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Biomedical subjects

E A Harris

Publications and source records attributed to E A Harris.

At least 37 records · Page 2Linked to original sources

Mass mortality of common dolphins (Delphinus delphis) in south west England due to incidental capture in fishing gear.

In the first quarter of 1992, 118 dolphin carcases, of which 54 were positively identified as common dolphins (Delphinus delphis), were found stranded on the coast of Cornwall and Devon. To determine the cause, detailed post mortem examinations were carried out on 38 of the carcases, and the results were compared with those from 20 common dolphins that stranded on the coast of Cornwall and Devon in the previous 15 months. There was no evidence that the deaths were due to an infectious or parasitic disease, or acute intoxication by any of the algal toxins, trace metals or chlorinated hydrocarbons measured. However, 30 of the 38 dolphins showed signs associated with incidental capture in fishing gear. Skin lesions characteristic of capture in a small-meshed net and the predominance of recently ingested Atlantic mackerel (Scomber scombrus) and pilchard (Sardina pilchardus) in the stomachs of the dolphins suggested that they had been caught in the trawl or purse seine nets used for these fish. There is insufficient information to explain why this high mortality occurred in 1992 and not in other years.

Animal Diseases↗

An unusual community outbreak of influenza A.

The Hong Kong H3N2 subtype of influenza A virus appeared in 1968 and since then has caused epidemics of varying degrees of severity. We describe a community outbreak of influenza A H3N2 which occurred in members of a bowls club in an English rural village in late April 1989. The explosive onset, high attack rate (34/41 = 83 per cent) in those exposed, and the clinical presentation initially suggested a toxic or allergic aetiology. Twenty-three persons consulted their general practitioners; before the diagnosis was made all cases were considered to merit antibiotic therapy and 17/23 were prescribed steroids or bronchodilators on account of persisting severe wheeze and chest tightness. One of the 23 was admitted to hospital. There were no deaths. Influenza vaccination is recommended for people at special risk but protective efficacy is relatively low and short-lived. Only two of the group had received influenza vaccination since the beginning of October 1988 and both became symptomatic. The use of amantadine for the prevention and early treatment of influenza A in selected situations merits serious consideration, provided the diagnosis is made sufficiently early.

Aged↗

Expression of the human gamma-globin gene after retroviral transfer to transformed erythroid cells.

Regulation of the human fetal (gamma) globin gene and a series of mutant gamma-globin genes was studied after retroviral transfer into erythroid cells with fetal or adult patterns of endogenous globin gene expression. Steady-state RNA from a virally transferred A gamma-globin gene with a normal promoter increased after induction of erythroid maturation of murine erythroleukemia cells and comprised from 2% to 23% of the mouse beta maj-globin RNA level. RNA expression from the virally transferred A gamma-globin gene comprised 23% of the endogenous G gamma- + A gamma-globin expression in K 562 cells after treatment with hemin. Expression from a virally transferred gamma- or beta-globin gene exceeded endogenous gamma- or beta-globin expression by a factor of 6 or more in the human erythroleukemia line KMOE, in which the endogenous globin genes are weakly inducible. In these experiments, no difference in expression was observed between the gene with the normal promoter and an A gamma-globin gene with a point mutation in its promoter (-196 C-to-T) that has been associated with hereditary persistence of fetal hemoglobin (HPFH). To test for cis-acting determinants located within the introns of the gamma-globin gene, expression was measured from a set of gamma-globin genes configured with either intron alone or with neither intron. In contrast to an intronless beta-globin gene, which is not expressed in MEL cells, the intronless gamma-globin gene was expressed in MEL cells at 24% of the level of an intron-containing gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Medical research.

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Government↗

High-level beta-globin expression after retroviral transfer of locus activation region-containing human beta-globin gene derivatives into murine erythroleukemia cells.

The locus activation region (LAR) of the human beta-globin-like gene cluster is characterized by a group of four DNase I hypersensitive sites, which arise specifically in erythroid tissues and are required for a normal pattern of beta-globin-like gene expression. The hypersensitive sites are found at positions 6.1, 10.9, 14.7, and 18 kilobase pairs (kbp) 5' of the epsilon-globin gene. Recently functional assays of the LAR that tested determinants for all four hypersensitive sites showed that expression of the human beta-globin gene was increased to normal or near-normal levels in both transgenic mice and erythroid cells. We constructed retroviral vectors with a human beta-globin gene and the determinant for a single hypersensitive site and measured beta-globin gene expression after retroviral infection of murine erythroleukemia cells. Fragments for the hypersensitive sites at -18 or -10.9 kbp increased human beta-globin RNA levels respectively to 35% or 132% of the endogenous mouse beta maj-globin RNA level. In addition, greater expression was also observed for the neomycin phosphotransferase RNA, which was transcribed from the retroviral LTR, showing that the LAR fragments activated expression from a heterologous promoter. In the context of gene-transfer experiments ultimately aimed at gene therapy, our results show that LAR determinants lead to an increased level of human beta-globin RNA expression after retroviral transfer into erythroid cells. But inclusion of LAR determinants in retroviral vectors also entails the potential risk of activating the expression of nonglobin genes in erythroid cells.

Animals↗

Prolonged measurement of respiratory tidal and minute volumes.

A method is described by which successive expiratory tidal and minute volumes are measured by a flow-resistance device (pneumotachometer) which is automatically calibrated up to three times per minute by intermittent collection of gas in a spirometer. Records of any duration, at rest or during exercise, can be made without interruption. The method automatically corrects for the composition of gas flowing through the pneumotachometer, and is suitable for minute-to-minute or breath-by-breath studies of gas exchange or respiratory timing.

Humans↗

Gas-mixing efficiency in a mathematical model of the lung.

Non-uniform composition of gas in the lungs may arise because of uneven dilution of alveolar with inspired gas by convection (bulk flow) or because of the finite rates of molecular diffusion in the small air-spaces. Such non-uniformity represents 'mixing inefficiency' which may be expressed by the difference between the effective dead-space ('ventilatory dead-space', VDV) and the actual airway dead-space ('Fowler dead-space', VDF). This expression of mixing inefficiency does not distinguish between convective and diffusive mechanisms. We show, from simulated gas wash-out of an asymmetrical, two-compartment model of the lung, that a third dead-space ('wash-out dead-space', VDW) enables this distinction to be made: VDV-VDW reveals convective, and VDW-VDF diffusive, mixing inefficiency. The position of the branch point subtending the two compartments greatly affects the outcome, however. When the branch point is relatively peripheral, inefficiency is mainly diffusive; when it is relatively central, inefficiency is mainly convective. These findings indicate how mixing efficiency may be measured more selectively than at present in real lungs.

Computer Simulation↗