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Biomedical subjects

P J Murphy

Publications and source records attributed to P J Murphy.

At least 19 recordsLinked to original sources

How red is a white eye? Clinical grading of normal conjunctival hyperaemia.

PURPOSE: To quantify the level of normal bulbar conjunctival hyperaemia using the Cornea and Contact Lens Research Unit (CCLRU) grading scale, and to investigate inter-observer agreement. METHODS: Bulbar conjunctival hyperaemia was assessed by two trained observers, using the CCLRU grading scale (zero to four units) interpolated into 0.1 increments, on the right eye of 121 healthy, non-contact lens-wearing subjects (male=58, female=63, median age=28 years, range 16-77). The eye was observed using a slit-lamp bio-microscope (x 10 magnification) under diffuse, white illumination. The subject's position of gaze was directed to allow grading of four quadrants: superior, nasal, inferior, and temporal conjunctiva. Bulbar redness was defined as the average of those four grades of conjunctival hyperaemia. A further twenty subjects were recruited to assess inter-observer agreement (male=8, female=12, median age=23 years). RESULTS: The average bulbar redness was 1.93 (+/-0.32 SD) units. The nasal (2.3+/-0.4) and temporal (2.1+/-0.4) quadrants were significantly redder than the superior (1.6+/-0.4) and inferior (1.7+/-0.4) quadrants (P<0.0001). Males had redder eyes than females by 0.2 units. Inter-observer 95% limits of agreement for bulbar redness was 0.38 units. CONCLUSIONS: The average bulbar redness of 1.9 units was higher than expected, reflecting the design of the grading scale. A bulbar redness of greater than 2.6 units may be considered abnormal, and a change in bulbar redness of > or =0.4 units may be significant.

Adolescent↗

Incidence and severity of keratoconus in Asir province, Saudi Arabia.

AIM: To assess the incidence and associated signs and symptoms of patients with keratoconus in Asir Province, Saudi Arabia. METHODS: 125 new keratoconus patients (51 male, 74 female; mean age 18.5 (SD 3.8) years; range 8--28 years) were recruited from referrals to the department of ophthalmology, Asir Central Hospital, over a 1 year period. Age, visual acuity, and keratometry were recorded along with clinical signs and symptoms. RESULTS: The incidence of keratoconus in Asir Province is 20 cases per 100,000 population. Also, the disease severity is high, as indicated by an early mean age (17.7 (3.6) years) with advanced stage keratoconus. Visual acuity, with either spectacles or rigid contact lenses, was 6/12 or better in 98% of eyes measured. Just over half (56%) of patients had atopic ocular disease. 16% of patients had a positive family history of the disease and 16% had atopic dermatitis (eczema and/or vitiligo). CONCLUSION: The incidence and severity of keratoconus in Asir Province, Saudi Arabia, is high with an early onset and more rapid progress to the severe disease stage at a young age. This might reflect the influence of genetic and/or environmental factor(s) in the aetiology of keratoconus.

Adolescent↗

The diversity of Phaseolus-nodulating rhizobial populations is altered by liming of acid soils planted with Phaseolus vulgaris L. in Brazil.

PCR-mediated restriction fragment length polymorphism (RFLP) analysis of the 16S-23S rRNA internally transcribed spacer (ITS) region and the 16S rRNA gene indicated that the rhizobial populations isolated from common bean (Phaseolus vulgaris L.) nodules in the unlimed soil from a series of five lime rates applied 6 years previously to plots of an acidic oxisol had less diversity than those from plots with higher rates of liming. Isolates affiliated with Rhizobium tropici IIB and Rhizobium leguminosarum bv. phaseoli were predominant independent of lime application. An index of richness based on the number of ITS groups increased from 2.2 to 5.7 along the soil liming gradient, and the richness index based on "species" types determined by RFLP analysis of the 16S rRNA gene varied from 0.5 to 1.4. The Shannon index of diversity, based on the number of ITS groups, increased from 1.8 in unlimed soil to 2.8 in limed soil, and, based on RFLP analysis of the 16S rRNA gene, ranged from 0.9 to 1.4. In the limed soil, the subpopulation of R. tropici IIB pattern types contained the largest number of ITS groups. In contrast, there were more R. leguminosarum bv. phaseoli types in the unlimed soil with the lowest pH than in soils with the highest pH. The number of ITS ("strain") groups within R. leguminosarum bv. phaseoli did not change with increased abundance of rhizobia in the soil, while with R. tropici IIB, the number of strain groups increased significantly. Some cultural and biochemical characteristics of Phaseolus-nodulating isolates were significantly related to changes in soil properties caused by liming, largely due to changes in the predominance of the rhizobial species groups.

