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R Morris

Publications and source records attributed to R Morris.

At least 37 records · Page 2Linked to original sources
PubMed2002

Antibodies in crevicular fluid: an epidemiological tool for investigation of waterborne disease.

A significant challenge in the epidemiological investigation of recreational waterborne disease is the establishment of a definite association between exposure to a contaminated water and infection. An increase in specific antibodies as a result of infection is a potent measure of disease exposure and its determination would enhance epidemiological studies of waterborne diseases. We report on the automated detection of HAV antibodies in crevicular fluid and its use in a field study. The method is easy to use, non-invasive, could be applied to volunteers of all ages and is comparable in sensitivity to serological procedures. Application to an epidemiological study of water recreationalists demonstrated that surfers were three times more likely to be immune to hepatitis A virus than either wind-surfers or a control group without recreational water contact.

Adolescent↗
PubMed2002

Antibody and radionuclide characteristics and the enhancement of the effectiveness of radioimmunotherapy by selective dose delivery to radiosensitive areas of tumour.

PURPOSE: Estimating the absorbed dose to tumour relative to normal tissues has often been used in the assessment of the therapeutic efficacy of radiolabelled antibodies for radioimmunotherapy. Typically, the calculations assume a uniform dose deposition and response throughout the tumour. However, the heterogeneity of the dose delivery and response within tumours can lead to a radiobiological effect inconsistent with dose estimates. The aim was to assess the influence of antibody and radionuclide characteristics on the heterogeneity of dose deposition. MATERIALS AND METHODS: Quantitative images of the temporal and spatial heterogeneity of a range of antibodies in tumour were acquired using radioluminography. Subsequent registration with images of tumour morphology then allowed the delineation of viable and necrotic areas of tumour and the measurement of the antibody concentration in each area. A tumour dosimetry model then estimated the absorbed dose from 131I and 90Y in each area. RESULTS: Tumour-specific antibodies initially localized in the viable radiosensitive areas of tumour and then penetrated further into tumour with continued tumour accretion. Multivalent antibodies were retained longer and at higher concentrations in viable areas, while monovalent antibodies had greater mobility. In contrast, non-specific antibodies penetrated into necrotic regions regardless of their size. As a result, multivalent, specific antibodies delivered a significantly larger dose to viable cells compared with monovalent antibodies, while non-specific antibodies deposited most of the dose in necrotic areas. There was a significant difference in dose estimates when assuming a uniform dose deposition and accounting for heterogeneity. The dose to the viable and necrotic areas also depended on the properties of the radionuclide where antibodies labelled with 131I generally delivered a higher dose throughout the tumour even though the instantaneous dose-rate distribution for 90Y was more uniform. CONCLUSIONS: The extent of heterogeneity of dose deposition in tumour is highly dependent on the antibody characteristics and radionuclide properties, and can enhance therapeutic efficacy through the selective dose delivery to the radiosensitive areas of tumour.

Animals↗
PubMed2001

Bisulfite-induced cytosine deamination rates in E. coli SSB:DNA complexes.

E. coli single-stranded binding protein (SSB) has been examined for its ability to modulate bisulfite-induced cytosine deamination rates in single-stranded DNA (ssDNA). We used a lacZ alpha-complementation reversion assay to detect C-->U rates at a single codon in M13mp2 DNA, whether in free ssDNA or in an SSB:ssDNA complex. When incubated at 37 degrees C, the average bisulfite-induced reversion rate constant was four-fold less in SSB:ssDNA complexes than in ssDNA, at a single codon. Across a 250 base pair target and over 23 scorable C-->U sites, the forward rate constant was 4.9-fold less in SSB:ssDNA complexes than in ssDNA alone. After treatment with N-uracil glycosylase, ssDNA incubated with bisulfite had reversion frequencies at the background rate of ssDNA incubated without bisulfite, indicating that virtually all mutations scored were due to C-->U events. The decrease in cytosine deamination rates occurred both in a single codon and over a 250 bp target, indicating that interactions between SSB and ssDNA reduce bisulfite-catalyzed mutations. The structural role of SSB is well recognized in multiple cellular processes; SSB can also function to minimize bisulfite-induced ssDNA mutations.

