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Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 271 records · Page 15Linked to original sources
PubMed1994

Grain dust-induced airflow obstruction and inflammation of the lower respiratory tract.

To investigate the relationship between the physiologic and biologic effects of grain dust inhalation, we exposed 15 nonsmoking, nonasthmatic, nonatopic male grain handlers to buffered saline and aqueous corn dust extract by inhalation challenge in a crossover study. The inhalation challenges to buffered saline and corn dust extract were separated by at least 14 d. Compared with buffered saline, inhalation of corn dust extract resulted in significant airflow obstruction, which was observed within 30 min of exposure and persisted for 5 h. Inhalation of corn dust extract resulted in an acute inflammatory response characterized by higher concentrations of neutrophils (p = 0.001), IL-1 beta (p = 0.001), IL-1RA (p = 0.001), IL-6 (p = 0.001), IL-8 (p = 0.001), and TNF-alpha (p = 0.04) in bronchoalveolar lavage (BAL) fluid. mRNA levels specific for IL-1 beta, IL-1RA, IL-6, and IL-8 from cells present in the BAL fluid were significantly greater after challenge with corn dust extract than after challenge with buffered saline. Importantly, no significant differences were observed in the concentration of lymphocytes or eosinophils in the BAL fluid following inhalation of corn dust extract, and the concentrations of histamine and 15-HETE were similar in BAL fluid after the two challenges. The maximal percentage decrease in FEV1 was significantly associated with the absolute neutrophil concentration in the BAL fluid (p = 0.001), as well as the concentration of TNF-alpha (p = 0.03), IL-1 beta (p = 0.005), IL-1RA (p = 0.001), IL-6 (p = 0.001), and IL-8 (p = 0.001) in the BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit.

Neutrophil infiltration is a prominent feature of Clostridium difficile-associated enteritis and colitis. The aim of this study was to examine the importance of neutrophil recruitment and neutrophil-mediated tissue damage in C. difficile toxin A-induced enteritis. Competitive binding experiments using purified 3H-toxin A demonstrated the presence of a single class of medium affinity receptors on rabbit neutrophils (Kd 7 x 10(-8) M). Pertussis toxin and the nonhydrolyzable GTP analog GTPgamma S both inhibited 3H-toxin A binding (by 56 and 65%, respectively), indicating that the rabbit neutrophil toxin A receptor is G protein linked. Toxin A elicited a dose-dependent (25-200 micrograms/ml) stimulation of neutrophil migration in vitro, and this functional effect was also pertussis toxin sensitive (69% inhibition). Treatment of neutrophils with R15.7, a blocking monoclonal antibody to the leuocyte adhesion molecule CD18, inhibited toxin A-stimulated neutrophil migration by 85% in vitro. Pretreatment of rabbits with R15.7 also prevented neutrophil infiltration of toxin A-exposed ileal loops in vivo as determined by histologic examination and by ileal tissue myeloperoxidase levels. Furthermore, R15.7 effected a substantial inhibition of fluid secretion (by 65%), mannitol permeability (by 66%), and histologic damage in toxin A-exposed ileal loops. Anti-CD18 (R15.7) had no inhibitory effect on cholera toxin enterotoxicity. These data demonstrate that C. difficile toxin A is a proinflammatory toxin whose enterotoxic effects are substantially dependent upon neutrophil recruitment.

Animals↗
PubMed1994

[Splenic arteriovenous fistula. Apropos of 2 cases and review of the literature].

Two cases of splenic arteriovenous fistula (SAVF) are reported and the literature pertaining to this disease is discussed. SAVF is a rare but curable cause of portal hypertension. Until recently, diagnosis was based and angiographic findings. However, it can now be reached with duplex-Doppler sonography, CT or MRI. Duplex-Doppler sonography highlights an enlarged splenic vein with a turbulent flow. CT scan detects the arterial aneurysms and shows the early opacification of the enlarged splenic vein. MRI depicts all the morphological abnormalities and flow-void due to time-of-flight losses may indicate the location of the fistula. Intra-arterial obliteration of the fistula is a good alternative to surgical procedure for treating SAVF in avoiding the potentially serious threat of gastrointestinal hemorrhage.

