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H S Cameron

Publications and source records attributed to H S Cameron.

8 recordsLinked to original sources
PubMed2000

Glucose-6-phosphatase mutation G188R confers an atypical glycogen storage disease type 1b phenotype.

Glycogen storage disease type 1a (GSD 1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). A variant (GSD 1b) is caused by a defect in the transport of glucose-6-phosphate (G6P) into the microsome and is associated with chronic neutropenia and neutrophil dysfunction. Mutually exclusive mutations in the G6Pase gene and the G6P transport gene establish GSD la and GSD 1b as independent molecular processes and are consistent with a multicomponent translocase catalytic model. A modified translocase/catalytic unit model based on biochemical data in a G6Pase knockout mouse has also been proposed for G6Pase catalysis. This model suggests coupling of G6Pase activity and G6P transport. A 5-mo-old girl with hypoglycemia, hepatomegaly, and lactic acidemia was diagnosed with GSD 1a. She also developed neutropenia, neutrophil dysfunction, and recurrent infections characteristic of GSD 1b. Homozygous G188R mutations of the G6Pase gene were identified, but no mutations in the G6P translocase gene were found. We have subsequently identified a sibling and two unrelated patients with similar genotypic/phenotypic characteristics. The unusual association of neutrophil abnormalities in patients with homozygous G188R mutations in the G6Pase gene supports a modified translocase/catalytic unit model.

Animals↗
PubMed2000

Transfection of alpha(1,3)fucosyltransferase antisense sequences impairs the proliferative and tumorigenic ability of human colon carcinoma cells.

Sialyl Lewis x and sialyl Lewis a are oncodevelopmental antigens involved in the pathogenesis of colon adenocarcinoma. Biosynthesis of these glycans is controlled by alpha(1,3/1,4)fucosyltransferases. We report the disruption of sialyl Lewis x/a biosynthesis and inhibition of colon carcinoma cell proliferation by stable transfection of antisense sequences directed at the human Lewis alpha(1,3/1,4)fucosyltransferase gene, FUT3, and the plasma alpha(1,3)fucosyltransferase gene, FUT6. COLO-205 cells expressed high levels of sialyl Lewis x/a, alpha(1,3)fucosyltransferase activity, and FUT3/6 transcripts, but COLO</205-derived antisense transfectant cell lines AS5C and AS7A did not. Sense transfectant S6G expressed higher levels of fucosyltransferase than parental COLO-205. Cellular proliferation assays showed marked correlative decreases in the growth of antisense lines and, conversely, increased growth of sense transfectants. Subcutaneous tumors created by injection of nude mice with antisense transfectant cell lines grew more slowly than those arising from control COLO-205 and sense transfectants. These results provide target validation for inhibition of carcinoma proliferation with antisense sequences directed at human fucosyltransferases.

Animals↗
PubMed1995

Expression of human chromosome 19p alpha(1,3)-fucosyltransferase genes in normal tissues. Alternative splicing, polyadenylation, and isoforms.

The human alpha(1,3)-fucosyltransferase genes FUT3, FUT5, and FUT6 form a cluster on chromosome 19p13.3. Expression was studied using reverse transcriptase-polymerase chain reaction, rapid amplification of cDNA ends, and Northern analyses. FUT3 and FUT6 were expressed at high levels, while FUT5 expression was lower and restricted to fewer cell types. Alternatively spliced transcripts were identified for FUT3 and FUT6 in kidney, liver, and colon. A 2.37-kilobase pair (kb) FUT3 transcript, detected at high levels in kidney and colon, was absent in liver. FUT6 expression was characterized by a 3.5-kb transcript present in kidney and liver, and a 2.5-kb transcript in colon and liver. Two polyadenylation sites were shown for FUT5, but absence of consensus sequences suggests reduced efficiency for cleavage and polyadenylation. Two polyadenylation sites were also shown for FUT6, with the alternatively spliced downstream signal in tissues expressing high levels of FUT6. In these tissues, additional splicing results in isoforms with catalytic domain deletions. No detectable alpha(1,3)- or alpha(1,4)-fucosyltransferase activity was found in assays of cells transfected with FUT6 isoform cDNAs. Thus, tissue-specific post-transcriptional modifications are associated with expression patterns of FUT3, FUT5, and FUT6.

