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Biomedical subjects

E Neuman

Publications and source records attributed to E Neuman.

At least 19 recordsLinked to original sources
PubMed2005

[The use of moderate hypothermia in neurosurgery].

Hypothermia is currently considered as the most effective neuroprotective method. In recent years hypothermia has been more and more applied in clinical conditions. Hypothermia has been used with promising results in severe head trauma where it can evidently decrease the intracranial pressure, improve cerebral perfusion pressure and by its direct neuroprotective effect it diminishes the secondary ischemic brain damage. Hypothermia has been widely used also during complicated neurosurgical operations when cerebral vessels are manipulated (operations of cerebral aneurysms, arteriovenous malformations, scull base tumours). Hypothermia has been recently tested also in some types of stroke, mainly in subarachnoid haemorrhage and ischaemic stroke.

Brain↗
PubMed2004

Stereotactic evacuation of spontaneous infratentorial hemorrhage with monitoring of intracerebral pressure.

INTRODUCTION: Based on our experience with stereotactic evacuation of spontaneous supratentorial hematomas this method has also been used for evacuation of spontaneous infratentorial hematoma by the transtentorial approach. MATERIAL AND METHOD: The authors present a series of 6 patients with spontaneous intracerebral hematomas evacuated by the frame-based stereotactic technique, with monitoring of intracranial pressure (ICP) during the stereotactic evacuation. This method was indicated in patients with stable neurological status according to Glasgow Coma Scale (GCS), more than 10. The frame-based stereotaxy with the Riechert-Mundinger apparatus with CT localisation of target and optimal trajectory was used. RESULTS: The presented values after stereotactic evacuation show reduction of the initial intraparenchymal ICP in all patients to values less than 20 mmHg. CONCLUSION: The measuring of the ICP and the analysis of dynamic changes during stereotactic evacuation suggest that this procedure can significantly reduce the ICP performed in connection with ICH and we believe that our results can improve management of patients with spontaneous infratentorial and supratentorial intracerebral hematoma. (Fig. 1, Ref. 21.).

Aged↗
PubMed1999

Is the LDL receptor-related protein involved in Alzheimer's disease?

LDL-related protein receptor (LRP) is the main receptor in the brain for apolipoprotein E. Moreover, the LRP gene is located on chromosome 12, the site of a potential Alzheimer's disease (AD) locus. We explored the association between the LRP gene and AD in 600 French Caucasian patients (37.8% men, mean age 72.0+/-8.0 years, mean age at onset 68.7+/-8.1 years) and age-matched controls (n=646, 37.0% men, mean age 72.5+/-8.2 years) and observed an association between a (TTTC) repeat at the 3' end of an Alu sequence in the LRP gene and the risk of developing AD. Three alleles were detected in this population [corresponding to 83, 87, and 91 base pairs (bp)], the 91-bp allele being associated with an increased risk of developing AD [all patients: odds ratio (OR) 1.6, P<0.01; late-onset AD: OR 1.8, P<0.01]. This suggests an association between the LRP locus and AD. However, in the light of studies related to the exon 3 LRP polymorphism and given the low strength of the association reported here, a biologically active variant may exist on chromosome 12, either in the LRP gene itself or in another gene in the vicinity.

Age of Onset↗
PubMed1998

Application of population pharmacokinetics to the phase II development of an anti-Alzheimer's disease compound, S12024.

Steady-state concentrations of S12024, a novel compound for treatment of Alzheimer's disease, were studied to determine the pharmacokinetic parameters of S12024 in Phase IIa patients and to assess the effect of patient characteristics on those pharmacokinetics. A prospective sparse sampling strategy was used to obtain oral repeated data (n = 285) from 89 patients, which were analyzed using a one-compartment model and the NONMEM computer program. The model suggested that apparent clearance of S12024 was influenced by the study and by patient age. In the Spanish study, apparent clearance was increased by 68% and 26% for doses of 100 mg and 300 mg, respectively, and patient age decreased oral clearance by approximately 10% per decade in the patient age range (50 to 90 years). Data from only a few patients in the Spanish study were probably responsible for the observed study influence on apparent clearance of S12024, and no measured covariates could explain this effect. The model provided an excellent characterization of the observed data and it predicted correctly the plasma concentrations from an earlier Phase I trial and a subsequent Phase IIb study. The present model, built from Phase IIa data, provides a basis for examining the influence of patient covariates and the magnitude of their effects on the pharmacokinetics of S12024. The study effect is probably an artefact that will disappear by further expanding of the population model in the future.

