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Biomedical subjects

A Becker

Publications and source records attributed to A Becker.

At least 199 records · Page 11Linked to original sources
PubMed1999

Disruption of latent inhibition in rats with postnatal hippocampal lesions.

Disruption of latent inhibition has been proposed as a possible model of cognitive abnormalities that underlie positive symptoms of a schizophrenia. We tested neonatal hippocampal lesioned rats in a latent inhibition paradigm. Lesions of the ventral hippocampus were induced by bilateral injections of ibotenic acid in 7 days old rats. The behavior of lesioned rats was tested postpubertally. We found a hyperresponsiveness to dopaminergic stimulation by apomorphine in locomotion tests. Latent inhibition was tested using the acquisition of a conditioned reaction in a two-way shuttle box. Sham operated control animals showed after preexposure of the to-be-conditioned stimulus (combined tone and light stimulus) a low acquisition. Ibotenic acid lesioned animals learned the conditioned reaction with and without preexposure in the same way, indicating disturbed latent inhibition. These results demonstrate disturbances in early postnatal hippocampal lesioned rats comparable with those seen in schizophrenic patients, thus further validating this procedure as a useful animal model of some aspects of schizophrenia.

Anesthesia↗
PubMed1999

The use of panoramic radiographs to localize displaced maxillary canines.

OBJECTIVE: The purpose of this investigation was to develop a reliable method of diagnosing the position of a displaced maxillary canine on the basis of a single panoramic radiograph. STUDY DESIGN: A total of 115 panoramic radiographs depicting 164 displaced maxillary canines were evaluated. The ratio of the width of the displaced canine to the width of the homolateral central incisor (the canine-incisor index) and the ratio of the width of the displaced canine to the width of the contralateral canine (the canine-canine index) were calculated. The height of the crown of each displaced canine was classified in the vertical plane, relative to the adjacent incisor, as apical, middle, or coronal. RESULTS: There was an overlap in the canine-incisor index ranges of the buccal (0.94-1. 45) and palatal (1.15-1.29) canines in the apical zone. In the middle and coronal zones, a clear difference could be seen between the canine-incisor indices of labially (0.78-1.11) and palatally (1.15-1.7) located canines. A cut-off point of 1.15 was determined. CONCLUSIONS: Provided that vertical restriction and the canine-incisor index are used, the panoramic radiograph can serve as a useful indicator for determining the position of an unerupted maxillary canine.

Adolescent↗
PubMed1999

Clinical practice guidelines for the use of albumin: results of a drug use evaluation in a Paris hospital. Tenon Hospital Paris.

Clinical practice guidelines on the prescription of albumin were instituted in our hospital according to a method which combined a review of the medical literature with experts points of view. Their broadcasting was based upon a daily patient-specific decision support which was well-documented by the prescribing physician. The method for assessing the impact was a six month analysis of the discrepancies between recommendations and clinical practice. Results were a better compliance with guidelines (25.5% before and 59% after developing recommendations), a decrease 70% in grams of albumin prescribed and in use of an increase synthetic colloids, and a savings of $57,208 per year.

Blood Volume↗
PubMed1999

Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase.

Pyruvate formate-lyase (PFL) from Escherichia coli uses a radical mechanism to reversibly cleave the C1-C2 bond of pyruvate using the Gly 734 radical and two cysteine residues (Cys 418, Cys 419). We have determined by X-ray crystallography the structures of PFL (non-radical form), its complex with the substrate analog oxamate, and the C418A,C419A double mutant. The atomic model (a dimer of 759-residue monomers) comprises a 10-stranded beta/alpha barrel assembled in an antiparallel manner from two parallel five-stranded beta-sheets; this architecture resembles that of ribonucleotide reductases. Gly 734 and Cys 419, positioned at the tips of opposing hairpin loops, meet in the apolar barrel center (Calpha-Sgamma = 3.7 A). Oxamate fits into a compact pocket where C2 is juxtaposed with Cys 418Sgamma (3.3 A), which in turn is close to Cys 419Sgamma (3.7 A). Our model of the active site is suggestive of a snapshot of the catalytic cycle, when the pyruvate-carbonyl awaits attack by the Cys 418 thiyl radical. We propose a homolytic radical mechanism for PFL that involves Cys 418 and Cys 419 both as thiyl radicals, with distinct chemical functions.

