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1.
Can Commun Dis Rep ; 44(1): 29-34, 2018 Jan 04.
Article in English | MEDLINE | ID: mdl-29770096

ABSTRACT

The goal of this document was to provide Canadian laboratories with a framework for consistent reporting and monitoring of multidrug resistant organisms (MDRO) and extensively drug resistant organisms (XDRO) for common gram-negative pathogens. This is the final edition of the interim recommendations, which were modified after one year of broad consultative review. This edition represents a consensus of peer-reviewed information and was co-authored by the Canadian Public Health Laboratory Network and the Canadian Association of Clinical Microbiology and Infectious Diseases. There are two main recommendations. The first recommendation provides standardized definitions for MDRO and XDRO for gram-negative organisms in clinical specimens. These definitions were limited to antibiotics that are commonly tested clinically and, to reduce ambiguity, resistance (rather than non-susceptibility) was used to calculate drug resistance status. The second recommendation identifies the use of standardized laboratory reporting of organisms identified as MDRO or XDRO. Through the broad consultation, which included public health and infection prevention and control colleagues, these definitions are ready to be applied for policy development. Both authoring organizations intend to review these recommendations regularly as antibiotic resistance testing evolves in Canada.

4.
Phytomedicine ; 14(1): 57-64, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17190645

ABSTRACT

Our proprietary preparation obtained by extraction of Chlorella pyrenoidosa cells, ONC-107 (Respondin), was recently found to selectively boost antibody response to the influenza vaccine in a human clinical trial. Respondin is a potent stimulator of mouse B cell proliferation and an activator of macrophages. Bioactivity-guided resolution concluded that Respondin is composed of a mixture of immunostimulatory principles of different chemical nature. A combination of size exclusion, anion exchange and hydrophobic interaction chromatography revealed that the bulk of the immunostimulatory activity resides in polysaccharide/protein complexes with molecular masses larger than 100 kDa that are composed primarily of galactose, rhamnose and arabinose.


Subject(s)
Cell Proliferation/drug effects , Chlorella , Immunologic Factors/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Animals , Cytokines/biosynthesis , Dose-Response Relationship, Drug , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/chemistry , Immunologic Factors/therapeutic use , In Vitro Techniques , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Spleen/cytology , Spleen/drug effects
5.
Am J Hum Genet ; 65(5): 1252-60, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10521290

ABSTRACT

Niemann-Pick type II disease is an autosomal recessive disorder characterized by a defect in intracellular trafficking of sterols. We have determined the intron/exon boundaries of eight exons from the conserved 3' portion of NPC1, the gene associated with most cases of the disease. SSCP analyses were designed for these exons and were used to identify the majority of mutations in 13 apparently unrelated families. Thirteen mutations were found, accounting for 19 of the 26 alleles. These mutations included eight different missense mutations (including one reported by Greer et al. [1998]), one 4-bp and two 2-bp deletions that generate premature stop codons, and two intronic mutations that are predicted to alter splicing. Two of the missense mutations were present in predicted transmembrane (TM) domains. Clustering of these and other reported NPC1 mutations in the carboxy-terminal third of the protein indicates that screening of these exons, by means of the SSCP analyses reported here, will detect most mutations. The carboxy-terminal half of the Npc1 protein shares amino acid similarity with the TM domains of the morphogen receptor Patched, with the largest stretch of unrelated sequence lying between two putative TM spans. Alignment of this portion of the human Npc1 protein sequence with Npc1-related sequences from mouse, yeast, nematode, and a plant, Arabidopsis, revealed conserved cysteine residues that may coordinate the structure of this domain. That 7 of a total of 13 NPC1 missense mutations are concentrated in this single Npc1-specific domain suggests that integrity of this region is particularly critical for normal functioning of the protein.


Subject(s)
Carrier Proteins , Conserved Sequence/genetics , Cysteine/genetics , Membrane Glycoproteins , Niemann-Pick Diseases/genetics , Proteins/genetics , Amino Acid Sequence , Canada , Cloning, Molecular , DNA Mutational Analysis , Exons , Humans , Intracellular Signaling Peptides and Proteins , Introns , Membrane Proteins/chemistry , Membrane Proteins/genetics , Molecular Sequence Data , Niemann-Pick C1 Protein , Polymorphism, Single-Stranded Conformational , Proteins/chemistry , Sequence Alignment
6.
Clin Genet ; 55(4): 248-55, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10361985

