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Biomedical subjects

J Law

Publications and source records attributed to J Law.

At least 19 recordsLinked to original sources

In vitro stability of EDTA and DTPA immunoconjugates of monoclonal antibody 2G3 labeled with indium-111.

Monoclonal antibody 2G3 directed against a high molecular weight glycoprotein on breast and ovarian cancer cells was conjugated with bicyclic DTPA (or EDTA) anhydride or benzyl isothiocyanate DTPA (benzyl DTPA) and labeled with 111In. DTPA anhydride was more reactive with the antibody than benzyl DTPA, and kinetics of labeling with 111In were more rapid for DTPA substituted 2G3 than for benzyl DTPA substituted 2G3. On the other hand, 111In-2G3 conjugates prepared using DTPA anhydride were subject to more extensive dimerization and higher losses in immunoreactivity than those prepared using benzyl DTPA. On the basis of measurement of transchelation to transferrin, the stability of 111In-2G3 prepared using DTPA anhydride or benzyl DTPA did not differ during incubation in human plasma for 6 days at 37 degrees C. These results suggest that an important advantage of benzyl DTPA over DTPA anhydride for preparing 111In-labeled antibodies is the prevention of intermolecular (and intramolecular) crosslinking during conjugation which ultimately leads to alterations in conformation and losses in immunoreactivity of the radioimmunoconjugate.

Antibodies, Monoclonal

Cloning and partial sequencing of the proteinase gene complex from Lactococcus lactis subsp. lactis UC317.

The proteinase genes from Lactococcus lactis subsp. lactis UC317 were identified on a plasmid, pCI310, which is a deletion derivative of a cointegrate between pCI301, the 75 kb Lac Prt plasmid from UC317 and the 38.5 kb cryptic plasmid from that strain. The prt genes were cloned using a replacement cloning strategy whereby fragments from pCI310 were exchanged with the equivalent fragments in pNZ521, which contains the cloned proteinase genes from L. lactis subsp. lactis SK112. This generated two plasmids which encoded a cell-envelope-associated and a secreted proteinase, respectively. Specific regions of the UC317 structural prtP gene known to encode seven of the amino acids essential for substrate cleavage specificity were sequenced and compared with the known sequences of prt genes from L. lactis strains SK112, Wg2 and NCDO763. In spite of various differences that were detected in the nucleotide sequence of this region, it appears that these seven amino acids in strains UC317 and NCDO763 are identical, and represent a combination of three of the amino acids from SK112 and four from Wg2. These results indicate that the UC317 proteinase is a natural hybrid of the SK112 and Wg2 proteinases.

Amino Acid Sequence

Improved image quality for dense breasts in mammography.

Within the UK breast scanning age range of 50-65 years, about 15% of breasts show a dense structure that is underexposed in conventional mammography. This gives rise to a severe reduction in contrast. Methods of improving this contrast by variation of exposure factors are explored, using a Dupont phantom that has a simulated dense breast structure. Results are assessed by considering measured contrast from a Perspex stepwedge, and by obtaining relative scores, on a scale of 1-10, from 15 radiologists involved in mammography. It is concluded from both these methods that approximately doubling the mAs at the normal kV is preferable to increasing the kV by more than a small amount. A modified mammographic technique on these lines could be valuable in selected cases where a previous conventional mammogram was available, i.e. assessment stage or repeat screening in a screening programme, or symptomatic patients. Practical problems in choosing exposure factors and the magnitude and implications of the increased dose are discussed.

Absorptiometry, Photon

A new phantom for mammography.

A new mammography phantom from Du Pont is described. It has a wider range of types of detail than in previous phantoms, including some which closely simulate breast tissues. Experience of its use, and comparisons with an earlier ("Barts") phantom, are reported. The Du Pont phantom appears to have greater sensitivity to changes in tube kV and focal spot size, and better discrimination between different film-screen combinations and between films from different breast screening centres.

Breast Neoplasms

Patient dose and risk in mammography.

Patient dose in mammography is estimated by two different methods which are compared and which give good agreement. A mean tissue dose of about 1 mGy per film is found for a breast of 4.5 cm compressed thickness. Variables which affect dose are then considered quantitatively, including compressed breast thickness, tube potential, grids, magnification and beam collimation. The variables having the greatest effect are breast thickness and magnification. For example, an 8 cm breast receives about four times the mean tissue dose of a 3.5 cm breast. Similarly, using a magnification factor of about 2, dose is increased about four times in the primary beam, but the adverse consequences may be largely removed with conventional collimation to part of the breast only. Finally, the dose estimates are combined with existing data on breast cancer induction to predict the risk of carcinogenesis in a breast screening programme. For example, in a screening centre performing 15,000 examinations per year, only one induced cancer is predicted in about 7 years of screening under average UK conditions of age and breast thickness.

