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Biomedical subjects

J L Thomson

Publications and source records attributed to J L Thomson.

At least 19 recordsLinked to original sources
PubMed2005

Colchicine and 2-methoxyestradiol Inhibit Human Angiogenesis.

BACKGROUND: Angiogenesis is a critical determinant of tumor growth and the development of metastases. Tubulin inhibitors have been shown to be effective inhibitors of angiogenesis. We hypothesized that colchicine, a well-know tubulin inhibitor and 2-methoxyestradiol (2 MeOH), a novel tubulin inhibitor, would limit the initiation of a human angiogenic response and would limit subsequent neovessel growth in a dose-dependent manner. METHODS: To test this hypothesis, we cultured full-thickness human placental vein discs from three placentas in a fibrin-thrombin clot model. Both colchicine and 2 MeOH were tested over a wide range of concentrations (10(-6) to 10(-12) M) to determine their effect on the percent of wells that initiated an angiogenic response (%I) and the subsequent growth (Angiogenic Index, 0-16 range) of vein-derived neovessels. RESULTS: Colchicine at doses of 10(-6) and 10(-8) M completely inhibited the angiogenic response (CI: 95%, P < 0.0001) but lower (10(-10) to 10(-12) M) doses did not significantly inhibit angiogenesis (P = NS). Effective in vitro colchicine levels far exceed achievable non-toxic human plasma levels. In contrast, 2-methoxyestradiol decreased initiation and angiogenic growth significantly at 10(-6) M (CI: 95%, P < 0.0001), but did not significantly decrease angiogenesis at doses of 10(-8), 10(-10), or 10(-12) M. In contrast to colchicine, human plasma levels of 10(-6) M 2 MeOH are achievable clinically with little or no associated toxicity. CONCLUSIONS: Effective in vitro drug levels of 2 MeOH can be achieved in vivo, suggesting that 2 MeOH may have a role in the clinical treatment of angiogenesis-dependent diseases.

2-Methoxyestradiol↗
PubMed1999

Expression of cyclooxygenase 1 and 2 by human gastric endothelial cells.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and cause gastric ulceration. NSAIDs also impair granulation tissue angiogenesis and healing of established gastric ulcers in humans. The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inhibition of either or both COX isoforms (COX-1 and COX-2). AIMS: To investigate COX expression by human gastric endothelial (HuGE) cells during angiogenesis in vitro. METHODS: COX-1 and COX-2 expression by HuGE cells was investigated by western blot analysis, indirect immunofluorescence, reverse transcriptase polymerase chain reaction, and measurement of prostaglandin E(2) synthesis. Plating onto basement membrane matrix and stimulation by phorbol ester were used as in vitro models of angiogenesis. RESULTS: Under normal culture conditions (30% serum), HuGE cells expressed COX-1 and low levels of COX-2. COX-2 expression was induced in HuGE cells in both angiogenesis models. Prostaglandin E(2) production and tubular structure formation by HuGE cells on basement membrane matrix was significantly inhibited by a selective COX-2 inhibitor (NS-398). CONCLUSION: Angiogenesis by HuGE cells in vitro was associated with induction of functional COX-2 expression. A selective COX-2 inhibitor significantly decreased HuGE cell angiogenesis on basement membrane matrix. Extrapolation of these data to human gastric ulcer angiogenesis in vivo suggests that selective COX-2 inhibitors could delay gastric ulcer healing to the same extent as traditional NSAIDs which are non-selective COX inhibitors.

Blotting, Western↗
PubMed1997

Photoreceptor rim protein: partial sequences of cDNA show a high degree of similarity to ABC transporters.

