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Biomedical subjects

G Donnelly

Publications and source records attributed to G Donnelly.

At least 19 recordsLinked to original sources
PubMed2003

Gas-phase detection of trinitrotoluene utilizing a solid-phase antibody immobilized on a gold film by means of surface plasmon resonance spectroscopy.

A multilayered biosensor was constructed and found to detect trinitrotoluene (TNT) in ppb concentrations in air both prior to and after detonation of TNT without use of a liquid phosphate buffered saline (PBS) superstrate. The biosensor surface was fabricated from a monoclonal antibody for TNT covalently bound to an 11,11'-dithio-bis(succinimidoylundecanoate) (DSU) self-assembled monolayer immobilized on a thin gold film bonded to a BK7 glass slide. The binding between the immobilized antibody and TNT antigen was detected using surface plasmon resonance spectroscopy (SPRS). Biosensor specificity for TNT was demonstrated with chemical homologues as well as against an unrelated explosive, RDX.

Air Pollutants↗
PubMed2001

Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system.

The relationship between the development of the enteric nervous system and interstitial cells of Cajal (ICC) in the human small intestine was investigated in a full-term infant who presented with intestinal pseudo-obstruction. Immunohistochemistry revealed absence of enteric nerves and ganglia but abundant c-Kit immunoreactivity associated with Auerbach's plexus (ICC-AP). However, c-Kit immunoreactivity associated with the deep muscular plexus (ICC-DMP) and intermuscular ICC was absent. Electron microscopy showed ICC-AP with a normal ultrastructure; ICC-DMP were seen but were severely injured, suggesting degeneration. In vitro recording of intestinal muscle showed slow wave activity as well as response to cholinergic stimulation. Fluoroscopic examination of the small bowel showed a variety of motor patterns, including rhythmic, propagating contractions. In conclusion, total absence of enteric nerves was associated with absence of normal ICC-DMP. However, a normal musculature, including a network of ICC-AP, allowed for generation of rhythmic, propagating contractile activity, suggesting the presence of functional motor activity.

Biological Clocks↗
PubMed2001

Regulation of slow wave frequency by IP(3)-sensitive calcium release in the murine small intestine.

Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca(2+), inositol 1,4,5,-trisphosphate (IP(3))-sensitive Ca(2+) release, and sarcoplasmic reticulum (SR) Ca(2+) content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a cytosolic Ca(2+) chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca(2+)-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP(3)-induced Ca(2+) release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP(3) synthesis with carbachol, norepinephrine, or phenylephrine acting on alpha(1)-adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP(3) receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca(2+)-induced Ca(2+) release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP(3)-sensitive Ca(2+) release and the rate of SR Ca(2+) refilling in regulation of intestinal slow wave frequency.

Adrenergic alpha-Agonists↗
PubMed2001

The myogenic component in distention-induced peristalsis in the guinea pig small intestine.

In an in vitro model for distention-induced peristalsis in the guinea pig small intestine, the electrical activity, intraluminal pressure, and outflow of contents were studied simultaneously to search for evidence of myogenic control activity. Intraluminal distention induced periods of nifedipine-sensitive slow wave activity with superimposed action potentials, alternating with periods of quiescence. Slow waves and associated high intraluminal pressure transients propagated aborally, causing outflow of content. In the proximal small intestine, a frequency gradient of distention-induced slow waves was observed, with a frequency of 19 cycles/min in the first 1 cm and 11 cycles/min 10 cm distally. Intracellular recording revealed that the guinea pig small intestinal musculature, in response to carbachol, generated slow waves with superimposed action potentials, both sensitive to nifedipine. These slow waves also exhibited a frequency gradient. In addition, distention and cholinergic stimulation induced high-frequency membrane potential oscillations (~55 cycles/min) that were not associated with distention-induced peristalsis. Continuous distention produced excitation of the musculature, in part neurally mediated, that resulted in periodic occurrence of bursts of distally propagating nifedipine-sensitive slow waves with superimposed action potentials associated with propagating intraluminal pressure waves that caused pulsatile outflow of content at the slow wave frequency.