Administration, Oral↗
PubMed1998

The very low density lipoprotein (VLDL) receptor is a genetic susceptibility factor for Alzheimer disease in a European Caucasian population.

The epsilon4 allele of the apolipoprotein E gene (APOE) constitutes a major genetic susceptibility factor for Alzheimer disease (AD). Recently, a polymorphic triplet (CGG) in the very low density lipoprotein receptor (VLDL-R) gene, coding for a receptor binding only apoE-containing lipoproteins, was associated with AD in a Japanese population but not in Caucasian American populations. We explored this association and the potential interaction with the APOE polymorphism in a Caucasian sample of sporadic AD and control subjects of similar ages of European origin. The allelic distribution of the VLDL-R polymorphism differed significantly between Japanese and Caucasian populations (p < 0.0001). However, in our population, the presence of at least one VLDL-R 5 repeat allele increased significantly (p < 0.0003) the probability to develop AD after 65 years of age in APOE epsilon4 allele bearers.

Aged↗
PubMed1997

Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein.

The Ras proto-oncogene is a central component of mitogenic signal-transduction pathways, and is essential for cells both to leave a quiescent state (G0) and to pass through the G1/S transition of the cell cycle. The mechanism by which Ras signalling regulates cell-cycle progression is unclear, however. Here we report that the retinoblastoma tumour-suppressor protein (Rb), a regulator of G1 exit, functionally links Ras to passage through the G1 phase. Inactivation of Ras in cycling cells caused a decline in cyclin D1 protein levels, accumulation of the hypophosphorylated, growth-suppressive form of Rb, and G1 arrest. When Rb was disrupted either genetically or biochemically, cells failed to arrest in G1 following Ras inactivation. In contrast, inactivation of Ras in quiescent cells prevented growth-factor induction of both immediate-early gene transcription and exit from G0 in an Rb-independent manner. These data suggest that Rb is an essential G1-specific mediator that links Ras-dependent mitogenic signalling to cell-cycle regulation.

3T3 Cells↗
PubMed1997

Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4.

Cyclin D1 plays an important role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy. We show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin D1 can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor.

Biomarkers, Tumor↗
PubMed1996

Structure and partial genomic sequence of the human E2F1 gene.

The E2F family of transcription factors appears to play a critical role in the transcription of certain genes required for cell cycle progression. E2F1, the first cloned member of this family, is regulated during the cell cycle at the mRNA level by changes in transcription of the E2F1 gene and at the protein level by complex formation with proteins such as the retinoblastoma gene product (pRB), cyclin A and DP1. E2F1 can override a pRB-induced G1/S block and can behave as an oncogene in certain cells. E2F1 was cloned and was found to contain seven exons. The dinucleotides at the 5' and 3' splice sites of intron 4 do not agree with consensus splice site sequences. Fluorescence in situ hybridization localized E2F1 to chromosome 20q11. Knowledge of the organization of E2F1 may facilitate identification of additional E2F family members, as well as detection of E2F1 abnormalities in human tumors.

Base Sequence↗
PubMed1996

Schizophreniform catatonia on 6 cases secondary to hydrocephalus with subthalamic mesencephalic tumor associated with hypodopaminergia.

This paper presents 6 patients with catatonia and subthalamic mesencephalic tumors with hydrocephalus involving the third and the lateral ventricles. This anatomic and psychiatric anomaly is investigated on the basis of personal observations and a review of the literature. These cases allow an interesting parallel to be traced between neurological clinical signs and psychiatric signs. Various anatomic and physiological models are discussed which emphasize specialized neuronal circuits (somewhat similar to those involved in Parkinson's disease) and certain specific neurotransmitters such as dopamine, together with the reactivity of these circuits to intracranial pressure variations. Once more, clinical and laboratory data on schizophrenia concur to suggest that organic etiology is the causal factor in a known psychiatric pathology.

