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Biomedical subjects

A Hughes

Publications and source records attributed to A Hughes.

At least 19 recordsLinked to original sources
PubMed1992

The superficial plexiform layer: a third retinal association area.

Electron microscopy enables the identification of a new association area in the mammalian retina. It is a region whose processes and synaptic junctions form a diffuse and intermittent layer bridging the boundary between the optic nerve fibre layer and ganglion cell layer. It involves displaced amacrine cells, retinal ganglion cells and probably interplexiform cell processes. Because it is close to the vitreal surface of the retina and has several properties of a plexiform layer, it has been named the superficial plexiform layer. It is much more sparse than the outer or inner plexiform layers in the rabbit, but contains a significant and substantial density of 6,100 synapses/mm2 near the visual streak. Morphological criteria distinguish two classes of synapses in the new association area. One has features of Colonnier's symmetric type and is formed by amacrine-like processes or their terminals, onto other amacrine-like processes or the cell bodies, dendrites and axon hillocks of some large ganglion cells. It makes up 79% of the population at a density of 4,800 synapses/mm2 in the examined sample. The second class arises from large processes of the fibre layer, which resemble axons rather than amacrine cell branches, has Colonnier's asymmetric form, and synapses onto a variety of other neuronal processes and cells. At a local density of 1,300/mm2 this type forms 21% of the population. A series of experiments including Wallerian degeneration, retrograde degeneration, electron microscopy and horseradish peroxidase (HRP) transport was employed to determine the nature of the large synapse-forming processes of the fibre layer that were the most amenable to investigation. It is concluded that the processes project into the optic nerve because they can be filled with HRP by retrograde transport from the end of the transected optic nerve. Although this result is based on limited evidence, it is complemented by the observation that the majority of the fibres undergo retrograde degeneration within 25 days of optic nerve section. It is concluded that the processes are either centrifugal fibres or the axons of retinal ganglion cells. The persistence of a relatively normal density of synapse-forming large fibres for seven days after optic nerve section, without Wallerian degeneration, argues that they are not the terminals of centrifugal axons. This conclusion is complemented by a separate class of profiles that did degenerate in this short period and are concluded to represent the centrifugal fibres. The large synapsing processes of the fibre layer are concluded to be the axons of some large ganglion cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Estrogen receptor-directed radiotoxicity with Auger electrons: specificity and mean lethal dose.

To assess the feasibility of using estrogen receptor-directed therapy with Auger electron-emitting ligands for therapy of estrogen receptor (ER)-containing cancers, we synthesized and evaluated the radiotoxicity of several 123I-labeled estrogens to specifically kill ER+ cells in culture. Auger electrons have been previously shown to be of short range, generally less than the dimensions of a cell, so that to use them therapeutically a mechanism is needed to deliver the Auger electron-emitting nuclide to the vicinity of the DNA. Since it is now well established that the estrogen receptor, when bound to estrogen, forms a high affinity association with distinct estrogen response elements in the DNA, we wished to test the hypothesis that a short exposure of cells to a 123I-labeled estrogen would be specifically radiotoxic to ER+ cells, and that the decays per cell needed for cell killing would be compatible with reasonable levels of receptor occupancy. Using the halodestannylation reaction with tributyl tin precursors of several estrogens and commercially available iodine-123, we prepared the iodoestrogens, E-17 alpha(-)[123I]-iodo-11 beta-methoxyestradiol and 2(-)[123I]iodo-1,1-bis(4-hydroxyphenyl)--2-phenylethylene, at high specific activities, in several cases at essentially the specific activity of 123I itself, 240,000 Ci/mmol. When various concentrations of either of the 123I-labeled estrogens were incubated for 1 h with a subline of ER+ Chinese hamster ovary cells and the washed cells plated for survival assays, a dose-dependent, unlabeled estradiol-inhibitable reduction in survival was observed. In contrast, Chinese hamster ovary cells not expressing estrogen receptor showed little sensitivity to the radiotoxicity of the 123I-labeled estrogens. Calculations based on the assayed residence time of the iodoestrogens in the cells indicate that several hundred decays per cell are sufficient to kill cells.

