known aspects of ER-regulated gene expression. In fact, the absence of blockade of AF2 by hydroxytamoxifen could explain why the benefits of tamoxifen observed up to 5 years become negative at longer time intervals and why resistance develops to tamoxifen. EM-800, the prodrug of EM-652, has been shown to prevent the development of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat, a well-recognized model of human breast cancer. It is of interest that the addition of dehydroepiandrosterone, a precursor of androgens, to EM-800, led to complete inhibition of tumor development in this model. Not only the development, but also the growth of established DMBA-induced mammary carcinoma was inhibited by treatment with EM-800. An inhibitory effect was also observed when medroxyprogesterone was added to treatment with EM-800. Uterine size was reduced to castration levels in the groups of animals treated with EM-800. An almost complete disappearance of estrogen receptors was observed in the uterus, vaginum and tumors in nude mice treated with EM-800. EM-652 was the most potent antiestrogen to inhibit the growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro when compared with ICI 182780, ICI 164384, hydroxytamoxifen, and droloxifene. Moreover, EM-652 and EM-800 have no stimulatory effect on the basal levels of cell proliferation in the absence of E2 while hydroxytamoxifen and droloxifene had a stimulatory effect on the basal growth of T-47D and ZR-75-1 cells. EM-652 was also the most potent inhibitor of the percentage of cycling cancer cells. (ABSTRACT TRUNCATED)

Animals↗
PubMedDate not supplied

Use of evidence in the process of practice change in a clinical team: a study-forming part of the Autocontrol Project.

The Autocontrol Project is concerned with the accessing, processing and communication of high quality information so that a clinical team can make and implement decisions for practice change, and then evaluate if improvement has been achieved. High quality information is used as evidence for change. In this study, we have evaluated how evidence is used by a clinical team to explain an identified problem of inappropriate use of blood gas tests. In an experimental study of the Surgical Intensive Care Unit, video recordings of team meetings of nurses and doctors were undertaken, structured according to a problem-based format. Evidence of current practice patterns derived from the hospital information system, as well as the results of a questionnaire to the unit's staff about knowledge and use of blood gas measurements, were supplied to the participants beforehand. At the second meeting, the output of the first meetings and a summarised analysis of pertinent literature were made available. This second meeting was required to finalise the list of causes of inappropriate blood gas use and propose pragmatic strategies for practice change. The video data of the meetings were coded to analyse the use of evidence, the categories of causes, issues and solutions proposed, and the quality of team interaction. The results indicate that in order to achieve consensus, the team used different types of evidence, including objective evidence of practice patterns, personal experience about direct and indirect organisational influences, and literature-based research evidence of best practice. Furthermore, group dynamics were favoured by the problem-based meeting structure, and a high level of cognitive critiquing between team members was observed. This research suggests that a combination of approaches involving identification of both operational factors (e.g. appropriate access to different types of evidence and meeting structure) and cognitive and behavioural approaches (e.g. ensuring expression of different viewpoints) is needed to support strategic decision-making for practice change in a clinical unit. This combined approach should favourably influence the provision of an effective and efficient evidence support environment for the clinical team.

Blood Gas Analysis↗
PubMedDate not supplied

Ethical issues in Alzheimer disease: the experience of a national Alzheimer society task force.

There has been increasing recognition of the ethical dilemmas that arise in the delivery of health care services and in planning and executing scientific research. Alzheimer disease (AD) and related dementias pose a particular challenge for families, care providers, and researchers because of the nature of the illness. Naturally, those at potential risk of developing the disease are eager for scientists to develop valid predictive tests for the disease. Alzheimer organizations have developed worldwide in response to the growing awareness and knowledge of the effects of dementia on individuals and their families. These organizations have played a role in advocating for research, increasing general awareness of the nature of the disease, and lobbying for more services for persons with dementia and their families. These organizations have also realized the increasing concern about the many ethical issues that arise in caring for those with AD and researching causes and cures. This paper describes a unique process one national Alzheimer society used to develop an Ethics Task Force to provide guidelines on ethical issues.

Aged↗