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Biomedical subjects

G Hughes

Publications and source records attributed to G Hughes.

At least 91 records · Page 5Linked to original sources
PubMed1999

Lack of interference of icodextrin on creatinine measurements.

Glucose has been reported to interfere in the analysis of creatinine by the Jaffe method. The potential interference of icodextrin and its primary metabolites (maltose, maltotriose, maltotetraose) on creatinine measurements has not previously been addressed. We evaluated the potential interference of icodextrin and its metabolites at various concentrations using both the Jaffe and Creatinine Plus methods. Interference was determined in samples containing 0.6-20 mg/dL creatinine in saline solution or in plasma (n = 6), and in dialysate samples (n = 6) spiked with icodextrin, maltose, maltotriose, and maltotetraose at concentrations up to twofold the level found in plasma and dialysate from patients treated using icodextrin. Results confirm that no interference occurs when using either the colorimetric Jaffe method or the enzymatic Creatinine Plus method at levels up to 65 g/L icodextrin, 2 g/L maltose, 2 g/L maltotriose, and 1 g/L maltotetraose, levels representing worst-case clinical concentrations. In addition, our results confirm that comparable values can be obtained using either the Jaffe or the Creatinine Plus method for the analysis of creatinine in uremic plasma and in dialysate samples.

Creatinine↗
PubMed1998

Is gene deletion in eukaryotes sequence-dependent? A study of nine deletion junctions and nineteen other deletion breakpoints in intron 7 of the human dystrophin gene.

Although large deletions comprise 65% of the mutations that underlie most cases of Duchenne and Becker muscular dystrophies, the DNA sequence characteristics of the deletions and the molecular processes leading to their formation are largely unknown. Intron 7 of the human dystrophin gene is unusually large (110 kb) and a substantial number of deletions have been identified with endpoints within this intron. The distribution of 28 deletion endpoints was mapped to local sequence elements by PCR. The break points were distributed among unique sequence, LINE-1, Alu, MIR, MER and microsatellite sequences with frequencies expected from the frequency of those sequences in the intron. Thus, deletions in this intron are not associated primarily with any one of those sequences in the intron. Nine deletion junctions were amplified and sequenced. Eight were deletions between DNA sequences with minimal homology (0-4 bp) and are therefore unlikely to be products of homologous recombination. In the ninth case, a complex rearrangement was found to be consistent with unequal recombinational exchange between two Alu sequences coupled with a duplication. We have hypothesized that a paucity of matrix attachment regions in this very large intron expanded by the insertion of many mobile elements might provoke a chromatin structure that stimulates deletions (McNaughton et al., 1997, Genomics 40, 294-304). The data presented here are consistent with that idea and demonstrate that the deletion sequences are not usually produced by homologous DNA misalignments.

Base Sequence↗
PubMed1998

Indirect methods for estimating prevalent HIV infections: adults in England and Wales at the end of 1993.

Two indirect methods were used to estimate the point prevalence of HIV infection in England and Wales at the end of 1993 using data on diagnosed HIV infections, AIDS cases, HIV-related deaths and HIV testing behaviour from unlinked anonymous surveys. The methods estimated the proportion of all prevalent HIV infections that diagnosed infections represented. Most of those exposed to HIV infection through injecting drug use or sexual intercourse between men had had their infections diagnosed compared to less than half of those exposed through heterosexual intercourse. The total estimated number of prevalent infections was 22,350 for the diagnosis interval method and 20,540 for the test history method, and about 56-57% of these were in homo/bisexual men. These indirect methods are cheap and simple applications of surveillance data which provide estimates that compare favourably with those produced by more complex methods.

England↗
PubMed1998

Fatal Clostridium perfringens sepsis from a pooled platelet transfusion.

A male patient with acute myeloid leukaemia received a pooled platelet preparation prepared by Optipress system on the last day of its shelf life. The patient collapsed after two-thirds of the contents had been transfused. Clostridium perfringens was isolated from the platelet bag within 18 h of the acute event. Metronidazole, gentamicin and Clostridium antiserum were then administered in addition to the broad spectrum antibiotics started previously. However, the patient died 4 days after the platelets were transfused. The cause of death was given as cardiovascular shock, entirely compatible with an overwhelming bacteraemic and septic episode. A coroner's verdict of accidental death due to transfusion of a contaminated unit of platelets was recorded. On subsequent investigation Cl. perfringens type A serotype PS68,PS80 (identical to that found in the platelet bag) was cultured from the venepuncture site of the arm of one of the donors who contributed towards the platelet pool. The donor had two young children and frequently changed nappies. Faecal contamination of the venepuncture site was the suspected source for the transmission of Cl. perfringens, an organism commonly found in the soil and intestinal tract of humans. This case dramatically highlights the consequences of transfusing a bacterially contaminated unit. It is vital that such incidents are investigated and reported so that the extent of transfusion-associated bacterial transmission can be monitored and preventative measures taken if possible.

