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J F Morrison

Publications and source records attributed to J F Morrison.

At least 37 records · Page 2Linked to original sources
PubMed1998

A novel in vitro bladder pelvic nerve afferent model in the rat.

OBJECTIVE: To develop an in vitro model to allow electrophysiological recordings from pelvic nerve afferents of the urinary bladder in the rat and to ascertain the stability and reproducibility of the model with time. MATERIALS AND METHODS: Six male Wistar rats (body weight approximately 100 g) were used in the study. The bladder (complete with accessory organs of prostate and seminal vesicles), urethra and penis, together with the attached pelvic nerve and L6/S1 nerve trunk, were removed intact and placed in a specially designed recording chamber containing oxygenated Krebs solution maintained at 30 degrees C. The bladder was catheterized urethrally and attached to a continuous-infusion pump and a pressure transducer. The L6/S1 nerve trunk was placed across a silicone-gel wall into a separate chamber containing liquid paraffin, in which multiunit recordings from pelvic nerve afferents originating from the bladder were made. The afferent nerve activities in response to repeated bladder distension with saline, at 0.04 mL/min for 8 min over 3 h, were compared using the paired t-test to assess the reproducibility of the model. Conduction velocity studies were also carried out to ascertain the proportion of C- and A delta-fibres in the multiunit recordings. RESULTS: Repeated bladder distension with saline over 3 h produced consistent and reproducible afferent nerve responses, signifying that the afferent nerves recorded in this study neither sensitize nor desensitize over time. This is an essential prerequisite when using this model to study the effects of pharmacological manipulation of the bladder on its afferent nerve response. Conduction velocity studies showed that approximately 30% of the afferent fibres recorded from were C-fibres with the remaining being A delta-fibres. CONCLUSIONS: An in vitro bladder pelvic nerve afferent model for the rat was developed successfully; it is stable and produces reproducible results with repeated bladder distension over at least 3 h.

Afferent Pathways↗
PubMed1998

The CD4+ T lymphocyte is a site of steroid resistance in asthma.

Phytohaemagglutinin (PHA)-induced T-cell proliferation is suppressed completely in steroid-sensitive asthma (SSA) by fluticasone propionate (FP). By contrast, in patients with steroid-resistant asthma (SRA), this proliferative response is only partially attenuated by steroids, which suggests that the T lymphocyte may harbour a key molecular defect in these patients. Both CD4+ and CD8+ T cells may be involved in orchestrating the inflammation underlying asthma. We examined whether CD4+ or CD8+ T cells isolated from SRA and SSA patients are equally susceptible to steroid suppression of PHA-induced proliferation. Complete suppression of CD4+ T-lymphocyte proliferation was seen in both SSA and control subjects at concentrations of 10(-9) M FP. In contrast, proliferation of CD4+ T cells from SRA patients was only partially inhibited, even at 10(-6) M FP. CD8+ responses from SRA, SSA and controls were all similar, with only a partial suppression of proliferation at 10(-6) M FP. Differential suppression by FP of CD4+ T cells has thus been demonstrated between SRA and SSA patients.

Adult↗
PubMed1998

Relationship between exhaled nitric oxide and childhood asthma.

The purpose of the study was to determine if exhaled nitric oxide levels in children varied according to their asthmatic and atopic status. Exhaled nitric oxide was measured in a sample of 93 children attending the North West Lung Centre, Manchester, United Kingdom, for the clinical evaluation of a respiratory questionnaire being developed as a screening tool in general practice. The clinical assessment included full lung function, skin prick testing, and exercise challenge. Children were said to be asthmatic either by consensus decision of three independent consultant pediatricians, who reviewed all the clinical results except the nitric oxide measurements, or by positive exercise test. Atopic asthmatic children had higher geometric mean exhaled nitric oxide levels (consensus decision, 12.5 ppb [parts per billion] 95% CI, 8.3 to 18. 8; positive exercise test, 12.2 ppb 95% CI, 7.6 to 19.7) than did nonatopic asthmatic children (3.2 ppb 95% CI, 2.3 to 4.6; 3.2 ppb 95% CI, 2.0 to 5.0), atopic nonasthmatic children (3.8 ppb 95% CI, 2. 7 to 5.5; 5.7 ppb 95% CI, 4.1 to 8.0), or nonatopic nonasthmatic children (3.4 ppb 95% CI, 2.8 to 4.1; 3.5 ppb 95% CI, 3.0 to 4.1). Thus, exhaled nitric oxide was raised in atopic asthmatics but not in nonatopic asthmatics, and these nonatopic asthmatics had levels of exhaled nitric oxide similar to those of the nonasthmatics whether atopic or not.

