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Biomedical subjects

M Dawson

Publications and source records attributed to M Dawson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Lymphadenopathy and non-suppurative meningo-encephalitis in calves experimentally infected with bovine immunodeficiency-like virus (FL112).

In an experiment on bovine immunodeficiency-like virus (BIV), the virological and serological aspects of which were reported in an earlier paper, three groups (A, B and C) of three calves were inoculated subcutaneously with a recently isolated strain (FL112). For group B and group C, the virus was suspended in milk, and for group C (controls) the viral suspension was subjected to pasteurization before inoculation. The calves were killed for necropsy 12 months later. Clinical assessment revealed subtle ataxia in two group A calves, which took the form of an intermittent "shifting" (from one leg to another) lameness, and palpable enlargement of the pre-scapular lymph nodes in one group B animal. At necropsy, haemal lymph nodes (0.1 to 0.5 cm in diameter), occurring singly, were observed in all animals. However, in groups A and B (but not C), enlarged haemal lymph nodes (< or = 2 cm in diameter) were also seen, occurring singly and in chains; and in one group A animal they occurred in grape-like clusters. In groups A and B (but not C), histopathological examination revealed generalized hyperplastic changes in lymph nodes, especially the haemal lymph nodes. This finding was particularly striking in the two clinically ataxic animals from group A, which also showed a non-suppurative meningo-encephalitis; the latter was possibly the cause of the subtle clinical signs. This study supports previous findings on lymphadenopathy resulting from experimental infection with BIV.

Animals↗
PubMed1998

Growth inhibition of DU-145 prostate cancer cells by a Bcl-2 antisense oligonucleotide is enhanced by N-(2-hydroxyphenyl)all-trans retinamide.

Hormonally insensitive prostate cancer is a relatively slow-growing, but usually fatal, disease with no long-term treatment options. Transformation of normal prostate cells to a malignant phenotype often involves corruption of the apoptotic machineries. Bcl-2 protein is one of the key inhibitors of apoptosis and is often unregulated in advanced prostate cancer. The prostate cancer cell line DU-145 was used as a model of a hormonally insensitive, advanced prostate cancer. Cell growth in liquid culture was significantly inhibited by antisense Bcl-2 oligonucleotides compared with control sense oligonucleotides; inhibition by these oligonucleotides was significantly enhanced on combination with the synthetic retinoid N-(2-hydroxyphenyl)all-trans-retinamide (2-HPR). Interestingly, growth inhibition occurred in the absence of apoptosis as measured using two assay techniques. We hypothesize that in these recalcitrant cells the apoptotic pathway is compromised at several levels, and Bcl-2 may play another role in promoting cell growth. The use of Bcl-2 antisense oligonucleotides plus 2-HPR may provide a novel approach to therapy of hormone-resistant prostate cancer.

Adenocarcinoma↗
PubMed1998

Civilian parachute injuries; 10 years on and no lessons learned.

The Maidstone Hospital provides trauma services to one of the largest parachute clubs in the United Kingdom. We studied injuries sustained at the club in 1994 and compared results with equivalent data from 1984. The injury rate for first time jumpers in the current study was 1.2%; half of these cases required admission for an average of 10 d. Individual morbidity and loss of productivity lasted far longer. No lessons had been learned from the first study. We question parachuting as a fund-raising venture and suggest re-evaluating the training of novice parachutists, perhaps with mandatory use of the safer rectangular parachute. At a time when healthcare rationing is an issue, individuals engaging in activities such as these might be required to indemnify themselves against the medical costs of injury currently met by the state.

Accidents↗
PubMed1997

Overexpression of eukaryotic initiation factor 4E (eIF4E) in breast carcinoma.

