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At least 919 records · Page 51Linked to original sources
PubMed2006

The prototypical inhibitor of cholesterol esterification, Sah 58-035 [3-[decyldimethylsilyl]-n-[2-(4-methylphenyl)-1-phenylethyl]propanamide], is an agonist of estrogen receptors.

We have shown recently that estrogen receptor (ER) ligands share a diphenyl ethane pharmacophore with Sah 58-035 [3-[decyldimethylsilyl]-N-[2-(4-methylphenyl)-1-phenylethyl]-propanamide], a prototypical inhibitor of the acyl-cholesterolacyl-transferase (ACAT), which enabled us to establish that ER ligands were potent inhibitors of ACAT and blocked the formation of foam cells. In the present study, we have tested whether this structural similarity means that Sah 58-035 is an ER modulator. We report that Sah 58-035 bound to ERalpha and ERbeta with an IC(50) of 2.9 and 3.1 microM, respectively. Docking studies using molecular modeling of Sah 58-035 with the X-ray structure of the ER showed that Sah 58-035 fits well into the ligand binding site known for 4-hydroxy-tamoxifen. Despite having high three-dimensional structural similarities with the pure antiestrogen ICI 164,384 [(N-n-butyl-N-methyl-11-[3,17beta-di-hydroxyestra-1,3, 5(10)-trien-7alpha-yl]-undecanamide], we showed that Sah 58-035 is an agonist of ER for transcription and cellular proliferation. These data showed that Sah 58-035 was an estrogen receptor agonist and that the size and the chemical nature of the side chain were critical for agonist versus antagonist activity on ER. This new molecular mechanism of action for Sah 58-035 has to be taken into account in understanding better its pharmacological activities. Moreover, these data give new structural insights into the understanding of agonist versus antagonist activities of ER ligands and also for the conception of new drugs with a dual ACAT inhibition and ER modulation potential and their evaluation in different pathologies where both targets are involved, such as atherosclerosis, Alzheimer's disease, and cancer.

Amides↗
PubMed1997

Laser Rapid Prototyping of Photonic Band-Gap Microstructures

Three-dimensional periodic microstructures of aluminum oxide, which are important for creating photonic band-gap structures (PBGs), were fabricated by laser rapid prototyping by means of laser-induced direct-write deposition from the gas phase. The structures consisted of layers of parallel rods forming a face-centered tetragonal lattice with lattice constants of 66 and 133 micrometers. These structures showed transmission minima centered around 4 terahertz (75 micrometers) and 2 terahertz (150 micrometers), respectively. PBGs will allow precise control of the optical properties of materials, including lasers without threshold.

Journal Article↗
PubMed1980

Automation of water bacteriological analysis: running test of an experimental prototype.

The experimental apparatus described enables continuous and automatic bacteriological water examination. It ensures the analysis and detection of Escherichia coli by incubation of the water samples and then detection of glutamic acid decarboxylase in coils according to the Technicon principles. The analysis is rapid: it is performed within 13 h with a sensitivity of better than 1 bacterium/100 ml, and 120 samples of 100 ml of water are examined in 24 h. Laboratory experiments and field testing showed that this prototype ensured a specific and sensitive analysis. They also provided information about the frequency of maintenance necessary to retain its efficiency. This device would allow, under the same conditions, the examination of liquid food products.

Autoanalysis↗
PubMed1997

Comparative sensitivities of Sabin and Mahoney poliovirus type 1 prototype strains and two recent isolates to low concentrations of glutaraldehyde.