Adolescent↗
PubMed1997

Characterization of human SHC p66 cDNA and its processed pseudogene mapping to Xq12-q13.1.

SHC is an adapter protein in the Ras-MAPkinase pathway that is involved in the regulation of cell growth and differentiation. The p46 and p52 isoforms are thought to be produced by the use of two alternative translation initiation sites in a 3.4-kb transcript from the SHCA gene, which maps to chromosome 1q21. The p66 isoform could be encoded by a different 3.8- or 2.8-kb transcript of the same gene or alternatively by a SHC-related gene. To characterize other putative genes coding for SHC-like proteins, primers from the 3' UTR of the SHCA gene were used to screen a yeast artificial chromosome (YAC) library by polymerase chain reaction (PCR). Two YAC clones, 20D11B and 36D1D, were isolated and used as probes for fluorescence in situ hybridization analysis. Both these probes hybridized to chromosome Xq12-q13.1. This novel SHC-related sequence was characterized by direct sequencing of vectorette library PCR products produced from clone 20D11B. A transcript of 3.2 kb that was 85% identical to the mouse Shc cDNA encoding the p66 isoform was identified. Sequence analysis demonstrated the presence of multiple stop codons identifying this isoform of SHC as a processed pseudogene. Using primers designed on the basis of the nucleotide sequence of the pseudogene, we have now amplified and sequenced a human cDNA that encodes the SHC p66 protein. Thus, we have characterized the human SHC p66 isoform cDNA and identified a processed SHC pseudogene that maps to chromosome Xq12-q13.1.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Slow-binding inhibition: the general case.

Two basic kinetic mechanisms have been described to account for the slow-binding inhibition of enzyme-catalyzed reactions. One mechanism involves the slow interaction of an inhibitor with enzyme (Mechanism A), while the other involves the rapid formation of an enzyme-inhibitor complex that undergoes a slow isomerization reaction (Mechanism B). But the initial interaction of enzyme and inhibitor may not necessarily be fast so that the free enzyme and the two forms of enzyme inhibitor complex are in steady-state equilibrium. This assumption would give rise to a more general form of Mechanism B. The present study has been concerned with attempts to determine whether it might be possible to distinguish between the three possible inhibition mechanisms by steady-state kinetic techniques. The approach to the investigation has been to derive theoretical data for the most general mechanism by using three different ratios for the two rate constants that determine which mechanism applies. The progress curve data were then fitted to the rate equations that describe the other two mechanisms. The results draw attention to the difficulties of deducing that experimental data conform to the most general mechanism. They also show how the values for the kinetic parameters, as determined from fits of the data to the equations that describe Mechanisms A and B, can be considerably in error.

Chemical Phenomena↗
PubMed1996

Excitatory and inhibitory A- and C-reflexes in pelvic parasympathetic efferent nerves elicited by single shock to A and C afferent fibers of perineal and limb somatic nerves in anesthetized rats.