Adult↗
PubMed1993

Expression of the double-stranded RNA-dependent protein kinase (p68) in squamous cell carcinoma of the head and neck region.

OBJECTIVE: p68 is an interferon-inducible protein kinase that is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have previously shown that p68 expression correlates with differentiation in a variety of tumors, including squamous cell carcinoma of the head and neck region. The current study aims to identify the prognostic significance of p68 expression in squamous cell carcinoma of the head and neck. DESIGN: Archival material from a cohort of 75 patients with primary squamous carcinomas of the head and neck was immunostained for p68 with the monoclonal antibody TJ4C4. Overall scores for p68 expression were tabulated based on staining intensity and percentage of immunoreactive tumor cells. Clinical information including tumor grade, stage, site, treatment, disease-free, and total survival was tabulated and compared by p68 expression group. SETTING: Veterans Administration Lakeside Medical Center and outpatient clinics (Northwestern University and Veterans Administration Lakeside Medical Center, Chicago, Ill). PATIENTS: Seventy-five consecutive patients with primary squamous cell carcinoma of the head and neck (excluding the esophagus), with tissue blocks available for study, a known primary site, no history of prior carcinoma, and demographic and follow-up information available. MAIN OUTCOME MEASURED: Disease-free and overall survival rates. RESULTS: While there was a wide range of outcomes within each group, as a group, high levels of p68 expression correlated with a lower incidence of recurrent or residual disease and longer disease-free and total survival times compared with groups with lower levels of p68 expression. These differences could not be explained on differences in patient age, tumor grade, and TNM stage. CONCLUSIONS: High-level p68 expression is associated with prolonged disease-free and overall survival in a series of patients with squamous cell carcinoma of the head and neck region. Additional study is needed to monitor changes in p68 expression with treatment or tumor progression.

Aged↗
PubMed1993

Ozone effect on respiratory syncytial virus infectivity and cytokine production by human alveolar macrophages.

This study was performed to evaluate the effect of ozone (O3) exposure at 1 ppm for 2 hr on the susceptibility/resistance of adult human alveolar macrophages (AM) to infection with respiratory syncytial virus (RSV) in vitro and on RSV-induced cytokine production by the AM. AM were first exposed to O3 or to filtered air and then infected with RSV at multiplicities of infection (m.o.i.) of 0.1, 1.0, and 10. The percentage RSV-infected AM and the amount of infectious virus released by the cells were determined at Days 2 and 4 after infection. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) levels in the supernatants were determined on Day 2. No difference in the percentage infected AM or in the amount of infectious RSV produced was found between control and O3-exposed cultures. However, O3-exposed AM infected with RSV at m.o.i. 1 produced less IL-1 in response to RSV infection than control AM: 63.6 pg/ml compared with 98.5 pg/ml. No difference in IL-1 was seen with m.o.i. 10. IL-6 levels were also decreased, but only after infection with m.o.i. 0.1. At this level of infection 830 pg/ml was produced by control AM as compared to 468.2 pg/ml by O3-exposed AM. TNF production was unaffected by O3 at all multiplicities of infection. Statistical analysis of the O3 effect on AM cytokine production induced by the different multiplicities, however, revealed no significant effect of O3. Based on these observations it appears unlikely that O3 alters susceptibility of AM to infection with RSV, nor does O3 dramatically alter cytokine production in response to RSV since effects on IL-1 and IL-6 secretion were only found with the lowest levels of infection which induced cytokine release.

Adolescent↗
PubMed1993

Correlation of the expression of double-stranded RNA-dependent protein kinase (p68) with differentiation in head and neck squamous cell carcinoma.

