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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 127 records · Page 7Linked to original sources
PubMed2000

Paradoxical increase of tyrosine hydroxylase-immunoreactive retinopetal fibers in the weaver mouse.

Weaver mice undergo apoptosis of the granule cell precursors of the cerebellum and nonapoptotic death of mesencephalic dopaminergic cells during post-natal development. In contrast, the number of retinal dopaminergic cells was transiently increased in weaver compared to control mice [C. Savy, E. Martin-Martinelli, A. Simon, C. Duyckaerts, C. Verney, C. Adelbrecht, R. Raisman-Vozari, J. Nguyen-Legros, Altered development of dopaminergic cells in the retina of weaver mice, J. Comp. Neurol. 1999;412:656-668]. While re-examining the retinas, we observed, in the nerve fiber layer, retinopetal tyrosine hydroxylase-immunoreactive fibers, which were dramatically increased in number throughout development and adulthood in the weaver compared to control mice.

Animals↗
PubMed2000

Mapping of a protective helper T cell epitope of human influenza A virus hemagglutinin.

The synthetic peptide comprising the 317-341 region of human influenza A virus (H1N1 subtype) hemagglutinin elicits peptide-specific antibody and helper T cell responses and confers protection against lethal virus infection. Molecular mapping of the 317-329 region, which encompasses the epitope recognized by peptide-specific T cells, revealed that the minimal size required for T cell activation was the 317-326 segment. The most likely peptide alignment, which placed 320Leu to pocket 1 of the I-E(d) peptide binding groove, was predicted by molecular mechanics calculations performed with the parental and with the Ala-substituted analogs. In line with the prediction data, the results of the peptide binding assay, where the relative binding efficiency to I-E(d) molecules expressed on the surface of antigen-presenting cells was monitored, identified the 320-326 core sequence interacting with the major histocompatibility class II peptide binding groove. Functional analysis of Ala-substituted variants by functional assays and by calculating the surface-accessible areas of the single peptidic amino acids in the I-E(d)-peptide complexes demonstrated that 324Pro is a primary contact residue for the T cell receptor. Our results show that this type of analysis offers a suitable tool for molecular mapping of helper T cell epitopes and thus provides valuable data for subunit vaccine design.

Alanine↗
PubMed2000

Study of vitamin E net mass transfer between alpha-tocopherol-enriched HDL and erythrocytes: application to asymptomatic hypercholesterolemic men.

We previously showed that hypercholesterolemic asymptomatic men had lower erythrocyte vitamin E content, despite normal plasma concentrations compared to normocholesterolemic men. We hypothesized that the reduced erythrocyte vitamin E concentration could be due to an impairment of transfer of vitamin E from plasma lipoproteins. We first developed a model for testing the ability of erythrocytes to accept vitamin E from high-density lipoproteins (HDL) pre-enriched in vitamin E, which allows to measure a net mass transfer of vitamin E from HDL to erythrocytes. Vitamin E-enriched HDL were obtained in controlled conditions of concentration and incubation time with a good reproducibility (CV </= 10%). The kinetic study of the net mass transfer of vitamin E to erythrocytes of healthy volunteers shows small inter- and intraindividual variations. The application of this model to erythrocytes of hyper- and normocholesterolemic men demonstrates that the reduced erythrocyte vitamin E content observed in hypercholesterolemic men was not due to a reduced ability of these cells to accept vitamin E from HDL. It might rather be due to an impairment of lipoproteins in the delivery of vitamin E to tissues, or to an oxidative stress which consumes antioxidants.

Biological Transport, Active↗
PubMed2000

Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane.

In a rebreathing anesthesia circuit, the inhaled anesthetic sevoflurane degrades into at least two products, termed "compound A" and "compound B." The enantiomer separation of the chiral compound B (1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane ) by capillary gas chromatography (cGC) using heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor alpha of 4.1 (at 30 degrees C) was found. Consequently, the enantiomers of compound B were isolated by preparative GC and their specific rotations were measured. In addition, their absolute configurations were determined by X-ray crystallography. To collect the X-ray data, single crystals of both enantiomers were grown in situ on the diffractometer. The levorotatory enantiomer B(-) has the R-configuration while the dextrorotatory enantiomer B(+) has the S-configuration. The elution order of the compound B enantiomers on heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin is R before S.

