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Biomedical subjects

B Hayes

Publications and source records attributed to B Hayes.

At least 19 recordsLinked to original sources
PubMed2002

Automated recognition of intracellular organelles in confocal microscope images.

Recognition of the localisation of intracellular proteins is essential to the understanding of their function. It is usually made through knowledge of and comparison to the distribution of well-characterised intracellular organelles by experts in cell biology. We have automated this process in order to achieve a more objective and quantitative assessment of the protein distribution within the cell, which can be employed by the less experienced cell biologist and may be utilised as a training program for inexperienced users, or as a high throughput localisation program for novel genes in functional analysis. Here we describe the development and testing of a classification system based on a modular neural network trained with sets of confocal sections through cell lines fluorescently stained for markers of key intracellular structures. The system functioned well in spite of the variability in pattern that occurs between individual cells and performed with 97% accuracy, which gives us confidence in the method and in its future development. It is envisaged that this program will aid the design of further experiments utilising colocalisation with known organelle marker proteins, in order to confirm putative trafficking pathways and protein--protein interactions of the protein of interest.

Animals↗
PubMed2001

Immunohistochemical localization of adenosine A1 receptors in human brain regions.

Adenosine exerts its physiological actions by binding to G-protein coupled receptors, four of which have been identified and cloned to date (A1, A2a, A2b and A3). Here we report the development of anti-human adenosine A1, receptor anti-peptide polyclonal antibodies and their use to define the distribution of A1, receptors in human brain regions, spinal cord and trigeminal ganglia by an immunohistochemical approach. Although the distribution of adenosine A1, receptor and its mRNA in the human brain has been investigated in the past by autoradiography and in situ hybridization, this is the first demonstration of localization of the A1, receptors by immunohistochemical means. Our localization data broadly agree with immunohistochemical data published for the human brain obtained using other experimental approaches. Furthermore, we have demonstrated the novel finding that abundant expression of the adenosine A1, receptor protein occurs in the trigeminal ganglia, which may be suggestive of a role of this receptor in analgesia.

Adult↗
PubMed2001

The life sciences Global Image Database (GID).

Although a vast amount of life sciences data is generated in the form of images, most scientists still store images on extremely diverse and often incompatible storage media, without any type of metadata structure, and thus with no standard facility with which to conduct searches or analyses. Here we present a solution to unlock the value of scientific images. The Global Image Database (GID) is a web-based (http://www.gwer.ch/qv/gid/gid.ht m ) structured central repository for scientific annotated images. The GID was designed to manage images from a wide spectrum of imaging domains ranging from microscopy to automated screening. The annotations in the GID define the source experiment of the images by describing who the authors of the experiment are, when the images were created, the biological origin of the experimental sample and how the sample was processed for visualization. A collection of experimental imaging protocols provides details of the sample preparation, and labeling, or visualization procedures. In addition, the entries in the GID reference these imaging protocols with the probe sequences or antibody names used in labeling experiments. The GID annotations are searchable by field or globally. The query results are first shown as image thumbnail previews, enabling quick browsing prior to original-sized annotated image retrieval. The development of the GID continues, aiming at facilitating the management and exchange of image data in the scientific community, and at creating new query tools for mining image data.

Biological Science Disciplines↗
PubMed2001

"Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients.

The results of a novel approach to the use of ketamine in refractory cancer pain are reported. In this prospective, multicenter, unblinded, open-label audit, 39 patients (with a total of 43 pains) received a short duration (3 to 5 days) ketamine infusion. The initial dose of 100 mg/24 hr was escalated if required to 300 mg/24 hr and then to a maximum dose of 500 mg/24hr. The overall response rate was 29/43 (67%). Analysis of results according to pain mechanisms showed that 15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who appeared to respond, it is possible that another concurrent intervention may have contributed in whole or part for the pain relief observed. After cessation of ketamine, 24/29 maintained good pain control, with a maximum documented duration of eight weeks. However, 5 of the initial 29 responders experienced a recurrence of pain within 24 hours, and ketamine was recommenced. Of these, 2 underwent another intervention for pain control while 3 continued on ketamine until their deaths between two and four weeks later. Twelve patients reported adverse psychomimetic effects, with the incidence rising with increasing dose. Four of these were non-responders and the ketamine was stopped. Eight were responders, and in 3 the adverse effects were rendered acceptable with dose reduction; the other 5 rejected a dose reduction. The results reported suggest the need for further investigation of the place of ketamine in cancer pain management.

