Three hospitals link clinical, financial data.
Explore the source record for details and available documents.
Clinical Medicine↗
Biomedical subjects
J London
Publications and source records attributed to J London.
The gene encoding a Prevotella loescheii lectin-like adhesin contains an interrupted sequence which causes a frameshift.
We cloned and sequenced the Prevotella loescheii gene plaA, which encodes a lectin-like adhesin that mediates the coaggregation of P. loescheii 1295 with Streptococcus oralis 34. A probe derived from the N-terminal amino acid sequence of the purified adhesin was used to identify the plaA gene from a P. loescheii genomic library constructed in lambda GEM-11. Sequence analysis of plaA indicates that the initial translation product contains a 22-amino-acid leader. The reading frame of the plaA gene is interrupted after amino acid 28 of the mature protein by a TAA termination codon. Amplification of the P. loescheii genomic DNA in the region surrounding this codon by the polymerase chain reaction followed by DNA sequencing of the cloned DNA fragment established that this stop codon was not an experimental artifact. A frameshift beginning 29 bp downstream of the ochre terminator was required to access the only large open reading frame in the gene. Amino acid sequences of six purified peptides derived by limited proteolysis of adhesin with endoproteinase Lys-C matched the downstream amino acid sequence derived by translation of the large open reading frame. The gene coding sequence of 2.4 kb contains sufficient information for the synthesis of an 89-kDa protein. A putative rho-independent terminator (delta G = -25.5 kcal/mol [ca. -107 kJ/mol]) was detected 38 bp downstream from the plaA stop codon.
Adhesins, Bacterial↗
Mass media as drug users' key information source on overdoses.
Explore the source record for details and available documents.
Drug Overdose↗
The organization engine: virtual data integration.
The Organization Engine is an early example of Virtual Data Integration--providing the appearance of integration at the desktop without modifying existing infrastructure. Starting with the Organization Engine, eight programming days were needed to provide uniform desktop access to a CODASYL-compliant hospital information system and to a MUMPS-based radiology information system (the technique is equally effective for relational and other data bases). The resulting tool provides a seamless integration of these two systems, image storage, pre-recorded audio, and document storage. In addition to providing uniform access, the tool allows healthcare providers to organize the data to suit their individual needs. The ease of this integration lies in two simple techniques: the transformation of data from all sources into a single, homogeneous representation, and the use of simple customization files to describe new object types and formats. The approach is sufficiently general to allow the integration of applications which present external interfaces of radically different forms. Two such forms are discussed here: data map publication and transactions.
Computer Communication Networks↗
Erythrocyte glycophorin B deficiency may occur by two distinct gene alterations.
The genomic DNA from rare persons whose erythrocytes are deficient in glycophorin B (GPB) (S-s-U- phenotype), was examined by Southern hybridizations using glycophorin B probes and was subdivided into two main categories. In the type I variant (Fav., M.H., S.K.), we found that the S-s-U- condition is generated by a large gene deletion extending from exons B2 to B4 of glycophorin B gene. Conversely, in the type II variant (Del.), the entire gene is present, and its promoter is almost similar to common Glycophorin A (GPA) and GPB as well as to type I promoters, except for four-point mutations, which do not occur in potential cis-acting elements. We concluded that the same phenotypic glycophorin B deficiency may occur by different gene alterations, including either a gene deletion or a mutation that might alter transcription or translation of the gene.
Blotting, Southern↗
Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study.
In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Promoter sequence and chromosomal organization of the genes encoding glycophorins A, B and E.
The promoter and exon 1 sequences of the genes encoding erythrocyte glycophorins GPA, GPB and GPE were investigated in detail, both from a genomic clone sorted out of a human leukocyte library and from genomic clones obtained by polymerase chain reaction amplification of total genomic DNA from control individuals and from GAP and/or GPB deletion variants. The three exons 1 and upstream sequences were shown to be highly homologous with only a few point mutations that did not affect the potential cis-acting elements (CACCC, NF-E1 and NF-E2) that are present in the same position within the three genes. Moreover, these genes share the same transcription start point. Analysis of the exon 1 and promoter sequences together with the gene defects occurring in the GP variants indicate that unequal cross-overs between the three genes are responsible for deletions and the generation of hybrid gene structures in which the promoter of one gene is brought close to another gene of the family. On the basis of these studies, a model of the gene organization is proposed to explain the rearrangements occurring in the variants.
Base Sequence↗
Structure of a streptococcal adhesin carbohydrate receptor.