Anesthetics, Inhalation↗
PubMed2000

[Proxy decision in health questions and advance designations by patients. A practice-oriented review of the legal and ethical problems in treating the incompetent patient].

Except in emergencies, the medical treatment of incompetent patients also has to be based upon an informed consent between the physician and a legitimate legal representative (durable power of attorney). Consequently, the German 'Betreuungsrecht' advices persons to designate in advance such a proxy or surrogate. However, an additional court-decision is demanded, if a medical measure poses significant risks for the future health or the life of the incompetent patient. On the base of the available epidemiologic data we illustrate that neither our medical nor our legal system could realistically cope with the practical consequences of this legislation: The vast majority of our present decisions in such cases is not covered by a legally valid informed consent, which implies possible forensic consequences. This article provides relevant clinical and legal advice on how to protect the legitimate interests of all concerned within the present framework, which should urgently be revised.

Animals↗
PubMed2000

Function-related regulation of the stability of MHC proteins.

Proteins must be stable to accomplish their biological function and to avoid enzymatic degradation. Constitutive proteolysis, however, is the main source of free amino acids used for de novo protein synthesis. In this paper the delicate balance of protein stability and degradability is discussed in the context of function of major histocompatibility complex (MHC) encoded protein. Classical MHC proteins are single-use peptide transporters that carry proteolytic degradation products to the cell surface for presenting them to T cells. These proteins fulfill their function as long as they bind their dissociable ligand, the peptide. Ligand-free MHC molecules on the cell surface are practically useless for their primary biological function, but may acquire novel activity or become an important source of amino acids when they lose their compact stable structure, which resists proteolytic attacks. We show in this paper that one or more of the stabilization centers responsible for the stability of MHC-peptide complexes is composed of residues of both the protein and the peptide, therefore missing in the ligand-free protein. This arrangement of stabilization centers provides a simple means of regulation; it makes the useful form of the protein stable, whereas the useless form of the same protein is unstable and therefore degradable.

Amino Acid Sequence↗
PubMed2000

Gender difference in the influence of smoking on arterial wall thickness.

BACKGROUND: We hypothesized that arterial wall thickening, an early atherogenic alteration, might be associated with smoking differently according to gender, considering the cardiovascular protection of female sex hormones. METHODS AND RESULTS: We measured ultrasonographically carotid and femoral intima-media thickness (IMT) in 194 men and 330 women without risk factors other than smoking. In men: (i) current smokers had greater carotid and femoral IMT (P<0.01, P<0.001) and former smokers had greater femoral IMT (P<0.01) than never smokers; (ii) in pooled never, current and former smokers carotid and femoral IMT correlated to current daily smoking (P<0.01) and lifelong smoking (P<0.001); and (iii) carotid and femoral IMT correlated to age in never smokers (P<0.001), current smokers (P<0.01, P<0.001) and former smokers (P<0.01), with greater slopes in current than in former smokers at carotid site (P<0.05) and in current than in never smokers at femoral site (P<0.05). In women: (i) IMT did not differ by smoking status; (ii) in pooled smokers and non smokers femoral IMT correlated to current daily smoking (P=0.01) and to lifelong smoking (P<0.01) with a lower slope than in men (P<0.001), while carotid IMT did not; and (iii) carotid and femoral IMT correlated to age in never smokers (P<0.001), current smokers (P<0.001, P<0.05) and former smokers (P<0.001, P<0.01) with no different slopes. CONCLUSION: Smoking-related increase in IMT existed in men but not in women, suggesting a possible protection of female gender from early structural arterial alteration of smoking.

Adolescent↗
PubMed2000

Distribution of ultrasonographically-assessed dimensions of common carotid arteries in healthy adults of both sexes.

