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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 271 records · Page 15Linked to original sources
PubMed1995

Smaller right ear (left hemisphere) advantage for dichotic fused words in patients with schizophrenia.

OBJECTIVE: The purposes of this study were to compare right ear (left hemisphere) advantage for dichotic words in schizophrenia and depression and to assess its association with antipsychotic medication, symptom ratings, and gender. METHOD: Thirty-two schizophrenic patients and 65 patients with major depression were given the Fused Rhymed Words Test, a dichotic listening measure of hemispheric dominance for language. RESULTS: An earlier finding of smaller left hemisphere advantage in schizophrenic patients was replicated. There was no significant change in ear advantage in a subgroup of the schizophrenic patients tested when they were taking neuroleptics and when they were not. The smaller left hemisphere advantage in the schizophrenic patients was not dependent on gender but was related to symptom ratings on the Positive and Negative Syndrome Scale. CONCLUSIONS: The findings are consistent with a left hemisphere dysfunction in schizophrenia, which is associated with positive symptoms.

Adult↗
PubMed1995

Computer planning of stereotactic iodine-125 seed brachytherapy for recurrent malignant gliomas.

At St Thomas' Hospital, we have developed a computer program on a Titan graphics supercomputer to plan the stereotactic implantation of iodine-125 seeds for the palliative treatment of recurrent malignant gliomas. Use of the Gill-Thomas-Cosman relocatable frame allows planning and surgery to be carried out at different hospitals on different days. Stereotactic computed tomography (CT) and positron emission tomography (PET) scans are performed and the images transferred to the planning computer. The head, tumour and frame fiducials are outlined on the relevant images, and a three-dimensional model generated. Structures which could interfere with the surgery or radiotherapy, such as major vessels, shunt tubing etc., can also be outlined and included in the display. Catheter target and entry points are set using a three-dimensional cursor controlled by a set of dials attached to the computer. The program calculates and displays the radiation dose distribution within the target volume for various catheter and seed arrangements. The CT co-ordinates of the fiducial rods are used to convert catheter co-ordinates from CT space to frame space and to calculate the catheter insertion angles and depths. The surgically implanted catheters are after-loaded the next day and the seeds left in place for between 4 and 6 days, giving a nominal dose of 50 Gy to the edge of the target volume. 25 patients have been treated so far.

Brachytherapy↗
PubMed1995

Phonetic variation in dysarthric speech as a function of sampling task.

Previous studies have demonstrated a number of ways in which normal speakers' phonetic performance varies across reading and spontaneous speech tasks. This study set out to investigate whether similar differences across speech sampling tasks were found in a mixed group of dysarthric subjects. A selection of segmental and prosodic parameters were investigated acoustically in the performance of five mild dysarthric speakers and five matched control subjects. The results demonstrated that breath-pause position, unstressed vowel duration and voice-onset time were subject to variation across sampling task in the speech produced by different types of dysarthric speaker. The results suggest that read material produced by dysarthric speakers may not be wholly representative of those speakers' spontaneous speech. Preliminary implications for clinical practice are discussed. The findings point to the need for further research to investigate the extent of such differences and their implications for dysarthria assessment, which up to the present has relied predominantly on read material.

Adult↗
PubMed1995

Pain and corneal foreign bodies.

The commonest cause for ocular pain, presenting to an ophthalmic emergency centre, is due to corneal foreign bodies. Although the problem is transient, the degree of morbidity is often underestimated. The object of this study was to assess the degree of pain associated with these lesions.

Adult↗
PubMed1995

Trends in operating department nursing. The role of the patient advocate.

Within the operating department the nurse is seen to take on the traditional role as a member of an integrated theatre team. A team can be defined as group of two or more people who recognise common goals and co-ordinate their efforts to achieve them. The operating department team's shared goal is: "the efficient and effective delivery of care with minimal trauma to the individual patient for the relief of suffering, the restoration of bodily function, a favourable post-operative outcome, contributing to the patient's optimal health and return to society, or death with dignity".

Forecasting↗
PubMed1995

Glutathione binding proteins in the gastrointestinal nematode Heligmosomoides polygyrus.

A glutathione-affinity matrix was used to identify glutathione-dependent protein(s) in somatic extracts of the nematode Heligmosomoides polygyrus. Polypeptides of 70-80 kDa were retained by the affinity matrix following the elution of H. polygyrus glutathione S-transferases by 5 mM glutathione. The 70-80-kDa polypeptides were subsequently eluted from the matrix by the addition of 20 mM glutathione and these polypeptides did not show glutathione S-transferase activity. The high-affinity H. polygyrus glutathione-binding proteins may be related to the uncharacterized purification hindering factors previously demonstrated during the isolation of glutathione S-transferases in several other helminths.

