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Biomedical subjects

I Morrison

Publications and source records attributed to I Morrison.

At least 19 recordsLinked to original sources
PubMed2006

The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival.

Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Long-term follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-alpha levels negatively correlated to tumour proliferation (rho=-0.697, P=0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (rho=0.452, P=0.05) and apoptosis (rho=0.587, P=0.01). Patient survival correlates to tumour pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI< or =0.6% and TNF-alpha levels > or =8148 pg ml(-1) correlate to improved survival (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNF-alpha and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected.

Adenocarcinoma↗
PubMed2004

Control of corrosion and aggression in drinking water systems.

Corrosion and/or aggression are common problems arising in pipelines transporting terrestrial waters. The kinetics and severity of such events depend on both the quality of the water being transported and the material properties of the pipeline. Irrespective of the nature of the problem, its solution (or at least its minimisation) is strongly linked to control of pH, calcium concentration and carbonate chemistry of the water (stabilisation). However, application of such chemistry to water treatment problems is complex and time consuming. Various numerical, graphical and computer techniques have been developed to address this, but these are either of insufficient accuracy, too time consuming or lacking in generality. In this paper algorithms are presented for solving a broad spectrum of problems related to control of mineral precipitation/aggression, pH and chemical dosing in water treatment. These have been incorporated into a computer software package, STASOFT, which offers the requisite framework for use in water treatment. Various stabilisation problems pertinent to water supply are addressed.

Chemical Precipitation↗
PubMed2002

Primary ciliary dyskinesia: age at diagnosis and symptom history.

UNLABELLED: Age at diagnosis and the symptom history of children with primary ciliary dyskinesia (PCD) are described by reviewing the case notes in the paediatric PCD clinic. Mean age at diagnosis was 4.4 y despite a history of neonatal respiratory distress in 37/55 cases, situs inversus in 38/55 cases and early onset troublesome rhinitis in 42/55. CONCLUSION: Diagnosis of PCD is often delayed despite the presence of typical symptoms early in life. The key clinical features of unexplained neonatal respiratory distress, early onset rhinitis, situs inversus and a productive cough are highlighted, which, especially when occurring in combination, makes early referral for specific testing for PCD mandatory.

Adolescent↗
PubMed2001

Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal.

Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent alpha-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III beta-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.

Alkaline Phosphatase↗
PubMed2000

Bovine tuberculosis: towards a future control strategy.

The Independent Scientific Group on Cattle TB was appointed by the Government in 1998 to implement and develop the research recommendations of the 1997 Krebs report on bovine tuberculosis in cattle and badgers. In this article, members of the group discuss the approach they are adopting in attempting to ensure that future control strategies are scientifically based. In a second article, to be published in next week's Veterinary Record, the group will consider the extent to which efforts to control the disease in cattle may be constrained by limitations in current testing procedures.

Animals↗
PubMed2000

Inelastic neutron scattering measurements and Ab initio calculations of hydrogen in single-crystal palladium

Using a single-crystal sample of PdH, we have measured the inelastic form factor for exciting the proton from its ground state to various excited states as a function of crystal orientation. Because of the anharmonicity of the potential well which splits otherwise degenerate states, each inelastic form factor could be measured individually. Agreement between theory and experiment is excellent, both with regard to the transition energies and to the modulation of the intensity, giving confidence in the quantum treatment of the proton and hence in the use of the model to predict other properties of the system.

Journal Article↗
PubMed2000

The future of physician's time.

Physicians' time is under assault in the current health care system. In particular, managed care payers are reducing compensation to physicians on a discounted fee-for-service basis. More demanding consumers, complex new technologies, and increased managerial and administrative burdens are placing further constraints on physicians' time. As we look ahead, it seems likely that these pressures will intensify and transform the ways in which physicians spend their time. Physicians will play eight key roles in the future: clinical data collector, shaman, health advisor and wellness coach, knowledge navigator, proceduralist, diagnostician, physician manager, and quality assurance specialist. They will need to lead the redesign of these roles and define the ways in which they should spend their time in the health care system of the new millennium.

Canada↗
PubMed2000

Approaches to higher-throughput pharmacokinetics (HTPK) in drug discovery.

With pressure on pharmaceutical companies to reduce time-to-market and improve the success rate of new drug candidates, higher-throughput pharmacokinetic (HTPK) support has become an integral part of many drug discovery programmes. This report details the amalgamation of robotics, new sample preparation technologies and highly sensitive and selective mass spectrometric detection systems to deliver the promise of HTPK. A historical perspective on automated bioanalysis with the current approaches and future prospects for the discipline are described.

Journal Article↗
PubMed1999

Monoclonal antibodies raised against Guillain-Barré syndrome-associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations.

Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.

Animals↗
PubMed1998

Fetal assessment based on fetal biophysical profile scoring. VIII. The incidence of cerebral palsy in tested and untested perinates.