Adult↗
PubMed1996

Lines of therapeutics research in Alzheimer's disease.

Therapeutic research is being stepped up to light Alzheimer's disease (AD), although its heterogeneity, the insufficiency of physiopathological knowledge, and the lack of a reference treatment impede the development of a drug to combat it. However, progress has opened up many avenues. Some recent approaches that have led to therapeutic research are identification of biochemical abnormalities, identification of dysfunction in several neurotransmitter systems (cholinergic, catecholaminergic, serotonergic, and peptidergic systems), and the study of senile plaques and neurofibrillary degeneration tangles. Although some types of therapy have been used for a long time (e.g., metabolic products such as nootropes), recently developed drugs target different systems: for example, neurotransmitter systems are important for symptomatic improvements in cognitive functions. The principal improvements expected with some new anticholinesterases whose role is to increase the available amount of central acetylcholine are in memory and attention. Second, retarding neuronal degeneration by acting on amyloid plaques is another possible future therapy. Here, protease inhibitors appear to be interesting tools. Third, the endototoxin etiology of neurodegenerative illnesses remains uncertain. After the first attempts with N-methyl-D-aspartate (NMDA) antagonists that had inescapable side effects, hopes rose with some new pharmacological tools such as the AMPA/kainate antagonists. Fourth, a possible stimulation of neuronal plasticity by neurotrophic factors such as nerve growth factor (NGF) constitutes another prospected research area. Fifth, the inflammatory aspects of degenerative diseases attract the attention of many laboratories and preliminary reports are hopeful. Finally, out of the established pharmacological tools, gene therapy, though still hypothetical, may become the expected treatment in the future. Pharmacotherapy used in the most common types of dementia has until now been largely palliative and dealt with symptoms. It is nonetheless not unreasonable to look forward to the development of drugs that will be able to combat the evolution of the dementia itself, rather than its symptoms. A list of different products developed to treat AD is concluded by an evaluation of the expected results and, in particular, the orientations likely to be necessary.

Aged↗
PubMed1996

Dentastic bond strength to dentin.

PURPOSE: To evaluate the shear bond strength to the dentin of permanent teeth and failure site of Dentastic hydrophilic dentin bonding agent. MATERIALS AND METHODS: Forty permanent noncarious molar teeth stored in distilled water were obtained. The teeth were cleaned with pumice and a rubber cup. The mesio-buccal surface of the teeth was ground flat with hand pressure with a series of SiC paper ending with the 600 grit to provide a uniform surface on dentin to which the resin composite could be applied. After preparing the tooth surface, the teeth were stored in distilled water for 48 hours. They were then divided at random into four groups of 10 specimens each: Group 1: Dentastic, five coats of primer; Group 2: Dentastic, three coats of primer; Group 3: Dentastic, five coats of primer, light-cured adhesive before resin bonding; Group 4: Dentastic, three coats of primer, light-cured adhesive before resin bonding. All specimens were thermocycled (500x) and sheared in a testing machine. After shear testing, the debonded sites of all samples were examined with a stereomicroscope and a scanning electron microscope. RESULTS: The results in MPa were: Group 1: 22.63 +/- 6.24; Group 2: 23.35 +/- 5.14; Group 3: 23.58 +/- 5.66; Group 4: 27.26 +/- 8.22. ANOVA and Student-Newman-Keuls showed no statistically significant difference between the groups. In all groups, all specimens failed at the dentin (dentin cohesive failure = dentin fracture) or at the resin (resin cohesive failure = resin fracture). This means that the bond strength of the product is stronger than the cohesive strengths of the dentin and the resin.

Analysis of Variance↗
PubMed1994

Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter.