Acetyltransferases↗
PubMed1999

Impact of guidelines implemented in a paris university hospital: application to the use of antiemetics by cancer patients.

AIMS: To assess the impact with time of guidelines on antiemetic use in an 850-bed Paris university hospital with a high proportion of cancer patients. METHODS: Guidelines on the use of antiemetics available in cancer chemotherapy were drafted according to the Delphi technique. Their implementation was based upon a patient-specific antiemetic prescription form. To assess the impact of guideline implementation over time, discrepancies between current practice and the guidelines were compared before guideline implementation (between March and August 1995) and after implementation (between March and August 1997, and March and August 1998). RESULTS: Before the Delphi panel's guidelines were implemented, 5-HT3 antagonists were inappropriately administered in 70% of cases. After guideline implementation, this proportion dropped significantly (P<0.0001, Fisher's exact test) to 22% between March and August 1997 and 28% between March and August 1998. CONCLUSIONS: Implementation of guidelines seems to have resulted in significant changes with time, although a causal relationship has not been demonstrated. The development of guidelines by our hospital's multidisciplinary working group helped the various consultants to adjust medical practices to take account of these changes.

Academic Medical Centers↗
PubMed1999

Living anatomy of the atrioventricular junctions. A guide to electrophysiological mapping. A Consensus Statement from the Cardiac Nomenclature Study Group, Working Group of Arrythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE. North American Society of Pacing and Electrophysiology.

Current nomenclature for atrioventricular junctions derives from a surgically distorted view, placing the valvar rings and the triangle of Koch in a single plane with antero-posterior and right-left lateral coordinates. Within this convention, the aorta is considered to occupy an anterior position, while the mouth of the coronary sinus is shown as being posterior. While this nomenclature has served its purpose for the description and treatment of arrhythmias dependent on accessory pathways and atrioventricular nodal re-entry, it is less than satisfactory for the description of atrial and ventricular mapping. To correct these deficiencies, a consensus document has been prepared by experts from the Working Group of Arrhythmias of the European Society of Cardiology, and the North American Society of Pacing and Electrophysiology. It proposes a new, anatomically sound, nomenclature that will be applicable to all chambers of the heart. In this report, we discuss its value as regards the description of the atrioventricular junctions, establishing the principles of this new nomenclature.

Atrioventricular Node↗
PubMed1999

Effect of 1alpha,25(OH)2-vitamin D3 on TNF alpha-mediated apoptosis of human primary osteoblast-like cells in vitro.

1alpha,25(OH)2-vitamin D3 is a hormone which potentially stimulates bone cell growth and differentiation. TNFalpha is one possible inductor for apoptosis; apoptosis being an important regulatoring factor for bone modelling and remodelling. We examined the influence of physiological levels (0.1 nM) 1alpha,25(OH)2-vitamin D3 on TNFalpha-mediated apoptosis in human osteoblast-like cells. These human cells were obtained from bone fragments obtained during orthopedic operations on patients without systemic bone disease. Treatment with 1alpha,25(OH)2-vitamin D3 for 8 weeks resulted in a significant reduction (30%) of viable cell number compared to untreated cells. Incubation with TNFalpha (100 ng/ml for 4 hours) only had limited effects on the rate of apoptosis in control cells. After pretreatment with 1alpha,25(OH)2-vitamin D3, induction of apoptosis increased up to 10% in human osteoblast-like cells. In parallel to the induction of apoptosis, 1alpha,25(OH)2-vitamin D3 stimulated osteocalcin and alkaline phosphatase as markers of mature osteoblasts. Our data suggest that 1alpha,25(OH)2-vitamin D3 has a stimulatory effect on TNFalpha-induced apoptosis in human osteoblast-like cells as a result of 1alpha,25(OH)2-vitamin D3-induced cell differentiation.