OBJECTIVE: The intent of this comparative clinical study was fourfold: (1) to determine the incidence of cerebral palsy in a large obstetric population, (2) to compare the incidence of cerebral palsy in patients at high risk referred for and managed according to the fetal biophysical profile score result with the incidence among unreferred and untested patients, (3) to determine the relationship, if any, between the last fetal biophysical profile score and the incidence of cerebral palsy, and (4) to categorize cases of cerebral palsy according to the clinical parameters and the probable time and nature of the damaging insult. STUDY DESIGN: In this retrospective 5-year comparative study (1987 to 1991) the incidence of cerebral palsy was determined by analysis of International Classification of Diseases, Ninth Revision, -coded related medical services. The clinical records were then sought and reviewed in index cases and obstetric, neonatal, and postnatal clinical data were abstracted. Cross-correlation with partial registries was done to confirm completeness of capture of index cases. The population of referred high-risk patients who received serial fetal biophysical profile scoring and were managed according to test results was determined by review of a prospective computer-stored database and by review of patient log books. The population of untested patients was calculated as the residual of total cases minus tested cases. The rate of cerebral palsy for all patients and for the tested and untested population was calculated and compared. The tested and untested perinates were compared for birth age, weight, and assigned timing or etiology of cerebral palsy. In the tested population the distribution of test results by last recorded biophysical profile score was determined and the relationship between the last test result and cerebral palsy and predictive accuracy parameters of the fetal biophysical profile score were calculated. RESULTS: The incidence of cerebral palsy among the 84,947 live births was 3.68 per 1000 live births (313 cases). The rate of cerebral palsy in the 26,290 referred high-risk tested patients was 1.33 per 1000 (35 cases) compared with a rate of 4.74 per 1000 live births in the 58,657 untested mixed low-risk/high-risk patients (278 cases). These differences were highly significant. A significant declining trend in the annual incidence of cerebral palsy was observed in the total population and the untested population, whereas the rate in the tested population remained relatively constant over the 5-year study interval. The differences in the cerebral palsy rate between the tested and untested population were not related to differences in gestational age, birth weight, or assigned timing or etiology category. In the tested population the relationship between the incidence of cerebral palsy and the last test fetal biophysical profile score was inverse, exponential, and highly significant. CONCLUSIONS: Antepartum assessment by fetal biophysical profile scoring is associated with a significant reduction in the incidence of cerebral palsy compared with untested patients. The relationship between the last test score and the incidence of cerebral palsy is inverse and exponential, suggesting that antenatal asphyxia is an important and potentially avoidable cause of cerebral palsy.

Birth Weight↗
PubMed1998

The class II membrane glycoprotein G of bovine respiratory syncytial virus, expressed from a synthetic open reading frame, is incorporated into virions of recombinant bovine herpesvirus 1.

The bovine herpesvirus 1 (BHV-1) recombinants BHV-1/eG(ori) and BHV-1/eG(syn) were isolated after insertion of expression cassettes which contained either a genomic RNA-derived cDNA fragment (BHV-1/eG(ori)) or a modified, chemically synthesized open reading frame (ORF) (BHV-1/eG(syn)), which both encode the attachment glycoprotein G of bovine respiratory syncytial virus (BRSV), a class II membrane glycoprotein. Northern blot analyses and nuclear runoff transcription experiments indicated that transcripts encompassing the authentic BRSV G ORF were unstable in the nucleus of BHV-1/eG(ori)-infected cells. In contrast, high levels of BRSV G RNA were detected in BHV-1/eG(syn)-infected cells. Immunoblots showed that the BHV-1/eG(syn)-expressed BRSV G glycoprotein contains N- and O-linked carbohydrates and that it is incorporated into the membrane of infected cells and into the envelope of BHV-1/eG(syn) virions. The latter was also demonstrated by neutralization of BHV-1/eG(syn) infectivity by monoclonal antibodies or polyclonal anti-BRSV G antisera and complement. Our results show that expression of the BRSV G glycoprotein by BHV-1 was dependent on the modification of the BRSV G ORF and indicate that incorporation of class II membrane glycoproteins into BHV-1 virions does not necessarily require BHV-1-specific signals. This raises the possibility of targeting heterologous polypeptides to the viral envelope, which might enable the construction of BHV-1 recombinants with new biological properties and the development of improved BHV-1-based live and inactivated vector vaccines.

Amino Acid Sequence↗
PubMed1997

The use of a mass-action model to validate the output from a stochastic simulation model of bovine viral diarrhoea virus spread in a closed dairy herd.

The spread of bovine virus diarrhoea virus (BVDV) in a closed dairy herd maintained under typical management conditions is studied using two approaches. In the first instance a stochastic computer model is used to simulate the month-to-month changes in the infection status of each animal. These results are contrasted with the results of a mass-action model which uses three differential equations. A comparison of the two approaches indicates that the results are in broad agreement. The stochastic approach has the benefit of providing an estimate of the probability of the infection becoming extinct and the herd becoming BVDV-free for different herd sizes.

Animals↗