Action Potentials↗
PubMed2000

Interstitial cells of cajal and inflammation-induced motor dysfunction in the mouse small intestine.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) play an important role in the control of gastrointestinal motility. We aimed to determine a potential role for ICC in the pathophysiology of inflammation-induced motor disorders. METHODS: Effects of Trichinella spiralis infection on electrical pacemaker activity, the structure of ICC associated with Auerbach's plexus, and in vivo motor patterns were studied in the mouse small intestine. RESULTS: Between days 1 and 15 after infection, structural damage occurred in the network of ICC, particularly in the processes connecting ICC to each other and to smooth muscle cells. This was associated with desynchronization of electrical pacemaker activity. Abnormal slow wave activity occurred, including doubling of frequency and electrical quiescence, leading to the development of ectopic pacemaker activity in vivo. In vivo motor patterns in the small intestine changed from consistent peristaltic contractile activity in control animals to periods of quiescence alternating with both orally and aborally propagating contractile activity in the presence of inflammation. Sixty days after infection, all parameters studied had returned to normal values. CONCLUSIONS: Inflammation-induced alterations in the network of ICC of the small intestine associated with Auerbach's plexus lead to disorganization of motor patterns. Because of the strong temporal correlation between damage to the ICC network, electrical uncoupling, the appearance of ectopic pacemaker activity, and the occurrence of retrograde peristalsis, it is concluded that ICC can play a major role in inflammation-induced motor disturbances.

Animals↗
PubMed1998

The effect of extracellular matrix on the growth of mouse olfactory tissue in vitro.

The aim of this study was to compare the capacity of extracellular matrix (ECM) components to support the growth and differentiation of olfactory tissue in vitro. Reconstituted basement membrane matrix (RBM) supported profuse neurite outgrowth from explants of olfactory bulb (OB), with no non-neuronal cell migration. In contrast, nasal tissue (NT) explants cultured on RBM produced profuse fibroblastic outgrowth, but no neurite outgrowth from olfactory sensory neurones (OSN). Three-dimensional collagen gels, on the other hand, supported extensive outgrowth of both non-neuronal and neurite outgrowth from OB and NT explants, mature OSNs in the latter being identified using antibodies against olfactory marker protein (OMP). These culture systems represent useful tools for investigating potential tropic influences of target tissue.

Animals↗
PubMed1998

Changes in murine jejunal morphology evoked by the bacterial superantigen Staphylococcus aureus enterotoxin B are mediated by CD4+ T cells.

Bacterial superantigens (SAgs) are potent T-cell stimuli that have been implicated in the pathophysiology of autoimmune and inflammatory disease. We used Staphylococcus aureus enterotoxin B (SEB) as a model SAg to assess the effects of SAg exposure on gut form and cellularity. BALB/c, SCID (lacking T cells) and T-cell-reconstituted SCID mice were treated with SEB (5 or 100 microg intraperitoneally), and segments of the mid-jejunum were removed 4, 12, or 48 h later and processed for histochemical or immunocytochemical analysis of gut morphology and major histocompatibility complex class II (MHC II) expression and the enumeration of CD3+ T cells and goblet cells. Control mice received saline only. SEB treatment of BALB/c mice caused a time- and dose-dependent enteropathy that was characterized by reduced villus height, increased crypt depth, and a significant increase in MHC II expression. An increase in the number of CD3+ T cells was observed 48 h after exposure to 100 microg of SEB. Enteric structural alterations were not apparent in SEB-treated SCID mice compared to saline-treated SCID mice. In contrast, SEB challenge of SCID mice reconstituted with a mixed lymphocyte population or purified murine CD4+ T cells resulted in enteric histopathological changes reminiscent of those observed in SEB-treated BALB/c mice. These findings implicate CD4+ T cells in this SEB-induced enteropathy. Our results show that SAg immune activation causes significant changes in jejunal villus-crypt architecture and cellularity that are likely to impact on normal physiological processes. We speculate that the elevated MHC II expression and increased number of T cells could allow for enhanced immune responsiveness to other SAgs or environmental antigens.

Animals↗
PubMed1995

An outbreak of gentamicin-resistant Klebsiella pneumoniae in a neonatal ward.

Gentamicin-resistant Klebsiella pneumoniae (GRKP) was isolated from nineteen patients in the neonatal ward of Sultan Qaboos University Hospital (SQUH) in Oman. Thirteen cases were infected and six were colonized. Two infected patients died due to septicaemia, eight cases occurred within SQUH and eleven cases were imported from other hospitals. Sixteen isolates were of the same serotype (K25), three were non typeable. Referred patients from peripheral hospitals were the source of the organism and hand carriage the probable vehicle of transmission. The first strain of gentamicin-sensitive Kleb. pneumoniae was isolated five months after combating the outbreak.