Our objective was to provide a description of 'normal' carotid artery dimensions which are increasingly used for detecting early atherosclerosis and predicting clinical complications. Far wall intima-media thickness (IMT), lumen diameter and cross-sectional area intima-media thickness (CSA-IMT) were measured on 1 cm-distal common carotid artery segments on both sides by B-mode ultrasound, using an automated computerized edge-detection program, in 133 men and 216 women aged 17-65 years and free from cardiovascular disease and traditional risk factors. IMT and CSA-IMT increased with age in both sexes and on both sides, while diameter did not, except on the right side in men. Women had lower diameter than men except on the left side at 30 years or below, while IMT did not differ between sexes except on the left side from 31 to 50 years where IMT was higher in men; as a result of their lower diameter, women had lower CSA-IMT than men except on the right side above 50 years. IMT was lower on the right side than on the left side in both sexes, except in 30-year old or younger men and 31- to 40-year old women, while diameter was higher on the right side than on the left side in men and women aged 31-40 years and in women aged 41-50 years; also CSA-IMT was lower on the right side than on the left side in both sexes above 40 years. These data provide reference values of carotid artery dimensions and show that age, sex and side of measurement should be taken into account in the interpretation of 'normal' values of IMT and diameter in clinical practice and trials.

Adolescent↗
PubMed2000

Behavioral evidence for brain-based ability factors in visuospatial information processing.

The present study examined possible parallels between the structure of human visuospatial abilities and the organization of the neural systems. Forty-eight participants were tested on seven speeded visuospatial tasks. Three of these tasks were constructed so as to rely primarily on known ventral stream functions and four were constructed so as to rely primarily on known dorsal stream functions. Both sets of tasks spanned approximately the same range of difficulty as indexed by both the speed and accuracy of decision making. Factor analysis of response times on the seven tasks revealed only two significant factors. The putative ventral stream tasks all loaded heavily on one factor (mean loading=0.843) but only weakly on the other factor (mean loading=0.222); the putative dorsal stream tasks showed the opposite pattern in that they all loaded heavily on the second factor (mean loading=0.828) but only weakly on the first factor (mean loading=0.229). These findings are consistent with the hypothesis that human visuospatial abilities can be classified using categories based on the specializations of underlying neural structures and systems.

Adult↗
PubMed2000

Pseudohypoparathyroidism type Ia. Albright hereditary osteodystrophy: a model for research on G protein-coupled receptors and genomic imprinting.

Pseudohypoparathyroidism type Ia (PHP Ia) is a hereditary endocrine disorder, characterised by resistance to parathyroid hormone (PTH), causing disturbance of calcium homeostasis, and to several other polypeptide hormones. Patients with PHP Ia exhibit a complex of somatic abnormalities, termed Albright hereditary osteodystrophy (AHO). Treatment with vitamin D derivatives alleviates symptoms of hypocalcemia and may prevent bone demineralisation. PTH, like many polypeptide hormones, exerts its effects via a G protein-coupled cell surface receptor. PHP Ia is caused by a heterozygous, inactivating mutation in the gene for the alpha-subunit of the Gs protein, which disrupts Gs-protein-coupled signal transduction pathways. Several mutations have been described. When the mutation is inherited from the mother, the offspring will develop PHP Ia, i.e., both hormonal resistance and somatic abnormalities. When the mutation is derived from the father, children will have normal hormone responses while exhibiting the somatic features of AHO; this form of the disorder is called pseudopseudohypoparathyroidism (PPHP). A combination of tissue-specific genomic imprinting and haploinsufficiency may explain the occurrence of PPHP, and the fact that not all Gs-mediated polypeptide hormone actions are affected equally. PHP may therefore serve as a model in studying the pleiotropic consequences of impaired Gs-mediated signal transduction.

Calcium↗
PubMed2000

Association of plasma viscosity and carotid thickening in a French working cohort.