Cytosine↗
PubMed2001

Water quality of Scottish rivers: spatial and temporal trends.

The Harmonised Monitoring Scheme (HMS) was initiated in 1974 and represents the best-organised source of temporal and spatial data describing water quality for the major mainland rivers of Scotland, England and Wales. This paper presents the first detailed analysis of HMS data for Scotland, and identifies temporal changes in water quality from 1974 to 1995. From a concomitant analysis of catchment land cover characteristics, water quality indices have been linked with potential 'drivers' of change, influencing both point and diffuse sources. Nitrate concentrations between rivers are highly correlated with the amount of arable land, and relationships exist between grassland cover, orthphosphate-P and suspended solids concentrations. Similarly, urban catchments are highly correlated with ammonium-N, orthophosphate-P and suspended solids. Spatial and temporal trends in water quality for the rivers of Scotland are discussed.

Agriculture↗
PubMed2001

The synthesis of pseudomycin C' via a novel acid promoted side-chain deacylation of pseudomycin A.

The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported.

Acylation↗
PubMed2001

How central is nitric oxide (NO) to the activation of c-fos in spinal neurones following noxious peripheral stimulation in the rat?

Intrathecal application of high doses of NO-donor compounds in the anaesthetised rat was not found to cause any induction of c-fos in spinal neurones. Furthermore, intrathecal injection of a NO-synthase (NOS) blocking drug did not alter the numbers of c-fos positive neurones induced by noxious stimulation. Additionally very little colocalization between NOS and c-fos following noxious stimulation was found. Collectively these data give no support for a role for NO in the noxiously evoked induction of c-fos.

Animals↗
PubMed2001

Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hormones and clinical outcomes.

This study explored the acute and long-term consequences of ultrarapid opioid detoxification (URD) in individuals with opioid dependence. In an open case series, seven patients underwent URD and subsequent treatment with daily naltrexone. Structured interviews, integrated rehabilitation and hair sampling were employed in the 12-week course of longitudinal follow-up. Cardiac and pulmonary physiology did not change significantly during the anesthesia phase of URD, but plasma ACTH and cortisol levels increased 15- and 13-fold, respectively. Marked withdrawal and tachypnea in all patients and respiratory distress in one patient occurred during the acute post-anesthesia phase. Withdrawal scores were significantly elevated for 3 weeks compared with baseline in the face of minimal self-reported craving for opioids. Anxiety, depression and vegetative symptoms improved gradually. Four patients remained abstinent of opioid use, two reported a brief period of opioid intake and one relapsed into daily opioid consumption. Given its effect on breathing and stress hormones, this procedure should be conducted by experienced anesthesiologists. The fact that URD and subsequent naltrexone treatment appears to cause a dissociation effect in the usual relationship between withdrawal and craving has implications for behavioral pharmacology. Further research is needed on the efficacy, safety, mechanisms and neurobiological sequelae of the procedure.

Adrenocorticotropic Hormone↗
PubMed2001

Issues concerning association studies for fine mapping a susceptibility gene for a complex disease.

The usefulness of association studies for fine mapping loci with common susceptibility alleles for complex genetic diseases in outbred populations is unclear. We investigate this issue for a battery of tightly linked anonymous genetic markers spanning a candidate region centered around a disease locus, and study the joint behavior of chi-square statistics used to discover and to localize the disease locus. We used simulation methods based on a coalescent process with mutation, recombination, and genetic drift to examine the spatial distribution of markers with large noncentrality parameters in a case-control study design. Simulations with a disease allele at intermediate frequency, presumably representing an old mutation, tend to exhibit the largest noncentrality parameter values at markers near the disease locus. In contrast, simulations with a disease allele at low frequency, presumably representing a young mutation, often exhibit the largest noncentrality parameter values at markers scattered over the candidate region. In the former cases, sample sizes or marker densities sufficient to detect association are likely to lead to useful localization, whereas, in the latter case, localization of the disease locus within the candidate region is much less likely, regardless of the sample size or density of the map. The effects of increasing sample size or marker density are also investigated. Based upon a single marker analysis, we find that a simple strategy of choosing the marker with the smallest associated P value to begin a laboratory search for the disease locus performs adequately for a common disease allele. We also investigated a strategy of pooling nearby sites to form multiple allele markers. Using multiple degree of freedom chi-square tests for two or three nearby sites, we found no clear advantage of this form of pooling over a single marker analysis. Genet. Epidemiol. 20:432-457, 2001. Published by Wiley-Liss, 2001.

