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Biomedical subjects

S Love

Publications and source records attributed to S Love.

At least 73 records · Page 4Linked to original sources
PubMed2001

The(13)C-octanoic acid breath test for detection of effects of meal composition on the rate of solid-phase gastric emptying in ponies.

The aim of this study was to apply the(13)C-octanoic acid breath test for detection of alterations in the rate of solid-phase gastric emptying, induced by changes in test meal composition, in ponies. After a 14 hour fast the ponies (n = 4) ingested a test meal with 0, 35 or 70 ml soya oil, and labelled with 250 mg(13)C-octanoic acid. Each pony was given each of the three test meals on three separate occasions, in a randomised order. Exhaled breath samples were collected for 12 hours after ingestion of the test meal. Breath samples were analysed by continuous flow isotope ratio mass spectrometry. Three indices of breath(13)C-enrichment were computed, half-dose recovery time (t 1/2), gastric emptying coefficient (GEC) and time to peak breath(13)C-excretion t(max). The(13)C-octanoic acid breath test was a reliable means of assessing the significantly decreased rate of gastric emptying in the pony, associated with addition of soya oil to the test meal.

Animal Feed↗
PubMed2001

Trigeminal neuralgia: pathology and pathogenesis.

There is now persuasive evidence that trigeminal neuralgia is usually caused by demyelination of trigeminal sensory fibres within either the nerve root or, less commonly, the brainstem. In most cases, the trigeminal nerve root demyelination involves the proximal, CNS part of the root and results from compression by an overlying artery or vein. Other causes of trigeminal neuralgia in which demyelination is involved or implicated include multiple sclerosis and, probably, compressive space-occupying masses in the posterior fossa. Examination of trigeminal nerve roots from patients with compression of the nerve root by an overlying blood vessel has revealed focal demyelination in the region of compression, with close apposition of demyelinated axons and an absence of intervening glial processes. Similar foci of nerve root demyelination and juxtaposition of axons have been demonstrated in multiple sclerosis patients with trigeminal neuralgia. Experimental studies indicate that this anatomical arrangement favours the ectopic generation of spontaneous nerve impulses and their ephaptic conduction to adjacent fibres, and that spontaneous nerve activity is likely to be increased by the deformity associated with pulsatile vascular indentation. Decompression of the nerve root produces rapid relief of symptoms in most patients with vessel-associated trigeminal neuralgia, probably because the resulting separation of demyelinated axons and their release from focal distortion reduce the spontaneous generation of impulses and prevent their ephaptic spread. The role of remyelination in initial symptomatic recovery after decompression is unclear. However, remyelination may help to ensure that relief of symptoms is sustained after decompression of the nerve root and may also be responsible for the spontaneous remission of the neuralgia in some patients. In addition to causing symptomatic relief, vascular decompression leads to rapid recovery of nerve conduction across the indented root, a phenomenon that, we suggest, is likely to reflect the reversal of compression-induced conduction block in larger myelinated fibres outside the region of demyelination. Trigeminal neuralgia can occur in association with a range of other syndromes involving vascular compression and hyperactivity of cranial nerves. Clinical observations and electrophysiological studies support the concept that demyelination and ephaptic spread of excitation underlie most, if not all, of these conditions.

Humans↗
PubMed2001

Assessment of the rate of solid-phase gastric emptying in ponies by means of the 13C-octanoic acid breath test: a preliminary study.

The aim of this study was to assess the feasibility of applying the 13C-octanoic acid breath test for assessment of gastric emptying in ponies by investigating the pattern of 13C enrichment in breath following the administration of a test meal +/- 13C-octanoic acid. After a 14 h fast, the ponies received either no meal (Test I) or a standardised test meal labelled with 0 mg (Test II), 125 mg (Test III), 250 mg (Test IV) or 500 mg (Test V) 13C-octanoic acid. For each test (I-V), exhaled breath samples were collected in duplicate at 1 h and immediately before ingestion of the test meal and at frequent intervals thereafter for 12 h. Breath samples were analysed by continuous flow isotope ratio mass spectrometry. Three indices of breath 13C-enrichment were computed; half dose recovery time (t1/2), gastric emptying coefficient (GEC) and time to peak breath 13C-enrichment t(max). For Tests I and II, the ratio of 13CO2:12CO2 remained stable for the duration of the sampling period. For Tests III, IV and V, an increase in the ratio of 13CO2:12CO2 was detected. The test was reproducible within individuals, and intersubject variation was low. Further validation studies of this noninvasive technique are justified.