PURPOSE: To isolate and sequence cDNA for bovine rim protein, a large membrane-bound glycoprotein found in photoreceptor outer segments. METHODS: Bovine rim protein was N-terminally sequenced (22 residues) and fragments were prepared by partial proteolysis. Two internal sequences of 21 and 18 amino acid residues were obtained from 35 kDa and 32 kDa fragments, respectively. Sense and anti-sense oligonucleotide primers were constructed, based on the peptide sequences derived from the 35 kDa and 32 kDa fragments, respectively, and the polymerase chain reaction (PCR) was used to amplify a 150 bp sequence from bovine retinal cDNA. RESULTS: The amplified sequence coded for the remainder of the peptide sequence determined from the 35 kDa fragment, which was not present in the primer, confirming that it was derived from the rim protein. The 150 bp sequence was translated to give a 50 amino acid peptide. Part of this peptide was compared with Dna sequence databases using the TFastA program, which found 94.6% identity with an EST derived from human retina and 86.1% identity to the mouse abc1 transporter. CONCLUSIONS: It is proposed that rim protein is a member of the ATP transporter family of proteins. It may be involved in transport of molecules involved in visual transduction across the photoreceptor disk membrane.

ATP-Binding Cassette Transporters↗
PubMed1996

Vasodilator responses of rat isolated tail artery enhanced by oxygen- dependent, photochemical release of nitric oxide from iron-sulphur-nitrosyls.

1. The vasodilator properties and photochemical decomposition of two synthetic iron-sulphur-nitrosyl clusters (cluster A: [Fe4S4(NO)4], tetranitrosyl-tetra-mu 3-sulphido-tetrahedro-tetrairon; and B:[Fe4S3 (NO)7]-1, heptanitrosyl-tri-mu 3-thioxotetraferrate(-1)) have been investigated. Experiments were carried out on isolated, internally-perfused segments of rat tail artery. 2. Bolus injections (10 microliters) of A or B ( > 0.25 mM) delivered into the internal perfusate generated sustained (or S-type) vasodilator responses, characterized by a persistent plateau of reduced tone due to NO released from clusters which enter and become trapped within endothelial cells. Clusters were therefore irradiated with visible laser light (lambda = 457.9 or 514.5 nm) either (a) in solution, while passing through a glass tube en route to the artery; or (b) when retained within the endothelium, by illuminating the artery directly during the plateau of an S-type response. Irradiation produced an additional vasodilator response, the magnitude of which depended upon wavelength and laser beam energy. 3. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (100 microM), had no effect on light-induced vasodilator responses. However, they were (a) blocked entirely by adding oxyhaemoglobin (5 microM) to the internal perfusate; and (b) greatly enhanced by the enzyme superoxide dismutase (150 u ml-1). 4. Photolysis of cluster B was measured by absorption spectroscopy and by detecting NO released with an electrochemical sensor. The photochemical reaction was found to be oxygen-dependent. The half-time for inactivation of cluster-derived NO was measured by interposing different lengths of tubing (i.e. time delays) between the photolysis tube and NO sensor. The steady-state probe current decayed exponentially with increasing delay time, with a t 1/2 of 21 s. The amplitudes of vasodilator responses of the tail artery also decreased exponentially by increasing the time delay (t 1/2 = 58 s). Superoxide dismutase (150 u ml-1) prevented this from happening, showing that "inactivation' of cluster-derived NO was caused by reaction with superoxide anions formed during photolysis. 5. We conclude that potentiation of vasodilator responses to iron-sulphur-nitrosyl clusters by visible light is due to an oxygen-dependent photochemical reaction which accelerates the release of ligated nitrosyl groups as free NO. Based on our measurements, we estimate that ca 100 pM NO is sufficient to produce a just-detectable additional vasodilatation and that the ED50 dose is ca 3.7 nM.

Animals↗
PubMed1993

Further experience at the Bristol Centre, following the installation of a second MRI unit.

A second magnetic resonance imaging (MRI) machine has been installed at the Bristol Centre, which therefore now has two systems (both 0.5T), working alongside, one being 5 years older than the other. This has allowed a virtual doubling of patient throughput. The financial cost of adding the necessary building extension and the comparative capital costs of the two machines, together with the differences in the cryogen requirements are itemized; as are the extra number of staff engaged. It is estimated that the new machine cost approximately half that of the original, bought in 1987, after allowing for inflation; and that the revenue costs have increased by only 25% in the first year, with a likely increase of about 45% in year two. One result has been that in Bristol, where there are now three MRI machines, myelography and knee arthrography as diagnostic procedures have almost disappeared.