Animals↗
PubMed1992

Celiprolol.

Explore the source record for details and available documents.

Antihypertensive Agents↗
PubMed1992

Understanding of Weil's disease among canoeists.

Although the risks of contracting Weil's disease in the UK are small, it can be a serious illness. Recently the disease has attracted public interest. This interest has prompted confusion and anxiety among recreational water user groups such as canoeists who had not previously seen themselves as being particularly at risk. In this paper, the experience of symptoms associated with Weil's disease among canoeists, their understanding and perceptions of the disease, and their compliance with preventive advice on the British Canoe Union (BCU) warning card, have been studied. Gaps in understanding and of adherence to preventive advice were identified. Accordingly, it was concluded that health education for canoeists could be improved. Consideration is being given by the BCU to the value of preparing a canoeist instructors' training pack.

Adolescent↗
PubMed1991

Sequence analysis of HLA-Bw53, a common West African allele, suggests an origin by gene conversion of HLA-B35.

In the West African population of the Gambia the class I antigen HLA-Bw53 is found at high frequency. We used the polymerase chain reaction to amplify cDNA from an individual homozygous for this allele and determined the nucleotide sequence of the polymorphic alpha 1 and alpha 2 domains. The HLA-Bw53 sequence is identical to HLA-B35 except for a short sequence at the 3' end of exon 2 (encoding the alpha 1 domain) which specifies a Bw4 rather than a Bw6 motif. This suggests an origin for HLA-Bw53 involving a gene conversion of HLA-B35 by an allele containing this Bw4 sequence. The alpha 2 domain shared by HLA-Bw53, -B35, and -Bw58 is particularly common in sub-Saharan Africans.

Adult↗
PubMed1991

Synthesis, purification and stability of no carrier added radioiodinated 1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene (IBHPE), a prototype triphenylethylene estrogen-receptor binding radiopharmaceutical.

A triphenylethylene compound [1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene; IBHPE] has been labeled by halodestannylation with 123I at a specific radioactivity of 13,200 Ci/mmol (by in vitro receptor assay) after HPLC purification. The corresponding 80mBr-labeled compound (BrBHPE), which has a 3-fold higher affinity for the estrogen receptor, was previously prepared and examined as a potential therapeutic radiopharmaceutical exploiting Auger electron toxicity. Stability of IBHPE was a concern because free iodide was generated when HPLC solvents were removed with a stream of nitrogen in a glass vial; however, decomposition was minimal when polypropylene vials were used, and ethanol solutions of [123I]IBHPE were stable for several days at 0-4 degrees C. Tissue distribution studies of IBHPE after intraperitoneal injection to mature female rats showed highest estradiol-inhibitable uptake in the peritoneal estrogen-receptor rich tissues (uterus, ovaries and vagina) at 30 min. Specific uptake (percent dose per gram) in the pituitary, and peritoneal target tissue-to-blood ratios were greater at 2 h than 30 min. In immature female rats, uterus-to-blood ratios of greater than 50, progressively lowered by increasing diethylstilbestrol levels, were obtained. These data demonstrate good binding of IBHPE to the estrogen receptor in vivo, in spite of extensive non specific binding in in vitro estrogen receptor assays. Most of the label in the uterus at 1 h after injection was still unchanged IBHPE. Our results suggest that IBHPE or related 123I-labeled iodovinyl triphenylethylenes could have diagnostic or therapeutic radiopharmaceutical utility.

Aging↗
PubMed1991

Risk factors for HIV-2 infection in The Gambia.

A serosurvey was carried out to assess the prevalence of HIV infection in The Gambia and the importance of possible risk factors. The overall prevalence of HIV-2 infection among the 4228 adults studied was 1.7% while that of HIV-1 was 0.1%. The prevalence of HIV-2 was similar in both sexes but higher among those greater than 25 years of age and those who lived in two small towns along a main transport route. Among men, multivariate analysis showed prevalence of HIV-2 infection was significantly greater among those in the more affluent occupations, those without a secondary education and those with a history of urethral discharge. Among women, infection was more frequent in divorcees and widows and those who had been married several times. The prevalence was also higher in individuals born in Guinea-Bissau and in an ethnic group which originated there.