Animal Feed↗
PubMed2001

Use of the 13C-octanoic acid breath test for assessment of solid-phase gastric emptying in dogs.

OBJECTIVE: To assess the 13C-octanoic acid breath test for determining gastric emptying in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Food was withheld for 12 hours before each test. Expired air was collected 30 minutes and immediately before each test and at frequent intervals thereafter for 6 hours. Concentration of 13CO2 in expired air was determined by use of continuous-flow isotope-ratio mass spectrometry. Basal concentration of 13CO2 was measured in dogs that were not fed a test meal. Effects of the standard unlabeled test meal on basal concentration of 13CO2 were then assessed. The optimum dose of substrate was determined by measuring 13CO2 concentration after ingestion of the standard test meal containing 50 or 100 mg of 13C-octanoic acid, whereas effect of energy density of the test meal on gastric emptying was determined after ingestion of the standard or high-energy labeled test meal. Gastric emptying coefficient (GEC), time to peak 13CO2 concentration (tmax), and half-dose recovery time (t(1/2)) were calculated. RESULTS: Basal concentration of 13CO2 in expired air was not significantly affected by ingestion of the unlabeled test meal. However, 13CO2 concentration significantly increased in a dose-dependent manner after ingestion of the labeled meal. Gastric emptying coefficient, and were significantly different between dogs fed the standard and high-energy test meals, indicating that ingestion of a high-energy meal delays gastric emptying. CONCLUSIONS AND CLINICAL RELEVANCE: The 13C-octanoic acid breath test may be a useful noninvasive and nonradioactive method for assessment of gastric emptying in dogs.

Animals↗
PubMed2000

Activation of caspase-3 in permanent and transient brain ischaemia in man.

Animal studies have shown brain ischaemia to cause oxidative damage to DNA and activation of caspase-3, leading to apoptosis. These changes may be exacerbated by reperfusion. To assess caspase-3 activation after transient and permanent brain ischaemia in man, we examined brain tissue from patients who had experienced a cardiac arrest with resuscitation or an atherothrombotic brain infarct, and died 12 h to 9 days later. Sections were immunostained for activated caspase-3 or the 89 kDa caspase-3-mediated cleavage product of poly(ADP-ribose) polymerase. Brain ischaemia caused activation of caspase-3 in macrophages/microglia. Some neurons showed delayed activation of caspase-3 after cardiac arrest, but very few in atherothrombotic infarcts. In man, activation of caspase-3 plays little part in neuronal death in atherothrombotic infarcts but may contribute to delayed death of neurons after cardiac arrest.

Adult↗
PubMed2000

Methods for detection of haematogenous dissemination of brain tissue after stunning of cattle with captive bolt guns.

Because of concern that the stunning of cattle with captive bolt guns (CBGs) could, if used on an animal with bovine spongiform encephalopathy (BSE), cause embolism of infective brain tissue and carcass contamination, the Ministry of Agriculture, Food and Fisheries commissioned research to assess the risk of haematogenous dissemination of CNS material after stunning. We have devised two methods to investigate this risk. The first involves the concentration of embolic tissue in buffy coat Cytoblocks that can be embedded for sectioning, microscopy and immunocytochemistry. The second method is an ELISA for the presynaptic protein, syntaxin 1B. The methods were validated by analysis of several bovine tissues, including blood samples deliberately contaminated with brain. We then studied jugular venous blood obtained before and after the stunning of 60 cattle with CBGs. Samples obtained, after stunning, from five of the cattle contained CNS tissue within the Cytoblocks and yielded positive syntaxin assays. Syntaxin was also detected in samples from one other animal that had been stunned with a pneumatically operated CBG. The described methods should allow an assessment of the risk of neuroembolism associated with different types of CBG and may also be useful in other contexts.

Abattoirs↗
PubMed2000

Amyloid beta-protein length and cerebral amyloid angiopathy-related haemorrhage.

The relationship between amyloid beta-protein (A beta) length and the apolipoprotein E (APOE) epsilon 2 allele, which is over-represented in cerebral amyloid angiopathy-related haemorrhage (CAAH), has not previously been examined. Of 57 CAA patients studied, 37 had CAAH. All patients, particularly those with CAAH had more blood vessels immunoreactive for A beta 40 than A beta 42 in both the leptomeninges and cerebral cortex. CAAH patients had more A beta 40-immunoreactive blood vessels in the leptomeninges (p < 0.001) and cortex (p = 0.027) than had non-haemorrhage patients. Cortical blood vessels, the usual source of haemorrhage in CAAH, were more frequently A beta 42 immunoreactive in APOE epsilon 2 carriers than in non-epsilon 2 carriers (p = 0.022). The APOE epsilon 2 allele may predispose to CAAH by increasing the seeding of cortical blood vessels by A beta 42.