Animals↗
PubMed1995

Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes.

We describe a stratagem for identifying new mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. GALT enzyme activity and isoforms were defined in erythrocytes from probands and their first-degree relatives. If the biochemical phenotypes segregated in an autosomal recessive pattern, we screened for common mutations by using multiplex PCR and restriction endonuclease digestions. If common mutant alleles were not present, the 11 exons of the GALT gene were amplified by PCR, and variations from the normal nucleotide sequences were identified by SSCP. The suspected region(s) was then analyzed by direct DNA sequencing. We identified 86 mutant GALT alleles that reduced erythrocyte GALT activity. Seventy-five of these GALT genomes had abnormal SSCP patterns, of which 41 were sequenced, yielding 12 new and 21 previously reported, rare mutations. Among the novel group of 12 new mutations, an unusual biochemical phenotype was found in a family whose newborn proband has classical galactosemia. He had inherited two mutations in cis (N314D-E203K) from his father, whose GALT activity was near normal, and an additional GALT mutation in the splice-acceptor site of intron C (IVSC) from his mother. The substitution of a positively charged E203K mutation created a unique isoform-banding pattern. An asymptomatic sister's GALT genes carries three mutations (E203K-N314D/N314D) with eight distinct isoform bands. Surprisingly, her erythrocytes have normal GALT activity. We conclude that the synergism of pedigree, biochemical, SSCP, and direct GALT gene analyses is an efficient protocol for identifying new mutations and speculate that E203K and N314D codon changes produce intraallelic complementation when in cis.

Base Sequence↗
PubMed1995

Telephone consultations in general practice: an additional or alternative service?

BACKGROUND: There is conflicting evidence about whether telephone consultations in general practice represent additional or alternative contacts with the general practitioner. AIM: A study set out to assess the characteristics of patients using the telephone to consult the general practitioner and whether telephone consultations were used as an additional or an alternative service to surgery consultations during surgery hours. METHOD: The study took place in one practice that has run a 'phone-in clinic' for five years. A questionnaire on perceptions of and attitudes towards telephone consultations was sent to 259 patients who consulted the general practitioner by telephone and to an age-sex matched group of patients whose medical records indicated that they had never consulted the general practitioner by telephone. For both groups, numbers of repeat prescriptions and consultations in the preceding year were determined from medical records. RESULTS: Those who consulted the doctor by telephone were significantly more likely to be aware of the phone-in clinic, to have a telephone at home, to have children aged under five years at home and to be receiving repeat prescriptions and repeat prescriptions for psychotropic drugs compared with those who had never consulted by telephone. Eleven of 226 patients who consulted be telephone (5%) indicated that they would definitely not have made a surgery appointment or home visit request (that is, they represented additional general practitioner workload) while 120 (53%) used the telephone consultation as an alternative to making a surgery appointment and 22 (10%) used the telephone consultation as an alternative to requesting a home visit. CONCLUSION: It appears that the telephone service was being used largely as an alternative access point to the doctor. General practitioners should not be apprehensive about the possible increase in workload generated by introducing telephone consultations, for example in phone-in clinics.

Attitude to Health↗
PubMed1994

An in vivo assay for members of the cAMP response element-binding protein family of transcription factors.

The CREB/ATF family of dimeric basic/leucine zipper (bZIP) transcription factors have been implicated in signal transduction by several agents including intracellular cAMP. The ubiquity of the cAMP-signaling pathway in mammalian cells has made it difficult to assay individual family members in their native form and dissect their roles in signal transduction. In light of observations that ATF1 exhibits several cell-specific characteristics and is allosterically regulated, the above problem has represented a particular limitation for studying ATF1. To address this we have exploited the modular nature of the bZIP domain to design fusion proteins that closely resemble native ATF1 but have altered DNA binding and dimerization specificity. The activity of these novel proteins can be monitored following their introduction into a cAMP-responsive cell type. Thus we describe an assay for members of the CREB family that should be generally applicable in a range of cell types and to other bZIP protein families.

Amino Acid Sequence↗
PubMed1994

Characterization of ligand binding by the human p55 tumour-necrosis-factor receptor. Involvement of individual cysteine-rich repeats.