The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance. To better understand this latter phenomenon, we have isolated the human E2F-1 promoter. The human E2F-1 promoter, fused to a luciferase cDNA, gave rise to cell cycle-dependent luciferase activity upon transfection into mammalian cells in a manner which paralleled previously reported changes in E2F-1 mRNA abundance. The E2F-1 promoter contains four potential E2F-binding sites organized as two imperfect palindromes. Gel shift and transactivation studies suggested that these sites can bind to E2F in vitro and in vivo. Mutation of the two E2F palindromes abolished the cell cycle dependence of the E2F-1 promoter. Thus, E2F-1 appears to be regulated at the level of transcription, and this regulation is due, at least in part, to binding of one or more E2F family members to the E2F-1 promoter.

Animals↗
PubMed1992

Regulation of MHC class I synthesis and expression by human neutrophils.

Human peripheral blood neutrophils (PMN) treated with granulocyte-macrophage CSF (GM-CSF) increase the amount of class I 42-kDa H chain and 12-kDa L chain, beta 2-microglobulin (beta 2m), that they synthesize by 2.1- and 2.6-fold, respectively. To determine whether the increase in translation was associated with an increase in levels of class I H chain transcript, RNA blot analysis was performed on PMN that had been cultured in the presence of GM-CSF. Under no conditions were there increased levels of class I H chain transcript when class I heterodimer protein synthesis was increased. In addition, there was neither an increase in the synthesis of H chain mRNA, as measured by transcription assay, nor an alteration in the degradation rates of class I H chain transcript in PMN cultured with GM-CSF. In situ hybridization demonstrated that both the percentage of PMN that expressed class I transcript and the relative amounts of transcript per cell in GM-CSF-cultured PMN were the same as those in control PMN. Although there is increased translation of class I heterodimer in PMN treated with GM-CSF, there is no increase in its expression on the plasma membrane. The maintenance of constant levels of class I on the plasma membrane is dependent on continued protein synthesis and is maintained by release of class I heterodimer and free beta 2m into the medium. Heterodimer is released in the context of plasma membrane-derived vesicles, whereas beta 2m is released as a soluble protein. Maintenance of constant levels of class I heterodimer on the plasma membrane is also regulated by constitutive internalization. Up to 30% of class I molecules bearing 125I-Fab-labeled mAb to class I are internalized over 2 h at 37 degrees C. Therefore, inducible synthesis of class I by PMN is likely a consequence of post-transcriptional regulation, whereas the continued synthesis of class I heterodimer is required for maintenance of its expression. Furthermore, there is no increase in class I expression, in spite of increased synthesis, due to the release of class I heterodimer and beta 2m and the internalization of class I heterodimer from the plasma membrane. Thus, PMN are capable of post-transcriptional regulation of protein synthesis and are able to modulate the expression of plasma membrane proteins by regulated expression, release, and internalization.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1991

The effect of body posture on exercise- and hyperventilation-induced asthma.

Recent studies have shown that swimming is of relatively low asthmogenicity, even under conditions of high respiratory heat (and/or water) loss (RHL). It has been suggested that the horizontal body position may contribute to swimming's low asthmogenicity. We studied the effects of upright and prone body postures on pulmonary function following exercise (EIA) and after nonexercise hyperventilation (HIA). Twelve asthmatic boys (aged 12 to 16 years) underwent two 8-min exercise sessions of shoulder flexion-extension and two 8-min isocapnic hyperventilation treatments, in a counterbalanced order, either while lying prone or standing upright. All tests were carried out in a climatic chamber at 10 +/- 1 degree C and 31 +/- 2 percent relative humidity. Minute ventilation (VE) was kept constant at a predetermined individual level during all treatments. No differences were observed in pulmonary functions between the prone and upright postures following either exercise (FEV1 = -20.5 +/- 18.7 percent vs -22.2 +/- 18.7 percent, respectively) or hyperventilation (FEV1 = -29.6 +/- 19.0 percent vs -29.7 +/- 20.2 percent). We conclude that body posture on land has no meaningful effect on the severity of bronchoconstriction in asthmatic children; however, in view of some conceivable physiologic benefits of the prone position in water, an interactive effect on swimming-induced asthma (SIA) of body posture and water immersion cannot be ruled out.

Adolescent↗