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B Becker

Publications and source records attributed to B Becker.

At least 73 records · Page 4Linked to original sources
PubMed1996

Non-structural protein 3 of hepatitis C virus inhibits phosphorylation mediated by cAMP-dependent protein kinase.

Inspection of the amino acid sequence of the non-structural region of the hepatitis C virus (HCV) gene product reveals a sequence of 14 amino acids, Arg1487-Arg-Gly-Arg-Thr-Gly-Arg-Gly-Arg-Arg-Gly-Ile-Tyr-Arg1500 , located in the non-structural protein, NS3. This sequence is highly similar to the inhibitory site of the heat-stable inhibitor of cAMP-dependent protein kinase (PKA) and to the autophosphorylation site in the hinge region of the PKA type II regulatory domain. A synthetic peptide that corresponds to the HCV sequence above and a set of shorter analogues act as competitive inhibitors of PKA. A 43.5-kDa fragment of NS3 that consists of residues 1189-1525 of the HCV polyprotein inhibits PKA in a similar range to the investigated synthetic peptides. In contrast to the short peptides, which show competitive inhibition, HCV-polyprotein-(1189-1525) influences PKA in a mixed-inhibition-type manner. A possible mechanism explaining these differences is the formation of complexes that consist of the protein substrate, the enzyme and the HCV-polyprotein-(1189-1525). Binding studies with PKA and the non-hydrolysable ATP analogue [14C]fluorosulfonylbenzoyladenosine and [3H]cAMP do not reveal any influence of the short HCV-derived peptides or HCV-polyprotein-(1189-1525) upon the affinity of PKA for these nucleotides. The complex interactions of the NS3 fragments could influence one of the most important signal pathways of the cell and, therefore, could possibly provide new pathological mechanisms for HCV infections of liver.

Amino Acid Sequence↗
PubMed1996

The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence.

Mature B cells co-express on their cell surface two classes of antigen receptor, the IgM and IgD immunoglobulins. The structural and functional differences between the two receptor classes are poorly understood. Recently two proteins of 29 and 31 kDa (BAP29 and BAP31) have been described that are preferentially associated with membrane IgD but only weakly with membrane IgM. We describe here the cloning of full-length murine and human BAP31 cDNAs encoding proteins of 245 and 246 amino acids respectively. The two BAP31 proteins are 95% identical. The BAP31 gene is ubiquitously expressed in murine tissues and is located on the X chromosome in both mouse and man. The murine BAP31 protein has 43% sequence identity to murine BAP29. Both proteins have a hydrophobic N-terminus and an alpha-helical C-terminus which ends with a KKXX motif implicated in vesicular transport. By a mutational analysis we have identified amino acids in the transmembrane sequence of the delta m chain that are critical for binding to BAP31/BAP29. A structural model of the BAPs and their potential functions are discussed.

Amino Acid Sequence↗
PubMed1996

All-trans-retinoyl beta-glucuronide: new procedure for chemical synthesis and its metabolism in vitamin A-deficient rats.

All-trans-retinoyl beta-glucuronide (RAG) was chemically synthesized in high yields (up to 79%) by a new procedure involving the reaction of the tetrabutylammonium salt of glucuronic acid with all-trans-retinoic acid (RA) via the imidazole or triazole derivative. When RAG was fed orally to vitamin A-deficient rats, RA was identified as the major metabolite in the serum within hours of administration of RAG. Very little or no RAG was detected in the serum. Thus RAG, which was not appreciably hydrolysed to RA in vitamin A-sufficient rats [Barua and Olson (1987) Biochem. J. 263, 403-409], was rapidly converted into RA in vitamin A-deficient rats.

Acitretin↗
PubMed1996

Identification of hazardous/harmful drinking among subcritically injured patients.