Interactions between complementary protein and carbohydrate structures on different genera of human oral bacteria have been implicated in the formation of dental plaque. The carbohydrate receptor on Streptococcus sanguis H1 (one of the primary colonizing species) that is specific for the adhesin on Capnocytophaga ochracea ATCC 33596 (a secondary colonizer) has been isolated from the streptococcal cell wall, purified, and structurally characterized. The hexasaccharide repeating unit of the polysaccharide was purified by reverse-phase, amino-bonded silica, and gel permeation high performance liquid chromatography. Earlier studies established that the repeating unit was a hexasaccharide composed of rhamnose, galactose, and glucose in the ration of 2:3:1, respectively. In the present study, determination of absolute configuration by gas chromatography of the trimethylsilyl (+)-2-butyl glycosides revealed that the rhamnose residues were of the L configuration while the hexoses were all D. 252Californium plasma desorption mass spectrometry of the native, the acetylated and the reduced and acetylated hexasaccharide determined that the molecular mass of the native hexasaccharide was 959, and that the 2 rhamnose residues were linked to each other at the nonreducing terminus of the linear molecule. Methylation analysis revealed the positions of the glycosidic linkages in the hexasaccharide and showed that a galactose residue was present at the reducing end. The structural characterization of the hexasaccharide was completed by one and two dimensional 1H and 13C NMR spectroscopy. Complete 1H and 13C assignments for each glycosyl residue were established by two-dimensional (1H,1H) correlation spectroscopy, homonuclear Hartmann-Hahn, and (13C,1H) correlation experiments. The configurations of the glycosidic linkages were inferred from the chemical shifts and coupling constants of the anomeric 1H and 13C resonances. The sequence of the glycosyl residues was determined by a heteronuclear multiple bond correlation experiment. These data show that the structure of the hexasaccharide repeating unit derived from the cell wall polysaccharide of S. sanguis H1 is: alpha-L-Rhap-(1----2)-alpha-L-Rhap-(1----3)-alpha-D-Galp- (1----3)-beta-D-Galp-(1----4)-beta-D-Glcp-(1----3)-alpha/beta-D-Gal.
Bacterial Adhesion↗
A novel gene member of the human glycophorin A and B gene family. Molecular cloning and expression.
A new gene closely related to the glycophorin A (GPA) and glycophorin B (GPB) genes has been identified in the normal human genome as well as in that of persons with known alterations of GPA and/or GPB expression. This gene, called glycophorin E (GPE), is transcribed into a 0.6-kb message which encodes a 78-amino-acid protein with a putative leader peptide of 19 residues. The first 26 amino acids of the mature protein are identical to those of M-type glycophorin A (GPA), but the C-terminal domain (residues 27-59) differs significantly from those of glycophorins A and B (GPA and GPB). The GPE gene consists of four exons distributed over 30 kb of DNA, and its nucleotide sequence is homologous to those of the GPA and GPB genes in the 5' region, up to exon 3. Because of branch and splice site mutations, the GPE gene contains a large intron sequence partially used as exons in GPA and GPB genes. Compared to its counterpart in the GPB gene, exon 3 of the GPE gene contains several point mutations, an insertion of 24 bp, and a stop codon which shortens the reading frame. Downstream from exon 3, the GPE and the GPB sequences are virtually identical and include the same Alu repeats. Thus, it is likely that the GPE and GPB genes have evolved by a similar mechanism. From the analysis of the GPA, GPB and GPE genes in glycophorin variants [En(a-), S-s-U- and Mk], it is proposed that the three genes are organized in tandem on chromosome 4. Deletion events within this region may remove one or two structural gene(s) and may generate new hybrid structures in which the promoter region of one gene is positioned upstream from the body of another gene of the same family. This model of gene organization provides a basis with which to explain the diversity of the glycophorin gene family.
Amino Acid Sequence↗
Uncommon pathways of metabolism among lactic acid bacteria.
A small number of lactic acid bacteria possess the ability to derive energy from organic molecules not utilized by the vast majority of representatives of this large group of microorganisms. Thus, strains of Lactobacillus casei and enterococci readily grow at the expense of substrates such as gluconate, malate and pentitols. Transport of gluconate and pentitols is catalysed by phosphotransferase systems unique to these bacteria. Similarly, the initial steps in pentitol dissimilation are mediated by enzymes found only in Lb. casei and Streptococcus avium.
Amino Acids↗
Purification and characterization of a Bacteroides loeschei adhesin that interacts with procaryotic and eucaryotic cells.