Adolescent↗
PubMed1991

Chloride and bicarbonate transport in rat resistance arteries.

1. The role of chloride and bicarbonate in the control of intracellular pH (pHi) was assessed in segments of rat mesenteric resistance arteries (internal diameter about 200 microns) by measurements of chloride efflux with 36Cl-, of pHi with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5 (and-6)-carboxyfluorescein (BCECF) and of membrane potential with intracellular electrodes. 2. The main questions addressed were whether the previously demonstrated sodium-coupled uptake of bicarbonate in these arteries was also coupled to chloride efflux, and whether sodium-independent Cl(-)-HCO3- exchange was present and played a role in regulation of pHi. 3. The 36Cl- efflux was unaffected by acidification induced by an NH4Cl pre-pulse in the presence as well as in the absence of bicarbonate. This was also true in sodium-free media and in vessels depolarized by high potassium. 4. The membrane potential was unaffected by the acidification associated with wash-out of NH4Cl, and the net acid extrusion during recovery of pHi from the acidification was not affected significantly by depolarization. 5. In the absence of bicarbonate, omission of extracellular chloride caused no change in pHi, but reduced 36Cl- efflux. By contrast, in the presence of bicarbonate, omission of chloride caused an increase in pHi but no change in 36Cl- efflux. Furthermore, the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) inhibited the increase in pHi seen in the presence of bicarbonate and reduced the 36Cl- efflux in the presence of bicarbonate. 6. The presence of bicarbonate had no significant effect on the rate of recovery of pHi or the rate of increase of intracellular acid equivalents after an NH4Cl induced alkalinization; also the buffering power was not significantly different in the absence and presence of bicarbonate. Moreover these parameters were not significantly affected by DIDS, although DIDS as previously demonstrated reduced the rate of recovery of pHi from acidification. 7. The membrane potential was not significantly affected by the alkalinization associated with addition of NH4Cl and the rate of recovery of pHi from the alkalinization was not affected by depolarization. 8. The effects of NH4Cl and PCO2 on 36Cl- efflux were complex and could not easily be explained by the changes in pHi.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Expression of MHC class II (Ia) antigen by the neonatal enterocyte: the effect of treatment with interferon-gamma.

Immunohistochemical techniques were used to probe the expression and inducibility of class II major histocompatibility complex (MHC) (Ia) antigens by the mouse enterocyte at various stages postpartum. Expression of Ia was related to both age and intestinal location. Ia antigen was not detected until at least 1 week post-weaning and was noted thereafter in both proximal and distal intestine. Both crypt and villus enterocytes were stained in the distal small intestine, but staining was restricted to the upper portion of the villus in the proximal small intestine. Moreover, the extent of staining and the intensity of staining were greater in the distal small intestine. The effect of a single injection of recombinant mouse interferon-gamma (IFN-gamma) on Ia expression by enterocytes of 16-day-old, suckling BDF1 mice was examined. Injection of distilled water (DW) or 1 to 2 x 10(4) U IFN-gamma did not induce enterocyte Ia expression. Doses of 4-10 x 10(4) U were effective inducers of Ia on crypt and, occasionally, on lower villus cells examined 24 hr later. Staining did not persist on the enterocyte beyond 48 hr. In conclusion, Ia is not normally expressed on small intestinal enterocytes of the mouse until after weaning; however, Ia expression can be induced earlier by treatment with IFN-gamma. It is not known whether failure to detect Ia expression prior to weaning reflects a lack of positive stimuli and/or the presence of inhibitory stimuli, possibly carried in the breast milk.

Aging↗
PubMed1990

Human immunodeficiency virus type 2 (HIV2).