The effects of single electrical shocks to myelinated A and unmyelinated C afferent fibers of perineal and limb somatic nerves on the reflex discharges in pelvic parasympathetic (L6/S1) efferent nerves to the bladder were examined in anesthetized central nervous system (CNS)-intact and acute spinal rats. When the bladder was empty, stimulation of perineal somatic inputs to the L6 and S1 segments from the perineo-femoral branch of a pudendal nerve produced excitatory A- and C-reflex discharge components in postganglionic parasympathetic efferent nerve branches on the bladder surface. When the bladder was expanded and pelvic efferent neurons were rhythmically active, additional inhibitory A- and C-reflex components could be seen. After acute spinal transection, the same stimuli elicited excitatory A- and C-reflex discharges of similar latency as those observed before the spinal transection, but were of larger amplitude and longer duration; resting activity in the pelvic nerve was low, and no evoked inhibitory reflex components could be observed. Electrical stimulation of afferents in the tibial nerve had no effect when the bladder pressure was low, but when the bladder was distended, early and late components of reflex inhibition and excitation of parasympathetic activity were visible in CNS-intact rats; these reflex responses were abolished following spinalization.

Anesthesia↗
PubMed1996

Non random usage of T cell receptor alpha gene expression in atopy using anchored PCR.

The T cell receptor (TCR) alpha beta heterodimer recognises antigenic peptide fragments presented by Class II MHC. This interaction initiates T cell activation and cytokine release with subsequent recruitment of inflammatory cells. Previous work from our group suggests a qualitative difference in variable alpha gene expression in atopy as compared to non atopic controls. In this study we examine TCR alpha repertoire using anchored PCR to provide a quantitative assessment of the V alpha and J alpha repertoire. One atopic (DRB1*0701,DRB1*15: DRB4*0101, DRB5*01: DQB1* 0303, DQB1*601/2) and one non-atopic (DRB1*0701,DRB1*03011/2: DRB4*01, DRB3*0x: DQB1* 0303, DQB1*0201/2) control were studied. Variable gene usage was markedly limited in the atopic individual. V alpha 1, 3, 8 accounted for 60% and J alpha 12, 31 30% of the gene usage. There was evidence of preferential V alpha-J alpha gene pairing and clonal expansion. We conclude that there is a marked non random TCR alpha gene distribution in atopy using both V alpha family and anchored PCR. This may be due in part to antigen driven clonal expansion.

Gene Expression↗
PubMed1996

The nitric oxide synthase inhibitor L-NAME reduces inhibitory components of somato-vesical parasympathetic reflexes in the rat.

Reflex discharges of pelvic postganglionic parasympathetic efferent fibers on the bladder surface induced by afferent volleys in the hindlimb nerve have been recorded in anesthetized rats, and the effects of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) on the reflex discharges have been investigated. Single electrical stimulation of the tibial nerve at intensities supramaximal for excitation of A- and C-afferents evoked a reflex discharge in the postganglionic parasympathetic efferents with four distinct components, i.e., two inhibitory components with latencies of 49 and 203 ms, respectively, and two excitatory components with latencies of 126 and 308 ms, respectively. These reflexes could be observed when the bladder was expanded, but not markedly when the bladder was empty. Intravenous administration of L-NAME resulted in (a) a reduction in the level of resting discharge, (b) a reduction in the size of the first inhibitory component, (c) the disappearance of the second inhibitory component and (d) the exaggeration of the late excitatory component. Intracisternal injection of L-NAME caused changes similar to those observed following intravenous injection. The results suggest that inhibitory components of the somato-pelvic parasympathetic reflex are mediated by pathways that utilize nitric oxide as a neurotransmitter or neuromodulator at the level of the brainstem.

Animals↗
PubMed1995

The temporal and cellular expression of c-fos and c-jun in mechanically stimulated rabbit latissimus dorsi muscle.