Significant intratypic differences in the glutaraldehyde (GTA) sensitivity of echovirus isolates have been shown. While exploring ways to optimize the study of GTA sensitivity of enteroviruses, we also observed intratypic differences in poliovirus type 1 isolates collected in France. A suspension procedure was used for assessing the virucidal effect of GTA at low concentrations (< or = 0.10%) against purified viruses. Two recent isolates of poliovirus type 1 tested were first fully characterized by the PCR restriction fragment length polymorphism (RFLP) test. The RFLP pattern of clinical isolate 5617 was similar to that of poliovirus type 1 LS-c, 2ab (Sabin strain), confirming the vaccine origin of strain 5617. The RFLP pattern of strain 5915 recovered from sewage was different from that of the Mahoney strain, suggesting a genetic variation in this wild isolate. We then analyzed under the same controlled conditions the GTA sensitivities of both isolates and their respective prototype strains. The wild Mahoney and 5915 strains exhibited significantly lower sensitivities to GTA than did the vaccine Sabin and 5617 strains. The inactivation rates of clinical isolates 5617 and 5915 were very similar to those of their corresponding reference Sabin and Mahoney strains. Both the conformational structure of the capsid of each strain and the amino acid constitution of structural polypeptides could be involved in the variations observed. The relevance of our comparative sensitivity studies to standardization of virucidal tests is discussed.

Animals↗
PubMed1969

Radiation sterilization of prototype military foods. 3. Pork loin.

Ten lots of pork loin, packed in cans, were inoculated with approximately 10(6)Clostridium botulinum spores per can. Each lot was seeded with a different strain; five type A and five type B strains were used. The pack comprised 5,690 cans, including controls, and contained about 10(9) spores per dose. The cans were irradiated with Co(60) in the range of 0 to 5.0 Mrad (0.5 Mrad increments) at 5 to 25 C, incubated for 6 months at 30 C, and examined for swelling, toxicity, and recoverable C. botulinum. The minimal experimental sterilizing dose (ESD) based on nonswollen, nontoxic, but nonsterile end points was 2.5 < ESD </= 3.0 Mrad, and based on non-spoiled sterile cans was 3.5 < ESD </= 4.0 Mrad. The theoretical minimal radiation dose (MRD), the 12D equivalent, varied with the method of computation: 4.74, 4.33 +/- 0.17, and 4.19 to 4.99 Mrad were obtained by the Weibull, Spearman-Karber, and Schmidt-Nank techniques, respectively. Calculation of D and MRD values by the conventional Schmidt-Nank method produced increasing values with rising dosage; this finding was compared with the data derived by the other two methods of calculation. Suggestions for estimating the MRD of a prototype radiation process are offered.

Animals↗
PubMed1971

Prototype of a fully automated device for determination of bacterial antibiotic susceptibility in the clinical laboratory.

A completely automated system for the performance of antibiotic susceptibility tests in the clinical laboratory is described. With a modicum of personnel involvement, data on 40 specimens tested against 13 antibiotics are obtained every hour after an initial 3-hr period. The step by step explanation of the functioning of this prototype system, based on a thoroughly tested manual model, is presented. The system compares well with the standard diffusion test and has a potential for application to other endeavors of the clinical microbiology laboratory with a comparable saving in time and labor.

Agar↗
PubMed2003

Ehrlichia chaffeensis: a prototypical emerging pathogen.

Ehrlichia chaffeensis is an obligately intracellular, tick-transmitted bacterium that is maintained in nature in a cycle involving at least one and perhaps several vertebrate reservoir hosts. The moderate to severe disease caused by E. chaffeensis in humans, first identified in 1986 and reported for more than 1,000 patients through 2000, represents a prototypical "emerging infection." Knowledge of the biology and natural history of E. chaffeensis, and of the epidemiology, clinical features, and laboratory diagnosis of the zoonotic disease it causes (commonly referred to as human monocytic ehrlichiosis [HME]) has expanded considerably in the period since its discovery. In this review, we summarize briefly the current understanding of the microbiology, pathogenesis, and clinical manifestations associated with this pathogen but focus primarily on discussing various ecological factors responsible for the recent recognition of this important and potentially life-threatening tick-borne disease. Perhaps the most pivotal element in the emergence of HME has been the staggering increases in white-tailed deer populations in the eastern United States during the 20th century. This animal serves as a keystone host for all life stages of the principal tick vector (Amblyomma americanum) and is perhaps the most important vertebrate reservoir host for E. chaffeensis. The contributions of other components, including expansion of susceptible human populations, growth and broadening geographical distributions of other potential reservoir species and A. americanum, and improvements in confirmatory diagnostic methods, are also explored.

Animals↗
PubMed1994

Construction and characterization of attenuated delta aroA delta virG Shigella flexneri 2a strain CVD 1203, a prototype live oral vaccine.

