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Biomedical subjects

M Hamel

Publications and source records attributed to M Hamel.

At least 19 recordsLinked to original sources
PubMed2006

Control of oestradiol secretion and of cytochrome P450 aromatase messenger ribonucleic acid accumulation by FSH involves different intracellular pathways in oestrogenic bovine granulosa cells in vitro.

The objective of this study was to determine the major intracellular signalling pathways used by FSH and insulin to stimulate cytochrome P450 aromatase (Cyp19) mRNA and oestradiol accumulation in oestrogenic bovine granulosa cells in vitro. Bovine granulosa cells from small follicles (2-4 mm diameter) were cultured for 6 days under non-luteinizing conditions in the presence of insulin at 100 ng/ml, or insulin (10 ng/ml) and FSH (1 ng/ml). On day 4 of culture, specific inhibitors of phosphatidylinositol 3-kinase (PI3K; LY-294002), protein kinase C (PKC; GF-109203X), protein kinase A (PKA; H-89) or mitogen-activated protein (MAP) kinase activation (PD-98059) were added. The addition of PI3K and PKC inhibitors, but not of PKA inhibitor, significantly decreased insulin-stimulated Cyp19 mRNA levels and oestradiol accumulation (P < 0.001). The PKA inhibitor significantly decreased FSH-stimulated Cyp19 mRNA abundance and oestradiol secretion, whereas PI3K and PKC inhibitors decreased oestradiol secretion without affecting Cyp19 mRNA accumulation. Inhibition of MAP kinase pathway significantly increased Cyp19 mRNA abundance in insulin- and FSH-stimulated cells. P450scc mRNA levels and progesterone secretion were not affected by any inhibitor in either experiment. Although FSH stimulates Cyp19 expression predominantly through PKA, oestradiol secretion is altered by PI3K and PKC pathways independently of Cyp19 mRNA levels. In addition, we suggest that Cyp19 is under tonic inhibition mediated through a MAP kinase pathway.

Animals↗
PubMed2003

[Lengthening temporalis myoplasty and transfacial nerve graft (VII-V). Technical note].

Authors report the first five cases of lengthening temporalis myoplasty associated with transfacial nerve grafting. After a follow-up period of 10 months and 8 months for the 2 first cases, temporalis reinnervation by the facial nerve could be observed. Nerve growth was documented by electromyography. Three other cases have been performed using this technique and are in the nerve growth phase. Operative technique is described in detail. Transfacial nerve grafting seems to help the transposed temporalis muscle obtain more facial function and therefore, improve the quality of the spontaneous smile. The temporalis muscle become double innervated (trigeminal and facial nerve). It should be indicated in children, young adults or in patients in whom physical therapy will be difficult.

Anastomosis, Surgical↗
PubMed2001

[Effect of the imidazoline receptor agonist moxonidine on hemodynamics, coronary circulation, metabolic ischemia markers and the neurohumoral system in patients with essential hypertension. Effects of moxonidine on coronary circulation].

Moxonidine is a new centrally active imidazoline-receptor agonist being effectively applied in the treatment of arterial hypertension due to its sympathicolytic potency. This is the first investigation regarding the effects of moxonidine on coronary and systemic hemodynamics, metabolic markers of ischemia and neurohumoral parameters in patients with essential hypertension (WHO I-II). We studied moxonidine (single dose of 0.4 mg p.o.) in 22 patients with left ventricular (LV) hypertrophy, ST segment depressions during exercise, pectanginal complaints and negative coronarograms. Assessments included arterial blood pressure, cardiac output, pulmonary artery pressure mean (PAPm), pulmonary capillary wedge pressure (PCWP) and coronary sinus flow (CSF) by intravascular Doppler technique. The moxonidine-induced parameter changes 2 hours later were as follows: a decrease in systolic/diastolic pressure by 28/10 mmHg, and in heart rate by 5 bpm, associated with a decline of PAPm by 17% and of PCWP by 26%. LV work was reduced by 26%, MVO2 by 18% and CSF by 16%. Average peak velocity in CS fell by 18% and coronary flow reserve (with adenosine) increased by 12%. CS-O2 saturation rose by 4%, accompanied by an increase in lactate extraction by 17%, a decrease in norepinephrine spillover by 30% and in arterial endotheline by 20%. In conclusion, moxonidine produces clinically relevant sympathicolysis with beneficial effects on hemodynamics, coronary circulation and neurohumoral parameters.