Brazil↗

Rapid skin anaesthesia using high velocity lignocaine particles: a prospective placebo controlled trial.

BACKGROUND: Local anaesthetic creams (EMLA and Ametop) are used widely to provide pain free intravenous cannulation. However, they take a minimum of 45 minutes to become effective. AIMS: To evaluate a prototype device, dermal Powderject lidocaine (DPL), that delivers high velocity lignocaine particles into the skin. METHODS: A total of 132 children (aged 4-12 years) were randomised to receive either a sham delivery or a delivery of DPL on the skin at the antecubital fossa, or back of hand. Pain of intravenous cannulation was assessed four minutes later using self reporting behaviours and blinded observation with standard pain assessment tools. The trial was designed to measure both efficacy of skin anaesthesia and potential skin damage with increasing driving pressure of the device (30 or 40 bar), and different lignocaine particle sizes (<38 micrometer or 38-53 micrometer) in a block randomised fashion. RESULTS: A total of 128 patients were evaluable. There was a trend towards improved anaesthesia at higher device pressures at the antecubital fossa with both self reporting and blinded observation. Acceptable analgesia was achieved in 90% of patients for high pressure at both particle sizes compared to 60% and 40% for the sham device using self reporting measures. The observed differences using the blinded observer were similar: 90% v 20% (40 bar and small particles v sham), and 80% v 40% (40 bar and large particles v sham). At the back of hand the differences between active and sham devices were not significant. The device was well tolerated and not associated with pain on deployment. One patient had mild petechiae and oedema after deployment (Draize score of 3). CONCLUSIONS: This prototype device appears to provide significant skin anaesthesia at the antecubital fossa, but not at the back of hand. The device is not painful to use and causes only minor short term skin changes.

Anesthesia, Dental↗

Stoichiometry, abundance, and functional significance of the hsp90/hsp70-based multiprotein chaperone machinery in reticulocyte lysate.

Rabbit reticulocyte lysate contains a multiprotein chaperone system that assembles the glucocorticoid receptor (GR) into a complex with hsp90 and converts the hormone binding domain of the receptor to its high affinity steroid binding state. This system has been resolved into five proteins, with hsp90 and hsp70 being essential and Hop, hsp40, and p23 acting as co-chaperones that optimize assembly. Hop binds independently to hsp70 and hsp90 to form an hsp90.Hop.hsp70 complex that acts as a machinery to open up the GR steroid binding site. Because purified hsp90 and hsp70 are sufficient for some activation of GR steroid binding activity, some investigators have rejected any role for Hop in GR.hsp90 heterocomplex assembly. Here, we counter that impression by showing that all of the Hop in reticulocyte lysate is present in an hsp90.Hop.hsp70 complex with a stoichiometry of 2:1:1. The complex accounts for approximately 30% of the hsp90 and approximately 9% of the hsp70 in lysate, and upon Sephacryl S-300 chromatography the GR.hsp90 assembly activity resides in the peak containing Hop-bound hsp90. Consistent with the notion that the two essential chaperones cooperate with each other to open up the steroid binding site, we also show that purified hsp90 and hsp70 interact directly with each other to form weak hsp90.hsp70 complexes with a stoichiometry of 2:1.

Animals↗

Evidence for iterative ratcheting of receptor-bound hsp70 between its ATP and ADP conformations during assembly of glucocorticoid receptor.hsp90 heterocomplexes.

hsp90 and hsp70 are essential components of a five-protein system, including also the nonessential cochaperones Hop, hsp40, and p23, that assembles glucocorticoid receptor (GR).hsp90 heterocomplexes and causes the simultaneous opening of the steroid binding pocket to access by steroid. The first event in assembly is the ATP-dependent and hsp40 (YDJ-1)-dependent binding of hsp70 to the GR, which primes the receptor for subsequent ATP-dependent activation by hsp90 [Morishima, Y., Murphy, P. J. M., Li, D. P., Sanchez, E. R., and Pratt, W. B. (2000) J. Biol. Chem. 275, 18054-18060]. Here, we demonstrate that, during the priming step, ATP-bound hsp70 is converted to GR-bound hsp70 that is approximately 1/3 in the ADP- and approximately 2/3 in the ATP-dependent conformation. In the second step, hsp90, which is provided in the non-nucleotide-bound state, is converted to GR-bound hsp90 in the ATP-dependent conformation. The ATPase activity of hsp70 is K(+)-dependent, and the priming step is K(+)-dependent. Surprisingly, the subsequent hsp90-dependent step, which is rate-limiting for receptor activation, is also potassium-dependent. This suggests that GR-bound hsp70 is also converted from the ATP-dependent to the ADP-dependent conformation while it cooperates with hsp90 to activate steroid binding activity. Because the priming step requires both sustained high levels of ATP and YDJ-1 for optimal activity and because both steps require potassium, we predict that receptor-bound hsp70 undergoes iterative ratcheting between its ATP- and ADP-dependent conformations in opening the hydrophobic steroid binding pocket.