We engineered an oral Shigella vaccine prototype that can invade intestinal epithelial cells but cannot undergo extensive intracellular replication or extend to adjacent epithelial cells. Strain CVD 1203, derived from wild-type Shigella flexneri 2a by introducing deletions in chromosomal aroA and invasion plasmid virG, was highly attenuated in the Sereny test. Two 10(9)-CFU orogastric doses (2 weeks apart) stimulated production of secretory immunoglobulin A antibodies to S. flexneri 2a and protected against conjunctival sac challenge with virulent S. flexneri 2a.

Administration, Oral↗
PubMed1998

Identification of three highly attenuated Salmonella typhimurium mutants that are more immunogenic and protective in mice than a prototypical aroA mutant.

A panel of Salmonella typhimurium 14028s mutants, which were previously shown to be highly attenuated in the BALB/c mouse model of infection, were analyzed for their potential as live Salmonella oral-vaccine candidates. A prototypical aroA mutant was chosen as a basis of comparison. From the panel of mutants initially chosen for this study, three mutants with comparable levels of attenuation elicited higher Salmonella-specific serum immunoglobulin G (IgG) and/or mucosal secretory-IgA antibody titers than the aroA vaccine strain. The three mutants, CL288, CL401, and CL554, also elicited a better protective immune response than the aroA control strain, after a single oral dose of 1 x 10(9) to 2 x 10(9) bacteria.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed2000

Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1.

We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1). However, the SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins. The prototypic gene in this cluster, set1, has been cloned and expressed. Recombinant SET1 stimulated the production of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed that set1 was distributed among other strains of S. aureus but not in the other staphylococcal species examined. Sequence analysis of the set1 genes from different strains revealed at least three allelic variants. The protein products of these allelic variants displayed a 100-fold difference in their cytokine-inducing potency. The distribution of allelic variants of the set genes among strains of S. aureus may contribute to differences in the pathogenic potential of this bacterium.

Amino Acid Sequence↗
PubMed2003

Borrelia burgdorferi population dynamics and prototype gene expression during infection of immunocompetent and immunodeficient mice.

The population dynamics of Borrelia burgdorferi were quantified by real-time PCR targeting the flaB gene in skin (inoculation site, noninoculation site, and ear), heart (heart base and ventricle), quadriceps muscle, and the tibiotarsal joint at 1, 2, 4, 6, and 8 weeks after intradermal inoculation in C3H and C3H-scid mice. In addition, RNA transcription was assessed for several prototype genes, including flaB, ospA, ospC, dbpA, arp, vlsE, fbp, oppA-2, and p37-42. Spirochete numbers were equivalent in C3H and C3H-scid mice at 1 or 2 weeks and then declined in C3H mice, but they continued to rise and then plateaued in C3H-scid mice. Gene transcription was likewise higher in C3H-scid mice than in C3H mice, particularly at 4 or more weeks of infection. Gene transcription showed variation among tissues, with the highest levels of transcription in heart and joint tissue, which are sites of inflammation.

Animals↗
PubMed1986

DNA environment of the aerobactin iron uptake system genes in prototypic ColV plasmids.

The aerobactin iron uptake system genes in the prototypic plasmid pColV-K30 are flanked by inverted copies of insertion sequence IS1 and by two distinct replication regions. To address the question of how these flanking regions may facilitate the maintenance and spread of the aerobactin system among the plasmids and chromosomes of enteric species, we investigated the DNA environment of 12 ColV plasmids. We found that the aerobactin system-specific genes are conserved in every plasmid phenotypically positive for the aerobactin system. The upstream IS1 and its overlapping replication region (REPI) are also conserved. This replication region was cloned from several ColV plasmids and found to be functional by transforming these cloned derivatives into a polA bacterial host. In contrast, the downstream flanking region is variable. This includes the downstream copy of IS1 and the downstream replication region (REPII). We infer from these results that sequences in addition to the two flanking copies of IS1, in particular the upstream region including REPI, have been instrumental in the preservation and possible spread of aerobactin genes among ColV plasmids and other members of the FI incompatibility group.

