Dark-adaptation of the human rod system

Following substantial bleaching, dark-adaptation thresholds of a complete rod monochromat and of a subject with normal colour vision were measured using a Wright colorimeter. When precautions were taken to ensure that the fixation point fell on the same retinal area during the threshold measurements as during the bleaching period, the dark-adaptation threshold curves of the rod monochromat followed exactly the same course as those of the normal subject subsequent to the cone-rod break of the long-term, normal dark-adaptation curve; irrespective of the intensity and the duration of the bleaching and the wavelength of the test stimulation. In contrast to the normal subject, however, the dark-adaptation curves of the rod monochromat showed no evidence of any cone function at photopic intensities. Furthermore, as opposed to previous measurements which show a simple linear relationship between fraction of bleached rhodopsin and log threshold, the present results show that there is a close linearity between log fraction of bleached rhodopsin and log threshold. This linear relationship is obtained despite varying extents of bleaching and subsequent dark-adaptation periods.     

Identification and characterization of a benzothiophene inhibitor of herpes simplex virus type 1 replication which acts at the immediate early stage of infection.

Analysis of a large compound library in a high throughput virus infection assay screen identified the benzothiophene PD146626 as a potent and specific inhibitor of herpes simplex virus type 1 (HSV-1) replication. PD146626 possessed an EC(50) and EC(90) against HSV-1 of 0.1 and 1 microM, respectively, and mediated no detectable cytotoxicity in cells at concentrations up to 1 microM. Western blot analyses and time of addition experiments demonstrated that in the presence of PD146626 HSV-1 underwent a specific block in viral gene expression at the immediate early stage. However, several observations indicated that a cellular function rather than a viral immediate early transactivator protein represented the molecular target for PD146626, including the lack of resistance of VP16 and ICP0 mutant viruses to the compound, the inability to select resistant strains of HSV-1 following exhaustive serial passaging of virus in the presence of the compound, and the sensitivity of human cytomegalovirus, which lacks VP16 and ICP0 homologs, to the compound. Moreover, kinetic studies suggested an unusual pattern of responsiveness of the host cell to PD146626, in that the compound could induce an extended antiviral state in cells after only a brief exposure. Together these results suggest that PD146626 targets a novel cellular function that is critical for the expression of HSV-1 immediate early genes but not host cell genes.     

Muscle ceramide content in man is higher in type I than type II fibers and not influenced by glycogen content

The purpose was to determine the relation between visual feedback gain and variability in force and whether visual gain-induced changes in force variability were associated with frequency-specific force oscillations and changes in the neural activation of the agonist muscle. Fourteen young adults (19–29 years) were instructed to accurately match the target force at 2 and 10% of their maximal voluntary contraction with abduction of the index finger. Force was maintained at specific visual feedback gain levels that varied across trials. Each trial lasted 20 s and the amount of visual feedback was varied by changing the visual gain from 0.5 to 1,474 pixels/N (13 levels; equals ~0.001–4.57°). Force variability was quantified as the standard deviation of the detrended force data. The neural activation of the first dorsal interosseus (FDI) was measured with surface electromyography. The mean force did not vary significantly with the amount of visual feedback. In contrast, force variability decreased from low gains compared to moderate gains (0.5–4 pixels/N: 0.09 ± 0.04 vs. 64–1,424 pixels/N: 0.06 ± 0.02 N). The decrease in variability was predicted by a decrease in the power of force oscillations from 0–1 Hz (~50%) and 3–7 Hz (~20%). The activity of the FDI muscle did not vary across the visual feedback gains. These findings demonstrate that in young adults force variability can be decreased with increased visual feedback gain (>64 pixels/N vs. 0.5–4 pixels/N) due to a decrease in the power of oscillations in the force from 0–1 and 3–7 Hz.     

