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Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Differences in arachidonic acid metabolism by human myelomonocytic cell lines.

The production of arachidonic acid metabolites by the HL60, ML3, and U937 human phagocyte cell lines was determined after incubation with interferon-gamma (IFN-gamma, 500 U/ml) or vehicle for 4 days. Cells were prelabeled with tritiated arachidonic acid, [3H]AA, for 4 h, and media supernatants were analyzed by high-performance liquid chromatography. None of the cell lines produced [3H]AA metabolites in large amounts during an unstimulated, basal release period (30 or 60 min). In response to 10 microM calcium ionophore A23187 incubation (30 min), undifferentiated and IFN-gamma-differentiated HL60 cells formed both cyclooxygenase products (thromboxane and prostaglandins) and lipoxygenase products (leukotrienes and hydroxyeicosatetraenoic acids). In contrast to the HL60 cells, IFN-gamma-differentiated U937 cells formed primarily cyclooxygenase products and undifferentiated and IFN-gamma-differentiated ML3 cells did not form any [3H]AA metabolites in response to A23187. These results indicate the need to be careful in selecting a cell line for use in a phagocyte assay system when cyclooxygenase and/or lipoxygenase products could influence the assay results.

Antigens, CD↗
PubMed1992

Evidence for occurrence of filovirus antibodies in humans and imported monkeys: do subclinical filovirus infections occur worldwide?

In the present serological study 120 monkey sera from different species originating from the Philippines, China, Uganda and undetermined sources and several groups of human sera comprising a total of 1288 specimens from people living in Germany were examined for the presence of antibodies directed against filoviruses (Marburg virus, strain Musoke/Ebola virus, subtype Zaire, strain Mayinga/Reston virus). Sera were screened using a filovirus-specific enzyme-linked immunosorbent assay (ELISA). ELISA-positive sera were then confirmed by the indirect immunofluorescence technique, Western blot technique, and a blocking assay, and declared positive when at least one confirmation test was reactive. Altogether 43.3% of the monkey sera and 6.9% of the human sera reacted positively with at least one of the three different filovirus antigens. The blocking assays show that antibodies, detected in the sera, are directed to specific filovirus antigens and not caused by antigenic cross-reactivity with hitherto unknown agents. Data presented in this report suggest that subclinical filovirus infections may also occur in humans and in subhuman primates. They further suggest that filoviruses are not restricted to the African continent.

Animals↗
PubMed1992

Radiotherapy of the rhabdomyosarcoma R1H of the rat: recovery from radiation injury in tumour and skin.

The response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation has been reported to be almost independent of the dose per fraction in the range from 0.43 to 10 Gy. To elucidate whether recovery from radiation injury is impaired in fractionated irradiation or not, tumours were exposed on 5 days per week over 6 weeks either to a single daily dose or to two daily fractions separated by an interfraction interval of 2 h. Tumour response was assessed by net growth delay. Skin damage was scored for comparison. A significant reduction in tumour response (p less than 0.009) and skin damage (p less than 0.001) was observed when the daily dose was administered in a twice daily irradiation regimen, indicating that recovery from radiation injury does occur in the course of fractionated irradiation in our tumour system. A tumour response was almost independent of the dose per fraction for time intervals between fractions of at least 8 h, a possible explanation might be that recovery is compensated by improved reoxygenation.

Animals↗
PubMed1992

Localization of endoderm-specific mRNAs in differentiating F9 embryoid bodies.

Primitive endoderm in the peri-implantation mouse embryo differentiates into two separate lineages, visceral and parietal endoderm (VE and PE). F9 teratocarcinoma cells, when grown in suspension in the presence of retinoic acid (RA), differentiate into embryoid bodies (EBs) which can be used as a model system to study the spatially appropriate induction of VE- and PE-specific gene expression. We have used a whole mount in situ hybridization technique to follow the localization of VE-specific AFP and PE-specific tPA mRNAs during EB differentiation. We show that the putative endoderm-specific markers are localized to the endoderm in mature EBs, and that AFP mRNA is localized to the apical edge of the VE in RA EBs. Surprisingly, prior to localization of endoderm-specific markers at the periphery of EBs, these genes are expressed at low to moderate levels in all cells of the EB. Our data suggest that the establishment of endoderm in EBs is position dependent and not the result of sorting out of predetermined, randomly distributed cells. Our observations also suggest a two-step process for establishing endoderm-specific gene expression, involving up-regulation of transcripts throughout the EB prior to the restriction of their expression to the outer differentiating cell layer.

Animals↗
PubMed1992

[Heroin abuse and methadone substitution in pregnancy].