The levels of c-fos and c-jun mRNA were measured by reverse transcription PCR in the rabbit latissimus dorsi muscle following three separate training regimes, i.e. passive stretch, 10 Hz electrical stimulation or a combination of the two. Both c-fos and c-jun mRNA expression peaked at around 1 h after imposing stretch and at around 4.5-6 h after the initiation of electrical stimulation. The combined stretch/electrical stimulation regime induced biphasic expression of both c-fos and c-jun mRNA, with peaks coinciding temporally with those for the individual regimes. Immunostaining with anti-Fos and anti-Jun antibodies revealed the accumulation of these proteins in both myofibre and interstitial cell nuclei following passive stretch. In contrast, following electrical stimulation the localization of immunoreactive c-Fos and c-Jun proteins was predominantly in interstitial cell nuclei. c-Fos and c-Jun immunoreactivity was also clearly colocalized in a proportion of myonuclei from stretched muscle. These findings suggest that the rapid induction of c-fos and c-jun is an early event in response to mechanical stretch and might trigger [via activator protein-1 (AP-1) transcriptional factors] events leading to muscle fibre hypertrophy. However, the involvement of AP-1 in inducing the phenotypic changes in muscle fibres as a result of electrical stimulation appears less clear.

Animals↗
PubMed1995

Yeast artificial chromosome cloning of the beta-catenin locus on human chromosome 3p21-22.

beta-Catenin has emerged as an important component of the adherens junctions between epithelial cells. As a result of studies of its interaction with the APC gene product, it has been implicated in the development of colorectal cancer. alpha-Catenin, beta-catenin, E-cadherin and APC appear to mediate contact inhibition in epithelia. As part of the study of the organization of the beta-catenin gene, we have isolated yeast artificial chromosomes (YACs) to characterize its intron/exon structure. YAC fluorescence in situ hybridization analysis and polymerase chain reaction analysis of somatic cell hybrid DNAs show that beta-catenin maps in the 3p21-22 region, the location of tumour-suppressor genes deleted in small-cell lung cancer (SCLC) and other disorders. beta-Catenin YACs will provide a source of microsatellite markers useful in loss of heterozygosity studies to assess the importance of beta-catenin deletions in SCLC.

Base Sequence↗
PubMed1995

Long-lasting facilitation and depression of periurethral skeletal muscle following acupuncture-like stimulation in anesthetized rats.

The effects of acupuncture-like stimulation on the tone of the partially filled bladder and on the periurethral electromyogram (EMG) were examined in urethane-anesthetized rats. Acupuncture-like stimuli were usually applied to the skin and underlying muscles (or other structures), either separately or together, for a period of 1 min; the effects were studied in spinal cord intact and in spinalized animals. Maps have been constructed showing the effects of acupuncture-like stimulation at different sites on the body surface and of similar stimulation applied to individual muscles, the urethra and the testis. When acupuncture-like stimuli were applied to the skin and underlying structures, in the rostral half of the body and the hindpaw, testis or urethra, these stimuli usually induced excitation of periurethral EMG activity. Depression of EMG activity was seen predominantly during stimulation of structures close to the urethra, but not opposed to it. When acupuncture-like stimuli were applied only to structure beneath the skin, depression of EMG activity usually occurred. Acupuncture-like stimulation of the bulbocavernosus, which partly overlies the proximal urethra produced depression of EMG activity in 50% of trials, but the incidence of similar effects from the more distant pubococcygeus, or the dorsal or ventral sacrococcygeal muscles was about 90-100%. Acupuncture-like stimulation for 1 min could produce either excitation or depression of periurethral EMG activity lasting about 5 or 6 min, depending on the site of insertion and rotation of the acupuncture needles. Excitation of short duration (less than 3 min) was consistently observed from areas of the body distant to the bladder, i.e. the nose, forepaw, forelimb, chest, abdominal wall and hindpaw. Longer lasting excitation of EMG activity was often seen from the penile urethra, perineal area and hindlimb. Depression of EMG activity with a duration of more than 3 min was consistently seen from the muscles at the base of the tail (sacrococcygeus) and perineal area (pubococcygeus and bulbocavernosus). The bladder was partially filled in these experiments, so that micturition contractions were never seen; acupuncture-like stimulation of the perineal area induced some increase in bladder tone in 40% of trials. In spinalized animals, the pattern of activity induced by acupuncture-like stimulation was similar to that seen in spinal cord intact animals and the durations of the effects were not significantly different in these two groups. The distribution of sites from which acupuncture-like stimuli can influence the activity of the lower urinary tract is discussed.

Acupuncture Therapy↗