Adult↗
PubMed2001

The wartime experience of Australian Army nurses in Vietnam, 1967-1971.

AIMS: To provide a synthesis of the experience of nursing in the Vietnam War. RATIONALE: War and nursing are linked unequivocally. As battles have raged over the centuries, nurses have attended the ill and wounded soldiers, nursing them back to health or into death and the study of this phenomenon forms a significant part of Australia's nursing history. However, a review of the Australian scholarly nursing and military history literature revealed that the experiences of Australian nurses in the Vietnam War has not been widely published. In an attempt to redress this gap in Australian nursing and military history, the aim of this study was to analyse the nature of the nursing work in the Vietnam War, and to increase awareness and understanding of the experience of nurses in the war within the nursing profession. METHODS: Using oral history interviews, this study investigated the nature of nursing work as experienced by 17 Australian Army nurses who served in the Australian Military Hospital in Vung Tau between 1967 and 1971. FINDINGS: The vast majority of the nursing sisters sent to Vietnam knew little about the type of work or the environment into which they were entering and were, therefore, clinically unprepared. It appeared that, by virtue of their being a nurse, it was an expectation that the nurses would adapt to the nature of their work in the war zone. However, this study also revealed that, although the nurses adapted professionally, their memories of their experiences have affected many personally. CONCLUSIONS: This paper will increase current knowledge significantly regarding the phenomenon of nursing in the Vietnam War, enabling a greater understanding of the experience.

Adult↗
PubMed2000

Investigation of an outbreak of gastroenteritis caused by Norwalk-like virus, using solid phase immune electron microscopy.

In February 1993, 95 persons (47 patients and 48 staff members) were affected by an hospital outbreak of viral gastroenteritis. Using direct electron microscopy (EM) the causative agent was identified as a small round structured virus. This was confirmed as a Norwalk-like virus using solid phase immune electron microscopy (SPIEM). Of 94 stool samples examined, 12 (13%) samples containing small round structured viruses (SRSV) were SPIEM positive for Norwalk-like virus. A further 25 (27%) samples contained small round featureless virus (SRFV) identified by direct EM and were negative on SPIEM. The illness was characterized by preceding influenza-like symptoms in 76% of cases followed by vomiting (76%), diarrhoea (79%) and abdominal pain (79%). One fatality was recorded. The outbreak lasted for 15 days, with a peak incidence of new cases amongst patients and staff occurring on day 5. It was controlled through a combination of ward closures, patient cohorting, suspension of duties for affected staff and disinfection procedures. Difficulties were encountered in the education of staff and in the implementation of environmental control measures. Screening of hospital catering services and a case control study, carried out among affected staff members, failed to identify a foodborne source. Consumption of tap water in the hospital was commoner among affected staff members than among controls, but this did not reach significance (P = 0.1).

Aged↗
PubMed1999

Abuse liability assessment of neuroprotectants.