Alternative Splicing↗
PubMed1995

Physical maps of human alpha (1,3)fucosyltransferase genes FUT3-FUT6 on chromosomes 19p13.3 and 11q21.

Sialyl Lewis x and related fucosylated glycans are differentially expressed in human cells and form ligands for selectin adhesion receptors. alpha(1,3)Fucosyltransferases (FUTs) that complete their biosynthesis also show tissue specificity. We have established physical maps of the FUT3-6 loci to study regulation of this gene family. FUT4 has previously been localized to chromosome 11q21; FUT3, FUT6, and now FUT5 are localized to chromosome 19p13.3. Conventional and pulsed-field gel electrophoresis mapping of total genomic DNA and large genomic clones were used to generate a fine map of both loci, defining the order, orientation, and distances between FUTs. A P1 clone with all three 19p FUT genes in tandem orientation was isolated and used to study regions flanking FUT3, -5, and -6. Our studies provide preliminary information to study regulation of human FUT genes.

Chromosome Mapping↗
PubMed1994

Molecular basis for Lewis alpha(1,3/1,4)-fucosyltransferase gene deficiency (FUT3) found in Lewis-negative Indonesian pedigrees.

The Le(a) and Le(b) human blood group antigens are synthesized in tissues producing exocrine secretions; they also circulate in plasma, where they are adsorbed by erythrocytes. They are synthesized by two fucosyltransferases, encoded by Lewis (FUT3) and secretor (FUT2) loci. This genetic model has been challenged because some erythrocyte Lewis-negative individuals express Lewis antigens in saliva. To define the molecular basis of this apparent discrepancy, we sequenced FUT3 in Lewis-negative individuals. We identified two single base pair changes. One, termed L1, yields a Leu-20-->Arg substitution in the enzyme's transmembrane domain. When expressed in COS-7 cells, enzyme substrate affinities are essentially identical to those of wild type. However, the mutant enzyme is found at substantially reduced levels in transfected cells. This suggests that the L1 mutation may alter the Golgi membrane anchoring of the enzyme. It was found alone in double dose in 10 of 30 erythrocyte Lewis-negative individuals, nine of whom express Lewis antigens in saliva. Therefore, L1 can account for erythrocyte/saliva-discrepant Lewis typing results. The L2 mutation creates an Ile-356-->Lys change in the enzyme's catalytic domain and inactivates the enzyme. It was found in double dose in 18 of 19 individuals bearing the double erythrocyte and salivary Lewis deficiency and can account for this phenotype.

Alleles↗
PubMed1987

Risks and benefits of elective hip replacement in the octogenarian.

We reviewed the records for 100 consecutive cases of elective hip replacement in 91 patients in their 80s (average age 82.8 years), all of whom lived in their own homes before surgery. In 92 cases the patients returned home, 59 within 3 weeks. The average duration of hospital stay was 20.1 days. In eight cases there were major complications, including three cases of myocardial infarction (one of them fatal) and two cases of pulmonary embolism (one of them fatal). In 15 cases there were moderate complications, including deep venous thrombosis (in 5) and urinary tract complications necessitating transurethral prostatectomy (in 2). In 44 cases there were minor complications, including the need for urinary catheterization (in 27) and brief periods of postoperative confusion (in 14). In 33 cases there were no complications; in 31 of these cases the patients returned directly home within 3 weeks. The preoperative risk rating of the American Society of Anesthesiologists (ASA) correlated well with the complication rates: the rates of major complications in cases with a rating of ASA class I, II or III were 0%, 6% and 15% respectively. In 49 of 52 cases in which the procedure had been performed more than 2 years previously, the patients were happy they had had the operation.

Aged↗