Anti-Bacterial Agents↗
PubMed1994

Transcranial Doppler sonography in headache-free migraineurs.

We used transcranial Doppler ultrasonography to determine whether intracranial blood velocities in 182 headache-free migraineurs (60 with aura, 122 without aura) differed from velocities in 38 nonheadache prone control subjects. During the headache-free period, migraineurs with and without aura had significantly elevated mean velocities in all intracranial arteries except the right internal carotid artery at the level of the siphon. Velocities in migraineurs with aura did not differ significantly from velocities in those without aura. Markedly increased velocities were noted in a subset of interictal migraineurs. Two explanations are possible: 1) Blood flow velocities may increase in response to a decrease in the cross sectional area of a vessel at or near the point of insonation. 2) Alterations at the level of the cerebral arteriole may affect regional cerebral blood flow, thereby changing blood flow velocities at the point of insonation. Transcranial Doppler sonography alone cannot sort out which process is responsible for the vascular response. This work may have therapeutic as well as diagnostic implications. When interictal flow velocities are markedly increased, it is possible that therapeutic agents with vasoconstrictor action might cause an excessive response. Further study is needed to clarify the sites of vasoreactivity as well as the magnitude of drug-induced vasoconstrictor response.

Adult↗
PubMed1991

Training family practice and internal medicine residents to counsel patients who smoke: improvement and retention of counseling skills.

This investigation builds on an earlier study by describing the final results of a training program that teaches internal medicine and family practice residents to counsel patients to stop smoking. In this study, 198 residents participated in a three-hour training program which included small group discussion and role-playing exercises. Videotaped observations of role-playing performances were used to assess behavioral outcomes related to counseling skills for 104 residents who completed pre-, immediate post-, and long-term follow-up testing. The present findings support previous results that show the training program has a significant positive effect on physician smoking cessation counseling skills. A subsample of residents continued to exhibit improved counseling skills one year after the initial educational interventions, suggesting that these skills can be retained over time.

Counseling↗
PubMed1988

Benefits and costs of lifestyle change to reduce risk of chronic disease.

Individuals do not benefit equally from attempts to change their lifestyles in an effort to lower their risk for disease or to improve their quality of life. A change in one lifestyle behavior may cause an increase in another risk factor and reduce the benefits of the anticipated change. The social environment exerts pressures and makes available resources that also influence the benefits and costs of a particular health behavior change. These pressures and resources vary depending on the individual and his or her social context. This article uses the target behavior of smoking as an example of a lifestyle change and considers the benefits and costs that interventionists need to be aware of if they are to effectively facilitate health behavior change. This approach requires the identification of resources at different levels of the environment (e.g., family, community, institutions) that may influence the cost/benefit ratio. Such an analysis is appropriate whether one is considering a model of individual behavior change or a public health model that seeks to intervene at the community-wide level to promote health and reduce disease risk among a large segment of the population. Specific recommendations based on this approach are offered and it is concluded that both individual and public health approaches are necessary to achieve optimal health behavior change in our population and to optimize the cost/benefit ratio of such change for all individuals.

Adult↗
PubMed1988

A residents' training program for the development of smoking intervention skills.

This article describes the results of a three-hour training program that teaches residents a patient-centered counseling approach to smoking cessation, emphasizing questioning and exploring feelings, rather than providing information. Fifty internal medicine and family practice residents affiliated with a university medical center were assessed before and after training using questionnaires and videotape documenting changes in their knowledge about smoking, attitudes concerning intervention, and intervention skills. The residents showed a significant increase in knowledge and perceived themselves as having significantly more influence on their patients who smoke after completion of the training program. Counseling skills improved significantly in the use of questions and exploring feelings as judged by blind evaluation of videotapes. The results of this three-hour training program suggest that physicians in training are responsive to the teaching of specialized skills deemed important for promoting health behavior changes in their patients.

Attitude of Health Personnel↗
PubMed1978

Group survival.

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Community Health Nursing↗
PubMed1977

Dreams.

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Dreams↗