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Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 217 records · Page 12Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

O2 as the regulatory signal for FNR-dependent gene regulation in Escherichia coli.

With an oxystat, changes in the pattern of expression of FNR-dependent genes from Escherichia coli were studied as a function of the O2 tension (pO2) in the medium. Expression of all four tested genes was decreased by increasing O2. However, the pO2 values that gave rise to half-maximal repression (pO(0.5)) were dependent on the particular promoter and varied between 1 and 5 millibars (1 bar = 10(5) Pa). The pO(0.5) value for the ArcA-regulated succinate dehydrogenase genes was in the same range (pO(0.5) = 4.6 millibars). At these pO2 values, the cytoplasm can be calculated to be well supplied with O2 by diffusion. Therefore, intracellular O2 could provide the signal to FNR, suggesting that there is no need for a signal transfer chain. Genetic inactivation of the enzymes and coenzymes of aerobic respiration had no or limited effects on the pO(0.5) of FNR-regulated genes. Thus, neither the components of aerobic respiration nor their redox state are the primary sites for O2 sensing, supporting the significance of intracellular O2. Non-redox-active, structural O2 analogs like CO, CN-, and N3-, could not mimic the effect of O2 on FNR-regulated genes under anaerobic conditions and did not decrease the inhibitory effect of O2 under aerobic conditions.

Aerobiosis↗
PubMed1996

Victimization and PTSD in individuals with substance use disorders: gender and racial differences.

There is a paucity of studies concerning the prevalence of crime-related posttraumatic stress disorder (CR-PTSD) in individuals with substance use disorders, despite documentation of particularly high prevalence rates of sexual and physical assault in this population. A central objective of the present investigation was to assess victimization experiences and CR-PTSD among individuals receiving inpatient treatment for substance use disorders and evaluate gender and racial differences in assault characteristics CR-PTSD prevalence rates. A total of 95 inpatients (34 men and 61 women; 41 African-Americans, 52 Caucasians, and 2 other minorities) were administered a structured interview to assess substance abuse/dependence, trauma, and PTSD. Approximately 90% of the participants had a lifetime history of sexual and/or physical assault, and approximately 50% had CR-PTSD. With the exception of rape, no gender differences in assault or CR-PTSD prevalence rates were observed. Women were more likely than men to perceive their life as endangered during a rape. Men were younger than women when they experienced their first (or only) aggravated assault and were more likely to have been assaulted by a family member. No racial differences were detected for assault or PTSD, although African-American patients were significantly more likely to identify cocaine as their primary drug than Caucasian patients. Given the strikingly high rate of comorbid CR-PTSD among substance use disordered patients, exploration of the type and timing of interventions would be of clinical interest.

Adolescent↗
PubMed1996

Disease management: a contracting primer.

This article provides an understanding of the issues and steps that are required for negotiating a disease management contract. Because most of the author's experience derives from representing pharmaceutical companies and other provider driven entities, the tenor of the comments often reflects that perspective on negotiations. This article focuses on disease management contracting whereby a provider network or case manager assumes risk relating to the cost of providing care to a certain type of patient.

Budgets↗