BACKGROUND: Eukaryotic initiation factor 4E (eIF-4E) is a 25-kilodalton phosphoprotein that binds specifically to mRNA as the initial step for mRNA translation. An elevated level of eIF4E has been associated with the up-regulation of various protooncogene products. Transfection of cell lines by viral vectors with eIF4E overexpression has resulted in malignant transformation. The objective in this study was twofold: to examine benign and malignant breast specimens for eIF4E expression, and to determine whether eIF4E overexpression may have prognostic potential. METHODS: Western blot analysis was performed on benign and malignant breast specimens using anti-eIF4E rabbit antiserum. Quantification was accomplished by developing blots with nitroblue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate and densitometry. Confirmation of eIF4E overexpression at the cellular level was performed using immunohistologic staining in situ. RESULTS: The authors examined 112 breast specimens for eIF4E protein expression. Of the 52 benign breast specimens examined, none showed eIF4E overexpression. All 12 ductal carcinoma in situ specimens were found to overexpress eIF4E in the intermediate range (mean elevation: 2.5-fold). Of the 48 breast carcinoma specimens examined, all had eIF4E elevation at levels of 3-30-fold (mean: 10.5 +/- 0.9-fold). Charts from 39 patients with Stage I, II, and III breast carcinoma were reviewed. In ten patients with eIF4E overexpression of < sevenfold, there was no recurrence or death from breast carcinoma. In the 29 breast carcinoma patients with > or = 7-fold eIF4E overexpression, 9 patients had breast carcinoma recurrences and 5 had died from disease at last follow-up. The median follow-up in this study was 34.5 months. CONCLUSIONS: Overexpression of eIF4E was observed in malignant breast specimens but not in normal or benign breast tissues. In patients with breast carcinoma, the group with high eIF4E overexpression (> or = 7-fold) experienced a worse clinical outcome (higher recurrences and death) compared with the group with low eIF4E overexpression (< 7-fold).

Blotting, Western↗
PubMed1997

Highly sensitive gas chromatographic-mass spectrometric method for morphine determination in plasma that is suitable for pharmacokinetic studies.

A sensitive method was devised to determine morphine plasma concentrations by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM) with nalorphine as the internal standard. This method was rugged, reliable, selective and sensitive and was used to determine the morphine content of over 2000 samples. Sample preparation involved extraction of basified sample using n-butyl chloride-chloroform (5:1) and evaporation of the extract to dryness. The residue was derivatised with pentafluoropropionic anhydride, evaporated to dryness, reconstituted in 40 microl toluene and injected onto the GC-MS. For a sample size of 1 ml, the limit of quantitation was 0.75 ng/ml (S/N ratio 10:1) and the estimated limit of detection was calculated to be 0.2 ng/ml (S/N ratio 3:1), expressed as morphine base. Precision (n=5) was 4.9% at 0.75 ng/ml, 6.8% at 1.5 ng/ml, 3.0% at 37.5 ng/ml and 2.3% at 150 ng/ml. Standard curves for the range of 0-750 ng/ml morphine in plasma were linear with all r2 values greater than 0.99. No interfering peaks were seen for either morphine or internal standard in the blank samples. The method is suitable for pharmacokinetic studies after subclinical doses of morphine where it has been used to study morphine plasma concentrations for 6 h after a dose of only 2 mg.

Administration, Inhalation↗
PubMed1997

Bovine immunodeficiency-like virus: inactivation in milk by pasteurisation.

Bioassay was used to determine whether bovine immunodeficiency-like virus (BIV) in milk was inactivated by pasteurisation. Three groups of three calves were inoculated with virus (BIV isolate FL112), milk seeded with virus and milk seeded with virus that had been pasteurised before inoculation, respectively. Seroconversion to BIV was monitored for 12 months by an indirect immunofluorescence assay. The presence of BIV proviral DNA in peripheral blood was determined by a nested polymerase chain reaction (PCR). The animals were euthanized and virus isolation and PCR were attempted on peripheral blood mononunclear cells, prescapular lymph node and spleen. Transmission of BIV was confirmed in the groups that were inoculated with the virus and with the virus in milk, but no evidence of its transmission was demonstrated in the group that received the pasteurised inoculum.

Animals↗
PubMed1997

Determination of subnanogram concentrations of fentanyl in plasma by gas chromatography-mass spectrometry: comparison with standard radioimmunoassay.

A method was devised to determine fentanyl plasma concentrations by GC-MS using selected-ion monitoring (SIM) with sufentanil as internal standard. This was compared with a commonly used commercial radioimmunoassay (RIA). Sample preparation for GC-MS involved basification of plasma then extraction using n-butyl chloride followed by concentration to dryness and reconstitution in toluene for chromatography. Using 1-ml plasma samples, the estimated limit of detection of fentanyl was 20 pg/ml. Blood samples for pharmacokinetic studies were split and assayed by GC-MS and RIA which had a limit of detection of 200 pg/ml. Pearson's r (r - 0.80, p < 0.0001) indicated the methods were highly correlated at all plasma concentrations. Owing to the greater sensitivity of the method, GC-MS is recommended over RIA for subnanogram determination of fentanyl in plasma.