There has been considerable interest in the potential of N-methyl-D-aspartate (NMDA) receptor antagonists in the treatment of a diverse group of neurological disorders including cerebral ischemia and neurodegeneration. The amino acids L-glutamate and L-aspartate have been shown to possibly mediate excitatory synaptic transmission in the central nervous system (CNS) via selective excitatory amino acid receptors. Competitive and noncompetitive antagonists acting at the NMDA receptors have been shown to possess relevant activity. However, NMDA antagonists can produce a variety of adverse neurobehavioral effects in both animals and humans. These adverse events are particularly pronounced with NMDA antagonists (phencyclidine (PCP), ketamine, and MK-801) that have dissociative anesthetic properties and block NMDA receptor-mediated responses by binding to the cation channel of the NMDA receptor complex. When a new pharmaceutical product demonstrates structural similarity and/or a similar pharmacological profile with a known drug of abuse, the characterization of its abuse potential is needed by the FDA for scientific review. The abuse liability assessment is based upon an evaluation of data on the chemistry, pharmacology (preclinical and clinical), pharmacokinetics, and pharmacodynamic profiles of the drug, and the adverse events/effects reported in clinical trials. The evaluation of the drug's abuse potential is determined relative to pharmacologically similar drugs. This includes determination of the drug's receptor binding efficacy, preclinical pharmacology, reinforcing efficacy, discriminative stimulus effects, dependence-producing potential, pharmacokinetics, and assessment of the clinical efficacy-safety database relative to abuse and clinical abuse liability studies. It has been well established that high-affinity noncompetitive NMDA antagonists have reinforcing efficacy and can serve as discriminative stimuli in operant procedures. In a variety of species in drug discrimination studies, each antagonist is capable of generalizing to the others, and it is believed that these effects may be mediated through the NMDA blockade. The generalization of each substance for another suggests production of common subjective effects in humans.

Animals↗
PubMed1997

Evidence for recovery of spatial learning following entorhinal cortex lesions in mice.

The influence of entorhinal cortex lesions on behaviour and concommitant changes in synaptophysin immunoreactivity (IR) in the denervated dentate gyrus was assessed. Male, C57/B6 mice received either bilateral (BI), unilateral (UNI), or no lesion (SHAM) to the entorhinal cortex. At various stages post-lesion the animals were evaluated in tests to examine neurological and cognitive (spatial and cued learning, Morris water maze) function. UNI lesioned animals from 6-36 days post-lesion showed no neurological nor marked cued learning deficit, yet a profound spatial learning deficit. However by 70 days post-lesion, spatial learning ability was clearly evident. In contrast, BI lesioned animals showed severe spatial learning deficits throughout the test period (6-70 days), cued learning was also impaired. In parallel groups of UNI lesioned mice, 6-36 days post-lesion there was a marked reduction (-40%) in synaptophysin IR in the dentate gyrus molecular layer. However by 70 days post-lesion a clear increase in this measure was noted. Changes in the expression of the growth associated protein, GAP43, were also noted over this period. Taken together, the present results suggest some recovery of spatial learning following unilateral entorhinal cortex lesions in mice. This behavioural recovery of a hippocampally dependant task may be associated with a recovery of function related to the synaptic remodelling and elevation of synapse number in the denervated hippocampus, as evidenced by changes in synaptophysin and GAP43 IR.

Animals↗
PubMed1997

Rat basophilic leukaemia (RBL) cells overexpressing Rab3a have a reversible block in antigen-stimulated exocytosis.

The rat basophilic leukaemia (RBL) cell line has been widely used as a convenient model system to study regulated secretion in mast cells. Activation of these cells through the high-affinity receptor for IgE (Fcepsilon-RI) results in degranulation and the extracellular release of mediators. There is good evidence of a role for GTPases in mast cell degranulation, and a number of studies with peptides derived from the Rab3a effector domain have suggested that Rab3a may function in this process. However, in neuroendocrine cells, overexpression of Rab3a can act as a negative regulator of stimulated exocytosis [Holz, Brondyk, Senter, Kuizon and Macara (1994) J. Biol. Chem. 269, 10229-10234; Johanes, Lledo, Roa, Vincent, Henry and Darchen (1994) EMBO J. 13, 2029-2037]. In order to study the function of Rab3a in RBL degranulation, we have generated clones of RBL cells stably expressing Rab3a, and show that in these haematopoietic cells Rab3a can also function as a negative regulator of exocytosis. Overexpression of a mutant form of Rab3a (Asn-135 to Ile), which is predicted to be predominantly GTP-bound, also inhibited degranulation. However, overexpression of a mutant form of Rab3a that was truncated at the C-terminus to remove the sites for geranylgeranylation failed to inhibit degranulation. The effect of Rab3a is specific to secretion, and we observe no effect of Rab3a on receptor-mediated endocytosis. The Rab3a-induced block in degranulation can be bypassed by stimulation of streptolysin-O-permeabilized cells with guanosine 5'-[gamma-thio]triphosphate. We conclude from these studies that Rab3a is implicated in an early stage of granule targeting, whereas fusion of granules with the plasma membrane is regulated by a distinct downstream GTP-binding protein or proteins.