Alkaline Phosphatase↗
PubMed1999

Peripheral blood mononuclear cells promote intestinal epithelial restitution in vitro through an interleukin-2/interferon-gamma-dependent pathway.

BACKGROUND: Acute intestinal mucosal inflammation is associated with recruitment of peripheral blood mononuclear cells (PBMN) into the mucosa and migration across the epithelium. It has recently been shown that several PBMN-derived cytokines, including transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) may modify intestinal epithelial cell function, resulting in rapid improvement of wound repair. Our aim was to characterize the modulating effects of PBMN on intestinal epithelial restitution, the initial step of wound healing. METHODS: PBMN were separated from whole blood, obtained from healthy volunteers, by using a density gradient. The effect of PBMN on intestinal epithelial restitution was assessed by using an in vitro coculture wounding model with non-transformed small-intestinal epithelial IEC-6 cells. RESULTS: Coculture of PBMN caused a significant enhancement of epithelial cell restitution in vitro. The modulatory effects of PBMN could be significantly blocked by adding immunoneutralizing anti-IL-2 or anti-IFN-gamma to the culture media, suggesting that PBMN may modulate intestinal epithelial migration through an IL-2- and IFN-gamma-dependent pathway. In contrast, PBMN-induced stimulation of intestinal epithelial restitution was not influenced by addition of anti-TGF-beta or anti-TNF-alpha, suggesting that these cytokines are not critical for the modulation of restitution by PBMN. CONCLUSIONS: These findings suggest that PBMN may promote intestinal epithelial wound repair by enhancing restitution through secretion of various cytokines, among them IL-2 and IFN-gamma, which are abundantly expressed in the course of several inflammatory diseases of the gut.

Animals↗
PubMed1999

Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a dominantly inherited disorder characterized by patent fontanelles, wide cranial sutures, hypoplasia of clavicles, short stature, supernumerary teeth, and other skeletal anomalies. We recently demonstrated that mutations in the transcription factor CBFA1, on chromosome 6p21, are associated with CCD. We have now analyzed the CBFA1 gene in 42 unrelated patients with CCD. In 18 patients, mutations were detected in the coding region of the CBFA1 gene, including 8 frameshift, 2 nonsense, and 9 missense mutations, as well as 2 novel polymorphisms. A cluster of missense mutations at arginine 225 (R225) identifies this residue as crucial for CBFA1 function. In vitro green fluorescent protein fusion studies show that R225 mutations interfere with nuclear accumulation of CBFA1 protein. There is no phenotypic difference between patients with deletions or frameshifts and those with other intragenic mutations, suggesting that CCD is generally caused by haploinsufficiency. However, we were able to extend the CCD phenotypic spectrum. A missense mutation identified in one family with supernumerary teeth and a radiologically normal skeleton indicates that mutations in CBFA1 can be associated exclusively with a dental phenotype. In addition, one patient with severe CCD and a frameshift mutation in codon 402 had osteoporosis leading to recurrent bone fractures and scoliosis, providing first evidence that CBFA1 may help maintain adult bone, in addition to its function in bone development.

Bone and Bones↗
PubMed1999

Crystal structure of brain-type creatine kinase at 1.41 A resolution.