Analgesics, Opioid↗
PubMed1997

Asymmetry of gait initiation in hemiparetic stroke subjects.

OBJECTIVE: To investigate symmetry of gait initiation in healthy and hemiparetic subjects. DESIGN: Survey. SETTING: Kinematic laboratory affiliated with a hospital-based department of rehabilitation. PATIENTS OR OTHER PARTICIPANTS: Ten healthy and 14 hemiparetic stroke subjects starting five times with their right and left leg, respectively. MAIN OUTCOME MEASURES: Duration of defined periods, step length, center of pressure, and center of mass were recorded and calculated using two triaxial force plates, contact switches, and a video camera system. RESULTS: Healthy subjects displayed a high degree of independence of kinetic and kinematic parameters of the starting limb. Hemiparetic patients showed differences with respect to the starting limb: when starting with the nonaffected leg, the swing period and step length was shorter and the center of pressure displayed a more marked medio-lateral sway with no corresponding initial movement of the center of mass; when starting with the affected leg the movement pattern of the center of pressure and center of mass was comparable to that of normal subjects. CONCLUSIONS: The trajectories of the center of pressure and center of mass and the symmetry parameters are in accordance with a higher degree of uncertainty when starting with the non-affected limb in hemiparetic subjects.

Aged↗
PubMed1997

Detection of Chlamydia psittaci DNA in avian clinical samples by polymerase chain reaction.

A polymerase chain reaction (PCR) assay was developed to detect. Chlamydia psittaci DNA in faeces and tissue samples from avian species. Primers were designed to amplify a 264 bp product derived from part of the 5' non-translated region and part of the coding region of the ompA gene which encodes the major outer membrane protein. Amplified sequences were confirmed by Southern hybridization using an internal probe. The sensitivity of the combined assay was found to be between 60 to 600 fg of chlamydial DNA (approximately 6 to 60 genome copies). The specificity of the assay was confirmed since PCR product was not obtained from samples containing several serotypes of C. trachomatis, strains of C. pneumoniae, the type strain of C. pecorum, nor from samples containing microorganisms commonly found in the avian gut flora. In this study, 404 avian faeces and 141 avian tissue samples received by the Central Veterinary Laboratory over a 6 month period were analysed by PCR, antigen detection ELISA and where possible, cell culture isolation. PCR performed favourably compared with ELISA and cell culture, or with ELISA alone. The PCR assay was especially suited to the detection of C. psittaci DNA in avian faeces samples. The test was also useful when applied to tissue samples from small contact birds associated with a case of human psittacosis where ELISA results were negative and chlamydial isolation was a less favourable method due to the need for rapid diagnosis.

Animals↗
PubMed1997

PCR-based fingerprinting of Mycobacterium bovis isolates.

We investigated a number of PCR-based strategies for sub-typing isolates of Mycobacterium bovis. A panel of 15 PCR primers, designed from random sequences, insertion sequences and repetitive elements, were analyzed for their ability to allow differentiation between eight M. bovis isolates. PCR products were analyzed using agarose gel electrophoresis and polyacrylamide gel electrophoresis. Random primer based PCR, conducted with a variety of primers did not differentiate between isolates of M. bovis. Successful differentiation between isolates was achieved by the amplification of fragments located between DNA repetitive elements and insertion sequences of the M. bovis genome. PCR primers designed from the major polymorphic tandem repeat (MPTR) region and from insertion sequences IS6110 and IS986 allowed differentiation between isolates of M. bovis. This study is presented as a first step towards the development of PCR-based methods to differentiate between isolates.

Animals↗
PubMed1996

Protein markers in cerebrospinal fluid from BSE-affected cattle.

Two-dimensional gel electrophoresis was used to analyse cerebrospinal fluid (CSF) from 75 suspect cases of bovine spongiform encephalopathy (BSE), 61 of which were confirmed by post mortem brain histopathology, and 38 normal cattle. CSF samples were also examined from cattle killed at periodic intervals through the incubation period following experimental challenge. Consistent changes were recorded in all CSF samples from the confirmed cases of natural BSE and also from cattle showing early signs of experimental disease. The changes consisted of an increased intensity of staining of apolipoprotein E and the presence of two protein spots, as yet unidentified, of molecular weights 35 and 36 kDa, both with a pI of 5.5. These changes were absent in the CSF samples from the normal cattle, from the clinically suspect cattle which were not confirmed as BSE and from the experimentally challenged cattle in the preclinical phase of infection.