p68 is an inducible protein kinase which is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have produced a monoclonal antibody (TJ4C4) which specifically detects p68, and which can be used to detect this antigen in formalin-fixed, paraffin-embedded tissues. Because p68 plays an important role in cellular protein synthesis, we hypothesized that it may correlate with normal and neoplastic cellular differentiation. One hundred and seventy-seven head and neck squamous cell carcinoma specimens, representing 82 patients, were studied. The relative amount, frequency, and distribution of p68 expression were determined by microscopic evaluation of ABC immunoperoxidase-stained specimens. A spectrum of immunoreactivity was detected in 156 of 177 tumors, as well as within the normal squamous epithelium. Normal, actively proliferating cells, such as the basal layer of squamous epithelium, expressed comparatively little p68. Increased p68 expression was noted to parallel the morphologic features of cellular differentiation. In neoplastic tissue, p68 expression also increased with the degree of cellular differentiation. These data demonstrate that the expression of p68 parallels the degree of cellular differentiation in squamous cell carcinoma of the head and neck region, as well as within normal squamous mucosa. Therefore, p68 may provide an objective biologic measure of cellular differentiation which does not depend on morphologic features.

Aged↗
PubMed1993

dcp gene of Escherichia coli: cloning, sequencing, transcript mapping, and characterization of the gene product.

Dipeptidyl carboxypeptidase is a C-terminal exopeptidase of Escherichia coli. We have isolated the respective gene, dcp, from a low-copy-number plasmid library by its ability to complement a dcp mutation preventing the utilization of the unique substrate N-benzoyl-L-glycyl-L-histidyl-L-leucine. Sequence analysis of a 2.9-kb DNA fragment revealed an open reading frame of 2,043 nucleotides which was assigned to the dcp gene by N-terminal amino acid sequencing and electrophoretic molecular mass determination of the purified dcp product. Transcript mapping by primer extension and S1 protection experiments verified the physiological significance of potential initiation and termination signals for dcp transcription and allowed the identification of a single species of monocistronic dcp mRNA. The codon usage pattern and the effects of elevated gene copy number indicated a relatively low level of dcp expression. The predicted amino acid sequence of dipeptidyl carboxypeptidase, containing a potential zinc-binding site, is highly homologous (78.8%) to the corresponding enzyme from Salmonella typhimurium. It also displays significant homology to the products of the S. typhimurium opdA and the E. coli prlC genes and to some metalloproteases from rats and Saccharomyces cerevisiae. No potential export signals could be inferred from the amino acid sequence. Dipeptidyl carboxypeptidase was enriched 80-fold from crude extracts of E. coli and used to investigate some of its biochemical and biophysical properties.

Amino Acid Sequence↗
PubMed1993

Respiratory syncytial virus-induced cytokine production by a human bronchial epithelial cell line.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infection in infants and young children, but the pathogenesis of RSV-induced inflammation is not well defined. We hypothesized that in vitro infection of a human bronchial epithelial cell line (BEAS) would induce production of proinflammatory cytokines. BEAS cells were infected with RSV, and cells and supernatants were assayed for cytokine mRNA and protein changes at several time points after infection. Cytokine mRNA in BEAS cells was measured by polymerase chain reaction of reverse-transcribed RNA from whole cell lysates; cytokine levels in supernatants were measured by bioassay or immunoassay. Our results indicated that interleukin-5ay or immunoassay. Our results indicated that interleukin-8 (IL-8) was induced at 4 h after infection (during the eclipse phase of RSV infection) with accumulation of IL-8 in supernatants by 24 h after infection. Increased levels of IL-6 and granulocyte macrophage colony-stimulating factor in supernatants were only detected by 96 h after infection, during the RSV replicative phase. Interferon-alpha and -gamma transcripts were not detectable at any time point. We conclude that the effects of RSV on airway inflammation may be at least partly mediated by sequential production of proinflammatory cytokines in infected airway epithelium.

Base Sequence↗
PubMed1993

Effect of storage temperature on the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase in rat liver and kidney homogenates.

The behavior of the catalytic activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase was tested in rat liver and kidney homogenates stored at 4, -20 and -70 degrees C and in corresponding tissue samples stored at -70 degrees C. The stabilities of enzymes were different for various enzymes and were dependent on the organ (liver, kidney) and the storage temperature. The storage temperature of -70 degrees C guaranteed the best stability and the five enzymes investigated were sufficiently stable in preserved tissue samples or in homogenates prepared with conventional mannit/sucrose homogenization solution. Under such conditions, these enzymes were stable over at least 4 or 1 weeks, respectively.