Aged↗
PubMed2000

Absence of cystatin C mutation in sporadic cerebral amyloid angiopathy-related hemorrhage.

In Icelandic pedigrees a cystatin C mutation, glutamine 68 (L68Q), causes autosomal dominant cerebral amyloid angiopathy-related hemorrhage (CAAH). We examined 33 patients with sporadic CAAH for this mutation. None carried L68Q and, including this report, only one of 52 published cases of sporadic CAAH has had the cystatin C mutation. Despite vascular colocalization of cystatin C with amyloid beta-protein, cystatin C L68Q is rare in sporadic CAAH.

Aged↗
PubMed2000

Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.

Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.

Aged↗
PubMed2000

Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I and large ribosomal RNA sequences and nuclear internal transcribed spacer I sequences from species of Cyathostominae and Strongylinae (Nematoda, Order Strongylida), parasites of the horse.

Three nucleotide data sets, one nuclear (ITS-2) and two mitochondrial (COI and l-rRNA), have been investigated in order to determine relationships among species of Strongylinae and Cyathostominae, intestinal parasites of the horse. The data exhibited a strong mutational bias towards A and T and in the COI gene, silent sites appeared to saturate rapidly partly due to this substitution bias. Thus, the COI gene was found to be less phylogenetically informative than the l-rRNA and ITS-2 genes. Combined analysis of the l-rRNA and ITS-2 genes supported a monophyletic clade of the cyathostomes with Tridentoinfundibulum gobi, which had previously been classified as a nematode of' uncertain origin'. The Strongylinae grouped consistently outside the clade containing the cyathostomes and T. gobi. Molecular analysis failed to provide strong evidence for the separation of cyathostomes into classical genera, as previously defined by morphological classification.

Animals↗
PubMed2000

Neuronal death in brain infarcts in man.

The mechanism of neuronal death in brain ischaemia remains unclear. Morphology, terminal transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) and immunohistochemistry for the pro-apoptotic enzyme caspase-3 (CASP3), for its substrates poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase catalytic subunit (DNA-PKCS) and for poly(ADP-ribose) (PAR), an end-product of PARP activity, were used to investigate neuronal death in brain infarcts from 15 men and 20 women, aged 46-95 years. The infarcts varied in age from 18 h to several months. Neuronal death was characterized morphologically by cell shrinkage, cytoplasmic hypereosinophilia and moderate nuclear pyknosis with later chromatin dispersal and disintegration, but not features of apoptosis. Occasional apoptotic bodies were seen but these appeared to be related to inflammatory cells, endothelial cells and occasional glia, including satellite cells. Neurones within infarcts showed strong nuclear and cytoplasmic labelling for CASP3 during the first 2 days after infarction. Neuronal DNA-PKCS, PARP and poly(ADP-ribose) immunoreactivity was demonstrable in scattered neurones in and adjacent to infarcts for 18-24 h but thereafter declined to below detectable levels in most cases. TUNEL labelled cells towards the edge of the infarcts, particularly at 2-4 days, but most of the labelling could be prevented by preincubation of the sections in diethyl pyrocarbonate to inactivate endogenous nucleases. Between 3 days and 3 weeks, CASP3 and DNA-PKCS were detected in proliferating capillaries and CASP3, PARP and poly(ADP-ribose) in infiltrating macrophages. Our findings indicate that neuronal death in human brain infarcts has some of the early biochemical features of programmed cell death, with upregulation of CASP3 and rapid disappearance of DNA-PKCS and PARP. However, the morphological changes are not those of apoptosis, the DNA cleavage occurs relatively late, and some of the TUNEL is probably mediated by the release of endogenous endonucleases during protease or microwave pretreatment of the damaged tissue.

Adult↗
PubMed2000

Damage and repair of DNA in HIV encephalitis.

Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV infection of CNS macrophages results in neuronal damage is not known. We examined the brains from 15 AIDS autopsies (8 with HIV encephalitis and 7 without) and 4 non-infected control autopsies for the presence of DNA strand breaks, for associated changes in the expression of the DNA repair enzymes KU80 and Poly (ADP-ribose) polymerase (PARP), and for accumulation of amyloid precursor protein (APP). Abundant DNA damage was observed with terminal transferase-mediated dUTP nick end-labeling (TUNEL), however, there was no morphologic evidence of significant neuroglial apoptosis. The DNA repair enzyme KU80 was immunocytochemically detectable in neuronal and glial cells in autopsy brains from patients with and without HIV encephalitis; however, in cases with HIV encephalitis the staining was more prominent than in the infected or non-infected controls without encephalitis. There was no difference in KU80 immunostaining in oligodendroglia from autopsies with and without encephalitis. Immunostaining for PARP was more intense in gray and white matter of cases with HIV encephalitis. No clear spatial relationship existed between expression of DNA repair enzymes and the spatial proximity of microglial nodules or HIV-infected macrophages. The cytoplasm of cortical and subcortical neurons immunostained for APP Stronger cortical neuronal APP staining was observed in cases without HIV encephalitis. Staining of deep gray matter neurons was similar, irrespective of the presence or absence of encephalitis. While foci of intense APP staining were noted in white matter not related to HIV infection, they were associated with foci of opportunistic infections (e.g. due to CMV or PML). We conclude that damaged DNA and altered patterns of expression of DNA repair proteins and APP are common findings in the brains of AIDS patients at autopsy, but do not have a spatial relationship to HIV-infected macrophages.

AIDS Dementia Complex↗
PubMed2000

Caecocaecal and caecocolic intussusceptions associated with larval cyathostomosis in four young horses.

This report describes the clinical and pathological features of 4 horses affected by caecocaecal or caecocolic intussusceptions associated with larval cyathostomiasis. In each case, there was clinical and/or pathological evidence of concurrent larval cyathostomosis. They all demonstrated variable signs including diarrhoea, pyrexia, weight loss and subcutaneous oedema and cyathostome larvae were identified in the faeces of 3 of the horses. These cases highlight the need to consider caecal intussusceptions as a possible complication in horses affected by larval cyathostomosis, especially where signs of abdominal pain are severe or persistent.

Animals↗
PubMed2000

Association of interleukin-1 gene polymorphisms with Alzheimer's disease.

Interleukin-1 (IL-1) is markedly overexpressed in Alzheimer's disease. We found the IL-1A 2,2 genotype in 12.9% of 232 neuropathologically confirmed Alzheimer's disease patients and 6.6% of 167 controls from four centers in the United Kingdom and United States (odds ratio, 3.0; controlled for age and for ApoE [apolipoprotein E] genotype). Homozygosity for both allele 2 of IL-1A and allele 2 of IL-1B conferred even greater risk (odds ratio, 10.8). IL-1 genotypes may confer risk for Alzheimer's disease through IL-1 overexpression and IL-1-driven neurodegenerative cascades.

Aged↗
PubMed1999

Chemically synthesized ubiquitin extension proteins detect distinct catalytic capacities of deubiquitinating enzymes.

We have used solid-phase chemistry to synthesize proteins equivalent to a human ubiquitin precursor (ubiquitin-52-amino-acid ribosomal protein fusion; UBICEP52) and representative of isopeptide-linked ubiquitin-protein conjugates [ubiquitin-(epsilonN)-lysine]; these proteins were precisely cleaved by a purified recombinant Drosophila deubiquitinating enzyme (DUB), UCH-D. Along with the previously synthesized ubiquitin-(alphaN)-valine, these synthetic proteins were used as substrates to assess the catalytic capacities of a number of diverse DUBs expressed in Escherichia coli: human HAUSP; mouse Unp; and yeast Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p. Distinct specificities of these enzymes were detected; notably, in addition to UCH-D, isopeptidase activity [ubiquitin-(epsilonN)-lysine cleavage] was only associated with Yuh1p, Unp, Ubp1p, and Ubp2p. Additionally, human placental 26S proteasomes were only able to cleave UBICEP52 and ubiquitin-(epsilonN)-lysine, suggesting that 26S proteasome-associated DUBs are class II-like. This work demonstrates that the synthetic approach offers an alternative to recombinant methods for the production of small proteins in vitro.

Animals↗
PubMed1999

Demographic characteristics of the equine population of northern Britain.

The size, composition and distribution of the equine population of Scotland and the five northernmost counties in England were estimated through a series of mailed questionnaire surveys of sentinel veterinary practices and horse owners. An estimated 96,622 equine animals were kept by an estimated 26,114 owners. The mean (sd) age of the population was 11.0 (7.5) years (range one month to 37 years). Thoroughbred or thoroughbred-cross animals were the most numerous, constituting 30 per cent (95 per cent confidence interval 27 to 33 per cent) of the total population. The ratio of males:females was 1:1.

Animals↗