Search PubMed⌕ Search

Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 181 records · Page 10Linked to original sources

Long-term semantic priming: a computational account and empirical evidence.

Semantic priming is traditionally viewed as an effect that rapidly decays. A new view of long-term word priming in attractor neural networks is proposed. The model predicts long-term semantic priming under certain conditions. That is, the task must engage semantic-level processing to a sufficient degree. The predictions were confirmed in computer simulations and in 3 experiments. Experiment 1 showed that when target words are each preceded by multiple semantically related primes, there is long-lag priming on a semantic-decision task but not on a lexical-decision task. Experiment 2 replicated the long-term semantic priming effect for semantic decisions with only one prime per target. Experiment 3 demonstrated semantic priming with much longer word lists at lags of 0, 4, and 8 items. These are the first experiments to demonstrate a semantic priming effect spanning many intervening items and lasting much longer than a few seconds.

Adult↗

Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial.

BACKGROUND: At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn's disease (CD). AIM: To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD. PATIENTS: Patients with active CD, who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied. METHODS: Methotrexate (12.5 mg weekly) or 6-mercaptopurine (50 mg daily), or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinically indicated. RESULTS: Eighty-four patients were included (methotrexate, 26 patients; 6-mercaptopurine, 32 patients; placebo, 26 patients). The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups. The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar. However, when each patient was evaluated as his or her own control, the reduction in steroid dose, the general well being, and the reduction in abdominal pain were significantly better in the methotrexate treated patients. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD.

Abdominal Pain↗

[MRI aspect of hepatic adenomatosis].

We report a case of hepatic adenomatosis demonstrated with MR imaging. The diagnosis can be suspected when this technique shows multiple hepatic lesions which present an iso-signal intensity on T1-wi, a hyperintense signal on T2-wi and rapid wash-in and wash-out of gadolinium. Injection of superparamagnetic iron oxide mag be useful in the characterization of the lesion: a decreased signal intensity after injection rules out the diagnosis of metastasis. Because of the unknown course of hepatic adenomatosis, histological proof and radiological follow-up are recommended.

Adenoma↗

Intracellular transport and processing of the Marburg virus surface protein in vertebrate and insect cells.

The surface protein (GP) of Marburg virus (MBG) is synthesized as a 90-kDa precursor protein which is cotranslationally modified by the addition of high-mannose sugars (140 kDa). This step is followed by the conversion of the N-linked sugars to endoglycosidase H (endo H)-resistant species and the addition of O-linked oliosaccharides leading to a mature protein of 170-200 kDa approximately 30 min after pulse labelling. The mature form of GP is efficiently transported to the plasma membrane. GP synthesized using the T7 polymerase-driven vaccinia virus expression system was transported with essentially the same kinetics as the authentic GP. However, the protein that is shown to appear 30 min after pulse labeling at the plasma membrane was slighly smaller (160 kDa) than GP incorporated into the virions (170 kDa). Using a recombinant baculovirus, GP was expressed at high levels in insect cells. Three different species could be identified: a 90-kDa unglycosylated GP localized in the cytoplasm and two 140-kDa glycosylated proteins. Characterization of the glycosylated GPs revealed that processing of the oligosaccharides of GP was less efficient in insect cells than in mammalian cells. The majority of GP remained endo H sensitive containing high-mannose type N-linked glycans, whereas only a small fraction became endo H resistant carrying processed N-glycans and O-glycans. Tunicamycin treatment of the GP-expressing cells demonstrated that N-glycosylation is essential for the transport of the MBG surface protein.

Animals↗

Termini of all mRNA species of Marburg virus: sequence and secondary structure.

The 3' and 5' ends of Marburg virus (MBG)-specific mRNA species have been determined using reverse transcription-PCR, rapid amplification of cDNA ends, or the reverse ligation-mediated PCR procedure after removal of cap structures with tobacco acid pyrophosphatase. The polyadenylation sites of all MBG-specific mRNAs were strictly conserved and corresponded to the predicted transcriptional stop signals of genomic RNA. Determination of the 5' ends of the mRNA species showed that mRNA synthesis started precisely at the first nucleotide of a highly conserved transcriptional start site. The 5' ends of the mRNA species can build a stable secondary structure with the conserved nucleotides always located in the stem region of a hairpin. Nucleotide substitutions in the conserved 5' regions are accompanied by compensatory mutations of the complementary nucleotide thus leading to a conservation of the secondary structures. Compensatory mutations were also found when 5' ends of mRNA of MBG strain Musoke were compared with MBG strain Popp or the closely related Ebola virus, indicating that the secondary structures will be conserved even if the sequence is altered.