Animals↗
PubMed1993

Interleukin-8 expression in normal nasal epithelium and its modulation by infection with respiratory syncytial virus and cytokines tumor necrosis factor, interleukin-1, and interleukin-6.

Inflammation in nasal and airway tissue caused by allergens, microbial infection, and air pollution are likely to be regulated by inflammatory mediators produced by airway epithelial cells. We have therefore investigated the baseline expression of a number of cytokine genes known to be important inducers and modulators of inflammation, in freshly isolated human nasal epithelium. Cells were obtained by superficial scraping of turbinate tissue, and cDNA for polymerase chain reaction (PCR) amplification was reverse-transcribed directly from lysates of 3 x 10(3) to 5 x 10(3) epithelial cells using random hexamers. Constitutive expression of relatively high levels of interleukin-8 (IL-8) mRNA but undetectable levels (< 1 mRNA copy/cell) of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-6, IL-1, or tumor necrosis factor (TNF) mRNA were found after PCR amplification of the cDNA. IL-8 protein, but not IL-6, was identified in the nasal epithelial cells by immunocytochemistry. Infection with respiratory syncytial virus (RSV) or stimulation of nasal epithelium for 4 h with TNF or IL-1 in vitro resulted in a 4- to 10-fold increase in IL-8 mRNA expression but not in the expression of detectable levels of mRNA for the other cytokines. IL-8 was secreted by RSV-, IL-1-, and TNF-stimulated as well as unstimulated nasal epithelial cells after 6 to 20 h of culture. Neither IL-6, GM-CSF, nor TNF activity/immunoreactivity was detectable in the culture supernatants. Thus, it appears that IL-8 is a major cytokine of human nasal epithelium, constitutively expressed and readily secreted upon virus infection or stimulation with IL-1 and TNF.

Adult↗
PubMed1993

Chemical nature and immunotoxicological properties of arachidonic acid degradation products formed by exposure to ozone.

Ozone (O3) exposure in vivo has been reported to degrade arachidonic acid (AA) in the lungs of rodents. The O3-degraded AA products may play a role in the responses to this toxicant. To study the chemical nature and biological activity of O3-exposed AA, we exposed AA in a cell-free, aqueous environment to air, 0.1 ppm O3, or 1.0 ppm O3 for 30-120 min. AA exposed to air was not degraded. All O3 exposures degraded > 98% of the AA to more polar products, which were predominantly aldehydic substances (as determined by reactivity with 2,4-dinitrophenylhydrazine and subsequent separation by HPLC) and hydrogen peroxide. The type and amount of aldehydic substances formed depended on the O3 concentration and exposure duration. A human bronchial epithelial cell line (BEAS-2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm O3 for 1 hr produced AA-derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from O3 degradation of AA in the cell-free system. In vitro, O3-degraded AA induced an increase in human peripheral blood polymorphonuclear leukocyte (PMN) polarization, decreased human peripheral blood T-lymphocyte proliferation in response to mitogens, and decreased human peripheral blood natural killer cell lysis of K562 target cells. The aldehydic substances, but not hydrogen peroxide, appeared to be the principal active agents responsible for the observed effects. O3-degraded AA may play a role in the PMN influx into lungs and in decreased T-lymphocyte mitogenesis and natural killer cell activity observed in humans and rodents exposed to O3.

Aldehydes↗
PubMed1993

Rapid screening of low molecular mass proteinuria: evaluation of the first immunochemical test strip for the detection of alpha 1-microglobulin in urine.

