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Biomedical subjects

G T Rogers

Publications and source records attributed to G T Rogers.

At least 37 records · Page 2Linked to original sources

A short computer program for calculating tissue distributions in tumour-bearing nude mice after administration of radiolabelled specific and non-specific antibodies.

The short computer program described provides for rapid calculation of tumour and normal tissue distribution data for radiolabelled specific antibody and non-specific immunoglobulin in the nude mouse xenograft model. Results are displayed in convenient tabular form and also as a bar graph. Facilities for providing a hard copy of all results are installed within the program.

Animals↗

Comparative tumour localization of antibody fragments and intact IgG in nude mice bearing a CEA-producing human colon tumour xenograft.

The dynamics of distribution of radiolabelled F(ab')2 fragments of a monoclonal anti-CEA antibody have been studied in the nude mouse bearing a CEA-producing human colon carcinoma. Our results showed that the fragment was rapidly cleared from all normal organs reaching about 1% of that injected by 24 hr. Specific tumour localization occurred as early as 2 hr after injection and was complete by 4 hr. The amount of fragment localized in tumour was 4% of the injected dose, equivalent to that obtained with the intact antibody. Greatly improved tumour:normal tissue ratios were obtained with the fragment compared to intact IgG. However, the residence time of the fragment was much shorter (24 hr) than that of intact antibody (more than 3 days). Tumour localization indices suggested that fragments were superior to intact IgG at locating tumour specifically. The specificity indices based on lung, spleen and liver were much higher than those for intact antibody, reflecting the lack of Fc-receptor binding of fragments and their reduced excretion by these organs. The 'fragment index' enabled tumour:normal tissue ratios for the fragment and intact IgG to be compared. Together with the distribution study at different time points, this simplifies the task of defining a 'time window' in which tumour imaging and therapy might be optimal.

Adenocarcinoma↗

A monoclonal antibody against a CEA-related antigen expressed on HT29 colon tumour cells.

A new monoclonal antibody, that binds to CEA and with low cross-reactivity with NCA, has been raised to an antigen expressed on HT29 colon tumour cells. This antibody (H58) reacts strongly with high-molecular-weight protein (50 X 10(4)) isolated from a crude plasma membrane preparation of HT29 cells as well as binding to purified CEA of molecular size (20 X 10(4)) isolated both from those cells and liver metastases of colon tumour. H58 binds to an epitope sterically unrelated to the binding site of the previously described anti-CEA monoclonal antibody MA/1 and our routine anti-CEA polyclonal serum PKIG. Augmented binding of antibody to either the cell membrane preparation or conventional CEA can be achieved using a mixture comprising equal weights of specific immunoglobulin from H58 and MA/1. The value of solid-phase binding assays using microtitre plates for selecting potentially useful antibodies is discussed.

Animals↗

The value of immunohistochemical markers in the diagnosis of cervical neoplasia.

This study was designed to determine whether immunohistochemical stains for tumour-associated markers may be useful in the detection and differential diagnosis of premalignant and malignant lesions of the cervix. The expression of four markers detected by monoclonal antibodies, human milk fat globule 1 and 2 (HMFG-1 and 2), Ca1 and anti-carcinoembryonic antigen (anti-CEA) on conventional histological sections of various cervical lesions has been investigated. None of these markers was specific for neoplastic lesions of the cervix and all four markers were expressed by metaplastic as well as neoplastic cells, and it was concluded that their application in the histopathological examination of the cervix is limited.

Antibodies↗

Binding studies on two different monoclonal antibodies raised against CEA.

Binding characteristics of two mouse monoclonal antibodies MA/1 and MA/200 raised to carcinoembryonic antigen (CEA) are presented. Double antibody radioimmunoassay and a solid phase assay confirmed that MA/1 binds weakly to CEA extracted from tumour tissue but strongly to CEA in patients' serum. Antibody MA/200 binds with high affinity to both 'tumour' and 'serum' CEA. Ligand-receptor relationship for MA/1 and MA/200 binding to both tumour CEA and CEA isolated from serum are presented from equilibrium binding data analysed by the method of Scatchard. Co-titration experiments also indicated that MA/1 and MA/200 and an established polyclonal anti-CEA bind to a similar subpopulation of CEA or CEA-like molecules, but the binding data demonstrate that their respective binding sites are chemically different.

Animals↗

Somatic-cell hybrids producing antibodies against CEA.

Monoclonal antibodies to carcinoembryonic antigen (CEA) promise improved specificity for the measurement of this widely expressed human cancer antigen. A mouse monoclonal antibody binds weakly to CEA in perchloric acid extracts of tumour but strongly to CEA similarly isolated from serum, and its spectrum of cancer detection differs from conventional antisera.

Animals↗

Application of monoclonal antibodies to purified CEA in clinical radioimmunoassay of human serum.