Base Sequence↗

Effect of not breastfeeding on the risk of diarrheal and respiratory mortality in children under 2 years of age in Metro Cebu, The Philippines.

The effects of not breastfeeding on mortality due to diarrhea and acute lower respiratory infection (ALRI) in children under 2 years of age were examined using data from a 1988-1991 longitudinal study of 9,942 children in Metro Cebu, The Philippines. Cox regression methods were used to study the magnitude of the risks, possible interactions with birth weight and nutritional status, and the effect of additional confounding factors. Not breastfeeding had a greater effect on diarrheal mortality than on ALRI mortality. In the first 6 months of life, failing to initiate breastfeeding or ceasing to breastfeed resulted in an 8- to 10-fold increase in the rate of diarrheal mortality. The rate of mortality associated with both ALRI and diarrhea was increased nearly six times by not breastfeeding, but the rate of ALRI mortality alone was not increased. The data also suggested that the risk of mortality associated with not breastfeeding was greater for low birth weight infants and infants whose mothers had little formal education. After age 6 months, the protective effects of breastfeeding dropped dramatically. These findings underscore the importance of promoting breastfeeding, especially during the first 6 months of life, and of targeting high risk groups such as low birth weight babies and those of low socioeconomic status.

Adult↗

Photoaffinity labelling of lactate dehydrogenase from pig heart with a bifunctional NAD(+)-analogue.

P1-N6-(4-azidophenylethyl)adenosine-P2-4-(3-azidopyridinio)b utyl diphosphate was synthesized with an [8-14C]adenine label. This bifunctional photoaffinity labelling reagent inactivates lactate dehydrogenase from pig heart upon irradiation with light of wavelength 300-380 nm. Stoichiometry of binding and enzymatic parameters suggest that the analogue is bound to the coenzyme binding site and that adjacent residues are modified. Four radioactive peptides were isolated by reverse-phase HPLC after tryptic digestion of the labelled protein. Amino-acid sequence analysis identified the peptides and correlation with the three-dimensional structure of dogfish lactate dehydrogenase reveals that the peptides correspond to positions affecting the coenzyme binding site, consistent with proper affinity labelling. Two of the peptides, Ile-77 --> Lys-81 and Asp-82 --> Asn-88, are located close to the adenine binding site. Low recovery of Thr-86 in combination with the detection of additional products in the sequence analysis indicates that this residue is modified by the photoaffinity label. The two other peptides (positions 119-124 and 318-328) are located next to the substrate binding site; their label is lost upon treatment with pyrophosphatase, showing that they are linked to the pyridinio moiety of the coenzyme analogue.

Affinity Labels↗

Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: a comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure.

Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and prostaglandins (PGE2) have been reported in humans as early as 3 hr and as late as 18 hr after exposure. The purpose of this study was to determine whether a broad range of inflammatory mediators are elevated in BAl fluid within 1 hr of exposure. We exposed eight healthy volunteers twice: once to 0.4 ppm ozone and once to filtered air. Each exposure lasted for 2 hr during which the subjects underwent intermittent heavy exercise (66 liters/min). BAL was performed 1 hr after the exposure. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE2, thromboxane B2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the recovery of total cells and alveolar macrophages, and decreased ability of alveolar macrophages to phagocytize Candida albicans. A comparison of these changes with changes observed in an earlier study in which subjects underwent BAL 18 hr after an identical exposure regimen indicates that IL-6 and PGE2 levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a were present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time.

Adolescent↗

Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production.

A number of epidemiological studies have associated increased cardiopulmonary mortality and hospital admissions with episodes of high particulate air pollution. Inhaled particles, with a mass median aerodynamic diameter <10 microm (PM10) reach the lower respiratory tract where they are phagocytized by alveolar macrophages (AM). Depending on particle composition, exposed AM may produce reactive oxygen species and inflammatory mediators resulting in vascular permeability changes, airway constriction, tissue injury, and inflammation. In the present study human and rat AM were reacted with a range of environmental particles, including oil fly ash (OFA), diesel dust (DD), and ambient air particles (UAP) collected in four urban centers. AM were tested for a chemiluminescence response induced by the particles as well as IL-6 and TNF production. While OFA in a dose range of 1000-10 microg/2-3 x 10(5) AM caused acute cytotoxicity above 100 microg in both human and rat AM (LDH release at 2 hr), DD and UAP were found to be nontoxic in the same dose range. However, after 20 hr of coincubation, UAP concentrations >167 microg/ml were also cytotoxic. Subcytotoxic concentrations of OFA induced a strong immediate chemiluminescence response by AM. A small but significant chemiluminescence response was induced by two out of three UAP tested, while no chemiluminescence was generated in response to DD. The magnitude of particle-induced chemiluminescence was not predictive of a cytokine response by either human or rat AM. TNF and IL-6 production was strongly induced by UAP over a range of noncytotoxic concentrations of particles. OFA induced only small amounts of TNF in a subset of human AM preparations, but not in rat AM. The AM cytokine response to UAP was partly inhibitable by polymyxin B, but not by the iron chelator deferoxamine, indicating that endotoxins but not transitional iron were cytokine-inducing moieties in the tested UAP preparations.