Plasma viscosity and intima-media thickness (IMT) are frequently associated with cardiovascular disease and its risk factors. We evaluated the association of rheologic and vascular factors in asymptomatic subjects. Plasma viscosity (coaxial cylinder viscometry) and both preintrusive and intrusive atherosclerosis in the carotid arteries (ultrasonography) were investigated in 246 men and 337 women aged 17 to 65 years from the AXA study, a prospective cohort of healthy workers. Plasma viscosity was positively related to age-adjusted mean bifurcation carotid artery IMT (P < .01 for men; P < .04 for women) and maximum carotid artery IMT (P < .01 for men; P < .02 for women), but not to mean common carotid artery IMT. Multivariate adjustment affected these relations to a greater extent in men than in women. The odds ratio (range) of having intrusive atherosclerosis in relation to 1 SD greater plasma viscosity was 2.27 (1.52 -3.38) in men and 1.63 (1.17-2.26) in women. Adjustment of age, waist-to-hip ratio, smoking, hypercholesterolemia, hypertension, diabetes, and fibrinogen had very little effect on the magnitude of these odds ratios. Thus, plasma viscosity was associated with carotid thickening, suggesting that rheologic factors are involved in the subclinical phase of atherosclerosis.

Adolescent↗
PubMed2000

A comparative study between classical stirred and ultrasonically-assisted dead-end ultrafiltration.

The aim of this work was to determine mass transfer coefficients in the cases of ultrasonically-assisted and classical stirred dead-end ultrafiltration. A comparative study was then performed, and mass transfer coefficients obtained under ultrasonic conditions are described by an empirical model. This correlation results from an analogy with what is observed using a stirred cell and involves the ultrasonic power as the main parameter. The hydrodynamics are assumed to depend on the intensity of the ultrasound effects illustrated by the agitation arising within the cell. This agitation is due to convective currents as well as physical effects due to cavitation. The concentration polarization phenomenon is therefore affected by this action of ultrasonic waves.

Journal Article↗
PubMed2000

Evaluation and treatment of low responders in assisted reproductive technology: a challenge to meet.

PURPOSE: To investigate the various methods of evaluation and treatment of patients with a low response to controlled ovarian hyperstimulation in assisted reproductive technologies (ART). METHODS: Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches. RESULTS: While a universally accepted definition for low responders is still lacking, these patients are reported to represent about 10% of the ART population. Several ovarian reserve screening techniques have been proposed; however, currently the best-characterized and most sensitive screening tools available are the basal day 3 serum follicle-stimulating hormone level and the clomiphene citrate challenge test. When abnormal, these tests allow physicians to counsel patients that their prognosis for conception is poor. Although the presence of a normal result does indicate better long-term chances for conception, on age-related decline in fecundity remains and patient age should still be considered when counseling patients with normal screening results. Several stimulation protocols have been applied in the low-response group with varying success. Recent studies show that the use of a minidose gonadotropin-releasing hormone-agonist protocol may result in significantly decreased cycle cancellations as well as increased clinical and ongoing pregnancies, and thus is proposed as a first-line therapy. Studies evaluating supplementary forms of treatment to the ovulation induction regimen show improved outcome when pretreating with oral contraceptives, whereas there seems to be no benefit from cotreatment with growth hormone or glucocorticoids. Blastocyst culture and transfer and assisted hatching in low responders are still under evaluation, whereas natural cycle in vitro fertilization may be used in cases of repeated failures as a last option before resorting to oocyte donation or adoption. Future possible forms of treatment like in vitro maturation of immature human oocytes, cytoplasm, and nuclear transfer currently are experimental in nature and their efficacy has still to be proven. CONCLUSIONS: The evaluation and treatment of low responders in ART remains a challenge. Understanding of the underlying etiology and pathophysiology of this disorder may help the clinician to approach it successfully.

Adult↗
PubMed2000

A right to life for the unborn? The current debate on abortion in Germany and Norbert Hoerster's legal-philosophical justification for the right to life.

Rights to life for unborn humans and to abortion with impunity are incompatible. This observation by the German legal philosopher Norbert Hoerster contains a fundamental criticism of the state regulation on abortion in Germany. The regulation regards abortion as unlawful, but declines to prosecute if the abortion is conducted within the first three months of pregnancy and the pregnant woman received counseling at least three days prior to terminating the pregnancy. In contrast to the German legislature, Hoerster is in favor of setting the beginning of a right to life at birth. With this suggestion and the consequent demand for a general legalization of abortion, Hoerster himself has become the target of harsh criticism. The following article analyzes Hoerster's position and that of his opponents against the background of the current abortion debate in Germany. The consequences for dealing with the handicaps of Hoerster's suggested regulations will also be addressed.