Double-antibody radioimmunoassay using a mouse monoclonal anti-CEA (MA/1) has been used to measure CEA in human serum. Low levels of MA/1-binding CEA have been found in serum from normal individuals and moderately raised levels are sometimes associated with certain non-malignant diseases. As with conventional anti-CEA, the MA/1 antibodies can recognize significant amounts of CEA in serum from patients with a variety of solid tumours. However they appear to recognize a different immunodeterminant and possibly a different population of CEA molecules to, or a subset of, those measured by two routine assays. Studies in which the MA/1 assay was directly compared with the results of the Charing Cross routine and Abbott EIA assays have indicated that different immunological forms of CEA may be expressed in the course of tumour progression but no prognostic value was evident in this study. Our results stress the need to resolve immunological specificities expressed by CEA-like molecules and evaluate their clinical importance.

Adult↗

Aged widows and OASDI: age at and economic status before and after receipt of benefits.

This article, which is based on panel data from the Retirement History Study, analyzes the economic status of widows in late middle age. Its objectives are threefold: (1) To describe the income, labor-force, and demographic characteristics of widows 2 to 3 years before they become eligible for old-age benefits under the old-age, survivors, and disability insurance (OASDI) program; (2) to examine the age at which they elect benefits and the characteristics associated with that decision; and (3) to compare their economic status before and after they begin collecting benefits. The findings show that employment during the pre-OASDI period greatly influenced a widow's benefit-timing decision. Among workers, the decision was related to earnings, occupation, job tenure, extent of employment, income from assets, pension coverage, monthly benefit amount, and work limitations. Earnings and monthly benefit amount were important pivotal variables. Although the majority of widows experienced a reduction in their standard of living after moving into beneficiary status, a sizable minority--made up mainly of the most economically disadvantaged--experienced and improvement.

Age Factors↗

Vesting of private pension benefits in 1979 and change from 1972.

This article examines the prevalence of vested private pension benefits in 1979 as reported by full-time private wage and salary workers actively participating in pension plans. It also analyzes the effect of selected demographic, economic, labor-force, and plan characteristics on vested status. Years of participation in a plan was by far the most important predictor of vested status. Age was positively related to vested status even after accounting for the longer plan participation of older workers. Evidence pertaining to occupation, size of firm, and type of employer plan suggests that multi-employer plans and those covering professional and managerial workers and the employees of the smallest firms have more rapid vesting schedules than plans covering other workers. Sex, race, union representation, and earnings had little meaningful effect on vested status. This article also examines change in the prevalence of vesting after passage of the Employee Retirement Income Security Act (ERISA) by comparing reported vested rates for 1972 and 1979. The proportion of plan participants reporting vested benefits rose substantially during this period, a finding suggestive of ERISA's substantial impact. The magnitude of the change is examined by years of service with employer, age, sex, earnings, occupation, and industry.

Adult↗

Preoperative carcinoembryonic antigen levels correlated with postoperative pathological staging in bronchial carcinoma.

Serum carcinoembryonic antigen (CEA) levels were obtained before operation in 214 patients undergoing diagnostic tests for suspected bronchial carcinoma, and the results correlated with the postoperative, pathological stage of disease. Positive CEA levels (greater than 10 ng/ml) were observed in 40% (8/20) of stage 1, 58.5% (31/53) of stage 2, 85.2% (69/81) of stage 3, and 92.3% (24/26) of stage 4 patients with bronchial carcinoma. Furthermore, the mean CEA levels increased with stage of disease, and the differences between mean levels were found to be significant in stages 1 and 2 versus 3 and 4 (p less than 0.001). This suggests a positive correlation between the preoperative CEA level and tumour burden defined by pathological staging. When the results were compared with the histological type of lung carcinoma, CEA elevations occurred most frequently with adenocarcinoma, followed by undifferentiated and squamous cell carcinoma, reflecting perhaps the origin of this oncofetal antigen from the endodermally derived bronchial mucosa. These data indicate that preoperative serum CEA levels quantitatively reflect the extent of tumour assessed pathologically at operation and confirm the potential usefulness of this antigen as a biological tumour marker in the management of bronchial neoplasms.

Bronchial Neoplasms↗

Extraction of CEA from tumour tissue, foetal colon and patients' sera, and the effect of perchloric acid.

The use of perchloric acid and water for the extraction of CEA from tumour and foetal tissues has been investigated. In the case of tumour, lower recoveries of CEA were obtained from perchloric acid extracts than from aqueous extracts of the same tissue. CEA has also been extracted with 3M KCl solution from insoluble perchloric acid residues of tumour homogenates and cancer patients' serum. Whilst a large proportion of CEA activity recovered from tumour was associated with the perchloric acid residue, the corresponding amounts from serum were very small. CEA elution volumes for each extract, obtained by assay of Sephadex G-200 column fractions, showed significant heterogeneity in molecular size. The purified CEA pools also showed quantitative variations in the binding profiles on Con A-Sepharose. It has been shown that perchloric acid modifies the carbohydrate in CEA, thus altering its Con A-binding properties. Preliminary experiments with foetal colon have demonstrated that, unlike colorectal CEA, a significant proportion of foetal CEA was not bound to ConA. Comparative immunodiffusion showed immunological identity of CEA from the various extracts, although the purified aqueous extract produced an additional precipitin reaction, indicating a second antigen which is relatively unstable or less soluble in perchloric acid.

Bronchial Neoplasms↗