ABSTRACT

Niemann-Pick type D (NPD) disease is a severe degenerative disorder of the nervous system characterized by the accumulation of tissue cholesterol and sphingomyelin. Because of a founder effect, it is unusually common in southwestern Nova Scotia, Canada. We have confirmed that almost all patients from 20 affected sibships descended on both sides from a small group of Acadians who settled in this region in about the year 1767. Previously using classic linkage analysis of this large kindred, we defined the critical gene region to a 13-cM chromosome segment between D18S869 and D18S66. Seven ESTs have been positioned within this interval. Carstea et al. (Niemann Pick C disease gene: homology to mediators of cholesterol homeostasis. Science 1997: 277: 232-235) recently demonstrated that one of these ESTs is the Niemann-Pick type C (NPCI) gene, the gene disrupted in most patients with NPC disease, and we have shown that a G3097-->T mutation in the NPC1 gene is also responsible for NPD. Here we report the development of five new polymorphic microsatellite markers and the testing for complete linkage disequilibrium in our single large NPD kindred that allowed us to reduce the NPD critical region to a 1-cM (1.3-1.6 Mb) interval between D18S1398 and D18S1108. In contrast, Carstea et al., using classic linkage analysis, required more than 18 unrelated NPC families to reduce the NPC1 critical region to a 5-cM interval. Our work supports the finding that NPD is an allelic variant of NPC1, and illustrates the power of large kindreds, which are common in Atlantic Canada and other relatively isolated areas, for gene mapping and identification.


Subject(s)
Carrier Proteins , Linkage Disequilibrium , Membrane Glycoproteins , Niemann-Pick Diseases/genetics , Base Sequence , Chromosomes, Artificial, Yeast , DNA Primers , Expressed Sequence Tags , Female , Founder Effect , Genetic Markers , Humans , Intracellular Signaling Peptides and Proteins , Male , Microsatellite Repeats , Niemann-Pick C1 Protein , Niemann-Pick Diseases/ethnology , Nova Scotia , Pedigree , Proteins/genetics , Sequence Tagged Sites
7.
Genome ; 41(3): 468-70, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9729783

ABSTRACT

Previous reports concerning the location of D18S44 with respect to the centromere have been ambiguous. Also, it has not been possible, based on formerly reported markers, to show that contigs WC18.0 and WC18.1 overlap. However, the data presented here definitively show, using FISH technology, that D18S44 (located on WC18.0) maps to proximal 18q. Furthermore, inter-Alu fingerprinting shows a clear overlap between WC18.0 and WC18.1, thereby establishing a complete contig between D18S44 and markers from WC18.1.


Subject(s)
Centromere , Chromosomes, Human, Pair 18 , DNA Fingerprinting , Repetitive Sequences, Nucleic Acid , Chromosomes, Artificial, Yeast , Humans , In Situ Hybridization, Fluorescence
8.
Am J Hum Genet ; 63(1): 52-4, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9634529

ABSTRACT

Niemann-Pick type D (NPD) disease is a progressive neurodegenerative disorder characterized by the accumulation of tissue cholesterol and sphingomyelin. This disorder is relatively common in southwestern Nova Scotia, because of a founder effect. Our previous studies, using classic linkage analysis of this large extended kindred, defined the critical gene region to a 13-cM chromosome segment between D18S40 and D18S66. A recently isolated gene from this region, NPC1, is mutated in the majority of patients with Niemann-Pick type C disease. We have identified a point mutation within this gene (G3097-->T; Gly992-->Trp) that shows complete linkage disequilibrium with NPD, confirming that NPD is an allelic variant of NPC1.


Subject(s)
Carrier Proteins , Membrane Glycoproteins , Niemann-Pick Diseases/genetics , Proteins/genetics , Alleles , Chromosomes, Human, Pair 13 , DNA Mutational Analysis , Genetic Linkage/genetics , Humans , Intracellular Signaling Peptides and Proteins , Lysosomal Storage Diseases/genetics , Niemann-Pick C1 Protein , Niemann-Pick Diseases/classification , Nova Scotia , Point Mutation/genetics , Polymerase Chain Reaction
9.
Am J Hum Genet ; 61(1): 139-42, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9245994

ABSTRACT

Niemann-Pick type II disease is a severe disorder characterized by accumulation of tissue cholesterol and sphingomyelin and by progressive degeneration of the nervous system. This disease has two clinically similar subtypes, type C (NPC) and type D (NPD). NPC is clinically variable and has been identified in many ethnic groups. NPD, on the other hand, has been reported only in descendants of an Acadian couple who lived in Nova Scotia in the early 18th century and has a more homogeneous expression resembling that of less severely affected NPC patients. Despite biochemical differences, it has not been established whether NPC and NPD are allelic variants of the same disease. We report here that NPD is tightly linked (recombination fraction .00; maximum LOD score 4.50) to a microsatellite marker, D18S480, from the centromeric region of chromosome 18q. Carstea et al. have reported that the NPC gene maps to this same site; therefore we suggest that NPC and NPD likely result from mutations in the same gene.