Adolescent↗

Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation and lung function changes.

Inhalation of O3 causes airways neutrophilic inflammation accompanied by other changes including increased levels of cyclo-oxygenase products of arachidonic acid in bronchoalveolar lavage fluid (BALF). Ozone O3 exposure also causes decreased forced vital capacity (FVC) and forced expiratory volume after 1 s (FEV(1)), associated with cough and substernal pain on inspiration, and small increases in specific airway resistance (SRAW). The spirometric decrements are substantially blunted by pretreatment with indomethacin. Since the O3-induced decrement in FVC is due to involuntary inhibition of inspiration, a role for stimulation of nociceptive respiratory tract afferents has been suggested and cyclo-oxygenase products have been hypothesized to mediate this stimulation. However, the relation (if any) between the O3-induced neutrophilic airways inflammation and decreased inspiratory capacity remains unclear. We studied the effects of pharmacologic inhibition of O3-induced spirometric changes on the inflammatory changes. Each of ten healthy men was exposed twice (5-week interval) to 0.4 ppm O3 for 2 h, including 1 h of intermittent exercise (ventilation 601*min(-1)). One-and-a-half hours prior to and midway during each exposure the subject ingested 800 mg and 200 mg, respectively, of the non-steroidal anti-inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in randomized, double-blind fashion. Spirometry and body plethysmography were performed prior to drug administration, and before and after O3 exposure. Immediately following postexposure testing, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed. Neither IBU nor PLA administration changed pre-exposure lung function. O3 exposure (with PLA) caused a significant 17 percent mean decrement in FEV(1) (P <0.01) and a 56 percent increase in mean SRAW. Following IBU pretreatment, O3 exposure induced a significantly lesser mean decrement in FEV(1) (7 percent) but still a 50 percent increase in mean SRAW. IBU pretreatment significantly decreased post-O3 BAL levels of prostaglandin E2 (PGE2) by 60.4 percent (P <0.05) and thromboxane B(2) (TxB(2)) by 25.5 percent (P <0.05). Of the proteins, only interleukin-6 was significantly reduced (45 percent, P <0.05) by IBU as compared to PLA pretreatment. As expected, O3 exposure produced neutrophilia in BALF. There was, however, no effect of IBU on this finding. None of the major cell types in the BALF differed significantly between pretreatments. We found no association between post-exposure changes of BALF components and pulmonary function decrements. We conclude that IBU causes significant inhibition of O3-induced increases in respiratory tract PGE(2) and TxB(2) levels concomitant with a blunting of the spirometric response. This is consistent with the hypothesis that the products of AA metabolism mediate inhibition of inspiration. However, IBU did not alter the modest SRAW response to O3.

Adult↗

Assessment of the combined orthodontic-surgical treatment from the patients' point of view. A longitudinal study.

In a longitudinal study, 40 patients who underwent a combined orthodontic-surgical treatment, were interviewed 4 weeks before operation and 1 week and/or half a year after surgery in order to evaluate patients' expectations and appraisal of the operation and their psycho-social situation. The comparisons between the patients' pre- and postoperative statements yielded the following picture: the patients showed a high degree of satisfaction with the result of the operation. They judged their postoperative facial appearance, with the help of a "semantic differential', to be significantly more attractive. Satisfaction also was expressed in a higher degree of psychological well-being and thus an increase in self-confidence and motivation. Postoperatively, the "Giessen test' showed also a distinctly positive change of the patients' mood and improved experiences with social interaction. Before the operation almost half of the patients feared sensitivity loss or disturbance. One out of 5 patients did in fact suffer from this problem--but not from pain--half a year after the operation. Some patients felt they had received insufficient prior information about the procedure and the risk of the operation. In spite of all burdens for the patients, the assessment of the result of the operation is (generally) positive, not only from the medical point of view.

Adolescent↗

Direction-selective adaptation and simultaneous contrast induced by stereoscopic (cyclopean) motion.

