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M Super

Publications and source records attributed to M Super.

At least 73 records · Page 4Linked to original sources
PubMed1992

Distinct and overlapping functions of allelic forms of human mannose binding protein.

Human mannose binding protein (MBP) is a C-type serum lectin involved in first-line host defense against a variety of bacterial, fungal and viral pathogens. Recently an association was found between low levels of serum MBP and an increased frequency of recurrent infections in infants. A particular genotype, in which glycine is substituted by aspartic acid at codon 54 of MBP in the fifth collagen repeat, shows apparent concordance with the clinical phenotype. We report, however, that this genotype occurs in 5% of the population and encodes a functional protein. Our results indicate that the Gly54Asp allele does not account for a deficiency state, but instead suggest that MBP may have two predominant allelic forms that have overlapping function and differ only in their ability to activate the classical pathway of complement.

Alleles↗
PubMed1992

The fragile X syndrome.

An amplification of a highly unstable DNA element has been identified at the fragile X locus in Xq27.3. This sequence appears to be both the source of the primary mutation causing the fragile X syndrome, apparently having its causative effect through the methylation of the FMR-1 HTF island and the region of cytogenetic fragility. The direct analysis of the genotype of carrier and affected individuals can be used as a direct diagnosis tool which will improve both the accuracy and speed of diagnosis. The identification of hereditary unstable DNA in a disease with such a wide level of non-penetrance and variable phenotype may give clues as to the basis of non-penetrance in other human genetic disorders.

Chromosome Fragility↗
PubMed1992

Milestones in cystic fibrosis.

The study of cystic fibrosis (CF) provides a fascinating insight into developments in medicine in the 20th century. Milestones include the first clear clinical descriptions in the 1930s, discovery of a sweat electrolyte abnormality, establishing the autosomal recessive mode of inheritance and improvements in treatment. Microdissection experiments on sweat glands allowed the main defect to be delineated as one of chloride transport. Location of the gene to chromosome 7 made prenatal diagnosis feasible and carrier detection in siblings. The CF gene--its product being the cystic fibrosis transmembrane conductance regulator (CFTR), and its major mutation Delta F508 was discovered in 1989. World-wide collaboration has resulted in discovery of more than 150 further mutations. Incorporation of CFTR into non-chloride transporting insect cells by conferring chloride transport, proved it a chloride channel. CFTR incorporated into adenovirus results in correction of the chloride transport defect in airway cells, bringing gene therapy closer.

Cystic Fibrosis↗
PubMed1992

The role of mannose-binding proteins in host defense.

The human mannose-binding protein (MBP) appears to function as an "ante-antibody" as its physiological role is in first line host defense. Low baseline serum levels are rapidly increased as part of the acute phase reactant and circulating MBP can act as a direct opsonin or activate the classical alternative complement pathway. MBP appears to selectively recognize an array of apparently disparate oligosaccharides that decorate gram-negative and gram-positive bacteria as well as certain parasites, yeasts, and fungi. MBP may be considered a "pattern" recognition molecule that has homologs in primitive life forms. Its ability to distinguish self from nonself indicates that it may play an important role in innate immunity.

Amino Acid Sequence↗
PubMed1992

Development, multiplexing, and application of ARMS tests for common mutations in the CFTR gene.

The amplification refractory mutation system (ARMS) is a simple, rapid and reliable method for the detection of any mutation involving single base changes or small deletions. We have applied ARMS methodology to the detection of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Single ARMS tests have been developed for 11 CFTR mutations found in the northwest of England. ARMS reactions for the most common mutations have been multiplexed to give a test which will detect the presence of the delta F508, G551D, G542X, and 621 + 1G----T mutations in a DNA sample. The multiplex test has been validated by the analysis of over 500 previously genotyped samples and has been found to be completely accurate. The rapid detection of the most common mutations has enabled early molecular confirmation of suspected cystic fibrosis in neonates, rapid typing of cystic fibrosis patients and their relatives, and testing of sperm and egg donors.

Base Sequence↗
PubMed1991

Molecular basis of opsonic defect in immunodeficient children.

Low serum mannose-binding protein (MBP) concentrations are associated with a common opsonic defect. Sequence analysis of the MBP gene in three children with recurrent infections, the opsonic defect, and low serum MBP concentrations showed a point mutation at base 230 of exon 1 causing a change of codon 54 from GGC to GAC. The replacement of glycine with an aspartic acid residue disrupts the fifth Gly-Xaa-Yaa repeat in the collagen-like domain of each 32 kD MBP peptide chain and probably prevents the formation of the normal triple helix. Study of sixteen members of the three families showed autosomal dominant co-inheritance of the mutation and low serum MBP concentrations.

Alleles↗
PubMed1991

A deletion mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) locus: Delta I507.