OBJECTIVES: To examine the relationship between a saliva alcohol test (SAT) and hazardous/harmful drinking, as measured by the Alcohol Use Disorders Identification Test (AUDIT), among a sample of subcritically injured patients. METHODS: Patients (n = 78) seeking treatment for a subcritical injury were saliva-tested for alcohol and interviewed regarding their drinking behaviors and related difficulties. Associations of SAT values with AUDIT results were determined. RESULTS: SAT results and hazardous/harmful drinking were not independent events (p < 0.001). Estimates of sensitivity and specificity (using a dichotomous SAT result [> or = 4 mmol/L] to identify positive AUDIT patients) were 65.2% and 83.6%, respectively. SAT-positive people had significantly higher AUDIT scores than did SAT-negative individuals (p < 0.0001). Patients experiencing assault-type injuries were much more likely to be SAT-positive than were patients incurring other types of injury. Discriminant function analysis suggests that AUDIT scores can successfully identify SAT-positive and SAT-negative patients; the analysis accounted for 42.5% of the variance and correctly classified 84.6% of the sample. CONCLUSIONS: The use of an easy-to-administer, noninvasive, routine SAT, among patients presenting for a subcritical injury in a hospital ED, provides a mechanism for the identification of individuals with a history of hazardous/harmful drinking. However, since discrimination of hazardous/harmful drinking is imperfect, some caution is warranted when conducting such screening activities.

Accident Proneness↗
PubMed1996

The secretory pathway of protists: spatial and functional organization and evolution.

All cells secrete a diversity of macromolecules to modify their environment or to protect themselves. Eukaryotic cells have evolved a complex secretory pathway consisting of several membrane-bound compartments which contain specific sets of proteins. Experimental work on the secretory pathway has focused mainly on mammalian cell lines or on yeasts. Now, some general principles of the secretory pathway have become clear, and most components of the secretory pathway are conserved between yeast cells and mammalian cells. However, the structure and function of the secretory system in protists have been less extensively studied. In this review, we summarize the current knowledge about the secretory pathway of five different groups of protists: Giardia lamblia, one of the earliest lines of eukaryotic evolution, kinetoplastids, the slime mold Dictyostelium discoideum, and two lineages within the "crown" of eukaryotic cell evolution, the alveolates (ciliates and Plasmodium species) and the green algae. Comparison of these systems with the mammalian and yeast system shows that most elements of the secretory pathway were presumably present in the earliest eukaryotic organisms. However, one element of the secretory pathway shows considerable variation: the presence of a Golgi stack and the number of cisternae within a stack. We suggest that the functional separation of the plasma membrane from the nucleus-endoplasmic reticulum system during evolution required a sorting compartment, which became the Golgi apparatus. Once a Golgi apparatus was established, it was adapted to the various needs of the different organisms.

Animals↗
PubMed1996

Enhanced prostaglandin synthesis after ultraviolet-B exposure modulates DNA synthesis of lens epithelial cells and lowers intraocular pressure in vivo.

