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Biomedical subjects

A Wright

Publications and source records attributed to A Wright.

At least 163 records · Page 9Linked to original sources

Tele-education: the virtual medical laboratory.

The virtual medical laboratory (VML) was conceived to provide an Internet-accessible resource, offering access for clinicians and scientists to an invaluable data archive at the institute of Laryngology and Otology, London. The Institute is home to the largest collection of temporal bone, laryngeal, skull and sinus sections in Europe. The skull and sinus collections include an extensive section consisting of animal material. These were contributions from zoos around the world. Over the last 50 years, samples have been carefully sectioned and stained by specialized technicians to produce histology slices of most regions of the head and neck. The aim of the project is to create a virtual medical laboratory, which will provide access to archived histological material as well as computerized tomography and magnetic resonance data. Central to this aim is the reconstruction of the internal anatomy of the temporal bone from two-dimensional histology slices, to create three-dimensional views that can be used for anatomical simulation and surgical training in otolaryngology. State-of-the-art three-dimensional reconstruction and rendering technology allows us to develop such a model. Computer-generated simulation could be made available to all hospitals in which otolaryngology is practised, via digital communication networks. We aim to develop core technology in our own specialty that is applicable to other fields of higher education, which have not been exposed to such modern teaching modalities. This has the potential to become an invaluable teaching resource for anatomists, surgeons and other scientists.

Computer Communication Networks↗

Kidney extracts from spontaneously hypertensive rats (SHR) have greater dopamine 1A receptor RNA-binding activity than extracts from normotensive Wistar-Kyoto (WKY) rats.

Rat kidney extracts contain a 52 kDa protein that binds to the 3' untranslated region of the dopamine 1A (D1A) receptor mRNA at a 243 base-long cis element starting at the stop codon and ending approximately 220 bases upstream of an AUUUA-rich region. The D1A receptor RNA-binding protein (D1A-BP) is redox-sensitive; free sulfhydryl groups on the protein are required for binding. Kidney extracts from SHR have significantly more D1A-BP activity than extracts from WKY rats. When kidney extracts were tested for binding to an 80-base RNA containing four AUUUA repeats, there was also greater binding activity in extracts from SHR. These increases are at least partly specific because there was no difference in catalase RNA-binding protein activity between the two rat strains. These data suggest D1A-BP and AUUUA-binding protein may play a role in posttranscriptional regulation of the D1A receptor in the hypertensive rat.

Animals↗

The discipline and literature of general practice.

In response to a review recently carried out by the Royal College of General Practitioners, the British Journal of General Practice is soon to be issued in a new and expanded format. While continuing to develop its primary role as a leading scientific journal of record, the journal will accommodate a monthly selection of integrated news, information and features. The editorial board welcomes the opportunities provided by these changes, but wishes to emphasize the continuing importance of general practice as a scientific discipline in its own right and to reaffirm its commitment to the publication of high-quality, peer-reviewed original research papers. It is hoped that the newlook journal will have a wide appeal. But, as the first-and still the foremost-journal of general practice in the world, it will continue to be a journal of record serving both its authors and the academic community worldwide.

Family Practice↗

Evidence that glutathione peroxidase RNA and manganese superoxide dismutase RNA bind the same protein.

Rat lung extract contains protein that binds to a cis element in the 3' untranslated region of glutathione peroxidase (GPx) mRNA; this region is located 200 bases downstream of the stop codon and 77 bases downstream of the selenocysteine insertion sequence. GPx mRNA-binding protein (GPx-BP) has the following characteristics in common with Mn superoxide dismutase mRNA-binding protein (MnSOD-BP): 1. RNA-binding activity is redox-sensitive; free sulfhydryl groups on the protein are required for binding. 2. RNA-binding activity is enriched in a 130,000 x g supernatant fraction and is inhibited by RNA in the polysomal fraction. 3. The MnSOD and GPx cis elements compete with each other for protein binding. 4. UV crosslinking studies with each probe reveal a [32P]-labeled protein of the same apparent molecular mass, 56 kDa. These observations provide evidence that MnSOD and GPx RNAs bind the same protein.