During the development of an amplification refractory mutation system (ARMS) assay for the detection of the Delta F508 mutation and corresponding normal locus in cystic fibrosis we discovered a family in which a further variant of the sequence exists. PCR amplification and direct sequencing of a region of exon 10 of the CFTR locus indicated the deletion of the three base pairs encoding isoleucine or isoleucine, or possibly the presence of a single base substitution in conjunction with the Delta F508 mutation. The resulting protein has a deletion of an isoleucine residue at position 507 as opposed to the previously described deletion of phenylalanine at position 508. We conclude that the loss of an isoleucine residue at position 507 (Delta I507) is another defective variant of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene product.

Amino Acid Sequence↗
PubMed1991

Use of the polymerase chain reaction to analyse sequence variation within a major neutralizing epitope of glycoprotein B (gp58) in clinical isolates of human cytomegalovirus.

The heterogeneity of low passage human cytomegalovirus (HCMV) strains was determined by HindIII typing of 28 clinical isolates from transplant patients. These data have shown that, in general, each patient's strain has a unique restriction profile, usually comprising combinations of HindIII sites present in one or more of the tissue culture-adapted strains AD169, Towne and Davis. To map sequence changes in a more refined manner we performed detailed analyses of 33 low passage clinical isolates, including those aforementioned, analysing a sequence within glycoprotein B containing a major neutralizing epitope. A 149 bp sequence containing the epitope (amino acids 608 to 625) was amplified using the polymerase chain reaction, the products were cloned and their DNA sequence was determined. Comparison of the DNA and deduced amino acid sequences with those of HCMV strain AD169 revealed that there was a high degree of conservation of the epitope between the 33 clinical isolates. However 10 of the isolates possessed silent mutations and three isolates contained mutations producing amino acid changes within the neutralizing epitope. The possible functional significance of these changes is discussed.

Amino Acid Sequence↗
PubMed1991

Medical genetics.

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Chromosome Aberrations↗
PubMed1990

Oocyte donation.

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Cystic Fibrosis↗
PubMed1990

CF screening.

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Cystic Fibrosis↗
PubMed1990

Delta F508 testing of the DNA bank of the Royal Manchester Children's Hospital.

Details of haplotype and delta F508 status from various populations represented in the cystic fibrosis (CF) DNA bank of the Royal Manchester Children's Hospital are provided, together with information on the association of genotype and clinical status. Clinical details and DNA analyses from native English in the North-West and South-West of England (Bath), from Lancashire Pakistani families and from Afrikaans Namibian families are compared. A 78.5% incidence of delta F508 has been found in English families. Compound heterozygotes with CF and only one delta F508 gene have an increased likelihood of having milder disease, with less Pseudomonas isolated from sputum and relatively more showing either no regular respiratory pathogens or colonisation with Staphylococcus. There is also a relative increase in meconium ileus in these compound heterozygotes. The diagnosis of CF may be in doubt in some subjects negative for delta F508. Some of the Bath families have unusual haplotypes for an English population and a compound heterozygote delta F508/delta I507 has been found. There is evidence from metD analysis of the founder effect in the Afrikaans Namibian families, who have a high delta F508 incidence.

Cystic Fibrosis↗
PubMed1990

The level of mannan-binding protein regulates the binding of complement-derived opsonins to mannan and zymosan at low serum concentrations.

When sera diluted to 5% in a buffer containing calcium and magnesium were incubated with mannan-coated ELISA plates, C4 fragments, properdin and factor B were bound to the plates as well as the expected opsonic C3 fragments, C3b and C3bi. The calcium-dependent lectin mannan-binding protein, which is structurally similar to C1q, was also shown to bind in this assay and analysis of sera from 179 healthy blood donors revealed that the binding levels of all these proteins were highly significantly correlated. Results obtained with a previously described C3b opsonic assay using zymosan also correlated with the mannan-binding levels. When the sera were diluted to 5% in the presence of Mg-EGTA there was no detectable binding of complement proteins to the mannan surface, confirming that no alternative pathway activation occurred at this serum concentration. When sera were diluted to 5% in a buffer containing EDTA in order to study immunoglobulin binding in the absence of complement activation, the levels of bound IgG1, IgG2, IgG3, IgA and IgM antibodies were found to be completely unrelated to the C3bi binding levels previously observed. The results suggest that in this experimental system using low concentrations of serum, mannan-binding protein initiates an antibody-independent mechanism of cleavage of the classical pathway component C4, which subsequently regulates the degree of cleavage of C3 and recruitment of alternative pathway proteins.

Carrier Proteins↗
PubMed1989

Association of low levels of mannan-binding protein with a common defect of opsonisation.

Failure to opsonise bakers' yeast (Saccharomyces cerevisiae) is a defect found in 5-7% of the general population. In this study, the presence of the defect was linked with low levels of mannan-binding protein (MBP), a calcium-dependent serum lectin. Purified MBP corrected the defect in a dose-dependent way in an in-vitro assay measuring the deposition of complement moieties on a mannan-coated surface. There was a highly significant correlation between the serum MBP level and the generation of C3b opsonins in a population of healthy blood donors. The median MBP level of ten children previously shown to have the functional opsonic defect was 4.9 micrograms/l (range 2.5-35.0 micrograms/l) compared with 143 micrograms/l (range 2.5-880 micrograms/l) for a paediatric control group.

Adolescent↗