Appointments and Schedules↗
PubMed1991

Cranial magnetic resonance imaging in patients with tuberous sclerosis and normal intellect.

The pattern of cerebral hamartomas among a population of patients with tuberous sclerosis and normal intellect was determined. All patients with tuberous sclerosis over 5 years old with normal intellect who were resident in the Bath health district were offered cranial scanning by magnetic resonance imaging. Cerebral axial and coronal images were obtained in 10 mm contiguous sections with a Picker 0.5 tesla magnetic resonance imaging unit. The number, size, and distribution of lesions found was recorded. Eleven of 13 eligible patients underwent scanning. Two patients had normal scans. Seven patients had between one and five subependymal nodules. Nine patients had between two and nine cerebral tubers best seen on T2 weighted images. Our findings suggest that the wrong conclusions may be drawn if the number of lesions alone is used to predict neurological outcome in tuberous sclerosis.

Adolescent↗
PubMed1990

M.R.I. in Alzheimer's disease.

At present, the clinical diagnosis of Alzheimer's disease is shown to be unreliable. In the absence of any laboratory or blood test, a study of the brain configuration using Magnetic Resonance Imaging, can help to demonstrate the differential atrophy involving the temporal lobe more than elsewhere, which is present in the majority of cases of Alzheimer's disease. Area measurements have been obtained in the coronal slice and comparison made between 20 controls and 10 patients suffering from early dementia.

Aged↗
PubMed1989

Experiences at the new magnetic resonance imaging centre at Bristol.

The magnetic resonance imaging unit in Bristol has been housed in a new purpose-built centre, shared between three District Health Authorities, but operated entirely separate from the National Health Service. Inasmuch as this is thought to be a unique arrangement, the publication of its finances and statistics have been readily tabulated at the end of its first year's operation, and may be of interest to others planning a similar organization.

Ambulatory Care Facilities↗
PubMed1985

Assessment of the Meditech Euroscanner for clinical use.

In April 1983, Prototype I of the Meditech Whole Body CT Scanner (Euroscanner) was installed at Frenchay Hospital as part of a Department of Health and Social Security (DHSS) trial to assess its function and reliability. After a few months usage, several modifications were made to the machine. The official trial therefore commenced on Prototype II in the middle of January 1984 and lasted until the end of July 1984. During that time a planned changeover took place in the Neuroradiological Department, with the replacement of a ten-year-old EMI 1010 head scanner by an IGE 8800. This meant that from the beginning of May until the end of July, the Meditech Scanner was the only available CT scanner in a busy Regional Department with District Hospital commitments as well. This paper provides a summary of the clinical experiences resulting from the use of the machine, and is a rider to that in which Greensmith et al (1985) describe the physical properties of the machine.

Diagnostic Errors↗
PubMed1983

Computed tomography in the investigation of dementia.

To assess the value of computed tomography in investigating patients with dementia, 500 consecutive patients presenting with a provisional clinical diagnosis of dementia of recent onset were reviewed and the results analysed in a computer. Most patients had either cerebral atrophy or infarction, but 82 patients had a normal scan and 42 others had tumours. More than 10% of all patients, including 5% with no other symptoms or signs, had a treatable lesion. Various associated symptoms and signs were useful pointers to such a treatable lesion and clearly indicated computed tomography. Accurate diagnosis is the cornerstone of proper management, and if a few patients with treatable lesions can be identified then the benefits to all concerned may be incalculable.

Age Factors↗
PubMed1983

Surface treatment studies aimed at streamlining fissure sealant application.