PURPOSE: To study the functional significance of prostaglandin synthesis after ultraviolet-B (UVB) exposure of cultured human lens epithelial cells and rabbit eyes in vivo. METHODS: Prostaglandin E2 (PGE2) was assayed using a radioimmunoassay (RIA) and mass spectroscopy. An immortalized human lens epithelial cell line (HLE-B3) was exposed to UV irradiation, and the synthesis of PGE2 was compared with the rabbit lens epithelial cell line N/N1003A. Intact human lenses were exposed to UVB in organ culture. [3H]Thymidine incorporation was measured in cultured lens epithelial cells by incubation with the radiolabel. The effects of isobutyl methyl xanthine (IBMX), an inhibitor of phosphodiesterase and of dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, on PGE2 synthesis and DNA synthesis, were determined. Rabbit eyes were exposed to UVB radiation in vivo. Intraocular pressure was measured at specific times after exposure. Aqueous humor was remove from rabbit eyes, and its PGE2 content was measured by RIA. RESULTS: Cultured human lens epithelial cells (HLE), like rabbit lens epithelial cells (RLE), showed a dose-dependent increase in basal PGE2 synthesis 24 hours after UVB exposure. However, the amount of PGE2 synthesis was 2000-fold higher in the rabbit cells. Ultraviolet-B radiation enhanced the incorporation of [3H]thymidine in lens epithelial cells. Pretreatment of cells with indomethacin reduce PGE2 synthesis and [3H]thymidine incorporation. The human and rabbit cells responded in a similar manner to changes in DNA synthesis after UVB exposure. The addition of IBMX or dbcAMP to indomethacin-treated, UVB-exposed cells restored DNA synthesis toward the levels observed in the UVB-exposed cells. An increase in the concentration of cAMP was observed in lens epithelial cells exposed to exogenous PGE2. PGE2 synthesis in intact human lenses also increased twofold 24 hours after UVB exposure. Exposure of the rabbit eye in vivo to an optimal dose of UVB produced an increase in the PGE2 levels of the lens and the aqueous humor. Measurements of the intraocular pressure (IOP) of the animals showed a decrease in IOP by 2.21 +/- 0.66 and 6.45 +/- 0.79 mm Hg (mean +/- SEM, P = 0.004, t-test) at 6 and 24 hours after UVB exposure, respectively. The decrease in IOP was prevented by pretreatment with indomethacin. Exposure of the rabbit lens to UVB radiation in vivo enhanced [3H]thymidine incorporation twofold into the lens. Pretreatment of rabbits with indomethacin before exposure reduced this response. CONCLUSIONS: Results indicate that UVB exposure enhances PGE2 synthesis in HLE cultures as well as in rabbit lenses irradiated in vivo. This increased PGE2 synthesis is related to the increase in DNA synthesis observed after UVB treatment. The modulation of DNA synthesis in cultured lens epithelial cells after UVB exposure may be mediated by a cAMP-dependent mechanism.

1-Methyl-3-isobutylxanthine↗
PubMed1996

The role of prostaglandins E2 and F2 alpha in ultraviolet radiation-induced cortical cataracts in vivo.

PURPOSE: Previous work has shown that exposure of lens epithelial cells or rabbit eyes in vivo to ultraviolet B (UVB) radiation enhanced prostaglandin (PG)E2 synthesis. Such enhanced PGE2 synthesis was related to the increased DNA synthesis that followed UVB exposure. The current study examined the relationship between enhanced prostaglandin synthesis and UVB-induced cataract formation. METHODS: Seventy albino (New Zealand white) rabbit eyes were exposed to UVB radiation in vivo. Fluence of radiation at the cornea was 2.8 J/cm2, 5.6 J/cm2, or 11.2 J/cm2. Eyes were examined 24 hours after UVB exposure and for as long as 10 days by slit lamp biomicroscopy. Mass spectrometry was used to measure PGE2, PGF2 alpha, and 6-keto-PGF1 alpha content of the lens and iris-ciliary body using authentic standards. To determine the effect of inhibition of prostaglandin synthesis on UVB-induced cataract formation, animals were given indomethacin intraperitoneally. Other pharmacologic agents, such as PGE2, PGF2 alpha, and misoprostol, were applied topically to the eye. The effect of UVB on K+ pump was determined by incubating isolated lenses with [86Rb+]. RESULTS: Twenty-four hours after UVB exposure, PGE2 and PGF2 alpha concentrations in aqueous humor were increased by 100- and 30-fold, respectively. Lens PGE2 and PGF2 alpha increased by 6- and 4-fold, respectively, after UVB radiation exposure. Pretreatment of animals with indomethacin prevented the rise in lens and aqueous humor PGE2 and PGF2 alpha levels. Furthermore, indomethacin was partially protective against UVB cataract formation and lowered cataract severity from stage 3 to stage 1, but it did not prevent UVB-induced lens changes completely. Topical application of PGE2 before UVB exposure completely prevented cataract formation in the UVB-exposed eye. In contrast, topical administration of PGF2 alpha increased cataract severity. UVB-induced cataract formation preceded changes in [86Rb]+ uptake in lenses subsequently incubated in K(+)-free Tyrode's. CONCLUSIONS: Enhanced synthesis of cyclooxygenase products of arachidonic acid metabolism in the lens is associated with UVB-induced cataract formation in albino rabbit eyes, and inhibition of cyclooxygenase by indomethacin decreased the severity of cataracts. PGE2, the principal arachidonic acid metabolite, appears to have a protective role because pretreatment of the eye with topical PGE2 completely prevented UVB-induced cataract formation, whereas PGF2 alpha increased the severity of the cataract. The evidence presented for a role of PGF2 alpha in the development of cataract suggests that caution be exercised in the use of PGF2 alpha derivatives in the therapy of glaucoma.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