Aged↗
PubMed2001

Deep sclerectomy with collagen implant in patients with glaucoma and high myopia.

PURPOSE: To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI), a nonpenetrating filtration procedure, in patients with glaucoma and high myopia. SETTING: Glaucoma Unit, Hôpital Ophtalmique Jules Gonin, Lausanne, Switzerland. METHODS: This nonrandomized prospective trial comprised 21 eyes of 21 highly myopic patients with medically uncontrolled primary or secondary open-angle glaucoma. Visual acuity, intraocular pressure (IOP), and slitlamp examinations were performed before as well as 1 and 7 days and 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 66 months postoperatively. Visual field examinations were repeated every 6 months. Exclusion criteria were known allergy to collagen, advanced lens opacity, and eye surgery or laser trabeculoplasty fewer than 6 months before enrollment. RESULTS: The mean follow-up was 44.0 months +/- 17.1 (SD). The mean preoperative IOP of 26.4 +/- 5.9 mm Hg dropped to 10.4 +/- 6.1 mm Hg at 48 months. Eighty-one percent of patients achieved an IOP below 21 mm Hg with or without medication at 48 months. Thirty-eight percent had an IOP below 21 mm Hg without medication. The mean number of medications per patient was reduced from 2.30 +/- 0.85 to 0.86 +/- 0.91. CONCLUSIONS: Deep sclerectomy with collagen implant provided reasonable control of IOP in patients with glaucoma and high myopia over a long-term follow-up. There were relatively few postoperative complications.

Adult↗
PubMed2001

[Actions of standardized extracts of Crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure].

Standardized extracts of Crataegus leaves and blossoms are said to have positive inotropic, positive dromotropic and negative bathmotropic effects. Clinical trials produce evidence for an improvement of symptoms in patients with congestive heart failure (NYHA II). In this trial the efficacy of a standardized extract of fresh Crataegus berries (Rob 10) on exercise tolerance and quality of life was studied in 88 patients. In a three-month placebo-controlled, randomized, double-blind trial these patients were treated with Rob 10 (3 x 25 drops daily). Total exercise time in bicycle ergometry was defined as primary efficacy variable, while quality of life (Minnesota Questionnaire), Dyspnea-Fatigue Index and the assessment of dyspnea by the patient on a visual analogous scale were chosen as secondary parameters. Investigations were performed after a two week placebo run-in period as well as 6 and 12 weeks after the onset of the study. Treatment with Rob 10 led to a increase of exercise time of 38.9 s vs placebo (95% confidence interval 5.7-72.1 s). Quality of life improved accordingly in favour of Rob 10. In the Minnesota Questionnaire, the total score fell by 31% (30.6 vs 44.1) under Rob 10 vs 18% (34.6 vs 42.4) under placebo. The Dyspnea-Fatigue Index demonstrated an increase of the total score of 12% (9.41 vs 8.37) vs 8% (8.92 vs 8.26) under administration of placebo. According to findings of the assessment of dyspnea by the patient, dyspnea decreased by 11% (50.5 vs 56.6 mm) vs 4% (54.8 vs 57.3 mm) under placebo. The present study proves the efficacy and safety of a standardized extract of fresh Crataegus berries (Rob 10) in patients with congestive heart failure (NYHA II) regarding the parameters evaluated.

Aged↗
PubMed2000

A novel high throughput screening assay for HCV NS3 helicase activity.

A novel assay for measurement of Hepatitis C virus (HCV) NS3 helicase activity was developed using Flashplate technology. This assay involves the use of a DNA duplex substrate and recombinant HCV NS3 produced in Escherichia coli. The DNA duplex consisted of a pair of oligonucleotides, one biotinylated, the other radiolabeled at their respective 5' termini. This DNA duplex was immobilized, via the biotin molecule, on the surface of a neutravidin-coated SMP103 Flashplate (NEN Life Science Products). Helicase activity results in the release of the radiolabeled oligonucleotide, which translates in signal reduction with respect to control wells. Biochemical characterization of the HCV NS3 helicase activity was performed using this assay. We demonstrated that the NS3-mediated unwinding is proportional to both the amount of DNA substrate in the well, and to the NS3 concentration in the reaction. Most of the NS3-mediated unwinding was achieved in the initial 60 min of incubation. As expected the reactions were ATP-dependent and found to be affected by the concentration of MgCl(2), MnCl(2), KCl, EDTA, and by pH. We found this assay to be highly reproducible since only slight variation was observed when a total of 68 helicase reactions were performed on one plate. Therefore, this Flashplate helicase assay is fast, convenient and reproducible. These criteria make it suitable for high throughput screening of potential NS3 helicase inhibitors.