Breast

Prophylaxis against hepatitis A for travel.

OBJECTIVE: To develop a rational practice policy for prophylaxis against hepatitis A for travellers to high risk areas. DESIGN: 18 Month prospective study of consecutive patients who requested prophylaxis against hepatitis A. SETTING: Inner city general practice. SUBJECTS: 104 Patients aged 15-61 (mean 30) assessed for risk factors for hepatitis A and put into groups depending on predictions from the risk factors of their immunity. MAIN OUTCOME MEASURES AND RESULTS: All patients were screened for antibody to hepatitis A virus. Of 52 patients with no risk factors 47 had no antibody and were thus susceptible to hepatitis A. All 27 patients with major risk factors (having been brought up in an endemic area or with a history of jaundice) were immune. Of 25 patients with minor risk factors (a history of previous travel in high risk areas, drug abuse, having lived in a squat or travelled rough, or having lived with someone who had jaundice) 12 were immune (p less than 0.001, chi 2 test). CONCLUSIONS: All travellers requesting prophylaxis against hepatitis A should be assessed for risk factors for previous exposure to hepatitis A. Those with no risk factors could be immunised with human normal immunoglobulin without screening. The remainder should be tested for hepatitis A antibody and those found to be susceptible should be immunised.

Adolescent

Integration and excision of plasmid DNA in Lactococcus lactis subsp. lactis.

The capacity of the 75-kb lactose-proteinase plasmid pCI301 from Lactococcus lactis subsp. lactis UC317 to recombine with the lactococcal chromosome was examined. Low-frequency integration of pCI301 sequences was detected following protoplast transformation of strain MG136Sm with total plasmid DNA from strain UC317. Excision of integrated sequences was subsequently observed at a low level. Excised sequences were rescued through recombination with and mobilization by the conjugative enterococcal plasmid pAMB1. Transconjugants harboring novel recombinant pCI301::pAMB1 plasmids, both pAMB1 and a pCI301 derivative, and pAMB1 only were isolated. The latter represents a class of transconjugant in which an elevated level of reintegration of pCI301 DNA in the recipient chromosome has occurred.

Chromosomes, Bacterial

Copying ability of preschool children with delayed language development.

Ninety-six 2 1/2-year-old children with delayed language development (identified by health visitors) and 100 controls were required to copy four simple items of the Griffiths Mental Development Scales, and were tested on the comprehension and expressive language scales of the Reynell Developmental Language Scales. The index children performed worse than the controls on all four copying tasks, and poor copying performance was related to both impaired language comprehension and expression. Copying by the index children was also poorer than their performance on two other non-verbal tasks. The implications for the assessment of children with delayed language development are considered, as well as theoretical implications with regard to the cognition/language debate.

Ethnicity

Measurement of x-ray tube potential in the mammographic region.

In mammography it is important to be able to measure x-ray tube potential with an accuracy of +/- 1 kV or better. Mammography x-ray sets generally use molybdenum for both target and filter. Consequently, a high proportion of the x-ray spectrum consists of characteristic radiation from the target. Devices for estimating tube potential such as penetrameters and digital kV meters, which depend on the relation between tube potential and the filtered x-ray spectrum, could be affected in their performance unless calibrated on similar x-ray sets. This paper reports tube potential measurements on a Mo/Mo x-ray set from 25 to 37 kV using the fluorescence technique, a manufacturer's potential divider, two penetrameters of different design and two digital meters of a single design. Agreement between all four techniques was good, being within the various combined experimental errors associated with each, from 37 down to 28 kV, below which the results diverged only slightly.

Calibration

Films, screens and cassettes for mammography.

Various film-screen combinations intended for mammography have been compared for image quality and for dose. Image quality was assessed as in an earlier paper, using a test object having details which are both realistic and quantitative. Relative doses required to give film densities of 1.0 were measured. The Kodak MinR-MinR combination was taken as a standard against which others were compared, and in general a lower dose was accompanied by poorer image quality. The Fuji NH film with Fuji Hi-Mammo screen was the sole exception, giving slightly better image quality at about half the dose required by the MinR combination. A number of cassettes were also compared with each other and with evacuated envelopes. The Dupont Cronex cassette and three carbon-fibre fronted cassettes all performed well in image quality.

Equipment Design