In the mid 1980's a second human retrovirus, capable of causing the acquired immunodeficiency syndrome (AIDS), was isolated from patients of West African origin. This virus, now called human immunodeficiency virus type 2 (HIV2), was found to be distinct from human immunodeficiency virus type 1 (HIV1) but closely related to simian immunodeficiency viruses (SIV). Although the genomes of HIV1 and HIV2 are similar there are significant differences in nucleotide and amino acid sequences, most marked with the envelope genes and proteins. Both viruses, however, bind to the same CD4 cellular receptor. HIV2 is largely confined to West Africa where it is the dominant HIV, though patients infected with HIV2 have been described in Europe and America. Its transmission, clinical features and immunological effects are similar to those associated with HIV1 infection. However, there is some suggestion that the incubation period from infection to clinical disease may be longer than with HIV1 and that HIV2 may be less pathogenic. Patients with sera that react with both HIV1 and HIV2 antigens have been described, but it is unclear whether this represents serological cross reactivity or true double virus infection. Testing for HIV2 antibodies may become increasingly necessary in HIV2 non-endemic areas.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The epidemiology of Haemophilus influenzae meningitis in children under five years of age in The Gambia, West Africa.

Haemophilus influenzae meningitis was studied over a 2-year period in children less than 5 years of age in a population-based, prospective study in The Gambia, West Africa. A total of 77 cases were recorded. The incidence was 60 cases/100,000 children less than 5 years of age and 297 cases/100,000 children less than 1 year of age. The peak prevalence was at the age of 5 months; 83% of the children were less than 1 year old and 45% were less than 6 months old. Only 55% of cases recovered completely. The distance to the nearest hospital was an important predisposing factor for a fatal outcome. Two cases were secondary. Many patients were anemic and underweight. The observations show that H. influenzae meningitis in The Gambia has an incidence as high as that in the USA, but that it has 10-fold more devastating outcome. If the infection is to be prevented by vaccination in The Gambia, immunization will have to be given very early in life.

Age Factors↗
PubMed1990

Information needs of patients and visitors in a district general hospital.

A survey of the information needs of patients and visitors to a large District General Hospital was conducted during a one-month period in 1988 to identify sources of information used by patients and their visitors, whether these sources were perceived as adequate and what improvements were suggested. The findings indicate that of 406 respondents, 37% had wanted to know more about a particular condition within the preceding 12 months. The most frequently used sources of information were general practitioners, hospital doctors and nurses, and written material. The most frequent inquires were about disease aetiology and prevention, and the treatment and prognosis of a wide range of medical conditions. Thirty-six per cent of the inquirers had received little or none of the information that they sought. Visitors were more likely than patients to be dissatisfied with presently available sources of information, and patients over 60 years old were more likely to be satisfied than younger groups. Dissatisified persons were most often seeking improved access to doctors and nurses, more explanations from these staff, and more readily available booklets and leaflets. The results are discussed in relation to previous findings with hospital in-patients. They support a stated need in the recent Government White Paper, Working For Patients, for patient information leaflets and for clear and sensitive explanations about what is happening to them in hospital.

Adolescent↗
PubMed1990

Water contamination in North Cornwall: a retrospective cohort study into the acute and short-term effects of the aluminum sulphate incident in July 1988.

IN JULY 1988 the drinking water supply of part of Cornwall was contaminated with 20 tons of aluminum sulphate solution. Emergency measures ensured that aluminum sulphate levels in most parts of the water distribution system were rapidly reduced, but residents were supplied with water containing raised concentrations of aluminum and other metals for at least a few days. A retrospective cohort study compared 480 individuals in the exposed area with 532 individuals resident in an area served by a different water supply. The exposed group were more likely to complain of all 18 symptoms in the questionnaire enquiry. They had a significantly higher relative risk of experiencing painful joints. These symptoms were reported by less than a quarter of the respondents exposed to contaminated water. This may represent a previously unrecognised acute effect of water contamination with aluminum sulphate, but the study does not exclude the possibility that the threshold for symptom reporting was lowered by anxiety and by the publicity associated with the incident. The overall response rate of the study was low (45%) and reflects the difficulties in both carrying out and interpreting environmental epidemiological studies of acute incidents.

Accidents, Occupational↗