Adenosine Diphosphate↗

Illusion processing in hemispatial neglect.

Twelve patients with hemispatial neglect and two control groups were tested to examine the effects of the Müller-Lyer and Judd illusions on bisection behaviour. The studies were designed to investigate whether neglect patients were indeed unaware of the left sides of the illusory figures. In Experiment 1, participants were asked to describe the illusory figures prior to bisection, whereas in Experiment 2, they compared two illusions whose fins, in the critical condition, differed on the left and then performed the bisection. It was found that the illusions worked equally well in all three groups. Interestingly, apart from one exception, almost all neglect patients explicitly reported the left-sided fins in Experiment 1. Only five patients failed to do so but only on an average of 16% of trials. In Experiment 2, six patients made errors in the comparison task but four of these patients did not neglect any left-sided fins in Experiment 1 (with the exception of three overall trials for LC and EdR). This finding seems a good indication that the two tasks differ in their requirements. The comparison task may be perceived as harder as it requires discrimination rather than detection and thus lead to more neglect type errors than the bisection task. In one neglect patient, the illusions consistently failed to work. This patient presented with an occipito-temporal and basal ganglia lesion and the mechanisms responsible for the processing of simple visual features might have possibly been impaired in her case.

Aged↗

Long-term time estimation is influenced by circadian phase.

The adaptive significance of a putative time sense in humans remains unclear as do the factors that underlie the capacity to gauge the passage of time. Here we show that the subjective assessment of relatively long durations varies systematically as a function of time of day. Specifically, the subjective clock ran relatively faster when the circadian oscillation of body temperature was on the rise and relatively slower on the declining portion of the temperature curve. The overall result was a rather labile clock that, on average, ran slow relative to physical time. The results provide a glimpse into an underexplored aspect of how humans use their endogenous clocks in the most fundamental way--to gauge the passage of time.

Adolescent↗

The minimum stimulus energy required to produce a cooling sensation in the human cornea.

PURPOSE: To estimate the minimum stimulus energy required to stimulate the corneal nerves, using a thermally cooling stimulus. METHODS: The localised temperature change produced in the pre-corneal tear film by the air-pulse stimulus of the Non-Contact Corneal Aesthesiometer (NCCA) was analysed using a thermal imaging camera. Assuming that the cornea behaves as a near perfect black-body, the threshold for energy loss was calculated by combining Stefan-Boltzmann's law and Kirchoff's law for imperfections in black-body radiation, taking into account the likely thermal conductivity of the human cornea. RESULTS: The average normal subject has a threshold for detecting a cooling effect when the local corneal tear film surface temperature drops from a mean of 33.2-32.9 degrees C (i.e. 0.3 degrees C), over a 1 mm diameter circular area (0.785 mm2), and a stimulus time duration of 0.9 s. This gives rise to a sensation threshold for perceiving a loss of heat energy of 7.0 ergs, or 7.0 x 10(-7) joules. CONCLUSION: The cornea possesses stimulus specific receptors, which have an exquisite sensitivity to a rapid, thermally cooling stimulus.

Cold Temperature↗

Extraocular phototransduction and circadian timing systems in vertebrates.

It is widely accepted that, for organisms with eyes, the daily regulation of circadian rhythms is made possible by light transduction through those organs. Yet, it has been demonstrated repeatedly in recent years that ocular light receptors that mediate vision, at least in mammals, are not the same photoreceptors involved in circadian regulation. Moreover, it has been recognized for many years that circadian regulation can occur in organisms without eyes. In fact, extraocular circadian phototransduction (EOCP) appears to be a phylogenetic rule for the vast majority of species. EOCP has been reported in every nonmammalian species studied to date. In mammals, however, the story is very different. This paper presents findings from studies that have examined specifically the capacity for EOCP in vertebrate species. In addition, the literature addressing noncircadian aspects of extraocular phototransduction is briefly discussed. Finally, possible mechanisms underlying EOCP are discussed, as are some of the implications of the presence, or absence, of EOCP across phylogeny.

Amphibians↗

The effect of long-term, daily contact lens wear on corneal sensitivity.

