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Biomedical subjects

J M Wilkinson

Publications and source records attributed to J M Wilkinson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Identification and tissue distribution of rabbit leucocyte antigens recognized by monoclonal antibodies.

Three monoclonal antibodies which recognize rabbit leucocytes have been characterized by immunofluorescence staining of a variety of cell populations and also by immunochemical techniques. The evidence obtained suggests that these antibodies recognize the rabbit equivalents of the CD58/LFA-3 (VC21), CD43/leukosialin (L11/135) and CD9 (MM2/57) antigens. A fourth antibody, RPN3/57, recognizes an antigen expressed strongly on T cells, thymocytes and neutrophils and at lower levels on platelets. It has not, however been possible to characterize the antigen recognized by RPN3/57 in molecular terms. Both L11/135 and RPN3/57 are useful reagents for the detection of T cells both by flow cytometry and by immunohistochemistry.

Animals↗
PubMed1991

Activation of human platelets by exposure to a monoclonal antibody, PM6/248, to glycoprotein IIb-IIIa.

Monoclonal antibody PM6/248, which recognizes the GPIIb-IIIa complex on human platelets, causes platelet aggregation in platelet-rich plasma or in gel-filtered platelet suspensions. Aggregation follows a concentration-dependent lag phase and reaches a maximum at 8 micrograms/ml. High concentrations of antibody (less than 30 micrograms/ml) produce complete inhibition of the aggregation response. Aggregation is accompanied by serotonin secretion and thromboxane A2 synthesis, neither of which are inhibited by high concentrations of antibody, and by the mobilization of intracellular Ca2+. The F(ab')2 fragment of PM6/248 does not cause platelet activation and pre-incubation of platelets with this fragment inhibits all platelet responses stimulated by the whole antibody. Pre-incubation with the F(ab')2 fragment of the anti-Fc gamma RII Mab, IV. 3, also inhibits all responses to PM6/248. These data indicate that platelet activation stimulated by PM6/248 is caused by cross-linking of GPIIb-IIIa to the Fc gamma RII which stimulates signal transduction across the plasma membrane through a conformational change in the Fc gamma RII.

Animals↗
PubMed1991

Assessment of osteoporosis at autopsy: mechanical methods compared to radiological and histological techniques.

Osteoporosis is a common problem in the elderly female population and pathological fractures are a frequent complication, but how should the pathologist assess the severity of the disease at autopsy? In this study we have compared subjective, semi-quantitative assessments of rib fracturability, vertebral compressibility, Singh index and histomorphometric methods against a 'gold standard' assessment, namely the force required to fracture the femoral neck. We have shown good correlations between rib fracturability. Singh index and the standard chosen. Poor correlation was shown between histomorphometric techniques and the standard. Our findings suggest that gross rib fracturability is a good indicator of osteoporosis in as far as bone fragility is an indicator of the severity of osteoporosis. However, as the population under examination was small, further studies in this area are clearly warranted in order to extend these findings.

Aged↗
PubMed1990

Vinculin is a permanent component of the membrane skeleton and is incorporated into the (re)organising cytoskeleton upon platelet activation.

Vinculin, a 130-kDa protein discovered in chicken gizzard smooth-muscle cells and subsequently also described in platelets, is believed to be involved in membrane-cytoskeleton interactions. In this study we investigated vinculin distribution in human blood platelets. Two skeletal fractions and a remaining cytosolic fraction were prepared with a recently described Triton X-100 lysis buffer causing minimal post-lysis breakdown by proteolysis. The presence of vinculin was demonstrated in the membrane skeleton and cytosol of resting and thrombin-activated human platelets. Upon thrombin stimulation vinculin also appeared in the cytoskeleton. this cytoskeletal incorporation was completed during the early stages of platelet aggregation and secretion, when the uptake of myosin, actin-binding protein and talin was still not maximal. We conclude therefore, that vinculin may play an important role in the structural (re)organisation of the human platelet cytoskeleton upon platelet activation.

Blood Platelets↗
PubMed1990

Tissue standard ratios for irregularly shaped radiotherapy fields.