Animals↗
PubMed1996

Potential role for retinoic acid receptor-gamma in the inhibition of breast cancer cells by selective retinoids and interferons.

Retinoids are known to inhibit the growth of a wide variety of cancer cells, including breast cancer cells. Advances made in recent years in the understanding of the molecular mechanisms of retinoid action have allowed the design of retinoids with selective activities. Such selective retinoids are of particular interest, because they may reduce the number of undesirable side effects observed with natural compounds. Here, we have compared the growth-inhibitory activities of natural retinoids with various selective retinoids, including anti-activator protein (AP)-1 selective compounds on estrogen receptor-positive and -negative breast cancer cell lines. In addition, we have investigated cooperativity between selective retinoids and IFNs and have begun to analyze the pathways that these two different growth inhibitors use for antagonizing breast cancer cell proliferation. We observe that several selective retinoids can inhibit breast cancer cells as efficiently as the natural compounds. Anti-AP-1-selective retinoids are as effective as retinoic acid receptor (RAR)-beta/gamma-selective compounds. This lets us conclude that retinoid-induced inhibition of breast cancer cell growth does not require retinoid receptor transactivation. Several synthetic retinoids including anti-AP-1-selective compounds show synergism with IFNs. However, true synergism between the two different types of growth regulators was seen only when both classes of molecules were used at low concentrations. RAR-beta/gamma and anti-AP-1-selective retinoids, but not RAR-alpha-selective compounds, induced increased RAR-gamma mRNA levels. Interestingly, IFNs at elevated concentrations (100 units/ml and higher) also induced increased RAR-gamma expression. Thus, when used at high concentrations, IFNs may activate growth-inhibitory pathways overlapping with those activated by retinoids. Because increased RAR-gamma expression is induced by the two different classes of breast cancer cell inhibitors, it is likely to have an important role in controlling the growth fo these cancer cells.

Antineoplastic Agents↗
PubMed1996

Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period.

Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.

Amino Acid Sequence↗
PubMed1996

Serological diagnosis of ovine enzootic abortion by comparative inclusion immunofluorescence assay, recombinant lipopolysaccharide enzyme-linked immunosorbent assay, and complement fixation test.

Since the 1950s, serological diagnosis of ovine enzootic abortion (OEA), caused by strains of Chlamydia psittaci, has been based mainly on the complement fixation test (CFT), which is neither particularly sensitive nor specific since antibodies to other chlamydial and enterobacterial pathogens may be detected. In this study. a recombinant enzyme-linked immunosorbent assay (rELISA) (medac, Hamburg, Germany), based on a unique chlamydial genus-specific epitope of Chlamydia trachomatis L2 lipopolysaccharide, was evaluated for sensitivity and specificity as a primary screening assay for OEA by comparison with the CFT. A comparative inclusion immunofluorescence assay (IFA), in which antibody titers to C. psittaci and Chlamydia pecorum were examined, was used as the reference test for 573 serum samples from four flocks. Reactivity to C. pecorum was measured since inapparent intestinal infections by C. pecorum are believed to be common in British flocks. In detecting positive sera from an abortion-affected flock, in which a C. pecorum infection was also suggested by IFA, the rELISA outperformed the CFT with significant evidence for increased sensitivity (P = 0.003). In two flocks in which C. pecorum infections alone were suggested by IFA, the rELISA and CFT were prone to detect low levels of false-positive results, but the values were not significant. The rELISA provided results in one flock in which sera that were anticomplementary could not be resolved by the CFT. In another flock in which abortion had not occurred but infection by both chlamydial species was suspected, no significant difference was found between the sensitivities of the rELISA and CFT. The rELISA could not differentiate ovine C. psittaci and C. pecorum infections but was shown to be a more sensitive primary screening test for OEA than was the CFT, particularly where abortion had occurred and even when antibodies due to additional inapparent infection(s) by C. pecorum were present.

Abortion, Veterinary↗
PubMed1996

Identification of n-acetylmethamphetamine in a sample of illicitly synthesized methamphetamine.

Analysis of illicit methamphetamine samples revealed the presence of a hitherto unreported impurity. This was identified as N-acetylmethamphetamine by synthesis and GC-MS. This impurity is believed to arise by transesterification of methamphetamine during reflux with propyl acetate. Other circumstantial evidence and intelligence data indicate that propyl acetate was used to increase yields of methamphetamine hydrochloride by azeotropic removal of water remaining after salt formation with aqueous hydrochloric acid.

Drug Contamination↗