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Biomedical subjects

S M Metcalfe

Publications and source records attributed to S M Metcalfe.

At least 37 records · Page 2Linked to original sources
PubMed1993

A comparative study of cyclosporine and its derivative SDZ IMM-125 in canine renal allografts.

The immunosuppressive efficacy of CsA and its derivative SDZ IMM-125 was compared in highly mismatched mongrel dogs in receipt of renal allografts. At an equal dose of 15 mg/kg/day and in the same drug vehicle, SDZ IMM-125 was not superior to CsA in prolonging allograft survival. Whole blood levels of SDZ IMM-125 were lower than those achieved for CsA. No specific drug-related side effects were noticed in this model.

Animals↗
PubMed1990

Tumour markers in breast cancer: a report on the extensive clinical use of B5 and CA15.3.

The B5 antigen is an integral component of human erythrocyte membranes which becomes enhanced in cancer patients. Here we have measured the correlation between B5 status and disease status in 456 patients with breast cancer. A B5-positive status was found in 45/335 (13%) of patients who were long-term disease free and without recurrence (group A), and in 12/53 (23%) of patients who were disease-free following recurrence (group B). In contrast, the majority of patients with progressive disease were B5 positive, including 27/41 (66%) with progressive relapsed disease (group C) and 21/27 (78%) whose disease was progressive from diagnosis (group D). In a similar analysis of CA15.3 in 289 patients, abnormally high marker levels were found in 1/210 group A; 1/35 group B; 20/29 group C; and 8/15 group D patients. Changes in B5 level showed a high correlation with disease behaviour: rising B5 levels occurred in 56 patients, of whom 50 (89%) were found to have recurrent disease. A decrease in B5 was associated with remission in 53/55 (96%) patients. CA15.3 is a marker for breast cancer which related to tumour bulk, and combination of CA15.3 with B5 increased sensitivity for active disease as 21/24 (88%) of patients with recently relapsed disease were positive for either B5 or CA15.3: 16/24 (67%) of these patients had a positive marker result at, or prior to, clinical diagnosis of their recurrence. Overall, the combined use of CA15.3 and B5 gave clinically relevant data which was more informative than either marker alone.

Antigens, Neoplasm↗
PubMed1990

Cyclosporine, FK506, and rapamycin. Some effects on early activation events in serum-free, mitogen-stimulated mouse spleen cells.

Both cyclosporine and FK506 (FK) inhibit Con A-stimulated mouse spleen cells from entering the cell division cycle at the G0/G1 interface. Rapamycin, a fungal metabolite structurally related to FK, acts later and blocks progress through the cell division cycle at some point in G1. The effect of CsA, FK, and rapamycin drug combinations appeared additive, while certain concentrations of FK and rapamycin appeared to be antagonistic. The early blockade of lymphocyte activation caused by CsA and by FK was not due to altered membrane transport kinetics, nor to perturbation of the dynamic behavior of actin. However, both drugs showed the same specific effects on gene activation over a profile of genes encoding oncoproteins, putative transcription factors, cyclophilin, heat-shock proteins, IL-2, and IL-2-R. Of note was the drug-associated super-induction of krox-24 and reduced induction of krox-20. Both krox-24 and krox-20 encode proteins containing zinc-binding fingers, and are likely to regulate gene transcription, and this is the first report of gene control mechanisms being specifically affected by CsA and by FK.

Actins↗
PubMed1989

B5 tumour marker and urine cytology in diagnosis and follow-up of transitional cell bladder cancer.

The correlation between a new tumor marker, B5, and tumour behaviour in bladder cancer was recorded and an assessment made of the value of combining the B5 test with urine cytology for predicting the presence of tumour. The study group included 57 new patients, of whom 32 were B5 positive at diagnosis and were well marked by B5 on follow-up. There were no false positive shifts in new patients who became free of observable tumour, whilst 1 of 13 patients with persistent disease showed a false negative shift. When the findings from 199 cystoscopies were compared with the results of B5 and urine cytology, B5 was found to improve the prediction of recurrent tumour over cytology alone. Moreover, a high incidence of occult malignancy (7/19) was found in patients where cystoscopy had failed to show recurrence but whose combined marker results were both positive.

Biomarkers, Tumor↗
PubMed1985

Cyclosporin-A binds lymphocyte surface receptors induced by activation.

Cyclosporin A (CyA) is a new immunosuppressive drug of very considerable and widespread interest not only for clinicians and transplant immunologists but also for cell biologists concerned with activation mechanisms, as it causes a selective blockade of lymphocyte proliferation. Clearly, the molecular biology of CyA action is of fundamental importance, and in attempting to understand this we have looked for a cell surface receptor. We used indirect staining with antibody (at 4 degrees C and in azide) to ensure that only those CyA molecules held at the cell surface would be seen. The drug molecules which partition into the cell membrane, due to the extreme lipophilicity of CyA, are not detected by extracellular antibody. This technique differs from other methods using a directly labelled drug, where it is not possible to discriminate between specific and non-specific binding. Using high sensitivity flow cytometric analysis we were unable to find CyA on resting lymphocytes, whereas lymphocytes activated by concanavalin A (Con A) or mixed lymphocyte reaction (MLR) showed a CyA-dependent increase in fluorescence.

Cyclosporins↗
PubMed1984

A new tumour marker tested in 98 patients with bladder carcinoma.

A new, indirect marker of human tumour has been tested in 98 patients with urothelial bladder carcinoma. The marker is detected by B5, a monoclonal antibody which agglutinates erythrocytes from tumour-bearing patients. Patients admitted for cystoscopy for diagnosis of bladder tumour, or for follow-up of known disease, were chosen to enable comparison between (a) B5 results and (b) visual assessment of tumour growth. Ninety per cent of those with new tumour (20) and, overall, 80% of patients with tumour (74), were B5 positive. These results were independent of tumour size and include very small recurrences, implying that B5 is a sensitive marker of tumour presence. The background incidence of B5 positive individuals is 18% in controls; a similar incidence occurs in patients who have been tumour-free for 9 months or more. Patients who had no visible tumour in this study, but who had tumour within 9 months, were often B5 positive (6/11). This may be due to the lifespan of erythrocytes causing a delay in change from B5 positive to B5 negative in those patients who will remain disease-free.

Antibodies, Monoclonal↗