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Biomedical subjects

J Sheppard

Publications and source records attributed to J Sheppard.

At least 19 recordsLinked to original sources

Cellular immunity in salmonids infected with the microsporidial parasite Loma salmonae or exposed to non-viable spores.

Following a per os challenge of naive rainbow trout with live spores of Loma salmonae, head kidney mononuclear cells (MNC) in culture were able to proliferate in response to crude soluble parasite extract or intact dead spores. A significant response was seen by week 2 post-exposure and a maximum response developed by week 6 or 8, respectively. During this initial challenge, spore filled cysts developed on the gills of challenged fish, and the cysts ruptured by week 12 as is typical for microsporidial gill disease of salmonids (MGDS). Two weeks following this, fish were re-challenged with live spores, and in these fish an enhanced in vitro proliferative response of MNC was immediately apparent, and spore filled cysts did not develop. In contrast, when naive trout were given dead spores by intraperitoneal injection, the most pronounced proliferative responses of MNC developed earlier (week 2 PE) and the response was greater when cells were incubated in vitro with dead spores rather than with crude soluble extract. When these fish were re-challenged per os with live spores, a heightened proliferation in MNC was observed 4 weeks after this exposure and the fish likewise resisted development of xenomas. In fish infected orally or injected intraperitoneally with spores, a marked increase in the response to the mitogen concanavalin A was seen for 22 weeks post-exposure when compared to controls not receiving any spores.

Animals↗

Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb.

The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs. This structural anisotropy indicates that the initially generated fluid differs significantly from the equilibrium liquid.

Journal Article↗

Direct observation of the alpha-epsilon transition in shock-compressed iron via nanosecond x-ray diffraction.

In situ x-ray diffraction studies of iron under shock conditions confirm unambiguously a phase change from the bcc (alpha) to hcp (epsilon) structure. Previous identification of this transition in shock-loaded iron has been inferred from the correlation between shock-wave-profile analyses and static high-pressure x-ray measurements. This correlation is intrinsically limited because dynamic loading can markedly affect the structural modifications of solids. The in situ measurements are consistent with a uniaxial collapse along the [001] direction and shuffling of alternate (110) planes of atoms, and are in good agreement with large-scale nonequilibrium molecular dynamics simulations.

Journal Article↗

Atomic-scale visualization of inertial dynamics.

The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.

Journal Article↗

Clocking femtosecond X rays.

Linear-accelerator-based sources will revolutionize ultrafast x-ray science due to their unprecedented brightness and short pulse duration. However, time-resolved studies at the resolution of the x-ray pulse duration are hampered by the inability to precisely synchronize an external laser to the accelerator. At the Sub-Picosecond Pulse Source at the Stanford Linear-Accelerator Center we solved this problem by measuring the arrival time of each high energy electron bunch with electro-optic sampling. This measurement indirectly determined the arrival time of each x-ray pulse relative to an external pump laser pulse with a time resolution of better than 60 fs rms.

Journal Article↗

Mannitol in cardioplegia as an oxygen free radical scavenger measured by malondialdehyde.

Oxygen free radicals (OFRs) are associated with ischaemia-reperfusion injury involving many organs, including the heart, which can lead to depressed cardiac function and abnormalities in the cardiac ultrastructure. This is seen upon the release of the aortic crossclamp when the ischaemic myocardium is reperfused in patients undergoing cardiopulmonary bypass (CPB). Various studies have shown that by adding OFR scavenging agents or antioxidants to the CPB prime or cardioplegia, cardiac performance improves. Mannitol is an osmotic diuretic with free radical scavenging properties, which has been shown to reduce the extent of ischaemic injury and improve the function of the myocardium. This study evaluated how effective mannitol is as an OFR scavenger by administering different concentrations of cardioplegia antegrade into the aortic root, thus maximising its effects directly upon the myocardium rather than being diluted in the CPB prime. Thirty-three patients undergoing primary coronary artery bypass grafting (CABG) were, by double blind random selection, allocated into one of three groups: group 1, a control group (consisting of 11 patients) receiving no mannitol; group 2 (11 patients), receiving a concentration of 4 g/l; and group 3 (11 patients), receiving 8 g/l. Three blood samples were taken directly from the coronary sinus during bypass: the first sample at the start of bypass, just prior to the crossclamp being applied; the second sample just after removal of the crossclamp; and the third sample just prior to termination of bypass. All samples were then centrifuged and the plasma analysed for malondialdehyde (MDA) using high-performance liquid chromatography (HPLC). MDA, an endproduct of lipid peroxidation, causes cellular damage and disruption of cell membranes when tissue antioxidants are exhausted. The more MDA produced, the greater the depletion of tissue antioxidants secondary to OR formation during reperfusion when the aortic crossclamp is removed. HPLC is a useful biochemical study; however, it is not a direct indicator of depressed myocardial function, such as an invasive test would be, and this should be borne in mind. Statistically, the results do not show a significant difference among the three groups or among the three samples. However, a trend can be seen, which shows lower levels of MDA in the two groups receiving mannitol and there is an indication of a rise in MDA levels upon the start of reperfusion in the two groups receiving mannitol, but not the control group. It is concluded that further samples would be needed to find a significant difference in MDA concentrations.