Acute Disease↗
PubMed1998

Immunoblotting analysis of schwannomin/merlin in human schwannomas.

HYPOTHESIS: Absent or reduced expression of schwannomin/merlin is associated with tumorigenesis of sporadic schwannomas. BACKGROUND: The neurofibromatosis type 2 (NF2) gene frequently is mutated in sporadic vestibular schwannomas. The protein product of the NF2 gene is called schwannomin or merlin. Little is known about the mutated forms of schwannomin/merlin present in schwannomas. METHODS: To investigate further the role of schwannomin/merlin in schwannoma tumorigenesis, immunoblotting experiments were performed. Antischwannomin/merlin-specific antibody that recognizes amino terminus of the protein was used to determine the expression levels of schwannomin/merlin in 16 sporadic vestibular schwannomas, 1 NF2-related vestibular schwannoma, and 5 spinal schwannomas. RESULTS: The antibody detects a protein of approximately 66 kDa in the Triton X-100-insoluble fraction of tumors. The expression of schwannomin/merlin was severely reduced, <35% of control, in 11 (50%) of 22 sporadic schwannomas and in 1 NF2-related vestibular schwannoma. The intensity of 66-kDa schwannomin/merlin band was moderately reduced, from 35-60%, in 7 (32%) of 22 schwannomas compared to the expression levels found in the human brain. Truncated forms of schwannomin/merlin were identified in three tumors with moderately reduced schwannomin/merlin. CONCLUSIONS: These results provide new evidence that inactivation of schwannomin/merlin is an important factor in tumorigenesis of sporadic schwannomas.

Adult↗
PubMed1998

New cases seen at genitourinary medicine clinics: England 1997.

Statistics from genitourinary medicine (GUM) clinics provide the most comprehensive source of data on the epidemiology of sexually transmitted infections (STI) in England. Between 1996 and 1997, the total number of diagnoses made in GUM clinics rose by 7% and total diagnoses of acute STIs by 9%. Diagnoses of genital Chlamydia trachomatis, genital warts and gonorrhoea rose by 20%, 8%, and 5%, respectively. Cases of infectious syphilis rose by 26%, most of which was attributable to an outbreak in Bristol. These rises followed substantial rises in acute STIs between 1995 and 1996, and were most pronounced among teenagers and homosexual and bisexual men. The continued growth in numbers of acute STIs is occurring despite the targeting of known risk groups in sexual health education and intervention programmes, and suggests that renewed efforts to improve sexual health are needed.

Adolescent↗
PubMed1997

Elevation of apolipoprotein E in the CSF of cattle affected by BSE.

The cerebrospinal fluid (CSF) of patients suffering from Creutzfeldt-Jakob disease (CJD) display two unique polypeptide chains by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In the absence of a well-defined ante-mortem diagnostic test for bovine spongiform encephalopathy (BSE), spinal fluid samples of eight normal cows and eight cows known to carry BSE by post-mortem histological analysis were investigated to verify if equivalent polypeptides were present. Proteins with similar migration to human CJD polypeptides were not detected. But surprisingly, a cluster of polypeptide spots that was faint or not detected in normal bovine CSF samples was found to be elevated or massively increased in BSE CSF samples (more than 10-fold increase). These elevated polypeptide chains were identified as apolipoprotein E.

Amino Acid Sequence↗
PubMed1997

Inactivation of the Fanconi anemia group C gene augments interferon-gamma-induced apoptotic responses in hematopoietic cells.