Animals↗

Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein.

The neuronal-specific Elav-like proteins (HuD, Hel-N, and HuC) contain three RNP-type concensus motifs and bind to AU-rich elements. We have identified and cloned a fourth member of this family (HuR) that is expressed in a wide variety of cell types. The purified recombinant protein binds avidly to the AU-rich element in c-fos and interleukin-3 mRNAs. In the case of the c-fos AU-rich element, HuR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Mutational analysis has shown that all three AU motifs are required for maximal binding.

Amino Acid Sequence↗

Antibodies that react with the capsular polysaccharide of Vibrio vulnificus are detectable in infected patients, and in persons without known exposure to the organism.

In serious infections with Vibrio vulnificus, IgG antibodies to the capsular polysaccharide of the infecting strain were demonstrable in patient serum. It was not possible to show that persons with probable increased exposure to V. vulnificus (shellfish industry workers) had increased levels of antibodies to any one of three capsular types tested when compared with persons who would be expected to have had minimal exposure to the organism (Seventh Day Adventists). Antibodies that reacted with the capsular polysaccharides were demonstrable in persons without a history of V. vulnificus infection, suggesting that cross-reacting antibodies are present in the general population.

Antibodies, Bacterial↗

Selective embryo reduction in a heterotopic pregnancy using potassium chloride injection resulting in a hematosalpinx.

OBJECTIVE: To incorporate conservative management of a heterotopic pregnancy using injection of KCl into the ectopic pregnancy (EP). DESIGN: A retrospective case report. SETTING: A patient referred to an academic institution in the division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, incorporating the ultrasound (US) and operating room facilities. INTERVENTION(S): Using US as a guide, KCl was injected into the chorionic cavity of an EP. MAIN OUTCOME MEASURE(S): Resolution of ectopic gestational tissue with resultant hematosalpinx requiring exploratory laparotomy. Uncomplicated prenatal course of intrauterine pregnancy. RESULT(S): Injection of KCl into the chorionic cavity of EP resulting in resolution of gestational tissue but complicated by hematosalpinx in the fallopian tube. CONCLUSION(S): Selective embryo reduction of a tubal heterotopic pregnancy remains a viable therapeutic option.

Fallopian Tube Diseases↗

A decision-making aid for long-term care waiting list policies: modelling first-come, first-served vs. needs-based criteria.

A chronic care hospital in London, Ontario, was faced with the question of whether to continue to admit applicants on a first-come, first-served basis, or to implement a needs-based admission criterion To provide information relevant to this decision, a simple computer modelling technique was used to model the waiting list under both policies. Analysis of the results indicated substantial variability in the need for care demonstrated by waiting list applicants, and individual placement priority under the two schemes. Descriptions of individuals affected by the proposed change in policy provided additional information. The information provided by the waiting list analysis contributed to the decision-making process about waiting list policy. The method used is applicable to waiting list management decisions in other institutions.

Computer Simulation↗

MDA435/LCC6 and MDA435/LCC6MDR1: ascites models of human breast cancer.

We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Untreated mice develop ascites following i.p. inoculation of 1 x 10(6) cells and have a reproducible life span of approximately 30 days, with all animals dying within a 48 h period. The in vivo response of MDA435/LCC6 ascites to several cytotoxic drugs, including doxorubicin, etoposide (VP-16), BCNU and mitomycin C, closely reflects the activity of these single agents in previously untreated breast cancer patients. MDA435/LCC6 cells also retain the anchorage-dependent and anchorage-independent in vitro growth properties of the parental MDA-MB-435 cells, and can be used in standard in vitro drug screening assays. The drug resistance pattern of the MDA435/LCC6 cells suggests that they may have few active endogenous drug resistance mechanisms. To generate a model for the screening of MDR1-reversing agents, MDA435/LCC6 were transduced with a retroviral vector directing the constitutive expression of the MDR1 cDNA, producing a cell line with a classical MDR1 resistance pattern (MDA435/LCC6MDR1). THese ascites models may be a viable alternative to the murine leukaemia ascites (L1210, P388) and, in conjunction with other breast cancer cell lines, facilitate the in vitro and in vivo screening of new cytotoxic drugs and drug combinations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Amino Acid Sequence↗

Osteoma of the internal auditory canal.