[Transmission of pathogenic human viruses by foods: hepatitis A epidemic caused by baked goods in the Euskirchen district)].

In the last few years many reports have documented that human pathogenic viruses are transmitted via food and can cause epidemics. Between November 1994 and February 1995 a HAV epidemic was recorded in the village and agricultural area of Euskirchen (Germany). 49 persons with HAV infections were registered. It seems that the epidemic started in a bakery and was caused by an employee who had spent his holidays in the Dominican Republic and came back already excreting the virus via his faeces. Two weeks later he developed a symptomatic illness. HAV is transmitted via a fecal-oral cycle. Lack of hygiene in food production and distribution cause the risk of secondary virus contamination. Virus transmission via food is first of all a problem in uncooked food. To ensure success in food safety in respect of foodborne human pathogenic viruses it is important to establish personal hygienic education, cleaning and disinfection plans and preventive measures such as immunization to avoid viruses in the food.

Disease Outbreaks↗
PubMed1996

Comparison between the effect of ipratropium bromide as a pressurized aerosol and as an aqueous pump spray on methacholine-induced rhinorrhoea.

Topical application of the anti-cholinergic drug ipratropium bromide is used for the treatment of rhinorrhoea. As the commercially-available pressurized aerosols are now largely being replaced by aqueous pump sprays, not containing CFC gases, we have compared these two types of sprays in a time-effect study of 20 normal persons, using the secretory response to nasal methacholine challenge as the effect parameter. Pre-treatment has been given as a single dose of 80 mg of ipratropium bromide, and 24 mg methacholine was used for challenge. The pressurized aerosol reduces rhinorrhoea with 60% (p < 0.05) and the effect lasts for at least 8 h. The corresponding value for the aqueous pump spray is 40% (p < 0.05) and the effect lasts for less than 4 h. The differences between the two sprays is significant 30 min, 1, 2 and 4 h after medication (p < 0.05). This finding is unexpected and we cannot offer a satisfactory explanation. The result indicates that changes in dosing and dose-frequency of ipratropium bromide may be necessary when patients are transferred from a pressurized spray to an aqueous pump spray.

Administration, Intranasal↗
PubMed1995

Synemin contains the rod domain of intermediate filaments.

We have screened a lambda gt11 cDNA library from chicken gizzard muscle with polyclonal antiserum to avian synemin. Immunopositive clones were characterized and sequenced. Computer searches identified primarily intermediate filament (IF) proteins as being homologous to the synemin clones. Synemin's sequence contained all structural features characteristic of the rod domain of IF proteins: (a) its length (approximately 310 amino acids), (b) the heptad repeat pattern of hydrophobic residues of coiled-coil proteins, (c) subdomain structure of the IF rod, by which helical subdomains (1A, 1B, 2A, and 2B) are separated by three short non-helical linker regions, and (d) several potential intrahelical ion pairs along the sequence. We also confirmed the presence of the IF rod domain at the protein level by immunoblotting a proteolytic digest of synemin by using a monoclonal antibody specific to the rod domain of IFs.

Amino Acid Sequence↗
PubMed1995

Alcohol use among subcritically injured emergency department patients.

