Commercially sensitive ethics.
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Biomedical subjects
Publications and source records attributed to E A Harris.
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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.
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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)
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.
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.
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.
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A case is presented of infection by Oesophagostomum, a nematode worm, producing a cutaneous nodule in man. Of the 70 individual cases reported in man it is believed that this is the first in which the worm has produced a lesion outside the gastro-intestinal tract and without evidence of bowel infection. This finding suggests either that the worm is able to achieve direct skin penetration or that it can be disseminated from the bowel via the bloodstream or the lymphatics. The pathology caused by Oesophagostomum and the possible modes of infection are discussed in relation to studies in animals, particularly simians and cattle.