Bacteriocin Plasmids↗
PubMed2000

Functional analysis of the small component of the 4-hydroxyphenylacetate 3-monooxygenase of Escherichia coli W: a prototype of a new Flavin:NAD(P)H reductase subfamily.

Escherichia coli W uses the aromatic compound 4-hydroxyphenylacetate (4-HPA) as a sole source of carbon and energy for growth. The monooxygenase which converts 4-HPA into 3,4-dihydroxyphenylacetate, the first intermediate of the pathway, consists of two components, HpaB (58.7 kDa) and HpaC (18.6 kDa), encoded by the hpaB and hpaC genes, respectively, that form a single transcription unit. Overproduction of the small HpaC component in E. coli K-12 cells has facilitated the purification of the protein, which was revealed to be a homodimer that catalyzes the reduction of free flavins by NADH in preference to NADPH. Subsequently, the reduced flavins diffuse to the large HpaB component or to other electron acceptors such as cytochrome c and ferric ion. Amino acid sequence comparisons revealed that the HpaC reductase could be considered the prototype of a new subfamily of flavin:NAD(P)H reductases. The construction of a fusion protein between the large HpaB oxygenase component and the choline-binding domain of the major autolysin of Streptococcus pneumoniae allowed us to develop a rapid method to efficiently purify this highly unstable enzyme as a chimeric CH-HpaB protein, which exhibited a 4-HPA hydroxylating activity only when it was supplemented with the HpaC reductase. These results suggest the 4-HPA 3-monooxygenase of E. coli W as a representative member of a novel two-component flavin-diffusible monooxygenase (TC-FDM) family. Relevant features on the evolution and structure-function relationships of these TC-FDM proteins are discussed.

Amino Acid Sequence↗
PubMed2001

Iron-sulfur flavoprotein (Isf) from Methanosarcina thermophila is the prototype of a widely distributed family.

A total of 35 homologs of the iron-sulfur flavoprotein (Isf) from Methanosarcina thermophila were identified in databases. All three domains were represented, and multiple homologs were present in several species. An unusually compact cysteine motif ligating the 4Fe-4S cluster in Isf is conserved in all of the homologs except two, in which either an aspartate or a histidine has replaced the second cysteine in the motif. A phylogenetic analysis of Isf homologs identified four subgroups, two of which were supported by bootstrap data. Three homologs from metabolically and phylogenetically diverse species in the Bacteria and Archaea domains (Af3 from Archaeoglobus fulgidus, Cd1 from Clostridium difficile, and Mj2 from Methanococcus jannaschii) were overproduced in Escherichia coli. Each homolog purified as a homodimer, and the UV-visible absorption spectra were nearly identical to that of Isf. After reconstitution with iron, sulfide, and flavin mononucleotide (FMN) the homologs contained six to eight nonheme iron atoms and 1.6 to 1.7 FMN molecules per dimer, suggesting that two 4Fe-4S or 3Fe-4S clusters and two FMN cofactors were bound to each dimer, which is consistent with Isf data. Homologs Af3 and Mj2 were reduced by CO in reactions catalyzed by cell extract of acetate-grown M. thermophila, but Cd1 was not. Homologs Af3 and Mj2 were reduced by CO in reactions catalyzed by A. fulgidus and M. jannaschii cell extracts. Cell extract of Clostridium thermoaceticum catalyzed CO reduction of Cd1. Our database sequence analyses and biochemical characterizations indicate that Isf is the prototype of a family of iron-sulfur flavoproteins that occur in members of all three domains.

Amino Acid Motifs↗
PubMed1997

Detection of Mycobacterium tuberculosis directly from sputum by using a prototype automated Q-beta replicase assay.