Three laboratory studies were carried out with the aim of improving or streamlining enamel surface treatment procedures in fissure sealing. In Study 1, the effect of reducing acid etch time from 60 s to 10 s was assessed by SEM and tensile bond strength measurements. Reduction in etch time produced a finer etch pattern, gave a reduced but still high, bond-strength, albeit with slightly poorer long-term adhesion. Study 2 showed that a conventional acid etch treatment could completely remove acquired pellicle, without prior prophylaxis. SEM studies and bond-strength measurements corroborated this view. In Study 3, compressed air and chemical drying agents were compared for drying speed and efficiency. Compressed air gave more rapid, thorough drying, and greater resultant bond strengths.

Acid Etching, Dental↗
PubMed1983

Isodense colloid cysts of the third ventricle: a diagnostic and therapeutic problem resolved by ventriculoscopy.

Eighteen patients with a colloid cyst of the 3rd ventricle presented to the Frenchay Hospital Neurosurgery Unit. The investigations included computed tomography (CT). Of these patients, 9 had radiographically isodense cysts that caused considerable diagnostic difficulties, being described only as an anterior 3rd ventricular space-occupying lesion and lateral ventricular dilatation in all but 2 cases. The clinical findings are described and the CT appearance is discussed. The new use of ventriculoscopy may resolve the problem rapidly; ventriculoscopy made the diagnosis in 5 cases and confirmed a CT diagnosis in 3 others. (It has also confirmed the diagnosis in 2 cases of hyperdense cysts.) Lately, it has been possible to aspirate the cyst contents endoscopically or, if the colloid is too viscous, to remove it with endoscopic rongeurs. After either of these procedures, the cyst wall can be coagulated with diathermy endoscopically. The method is described, and the advantages over other investigations and treatment are discussed.

Adolescent↗
PubMed1981

Computed tomographic appearances in microgliomatosis.

The computed tomography (CT) appearances of 11 patients with microgliomatosis have been reviewed, and as a result it is possible to suggest that there may be typical features for the recognition of such tumours. In this series three fairly distinctive patterns were encountered. In view of their reputed response to radiotherapy, there is a strong case for making the diagnosis of such lesions, and CT has given the opportunity of alerting the surgeon and the pathologist to the likelihood of their presence at an early stage.

Aged↗
PubMed1981

The effect of salivary contamination on fissure sealant--enamel bond strength.

The effect of accidental salivary contamination on the retention of fissure sealants is investigated via in vitro bond tests and scanning electron microscopy. The strength of the bond between sealant and saliva contaminated and washed enamel (168 +/- 14 kg cm-2) is not found to be significantly different from the bond strength to uncontaminated enamel (174 +/- kg cm-2). Unwashed contaminated enamel gives significantly reduced bond strength (68 +/- 11 kg cm-2).

Dental Bonding↗
PubMed1978

Computerised axial tomography in posterior fossa lesions.

The author found that 191 patients out of the first 6000 examined by the EMI brain scanner had lesions in the posterior fossa. Appearances in acoustic tumours, meningiomas, astrocytomas, haemangioblastomas, medulloblastomas, gliomas of the brain stem and metastases are described.

Astrocytoma↗
PubMed1978

Computerised axial tomography and acute neurological problems of childhood.

The results of computerised axial tomography (CAT) in 80 children with neurological symptoms and/or signs of less than 3 months' duration are discussed in relation firstly to intracranial pathology and secondly to clinical presentation. 26 children had intracranial space-occupying lesions (tumour, abscess, haemorrhage, infarct). CAT was abnormal in 25 of these and diagnostic in 18. A further 20 children had meningitis or encephalitis, and CAT was abnormal in 12. In contrast with this high rate of scans showing pathology, CAT was abnormal in only 4 of the remaining 34 children who had less definite or no intracranial disease. Analysis of clinical presentation showed that 42 of 69 children presented with persisting neurological signs and of these, 25 had an intracranial space-occupying lesion and 29 had abnormal CAT. Only 5 of 27 children who had symptoms alone or signs lasting less than 24 hours had abnormal CAT, and no intracranial lesion requiring specific treatment was missed. CAT is useful for demonstrating the site, size, and nature of many lesions. The scan may not initially be abnormal in brain stem gliomas and in small subdural collections of fluid.

Adolescent↗