Animals↗
PubMed1997

Exit of the pre-TCR from the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thymocytes.

A major issue is whether surface expression of the pre-TCR is necessary for signaling the development of immature thymocytes. To address this question, we generated transgenic mice expressing a TCRbeta chain that had a strong endoplasmic reticulum (ER) retrieval signal (TCRbetaER) and that was expressed intracellularly but failed to reach the cell surface. In TCRbetaER transgenic mice, there was a failure of allelic exclusion. Also, the transgene failed to rescue the developmental defects observed in TCRbeta-null mice. In contrast, TCRbeta transgenes with a mutant ER retrieval sequence or lacking this sequence signaled efficient allelic exclusion and suppressed the TCRbeta-/- defect. These data show that exit of the pre-TCR from the ER/cis-Golgi is required for progression through the double-negative thymocyte checkpoint.

Alleles↗
PubMed1996

Development of circadian rhythmicity of temperature in full-term normal infants.

Twelve full-term infants (7 girls and 5 boys) with normal neurological, behavioral and somatic development were followed at regular intervals during the first 5 months of life to appreciate the development of circadian rectal temperature rhythmicity. Activity and temperature (oral at birth, rectal thereafter) were monitored for a minimum of 60 hours on seven separate occasions: at birth, 3 weeks, 6 weeks, 8 weeks, 10 weeks, 16 weeks and 20 weeks of age. Activity was measured using an actigraph worn on the infant's wrist, and rectal temperature was measured using a rectal probe attached to a portable microprocessor (Vitalog TM). Data points were collected every 2 minutes. No fewer than ten infants were monitored at each session, and no infant missed more than one session. Missing recordings were due to equipment malfunctions, probe expulsions and minor health problems. Six infants out of 12 were successfully monitored at each of the first four sessions, from birth to 8 weeks of age inclusively, and two subjects were successfully monitored at all seven sessions. Periodic regression analysis was performed by least squares curve fit with secondary analysis of variance. Analysis of covariance was performed on repeated measures. There was no evidence of rectal temperature circadian rhythmicity at 3 weeks. Two infants demonstrated a circadian rhythmicity at 6 weeks, and all infants had a circadian rhythmicity at 10 weeks post-natal age. At the time of the first observance of circadian rhythmicity of rectal temperature, the mean delta in temperature from peak to trough was 0.6 +/- 0.3 degrees C. This delta was greater at the 16th week, with a mean value of 1.2 +/- 0.3 degrees C. The trough was seen during the first part of the long nocturnal inactivity period. Circadian rhythmicity of rectal temperature was always observed in the studied subjects before the establishment of a consolidated, long daytime wake period.

Body Temperature Regulation↗
PubMed1996

The quality of hospital discharge: a survey of discharge arrangements for the over-65s.