The adhesin of Bacteroides loeschei PK1295 that mediates coaggregation with Streptococcus sanguis 34 and hemagglutination of erythrocytes was purified to electrophoretic homogeneity. The lectinlike protein has an estimated native Mr of 450,000 and consists of six subunits of identical molecular weight (Mr 75,000). The purified adhesin appears to be a basic protein with a pI between 7.4 and 8.0. Amino acid and N-terminal sequence analyses were carried out with the purified protein. These indicated that the protein contains a large number of Asx and Glx residues as well as basic amino acid residues. The binding site of the pure adhesin retained its native configuration during purification. When preincubated with streptococcal partner cells at pH 4.6, the adhesin prevented B. loeschei cells from coaggregating with the streptococci. An adhesin preparation adjusted to a pH of 6.8 rapidly agglutinated both streptococci and neuraminidase-treated erythrocytes. Galactosides inhibited the agglutination reactions.
Adhesins, Bacterial↗
Alerting drug abusers to overdose threats: the media's role.
Explore the source record for details and available documents.
Communication↗
Buspirone in depressed outpatients: a controlled study.
One hundred fifty-five outpatients suffering from major depression with significant anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Twenty-nine percent of buspirone and 40 percent of placebo patients discontinued treatment before 8 weeks. Major efficacy measures were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D retardation and anxiety factors, the HAM-D Rickels and Bech core depression clusters, the Clinical Global Impressions (CGI), and the Hopkins Symptom Checklist (HSCL). Results were consistent across all outcome measures, including the two core depression clusters, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35 percent of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Buspirone was found to be safe and well-tolerated by patients with major depression and concomitant anxiety at doses of up to 90 mg/day.
Anxiety Disorders↗
A placebo-controlled study of enciprazine in the treatment of generalized anxiety disorder: a preliminary report.
Enciprazine is a propanolamine derivative with a preclinical profile similar to buspirone but with less affinity for the postsynaptic dopamine receptor (Linden et al. 1988). We report on the outcome, using intent-to-treat data, of a 5-week, double-blind trial comparing three dose strengths of enciprazine (5 mg t.i.d., 10 mg t.i.d., and 20 mg t.i.d.) to placebo. A dose escalation was permitted after 2 weeks of active drug treatment, which 61 percent of patients overall took advantage of. A "last observation carried forward" (LOCF) analysis found a mean improvement in Hamilton Anxiety Scale (HAM-A) scores by Week 5 of -11.0 for the combined enciprazine treatment groups, and -4.4 for the placebo group (p less than .05). Fifty-two percent of enciprazine patients were judged to be "much" or "very much" improved, whereas none of the placebo patients were judged to have comparable improvement. Enciprazine was well-tolerated, with low levels of sedative and asthenic side effects reported. The compound appears to have promise as an anxiolytic agent.
Adult↗
Structure of the 5' flanking region of the gene encoding human glycophorin A and analysis of its multiple transcripts.
Glycophorin A (GPA), the major sialoglycoprotein of human erythrocytes, is the carrier for blood group MN antigens and a receptor for viruses, bacteria and parasites. (1) Three distinct GPA mRNAs (1.0, 1.7 and 2.2 kb) have been previously identified in erythroid tissues by Northern-blot analysis. It is shown here by sequence analysis of several human fetal liver cDNAs, and by transcription start point (tsp) determination using primer extension analysis, that the production of the multiple GPA mRNAs is governed by poly(A) site choice generating 3'-untranslated regions of different length, and not by the tsp heterogeneity, since all messages exhibit the same cap site (tsp). (2) The structural gene encoding GPA has been recently cloned [Vignal et al., Eur. J. Biochem. 184 (1989) 337-344; Kudo and Fukuda, Proc. Natl. Acad. Sci. USA 86 (1989) 4619-4623] and we have now determined the sequence of a DNA genomic fragment upstream from the tsp. This fragment does not contain the typical TATA and CAAT boxes found in a number of tissue-specific genes, but contains typical motifs like the CACC, nuclear factor erythroid 1 and 2 elements, which have been identified recently in several erythroid-specific promoters, therefore suggesting that transcription of these genes might be regulated by the same or analogous factors.
Amino Acid Sequence↗
Molecular analysis of glycophorin A and B gene structure and expression in homozygous Miltenberger class V (Mi. V) human erythrocytes.