A new semiquantitative immunochemical test strip for urinary alpha 1-microglobulin, a marker protein for tubular proteinuria, was assessed. This test strip has four colour zones, reflecting alpha 1-microglobulin concentrations of ca. 10, 25, 50, and 80 mg/l. alpha 1-Microglobulin concentrations were measured by means of the test strip and an immunonephelometric method in 330 samples collected as the second voided morning urine. The reading time of the test strip must be strictly observed. Reading one minute earlier or later than the 5 min stated in the instructions led to misclassification of over 70% of the results. Correlation between both methods was highly significant, with a Spearman rank correlation coefficient of rs = 0.84 (P < 0.001). There was a partial overlap of the test strip results in different concentration ranges. An elevation of alpha 1-microglobulin was defined as > 25 mg/l, calculated as the upper limit of the central 95% interval of alpha 1-microglobulin concentration in urine samples measured in a previous study of 304 healthy adults. Using this definition of alpha 1-microglobulin elevation, a sensitivity of 97.5%, specificity of 73.6%, a false-positive rate of 16.6%, and a false-negative rate of 0.9% of the test strip results were obtained. A fraction of 82.4% of the 330 samples investigated was correctly classified as having increased alpha 1-microglobulin concentration or not. Methodical improvements of the test strip are necessary to reduce overlapping results, in order to make the test suitable for screening purposes.

Humans↗
PubMed1993

The determinants of use of maternal and child health services in Metro Cebu, the Philippines.

The determinants of the use of family planning, prenatal care, childhood immunizations and oral rehydration salts (ORS) were studied with survey data of 8000 women in Metro Cebu, the Philippines. Polytomous logistic regression methods were used. The level of maternal education was the most consistent and important determinant of use of these four health services in both urban and rural areas. For example, the estimated odds of using modern contraception increased by six and eleven per cent for each additional year of schooling in urban and rural strata respectively. Economic status and access to service variables had less consistent patterns: women's work status, for example, was associated only with contraceptive use.

Adolescent↗
PubMed1992

Action of derivatives of mu-conotoxin GIIIA on sodium channels. Single amino acid substitutions in the toxin separately affect association and dissociation rates.

We have studied binding and block of sodium channels by 12 derivatives of the 22-residue peptide mu-conotoxin GIIIA (mu-CTX) in which single amino acids were substituted as follows: Arg or Lys by Gln, Gln-18 by Lys, Asp by Asn, and HO-Pro by Pro. Derivatives were synthesized as described by Becker et al. [(1989) Eur. J. Biochem. 185, 79]. Binding was measured by displacement of labeled saxitoxin from eel electroplax membranes (100 mM choline chloride, 10 mM HEPES-NaOH, pH 7.4). Blocking kinetics were evaluated from steady-state, single-channel recordings from rat skeletal muscle sodium channels incorporated into planar, neutral phospholipid/decane bilayers (200 mM NaCl, 10 mM HEPES-NaOH, pH 7.0). Blocking events generally appeared as periods of seconds to minutes in which current through the single channel was completely eliminated. A notable exception was seen for the substitution Arg-13-Gln for which the "blocked" events showed measurable conductances of about 20-40% of the open state. The substitution of Arg-13 reduced binding to electroplax membranes to undetectable levels and increased the apparent dissociation constant determined for skeletal muscle channels by greater than 80-fold compared with the native peptide. Other substitutions caused smaller decreases in affinity. The decreased potency of the toxin derivatives resulted both from increases in the rates of dissociation from the channel, and from decreases in association rates. Our data support the suggestion by Sato et al. [(1991) J. Biol. Chem. 265, 16989] that Arg-13 associates intimately with the binding site on the channel. In addition, our results suggest that certain residues affect almost exclusively the approach and docking of the toxin with its binding site, others appear to be important only to the strength of the association once binding has taken place, and yet others affect both.

Amino Acid Sequence↗
PubMed1992

Self-organizing neural network that discovers surfaces in random-dot stereograms.

The standard form of back-propagation learning is implausible as a model of perceptual learning because it requires an external teacher to specify the desired output of the network. We show how the external teacher can be replaced by internally derived teaching signals. These signals are generated by using the assumption that different parts of the perceptual input have common causes in the external world. Small modules that look at separate but related parts of the perceptual input discover these common causes by striving to produce outputs that agree with each other. The modules may look at different modalities (such as vision and touch), or the same modality at different times (for example, the consecutive two-dimensional views of a rotating three-dimensional object), or even spatially adjacent parts of the same image. Our simulations show that when our learning procedure is applied to adjacent patches of two-dimensional images, it allows a neural network that has no prior knowledge of the third dimension to discovery depth in random dot stereograms of curved surfaces.

Artificial Intelligence↗