PURPOSE: To assess the effect of long-term, daily-wear soft contact lenses and rigid gas permeable (RGP) contact lenses on corneal sensitivity using a noninvasive, air-pulse stimulus. METHODS: The central and peripheral (temporal, medial, inferior) corneal sensation thresholds of 40 non-lens wearers, 40 soft lens wearers, and 40 RGP lens wearers were assessed using the Non-Contact Corneal Aesthesiometer (NCCA). The individuals who wore contact lenses were grouped according to the number of years of lens wear (10 years or less, 11-20 years, and 21 years or more). RESULTS: Although a significant reduction in corneal sensitivity was found between the contact lens wearers and non-lens wearers (p = 0.000), no difference was found between the two lens-type subgroups (p = 0.939). This pattern of significance was repeated at each of the peripheral test locations. No relationship between corneal sensitivity and years of lens wear was found centrally (r2 = 0.004) or at any of the peripheral test locations. No significant difference was found between the central corneal sensation thresholds for the different subgroups of lens wear duration (p = 0.469) or for any of the peripheral test locations. CONCLUSIONS: Both soft and RGP lens wear produce a similar type of corneal sensitivity loss, although the mechanism for this loss is different for the two lens types. The extent of sensitivity loss is not related to the duration of lens wear and appears to plateau after the first few months of wear. No topographical variation in sensitivity loss was found with lens type or with the duration of lens wear.

Adult↗

The effect of scleral search coil lens wear on the eye.

BACKGROUND/AIM: Scleral search coils are used to measure eye movements. A recent abstract suggests that the coil can affect the eye by decreasing visual acuity, increasing intraocular pressure, and damaging the corneal and conjunctival surface. Such findings, if repeated in all subjects, would cast doubt on the credibility of the search coil as a reliable investigative technique. The aim of this study was to reassess the effect of the scleral search coil on visual function. METHODS: Six volunteer subjects were selected to undergo coil wear and baseline measurements were taken of logMAR visual acuity, non-contact tonometry, keratometry, and slit lamp examination. Four drops of 0.4% benoxinate hydrochloride were instilled before insertion of the lens by an experienced clinician. The lens then remained on the eye for 30 minutes. Measurements of the four ocular health parameters were repeated after 15 and 30 minutes of lens wear. The lens was then removed and the health of the eye reassessed. RESULTS: No obvious pattern of change was found in logMAR visual acuity, keratometry, or intraocular pressure. The lens did produce changes to the conjunctival and corneal surfaces, but this was not considered clinically significant. CONCLUSION: Search coils do not appear to cause any significant effects on visual function. However, thorough prescreening of subjects and post-wear checks should be carried out on all coil wearers to ensure no adverse effects have been caused.

Adult↗

Early production of rhizopine in nodules induced by Sinorhizobium meliloti strain L5-30.

The rhizopine L-3-O-methyl-scyllo-inosamine (3-O-MSI) is metabolized by approximately 10% of the strains of Rhizobium leguminosarum by. viciae and Sinorhizobium meliloti. Rhizopine strains enjoy a substantial competitive advantage in nodulation, which is manifest before 14 days post-inoculation, implying that rhizopine is produced before this time. We were able to detect this compound in the roots of alfalfa (Medicago sativum L. cv. Hunter River) four days after germination (six days post-infection) with S. meliloti strain L5-30 by gas chromatography-mass spectrometry (GC-MS). At four days, nodules were not visible, and the concentration of rhizopine was extremely low, estimated at 67 pg/gfw (picograms/gram fresh weight). The amount increased gradually but remained low until 16 days, when there was a 50-fold increase from day four, by which time nodules were well established. This pattern of synthesis is consistent with previous studies indicating that rhizopine synthesis is regulated by nifA/ntrA regulatory genes, which are maximally expressed in bacteroids at the onset of nitrogen fixation. However, the low level of rhizopine synthesis must be responsible for the early effects on competition for nodulation. Production of rhizopine at this time most likely results from micro-aerobic induction of mos genes in free-living bacteria, either in the infection threads or in the rhizosphere.

Gas Chromatography-Mass Spectrometry↗

Enhancement of REM sleep during extraocular light exposure in humans.

This study examined the effects on sleep of light administered to an extraocular site. A 3-h photic stimulus was applied to the popliteal region during sleep in 14 human subjects. Each subject also underwent a control stimulus condition during a separate laboratory session. The proportion of rapid eye movement (REM) sleep during the 3-h light administration session increased by an average of 31% relative to the control condition. The frequency but not the duration of REM episodes was altered during light exposure, thereby shortening the REM/non-REM (NREM) cycle length. No other sleep stages were significantly affected during light administration nor was sleep architecture altered after the light-exposure interval. These results confirm that extraocular light is transduced into a signal that is received and processed by the human central nervous system. In addition, they expand to a novel sensory modality previous findings that REM sleep can be enhanced by sensory stimulation.

Circadian Rhythm↗