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G Barnes

Publications and source records attributed to G Barnes.

At least 73 records · Page 4Linked to original sources
PubMed1993

De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.

Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.

Adult↗
PubMed1993

A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins.

We have previously used exon amplification to identify the ADD1 gene in cosmid Y24 from the Huntington's disease (HD) region of 4p16.3. The same technique has now yielded a second gene from this cosmid. This gene appears to encode a novel member of a superfamily of transporter proteins that includes active and passive transporters in a number of species. The predicted protein of 455 amino acids displays sequence similarity with the E. coli tetracycline resistance efflux protein encoded by cloning vector pBR322, and with a number of related transporters. This gene should open a route to isolating additional mammalian members of this growing superfamily.

Amino Acid Sequence↗
PubMed1993

Gametic but not somatic instability of CAG repeat length in Huntington's disease.

Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD) chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD repeat showed no evidence of somatic instability in a comparison of blood, lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD twins displayed identical CAG repeat lengths suggesting that repeat size is determined in gametogenesis. In contrast with the fragile X syndrome and with HD somatic tissue, mosaicism was readily detected as a diffuse spread of repeat lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree of gametic mosaicism coinciding with the longest somatic CAG repeats. These data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.

Adolescent↗
PubMed1992

Sequence-tagged sites (STSs) spanning 4p16.3 and the Huntington disease candidate region.

The generation of sequence-tagged sites (STSs) has been proposed as a unifying approach to correlating the disparate results generated by genetic and various physical techniques being used to map the human genome. We have developed an STS map to complement the existing physical and genetic maps of 4p16.3, the region containing the Huntington disease gene. A total of 18 STSs span over 4 Mb of 4p16.3, with an average spacing of about 250 kb. Eleven of the STSs are located within the primary candidate HD region of 2.5 Mb between D4S126 and D4S168. The availability of STSs makes the corresponding loci accessibility to the general community without the need for distribution of cloned DNA. These STSs should also provide the means to isolate yeast artificial chromosome clones spanning the HD candidate region.

Base Sequence↗
PubMed1992

Assay by polymerase chain reaction (PCR) of multi-allele polymorphisms in the Huntington's disease region of chromosome 4.

The Huntington's disease-linked D4S115 marker has been converted from a DNA blot assay to a more sensitive and rapid polymerase chain reaction (PCR) assay. PCR amplification of a tandem repeat at D4S115 revealed 7 allelic fragments, ranging in size from approximately 610 to 915 bp, differing in their apparent copy number of a approximately 55 bp core repeat. This repeat unit differs strikingly in sequence from the repeat units of other multi-allele markers from chromosome region 4p 16.3, arguing that the VNTR (Variable Number of Tandem Repeats) loci clustered in this region did not arise from a common ancestral sequence. The D4S115 marker can be assayed simultaneously with PCR products from D4S125, D4S95 and D4S43 on a single agarose gel, providing a rapid scan for successful amplification of these difficult-to-assay VNTRs, and for inheritance of the entire candidate Huntington's disease region. This approach should help to increase the speed, informativeness and accuracy of presymptomatic and prenatal linkage testing in this devastating disorder.

Alleles↗
PubMed1992

The Huntington's disease candidate region exhibits many different haplotypes.

Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180.

Alleles↗
PubMed1992

Yeast proteins associated with microtubules in vitro and in vivo.

Conditions were established for the self-assembly of milligram amounts of purified Saccharomyces cerevisiae tubulin. Microtubules assembled with pure yeast tubulin were not stabilized by taxol; hybrid microtubules containing substoichiometric amounts of bovine tubulin were stabilized. Yeast microtubule-associated proteins (MAPs) were identified on affinity matrices made from hybrid and all-bovine microtubules. About 25 yeast MAPs were isolated. The amino-terminal sequences of several of these were determined: three were known metabolic enzymes, two were GTP-binding proteins (including the product of the SAR1 gene), and three were novel proteins not found in sequence databases. Affinity-purified antisera were generated against synthetic peptides corresponding to two of the apparently novel proteins (38 and 50 kDa). Immunofluorescence microscopy showed that both these proteins colocalize with intra- and extranuclear microtubules in vivo.

Alkaloids↗
PubMed1992

A novel G protein-coupled receptor kinase gene cloned from 4p16.3.

Within the Huntington's disease (HD) candidate region of 4p16.3, the D4S127 locus displays strong linkage disequilibrium with the defect and anchors a conserved haplotype found on many HD chromosomes. To isolate genes from this region we have applied the exon amplification technique to overlapping cosmids spanning D4S127. Here, we report the discovery of a new gene encoding a novel member of a family of protein kinases that specifically phosphorylate the activated forms of G protein-coupled receptors. Such kinases are thought to participate in desensitization of specific receptors, thereby blocking further signal transduction. This gene must now be carefully scrutinized to determine whether it might be involved in HD.

Amino Acid Sequence↗
PubMed1992

Eye tests in the elderly: factors associated with attendance and diagnostic yield in non-attenders.

Patients aged 60-75 years registered with one inner city general practice were sent a questionnaire asking when they last received an eye check by an optometrist. Of the 193 (77%) who responded, 110 (59%) had attended in the last 2 years, and 138 (74%) in the last 3 years. Males and those with mobility problems were less likely to have had their eyes checked. Seventy-seven previous non-attenders were offered an appointment with an optometrist and this was accepted by 34 (44%). These individuals showed a high level of ophthalmic morbidity. Discussion of optometric checks should be included in general practice health checks and the elderly surveillance programme.

