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Biomedical subjects

L McCallum

Publications and source records attributed to L McCallum.

10 recordsLinked to original sources

The VR2 epitope on the PorA P1.7-2,4 protein is the major target for the immune response elicited by the strain-specific group B meningococcal vaccine MeNZB.

A protracted epidemic of group B meningococcal disease in New Zealand led to the testing of a strain-specific tailor-made vaccine, MeNZB. Immunogenicity levels achieved during age group trials enabled New Zealand's regulatory authority to grant licensure to deliver MeNZB to all individuals under age 20. During the trials target strains for serum bactericidal antibody measurements included the vaccine target strain NZ98/254 and two comparator epidemic-type strains (NZ94/167 and NZ02/09). In this study, 12 other strains differing variously from the vaccine strain by their capsular group, PorB type, and PorA variable region specificities, or PorA expression, were used as target strains. The PorA specificity of the serum bactericidal antibody responses to the vaccine was determined for 40 vaccinees. Sets of 10 pre- and postvaccination sera were chosen randomly from the young infant, older infant, toddler, and school-age group trials. Antibody recognition of linearized PorA proteins was also determined using immunoblotting. Across all age groups vaccine-induced serum bactericidal antibodies specifically targeted the VR2 P1.4 epitope of the PorA P1.7-2,4 protein irrespective of the PorB type and/or capsular type of the target strain. Deletion of amino acids within the VR2 epitope or replacement of the epitope through genetic exchange allowed strains variously to resist antibody-directed complement-mediated lysis and negated PorA-specific antibody recognition in immunoblots. The demonstration that the immunodominant antibody response was specifically for the VR2 P1.4 epitope of the PorA protein supports the public health decision to use a strain-specific vaccine for the control of New Zealand's epidemic of meningococcal disease.

Amino Acid Sequence↗

Validation of the serum bactericidal assay for measurement of functional antibodies against group B meningococci associated with vaccine trials.

Provisional licensure of the trial vaccine, MeNZB, required demonstration of immune responses in vaccines, as measured by a validated Serum Bactericidal Assay (SBA). Reported are the investigations undertaken to define test parameters, lower limits of quantitation and measurement of SBA reproducibility. Results helped to formulate the operating procedure for the measurement of serum bactericidal antibodies during six age-group MeNZB vaccine trials. The lower limit of quantitation was determined as a titre of 4. A four-fold rise in antibody (sero-conversion) from a pre-vaccination titre of 2 (<4) required a minimum post-vaccination titre of 8, a more stringent measurement than has been used in other published studies.

Antibodies, Bacterial↗

AIDS impact.

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Acquired Immunodeficiency Syndrome↗

The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial.

The relation between serum albumin levels and subsequent incidence of myocardial infarction and coronary heart disease deaths was evaluated using stored serum from the Multiple Risk Factor Intervention Trial (MRFIT). There were 91 coronary heart disease deaths, 113 myocardial infarction patients, and 405 controls matched to cases within 5 years of age, treatment group, and clinic site. There was a highly significant inverse relation between serum albumin level and risk of coronary heart disease. Individuals with a baseline level of serum albumin greater than or equal to 4.7 g/dl had an odds ratio of 0.45 as compared with individuals with a baseline level of serum albumin less than 4.4 g/dl. The relation persisted after adjusting for other cardiovascular risk factors (blood pressure, smoking, and serum cholesterol). The association was stronger for coronary heart disease deaths than for surviving myocardial infarction patients, and for cigarette smokers as compared with cigarette nonsmokers. The deaths studied occurred in the time period at least 6 years after the sera had been obtained and up to 10.5 years of follow-up, and the myocardial infarctions studied occurred within the first 6.5 years of follow-up. There was no consistent relation between time and death due to coronary heart disease or myocardial infarction and albumin levels. Albumin levels are related to the acute phase reaction. Lower albumin levels may be a marker of persistent injury to arteries and progression of atherosclerosis and thrombosis. The consistent relation between albumin and coronary heart disease risk requires further evaluation.

Adult↗

Iris colour and the influence of local anaesthetics on pre-corneal tear film stability.

Using non-invasive methods we report here that the stability of the pre-corneal tear film is lower in the brown eye than in the blue eye. The average stability in the blue eye is 15.8 sec (SD +/- 5.8) and in the brown eye it is 12.3 sec (SD +/- 2.9). On average, instillation of topical anaesthetics, benoxinate hydrochloride (0.4%) or amethacaine hydrochloride (0.5%), depress the stability of the pre-corneal tear film in blue eyes but not in brown eyes.

Administration, Topical↗

Urothelial susceptibility to tumor cell implantation: comparison of cauterization with N-methyl-N-nitrosourea.

To determine whether or not transitional cell carcinoma cells will preferentially implant and grow on an altered urothelial surface, cauterization and instillation of N-methyl-N-nitrosourea (MNU) were used to alter the murine bladder urothelium. Transplantable tumor cells (2.09 X 10(6) ) were placed into the bladders of 53 mice. Tumor cell implantation occurred in only 6 per cent of the mice with a normal bladder, whereas tumors were present in 28 per cent of mice pretreated with intravesical MNU and in 67 per cent of mice which had a portion of the bladder cauterized prior to insertion of tumor cells (p less than 0.005). This study not only establishes the optimal technique for implantation in this experimental model, but also suggests that seeding may be a contributory factor in the high recurrence rate following endoscopic treatment of bladder tumors in man.

Animals↗

Evaluation of cystography for detection of bladder carcinoma in mice: comparison with urinary cytology.

Cystography was compared to urinary cytology in an effort to determine whether or not this modality might be useful in the detection of FANFT-induced bladder tumors in mice. Compared to gross examination of the bladders in 24 mice, cystography had the same degree of accuracy as urinary cytology--79.2 per cent. Comparison of the cystographic and cytologic diagnoses with histology revealed that cytology was more accurate, 79.2 vs 66.6 per cent. Cystography was especially helpful in detecting papillary tumors while cytology was more accurate in the detection of high-grade, high-stage tumors or carcinoma in situ (CIS). Cystography in mice can complement cytology as an additional useful technique for detection of bladder carcinoma.

Animals↗