OBJECTIVES: To determine the incidence of alcohol use in subcritically injured patients presenting to the ED, by using a saliva alcohol test (SAT) at ED triage during the ED initial assessment; to compare the incidence of alcohol use revealed by the SAT with documentation of alcohol use by ED nurses and emergency physicians (EPs) blinded to the SAT results; and to describe the demographics of the SAT-positive, subcritically injured population. METHODS: A blinded, prospective, observational evaluation of ED patients presenting with subcritical injuries was performed. The patients were tested for alcohol use with an SAT, and a subsequent record review was conducted for extraction of demographic data and evidence of documentation of alcohol use by ED nurses and EPs blinded to the SAT results. RESULTS: During the study, 791 subcritically injured patients had SATs performed. Twenty-one percent of these patients were found to be alcohol-positive by SAT. Either the ED nurse or the EP documented a clinical impression of alcohol use for 52% of the SAT-positive patients. There were higher SAT-positive rates among men (24%), victims of assault (47%), and patients arriving at night (41%). CONCLUSIONS: While the SAT identified 21% of the subcritically injured patient population as alcohol-positive, ED nurse and EP documentation did not identify half of these alcohol-positive patients. Many of these patients may be at risk for additional injuries related to their drinking behavior.

Adolescent↗
PubMed1995

Injury as a motivator to reduce drinking.

OBJECTIVES: To identify predictors of readiness to change drinking behavior by minor-injury patients who had positive saliva alcohol tests (SATs) in the ED. To develop and test a model intended to be prognostic of readiness to change, which included predispositional and injury-event-related variables. METHODS: An on-site survey was conducted of minor-injury ED patients sampled consecutively during predesignated periods. Patients were identified as SAT-positive during their screening evaluations. After giving their consent, they were administered a self-report battery that assessed predispositional and injury-event-related variables as well as readiness to change their drinking. Predictors of readiness to change drinking were tested with regression analyses. RESULTS: Twenty-four SAT-positive patients participated; there were 18 men and six women (average age 34 years). Preinjury predispositional variables were by themselves unrelated to the patient's readiness to change while in the ED. Aversiveness of the injury and perception of degree of alcohol involvement were injury-event-related variables predictive of readiness to change (p < 0.008). Negative consequences attributed to drinking prior to the injury event strengthened the association of injury aversiveness and alcohol involvement with readiness to change (p < 0.0075). CONCLUSION: Interventions to decrease drinking in this population should focus on increasing patient awareness of the association between drinking, injuries, and other alcohol-related negative consequences.

Adult↗
PubMed1995

Aiming for consistency in the way teachers sign.

A four year study examined the effects of a sign communication intervention program designed to enhance teachers' ability to consistently code English into sign. The secondary goal of the project was to help teachers use American Sign Language as an intervention tool for enhancing students' comprehension of instructions. Starting with an initial sign to speech ratio of 59.8% and 66.2%, two teachers were able to improve their ratio to 98.9% and 89.7% respectively. The basic components of the intervention program are presented along with their rationale. A breakdown of the sign to speech ratio is provided in an examination of how effectively the teachers coded articles, pronouns, sign markers, and the verb "to be."

Deafness↗
PubMed1995

Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein.