Two soluble tumour-necrosis-factor-alpha(TNF)-binding proteins are derived from the extracellular domains of the p55 and p75 TNF receptors. They are considered to play a pivotal regulatory role in TNF-mediated inflammatory processes, including diseases such as rheumatoid arthritis, by competing with the cell surface receptors for TNF and lymphotoxin (LT, tumour-necrosis factor beta). The extracellular domains of the two receptors each contain four similar cysteine-rich repeats of about 40 amino acids, in common with several other cell surface proteins including the p75 nerve-growth-factor receptor and the CD40 and Fas antigens. The aim of this study was to characterize the involvement of the four cysteine-rich repeats of the human p55 TNF receptor in TNF and LT binding by both membrane-bound and soluble forms of the receptor. Individual repeats were systematically deleted by PCR mutagenesis and the variants transiently expressed in COS cells. Immunoprecipitated receptor variants exhibited the expected sizes on SDS/PAGE gels, and bound a panel of conformation-dependent anti-(TNF receptor) antibodies. Binding of TNF by the four soluble derivatives was compared with binding by the wild-type soluble receptor using a TNF-affinity column and a BIAcore Biosensor, by measurement of their ability to inhibit TNF cytotoxicity on WEHI cells, and 125I-TNF binding to U937 cells. delta 4, which lacks the fourth cysteine-rich repeat, bound TNF comparably with the full-length soluble receptor. TNF-binding affinity was unaltered by deletion of the fourth membrane-proximal cysteine-rich repeat, as determined by Scatchard analysis of the transmembrane derivatives. We conclude that the fourth cysteine-rich repeat is not required for TNF binding. In contrast, both the soluble and the transmembrane derivatives lacking any one of the first, second or third repeats failed to bind TNF. Although we cannot entirely exclude the possibility that this may be due to indirect conformational change, rather than the removal of essential epitopes, our results suggest that the first three repeats are each required for TNF binding by both the soluble and the cell-surface receptor.

Antibodies, Monoclonal↗
PubMed1994

Phosphoramidon does not inhibit endogenous endothelin-1 release stimulated by hemorrhage, cytokines and hypoxia in rats.

The role of phosphoramidon-sensitive endothelin converting enzyme in the release of endogenous endothelin-1 was investigated in anesthetized rats. Intravenous infusion of phosphoramidon 0.3 mg/kg/min did not suppress the release of endothelin-1 stimulated by hemorrhage or cytokines. Elevation of endothelin-1 in rats subjected to hypoxia was not modified by phosphoramidon (0.1 or 0.3 mg/kg/min for 2 h). A high dose of phosphoramidon (10 mg/kg i.v. +0.1 mg/kg/min) significantly potentiated the hypoxia-induced increases in plasma endothelin-1 levels. Increases in endothelin-1 release caused by bilateral nephrectomy were further enhanced by hypoxia. It is concluded that the release of endogenous endothelin-1 release stimulated by hemorrhage, cytokines and hypoxia is resistant to inhibition by phosphoramidon, and at high doses, phosphoramidon potentiates hemorrhage- and hypoxia-induced increases in endothelin-1 levels, most likely by preventing its degradation.

Animals↗
PubMed1994

YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes.

Interferon gamma (IFN-gamma) is the most potent inducer of class II major histocompatibility complex (MHC) genes. This induction is uniquely mediated by three DNA elements in the promoter region of class II MHC genes. One of these DNA elements, Y, contains an inverted CCAAT box. Previously, we have screened a lambda gt11 library for Y-binding proteins and identified the YB-1 gene. Here we provide evidence that YB-1 can repress the IFN-gamma induction of class II MHC promoter as well as the Invariant chain (Ii) gene which also contains a Y element in its promoter. This was demonstrated by cotransfecting a YB-1 expression vector with promoter-reporter gene constructs. As an alternate approach, an efficient transient transfection system was developed which resulted in a > 70% transfection efficiency. Transfection of YB-1 by this procedure resulted in the near abrogation of IFN-gamma induced HLA-DR antigen and mRNA expression. These findings show the functional suppression of class II MHC gene induction by the YB-1 protein.

Animals↗
PubMed1994

Detection of rotational modulation in the coronal extreme-ultraviolet emission from V711 Tauri?