A three-phase study comprising semi-structured interviews with patients and/or their carers, follow-up postal questionnaires, and a postal survey of the views of professionals involved in the discharge of participating patients was conducted to assess the quality of arrangements for patients over 65 years of age, discharged from hospitals in Chester and Ellesmere Port in the United Kingdom. A large majority of patients (80%) felt they had been adequately consulted about arrangements for their discharge, but less than 2% of health and social care professionals considered all discharges satisfactory. This apparent disparity between patient and professional views may be explained by low levels of expectation among patients in this aspect of their care and their reluctance to express views which they fear may compromise future care. Continuing difficulties with interprofessional communication and liaison suggest that further attention to discharge management is required if improvements are to be effected.

Aged↗
PubMed1996

Identification of a novel member of the Rab8 family from the rat basophilic leukaemia cell line, RBL.2H3.

We describe the cloning of a cDNA from the rat basophilic leukaemia cell line (RBL.2H3) encoding a novel member of the Rab family of small GTP binding proteins. The novel clone, which we call Rab8b, is most highly related to the Rab8 family with substantial divergence in the variable C-terminal domain. Northern blot analysis reveals highest levels of expression of Rab8b in the spleen, testis and brain, which is in marked contrast to the tissue distribution of Rab8. The Rab8b cDNA was modified to introduce a c-myc epitope tag at the extreme N terminus of the protein, and transient transfection studies were performed to analyse the intracellular localization of Rab8b by confocal microscopy. Transient expression of the c-myc/Rab8b fusion protein in both PC12 and RBL.2H3 cells shows staining of both the plasma membrane and ill-defined vesicular structures, and in the case of RBL.2H3 cells appears to induce striking outgrowths of the plasma membrane.

Amino Acid Sequence↗
PubMed1994

The effect of sampling condition on children's productions of consonant clusters.

An investigation was conducted to compare the effects of single word and connected speech sampling conditions on the production of consonant clusters. Speech samples were obtained from 40 children with speech sound impairments who were aged 3 years: 6 months to 5 years. The children's productions of 36 commonly occurring consonant clusters were compared across the two sampling conditions. Overall children's productions were more similar than different. Differences between the sampling conditions were apparent for three of the eight phonological processes studied, namely, cluster reduction, final consonant deletion, and epenthesis. Of 12 fine phonetic variations, only aspirated stops showed a significant difference between the sampling conditions. There was a wide range of individual variation.

Child Language↗
PubMed1993

Dynamics of electroencephalographic sleep spindles and slow wave activity in men: effect of sleep deprivation.

Recent developments in the understanding of the neurophysiological mechanisms underlying electroencephalographic (EEG) slow waves and sleep spindles imply an inverse relationship between these two EEG activities. The interrelationship between slow wave activity (0.75-4.5 Hz) and sleep-spindle activity (12-15 Hz) in electroencephalograms recorded in nine male subjects, during nocturnal baseline sleep and during recovery sleep from 40 h of wakefulness, was analyzed by power spectral analysis based on the fast Fourier transform and by transient patterns detection algorithms. Both techniques revealed that spindle activity was highest in sleep stage 2, increased over consecutive non-rapid-eye-movement sleep (non-REM sleep) episodes and was suppressed during recovery sleep. In contrast, slow wave activity decreased over consecutive non-REM sleep episodes and was enhanced during recovery sleep. Analysis of the dynamics of spindle and slow-wave activity within non-REM sleep episodes demonstrated that in the initial 20% of these episodes both spindle activity and slow wave activity increased, whereafter slow wave activity continued to increase but the average amplitude of spindles and total spindle activity, but not spindle density, decreased. At the end of non-REM sleep episodes the reverse pattern was observed. Sleep deprivation induced a more rapid rise of both spindle and slow wave activity in the very beginning of sleep. These data demonstrate that when averaged per sleep episode or non-REM sleep episode an inverse relationship between SWA and spindle activity exists but that in the initial and final part of non-REM sleep episodes the association between these two activities is positive. This biphasic relationship is discussed with reference to the hypothesis that the transition from sleep spindles to slow waves is dependent on a progressive hyperpolarization of thalamo-cortical neurons.

Adult↗