A method of calculating dose for a 6 MV X-ray beam using tissue standard ratios (TSR) is described. TSRs may be divided into a primary component and a scatter component, and the latter can then be further divided into contributions from elemental scattering volumes of 1 cm x 1 cm cross-sectional area at 1 m from the source. The magnitude of the various components have been determined by analysing measurements of square and rectangular fields, involving the fitting of the scatter data to an exponential function of radial distance from the scatter element. The coefficient and exponent of this function were found to be functions of depth, and this variation is described. A method of utilizing reconstructed scatter data that is compatible with the motion of a multileaf collimator system is presented. Results obtained by re-combining the data for various non-standard geometries are compared with further experimental work.

Humans↗
PubMed1990

New concepts in the treatment of Parkinson's disease.

Carbidopa/levodopa remains the most potent drug for the treatment of Parkinson's disease. Several newer medications may help stabilize and improve such problems as fluctuating responses to the medication, drug-induced dyskinesias and refractory symptoms. Patients with fluctuating responses that do not respond to adjustments in the carbidopa/levodopa dose may benefit from the addition of a direct-acting dopamine agonist, such as pergolide or bromocriptine. While carbidopa/levodopa and the direct-acting dopamine agonists have a proven track record as symptomatic treatment, they probably do not alter the pathologic process underlying this progressive condition. On the other hand, two studies have shown that selegiline might slow the progression of Parkinson's disease, independent of any direct effects on symptoms.

Antiparkinson Agents↗
PubMed1989

The ICRU recommendations for reporting intracavitary therapy in gynaecology and the Manchester method of treating cancer of the cervix uteri.

The recommendations of the International Commission on Radiation Units and Measurements for reporting intracavitary therapy have been considered with particular regard to the Manchester method of treating cancer of the cervix uteri. The total reference air kerma is calculated and tabulated as a function of prescription for the standard Manchester applicator arrangements. Furthermore, it is shown that the volume contained within a particular isodose surface may be determined, with very acceptable accuracy, from the total reference air kerma by the use of a simple empirical expression.

Brachytherapy↗
PubMed1989

Pain relief in terminally ill patients.

A systematic approach to identifying the cause of pain and rational use of drug therapy are keys to providing pain relief to cancer patients. Aspirin, acetaminophen and nonsteroidal anti-inflammatory drugs are effective for mild to moderate pain, and they enhance the effectiveness of weak oral narcotics, such as codeine. For severe pain, morphine is the drug of choice. A variety of adjuvant drugs can be used to enhance the effect of narcotics and to treat specific side effects of the disease or of therapy. For the terminally ill patient, a peaceful death with dignity should always be possible.

Adjuvants, Pharmaceutic↗
PubMed1988

A monoclonal antibody (PL/IM 430) to human platelet intracellular membranes which inhibits the uptake of Ca2+ without affecting the Ca2+ +Mg2+-ATPase.

To probe the structure-function relationships of proteins present in the endoplasmic reticulum-like intracellular membranes of human blood platelets a panel of monoclonal antibodies have been raised, using as immunogen highly purified platelet intracellular membrane vesicles isolated by continuous flow electrophoresis [Menashi, Weintroub & Crawford (1981) J. Biol. Chem. 256, 4095-4101]. Four of these antibodies recognize a single 100 kDa polypeptide in the platelet membrane by immunoblotting. One antibody PL/IM 430 (of IgG1 subclass) inhibited (approximately 70%) the energy-dependent uptake of Ca2+ into the vesicles without affecting the Ca2+ +Mg2+-ATPase activity or the protein phosphorylation previously shown to proceed concomitantly with Ca2+ sequestration [Hack, Croset & Crawford (1986) Biochem. J. 233, 661-668]. The inhibition is independent of ATP concentration over a range 0-2 mM-ATP but shows dose-dependency for external [Ca2+] with maximum inhibition of Ca2+ translocation at concentrations of Ca2+ greater than 500 nM. This capacity of the antibody PL/IM 430 functionally to dislocate components of the intracellular membrane Ca2+ pump complex may have value in structural studies.

Adenosine Triphosphate↗
PubMed1988

Characterization of a monoclonal antibody ITI-Pl 1 directed against human platelet membrane glycoprotein IIb using extracts of whole platelets and platelet surface and intracellular membranes.

