[The use of telemetric intracranial pressure monitoring in the differential diagnosis of idiopathic intracranial hypertension - a case report]. / Vyuzití telemetrického monitorování intrakraniálního tlaku v diferenciální diagnostice idiopatické nitrolební hypertenze - kazuistika.

Idiopathic intracranial hypertension is a disorder that results from an increase of intracranial pressure with unknown cause. A single measurement of intracranial pressure only provides data at one given point in time. Therefore, telemetric monitoring of intracranial pressure was performed in a patient with fluctuating headache and significantly impaired vision, which together accounted for 226.2 hours of recording during normal daily activities. Elevated intracranial pressure was not found during monitoring, so we did not indicate the patient for shunt surgery.

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.

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.

[The use of moderate hypothermia in neurosurgery]. / Pouzití mírné hypotermie v neurochirurgii

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.

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.

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.

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.

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.

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.).

Effect of APF gel on a glass ionomer cement: an SEM study.

This SEM study evaluated the micromorphological effect of a 1.23 percent acidulated phosphate fluoridated gel (Oral B)(APF) on the surface of a glass ionomer cement (Ketac-Fil). Glass ionomer (GI) cylinders (area 6.69 mm) were prepared and divided into seven groups of ten specimens each: Group 1, glaze, no polishing; Group 2, glaze, polishing, glaze; Group 3, glaze, no polishing, APF for four minutes; Group 4, glaze, polish, glaze, APF for four minutes; Group 5, no glaze, no polish, APF for four minutes; Group 6, no glaze, polish, APF for four minutes; Group 7, glaze, polish, two coats of glaze, APF for four minutes. The glass ionomer was handled according to manufacturer's instructions, except for groups 5 and 6, where no glaze was used. Polishing was done with medium Sof-Lex discs, using slow-speed and water. The glaze resin (Ketac-Glaze) was painted with a brush over the GI surface and cured with visible light (Demetron) for thirty seconds. In Group 7, the first coat was cured and then the second coat was applied. The APF was applied with a cotton applicator for four minutes, rinsed, and dried. All specimens were then mounted on aluminum stubs, coated, and evaluated under the SEM. The results indicated that the glaze tends to contract or incorporate into the GI matrix in all groups. When APF was used over the GI, the amount of glaze remaining over the surface was diminished, exposing the GI surface. When two coats of the glaze were used, minimal GI surface was exposed after APF treatment.

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.

Granulocyte-macrophage colony-stimulating factor increases synthesis and expression of CR1 and CR3 by human peripheral blood neutrophils.

Polymorphonuclear leukocytes (PMN) constitutively synthesize various plasma membrane proteins including CR1(3) (CD35), CR3 (or Mac-1) alpha-chain (CD11b) and MHC class I. PMN are also able to up-regulate rapidly the expression of CR1 and CR3 to the plasma membrane in response to agonists such as FMLP. To determine whether constitutive PMN translation was static or up-regulatable, PMN were cultured in the presence or absence of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) for 8 h. CR1, CR3 and class I proteins immunoprecipitated from lysates of 35S-methionine pulse-labeled PMN were resolved by SDS-PAGE, fluorographed and quantified by densitometry. GM-CSF-treated PMN synthesized 4.5-fold more class I protein, 3.7-fold more CR1, 2.4-fold more CD11b and 3.4-fold more CR3 beta-chain (CD18), compared with untreated control cells. Actinomycin D treatment of replicate samples of PMN decreased the amount of these proteins synthesized by each group of PMN from 30 to 90%, implying that continued translation was required for the increases in protein synthesis. Nascent CR and class I proteins were inserted into the plasma membrane of PMN, thereby supplementing the molecules already expressed on the cell surface. In addition to these longer term effects of GM-CSF, we observed its acute up-regulatory effects on PMN. GM-CSF induced a five- to 12-fold increase in the expression of CR1 and CR3 on the PMN cell surface within 30 min. These increases were both dose- and time-dependent with maximum up-regulation occurring at 25 pM and at 30 min. In contrast to the long term biosynthetic events, this rapid up-regulation was not dependent on protein synthesis but was due instead to mobilization of CR from intracellular compartments similar to those up-regulated by FMLP. These results demonstrate that PMN can respond to microenvironmental stimuli such as GM-CSF both by rapidly up-regulating and increasing translation and expression of functionally important plasma membrane proteins.

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.