Case-Control Studies↗
PubMed2001

Naming and verbal memory skills in adults with Attention Deficit Hyperactivity Disorder and Reading Disability.

Research suggests that children with Attention Deficit Hyperactivity Disorder (ADHD) and Reading Disability (RD) can be differentiated based on their performance on measures of naming and verbal memory. It is not known whether this same pattern characterizes adults with these disorders. In this study, adults with and without ADHD and RD were compared on naming and verbal memory abilities. Results did not support the hypothesis that adults with ADHD and RD are significantly different from each other, or from a contrast group, on naming and verbal memory measures after controlling for Full-Scale IQ (FSIQ). These results were replicated across two sets of classification criteria used to identify diagnostic groups. Factors that could account for the inconsistency in research findings with children and adult subjects are discussed.

Adolescent↗
PubMed2001

A nonsense mutation in the alpha1 subunit of the inhibitory glycine receptor associated with bovine myoclonus.

Inherited congenital myoclonus of Poll Hereford calves is an autosomal recessive disease characterized by hyperesthesia and myoclonic jerks of the skeletal musculature that occur both spontaneously and in response to sensory stimuli. Binding studies have previously shown that myoclonus is associated with specific loss of [(3)H]strychnine-binding sites from spinal cord and brain stem in affected calves. In order to identify the mutation responsible for myoclonus, we examined the candidate genes, glycine receptor alpha1 (Glra1) and beta (Glrb) subunits, in affected and normal cattle. A nonsense mutation was found at amino acid 24, located in exon 2 of the Glra1 gene in both cDNA and genomic sequences from affected but not control animals. Immunohistochemistry, with a monoclonal antibody to alpha and beta subunits of the glycine receptor, revealed a loss of cell surface immunoreactivity in myoclonic animals, suggesting a failure in the assembly of the receptor that could explain the characteristic phenotype of the disease.

Alleles↗
PubMed2001

Evidence that nitric oxide-induced synthesis of cGMP occurs in a paracrine but not an autocrine fashion and that the site of its release can be regulated: studies in dorsal root ganglia in vivo and in vitro.

As nitric oxide is a gas, it cannot be stored and has to be synthesized as required. This suggests that it could be released wherever nitric oxide synthase (NOS) is activated and due to its unstable state will react with appropriate targets at this site of production. In both dissociated dorsal root ganglion (DRG) cultures and in acutely isolated, but intact, DRG, treatment with capsaicin or bradykinin caused cGMP synthesis, which could be blocked by NOS inhibitors. The cGMP was synthesized in cells different from those expressing the neuronal isoform of NOS (nNOS). In dissociated cultures many of the cells stimulated to produce cGMP were neurons, whereas in isolated ganglia they were always satellite glia cells. Surprisingly, the satellite glia cells surrounding the nNOS-containing neurons did not contain cGMP. Following nerve section in adult rats, many axotomized ganglion neurons expressed nNOS. Again in these axotomized ganglia, most cGMP was expressed in the satellite glia surrounding nNOS-negative neurons. However, an nNOS-selective inhibitor reduced the cGMP present in these axotomized ganglia, suggesting that the cGMP synthesized is stimulated by NO (nitrogen monoxide) produced by nNOS. In both dissociated cultures and axotomized ganglia, nNOS-containing processes were observed close to cGMP-positive cells. These observations lead to the suggestion that NO acts in a paracrine fashion when stimulating the synthesis of cGMP and may not be synthesized at all sites containing nNOS.

Animals↗
PubMed2001

Prospects for association-based fine mapping of a susceptibility gene for a complex disease.