A monoclonal antibody (mAb) termed ITI-Pl 1 has been prepared by the hybridoma procedure. Using immuno-absorption and crossed immunoelectrophoresis of Triton X-100 extracts of untreated and EDTA-treated human platelets it was shown to be directed against the surface membrane glycoprotein IIb (GP IIb). This mAb binds to whole platelets independently of ADP-stimulation and the presence of Ca2+-ions. It saturates at around 870 ng/10(8) cells corresponding to approximately 35,800 molecules/platelet. ITI-Pl 1 did not significantly inhibit GP IIb-IIIa dependent functions such as platelet aggregation or fibrinogen binding. Immunofluorescence could be demonstrated using ITI-Pl 1 and intact normal platelets, but not with platelets from a Glanzmann's thrombasthenia patient. Crossed immuno-electrophoresis with platelet extracts from four different thrombasthenic patients gave a line precipitate in the intermediate gel with 125I-labelled ITI-Pl 1 and autoradiography indicating trace amounts of free GP IIb or the GP IIb-IIIa complex. The epitope on GP IIb detected by ITI-Pl 1 is not destroyed by neuraminidase treatment. Thus the mAb also interacts with neuraminidase-treated GP IIb-IIIa complex in highly purified platelet surface membrane fractions as well as with GP IIb-IIIa from untreated internal membranes isolated by continuous flow electrophoresis.

Animals↗
PubMed1987

Strategic hand use preferences and hemispheric specialization in tactual reading: impact of the demands of perceptual encoding.

Four reading-related, information-processing tasks were administered to right-handed blind readers of braille who differed in level of reading skill and in preference for using the right hand or the left hand when required to read text with just one hand. The tasks were letter identification, same-different matching of letters that differed in tactual similarity, short-term memory for lists of words that varied in tactual and phonological similarity, and paragraph reading with and without a concurrent memory load of digits. The results showed interactions between hand preference and the hand that was actually used to read the stimulus materials, such that left preferrers were significantly faster and more accurate with their left hands than with their right hands whereas right preferrers were slightly but usually not significantly faster with their right hands than with their left hands. In all cases, the absolute magnitude of the left-hand advantage among left preferrers was substantially larger than the right-hand advantage among right preferrers. The results suggest that encoding strategies for dealing with braille are reflected in hand preference and that such strategies operate to modify an underlying but somewhat plastic superiority of the right hemisphere for dealing with the perceptual requirements of tactual reading. These requirements are not the same as those of visual reading, leading to some differences in patterns of hemispheric specialization between readers of braille and readers of print.

Adolescent↗
PubMed1987

The application of cost-benefit analysis when considering action to reduce environmental dose rates in hospitals.

Cost-benefit analysis, in which a monetary value is assigned to radiation-induced health detriment, is used to establish whether a proposed course of action to reduce the dose rate in a particular environment is reasonable in the "as low as reasonably achievable" context. The instantaneous dose rate is used in conjunction with a use factor and a man-occupancy factor to establish a dose accumulation rate. This, in turn, is used to calculate what capital expenditure on radiation protection measures is reasonable. Such an approach provides an objective method of assessing and comparing radiation protection problems and leads to better consistency in allocating available resources.

Cost-Benefit Analysis↗
PubMed1986

Expression of troponin T in atria and ventricles of avian and mammalian hearts.

The expression of troponin T in atria and ventricles of adult chicken, rabbit and beef hearts has been studied by two dimensional electrophoresis of soluble extracts from these tissues. The monoclonal antibody, T1/61, has been used to detect the presence of troponin T in the chicken samples. In the chicken only one form of troponin T has been found which is resolved into two spots that probably are due to phosphorylated and non phosphorylated forms. The gels of chicken atria and ventricles are identical with the same patterns, not only of troponin T but also of tropomyosin and myosin light chains. In rabbit and beef the position of troponin T can be located by comparison with the chicken. In the beef it is possible that two forms are present but in the rabbit there appears to be only one. The gels of atria and ventricles of rabbit and beef hearts show differences only in the myosin light chains whereas the expression of tropomyosin is the same. In beef, beta-tropomyosin is found in both tissues. On the evidence of these gels there are no differences in the expression of troponin T or tropomyosin between the atria and ventricles of any of the hearts studied.

Animals↗
PubMed1985

Identification of multiple variants of fast muscle troponin T in the chicken using monoclonal antibodies.