Subject(s)
Chromosomes, Human, Pair 18 , Genetic Linkage , Niemann-Pick Diseases/genetics , Female , Humans , Male , Niemann-Pick Diseases/classification
10.
Virology ; 224(2): 510-6, 1996 Oct 15.
Article in English | MEDLINE | ID: mdl-8874511

ABSTRACT

The catalytic activity of the adenovirus cysteine peptidase is increased by a specific 11-amino-acid peptide adduct (GVQSLKRRRCF, referred to as pVIc). To identify additional peptides which might bind and alter the activity of the protease, a cysteine-constrained random peptide phage library was screened. Of 29 different phages which were isolated, 7 contained the consensus sequence VEGGS. Despite a superficial similarity to the substrate cleavage site of the protease, the peptide was not digested by the enzyme. VEGGS and pVIc altered protease activity similarly without sharing sequence similarity. To similar degrees, pVIc and VEGGS (a) stimulated the activity of the recombinant protease, (b) had no effect on viral protease, (c) increased the fluorescence emission of tryptophan residues in the protease, suggesting a conformational change, and (d) inhibited wt virus infection, but rescued ts1 infection at the nonpermissive temperature. The experiments also suggest that once the protease has been stimulated by one peptide, the other peptide has no further activity on the recombinant adenovirus cysteine protease, suggesting that the two peptides bring about the same change on the protease via different binding sites.


Subject(s)
Adenoviruses, Human/enzymology , Cysteine Endopeptidases/metabolism , Amino Acid Sequence , Bacteriophages/genetics , Binding Sites , Humans , Ligands , Molecular Sequence Data , Peptides/metabolism , Substrate Specificity , Tryptophan , Tumor Cells, Cultured
12.
J Pediatr ; 109(1): 20-4, 1986 Jul.
Article in English | MEDLINE | ID: mdl-3522836

ABSTRACT

We describe four children with severe supraglottic infections caused by group A beta-hemolytic streptococci. In each case the clinical presentation suggested Hemophilus influenzae epiglottitis. In only one patient was there significant involvement of the epiglottis, whereas all had striking inflammation of the aryepiglottic folds. Group A beta-hemolytic streptococcus was isolated in blood cultures in two patients and from the supraglottic area and trachea in two others. Fever persisted for 6 to 22 days, and tracheal intubation was necessary for 2 to 16 days, despite appropriate antibiotic therapy. The evolution of streptococcal supraglottitis may be protracted, and it must be managed accordingly.


Subject(s)
Epiglottitis/diagnosis , Laryngitis/diagnosis , Streptococcal Infections/diagnosis , Child , Child, Preschool , Diagnosis, Differential , Epiglottitis/drug therapy , Epiglottitis/microbiology , Female , Haemophilus Infections/diagnosis , Haemophilus influenzae , Humans , Male , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcus pyogenes/isolation & purification
13.
Can Anaesth Soc J ; 33(1): 57-62, 1986 Jan.
Article in English | MEDLINE | ID: mdl-3948048

ABSTRACT

The incidence of nausea and vomiting after strabismus surgery was studied in 64 children aged one to six years. Incidence was determined in the post-anaesthesia recovery room (PARR), in the same day surgery (SDS) unit, and at home on days one and two after the operation. After induction of anaesthesia, the children received an intravenous injection of droperidol (50 micrograms . kg-1) or saline in a double-blind randomized fashion, and an intravenous injection of glycopyrrolate (7.5 micrograms . kg-1) or atropine (10 micrograms . kg-1) in an open randomized fashion. The incidence of emetic symptoms was highest in the SDS unit and at home on day one. Droperidol slightly but significantly delayed awakening and was not, at least in this particular age group, associated with any difference in postoperative sickness. Despite theoretical advantages, glycopyrrolate offered no significant benefit over atropine as far as postoperative emesis was concerned.


Subject(s)
Nausea/epidemiology , Postoperative Complications/epidemiology , Strabismus/surgery , Vomiting/epidemiology , Anesthesia, General , Anesthesia, Intravenous , Child , Child, Preschool , Double-Blind Method , Droperidol/therapeutic use , Female , Glycopyrrolate/therapeutic use , Halothane , Humans , Infant , Male , Nausea/prevention & control , Nitrous Oxide , Postoperative Complications/prevention & control , Prospective Studies , Time Factors , Vomiting/prevention & control
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