Three hospitals link clinical, financial data.
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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.
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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.
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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↗
Isolation of cDNA clones and complete amino acid sequence of human erythrocyte glycophorin C.
Two cDNA clones for glycophorin C, a transmembrane glycoprotein of the human erythrocyte which carries the blood group Gerbich antigens, have been isolated from a human reticulocyte cDNA library. The clones were identified with a mixture of 32 oligonucleotide probes (14-mer) which have been synthetized according to the amino acid sequence Asp-Pro-Gly-Met-Ala present in the N-terminal tryptic peptide of the molecule. The primary structure of glycophorin C deduced from the nucleotide sequence of the 460 base-pair insert of the pGCW5 clone indicates that the complete protein is a single polypeptide chain of 128 amino acids clearly organized in three distinct domains. The N-terminal part (residues 1-57, approximately) which is N- and O-glycosylated is connected to a hydrophilic C-terminal domain (residues 82-128, approximately) containing 4 tyrosine residues by a hydrophobic stretch of nonpolar amino acids (residues 58-81, approximately) probably interacting with the membrane lipids and permitting the whole molecule to span the lipid bilayer. Northern blot analysis using a 265-base-pair restriction fragment obtained by DdeI digestion of the inserted DNA shows that the glycophorin C mRNA from human erythroblasts is approximately 1.4 kilobases long and is present in the human fetal liver and the human K562 and HEL cell lines which exhibit erythroid features. The glycophorin C mRNA, however, is absent from adult liver and lymphocytes, indicating that this protein represents a new erythrocyte-specific probe which might be useful to study erythroid differentiation.
Amino Acid Sequence↗
Peanut agglutinin. II. Characterization of the Thy-1, Tla and Ig phenotype of peanut agglutinin-positive cells in adult, embryonic and nude mice using double immunofluorescence.
The Thy-1, Tla and Ig phenotype of peanut agglutinin (PNA)-binding cells was characterized in various strains of mice. In the thymus, PNA was found to bind principally but not exclusively to the Thy-1+ Tla + Ig-- steroid-sensitive cortical thymocytes. Thy1 + Tla -- Ig -- steroid-resistant cells are not labeled with PNA. In other lymphoid organs, PNA bound to a minority of T or null cells but generally not to B cells. During ontogeny, PNA + and PNA -- T lineage cells appear simultaneously in the liver at day 10 of gestation, in the thymus at day 11 and in the spleen at day 18. No evidence was found for a maturation from PNA + to PNA -- cells. Prethymocytes present in nude mice were also divided into a PNA + and PNA -- population.
Animals↗
Peanut agglutinin. III. Study of T lymphocyte differentiation during murine ontogeny.
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Animals↗
Peanut agglutinin. IV. A tool for studying human mononuclear cell differentiation.
Peanut agglutinin (PNA) has previously been shown to be a 'marker' for early T subpopulations in mice. We have investigated whether it could also be used in the study of human mononuclear cells. 50--60% of human thymocytes have binding sites for PNA. When separated on a discontinuous Ficoll gradient, the PNA-positive thymocytes are found preferentially in the layers corresponding to the immunoincompetent cells. In the peripheral blood only 5% of the mononuclear cells are PNA-positive and we have shown that these cells are monocytes. In tonsils 13% of PNA+ cells are found and they are mostly lymphocytes. Thus, PNA is a marker for some T cell subsets present in the thymus and tonsils.
Adult↗