Abortion, Illegal↗
PubMed2000

Surveillance for nosocomial and central line-related infections among pediatric hematology-oncology patients.

OBJECTIVE: To determine the incidence of all nosocomial infections (NIs) in pediatric hematology-oncology patients, as well as central venous access device (CVAD)-associated infections acquired during home care. DESIGN: Prospective surveillance study. SETTING: The Pediatric Hematology and Oncology Department at the University Hospital Bonn. PATIENTS: All patients admitted from January through October 1998 (surveillance period). METHODS: Standardized surveillance system based on the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance System. RESULTS: A total of 143 patients were hospitalized for 3,701 days (776 admissions) during the surveillance period. Of the 40 NIs detected, 26 were CVAD-related, with 21 bloodstream infections (BSIs) and 5 local infections. Four were Clostridium difficile-associated diarrheal illnesses, 3 were pneumonias, and 7 were other infections. The incidence of NIs was 10.8 per 1,000 patient-days (5.2 NIs/100 admissions). The overall CVAD-related BSI rate was 7.4 per 1,000 utilization days, without a significant difference between implanted infusion ports and tunneled catheters. In addition, 7 CVAD-related infections occurred during home care. All 8 BSIs associated with tunneled catheters and 13 (76%) of the 17 BSIs associated with ports were acquired nosocomially. For inpatients and outpatients combined, the exit sites of tunneled catheters were more likely to become locally infected than were the needle entry sites of ports (relative risk, 8.0; P=.007). In 30 (75%) of the 40 NIs, the affected patients had severe neutropenia (<500/mm3) at the time of infection. CONCLUSIONS: Most NIs in the pediatric hematology-oncology patients were associated with CVAD devices. Although many infections in this high-risk population may not be preventable through infection control measures, the careful evaluation of specific infection rates permits the identification of risk factors that may be targeted by infection control programs. Prospective surveillance for NIs on pediatric oncology units is an indispensable tool for this internal quality control.

Adolescent↗
PubMed2000

A repetitive sequence of Epstein-Barr virus nuclear antigen 6 comprises overlapping T cell epitopes which induce HLA-DR-restricted CD4(+) T lymphocytes.

Most human adults carry the Epstein-Barr virus (EBV) and develop immunological memory against the structural and the virus-encoded cellular proteins. The EBV nuclear antigen 6 (EBNA6) elicits cytotoxic T cell responses and it also maintains a persistent antibody response. The majority of sera from EBV-seropositive individuals reacts with a synthetic peptide, p63, comprising 21 amino acids of a repetitive region of EBNA6. CD4(+) T lymphocytes, with specificity for p63, could be recalled from the T cell repertoire of EBV carriers that expressed certain HLA-DR allotypes which were identified as good binders of p63 by an in vitro flow cytometric assay. Analysis of the HLA-DR/p63 interaction by molecular mechanics calculations indicated the presence of multiple overlapping epitopes which were predicted to bind in a HLA-DRB1 allo- and subtype-specific manner. Specific activation of p63-selected long-term CD4(+) T cell cultures resulted in a proliferative response, in the production of IL-2 and in the secretion of high levels of tumor necrosis factor as measured by bioassays. Proliferation and cytokine production of p63-specific T cells could be induced by p63-loaded HLA-DR-matched antigen-presenting cells and by B cells co-expressing relevant HLA-DR molecules and EBNA6. Our results show that peptides of an EBNA6 repeat region induce CD4(+) T cells which can react with EBNA6-carrying cells in many individuals. We suggest that these T(h) cells may be important in conditioning dendritic cells for initiation potent virus-specific immune responses, provide help for EBV-specific B cells, drive IgG isotype switch and support the sustained effector function of memory cytotoxic T lymphocytes.

Adult↗