The potential of association studies for fine-mapping loci with common disease susceptibility alleles for complex genetic diseases in outbred populations is unclear. For a battery of tightly linked anonymous genetic markers spanning a candidate region centered around a disease locus, simulation methods based on a coalescent process with mutation, recombination, and genetic drift were used to study the spatial distribution of markers with large noncentrality parameters in a case-control study design. Simulations with a disease allele at intermediate frequency, presumably representing an old mutation, tend to exhibit the largest noncentrality parameter values at markers near the disease locus. In contrast, simulations with a disease allele at low frequency, presumably representing a young mutation, often exhibit the largest noncentrality parameter values at markers scattered over the candidate region. In the former case, sample sizes or marker densities sufficient to detect association are likely to lead to useful localization, whereas, in the latter case, localization of the disease locus within the candidate region is much less likely, regardless of the sample size or density of the map. The simulations suggest that for a single marker analysis, the simple strategy of choosing the marker with smallest associated P value to begin a laboratory search for the disease locus performs adequately for a common disease allele.

Alleles↗
PubMed2001

Inhibition of neuronal nitric oxide synthase results in neurodegenerative changes in the axotomised dorsal root ganglion neurons: evidence for a neuroprotective role of nitric oxide in vivo.

In axotomised adult rat dorsal root ganglion (DRG), many neurons show a marked increase in expression of neuronal nitric oxide synthase (nNOS). It has been established that NO functions as a neuron-glial signalling molecule by generating cGMP in glia cells that surround the neuron in DRG. Furthermore, in cultures of dissociated DRG deprived of nerve growth factor, many neurons expressed nNOS and cGMP and subsequently died if either enzyme's activity was inhibited suggesting that NO-cGMP pathway could be neuroprotective in stressed DRG neurons. This has now been tested in vivo. It was found, 10 days after sciatic axotomy that nNOS was expressed in 36% of DRG neurons in the L5 and L6 ganglia giving rise to the damaged nerve, compared with 6% in contralateral ganglia. Almost all nNOS neurons and 24% of non-nNOS neurons expressed c-Jun in their nuclei. Ten days following axotomy, treatment with the relatively selective nNOS-blocker, 1-(2-trifluoromethylphenyl) imidazole (TRIM), caused morphology changes in approximately 50% of neurons that consisted of vacuolations, blebbing and highly irregular cell boundaries. Sham operated, TRIM treated, nerve-sectioned, vehicle treated, and controls did not show these changes. These observations further support the view that NO could be neuroprotective in some injured/stressed primary sensory neurons.

Animals↗
PubMed2001

Orexin-A immunoreactive neurons in the rat hypothalamus do not contain neuronal nitric oxide synthase (nNOS).

The lateral hypothalamic area (LHA), a key site involved in the central control of feeding and energy homeostasis, contains populations of neurons that produce the orexin peptides or nitric oxide, two chemical factors that increase food intake. In this study, we used immunohistochemistry to investigate the possibility that rat LHA neurons co-express orexin-A and neuronal nitric oxide synthase (nNOS). The orexin-A and nNOS cell populations in the LHA showed extensive overlap without co-localization, and no evidence of direct anatomic contact was found. The finding that LHA neurons do not co-localize orexin-A and nNOS may suggest that the actions of the orexins and nitric oxide on food intake are mediated via independent mechanisms, however, nitric oxide is a diffusible molecule and could potentially affect the activity of orexin neurons via a non-synaptic mechanism.

Animals↗
PubMed2001

Choroidal detachment and expulsive choroidal hemorrhage.

ECH occurring during open globe surgery is no longer synonymous with loss of the eye. If the eye is closed immediately (i.e., the hemorrhage does not become expulsive) and modern secondary reconstruction techniques are applied, the prognosis is good. Prophylaxis, however, is the ultimate goal, achieved by a conscious consideration of all risk factors and planning of the surgical intervention accordingly ECH nevertheless can occur, for which the surgeon must be mentally prepared and then act swiftly, based on a previously designed strategy. All ophthalmologists performing (especially open globe) surgery should remain alert. Although new techniques such as small, self-sealing incisions and phacoemulsification have lowered the ECH risk, it is still not zero. (3,44,71) Once the wound is closed and the bleeding has stopped, maneuvers such as drainage or even proceeding with the original surgery can be considered, but the risks of such a course must be carefully analyzed first. Comprehensive secondary reconstruction is best placed in the hands of specialists.

Choroid Diseases↗