The pre- and postnatal data of 20 pregnant heroin addicts and their neonates are described. 16 women were treated with methadone to prevent withdrawal symptoms. A relatively stabile prenatal condition with a decrease of complications was achieved. On the other hand, the neonates suffered from severe withdrawal symptoms including seizures in spite of intensive paediatric care and prophylactic treatment with barbiturates. After a mean follow-up of one to two years a relatively good neurological development of the children was observed.

Asphyxia Neonatorum↗
PubMed1992

Diet-induced dermatitis response of hairless rats to systemic treatment with cyclosporin A (Sandimmun), cyclosporin H and FK506.

Weaned hairless rats were fed a diet deficient in fat, magnesium and folacin. After approximately 1 week, an erythematous dermatitis developed which was associated with extreme generalized pruritus. Scratching led to excoriations and hemorrhagic crusting. The acute stage (pruritic rash) resolved after several days and was followed by sporadic non-itching relapses. Subsequent to the onset of symptoms, rats were treated orally, once daily for 3 days with CyA, CyH or FK506. The immunosuppressants CyA and FK506 caused a dose-dependent inhibition of symptoms in contrast to CyH. The immediate clinical response was associated with changes in blood histamine, white blood cell counts and histological parameters. Since CyH is known to lack immunosuppressive activity, these results may indicate that the cutaneous changes induced by the nutritional deficiency are associated with immunological abnormalities. The results may also indicate mechanisms influenced by CyA and FK506 but not by CyH; for example, release of chemical mediators from inflammatory cells.

Animals↗
PubMed1992

Respiratory syncytial virus infection of human primary nasal and bronchial epithelial cell cultures and bronchoalveolar macrophages.

In adults, clinical symptoms caused by respiratory syncytial virus (RSV) are usually confined to the upper respiratory tract, whereas RSV infection in infants frequently causes bronchiolitis and pneumonia. The preferential localization of RSV infection to the upper airways may partially be due to protective immunity, but may also depend on a difference in susceptibility of epithelial cells from upper and lower airways, or on antiviral activities of bronchoalveolar macrophages (AM). In this study, we have compared the susceptibility of primary adult human nasal epithelium, primary adult human bronchial epithelium, a human bronchial epithelial cell line (BEAS-2B), and adult human AM to infection with RSV. The cell cultures were infected with multiplicities of infection (moi) of 1 and 0.1. Virus release into the supernatants was assayed at days 1, 2, 4, and 7, and the percentage of virus-positive cells determined by immunofluorescence at the same time points. Similar proportions of nasal epithelial cells (NE) and bronchial epithelial cells (BE) were infected with RSV. Approximately 50 to 75% (with moi 1) and 2 to 10% (with moi 0.1) of the cells were infected by 24 h; almost all the cells were RSV positive by day 4. However, BE released less infectious RSV than do NE. With moi 0.1, 10-fold less virus was released over 4 days of culture. By days 4 to 7, cytopathic effects (CPE) were maximal in all epithelial cell cultures, but CPE developed latest in BE infected with moi 0.1. AM were also productively infected with RSV, with peak virus production at day 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Modulation of eicosanoid production by human alveolar macrophages exposed to silica in vitro.

Repeated inhalation of silica dust can lead to inflammation and fibrosis in human lung and in experimental animal models. The alveolar macrophage is believed to play a pivotal role in this process. Numerous macrophage-derived growth factors, cytokines, and arachidonic acid metabolites have been shown to contribute to inflammation and fibrosis. The objective of this study was to determine the eicosanoid production by human alveolar macrophages in response to silica exposure in vitro and to assess the contribution of alveolar macrophages to silica-induced fibrosis and inflammation. Macrophages were obtained from healthy volunteers and were incubated for 3 or 24 hr in the presence of silica (100, 60, and 0 micrograms/mL). Supernatants were removed for eicosanoid analysis. Eicosanoids were analyzed by both high performance liquid chromatography and radioimmunoassay. The data suggest that silica causes an increased release of leukotriene B4, leukotrienes C4/D4/E4, and 5-hydroxyeicosatetraenoic acid (5-HETE) after 3 hr and decreases in prostaglandin E2 and thromboxane B2 production after 24 hr of exposure to 100 micrograms/mL silica. In addition, 12-HETE and 15-HETE production remained unchanged at either time point. These opposing effects seen with the metabolites of lipoxygenase and cyclooxygenase pathways could contribute to silica-induced fibrosis. The pattern of eicosanoid production after exposure to silica was different from that obtained when macrophages were stimulated with lipopolysaccharide for 3 or 24 hr, indicating that the response to the particles was not just due to general cellular activation.