Two monoclonal antibodies, T1/7 and T1/61, have been prepared which are specific for chicken fast muscle troponin T. Both are of the IgG gamma 1 subclass. Both antibodies cross-react strongly with human fast and chicken cardiac troponin T, but while T1/7 reacts weakly with rabbit fast troponin T, T1/61 does not. The antibodies can be used for fibre typing of both chicken and human muscle. The antibodies have been used to identify fast troponin T on two-dimensional maps of proteins from a variety of chicken muscles by electrophoretic transfer to nitrocellulose followed by immunoperoxidase staining. Using this technique five variant forms of fast troponin T have been identified. Two variants, fBT1 and fBT2, are expressed in breast muscle, while the other three, fLT1, fLT2 and fLT3 are expressed in leg muscle. Of the leg muscle variants, fLT1 and fLT2 correspond to the two forms described previously [Wilkinson, J.M., Moir, A.J.G. and Waterfield, M.D. (1984) Eur. J. Biochem. 143, 47-56]. The third variant, fLT3, has not been described before and is expressed in muscles which have a high content of slow fibres. In addition to these clearly defined variant forms immunostaining reveals multiple minor variants of troponin T present in leg muscle which may reflect complex RNA processing of the troponin T gene transcript.

Animals↗
PubMed1985

The Manchester System and the BCRU recommendations for brachytherapy source specification.

The decision to endorse and implement the BCRU recommendation has been taken after careful consideration and discussion amongst those currently active in brachytherapy treatment at the Christie Hospital, Manchester. We believe it to be both logical and scientifically sound. The practical measures discussed here outline how the Manchester System will operate with the new method of source specification, and we urge other users of the Manchester System throughout the world to adopt similar measures and accept the BCRU recommendations also.

Brachytherapy↗
PubMed1984

The expression of multiple forms of troponin T in chicken-fast-skeletal muscle may result from differential splicing of a single gene.

Troponin T isolated from chicken fast skeletal muscle has been shown to be present in three different molecular forms, one in breast and two in leg muscle. The three forms differ in both size and charge. Troponin T from breast muscle has a molecular mass of 33.5 kDa and a pI of about 7. Of the two leg muscle forms the larger has a molecular mass of 30.5 kDa and a pI of about 8.5 and the smaller a molecular mass of 29.8 kDa and a pI of about 10. Considerably more heterogeneity has been found in the leg than in the breast muscle proteins although this is not reflected in their N-terminal sequences. The reason for this is not clear. Troponin T from breast or leg muscle can be phosphorylated with troponin T kinase at the single serine residue at the N-terminus. No difference in the rate or extent of phosphorylation could be found between proteins from breast or leg muscle. The three proteins have been shown to differ only in the amino acid sequence of their N-terminal tryptic peptides. These peptides are of different length, that from breast troponin T being 58 residues and those from leg troponin T being 36 and 42 residues, these differences account for the difference in molecular mass of the parent proteins. Despite this difference the sequence of the first 12 and last 14 residues is identical in all three N-terminal peptides. The remainder of the sequence of the smallest peptide is also repeated in the other two but they each contain an extra piece of unique sequence. On the basis of these sequences it is proposed that chicken troponin T is coded for by a single gene containing, at the 5' end, a number of small exons and that three different mRNA molecules may be produced by alternative pathways of RNA splicing. The possible significance of these N-terminal sequence variations is discussed.

Amino Acid Sequence↗
PubMed1984

Cell surface glycoproteins of rabbit lymphocytes: characterization with monoclonal antibodies.

The structural characteristics of antigens recognized by a panel of monoclonal antibodies prepared against a rabbit T-lymphocyte cell line have been investigated. Those antigens which could be isolated using immunoadsorbents prepared from the monoclonal antibodies had mol. wts of 42,000, 90,000 and 120,000. The 42,000 mol. wt molecule is similar or identical to a rabbit class I major histocompatibility complex antigen and its characterization has been reported elsewhere. Three different 90,000 mol. wt proteins can be distinguished by their reactivity with lectins and by sequential immunoprecipitation. The 120,000 mol. wt protein is a very abundant surface glycoprotein that appears to be a specific marker for T-cells in the rabbit. It is the immunodominant antigen in a lentil lectin bound glycoprotein pool. Over half of the antibodies were directed against this antigen. All antigens detected by the panel of monoclonal antibodies have been detected on normal lymphoid cells.

Animals↗