Animals↗
PubMed2000

A study of nonpatient preadolescent Rorschach protocols.

There is a paucity of peer-reviewed, nonpatient Rorschach studies in psychological journals, particularly for children. This study examined 100 preteenage children, using the Comprehensive System to code their Rorschach protocols. The participants were also evaluated with the Conners Parent Rating Scale-93 (Conners, 1989) and 5 exclusionary behavior criteria. The 100 participants demonstrated better than average behaviors. The results presented include all the ratios and indexes found in the nonpatient statistics for the Comprehensive System. We discuss interrater reliability issues and offer recommendations for further cross-validating research.

Child↗
PubMed1998

The R1 subunit of herpes simplex virus ribonucleotide reductase is a good substrate for host cell protein kinases but is not itself a protein kinase.

The N terminus of the R1 subunit of herpes simplex virus type 2 ribonucleotide reductase is believed to be a protein kinase domain mainly because the R1 protein was phosphorylated in a protein kinase assay on blot. Using Escherichia coli and adenovirus expression vectors to produce R1, we found that, whereas the reductase activity of both recombinant proteins was similar, efficient phosphorylation of R1 and casein in the presence of Mg2+ was obtained only with the R1 purified from eukaryotic cells. Phosphorylation of this R1, in solution or on blot, results mainly from the activity of casein kinase II (CKII), a co-purifying protein kinase. Labeling on blot occurs from CKII leakage off the membrane and its subsequent high affinity binding to in vivo CKII-phosphorylated R1. CKII target sites were mapped to an acidic serine-rich segment of the R1 N terminus. Improvement in purification of the R1 expressed in eukaryotic cells nearly completely abolished its phosphorylation potential. An extremely low level of phosphorylation observed in the presence of Mn2+ with the R1 produced in E. coli was probably due to an unidentified prokaryotic protein kinase. These results provide evidence that the herpes simplex virus type 2 R1 does not possess an intrinsic protein kinase activity.

Adenosine Triphosphate↗
PubMed1998

[Asthenopic symptoms in cervical vertebrae syndrome].

The vertebral cervical syndrome is a clinical entity defined as a dysfunction of the cranio-cervical junction of traumatic or non traumatic cause. The authors report on asthenopic disorders occurring in such a syndrome. The fusion amplitude and the accommodation power were reduced in all patients and were a cause of delayed job recurrence. The treatment of fusion was long, painful and, in some cases, not successful. A depressive status associated with a prolonged job interruption were bad prognosis factors. A differential diagnosis has to be made with the so-called insurance neurotic reaction.

Accommodation, Ocular↗
PubMed1997

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

Adult↗
PubMed1996

Identification and functional analysis of Ly-6A/E as a thymic and bone marrow stromal antigen.

We recently described an mAb (MTS23) reactive with a membrane Ag expressed on a subset of thymic medullary stromal cells. This Ag is also constitutively expressed at high levels on peripheral B cells, macrophages, and thymic and splenic dendritic cells of C57BL/6 mice. A number of stromal cell lines derived from thymus and bone marrow also stain with MTS23, but thymocytes and peripheral T cells only weakly express the Ag detected by MTS23. Here we show that the molecule detected by MTS23 is a member of the Ly-6 family of phosphatidylinositol-anchored membrane proteins. Treatment of stromal cells with phosphatidylinositol-phospholipase C before staining completely abolished expression. Using transient expression of 293T cells and a cDNA library of a stromal cell line cloned into the pEF-BOS vector, a cDNA encoding the MTS23-target Ag was isolated. Partial sequencing and restriction enzyme mapping revealed that it represents the Ly-6A/E protein. While the physiologic significance of the presence of Ly-6 molecules on stromal cells is not clear, it has been known for some time that, at least in lymphocytes, cellular activation events can be induced upon Ly-6 engagement. We now demonstrate that Ly-6 also functions as a signal transduction molecule on stromal cells, in that granulocyte-macrophage CSF can be produced by a variety of stromal cell lines upon mAb-mediated cross-linking of Ly-6. Together with the dramatic up-regulation of Ly-6 expression on stromal cells upon IFN-gamma treatment, this is the first indication of a biologic function of an Ly-6 gene product on nonhemopoietic cells. The results suggest that Ly-6 may play a role in the cross-talk between lymphocyte precursors and stromal cells.