Adult↗
PubMed1991

Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages.

Human alveolar macrophages (AM) are susceptible to infection with respiratory syncytial virus (RSV), but the infection is abortive after the initial cycles of virus replication. We have investigated if RSV infection of AM results in the production of cytokines TNF, IL-6, and IL-8, all of which may modulate inflammatory and immune responses to the virus, as well as may directly protect respiratory epithelial cells against spread of infection. Within 1 h after interaction with RSV, increased mRNA levels were found for all three cytokines. Peak expression of the mRNAs occurred at 3 to 6 h. The virus most effectively induced TNF mRNA expression greater than IL-6 mRNA greater than IL-8 mRNA, as compared to cytokine mRNA expression induced by bacterial endotoxin. Inactivated virus was almost as effective as live virus in inducing and maintaining increased IL-6 and IL-8 mRNA over 16 h, whereas live infectious RSV was necessary for maintaining TNF mRNA expression over the same time. Protein concentrations of the different cytokines in the supernatants of infected AM reflected the increased levels of mRNA in the cells. Despite the high levels of cytokines with possible antiviral activity (TNF and IL-6) in the AM supernatants, neither supernatants nor rTNF when added to bronchial epithelial cells protected them from infection with RSV. However, TNF, IL-1, and RSV, but not IL-6, induced IL-8 and IL-6 mRNA expression by the bronchial epithelial cells suggesting that cytokines produced by RSV-infected AM may be more important in modulating the inflammatory response in infection than directly interfering with virus infection/replication of airway epithelium.

Adolescent↗
PubMed1991

Modulation of human alveolar macrophage properties by ozone exposure in vitro.

We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.

Adult↗
PubMed1991

Solution structure of mu-conotoxin GIIIA analysed by 2D-NMR and distance geometry calculations.

We have investigated the structure of mu-conotoxin GIIIA by 2D-NMR methods. The assignment of 1H NMR spectra and a quantitative analysis of NOE and J-coupling data are presented. These results were used for the calculation of secondary structure elements of mu-conotoxin GIIIA. Distance geometry calculations were carried out to define the global folding of the peptide.

Amino Acid Sequence↗
PubMed1991

Community health survey of Oukasie, 1987.

A series of surveys were conducted at the request of the community of Oukasie to determine certain public health information in the township, a peri-urban black community. This article describes two of these surveys. The first, a census and partial demographic survey, showed that the total black population was around 6,300 with a mean household occupancy of 4.1. Some of the estimated vital statistics calculated were an infant mortality rate of 36.6/1,000, a crude birth rate of 28.0/1,000, a crude death rate of 6.5/1,000, and a general fertility rate of 99.3/1,000. The second survey into the nutritional and immunisation status of children aged under 5 years showed that 20% of children were underweight and nearly half were incompletely immunised at 1 year of age. These studies, involving local community and student volunteers, were rapidly and inexpensively done and provide basic public health information.

Adolescent↗
PubMed1991

Effect of ozone on immunoglobulin production by human B cells in vitro.

Animal studies indicate that ozone (O3) inhalation results in reduced ability to generate a humoral response to soluble and particulate antigens. In this study, human lymphocytes have been exposed to O3 in vitro (1.0, 0.5, and 0.1 ppm/2 h) and then evaluated for the ability of B cells to produce immunoglobulin G (IgG) in response to the T-cell-dependent stimulus pokeweed mitogen (PWM), and to the T-cell-independent stimulus Staphylococcus aureus Cowan I strain (SAC). Suppression of IgG production was found with O3-exposed PWM-stimulated lymphocytes, while no effect of O3 was seen with SAC-stimulated cells, suggesting that T cells, but not B cells, were sensitive to O3. However, exposing either cell type alone to O3 indicated that both T cells and B cells were affected by the pollutant. The O3-exposed B cells produced less IgG in response to PWM but produced more IgG in response to SAC. On the other hand, O3-exposed T cells were suppressive in both PWM and SAC responses. Since the differentiation of B cells into plasma cells is regulated by complex interactions of cytokines secreted by T cells and antigen-presenting cells, possible O3-induced alterations in secretion of some of these regulatory lymphokines (IL-2, IL-4, IL-6, and IFN-gamma) were investigated in lymphocyte cultures stimulated with PWM. A decrease in IL-2 production was found, while in contrast, IL-6 production was significantly increased. IFN-gamma secretion was not altered, and IL-4 levels were below the limits of detectability. These results suggest that O3-induced changes in IgG production may be mediated by altered production by T cells of important immunoregulatory molecules, in addition to any direct effects of O3 on the IgG-producing cells themselves.

B-Lymphocytes↗