Synapses are highly specialized sites of cell-cell contact involved in signal transfer. The molecular mechanisms modulating the assembly and stability of synapses are unknown. We previously reported the identification of a 90 kDa synapse-associated protein, SAP90, that is localized at the presynaptic termini of inhibitory GABAergic synapses. SAP90 is a mosaic protein composed of three 90 amino acid residue repeats, an SH3 domain and a region homologous to guanylate kinases. SAP90 shares domain specific homology with a family of proteins involved in the assembly and possibly stability of sites of cell contact. These include the product of the lethal(1) discs-large-1 (dlgA) tumor suppressor gene and the zonula occludens proteins ZO-1, ZO-2. The further characterization of cDNA clones encoding components of synaptic junctions has lead to the identification of a 97 kDa protein, called SAP97, that exhibits a strong overall sequence similarity to SAP90. The present study was undertaken to determine the spatial distribution of SAP97, and to reveal further clues to the possible roles of these proteins in synapses. Light and immunoelectron microscopic analysis of the rat hippocampal formation revealed that SAP97 is localized in the presynaptic nerve termini of excitatory synapses. In other brain regions, SAP97 is found in and along bundles of unmyelinated axons. SAP97 is not restricted to the CNS, but is also present at the basal lateral membrane between a variety of epithelial cells. In cultured T84 cells, it is restricted to the cytoplasmic surface of the plasma membranes between adjacent cells, but not at the edges of cells lacking cell-cell contact suggesting a role for SAP97 in cell adhesion. These data suggest that members of the SAP90/SAP97 subfamily may be involved in the site specific assembly, stability or functions of membrane specialization at sites of cell-cell contact.

Adaptor Proteins, Signal Transducing↗
PubMed1995

[Clinical diagnosis in sleep laboratory patients based on ICD-10, DSM-III-R and ICSD classification criteria].

For the diagnosis of sleep disorders, 3 different standardized classification systems are available: the International Statistical Classification of Diseases and Related Health Problems (ICD-10), the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R/DSM-IV) and the International Classification of Sleep Disorders (ICSD). These 3 classification schemata were comparatively evaluated in 50 sleep-disturbed patients who were admitted within 1 year to a non-specialized sleep laboratory for diagnostic evaluation and treatment. 17 female and 33 male sleep-disturbed patients, aged 54 +/- 12 years, were recorded polysomnographically in 3 subsequent nights (adaptation night, baseline/diagnosis night, treatment night) for measuring objective sleep quality. The subjective sleep quality as well as the subjective and objective awakening quality was assessed by means of rating scales, as well as psychometric and psychophysiological test battery. During the day, EEG, EEG-mapping, psychodiagnostic tests as well as, in many cases, pulmonary function, otolaryngological, CT, MRT and pharyngometric investigations were carried out. Psychic disorders were the leading cause for sleep problems in all 3 classification systems. Based on the ICD-10, the most frequent diagnosis was non-organic insomnia (46%), followed by sleep apnea (18%) and other organic sleep disorders (14%). Based on the DSM-III-R, 46% of the patients were diagnosed as insomnias based on another mental disorder, 38% as organic hypersomnias and 14% as parasomnias. Based on the ICSD Classification, sleep disorders associated with anxiety disorders were leading (30%), followed by sleep disorders based on affective disorders (16%), obstructive snoring (14%), primary snoring (8%) and sleep disorders based on neurological disorders (6%). While the broader ICD-10 and DSM-III-R diagnoses are syndrome-etiologically oriented and may be easily utilized by the practicing physician, the more narrowly defined, extensive, pathogenetically oriented polysomnographic features including ICSD diagnoses are suited better for the specialist.

Adult↗
PubMed1994

Assessment of a positive selection technique using an avidin column to isolate human peripheral blood T cell subsets.

The current studies were designed to assess a new technique for positively selecting human T cells from whole peripheral blood mononuclear cells using the minimal amount of monoclonal antibody required to bind the T cell to an avidin column indirectly via a biotin-conjugated secondary antibody. Positive selection of T cells has previously been avoided because the saturating amounts of antibodies required for other isolation procedures can lead to aberrant results in assays of T cell activation and function. The avidin column technique for obtaining purified T cell subsets was compared to a multi-step procedure that included negative selection panning. The positive selection technique was easily performed within 4 h whereas the negative selection technique required a minimum of 12 h to complete. The avidin column technique proved to be a rapid and simple method for isolating T cell subsets of high purity and normal functional capabilities. Since minimal amounts of monoclonal antibodies were used for the purification protocol, no consistent inhibitory or stimulatory effect of the residual antibody was noted in assays of activation and proliferation of positively selected T cells compared to T cells isolated by negative selection panning.

Adult↗