Aged↗
PubMed1992

A recombination event that redefines the Huntington disease region.

We report both a recombination event that places the Huntington disease gene proximal to the marker D4S98 and an extended linkage-disequilibrium study that uses this marker and confirms the existence of disequilibrium between it and the HD locus. We also report the cloning of other sequences in the region around D4S98, including a new polymorphic marker R10 and conserved sequences that identify a gene in the region of interest.

Chromosomes, Human, Pair 4↗
PubMed1991

Randomised controlled trial comparing oral and intravenous rehydration therapy in children with diarrhoea.

OBJECTIVE: To determine the effectiveness of oral rehydration in children with moderate dehydration caused by gastroenteritis, and to compare the complications of oral and intravenous treatment. DESIGN: Randomised controlled trial. SETTING: Emergency department and infectious diseases ward in a large urban teaching hospital. PATIENTS: 111 children aged 3-36 months who had been previously healthy, had had diarrhoea for seven days or less, had clinical signs of dehydration, and were not in shock. Six children were withdrawn because the diagnosis was incorrect (four in oral group, two in intravenous group) and one (oral group) was withdrawn at her parents' request. INTERVENTIONS: Oral rehydration fluid was given by mouth or nasogastric tube, or both to 52 children. The remaining 52 received intravenous rehydration fluids but were allowed to drink. MAIN OUTCOME MEASURES: Success or failure of rehydration. Number of times child vomited or passed stool after starting treatment. Time taken to rehydrate. RESULTS: Oral treatment failed in two children (failure rate 3.8%, upper 95% confidence limit 11.6%) and intravenous treatment in none. Vomiting was more common in the oral group (p less than 0.01): 26 of 50 children (52%) in the oral group and 11 of 50 (22%) in the intravenous group vomited during rehydration. There was no significant difference between the two treatment groups in the number of stools passed during rehydration (p = 0.09). None of the children had serious complications of treatment. CONCLUSION: Rehydration by mouth or nasogastric tube is a safe and effective treatment for moderately dehydrated children with gastroenteritis.

Administration, Oral↗
PubMed1990

Electromyographic analysis of brachioradialis to flexor pollicis longus tendon transfer in quadriplegia.

Electromyography was done in patients at the C6 level of quadriplegia after transfer of the brachioradialis to the flexor pollicis longus to restore lateral pinch and transfer of the posterior deltoid to the triceps to restore elbow extension. The relationship of the integrated electromyogram to pinch force during a graduated isometric contraction enabled characterization of the motor recruitment pattern. After tendon transfer, the pattern of the electromyographic response for the brachioradialis was the same as in the flexor pollicis longus in normal subjects, and the posterior deltoid after transfer to the triceps fired synergistically with the brachioradialis. These findings indicate reeducation of transferred muscles occurred after surgery and that they functioned as active primary motors.

Adult↗
PubMed1990

Binding of alpha-fetoprotein by immobilized monoclonal antibodies during episodes of zero-gravity obtained by parabolic flight.

Alpha-fetoprotein (AFP), a single chain polypeptide which is synthesized by the liver and yolk sac of the human fetus, provided a model ligand for assessing the effects of microgravity on ligand binding to surface-immobilized model receptor molecules. Monoclonal antibodies, used as receptors for AFP, were immobilized by covalent attachment to latex microparticles. Zero gravity environment was obtained by parabolic flight aboard NASA 930, a modified KC-135 aircraft. During the onset of an episode of zero gravity, ligand and receptor were mixed. Timed incubation (20 s) was terminated by centrifugation, the supernatant removed, and microparticles were assessed for bound AFP by immunochemical methods. The extent of binding was not influenced by microgravity, when compared with 1-G controls, which suggests that aberrant cellular activities observed in microgravity are not the simple expression of altered macromolecular interactions.

Antibodies, Monoclonal↗
PubMed1989

Clinical signs of dehydration in children.

102 children with acute gastroenteritis were thought by the admitting junior doctors to be 5% or more dehydrated. As judged by subsequent weight recovery in hospital, the main indicators of mild to moderate dehydration were decreased peripheral perfusion, deep breathing, decreased skin turgor, high urea, low pH, and a large base deficit; a history of increased thirst was just short of statistical significance. Dehydration was not indicated by a history of oliguria, by the presence of restlessness or lethargy, sunken eyes, dry mouth, or a sunken fontanelle or by the absence of tears. Clinical signs of dehydration became apparent at 3-4% rather than 5% dehydration. The degree of dehydration was overestimated by a mean of 3.2%; this caused unnecessary hospital admissions and overtreatment with intravenous fluid.

Acute Disease↗
PubMed1989

Needle localization and surgical management of occult breast lesions.

Screening mammography can locate small breast cancer lesions not detectable on physical examination. In this study, the records of 57 patients undergoing radiographically guided preoperative needle localization were reviewed for the period August 1986 to May 1988. Of the 57 cases, 15.8% were positive for cancer and 84.2% were benign breast lesions. Invasive ductal carcinoma was the pathologic diagnosis in all malignant biopsies, except for one case of carcinoma in situ. All positive lesions had shown as microcalcifications on mammogram. The authors examine the criteria for biopsy and discuss their experience with needle localization of occult breast lesion suspicious of breast cancer.

Adult↗