In the Miltenberger class V (Mi. V) condition, red cells lack glycophorin A (GPA) and glycophorin B (GPB) but carry instead an unusual glycoprotein thought to be a hybrid molecule produced by the unequal crossing-over between the closely linked genes encoding for GPA and GPB. By Western blot analysis with rabbit anti-GPA antibodies specific for discrete domains of GPA, it was found that the Mi. V glycoprotein (donor F. M.) contains approximately 60 amino acid residues of GPA at its N-terminus. As a preliminary approach to the molecular analysis of this variant the restriction maps of the GPA and GPB genes were established by Southern blot analysis of genomic DNA and from genomic clones isolated from a human leukocyte library constructed in lambda EMBL4. The GPA and GPB genes cover about 30 kb of DNA and are organized into seven exons (A-1-A-7) and five exons (B-1-B-5), respectively. In addition to the normal genes, a third gene (named inv), closely resembling the GPA and GPB genes, was also identified. In the homozygous Mi. V individual the normal GPA and GPB genes were absent, but an unusual form of gene structure was detected by Southern blot analysis. The Mi. V glycoprotein gene was composed of exon B-1 of the GPB gene followed by exons A-2 and A-3 of the GPA gene and the exons B-3, B-4 and B-5 of the GPB gene. Exon B-1 can be distinguished from exon A-1 of GPA since it is located within a different restriction fragment, but both encode the same amino acid sequence (N-terminal region of the signal peptides). Using the polymerase chain reaction, the junction between exon A-3 and exon B-3 was confirmed by amplification of the DNA region where the putative crossing-over has occurred and it was deduced that the Mi. V glycoprotein is a hybrid molecule composed of amino acid residues 1-58 from GPA fused to amino acid residues 27-72 of GPB. In addition, the finding that part of the signal peptide and the 5'-untranslated region are derived from GPB suggests that the genetic background of the Mi. V variant is rather complex and may involve a cascade of recombination or gene conversion events.
Amino Acid Sequence↗
Human erythrocyte glycophorin C. Gene structure and rearrangement in genetic variants.
We have previously shown that a deletion of approximately 3 kilobases in the unique glycophorin C (GPC) gene, which encodes for the human erythrocyte glycophorins C and D, is associated with the Gerbich (Ge) blood group deficiency (Ge-2,-3 and Ge-2,+3 types) (Le van Kim, C., Colin, Y., Blanchard, D., Dahr, W., London, J. & Cartron, J.P. (1987) Eur. J. Biochem. 165, 571-579). We have now isolated and characterized the structure of the GPC gene from the common Ge+2,+3 donors and from a Ge-2,-3 variant (Ge-2,-3 gene). The GPC gene is organized in four exons distributed over 13.5-kilobase pairs (kbp) DNA and contains two directly repeated domains of 3.4 kbp in length which are likely derived from the recent duplication of a unique ancestral domain. Restriction mapping and sequence analysis indicate that a 3.4-kbp deletion within this gene, arising probably by unequal crossing over between the two repeated domains, is responsible for the formation of the Ge-2,-3 gene. The breakpoints of the deletion are located within introns 2 and 3, and therefore exon 3 is removed. The defective gene is transcribed as a mRNA with a continuous open reading frame extending over 300 nucleotides which is translated into an unusual sialoglycoprotein present on Ge-2,-3 red cells. The primary structure of this new glycoprotein has been deduced from nucleotide sequencing. It is proposed in addition, that another 3.4-kb deletion within the GPC gene eliminates exon 2 only by a similar mechanism and generates a defective gene encoding for the abnormal glycoprotein present on Ge-2,+3 erythrocytes. Interestingly, the same deletion which lead to the rare Ge-2,-3 genetic condition, occurred spontaneously and frequently in the cloned GPC gene during the propagation of the recombinant phages in Escherichia coli. From these observations we suggest that the Ge-2,-3 and Ge-2,+3 genes might represent the two allelic forms of a unique ancestral form of the GPC gene, following successive internal duplication and deletion events.
Amino Acid Sequence↗
Use of adhesin-specific monoclonal antibodies to identify and localize an adhesin on the surface of Capnocytophaga gingivalis DR2001.
Monoclonal antibodies capable of inhibiting coaggregation between Capnocytophaga gingivalis DR2001 and Actinomyces israelii PK16 were used to identify the adhesin on C. gingivalis that mediates the interaction. The monoclonal antibodies were used to demonstrate that a 140-kilodalton polypeptide found in the outer membrane of C. gingivalis was the adhesin responsible for coaggregation. A coaggregation-defective mutant that was unable to coaggregate with A. israelii lacked this large polypeptide. The monoclonal antibodies were also used to estimate the number of binding sites on the surfaces of individual cells and show how the adhesin molecules were arranged on the outer membrane. Values of between 220 and 280 were obtained for the number of adhesin molecules per cell. Immunoelectron microscopy performed with the monoclonal antibodies revealed that the adhesin molecules were arranged nonuniformly on the bacterial surface and occurred singly, in pairs, and in small clusters.
Actinomyces↗