Across four experiments, this study investigated direction-specific adaptation and simultaneous contrast induced by moving binocular disparity information (stereoscopic motion). The stimuli were moving arrays of stereoscopic dots created from dynamic random-element stereograms. Experiments 1 and 2 examined the effects of adaptation to motion in a given direction on the apparent direction of test motion. Results showed that the direction of test motion appeared repulsed away from the direction of adapting motion (repulsion aftereffect) by as much as 20 deg or more when directions of adapt and test were similar. Experiment 3 investigated transfer of the repulsion aftereffect across the stereoscopic and luminance domains by employing stereoscopic adapting motion and luminance test motion or vice versa. Results showed that the repulsion aftereffect transferred across the two stimulus domains. Experiment 4 investigated direction-specific contrast by measuring the perceived direction of two stereoscopic arrays presented simultaneously and moving in different directions. Results showed that the directions of the arrays appeared repulsed away from one another when their directions were similar. Taken together, these results suggest that the direction of stereoscopic motion is coded in the activity of directionally selective mechanisms, as is the case for luminance-domain motion. Transfer of the repulsion aftereffect between stereoscopic and luminance domains indicates the two kinds of motion perception are mediated by a common substrate.

Adaptation, Ocular↗

2,3,7,8-TCDD induces cytochrome P450 enzyme activity but not proliferation or phenotypical changes in human peripheral blood lymphocytes.

In contrast to the well documented immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans accidentally or occupationally exposed to dioxin. More recently, a dose-dependent decrease of specific subpopulations of mitogen-activated human peripheral blood lymphocytes (PBL), including helper-inducer/memory cells (CD4+CD29+) and B cells (CD20+), was reported after in vitro treatment with dioxin concentrations as low as 10(-12)-10(-14) M TCDD [1]. Therefore, the direct effects of dioxin on human PBL subpopulations have been studied in more detail, in order to assess the availability of a sensitive indicator system for human dioxin exposure. PBL from healthy volunteers were stimulated with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody (OKT3) and treated with 10(-7)-10(-14) M TCDD for 3-4 days. Cytochrome P450 (CYP1A1) enzyme induction was determined by the ethoxy-resorufin-O-deethylase (EROD) assay. Percentages of the different lymphocytes subsets, including CD2 (T cells), CD4, CD45 RA (suppressor-inducer/ virgin T cells), CD4, CD29, CD8, CD19 (B cells), as well as interleukin 2 (IL-2) receptor (CD25) and class II antigen (human leukocyte antigen HLA-DR) expression, were analyzed by flow cytometry. The proliferative activity was determined by 3H-thymidine uptake after 3-4 days of culture. In the present study, all stimulated lymphocyte cultures showed a significant increase of CYP1A1 activity at dioxin concentrations of 10(-7) and 10(-9) M. In contrast, alterations in surface antigen expression or suppression of proliferative responses did not occur in the mitogen-activated PBL over the whole concentration range of TCDD. These results clearly demonstrate that lymphoproliferation, as well as phenotypes of human PBL, are not affected by dioxin treatment and thus are not useful as sensitive biomarkers in human exposure studies.

Adolescent↗

Interactions between a pore-blocking peptide and the voltage sensor of the sodium channel: an electrostatic approach to channel geometry.

Few experimental data illuminate the relationship between the molecular structures that mediate ion conduction through voltage-dependent ion channels and the structures responsible for sensing transmembrane voltage and controlling gating. To fill this void, we have used a strongly cationic, mutated mu-conotoxin peptide, which only partially blocks current through voltage-dependent sodium channels, to study voltage-dependent activation gating in both bound and unbound channels. When the peptide binds to the ion-conducting pore, it inhibit channel opening, necessitating stronger depolarization for channel activation. We show that this activation shift could result entirely from electrostatic inhibition of the movement of the voltage-sensing S4 charges and estimate the approximate physical distance through which the S4 charges move.

Animals↗

Risk factors for wasting and stunting among children in Metro Cebu, Philippines.

Risk factors for wasting and stunting were examined in a longitudinal study of 18 544 children younger than 30 mo in Metro Cebu, Philippines. Measures of household demographic and socioeconomic characteristics, maternal characteristics and behavior, and child biological variables were analyzed cross-sectionally in six child age-residence strata by using logistic regression. Our results support biological and epidemiologic evidence that wasting and stunting represent different processes of malnutrition. They also indicate that the principal risk factors for stunting and wasting in infants < 6 mo of age were either maternal behaviors or child biological characteristics under maternal control, eg, breast-feeding status and birth weight. After 6 mo of age, household socioeconomic characteristics emerged with behavioral and biological variables as important determinants of malnutrition, eg, father's education and presence of a television and/or radio. Household socioeconomic status influenced the risk of stunting earlier in rural than in urban barangays. Implications of the results for interventions are discussed.

Aging↗