‘The analytic–synthetic distinction and conceptual analyses of basic health concepts’

Within philosophy of medicine it has been a widespread view that there are important theoretical and practical reasons for clarifying the nature of basic health concepts like disease, illness and sickness. Many theorists have attempted to give definitions that can function as general standards, but as more and more definitions have been rejected as inadequate, pessimism about the possibility of formulating plausible definitions has become increasingly widespread. However, the belief that no definitions will succeed since no definitions have succeeded is an inductive objection, open to realist responses. The article argues that an influential argument from philosophy of language constitutes a more fundamental objection. I use disease as an example and show that this argument implies that if a common understanding of disease can be analysed into a definition, then this is a non-trivial definition. But any non-trivial analysis must be viciously circular: the analysis must presuppose that disease can be defined, but this is what the analysis is supposed to yield as a result. This means, the article concludes, that disease and other controversial health concepts do not have analyses grounded in a common language. Stipulative and contextual definitions can have local significance, but the normative roles of such definitions are at the same time limited.     

Incidence of Lip Cancer in the Male Norwegian Agricultural Population

OBJECTIVE: To explore lip cancer (LC) associations with work environmental exposures in a record-linkage study of Norwegian farmers. We hypothesize immunosuppressive substances (e.g. mycotoxins, pesticides) to influence LC incidence. METHODS: A cohort of 131,243 male Norwegian farmers born 1925-1971 was established by cross-linkage of national registers and followed up through 1999 for incident LC, (ICD-7 site 140) in the Cancer Registry of Norway. Farm production data from agricultural censuses 1969-1979 and meteorological data on solar radiation and fungal forecasts (events of wet and temperate conditions known to favour fungal growth and mycotoxin formation) served as exposure proxies. Adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated using Poisson regression. RESULTS: We identified 108 LC cases (rate 4.4 per 100,000 person-years). We found LC to be moderately associated with horses on the farm (RR = 1.6, CI = 1.0-2.4), construction work employment (RR = 1.7, CI = 1.1-2.6), pesticide use (RR = 0.7, CI = 0.4-1.0), grain production (RR = 1.3, CI = 0.9-2.1) and increasing levels of fungal forecasts (RR = 1.6, CI = 0.9-2.8 in the highest two quartiles). CONCLUSION: Moderate associations of LC with grain production and fungal forecasts and the negative association with pesticide could possibly be explained by exposure to immunosuppressive mycotoxins. Some of the associations observed could be explained by solar exposure.     

Olivary afferents from the pretectal nuclei in the cat

Summary The organization of the projection from the pretectal region to the inferior olive in the cat was studied by means of retrograde protein tracing and experimental degeneration. Small injections of horseradish peroxidase (HRP) were made into various parts of the inferior olive from a ventral approach. The number of nerve cells in the pretectal nuclei retrogradely labelled with HRP was counted and put in relation to the site of injection. Labelled cells were only found in the posterior pretectal nucleus (NPP), the nucleus of the optic tract (NOT) and the anterior pretectal nucleus (NPA). Most labelled cells were found in NPP and NOT in cases in which the rostral or caudal levels of the principal olive were labelled by the injection. NAP labelling occurred in one case with a very rostral injection of the inferior olive. Unilateral electrolytical destruction of the pretectal region produced terminal degeneration in the ipsilateral inferior olive. The heaviest ipsilateral degeneration was found in the upper half of the principal and dorsal accessory olives, and caudally in the ventrolateral outgrowth, the dorsal cap and nucleus with the adjacent part of the medial accessory olive. Some functional implications of the findings are discussed.     

The origin and termination of the dentatorubral fibres in the cat as studied with retrograde and anterograde transport of peroxidase labelled lectin

Summary The dentatorubral projection in the cat was studied by means of retrograde and anterograde transport after implantations of crystalline wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the red and dentate nuclei, respectively. Our retrograde transport findings give evidence that rubral afferents originate in the contralateral dentate nucleus, mainly dorsally in its central part. The dentate implantations (with no contamination of the adjacent interposed nuclei) show that in the cat the great majority of the dentatofugal fibres leave the ipsilateral brachium conjunctivum to decussate below the red nucleus. Scattered crossing fibres also penetrate the contralateral red nucleus at all caudorostral levels on their way to the contralateral thalamus. Terminal fibres were found only in the rostral part of the red nucleus, but no retrogradely labelled rubral cells were observed. The findings are discussed in relation to previous studies on the dentatorubral projection.