Excitable cells and tissues like muscle or brain show a highly fluctuating consumption of ATP, which is efficiently regenerated from a large pool of phosphocreatine by the enzyme creatine kinase (CK). The enzyme exists in tissue--as well as compartment-specific isoforms. Numerous pathologies are related to the CK system: CK is found to be overexpressed in a wide range of solid tumors, whereas functional impairment of CK leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. The crystal structure of chicken cytosolic brain-type creatine kinase (BB-CK) has been solved to 1.41 A resolution by molecular replacement. It represents the most accurately determined structure in the family of guanidino kinases. Except for the N-terminal region (2-12), the structures of both monomers in the biological dimer are very similar and closely resemble those of the other known structures in the family. Specific Ca2+-mediated interactions, found between two dimers in the asymmetric unit, result in structurally independent heterodimers differing in their N-terminal conformation and secondary structure. The high-resolution structure of BB-CK presented in this work will assist in designing new experiments to reveal the molecular basis of the multiple isoform-specific properties of CK, especially regarding different subcellular locations and functional interactions with other proteins. The rather similar fold shared by all known guanidino kinase structures suggests a model for the transition state complex of BB-CK analogous to the one of arginine kinase (AK). Accordingly, we have modeled a putative conformation of CK in the transition state that requires a rigid body movement of the entire N-terminal domain by rms 4 A from the structure without substrates.

Adenosine Triphosphate↗
PubMed1999

ESCWGA/NASPE/P experts consensus statement: living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. Working Group of Arrhythmias of the European Society of Cardiology. North American Society of Pacing and Electrophysiology.

Current nomenclature for the AV junctions derives from a surgically distorted view, placing the valvar rings and the triangle of Koch in a single plane with anteroposterior and right-left lateral coordinates. Within this convention, the aorta is considered to occupy an anterior position, whereas the mouth of the coronary sinus is shown as being posterior. Although this nomenclature has served its purpose for the description and treatment of arrhythmias dependent on accessory pathways and AV nodal reentry, it is less than satisfactory for the description of atrial and ventricular mapping. To correct these deficiencies, a consensus document has been prepared by experts from the Working Group of Arrhythmias of the European Society of Cardiology and from the North American Society of Pacing and Electrophysiology. It proposes a new, anatomically sound, nomenclature that will be applicable to all chambers of the heart. In this report, we discuss its value for description of the AV junctions and establish the principles of this new nomenclature.

Atrioventricular Node↗
PubMed1999

The etiology of palatal displacement of maxillary canines.

OBJECTIVES: To test the hypothesis that palatal displacement of the maxillary canine is completely under genetic influence. DESIGN: A randomized controlled design studied cases affected by a severe expression of lateral incisor anomaly on one side and by milder expression of the same anomaly on the other. Comparison of frequency of occurrence of unilateral palatally displaced canine measured in each. Each side acted as control for the other within the same individual. SETTING AND SAMPLE POPULATION: The Departments of Orthodontics of the Universities of Jerusalem and Tel Aviv and in private practice. From approximately 12,000 consecutively treated patients, all those exhibiting an anterior maxilla with a missing lateral incisor on one side, a peg-shaped or reduced lateral incisor on the other, and a palatally displaced canine (n = 19). OUTCOME MEASURE: Missing lateral incisors, peg-shaped, and reduced lateral incisors (all genetically determined characters) have been shown to be associated with palatal displacement of the canine. The canine displacement is presumed by some authorities to be similarly genetically determined. If this is so, then the impacted canine should occur with equal frequency on either side in the patient with a missing lateral incisor on one side and a peg-shaped or reduced lateral incisor on the other. RESULTS: The canine aberration occurred far more frequently on the side of the diminutive lateral incisor. CONCLUSION: There is an environmental factor involved in the palatal displacement of maxillary canines.

Anodontia↗
PubMed1999

Reliability of a method for the localization of displaced maxillary canines using a single panoramic radiograph.

The present study was initiated to determine the validity and reproducibility of a method previously reported for localization of displaced maxillary canines by panoramic radiographs. Eleven dental specialists (five orthodontists, five surgeons, and one radiologist) and five (final year) dental students were asked to interpret initial panoramic radiographs of 20 patients with 26 unerupted canines. The method contends that, provided that the radiographic image of the unerupted canines superimposes on the root of the lateral incisor at a height coronal to the apical third, a ratio between the widest mesiodistal dimension of the affected canine and the homolateral central incisor [Canine-Incisor Index (CII)] of more than 1.15 indicates palatal displacement. Among the observers, the measurement error was small, insufficient to cause overlap between the ranges of values for the CII of buccal and palatal canines. Inter-observer reproducibility was high. Without exception, all observers correctly diagnosed the location of each of the impacted canines. The CII cut-off point of 1.15, which was arbitrarily chosen in the previous work, was shown to be valid to differentiate buccal from palatal displacement. The present method is rapid, simple, accurate, and easily taught to dental students or dental specialists, with the simplest of initial instruction. While confirmations with other radiographic techniques is strongly advised before a definitive treatment is undertaken, this method has merit in providing more information than has been available from the panoramic radiograph hitherto, to satisfy the needs of an initial orthodontic consultation.