The RS CVn binary V711 Tauri was observed by the Extreme Ultraviolet Explorer satellite (EUVE) twice during the latter half of 1992, for periods lasting several days. Light curves for the waveband 60-180 angstroms derived from the all-sky survey scanning in August and from a pointed calibration observation made in October both exhibit a modulation of about 40%. The modulation in both data sets is very similar, with minimum flux occurring near orbital phase phi=0.5. Analysis using a two-temperature optically thin plasma emission model reveals that most of the detected extreme ultraviolet (EUV) flux emanates from hot (approximately 10(7) K) coronal plasma. The modulation is probably mostly due to either flare-like activity or to rotational occultation of a long-lived, compact, and especially bright coronal structure on the more active star of the system. The phased data support the latter hypothesis. This coronal structure is then likely to be associated with the persistent spot patterns seen on V711 Tau when using Doppler and photometric surface imaging techniques. Comparison with contemporaneous Stromgren b-band photometry indicates that the optical minimum light leads the EUV maximum light by 90 degrees in phase.

Astronomy↗
PubMed1994

The molecular forms of acetylcholinesterase from Necator americanus (Nematoda), a hookworm parasite of the human intestine.

Necator americanus (Nematoda: Strongyloidea), a human hookworm parasite, is known to release considerable amounts of acetylcholinesterase (AChE) [Pritchard, D. I., Leggett K. V., Rogan, M. T., McKean, P. G. & Brown, A. (1991) Necator americanus secretory acetylcholinesterase and its purification from excretory/secretory products by affinity chromatography, Parasite Immunol. 13, 187-199]. The present study deals with AChE activity recovered in sequential somatic extracts, and excretory/secretory products, of the adult stage of the parasite. 97% of AChE was extractable in low-salt and high-salt detergent-free buffers, and only 3% was solubilised by a further extraction in the presence of Triton X-100. AChE in all three extracts was affected by the AChE inhibitors eserine, bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide and edrophonium chloride, but was resistant to the effects of tetramonoisopropylpyrophosphortetramide, a butyrylcholinesterase inhibitor. Sucrose density centrifugation revealed that AChE in all somatic extracts (low-salt, high-salt and detergent) resolved almost exclusively as a single peak between 6.9-7.5 S, while excretory/secretory products resolved at 8.2 S. These values are all compatible with dimers of catalytic subunits and no evidence was found for the presence of higher oligomers such as asymmetric forms. The only sample to show a shift in sedimentation following the inclusion of detergent (Triton X-100, Brij 96) in the gradient was a component of the detergent-soluble extract, indicating the existence of a minor amphiphilic form. In low-salt-soluble and high-salt-soluble extracts, AChE was solubilised as a hydrophilic globular form, probably a dimeric G2. The analysis of diisopropylfluorophosphate-labelled extracts by SDS/PAGE, and unlabelled extracts by immunoblotting using a polyvalent antiserum to N. americanus AChE, indicated that the AChE isolated in each extract was biochemically and immunologically similar. The banding patterns obtained were comparable to that seen when purified AChE was analysed by SDS/PAGE and immunoblotted. This suggests that the basic catalytic subunit has a mass of 66-70 kDa with the active site being located in a 30-kDa domain. All experimental data indicate the existence of only one AChE class in Necator homologous to AChE of class B from Caenorhabditis elegans. The solubility characteristics and globular nature of this hookworm AChE suggest that its major function is as an excretory or secretory product. This again raises the question of the true biological function of this 'non-cholinergenic' nematode secretion.

Acetylcholinesterase↗
PubMed1994

The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular carcinomas.

Using digoxigenin-labelled, synthetic oligonucleotide probe cocktails of angiogenin and bFGF genes, the expression of the two genes was observed by in situ hybridization in ten colonic adenocarcinomas, seven gastric adenocarcinomas, and four hepatocellular carcinomas. The angiogenin gene was expressed in eight of the ten cases of colonic adenocarcinoma and in all of the four cases where dysplastic glands were found. Angiogenin expression was evident in four of the seven cases of gastric adenocarcinoma. bFGF expression was detected in only five of the seven gastric carcinoma cases. The mRNAs for angiogenin and bFGF were mainly cytoplasmic in distribution and were only occasionally seen in the nuclei of the positive cells. Neither the angiogenin gene mRNA nor the bFGF mRNA was expressed in the four cases of hepatocellular carcinoma. It is postulated that the angiogenin gene may play an important role in angiogenesis in colonic adenocarcinomas; in gastric cancers, both angiogenin and bFGF were involved in this process. For hepatocellular carcinomas, neither angiogenin nor bFGF production appeared to be related to angiogenesis.

Adenocarcinoma↗