Adult↗

Use of conductivity to monitor the treatment of acid mine drainage by sulphate-reducing bacteria.

Measurements of electrical conductivity were obtained during treatment of acid mine drainage (AMD) by sulphate-reducing bacteria (SRB) in fed-batch column reactors. The advantages of this method are that it is non-invasive, non-destructive, and rapid, giving real-time information. Conductivity measurements were taken on an hourly basis throughout the course of several experiments in which the SRB were exposed to different quantities of fresh AMD. Simultaneous measurements were taken in a column in which no SRB were present but were also exposed to the same volumes of fresh AMD. As treatment of the AMD progressed, increases in conductivity were measured, generally localized to two regions in the gravel bed: the top and bottom 10 cm (4"). Changes in conductivity were not always coincident with changes in ORP and pH, indicating that conductivity may be a more sensitive tool for locating and monitoring specific zones of SRB activity.

Biodegradation, Environmental↗

Complacent and conflicting scientific expertise in British and American drug regulation: clinical risk assessment of triazolam.

This paper presents a case study in the production and interpretation of regulatory science, focusing on the conflicting British and American clinical risk assessments of triazolam (Halcion) - the most controversial sleeping pill in the world. The regulation of triazolam is shown to be more permissive in the USA than in the UK. Six principal socio-political factors are put forward to explain this; differential regulatory trust; regulators' socio-technical data selections; medico-scientific disciplinary influences; organizational and professional interests; conflicts of interest of expert advisers; and the growth of the neo-liberal regulatory state. The risk assessments of both the British and American regulatory agencies are shown to be complacent relative to technical standards which the agencies themselves later accepted. It is suggested that, when the interests of pharmaceutical manufacturers and patients diverge, regulatory assessments are crucially affected by whether regulators are predisposed to award the benefit of the scientific doubts to the manufacturers or patients, and by the balance of such predispositions both within and between regulatory institutions of scientific expertise. The triazolam case indicates that the amount of trust placed in the pharmaceutical industry by the British American regulatory systems may hamper detection of flaws in manufacturers' medical data in a timely manner and, as a consequence, compromise patients' interests. Some policy implications for drug regulation are sketched.

Clinical Medicine↗

The clinical task.

Explore the source record for details and available documents.

Community Health Services↗

Latrine ownership as a protective factor in inflammatory trachoma in Egypt.

We investigated the association between inflammatory trachoma in children aged 1-5 and environmental and sociodemographic risk factors in a rural Nile Delta hamlet. Inflammatory trachoma clustered in households, emphasising the child-to-child nature of transmission in the hamlet. Multiple logistic regression analysis revealed three factors predicting inflammatory trachoma in children: the absence of a latrine in the household, school-age siblings with inflammatory trachoma, and additional same-age siblings (with or without disease) in the household. In the Egyptian setting the presence of pit latrines in all houses, even when full and unscreened, might result in a reduction in trachoma prevalence in this population from the current 49% to 35%. The construction of pit latrines may offer the simplest and most acceptable environmental method for reducing trachoma in this trachoma endemic area.

Child, Preschool↗

Trachoma and blindness in the Nile Delta: current patterns and projections for the future in the rural Egyptian population.

A population based survey of trachoma and blindness was conducted in a rural Nile Delta hamlet. Trachoma remains hyperendemic in this region. Active trachoma was common among preschool children; over half had moderate to severe disease. Of residents 25 years old 90% had substantial conjunctival scarring. Severe conjunctival scarring was commoner among women (84%) than men (58%), and three-quarters of older women had trichiasis/entropion compared with 57% of older men. Males and females had equivalent age specific rates of inflammatory disease. Blindness was associated with old age; 17% of residents aged 50 and over were blind. Estimates of blindness based on this survey and other surveys in Egypt indicate that blindness is still a serious public health problem in rural Egypt. The number of blind persons in Egypt will increase from an estimated 420,000 in 1980 to 868,000 by the year 2020. The current crude blindness rate of 1.8% is expected to increase to 2.3% in the year 2000 and to 3.2% in 2020.

Adolescent↗