We have adapted an assay for the direct detection of Mycobacterium tuberculosis using a prototype automated instrument platform in which probes are amplified with Q-beta replicase. The assay was based on amplification of specific detector probe following four cycles of background reduction (reversible target capture) in a closed disposable pack. The assay signal was the time required for fluorescence to exceed background levels (response time [RT]). RT was inversely related to the number of M. tuberculosis rRNA target molecules in the sample. Equivalent signals and noises were observed in assays containing either sputum or buffer. All mock samples containing > or = 10 CFU of M. tuberculosis responded in the assay (average RT, 13.91 min), while most (83%) samples containing as many as 10(7) CFU of Mycobacterium avium gave no response during a 25-min amplification reaction. The samples containing M. avium which did respond had an average RT of 17.04 min. Seventy-five percent (167 of 223) of samples containing no target gave no responses; the remaining 25% had an average RT of 15.53 min. Eighty-three frozen sputum samples were tested to develop a candidate cutoff RT for the assay prior to more extensive clinical testing. After resolution of discrepant results and with a 14-min RT cutoff, 30 of 38 M. tuberculosis-positive samples were positive by the assay; 1 of 45 negative samples responded within 14 min. Assay sensitivity, specificity, and positive and negatives predictive values in this pilot study were 79, 98, 97, and 85%, respectively.

DNA Probes↗
PubMed1999

Klebsiella pneumoniae lipopolysaccharide O typing: revision of prototype strains and O-group distribution among clinical isolates from different sources and countries.

We have previously described an inhibition enzyme-linked immunosorbent assay method for the O typing of O1 lipopolysaccharide from Klebsiella pneumoniae which overcomes the technical problems and limitations of the classical O-typing method. In this study, we have extended the method to all of the currently recognized O types. The method was validated by studying the prototype strains that have defined the O groups by the classical tube agglutinatination O-typing method. Based on these results, we confirmed the O types of 60 of 64 typeable strains, and we propose a revised O-antigenic scheme, with minor but necessary changes, consisting of serogroups or serotypes O1, O2, O2ac, O3, O4, O5, O7, O8, and O12. Application of this typing method to 638 K. pneumoniae clinical isolates from Denmark, Spain, and the United States from different sources (blood, urine, and others) showed that up to 80% of these isolates belong to serotypes or serogroups O1, O2, O3, and O5, independently of the source of isolation, and that a major group of nontypeable isolates, representing about 17% of the total, consists of half O+ and half O- strains. Differences were observed, however, in the prevalence of the lipopolysaccharide O types or groups, depending on the country and isolation source.

Denmark↗
PubMed1999

Evaluation of the prototype Roche DNA amplification kit incorporating the new SSK145 and SKCC1B primers in detection of human immunodeficiency virus type 1 DNA in Zimbabwe.

We assessed the sensitivity and specificity of a newly developed DNA PCR kit (Roche Diagnostic Corporation, Indianapolis, Ind.) that incorporates primers for all the group M viruses for the detection of human immunodeficiency virus (HIV) type 1 (HIV-1) infection in Zimbabwe. A total of 202 whole-blood samples from adults whose HIV status was known were studied. This included 100 HIV-1-positive and 102 HIV-1-negative samples selected on the basis of concordant results obtained with two enzyme-linked immunosorbent assay kits. The prototype Roche DNA PCR assay had a 100% sensitivity for the detection of HIV-1 DNA and a specificity of 100%. We conclude that the new Roche DNA PCR kit is accurate for the detection of HIV DNA in Zimbabwean samples, in which HIV-1 subtype C dominates.

Adult↗
PubMed2000

Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients.

The correlation between the prototype AMPLICOR CMV MONITOR test (Roche Molecular Systems), a quantitative PCR assay, and the cytomegalovirus (CMV) pp65 antigenemia assay was evaluated in transplant recipients. Sequential blood specimens were collected on 29 patients (491 specimens), the leukocyte fraction was tested by CMV antigenemia, and quantitative PCR was performed on plasma specimens. None of the 15 patients (242 specimens) who were antigenemia negative were positive for CMV DNA by PCR, and none of these patients developed active CMV disease. There were 14 antigenemia-positive patients, 8 of whom developed active CMV disease. In all patients, there was a good association between the antigenemia and PCR assays. Ganciclovir-resistant virus was isolated from three patients with active CMV disease. These three patients had persistently elevated levels of antigenemia and CMV DNA by PCR when resistance to ganciclovir developed. This standardized, quantitative CMV PCR assay on plasma has clinical utility for the diagnosis of active disease and in monitoring the response to antiviral therapy in transplant recipients.

Adolescent↗