Adolescent↗
PubMed1999

New mobilizable vectors suitable for gene replacement in gram-negative bacteria and their use in mapping of the 3' end of the Xanthomonas campestris pv. campestris gum operon.

We describe useful vectors to select double-crossover events directly in site-directed marker exchange mutagenesis in gram-negative bacteria. These vectors contain the gusA marker gene, providing colorimetric screens to identify bacteria harboring those sequences. The applicability of these vectors was shown by mapping the 3' end of the Xanthomonas campestris gum operon, involved in biosynthesis of xanthan.

Base Sequence↗
PubMed1999

Histamine H3 receptor blockade improves cardiac function in canine anaphylaxis.

In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins, and leukotrienes on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. In a ragweed model of anaphylaxis, we examined whether pretreatment with H1, H2, H3 receptor blockers, and cyclooxygenase and leukotriene pathway inhibitors was useful in preventing the depression in left ventricular (LV) contractility known to occur in this model. The dose of allergen was varied to produce similar degrees of shock between treatments. The animals were studied under pentobarbital anesthesia in which the treatment studies were approximately 3 wk apart. LV volumes were measured by sonomicrometric techniques. During challenge, mean arterial blood pressure (Pa), cardiac output (Q), and LV end-diastolic pressure (LVEDP) decreased approximately 50% compared with preshock values in all treatments. Histamine H3 receptor blockade was associated with higher heart rates (HR) and higher stroke work (SW) (p < 0.05) as compared with the other treatment studies. We conclude that histamine H3 activation by inhibiting adrenergic neural norepinephrine release contributes to cardiovascular collapse in AS.

Anaphylaxis↗
PubMed1999

The relationship of mutations in the MTHFR, prothrombin, and PAI-1 genes to plasma levels of homocysteine, prothrombin, and PAI-1 in children and adults.

Studies in adults have demonstrated that the genetic mutations C677T methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210A, and the 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene are associated with elevated plasma levels of homocysteine. prothrombin and PAI-1, respectively and with an increased risk of thrombosis. No similar data is available in children. Therefore, we assessed the relationship of plasma levels of homocysteine, prothrombin and PAI-1 with their respective mutations in 197 normal children, compared to 40 adults. By stepwise multiple regression, homocysteine was positively associated with age, PAI-1 activity was negatively associated with age, while PAI-1 antigen and prothrombin levels were associated with gender, being higher in girls than boys. When the genotypes were added to the regression model as additional explanatory variables, the MTHFR genotype accounted for 2.9% of the variance of homocysteine (p = 0.024), and the PAI-1 gene accounted for 2.7% of the variance of PAI-1 antigen levels (p = 0.023). Of children homozygous for the MTHFR mutation, 35% had homocysteine levels > or = the age-specific 95th percentile, compared to 2% heterozygotes and 5% wild type normals (p = 0.0001). The mean homocysteine level was higher in children homozygous for the MTHFR gene (8.4 micromol/1) than in heterozygotes (5.5 micromol/l), p <0.05. Of children homozygous for the 4G polymorphism of the PAI-1 gene, 19% had PAI-1 activity levels > or = the age-specific 95th percentile, compared to 2% of heterozygotes and 3% of wild type normals (p = 0.003). Studies of the incidence of the MTHFR, prothrombin, and PAI-1 4G/5G genotypes in children with thrombosis, when compared to these healthy normals, will provide evidence as to which of these genes are associated with thrombophilia.

Adolescent↗