- Email: [email protected]
Pancreastatin immunoreactivity in the circulation of patients with carcinoid tumours
47 PRESENCE OF IMMUNOREACTIVE ENDOTHELIN IN HUMAN SALIVA AND IN THE SALIVARY GLANDS OF RAT
H.C. LAM, K. TAKAHASHI, M.A. GHATEI, K. SUDA, S.M. KANSE and S.R. BLOOM, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 ONN, U.K. Endothelin (ET) is a potent vasoconstricting peptide with multiple isoforms that was originally isolated from vascular endothelial cells. The present work has investigated the presence of immunoreactive endothelin (IR-ET) in human saliva and salivary glands of rat by radioimmunoassay. ~ae average concentrations (mean ± SEM) of IR-ET in mixed-saliva taken from normal volunteers (age range:20-40) were as follows: men (n=9) 2.0 ± 0.2 pmol/I, and women (n=6) 2.1 ± 0.4 pmol/I and there was no significant difference between the means of IR-ET in both sexes. IR-ET could also be detected in male rat parotid glands with an average concentration of 19.2 ± 2.2 fmol/g wet weight (n=10). The dilution curves of both human mixed saliva extract and rat parotid gland extract parallelled the standard curve. Fast protein liquid chromatography (FPLC) of human mixed saliva extract revealed 5 peaks: one eluting just after the void volume, one peak in a position between endothelin-1 and -3, and the other three in the positions of synthetic endothelin-1, -2, and -3, respectively. Similar FPLC pattern of rat parotid gland extract was noted except that there was no peak after the void volume. Exogenous added ET-1 changed partially to materials eluting in the position between ET-1 and ET-3 by FPLC when incubated in human saliva for 6 hours. In contrast, exogenous added ET-2 and ET-3 were both stable in human saliva. These results provide the first demonstration of IR-ET in human mixed saliva and the salivary glands may be one of its possible sources of origin.
PANCREASTATIN IMMUNOREACTIVITY WITH CARCINOID TUMOURS
IN THE CIRCULATION
OF PATIENTS
S.J. LINDEN, C.F. JOHNSTON, R.T. CUNNINGHAM and K.D. BUCHANAN, Department of Medicine, The Queen's University of Belfast, Belfast, N.Ireland Using a C-terminally directed porcine pancreastatin (PST) radioimmunoassay, we have measured plasma from patients with either metastatic carcinoid disease with carcinoid syndrome (n=9), or with non-metastatic tumours (n=4). In addition, plasmas from patients (n=6) undergoing clinical management for their syndromes with somatostatin analogue, SMS 201-995, and from patients (n=2) after intra-hepatic arterial administration of streptozotocin and floxuridine were collected and measured for pancreastatin content. PST levels were significantly elevated, range 42-2472 pmol/l (normal range: 4-37.5 pmol/l) in patients with carcinoid syndrome, but were normal in patients with non-metastatic carcinoid tumours, clinically cured after primary tumour resection. Two patients were poor responders and PST levels remained consistently high. Four patients showed a definite clinical improvement with concomitant falls in PST levels. Post-chemotherapy, one patient responded well and levels fell to below baseline levels between 3 and 24 hours. In the second patient, coincidental peaks of PST and NSE, 24 hours post-chemotherapy, pre-empted a gross deterioration in symptomatology on day 4. Thus, a PST radioimmunoassay may be useful in the diagnosis and prognosis of patients with carcinoid syndrome.
H.C. LAM, K. TAKAHASHI, M.A. GHATEI, K. SUDA, S.M. KANSE and S.R. BLOOM, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 ONN, U.K. Endothelin (ET) is a potent vasoconstricting peptide with multiple isoforms that was originally isolated from vascular endothelial cells. The present work has investigated the presence of immunoreactive endothelin (IR-ET) in human saliva and salivary glands of rat by radioimmunoassay. ~ae average concentrations (mean ± SEM) of IR-ET in mixed-saliva taken from normal volunteers (age range:20-40) were as follows: men (n=9) 2.0 ± 0.2 pmol/I, and women (n=6) 2.1 ± 0.4 pmol/I and there was no significant difference between the means of IR-ET in both sexes. IR-ET could also be detected in male rat parotid glands with an average concentration of 19.2 ± 2.2 fmol/g wet weight (n=10). The dilution curves of both human mixed saliva extract and rat parotid gland extract parallelled the standard curve. Fast protein liquid chromatography (FPLC) of human mixed saliva extract revealed 5 peaks: one eluting just after the void volume, one peak in a position between endothelin-1 and -3, and the other three in the positions of synthetic endothelin-1, -2, and -3, respectively. Similar FPLC pattern of rat parotid gland extract was noted except that there was no peak after the void volume. Exogenous added ET-1 changed partially to materials eluting in the position between ET-1 and ET-3 by FPLC when incubated in human saliva for 6 hours. In contrast, exogenous added ET-2 and ET-3 were both stable in human saliva. These results provide the first demonstration of IR-ET in human mixed saliva and the salivary glands may be one of its possible sources of origin.
PANCREASTATIN IMMUNOREACTIVITY WITH CARCINOID TUMOURS
IN THE CIRCULATION
OF PATIENTS
S.J. LINDEN, C.F. JOHNSTON, R.T. CUNNINGHAM and K.D. BUCHANAN, Department of Medicine, The Queen's University of Belfast, Belfast, N.Ireland Using a C-terminally directed porcine pancreastatin (PST) radioimmunoassay, we have measured plasma from patients with either metastatic carcinoid disease with carcinoid syndrome (n=9), or with non-metastatic tumours (n=4). In addition, plasmas from patients (n=6) undergoing clinical management for their syndromes with somatostatin analogue, SMS 201-995, and from patients (n=2) after intra-hepatic arterial administration of streptozotocin and floxuridine were collected and measured for pancreastatin content. PST levels were significantly elevated, range 42-2472 pmol/l (normal range: 4-37.5 pmol/l) in patients with carcinoid syndrome, but were normal in patients with non-metastatic carcinoid tumours, clinically cured after primary tumour resection. Two patients were poor responders and PST levels remained consistently high. Four patients showed a definite clinical improvement with concomitant falls in PST levels. Post-chemotherapy, one patient responded well and levels fell to below baseline levels between 3 and 24 hours. In the second patient, coincidental peaks of PST and NSE, 24 hours post-chemotherapy, pre-empted a gross deterioration in symptomatology on day 4. Thus, a PST radioimmunoassay may be useful in the diagnosis and prognosis of patients with carcinoid syndrome.