Hematopoietic progenitor cells (HPC) from mice nullizygous at the Fanconi anemia (FA) group C locus (FAC -/-) are hypersensitive to the mitotic inhibitory effects of interferon (IFN-gamma). We tested the hypothesis that HPC from the bone marrow of Fanconi group C children are similarly hypersensitive and that the fas pathway is involved in affecting programmed cell death in response to low doses of IFN-gamma. In normal human and murine HPC, IFN-gamma primed the fas pathway and induced both fas and interferon response factor-1 (IRF-1) gene expression. These IFN-gamma-induced apoptotic responses in HPC from the marrow of a child with FA of the C group (FA-C) and in FAC -/- mice occurred at significantly lower IFN doses (by an order of magnitude) than did the apoptotic responses of normal HPC. Treatment of FA-C CD34+ cells with low doses of recombinant IFN-gamma, inhibited growth of colony forming unit granulocyte-macrophage and burst-forming unit erythroid, while treatment with blocking antibodies to fas augmented clonal growth and abrogated the clonal inhibitory effect of IFN-gamma. Transfer of the normal FAC gene into FA-C B-cell lines prevented mitomycin C-induced apoptosis, but did not suppress fas expression or inhibit the primed fas pathway. However, the kinetics of Stat1-phosphate decay in IFN-gamma-treated cells was prolonged in mutant cells and was normalized by transduction of the normal FAC gene. Therefore, the normal FAC protein serves, in part, to modulate IFN-gamma signals. HPC bearing inactivating mutations of FAC fail to normally modulate IFN-gamma signals and, as a result, undergo apoptosis executed through the fas pathway.

Anemia, Aplastic↗
PubMed1997

The evolution of an intron: analysis of a long, deletion-prone intron in the human dystrophin gene.

The sequence of a 112-kb region of the human dystrophin (DMD/BMD) gene encompassing the deletion prone intron 7 (110 kb) and the much shorter intron 8 (1.1 kb) has been determined. Recognizable insertion sequences account for approximately 40% of intron 7. LINE-1 and THE-1/LTR sequences occur in intron 7 with significantly higher frequency than would be expected statistically while Alu sequences are underrepresented. Intron 7 also contains numerous mammalian-wide interspersed repeats, a diverse range of medium reiteration repeats of unknown origin, and a sequence derived from a mariner transposon. By contrast, the shorter intron 8 contains no detectable insertion sequences. Dating of the LI and Alu sequences suggests that intron 7 has approximately doubled in size within the past 130 million years, and comparison with the corresponding intron from the pufferfish (Fugu rubripes) suggests that the intron has expanded some 44-fold over a period of 400 million years. The possible contribution of the insertion elements to the instability of intron 7 is discussed.

Base Composition↗
PubMed1997

A two-dimensional protein map of human amniotic fluid at 17 weeks' gestation.

Using updated technical procedures (immobilized pH gradients for isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: IPG/SDS-PAGE) we provide a two-dimensional (2-D) map of amniotic fluid (AF) proteins. This map comprises over 800 silver-stained spots. Over 150 spots have been identified by matching on the net with human plasma and cerebrospinal fluid maps available from SWISS 2DPAGE database; several additional spots were assigned by immunoblotting and/or microanalytical techniques. This report details our investigation on AF proteins focusing on the 17th week of gestation, when AF is most commonly used for clinical evaluation of fetal disorders. As a whole, the map displays a number of potential markers for fetal development and for gestation abnormalities. The 2-D electrophoretic technique allows the monitoring of all these proteins at the same time along with additional spots that may prove of diagnostic significance.

Adult↗
PubMed1997

Protein expression profiles in human breast ductal carcinoma and histologically normal tissue.

Reference two-dimensional (2-D) gels are presented for human breast ductal carcinoma and histologically normal tissue. Whole biopsy fragments were analyzed, including epithelial and nonepithelial components. Thirty-five spots have been assigned by gel matching to the human liver SWISS-2DPAGE reference map and/or to the human primary keratinocyte IPG map from the Danish Center for Human Genome. N-terminal microsequencing was applied to confirm randomly chosen matching assignments and to identify six new spots. Protein expression profiles in ductal carcinoma and in normal breast tissue appeared to be similar, except for a pattern consisting of 32 spots, which were highly expressed in all carcinoma specimens, and less intense and occasionally undetectable in normal tissue. This difference was statistically significant. Assignment has been obtained for several spots, namely GRP94, GRP78, GRP75, mitochondrial HSP60, calreticulin, protein disulfide isomerase, peptidyl-prolyl cis-trans isomerase, collagen-binding protein 2, fructose bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, thioredoxin, cytochrome c oxidase VA subunit, tubulin beta isoform and macrophage migration inhibitory factor (MIF). The cancer- and tissue-specificity of the described pattern was assessed by matching to the Swiss-2DPAGE human liver, hepatoma, lymphoma, erythroleukemia reference maps. The pattern of 32 spots was found to be indicative of epithelial neoplasia.

Aged↗