We present a case of an osteoma of the internal auditory canal, which was surgically removed with symptomatic improvement. We describe CT, MRI, histological and operative findings, with a review of the proposed aetiology. The implications for imaging in the investigation of retrocochlear lesions are discussed.

Adult↗

European Gene Mapping Project (EUROGEM): breakpoint panels for human chromosomes based on the CEPH reference families. Centre d'Etude du Polymorphisme Humain.

Meiotic breakpoint panels for human chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 17, 18, 20 and X were constructed from genotypes from the CEPH reference families. Each recombinant chromosome included has a breakpoint well-supported with reference to defined quantitative criteria. The panels were constructed at both a low-resolution, useful for a first-pass localization, and high-resolution, for a more precise placement. The availability of such panels will reduce the number of genotyping experiments necessary to order new polymorphisms with respect to existing genetic markers. This paper shows only a representative sample of the breakpoints detected. The complete data are available on the World Wide Web (URL http:/(/)www.icnet.uk/axp/hgr/eurogem++ +/HTML/data.html) or by anonymous ftp (ftp.gene.ucl.ac.uk in/pub/eurogem/maps/breakpoints).

Chromosome Mapping↗

Prevalence of low back pain in the community: implications for service provision in Bradford, UK.

STUDY OBJECTIVE: To assist a purchasing district in the planning of services for low back pain by assessing the prevalence of symptoms and the current involvement of primary, secondary, and complementary care in the treatment of low back pain. In the light of these findings, to assess further the potential impact of a new system of open access to physical therapy, as recommended by the British Clinical Standards Advisory Group (CSAG). DESIGN: A two-stage cross sectional survey approach using postal questionnaires. SUBJECTS: Altogether 1437 men and 1747 women aged 25-64 years, randomly selected from the family health services association register in Bradford. MAIN RESULTS: An annual incidence of 4.7% for low back pain was found, with lifetime, 12 month period, and point prevalences of 59%, 39%, and 19% respectively. Over a one year period, 50.3% of episodes were acute (< 2 weeks), 21% were subacute (2 weeks-3 months), and 26% were chronic (over 3 months) in duration. Altogether 17.8% of the population in this age range experienced referred pain, numbness, or tingling, and 6.4% took time off work as a result of low back pain. In the same year, 20% of the population in the same age range consulted no-one about their pain, 13.7% were treated at the primary care level, 4% received secondary care, and 3% visited a complementary therapist. One fifth of those who did not consult a professional experienced severe pain during episodes. Prevalence estimates indicate that an emphasis on early intervention and primary care management of simple low back pain as recommended by the CSAG could generate a 131% surge in demand for physical therapy. CONCLUSIONS: Local prevalence estimates may allow purchasers to estimate the potential effects of a shift in management policy for low back pain and to highlight areas of unmet need in terms of resources and patient education.

Adult↗

Dinucleotide-binding site of bovine liver catalase mimics a catalase mRNA-binding protein domain.

Rat lung contains protein that interacts with catalase mRNA to form specific, redox-sensitive RNA-protein complexes. The studies in this report were aimed at determining whether catalase protein binds its own RNA. We found that rat catalase RNA binds NADPH-depleted bovine liver catalase (Sigma) but does not bind bovine liver catalase in the presence of NADPH. Complex formation between liver catalase and catalase RNA is competitively eliminated by a CA dinucleotide repeat. These data suggest the dinucleotide binding site of catalase mimics or is homologous to a catalase RNA-binding protein domain. These findings support the hypothesis that a class of RNA-binding proteins may have evolved from (di)nucleotide binding enzymes (M. W. Hentze. Trends Biol. Sci. 19: 101, 1994). When bovine liver catalase from two other commercial sources (Calbiochem and Boehringer) was used, we could not detect binding to catalase RNA. We have not yet been able to identify the basis for this difference. Thus the physiological importance of our observation of the NADPH-sensitive protein binding to catalase RNA cannot be assessed at this time.

Animals↗