Animals↗
PubMed1996

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. I: nosology, sex and age of onset.

BACKGROUND: Little is known about the long-term outcome of schizophrenia that has its onset during childhood and early adolescence (early-onset schizophrenia, or EO-SZ). Whether or not EO-SZ is an aetiologically separate form of schizophrenia (SZ) is unresolved. METHOD: The study was a 14.8-year follow-up, using methods such as systematic sampling, evaluation of possible non-respondent bias, consensus best-estimate diagnoses (DSM-III-R) made independently in childhood and adulthood, measures of positive and negative dimensions, of non-psychotic behaviour disturbances (NPBD) and of developmental problems before the appearance of SZ. RESULTS: There was high stability of EO-SZ (n = 40) diagnoses (mean onset at 14.0 years) until adulthood (mean age at follow-up 28.8 years) but a lower stability of positive and negative schizophrenic dimensions. There was a poor outcome of EO-SZ, a strong over-representation of males but few gender differences, and no effect of age of onset on clinical features and outcome. CONCLUSIONS: EO-SZ taken as a whole shows no qualitative differences to adult-onset SZ. However, a distinction through the onset of preschizophrenic developmental problems or NPBD might be a way to investigate heterogeneity within EO-SZ.

Adolescent↗
PubMed1996

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome.

BACKGROUND: The aim of this study was to verify the presence and stability across life of the positive/negative distinction in early-onset schizophrenia (EO-SZ) through a longitudinal factor analysis of the schizophrenic dimensions, and to identify the factors predicting several indices of long-term outcome for EO-SZ. METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in a specific catchment area comprised the sample. RESULTS: Across a 14.8-year follow-up, longitudinal factor analysis identified two separate factors corresponding to the positive and negative symptom dimensions. We also observed that: the GAS rated over the last three years of adult illness and the severity of negative symptoms during the stabilised interepisode intervals in adulthood were the indices of adult outcome that were most easily predicted; and the best childhood predictors of adult outcome were premorbid functioning and severity of positive and negative symptoms during acute episodes. CONCLUSIONS: The presence of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid developmental problems was not related to severity of outcome, in contrast to the former variables.

Adolescent↗
PubMed1995

Motivation in later life: theory and assessment.

A framework that has been found useful in research on young adults, Deci and Ryan's self-determination theory [1, 2], is suggested as a promising direction for research on motivation in later life. The theory proposes the existence of four types of motivation (intrinsic, self-determined extrinsic, nonself-determined extrinsic, and amotivation) which are assumed to have varying consequences for adaptation and well-being. A previously published French measure of motivational styles which is known to be reliable and valid was translated into English and was tested on seventy-seven nursing home residents (aged 60 to 98 years). It was found that the four motivational styles can be reliably measured; that the intercorrelations between the motivational styles are consistent with theoretical predictions; and that the four types of motivation are related to other important aspects of the lives of elderly people in a theoretically meaningful manner. Suggestions are made for further research using self-determination theory and the present scales.

Aged↗
PubMed1995

Immunomodulatory and antiviral activities of 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-fluorocytidine.

Two dideoxynucleosides, 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-flurocytidine, containing unnatural L-configuration in their sugar moieties, were synthesized and assayed for antiviral activities. Both compounds were shown to possess potent anti-human immunodeficiency virus type 1 and antihepatitis B virus activities, while demonstrating no anti-herpes simplex viruses 1 and 2 activity. These two compounds exhibited in vitro cellular toxicities for several leukocytic cell lines and were shown to inhibit phytohemagglutinin-stimulated human peripheral blood mononuclear leukocyte proliferations. At inhibitory concentrations, both compounds caused accumulations of cells in the S phase. While demonstrating no obvious morphological toxicity in vivo in mice at concentrations of 75 and 150 mg/kg, 2',3'-dideoxy-beta-L-5-fluorocytidine- treated animals were shown to have considerable increases in CD4/CD8 double positive T lymphocyte population in their blood circulation.

Animals↗
PubMed1990

Predictors and consequences of aggressive behavior by community-based dementia patients.

The frequency, nature, context, and caregivers' reactions to aggressive behavior in 213 dementia patients residing in the community was studied. Aggression was reported in 57.2% of the patients and in 10.6% of the caregivers. Predictors of patient aggression were greater frequency of behavior and memory problems, premorbid aggression, and a more troubled premorbid social relationship between patient and caregiver. Patient aggression predicted the decision to discontinue home care.

Aged↗